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Use of Comprehensive Geriatric Assessment in Oncology Patients to Guide Treatment Decisions and Predict Chemotherapy Toxicity
Age is a well recognized risk factor for cancer development. The population of older Americans is growing, and by 2030, 20% of the US population will be aged ≥ 65 years.1 While 25% of all new cancer cases are diagnosed in people aged 65 to 74 years, more than half of cancers occur in individuals aged ≥ 70 years, with even higher rates in those aged ≥ 75 years.2 Although cancer rates have declined slightly overall among people aged ≥ 65 years, this population still has an 11-fold increased incidence of cancer compared with that of younger individuals.3 With a rapidly growing older population, there will be increasing demand for cancer care.
Treatment of cancer in older individuals often is complicated by medical comorbidities, frailty, and poor functional status. Distinguishing patients who can tolerate aggressive therapy from those who require less intensive therapy can be challenging. Age-related physiologic changes predispose older adults to an increased risk of therapy-related toxicities, resulting in suboptimal therapeutic benefit and substantial morbidity. For example, cardiovascular changes can lead to reduction of the cardiac functional reserve, which can increase the risk of congestive heart failure. Similarly, decline in renal function leads to an increased potential for nephrotoxicity.4 Although patients may be of the same chronologic age, their performance, functional, and biologic status may be quite variable; thus, tolerance to aggressive treatment is not easily predicted. The comprehensive geriatric assessment (CGA) may be used as a global assessment tool to risk stratify older patients prior to oncologic treatment decisions.
Health care providers (HCPs), including physician assistants, nurse practitioners, clinical nurse specialists, nurses, and physicians, routinely participate in every aspect of cancer care by ordering and interpreting diagnostic tests, addressing comorbidities, managing symptoms, and discussing cancer treatment recommendations. HCPs in oncology will continue to play a vital role in the coordination and management of older patients with cancer. However, in general, CGA has not been a consistent part of oncology practices, and few HCPs are familiar with the benefits of CGA screening tools.
What Is Geriatric Assessment?
Geriatric assessment is a multidisciplinary, multidimensional process aimed at detecting medical, psychosocial, and functional issues of older adults that are not identified by traditional performance status measures alone. It provides guidance for management of identified problems and improvement in quality of life.6 CGA was developed by geriatricians and multidisciplinary care teams to evaluate the domains of functional, nutritional, cognitive, psychosocial, and economic status; comorbidities; geriatric syndromes; and mood, and it has been tested in both clinics and hospitals.7 Although such assessment requires additional time and resources, its goals are to identify areas of vulnerability, assist in clinical decisions of treatable health problems, and guide therapeutic interventions.6 In oncology practice, the assessment not only addresses these global issues, but also is critical in predicting toxicity and survival outcomes in older oncology patients.
Components of CGA
Advancing age brings many physiologic, psychosocial, and functional challenges, and a cancer diagnosis only adds to these issues. CGA provides a system of assessing older and/or frail patients with cancer through specific domains to identify issues that are not apparent on routine evaluation in a clinic setting before and during chemotherapy treatments. These domains include comorbidity, polypharmacy, functional status, cognition, psychological and social status, and nutrition.8
Comorbidity
The prevalence of multiple medical problems and comorbidities, including cancer, among people aged > 65 years is increasing.9 Studies have shown that two-thirds of patients with cancer had ≥ 2 medical conditions, and nearly one quarter had ≥ 4 medical conditions.10 In older adults, common comorbidities include cardiovascular disease, hypertension, diabetes mellitus, and dementia. These comorbidities can impact treatment decisions, increase the risk of disease, impact treatment-related complications, and affect a patient’s life expectancy.11 Assessing comorbidities is essential to CGA and is done using the Charlson Comorbidity Index and/or the Cumulative Illness Rating Scale.12
The Charlson Comorbidity Index was originally designed to predict 1-year mortality on the basis of a weighted composite score for the following categories: cardiovascular, endocrine, pulmonary, neurologic, renal, hepatic, gastrointestinal, and neoplastic disease.13 It is now the most widely used comorbidity index and has been adapted and verified as applicable and valid for predicting the outcomes and risk of death from many comorbid diseases.14 The Cumulative Illness Rating Scale has been validated as a predictor for readmission for hospitalized older adults, hospitalization within 1 year in a residential setting, and long-term mortality when assessed in inpatient and residential settings.15
Polypharmacy
Polypharmacy (use of ≥ 5 medications) is common in older patients regardless of cancer diagnosis and is often instead defined as “the use of multiple drugs or more than are medically necessary.”16 The use of multiple medications, including those not indicated for existing medical conditions (such as over‐the‐counter, herbal, and complementary/alternative medicines, which patients often fail to declare to their specialist, doctor, or pharmacist) adds to the potential negative aspects of polypharmacy that affect older patients.17
Patients with cancer usually are prescribed an extensive number of medicines, both for the disease and for supportive care, which can increase the chance of drug-drug interactions and adverse reactions.18 While these issues certainly affect quality of life, they also may influence chemotherapy treatment and potentially impact survival. Studies have shown that the presence of polypharmacy has been associated with higher numbers of comorbidities, increased use of inappropriate medications, poor performance status, decline in functional status, and poor survival.18
Functional Status
Although Eastern Cooperative Oncology Group (ECOG) performance status and Karnofsky Performance Status are commonly used by oncologists, these guidelines are limited in focus and do not reliably measure functional status in older patients. Functional status is determined by the ability to perform daily acts of self-care, which includes assessment of activities of daily living (ADLs) and instrumental activities of daily living (IADLs). ADLs refer to such tasks as bathing, dressing, eating, mobility, balance, and toileting.19 IADLs include the ability to perform activities required to live within a community and include shopping, transportation, managing finances, medication management, cooking, and cleaning.11
Physical functionality also can be assessed by measures such as gait speed, grip strength, balance, and lower extremity strength. These are more sensitive and shown to be associated with worse clinical outcomes.20 Grip strength and gait speed, as assessed by the Timed Up and Go test or the Short Physical Performance Battery measure strength and balance.12 Reduction in gait speed and/or grip strength are associated with adverse clinical outcomes and increased risk of mortality.21 Patients with cancer who have difficulty with ADLs are at increased risk for falls, which can limit their functional independence, compromise cancer therapy, and increase the risk of chemotherapy toxicities.11 Impaired hearing and poor vision are added factors that can be barriers to cancer treatment.
Cognition
Cognitive impairment in patients with cancer is becoming more of an issue for oncology HCPs as both cancer and cognitive decline are more common with advancing age. Cognition in cancer patients is important for understanding their diagnosis, prognosis, treatment options, and adherence. Impaired cognition can affect decision making regarding treatment options and administration. Cognition can be assessed through validated screening tools such as the Mini-Mental State Examination and Mini-Cog.11
Psychological and Social Status
A cancer diagnosis has a major impact on the mental and emotional state of patients and family members. Clinically significant anxiety has been reported in approximately 21% of older patients with cancer, and the incidence of depression ranges from 17 to 26%.22 In older patients with, psychologic distress can impact cancer treatment, resulting in less definitive therapy and poorer outcomes.23 All patients with cancer should be screened for psychologic distress using standardized methods, such as the Geriatric Depression Scale or the General Anxiety Disorder-7 scale.24 A positive screen should lead to additional assessments that evaluate the severity of depression and other comorbid psychological problems and medical conditions.
Social isolation and loneliness are factors that can affect both depression and anxiety. Older patients with cancer are at risk for decreased social activities and are already challenged with issues related to home care, comorbidities, functional status, and caregiver support.23 Therefore, it is important to assess the social interactions of an older and/or frail patient with cancer and use social work assistance to address needs for supportive services.
Nutrition
Nutrition is important in any patient with cancer undergoing chemotherapy treatment. However, it is of greater importance in older adults, as malnutrition and weight loss are negative prognostic factors that correlate with poor tolerance to chemotherapy treatment, decline in quality of life, and increased mortality.25 The Mini-Nutritional Assessment is a widely used validated tool to assess nutritional status and risk of malnutrition.11 This tool can help identify those older and/or frail patients with cancer with impaired nutritional status and aid in instituting corrective measures to treat or prevent malnutrition.
Effectiveness of CGA
Multiple randomized controlled clinical trials assessing the effectiveness of CGA have been conducted over the past 3 decades with overall positive outcomes related to its value.26 Benefits of CGA can include overall improved medical care, avoidance of hospitalization or nursing home placement, identification of cognitive impairment, and prevention of geriatric syndrome (a range of conditions representing multiple organ impairment in older adults).27
In oncology, CGA is particularly beneficial, as it can identify issues in nearly 70% of patients that may not be apparent through traditional oncology assessment.28 A systematic review of 36 studies assessing the prognostic value of CGA in elderly patients with cancer receiving chemotherapy concluded that impaired performance and functional status as well as a frail and vulnerable profile are important predictors of severe chemotherapy-related toxicity and are associated with a higher risk of mortality.29 Therefore, CGA should be an integral part of the evaluation of older and/or frail patients with cancer prior to chemotherapy consideration.
Several screening tools have been developed using information from CGA to assess the risk of severe toxicities. The most commonly used tools for predicting toxicity include the Cancer and Aging Research Group (CARG) chemotoxicity calculator and the Chemotherapy Risk Assessment Scale for High-Age Patients (CRASH).30,31 Although these tools are readily available to facilitate CGA, and despite their proven beneficial outcome and recommended usage by national guidelines, implementation of these tools in routine oncology practice has been challenging and slow to spread. Unless these recommended interventions are effectively implemented, the benefits of CGA cannot be realized. With the expected surge in the number of older patients with cancer, hopefully this will change.
Geriatric Assessment Screening Tools
A screening tool recommended for use in older and/or frail patients with cancer allows for a brief assessment to help clinicians identify patients in need of further evaluation by CGA and to provides information on treatment-related toxicities, functional decline, and survival.32 The predictive value and utility of geriatric assessment screening tools have been repeatedly proven to identify older and/or frail adults at risk for treatment-related toxicities.12 The CARG and the CRASH are validated screening tools used in identifying patients at higher risk for chemotherapy toxicity. These screening tools are intended to provide guidance to the clinical oncology practitioner on risk stratification of chemotherapy toxicity in older patients with cancer.33
Both of these screening tools provide similar predictive performance for chemotherapy toxicity in older patients with cancer.34 However, the CARG tool seems to have the advantage of using more data that had already been obtained during regular office visits and is clear and easy to use clinically. The CRASH tool is slightly more involved, as it uses multiple geriatric instruments to determine the predictive risk of both hematologic and nonhematologic toxicities of chemotherapy.
CARG Chemotoxicity Calculator
Hurria and colleagues originally developed the CARG tool from data obtained through a prospective multicenter study involving 500 patients with cancer aged ≥ 65 years.35 They concluded that chemotherapy-related toxicity is common in older adults, with 53% of patients sustaining grade 3 or 4 treatment-related toxicities and 2% treatment-related mortality.12 This predictive model for chemotherapy-related toxicity used 11 variables, both objective (obtained during a regular clinical encounter: age, tumor type, chemotherapy dosing, number of drugs, creatinine, and hemoglobin) and subjective (completed by patient: number of falls, social support, the ability to take medications, hearing impairment, and physical performance), to determine at-risk patients (Table 1).31
Compared with standard performance status measures in oncology practice, the CARG model was better able to predict chemotherapy-related toxicities. In 2016, Hurria and colleagues published the results of an updated external validation study with a cohort of 250 older patients with cancer receiving chemotherapy that confirmed the prediction of chemotherapy toxicity using the CARG screening tool in this population.31 An appealing feature of this tool is the free online accessibility and the expedited manner in which screening can be conducted.
CRASH Score
The CRASH score was derived from the results of a prospective, multicenter study of 518 patients aged ≥ 70 years who were assessed on 24 parameters prior to starting chemotherapy.30 A total of 64% of patients experienced significant toxicities, including 32% with grade 4 hematologic toxicity and 56% with grade 3 or 4 nonhematologic toxicity. The hematologic and nonhematologic toxicity risks are the 2 categories that comprise the CRASH score. Both baseline patient variables and chemotherapy regimen are incorporated into an 8-item assessment profile that determines the risk categories (Table 2).30
Increased risk of hematologic toxicities was associated with increased diastolic blood pressure, increased lactate dehydrogenase, need for assistance with IADL, and increased toxicity potential of the chemotherapy regimen. Nonhematologic toxicities were associated with ECOG performance score, Mini Mental Status Examination and Mini-Nutritional Assessment, and increased toxicity of the chemotherapy regimen.12 Patient scores are stratified into 4 risk categories: low, medium-low, medium-high, and high.30 Like the CARG tool, the CRASH screening tool also is available as a free online resource and can be used in everyday clinical practice to assess older and/or frail adults with cancer.
Conclusions
In older adults, cancer may significantly impact the natural course of concurrent comorbidities due to physiologic and functional changes. These vulnerabilities predispose older patients with cancer to an increased risk of adverse outcomes, including treatment-related toxicities.36 Given the rapidly aging population, it is critical for oncology clinical teams to be prepared to assess for, prevent, and manage issues for older adults that could impact outcomes, including complications and toxicities from chemotherapy.35 Studies have reported that 78 to 93% of older oncology patients have at least 1 geriatric impairment that could potentially impact oncology treatment plans.37,38 This supports the utility of CGA as a global assessment tool to risk stratify older and/or frail patients prior to deciding on subsequent oncologic treatment approaches.5 In fact, major cooperative groups sponsored by the National Cancer Institute, such as the Alliance for Clinical Trials in Oncology, are including CGA as part of some of their treatment trials. CGA was conducted as part of a multicenter cooperative group study in older patients with acute myeloid leukemia prior to inpatient intensive induction chemotherapy and was determined to be feasible and useful in clinical trials and practice.39
Despite the increasing evidence for benefits of CGA, it has not been a consistent part of oncology practices, and few HCPs are familiar with the benefits of CGA screening tools. Although oncology providers routinely participate in every aspect of cancer care and play a vital role in the coordination and management of older patients with cancer, CGA implementation into routine clinical practice has been slow in part due to lack of knowledge and training regarding the use of GA tools.
Oncology providers can easily incorporate CGA screening tools into the history and physical examination process for older patients with cancer, which will add an important dimension to these patient evaluations. Oncology providers are not only well positioned to administer these screening tools, but also can lead the field in developing innovative ways for effective implementation in busy routine oncology clinics. However, to be successful, oncology providers must be knowledgeable about these tools and understand their utility in guiding treatment decisions and improving quality of care in older patients with cancer.
1. Sharless NE. The challenging landscape of cancer and aging: charting a way forward. Published January 24, 2018. Accessed April 16, 2021. https://www.cancer.gov/news-events/cancer-currents-blog/2018/sharpless-aging-cancer-research
2. National Cancer Institute. Age and cancer risk. Updated March 5, 2021. Accessed April 16, 2021. https://www.cancer.gov/about-cancer/causes-prevention/risk/age
3. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin. 2019;69(1):7-34. doi:10.3322/caac.21551 4. Sawhney R, Sehl M, Naeim A. Physiologic aspects of aging: impact on cancer management and decision making, part I. Cancer J. 2005;11(6):449-460. doi:10.1097/00130404-200511000-00004
5. Kenis C, Bron D, Libert Y, et al. Relevance of a systematic geriatric screening and assessment in older patients with cancer: results of a prospective multicentric study. Ann Oncol. 2013;24(5):1306-1312. doi:10.1093/annonc/mds619
6. Loh KP, Soto-Perez-de-Celis E, Hsu T, et al. What every oncologist should know about geriatric assessment for older patients with cancer: Young International Society of Geriatric Oncology position paper. J Oncol Pract. 2018;14(2):85-94. doi:10.1200/JOP.2017.026435
7. Cohen HJ. Evolution of geriatric assessment in oncology. J Oncol Pract. 2018;14(2):95-96. doi:10.1200/JOP.18.00017
8. Wildiers H, Heeren P, Puts M, et al. International Society of Geriatric Oncology consensus on geriatric assessment in older patients with cancer. J Clin Oncol. 2014;32(24):2595-2603. doi:10.1200/JCO.2013.54.8347
9. American Cancer Society. Cancer facts & figures 2019. Accessed April 16, 2021. https://www.cancer.org/research/cancer-facts-statistics/all-cancer-facts-figures/cancer-facts-figures-2019.html
10. Williams GR, Mackenzie A, Magnuson A, et al. Comorbidity in older adults with cancer. J Geriatr Oncol. 2016;7(4):249-257. doi:10.1016/j.jgo.2015.12.002
11. Korc-Grodzicki B, Holmes HM, Shahrokni A. Geriatric assessment for oncologists. Cancer Biol Med. 2015;12(4):261-274. doi:10.7497/j.issn.2095-3941.2015.0082
12. Li D, Soto-Perez-de-Celis E, Hurria A. Geriatric assessment and tools for predicting treatment toxicity in older adults with cancer. Cancer J. 2017;23(4):206-210. doi:10.1097/PPO.0000000000000269
13. Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987;40(5):373-383. doi:10.1016/0021-9681(87)90171-8
14. Huang Y, Gou R, Diao Y, et al. Charlson comorbidity index helps predict the risk of mortality for patients with type 2 diabetic nephropathy. J Zhejiang Univ Sci B. 2014;15(1):58-66. doi:10.1631/jzus.B1300109
15. Osborn KP IV, Nothelle S, Slaven JE, Montz K, Hui S, Torke AM. Cumulative Illness Rating Scale (CIRS) can be used to predict hospital outcomes in older adults. J Geriatric Med Gerontol. 2017;3(2). doi:10.23937/2469-5858/1510030
16. Maher RL, Hanlon J, Hajjar ER. Clinical consequences of polypharmacy in elderly. Expert Opin Drug Saf. 2014;13(1):57-65. doi:10.1517/14740338.2013.827660
17. Shrestha S, Shrestha S, Khanal S. Polypharmacy in elderly cancer patients: challenges and the way clinical pharmacists can contribute in resource-limited settings. Aging Med. 2019;2(1):42-49. doi:10.1002/agm2.12051
18. Sharma M, Loh KP, Nightingale G, Mohile SG, Holmes HM. Polypharmacy and potentially inappropriate medication use in geriatric oncology. J Geriatr Oncol. 2016;7(5):346-353. doi:10.1016/j.jgo.2016.07.010
19. Norburn JE, Bernard SL, Konrad TR, et al. Self-care and assistance from others in coping with functional status limitations among a national sample of older adults. J Gerontol B Psychol Sci Soc Sci. 1995;50(2):S101-S109. doi:10.1093/geronb/50b.2.s101
20. Fragala MS, Alley DE, Shardell MD, et al. Comparison of handgrip and leg extension strength in predicting slow gait speed in older adults. J Am Geriatr Soc. 2016;64(1):144-150. doi:10.1111/jgs.13871
21. Owusu C, Berger NA. Comprehensive geriatric assessment in the older cancer patient: coming of age in clinical cancer care. Clin Pract (Lond). 2014;11(6):749-762. doi:10.2217/cpr.14.72
22. Weiss Wiesel TR, Nelson CJ, Tew WP, et al. The relationship between age, anxiety, and depression in older adults with cancer. Psychooncology. 2015;24(6):712-717. doi:10.1002/pon.3638
23. Soto-Perez-de-Celis E, Li D, Yuan Y, Lau YM, Hurria A. Functional versus chronological age: geriatric assessments to guide decision making in older patients with cancer. Lancet Oncol. 2018;19(6):e305-e316. doi:10.1016/S1470-2045(18)30348-6
24. Andersen BL, DeRubeis RJ, Berman BS, et al. Screening, assessment, and care of anxiety and depressive symptoms in adults with cancer: an American Society of Clinical Oncology guideline adaptation. J Clin Oncol. 2014;32(15):1605-1619. doi:10.1200/JCO.2013.52.4611
25. Muscaritoli M, Lucia S, Farcomeni A, et al. Prevalence of malnutrition in patients at first medical oncology visit: the PreMiO study. Oncotarget. 2017;8(45):79884-79886. doi:10.18632/oncotarget.20168
26. Ekdahl AW, Axmon A, Sandberg M, Steen Carlsson K. Is care based on comprehensive geriatric assessment with mobile teams better than usual care? A study protocol of a randomised controlled trial (the GerMoT study). BMJ Open. 2018;8(10)e23969. doi:10.1136/bmjopen-2018-023969
27. Mohile SG, Dale W, Somerfield MR, et al. Practical assessment and management of vulnerabilities in older patients receiving chemotherapy: ASCO guideline for geriatric oncology. J Clin Oncol. 2018;36(22):2326-2347. doi:10.1200/JCO.2018.78.8687
28. Hernandez Torres C, Hsu T. Comprehensive geriatric assessment in the older adult with cancer: a review. Eur Urol Focus. 2017;3(4-5):330-339. doi:10.1016/j.euf.2017.10.010
29. Janssens K, Specenier P. The prognostic value of the comprehensive geriatric assessment (CGA) in elderly cancer patients (ECP) treated with chemotherapy (CT): a systematic review. Eur J Cancer. 2017;72(1):S164-S165. doi:10.1016/S0959-8049(17)30611-1
30. Extermann M, Boler I, Reich RR, et al. Predicting the risk of chemotherapy toxicity in older patients: The Chemotherapy Risk Assessment Scale for High‐Age Patients (CRASH) score. Cancer. 2012;118(13):3377-3386. doi:10.1002/cncr.26646
31. Hurria A, Mohile S, Gajra A, et al. Validation of a prediction tool for chemotherapy toxicity in older adults with cancer. J Clin Oncol. 2016;34(20):2366-2371. doi:10.1200/JCO.2015.65.4327
32. Decoster L, Van Puyvelde K, Mohile S, et al. Screening tools for multidimensional health problems warranting a geriatric assessment in older cancer patients: an update on SIOG recommendations. Ann Oncol. 2015;26(2):288-300. doi:10.1093/annonc/mdu210
33. Schiefen JK, Madsen LT, Dains JE. Instruments that predict oncology treatment risk in the senior population. J Adv Pract Oncol. 2017;8(5):528-533.
34. Ortland I, Mendel Ott M, Kowar M, et al. Comparing the performance of the CARG and the CRASH score for predicting toxicity in older patients with cancer. J Geriatr Oncol. 2020;11(6):997-1005. doi:10.1016/j.jgo.2019.12.016
35. Hurria A, Togawa K, Mohile SG, et al. Predicting chemotherapy toxicity in older adults with cancer: a prospective multicenter study. J Clin Oncol. 2011;29(25):3457-3465. doi:10.1200/JCO.2011.34.7625
36. Mohile SG, Velarde C, Hurria A, et al. Geriatric assessment-guided care processes for older adults: a Delphi consensus of geriatric oncology experts. J Natl Compr Canc Netw. 2015;13(9):1120-1130. doi:10.6004/jnccn.2015.0137
37. Schiphorst AHW, Ten Bokkel Huinink D, Breumelhof R, Burgmans JPJ, Pronk A, Hamaker ME. Geriatric consultation can aid in complex treatment decisions for elderly cancer patients. Eur J Cancer Care (Engl). 2016;25(3):365-370. doi:10.1111/ecc.12349
38. Schulkes KJG, Souwer ETD, Hamaker ME, et al. The effect of a geriatric assessment on treatment decisions for patients with lung cancer. Lung. 2017;195(2):225-231. doi:10.1007/s00408-017-9983-7
39. Klepin HD, Ritchie E, Major-Elechi B, et al. Geriatric assessment among older adults receiving intensive therapy for acute myeloid leukemia: report of CALGB 361006 (Alliance). J Geriatr Oncol. 2020;11(1):107-113. doi:10.1016/j.jgo.2019.10.002
Age is a well recognized risk factor for cancer development. The population of older Americans is growing, and by 2030, 20% of the US population will be aged ≥ 65 years.1 While 25% of all new cancer cases are diagnosed in people aged 65 to 74 years, more than half of cancers occur in individuals aged ≥ 70 years, with even higher rates in those aged ≥ 75 years.2 Although cancer rates have declined slightly overall among people aged ≥ 65 years, this population still has an 11-fold increased incidence of cancer compared with that of younger individuals.3 With a rapidly growing older population, there will be increasing demand for cancer care.
Treatment of cancer in older individuals often is complicated by medical comorbidities, frailty, and poor functional status. Distinguishing patients who can tolerate aggressive therapy from those who require less intensive therapy can be challenging. Age-related physiologic changes predispose older adults to an increased risk of therapy-related toxicities, resulting in suboptimal therapeutic benefit and substantial morbidity. For example, cardiovascular changes can lead to reduction of the cardiac functional reserve, which can increase the risk of congestive heart failure. Similarly, decline in renal function leads to an increased potential for nephrotoxicity.4 Although patients may be of the same chronologic age, their performance, functional, and biologic status may be quite variable; thus, tolerance to aggressive treatment is not easily predicted. The comprehensive geriatric assessment (CGA) may be used as a global assessment tool to risk stratify older patients prior to oncologic treatment decisions.
Health care providers (HCPs), including physician assistants, nurse practitioners, clinical nurse specialists, nurses, and physicians, routinely participate in every aspect of cancer care by ordering and interpreting diagnostic tests, addressing comorbidities, managing symptoms, and discussing cancer treatment recommendations. HCPs in oncology will continue to play a vital role in the coordination and management of older patients with cancer. However, in general, CGA has not been a consistent part of oncology practices, and few HCPs are familiar with the benefits of CGA screening tools.
What Is Geriatric Assessment?
Geriatric assessment is a multidisciplinary, multidimensional process aimed at detecting medical, psychosocial, and functional issues of older adults that are not identified by traditional performance status measures alone. It provides guidance for management of identified problems and improvement in quality of life.6 CGA was developed by geriatricians and multidisciplinary care teams to evaluate the domains of functional, nutritional, cognitive, psychosocial, and economic status; comorbidities; geriatric syndromes; and mood, and it has been tested in both clinics and hospitals.7 Although such assessment requires additional time and resources, its goals are to identify areas of vulnerability, assist in clinical decisions of treatable health problems, and guide therapeutic interventions.6 In oncology practice, the assessment not only addresses these global issues, but also is critical in predicting toxicity and survival outcomes in older oncology patients.
Components of CGA
Advancing age brings many physiologic, psychosocial, and functional challenges, and a cancer diagnosis only adds to these issues. CGA provides a system of assessing older and/or frail patients with cancer through specific domains to identify issues that are not apparent on routine evaluation in a clinic setting before and during chemotherapy treatments. These domains include comorbidity, polypharmacy, functional status, cognition, psychological and social status, and nutrition.8
Comorbidity
The prevalence of multiple medical problems and comorbidities, including cancer, among people aged > 65 years is increasing.9 Studies have shown that two-thirds of patients with cancer had ≥ 2 medical conditions, and nearly one quarter had ≥ 4 medical conditions.10 In older adults, common comorbidities include cardiovascular disease, hypertension, diabetes mellitus, and dementia. These comorbidities can impact treatment decisions, increase the risk of disease, impact treatment-related complications, and affect a patient’s life expectancy.11 Assessing comorbidities is essential to CGA and is done using the Charlson Comorbidity Index and/or the Cumulative Illness Rating Scale.12
The Charlson Comorbidity Index was originally designed to predict 1-year mortality on the basis of a weighted composite score for the following categories: cardiovascular, endocrine, pulmonary, neurologic, renal, hepatic, gastrointestinal, and neoplastic disease.13 It is now the most widely used comorbidity index and has been adapted and verified as applicable and valid for predicting the outcomes and risk of death from many comorbid diseases.14 The Cumulative Illness Rating Scale has been validated as a predictor for readmission for hospitalized older adults, hospitalization within 1 year in a residential setting, and long-term mortality when assessed in inpatient and residential settings.15
Polypharmacy
Polypharmacy (use of ≥ 5 medications) is common in older patients regardless of cancer diagnosis and is often instead defined as “the use of multiple drugs or more than are medically necessary.”16 The use of multiple medications, including those not indicated for existing medical conditions (such as over‐the‐counter, herbal, and complementary/alternative medicines, which patients often fail to declare to their specialist, doctor, or pharmacist) adds to the potential negative aspects of polypharmacy that affect older patients.17
Patients with cancer usually are prescribed an extensive number of medicines, both for the disease and for supportive care, which can increase the chance of drug-drug interactions and adverse reactions.18 While these issues certainly affect quality of life, they also may influence chemotherapy treatment and potentially impact survival. Studies have shown that the presence of polypharmacy has been associated with higher numbers of comorbidities, increased use of inappropriate medications, poor performance status, decline in functional status, and poor survival.18
Functional Status
Although Eastern Cooperative Oncology Group (ECOG) performance status and Karnofsky Performance Status are commonly used by oncologists, these guidelines are limited in focus and do not reliably measure functional status in older patients. Functional status is determined by the ability to perform daily acts of self-care, which includes assessment of activities of daily living (ADLs) and instrumental activities of daily living (IADLs). ADLs refer to such tasks as bathing, dressing, eating, mobility, balance, and toileting.19 IADLs include the ability to perform activities required to live within a community and include shopping, transportation, managing finances, medication management, cooking, and cleaning.11
Physical functionality also can be assessed by measures such as gait speed, grip strength, balance, and lower extremity strength. These are more sensitive and shown to be associated with worse clinical outcomes.20 Grip strength and gait speed, as assessed by the Timed Up and Go test or the Short Physical Performance Battery measure strength and balance.12 Reduction in gait speed and/or grip strength are associated with adverse clinical outcomes and increased risk of mortality.21 Patients with cancer who have difficulty with ADLs are at increased risk for falls, which can limit their functional independence, compromise cancer therapy, and increase the risk of chemotherapy toxicities.11 Impaired hearing and poor vision are added factors that can be barriers to cancer treatment.
Cognition
Cognitive impairment in patients with cancer is becoming more of an issue for oncology HCPs as both cancer and cognitive decline are more common with advancing age. Cognition in cancer patients is important for understanding their diagnosis, prognosis, treatment options, and adherence. Impaired cognition can affect decision making regarding treatment options and administration. Cognition can be assessed through validated screening tools such as the Mini-Mental State Examination and Mini-Cog.11
Psychological and Social Status
A cancer diagnosis has a major impact on the mental and emotional state of patients and family members. Clinically significant anxiety has been reported in approximately 21% of older patients with cancer, and the incidence of depression ranges from 17 to 26%.22 In older patients with, psychologic distress can impact cancer treatment, resulting in less definitive therapy and poorer outcomes.23 All patients with cancer should be screened for psychologic distress using standardized methods, such as the Geriatric Depression Scale or the General Anxiety Disorder-7 scale.24 A positive screen should lead to additional assessments that evaluate the severity of depression and other comorbid psychological problems and medical conditions.
Social isolation and loneliness are factors that can affect both depression and anxiety. Older patients with cancer are at risk for decreased social activities and are already challenged with issues related to home care, comorbidities, functional status, and caregiver support.23 Therefore, it is important to assess the social interactions of an older and/or frail patient with cancer and use social work assistance to address needs for supportive services.
Nutrition
Nutrition is important in any patient with cancer undergoing chemotherapy treatment. However, it is of greater importance in older adults, as malnutrition and weight loss are negative prognostic factors that correlate with poor tolerance to chemotherapy treatment, decline in quality of life, and increased mortality.25 The Mini-Nutritional Assessment is a widely used validated tool to assess nutritional status and risk of malnutrition.11 This tool can help identify those older and/or frail patients with cancer with impaired nutritional status and aid in instituting corrective measures to treat or prevent malnutrition.
Effectiveness of CGA
Multiple randomized controlled clinical trials assessing the effectiveness of CGA have been conducted over the past 3 decades with overall positive outcomes related to its value.26 Benefits of CGA can include overall improved medical care, avoidance of hospitalization or nursing home placement, identification of cognitive impairment, and prevention of geriatric syndrome (a range of conditions representing multiple organ impairment in older adults).27
In oncology, CGA is particularly beneficial, as it can identify issues in nearly 70% of patients that may not be apparent through traditional oncology assessment.28 A systematic review of 36 studies assessing the prognostic value of CGA in elderly patients with cancer receiving chemotherapy concluded that impaired performance and functional status as well as a frail and vulnerable profile are important predictors of severe chemotherapy-related toxicity and are associated with a higher risk of mortality.29 Therefore, CGA should be an integral part of the evaluation of older and/or frail patients with cancer prior to chemotherapy consideration.
Several screening tools have been developed using information from CGA to assess the risk of severe toxicities. The most commonly used tools for predicting toxicity include the Cancer and Aging Research Group (CARG) chemotoxicity calculator and the Chemotherapy Risk Assessment Scale for High-Age Patients (CRASH).30,31 Although these tools are readily available to facilitate CGA, and despite their proven beneficial outcome and recommended usage by national guidelines, implementation of these tools in routine oncology practice has been challenging and slow to spread. Unless these recommended interventions are effectively implemented, the benefits of CGA cannot be realized. With the expected surge in the number of older patients with cancer, hopefully this will change.
Geriatric Assessment Screening Tools
A screening tool recommended for use in older and/or frail patients with cancer allows for a brief assessment to help clinicians identify patients in need of further evaluation by CGA and to provides information on treatment-related toxicities, functional decline, and survival.32 The predictive value and utility of geriatric assessment screening tools have been repeatedly proven to identify older and/or frail adults at risk for treatment-related toxicities.12 The CARG and the CRASH are validated screening tools used in identifying patients at higher risk for chemotherapy toxicity. These screening tools are intended to provide guidance to the clinical oncology practitioner on risk stratification of chemotherapy toxicity in older patients with cancer.33
Both of these screening tools provide similar predictive performance for chemotherapy toxicity in older patients with cancer.34 However, the CARG tool seems to have the advantage of using more data that had already been obtained during regular office visits and is clear and easy to use clinically. The CRASH tool is slightly more involved, as it uses multiple geriatric instruments to determine the predictive risk of both hematologic and nonhematologic toxicities of chemotherapy.
CARG Chemotoxicity Calculator
Hurria and colleagues originally developed the CARG tool from data obtained through a prospective multicenter study involving 500 patients with cancer aged ≥ 65 years.35 They concluded that chemotherapy-related toxicity is common in older adults, with 53% of patients sustaining grade 3 or 4 treatment-related toxicities and 2% treatment-related mortality.12 This predictive model for chemotherapy-related toxicity used 11 variables, both objective (obtained during a regular clinical encounter: age, tumor type, chemotherapy dosing, number of drugs, creatinine, and hemoglobin) and subjective (completed by patient: number of falls, social support, the ability to take medications, hearing impairment, and physical performance), to determine at-risk patients (Table 1).31
Compared with standard performance status measures in oncology practice, the CARG model was better able to predict chemotherapy-related toxicities. In 2016, Hurria and colleagues published the results of an updated external validation study with a cohort of 250 older patients with cancer receiving chemotherapy that confirmed the prediction of chemotherapy toxicity using the CARG screening tool in this population.31 An appealing feature of this tool is the free online accessibility and the expedited manner in which screening can be conducted.
CRASH Score
The CRASH score was derived from the results of a prospective, multicenter study of 518 patients aged ≥ 70 years who were assessed on 24 parameters prior to starting chemotherapy.30 A total of 64% of patients experienced significant toxicities, including 32% with grade 4 hematologic toxicity and 56% with grade 3 or 4 nonhematologic toxicity. The hematologic and nonhematologic toxicity risks are the 2 categories that comprise the CRASH score. Both baseline patient variables and chemotherapy regimen are incorporated into an 8-item assessment profile that determines the risk categories (Table 2).30
Increased risk of hematologic toxicities was associated with increased diastolic blood pressure, increased lactate dehydrogenase, need for assistance with IADL, and increased toxicity potential of the chemotherapy regimen. Nonhematologic toxicities were associated with ECOG performance score, Mini Mental Status Examination and Mini-Nutritional Assessment, and increased toxicity of the chemotherapy regimen.12 Patient scores are stratified into 4 risk categories: low, medium-low, medium-high, and high.30 Like the CARG tool, the CRASH screening tool also is available as a free online resource and can be used in everyday clinical practice to assess older and/or frail adults with cancer.
Conclusions
In older adults, cancer may significantly impact the natural course of concurrent comorbidities due to physiologic and functional changes. These vulnerabilities predispose older patients with cancer to an increased risk of adverse outcomes, including treatment-related toxicities.36 Given the rapidly aging population, it is critical for oncology clinical teams to be prepared to assess for, prevent, and manage issues for older adults that could impact outcomes, including complications and toxicities from chemotherapy.35 Studies have reported that 78 to 93% of older oncology patients have at least 1 geriatric impairment that could potentially impact oncology treatment plans.37,38 This supports the utility of CGA as a global assessment tool to risk stratify older and/or frail patients prior to deciding on subsequent oncologic treatment approaches.5 In fact, major cooperative groups sponsored by the National Cancer Institute, such as the Alliance for Clinical Trials in Oncology, are including CGA as part of some of their treatment trials. CGA was conducted as part of a multicenter cooperative group study in older patients with acute myeloid leukemia prior to inpatient intensive induction chemotherapy and was determined to be feasible and useful in clinical trials and practice.39
Despite the increasing evidence for benefits of CGA, it has not been a consistent part of oncology practices, and few HCPs are familiar with the benefits of CGA screening tools. Although oncology providers routinely participate in every aspect of cancer care and play a vital role in the coordination and management of older patients with cancer, CGA implementation into routine clinical practice has been slow in part due to lack of knowledge and training regarding the use of GA tools.
Oncology providers can easily incorporate CGA screening tools into the history and physical examination process for older patients with cancer, which will add an important dimension to these patient evaluations. Oncology providers are not only well positioned to administer these screening tools, but also can lead the field in developing innovative ways for effective implementation in busy routine oncology clinics. However, to be successful, oncology providers must be knowledgeable about these tools and understand their utility in guiding treatment decisions and improving quality of care in older patients with cancer.
Age is a well recognized risk factor for cancer development. The population of older Americans is growing, and by 2030, 20% of the US population will be aged ≥ 65 years.1 While 25% of all new cancer cases are diagnosed in people aged 65 to 74 years, more than half of cancers occur in individuals aged ≥ 70 years, with even higher rates in those aged ≥ 75 years.2 Although cancer rates have declined slightly overall among people aged ≥ 65 years, this population still has an 11-fold increased incidence of cancer compared with that of younger individuals.3 With a rapidly growing older population, there will be increasing demand for cancer care.
Treatment of cancer in older individuals often is complicated by medical comorbidities, frailty, and poor functional status. Distinguishing patients who can tolerate aggressive therapy from those who require less intensive therapy can be challenging. Age-related physiologic changes predispose older adults to an increased risk of therapy-related toxicities, resulting in suboptimal therapeutic benefit and substantial morbidity. For example, cardiovascular changes can lead to reduction of the cardiac functional reserve, which can increase the risk of congestive heart failure. Similarly, decline in renal function leads to an increased potential for nephrotoxicity.4 Although patients may be of the same chronologic age, their performance, functional, and biologic status may be quite variable; thus, tolerance to aggressive treatment is not easily predicted. The comprehensive geriatric assessment (CGA) may be used as a global assessment tool to risk stratify older patients prior to oncologic treatment decisions.
Health care providers (HCPs), including physician assistants, nurse practitioners, clinical nurse specialists, nurses, and physicians, routinely participate in every aspect of cancer care by ordering and interpreting diagnostic tests, addressing comorbidities, managing symptoms, and discussing cancer treatment recommendations. HCPs in oncology will continue to play a vital role in the coordination and management of older patients with cancer. However, in general, CGA has not been a consistent part of oncology practices, and few HCPs are familiar with the benefits of CGA screening tools.
What Is Geriatric Assessment?
Geriatric assessment is a multidisciplinary, multidimensional process aimed at detecting medical, psychosocial, and functional issues of older adults that are not identified by traditional performance status measures alone. It provides guidance for management of identified problems and improvement in quality of life.6 CGA was developed by geriatricians and multidisciplinary care teams to evaluate the domains of functional, nutritional, cognitive, psychosocial, and economic status; comorbidities; geriatric syndromes; and mood, and it has been tested in both clinics and hospitals.7 Although such assessment requires additional time and resources, its goals are to identify areas of vulnerability, assist in clinical decisions of treatable health problems, and guide therapeutic interventions.6 In oncology practice, the assessment not only addresses these global issues, but also is critical in predicting toxicity and survival outcomes in older oncology patients.
Components of CGA
Advancing age brings many physiologic, psychosocial, and functional challenges, and a cancer diagnosis only adds to these issues. CGA provides a system of assessing older and/or frail patients with cancer through specific domains to identify issues that are not apparent on routine evaluation in a clinic setting before and during chemotherapy treatments. These domains include comorbidity, polypharmacy, functional status, cognition, psychological and social status, and nutrition.8
Comorbidity
The prevalence of multiple medical problems and comorbidities, including cancer, among people aged > 65 years is increasing.9 Studies have shown that two-thirds of patients with cancer had ≥ 2 medical conditions, and nearly one quarter had ≥ 4 medical conditions.10 In older adults, common comorbidities include cardiovascular disease, hypertension, diabetes mellitus, and dementia. These comorbidities can impact treatment decisions, increase the risk of disease, impact treatment-related complications, and affect a patient’s life expectancy.11 Assessing comorbidities is essential to CGA and is done using the Charlson Comorbidity Index and/or the Cumulative Illness Rating Scale.12
The Charlson Comorbidity Index was originally designed to predict 1-year mortality on the basis of a weighted composite score for the following categories: cardiovascular, endocrine, pulmonary, neurologic, renal, hepatic, gastrointestinal, and neoplastic disease.13 It is now the most widely used comorbidity index and has been adapted and verified as applicable and valid for predicting the outcomes and risk of death from many comorbid diseases.14 The Cumulative Illness Rating Scale has been validated as a predictor for readmission for hospitalized older adults, hospitalization within 1 year in a residential setting, and long-term mortality when assessed in inpatient and residential settings.15
Polypharmacy
Polypharmacy (use of ≥ 5 medications) is common in older patients regardless of cancer diagnosis and is often instead defined as “the use of multiple drugs or more than are medically necessary.”16 The use of multiple medications, including those not indicated for existing medical conditions (such as over‐the‐counter, herbal, and complementary/alternative medicines, which patients often fail to declare to their specialist, doctor, or pharmacist) adds to the potential negative aspects of polypharmacy that affect older patients.17
Patients with cancer usually are prescribed an extensive number of medicines, both for the disease and for supportive care, which can increase the chance of drug-drug interactions and adverse reactions.18 While these issues certainly affect quality of life, they also may influence chemotherapy treatment and potentially impact survival. Studies have shown that the presence of polypharmacy has been associated with higher numbers of comorbidities, increased use of inappropriate medications, poor performance status, decline in functional status, and poor survival.18
Functional Status
Although Eastern Cooperative Oncology Group (ECOG) performance status and Karnofsky Performance Status are commonly used by oncologists, these guidelines are limited in focus and do not reliably measure functional status in older patients. Functional status is determined by the ability to perform daily acts of self-care, which includes assessment of activities of daily living (ADLs) and instrumental activities of daily living (IADLs). ADLs refer to such tasks as bathing, dressing, eating, mobility, balance, and toileting.19 IADLs include the ability to perform activities required to live within a community and include shopping, transportation, managing finances, medication management, cooking, and cleaning.11
Physical functionality also can be assessed by measures such as gait speed, grip strength, balance, and lower extremity strength. These are more sensitive and shown to be associated with worse clinical outcomes.20 Grip strength and gait speed, as assessed by the Timed Up and Go test or the Short Physical Performance Battery measure strength and balance.12 Reduction in gait speed and/or grip strength are associated with adverse clinical outcomes and increased risk of mortality.21 Patients with cancer who have difficulty with ADLs are at increased risk for falls, which can limit their functional independence, compromise cancer therapy, and increase the risk of chemotherapy toxicities.11 Impaired hearing and poor vision are added factors that can be barriers to cancer treatment.
Cognition
Cognitive impairment in patients with cancer is becoming more of an issue for oncology HCPs as both cancer and cognitive decline are more common with advancing age. Cognition in cancer patients is important for understanding their diagnosis, prognosis, treatment options, and adherence. Impaired cognition can affect decision making regarding treatment options and administration. Cognition can be assessed through validated screening tools such as the Mini-Mental State Examination and Mini-Cog.11
Psychological and Social Status
A cancer diagnosis has a major impact on the mental and emotional state of patients and family members. Clinically significant anxiety has been reported in approximately 21% of older patients with cancer, and the incidence of depression ranges from 17 to 26%.22 In older patients with, psychologic distress can impact cancer treatment, resulting in less definitive therapy and poorer outcomes.23 All patients with cancer should be screened for psychologic distress using standardized methods, such as the Geriatric Depression Scale or the General Anxiety Disorder-7 scale.24 A positive screen should lead to additional assessments that evaluate the severity of depression and other comorbid psychological problems and medical conditions.
Social isolation and loneliness are factors that can affect both depression and anxiety. Older patients with cancer are at risk for decreased social activities and are already challenged with issues related to home care, comorbidities, functional status, and caregiver support.23 Therefore, it is important to assess the social interactions of an older and/or frail patient with cancer and use social work assistance to address needs for supportive services.
Nutrition
Nutrition is important in any patient with cancer undergoing chemotherapy treatment. However, it is of greater importance in older adults, as malnutrition and weight loss are negative prognostic factors that correlate with poor tolerance to chemotherapy treatment, decline in quality of life, and increased mortality.25 The Mini-Nutritional Assessment is a widely used validated tool to assess nutritional status and risk of malnutrition.11 This tool can help identify those older and/or frail patients with cancer with impaired nutritional status and aid in instituting corrective measures to treat or prevent malnutrition.
Effectiveness of CGA
Multiple randomized controlled clinical trials assessing the effectiveness of CGA have been conducted over the past 3 decades with overall positive outcomes related to its value.26 Benefits of CGA can include overall improved medical care, avoidance of hospitalization or nursing home placement, identification of cognitive impairment, and prevention of geriatric syndrome (a range of conditions representing multiple organ impairment in older adults).27
In oncology, CGA is particularly beneficial, as it can identify issues in nearly 70% of patients that may not be apparent through traditional oncology assessment.28 A systematic review of 36 studies assessing the prognostic value of CGA in elderly patients with cancer receiving chemotherapy concluded that impaired performance and functional status as well as a frail and vulnerable profile are important predictors of severe chemotherapy-related toxicity and are associated with a higher risk of mortality.29 Therefore, CGA should be an integral part of the evaluation of older and/or frail patients with cancer prior to chemotherapy consideration.
Several screening tools have been developed using information from CGA to assess the risk of severe toxicities. The most commonly used tools for predicting toxicity include the Cancer and Aging Research Group (CARG) chemotoxicity calculator and the Chemotherapy Risk Assessment Scale for High-Age Patients (CRASH).30,31 Although these tools are readily available to facilitate CGA, and despite their proven beneficial outcome and recommended usage by national guidelines, implementation of these tools in routine oncology practice has been challenging and slow to spread. Unless these recommended interventions are effectively implemented, the benefits of CGA cannot be realized. With the expected surge in the number of older patients with cancer, hopefully this will change.
Geriatric Assessment Screening Tools
A screening tool recommended for use in older and/or frail patients with cancer allows for a brief assessment to help clinicians identify patients in need of further evaluation by CGA and to provides information on treatment-related toxicities, functional decline, and survival.32 The predictive value and utility of geriatric assessment screening tools have been repeatedly proven to identify older and/or frail adults at risk for treatment-related toxicities.12 The CARG and the CRASH are validated screening tools used in identifying patients at higher risk for chemotherapy toxicity. These screening tools are intended to provide guidance to the clinical oncology practitioner on risk stratification of chemotherapy toxicity in older patients with cancer.33
Both of these screening tools provide similar predictive performance for chemotherapy toxicity in older patients with cancer.34 However, the CARG tool seems to have the advantage of using more data that had already been obtained during regular office visits and is clear and easy to use clinically. The CRASH tool is slightly more involved, as it uses multiple geriatric instruments to determine the predictive risk of both hematologic and nonhematologic toxicities of chemotherapy.
CARG Chemotoxicity Calculator
Hurria and colleagues originally developed the CARG tool from data obtained through a prospective multicenter study involving 500 patients with cancer aged ≥ 65 years.35 They concluded that chemotherapy-related toxicity is common in older adults, with 53% of patients sustaining grade 3 or 4 treatment-related toxicities and 2% treatment-related mortality.12 This predictive model for chemotherapy-related toxicity used 11 variables, both objective (obtained during a regular clinical encounter: age, tumor type, chemotherapy dosing, number of drugs, creatinine, and hemoglobin) and subjective (completed by patient: number of falls, social support, the ability to take medications, hearing impairment, and physical performance), to determine at-risk patients (Table 1).31
Compared with standard performance status measures in oncology practice, the CARG model was better able to predict chemotherapy-related toxicities. In 2016, Hurria and colleagues published the results of an updated external validation study with a cohort of 250 older patients with cancer receiving chemotherapy that confirmed the prediction of chemotherapy toxicity using the CARG screening tool in this population.31 An appealing feature of this tool is the free online accessibility and the expedited manner in which screening can be conducted.
CRASH Score
The CRASH score was derived from the results of a prospective, multicenter study of 518 patients aged ≥ 70 years who were assessed on 24 parameters prior to starting chemotherapy.30 A total of 64% of patients experienced significant toxicities, including 32% with grade 4 hematologic toxicity and 56% with grade 3 or 4 nonhematologic toxicity. The hematologic and nonhematologic toxicity risks are the 2 categories that comprise the CRASH score. Both baseline patient variables and chemotherapy regimen are incorporated into an 8-item assessment profile that determines the risk categories (Table 2).30
Increased risk of hematologic toxicities was associated with increased diastolic blood pressure, increased lactate dehydrogenase, need for assistance with IADL, and increased toxicity potential of the chemotherapy regimen. Nonhematologic toxicities were associated with ECOG performance score, Mini Mental Status Examination and Mini-Nutritional Assessment, and increased toxicity of the chemotherapy regimen.12 Patient scores are stratified into 4 risk categories: low, medium-low, medium-high, and high.30 Like the CARG tool, the CRASH screening tool also is available as a free online resource and can be used in everyday clinical practice to assess older and/or frail adults with cancer.
Conclusions
In older adults, cancer may significantly impact the natural course of concurrent comorbidities due to physiologic and functional changes. These vulnerabilities predispose older patients with cancer to an increased risk of adverse outcomes, including treatment-related toxicities.36 Given the rapidly aging population, it is critical for oncology clinical teams to be prepared to assess for, prevent, and manage issues for older adults that could impact outcomes, including complications and toxicities from chemotherapy.35 Studies have reported that 78 to 93% of older oncology patients have at least 1 geriatric impairment that could potentially impact oncology treatment plans.37,38 This supports the utility of CGA as a global assessment tool to risk stratify older and/or frail patients prior to deciding on subsequent oncologic treatment approaches.5 In fact, major cooperative groups sponsored by the National Cancer Institute, such as the Alliance for Clinical Trials in Oncology, are including CGA as part of some of their treatment trials. CGA was conducted as part of a multicenter cooperative group study in older patients with acute myeloid leukemia prior to inpatient intensive induction chemotherapy and was determined to be feasible and useful in clinical trials and practice.39
Despite the increasing evidence for benefits of CGA, it has not been a consistent part of oncology practices, and few HCPs are familiar with the benefits of CGA screening tools. Although oncology providers routinely participate in every aspect of cancer care and play a vital role in the coordination and management of older patients with cancer, CGA implementation into routine clinical practice has been slow in part due to lack of knowledge and training regarding the use of GA tools.
Oncology providers can easily incorporate CGA screening tools into the history and physical examination process for older patients with cancer, which will add an important dimension to these patient evaluations. Oncology providers are not only well positioned to administer these screening tools, but also can lead the field in developing innovative ways for effective implementation in busy routine oncology clinics. However, to be successful, oncology providers must be knowledgeable about these tools and understand their utility in guiding treatment decisions and improving quality of care in older patients with cancer.
1. Sharless NE. The challenging landscape of cancer and aging: charting a way forward. Published January 24, 2018. Accessed April 16, 2021. https://www.cancer.gov/news-events/cancer-currents-blog/2018/sharpless-aging-cancer-research
2. National Cancer Institute. Age and cancer risk. Updated March 5, 2021. Accessed April 16, 2021. https://www.cancer.gov/about-cancer/causes-prevention/risk/age
3. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin. 2019;69(1):7-34. doi:10.3322/caac.21551 4. Sawhney R, Sehl M, Naeim A. Physiologic aspects of aging: impact on cancer management and decision making, part I. Cancer J. 2005;11(6):449-460. doi:10.1097/00130404-200511000-00004
5. Kenis C, Bron D, Libert Y, et al. Relevance of a systematic geriatric screening and assessment in older patients with cancer: results of a prospective multicentric study. Ann Oncol. 2013;24(5):1306-1312. doi:10.1093/annonc/mds619
6. Loh KP, Soto-Perez-de-Celis E, Hsu T, et al. What every oncologist should know about geriatric assessment for older patients with cancer: Young International Society of Geriatric Oncology position paper. J Oncol Pract. 2018;14(2):85-94. doi:10.1200/JOP.2017.026435
7. Cohen HJ. Evolution of geriatric assessment in oncology. J Oncol Pract. 2018;14(2):95-96. doi:10.1200/JOP.18.00017
8. Wildiers H, Heeren P, Puts M, et al. International Society of Geriatric Oncology consensus on geriatric assessment in older patients with cancer. J Clin Oncol. 2014;32(24):2595-2603. doi:10.1200/JCO.2013.54.8347
9. American Cancer Society. Cancer facts & figures 2019. Accessed April 16, 2021. https://www.cancer.org/research/cancer-facts-statistics/all-cancer-facts-figures/cancer-facts-figures-2019.html
10. Williams GR, Mackenzie A, Magnuson A, et al. Comorbidity in older adults with cancer. J Geriatr Oncol. 2016;7(4):249-257. doi:10.1016/j.jgo.2015.12.002
11. Korc-Grodzicki B, Holmes HM, Shahrokni A. Geriatric assessment for oncologists. Cancer Biol Med. 2015;12(4):261-274. doi:10.7497/j.issn.2095-3941.2015.0082
12. Li D, Soto-Perez-de-Celis E, Hurria A. Geriatric assessment and tools for predicting treatment toxicity in older adults with cancer. Cancer J. 2017;23(4):206-210. doi:10.1097/PPO.0000000000000269
13. Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987;40(5):373-383. doi:10.1016/0021-9681(87)90171-8
14. Huang Y, Gou R, Diao Y, et al. Charlson comorbidity index helps predict the risk of mortality for patients with type 2 diabetic nephropathy. J Zhejiang Univ Sci B. 2014;15(1):58-66. doi:10.1631/jzus.B1300109
15. Osborn KP IV, Nothelle S, Slaven JE, Montz K, Hui S, Torke AM. Cumulative Illness Rating Scale (CIRS) can be used to predict hospital outcomes in older adults. J Geriatric Med Gerontol. 2017;3(2). doi:10.23937/2469-5858/1510030
16. Maher RL, Hanlon J, Hajjar ER. Clinical consequences of polypharmacy in elderly. Expert Opin Drug Saf. 2014;13(1):57-65. doi:10.1517/14740338.2013.827660
17. Shrestha S, Shrestha S, Khanal S. Polypharmacy in elderly cancer patients: challenges and the way clinical pharmacists can contribute in resource-limited settings. Aging Med. 2019;2(1):42-49. doi:10.1002/agm2.12051
18. Sharma M, Loh KP, Nightingale G, Mohile SG, Holmes HM. Polypharmacy and potentially inappropriate medication use in geriatric oncology. J Geriatr Oncol. 2016;7(5):346-353. doi:10.1016/j.jgo.2016.07.010
19. Norburn JE, Bernard SL, Konrad TR, et al. Self-care and assistance from others in coping with functional status limitations among a national sample of older adults. J Gerontol B Psychol Sci Soc Sci. 1995;50(2):S101-S109. doi:10.1093/geronb/50b.2.s101
20. Fragala MS, Alley DE, Shardell MD, et al. Comparison of handgrip and leg extension strength in predicting slow gait speed in older adults. J Am Geriatr Soc. 2016;64(1):144-150. doi:10.1111/jgs.13871
21. Owusu C, Berger NA. Comprehensive geriatric assessment in the older cancer patient: coming of age in clinical cancer care. Clin Pract (Lond). 2014;11(6):749-762. doi:10.2217/cpr.14.72
22. Weiss Wiesel TR, Nelson CJ, Tew WP, et al. The relationship between age, anxiety, and depression in older adults with cancer. Psychooncology. 2015;24(6):712-717. doi:10.1002/pon.3638
23. Soto-Perez-de-Celis E, Li D, Yuan Y, Lau YM, Hurria A. Functional versus chronological age: geriatric assessments to guide decision making in older patients with cancer. Lancet Oncol. 2018;19(6):e305-e316. doi:10.1016/S1470-2045(18)30348-6
24. Andersen BL, DeRubeis RJ, Berman BS, et al. Screening, assessment, and care of anxiety and depressive symptoms in adults with cancer: an American Society of Clinical Oncology guideline adaptation. J Clin Oncol. 2014;32(15):1605-1619. doi:10.1200/JCO.2013.52.4611
25. Muscaritoli M, Lucia S, Farcomeni A, et al. Prevalence of malnutrition in patients at first medical oncology visit: the PreMiO study. Oncotarget. 2017;8(45):79884-79886. doi:10.18632/oncotarget.20168
26. Ekdahl AW, Axmon A, Sandberg M, Steen Carlsson K. Is care based on comprehensive geriatric assessment with mobile teams better than usual care? A study protocol of a randomised controlled trial (the GerMoT study). BMJ Open. 2018;8(10)e23969. doi:10.1136/bmjopen-2018-023969
27. Mohile SG, Dale W, Somerfield MR, et al. Practical assessment and management of vulnerabilities in older patients receiving chemotherapy: ASCO guideline for geriatric oncology. J Clin Oncol. 2018;36(22):2326-2347. doi:10.1200/JCO.2018.78.8687
28. Hernandez Torres C, Hsu T. Comprehensive geriatric assessment in the older adult with cancer: a review. Eur Urol Focus. 2017;3(4-5):330-339. doi:10.1016/j.euf.2017.10.010
29. Janssens K, Specenier P. The prognostic value of the comprehensive geriatric assessment (CGA) in elderly cancer patients (ECP) treated with chemotherapy (CT): a systematic review. Eur J Cancer. 2017;72(1):S164-S165. doi:10.1016/S0959-8049(17)30611-1
30. Extermann M, Boler I, Reich RR, et al. Predicting the risk of chemotherapy toxicity in older patients: The Chemotherapy Risk Assessment Scale for High‐Age Patients (CRASH) score. Cancer. 2012;118(13):3377-3386. doi:10.1002/cncr.26646
31. Hurria A, Mohile S, Gajra A, et al. Validation of a prediction tool for chemotherapy toxicity in older adults with cancer. J Clin Oncol. 2016;34(20):2366-2371. doi:10.1200/JCO.2015.65.4327
32. Decoster L, Van Puyvelde K, Mohile S, et al. Screening tools for multidimensional health problems warranting a geriatric assessment in older cancer patients: an update on SIOG recommendations. Ann Oncol. 2015;26(2):288-300. doi:10.1093/annonc/mdu210
33. Schiefen JK, Madsen LT, Dains JE. Instruments that predict oncology treatment risk in the senior population. J Adv Pract Oncol. 2017;8(5):528-533.
34. Ortland I, Mendel Ott M, Kowar M, et al. Comparing the performance of the CARG and the CRASH score for predicting toxicity in older patients with cancer. J Geriatr Oncol. 2020;11(6):997-1005. doi:10.1016/j.jgo.2019.12.016
35. Hurria A, Togawa K, Mohile SG, et al. Predicting chemotherapy toxicity in older adults with cancer: a prospective multicenter study. J Clin Oncol. 2011;29(25):3457-3465. doi:10.1200/JCO.2011.34.7625
36. Mohile SG, Velarde C, Hurria A, et al. Geriatric assessment-guided care processes for older adults: a Delphi consensus of geriatric oncology experts. J Natl Compr Canc Netw. 2015;13(9):1120-1130. doi:10.6004/jnccn.2015.0137
37. Schiphorst AHW, Ten Bokkel Huinink D, Breumelhof R, Burgmans JPJ, Pronk A, Hamaker ME. Geriatric consultation can aid in complex treatment decisions for elderly cancer patients. Eur J Cancer Care (Engl). 2016;25(3):365-370. doi:10.1111/ecc.12349
38. Schulkes KJG, Souwer ETD, Hamaker ME, et al. The effect of a geriatric assessment on treatment decisions for patients with lung cancer. Lung. 2017;195(2):225-231. doi:10.1007/s00408-017-9983-7
39. Klepin HD, Ritchie E, Major-Elechi B, et al. Geriatric assessment among older adults receiving intensive therapy for acute myeloid leukemia: report of CALGB 361006 (Alliance). J Geriatr Oncol. 2020;11(1):107-113. doi:10.1016/j.jgo.2019.10.002
1. Sharless NE. The challenging landscape of cancer and aging: charting a way forward. Published January 24, 2018. Accessed April 16, 2021. https://www.cancer.gov/news-events/cancer-currents-blog/2018/sharpless-aging-cancer-research
2. National Cancer Institute. Age and cancer risk. Updated March 5, 2021. Accessed April 16, 2021. https://www.cancer.gov/about-cancer/causes-prevention/risk/age
3. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin. 2019;69(1):7-34. doi:10.3322/caac.21551 4. Sawhney R, Sehl M, Naeim A. Physiologic aspects of aging: impact on cancer management and decision making, part I. Cancer J. 2005;11(6):449-460. doi:10.1097/00130404-200511000-00004
5. Kenis C, Bron D, Libert Y, et al. Relevance of a systematic geriatric screening and assessment in older patients with cancer: results of a prospective multicentric study. Ann Oncol. 2013;24(5):1306-1312. doi:10.1093/annonc/mds619
6. Loh KP, Soto-Perez-de-Celis E, Hsu T, et al. What every oncologist should know about geriatric assessment for older patients with cancer: Young International Society of Geriatric Oncology position paper. J Oncol Pract. 2018;14(2):85-94. doi:10.1200/JOP.2017.026435
7. Cohen HJ. Evolution of geriatric assessment in oncology. J Oncol Pract. 2018;14(2):95-96. doi:10.1200/JOP.18.00017
8. Wildiers H, Heeren P, Puts M, et al. International Society of Geriatric Oncology consensus on geriatric assessment in older patients with cancer. J Clin Oncol. 2014;32(24):2595-2603. doi:10.1200/JCO.2013.54.8347
9. American Cancer Society. Cancer facts & figures 2019. Accessed April 16, 2021. https://www.cancer.org/research/cancer-facts-statistics/all-cancer-facts-figures/cancer-facts-figures-2019.html
10. Williams GR, Mackenzie A, Magnuson A, et al. Comorbidity in older adults with cancer. J Geriatr Oncol. 2016;7(4):249-257. doi:10.1016/j.jgo.2015.12.002
11. Korc-Grodzicki B, Holmes HM, Shahrokni A. Geriatric assessment for oncologists. Cancer Biol Med. 2015;12(4):261-274. doi:10.7497/j.issn.2095-3941.2015.0082
12. Li D, Soto-Perez-de-Celis E, Hurria A. Geriatric assessment and tools for predicting treatment toxicity in older adults with cancer. Cancer J. 2017;23(4):206-210. doi:10.1097/PPO.0000000000000269
13. Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987;40(5):373-383. doi:10.1016/0021-9681(87)90171-8
14. Huang Y, Gou R, Diao Y, et al. Charlson comorbidity index helps predict the risk of mortality for patients with type 2 diabetic nephropathy. J Zhejiang Univ Sci B. 2014;15(1):58-66. doi:10.1631/jzus.B1300109
15. Osborn KP IV, Nothelle S, Slaven JE, Montz K, Hui S, Torke AM. Cumulative Illness Rating Scale (CIRS) can be used to predict hospital outcomes in older adults. J Geriatric Med Gerontol. 2017;3(2). doi:10.23937/2469-5858/1510030
16. Maher RL, Hanlon J, Hajjar ER. Clinical consequences of polypharmacy in elderly. Expert Opin Drug Saf. 2014;13(1):57-65. doi:10.1517/14740338.2013.827660
17. Shrestha S, Shrestha S, Khanal S. Polypharmacy in elderly cancer patients: challenges and the way clinical pharmacists can contribute in resource-limited settings. Aging Med. 2019;2(1):42-49. doi:10.1002/agm2.12051
18. Sharma M, Loh KP, Nightingale G, Mohile SG, Holmes HM. Polypharmacy and potentially inappropriate medication use in geriatric oncology. J Geriatr Oncol. 2016;7(5):346-353. doi:10.1016/j.jgo.2016.07.010
19. Norburn JE, Bernard SL, Konrad TR, et al. Self-care and assistance from others in coping with functional status limitations among a national sample of older adults. J Gerontol B Psychol Sci Soc Sci. 1995;50(2):S101-S109. doi:10.1093/geronb/50b.2.s101
20. Fragala MS, Alley DE, Shardell MD, et al. Comparison of handgrip and leg extension strength in predicting slow gait speed in older adults. J Am Geriatr Soc. 2016;64(1):144-150. doi:10.1111/jgs.13871
21. Owusu C, Berger NA. Comprehensive geriatric assessment in the older cancer patient: coming of age in clinical cancer care. Clin Pract (Lond). 2014;11(6):749-762. doi:10.2217/cpr.14.72
22. Weiss Wiesel TR, Nelson CJ, Tew WP, et al. The relationship between age, anxiety, and depression in older adults with cancer. Psychooncology. 2015;24(6):712-717. doi:10.1002/pon.3638
23. Soto-Perez-de-Celis E, Li D, Yuan Y, Lau YM, Hurria A. Functional versus chronological age: geriatric assessments to guide decision making in older patients with cancer. Lancet Oncol. 2018;19(6):e305-e316. doi:10.1016/S1470-2045(18)30348-6
24. Andersen BL, DeRubeis RJ, Berman BS, et al. Screening, assessment, and care of anxiety and depressive symptoms in adults with cancer: an American Society of Clinical Oncology guideline adaptation. J Clin Oncol. 2014;32(15):1605-1619. doi:10.1200/JCO.2013.52.4611
25. Muscaritoli M, Lucia S, Farcomeni A, et al. Prevalence of malnutrition in patients at first medical oncology visit: the PreMiO study. Oncotarget. 2017;8(45):79884-79886. doi:10.18632/oncotarget.20168
26. Ekdahl AW, Axmon A, Sandberg M, Steen Carlsson K. Is care based on comprehensive geriatric assessment with mobile teams better than usual care? A study protocol of a randomised controlled trial (the GerMoT study). BMJ Open. 2018;8(10)e23969. doi:10.1136/bmjopen-2018-023969
27. Mohile SG, Dale W, Somerfield MR, et al. Practical assessment and management of vulnerabilities in older patients receiving chemotherapy: ASCO guideline for geriatric oncology. J Clin Oncol. 2018;36(22):2326-2347. doi:10.1200/JCO.2018.78.8687
28. Hernandez Torres C, Hsu T. Comprehensive geriatric assessment in the older adult with cancer: a review. Eur Urol Focus. 2017;3(4-5):330-339. doi:10.1016/j.euf.2017.10.010
29. Janssens K, Specenier P. The prognostic value of the comprehensive geriatric assessment (CGA) in elderly cancer patients (ECP) treated with chemotherapy (CT): a systematic review. Eur J Cancer. 2017;72(1):S164-S165. doi:10.1016/S0959-8049(17)30611-1
30. Extermann M, Boler I, Reich RR, et al. Predicting the risk of chemotherapy toxicity in older patients: The Chemotherapy Risk Assessment Scale for High‐Age Patients (CRASH) score. Cancer. 2012;118(13):3377-3386. doi:10.1002/cncr.26646
31. Hurria A, Mohile S, Gajra A, et al. Validation of a prediction tool for chemotherapy toxicity in older adults with cancer. J Clin Oncol. 2016;34(20):2366-2371. doi:10.1200/JCO.2015.65.4327
32. Decoster L, Van Puyvelde K, Mohile S, et al. Screening tools for multidimensional health problems warranting a geriatric assessment in older cancer patients: an update on SIOG recommendations. Ann Oncol. 2015;26(2):288-300. doi:10.1093/annonc/mdu210
33. Schiefen JK, Madsen LT, Dains JE. Instruments that predict oncology treatment risk in the senior population. J Adv Pract Oncol. 2017;8(5):528-533.
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Screening High-Risk Women Veterans for Breast Cancer
The number of women seeking care from the Veterans Health Administration (VHA) is increasing.1 In 2015, there were 2 million women veterans in the United States, which is 9.4% of the total veteran population. This group is expected to increase at an average of about 18,000 women per year for the next 10 years.2 The percentage of women veterans who are US Department of Veterans Affairs (VA) users aged 45 to 64 years rose 46% from 2000 to 2015.1,3-4 It is estimated that 15% of veterans who used VA services in 2020 were women.1 Nineteen percent of women veterans are Black.1 The median age of women veterans in 2015 was 50 years.5 Breast cancer is the leading cancer affecting female veterans, and data suggest they have an increased risk of breast cancer based on unique service-related exposures.1,6-9
In the US, about 10 million women are eligible for breast cancer preventive therapy, including, but not limited to, medications, surgery, or lifestyle changes.10 Secondary prevention options include change in surveillance that can reduce their risk or identify cancer at an earlier stage when treatment is more effective. The United States Preventive Services Task Force, the National Comprehensive Cancer Network, the American Society for Clinical Oncology, the National Institute for Health and Care Excellence, and the Oncology Nursing Society recommend screening women aged ≥ 35 years to assess breast cancer risk.11-18 If a woman is at increased risk, she may be a candidate for chemoprevention, prozphylactic surgery, and possibly an enhanced screening regimen.
Urban and minority women are an understudied population. Most veterans (75%) live in urban or suburban settings.19,20 Urban veteran women constitute an important potential study population.
Chemoprevention measures have been underused because of factors involving both women and their health care providers. A large proportion of women are unaware of their higher risk status due to lack of adequate screening and risk assessment.21,22 In addition to patient lack of awareness of their high-risk status, primary care physicians are also reluctant to prescribe chemopreventive agents due to a lack of comfort or familiarity with the risks and benefits.23-26 The STAR2015, BCPT2005, IBIS2014, MAP3 2011, IBIS-I 2014, and IBIS II 2014 studies clearly demonstrate a 49 to 62% reduction in risk for women using chemoprevention such as selective estrogen receptor modulators or aromatase inhibitors, respectively.27-32 Yet only 4 to 9% of high-risk women not enrolled in a clinical trial are using chemoprevention.33-39
The possibility of developing breast cancer also may be increased because of a positive family history or being a member of a family in which there is a known susceptibility gene mutation.40 Based on these risk factors, women may be eligible for tailored follow-up and genetic counseling.41-44
Nationally, 7 to 10% of the civilian US population will experience posttraumatic stress disorder (PTSD).45 The rates are remarkably higher for women veterans, with roughly 20% diagnosed with PTSD.46,47 Anxiety and PTSD have been implicated in poor adherence to medical advice.48,49
In 2014, a national VA multidisciplinary group focused on breast cancer prevention, detection, treatment, and research to address breast health in the growing population of women veterans. High-risk breast cancer screenings are not routinely carried out by the VA in primary care, women’s health, or oncology services. Furthermore, the recording of screening questionnaire results was not synchronized until a standard questionnaire was created and approved as a template by this group in the VA electronic medical record (EMR) in 2015.
Several prediction models can identify which women are at an increased risk of developing breast cancer. The most commonly used risk assessment model, the Gail breast cancer risk assessment tool (BCRAT), has been refined to include women of additional ethnicities (https://www.cancer.gov/bcrisktool).
This pilot project was launched to identify an effective manner to screen women veterans regarding their risk of developing breast cancer and refer them for chemoprevention education or genetic counseling as appropriate.
Methods
A high-risk breast cancer screening questionnaire based on the Gail BCRAT and including lifestyle questions was developed and included as a note template in the VA EMR. The James J. Peters VA Medical Center, Bronx, NY (JJPVAMC) and the Washington DC VA Medical Center (DCVAMC) ran a pilot study between 2015 and 2018 using this breast cancer screening questionnaire to collect data from women veterans. Quality Executive Committee and institutional review board approvals were granted respectively.
Eligibility criteria included women aged ≥ 35 years with no personal history of breast cancer. Most patients were self-referred, but participants also were recruited during VA Breast Cancer Awareness month events, health fairs, or at informational tables in the hospital lobbies. After completing the 20 multiple choice questionnaire with a study team member, either in person or over the phone, a 5-year and lifetime risk of invasive breast cancer was calculated using the Gail BCRAT. A woman is considered high risk and eligible for chemoprevention if her 5-year risk is > 1.66% or her lifetime risk is ≥ 20%. Eligibility for genetic counseling is based on the Breast Cancer Referral Screening Tool, which includes a personal or family history of breast or ovarian cancer and Jewish ancestry.
All patients were notified of their average or high risk status by a clinician. Those who were deemed to be average risk received a follow-up letter in the mail with instructions (eg, to follow-up with a yearly mammogram). Those who were deemed to be high risk for developing breast cancer were asked to come in for an appointment with the study principal investigator (a VA oncologist/breast cancer specialist) to discuss prevention options, further screening, or referrals to genetic counseling. Depending on a patient’s other health factors, a woman at high risk for developing breast cancer also may be a candidate for chemoprevention with tamoxifen, raloxifene, exemestane, anastrozole, or letrozole.
Data on the participant’s lifestyle, including exercise, diet, and smoking, were evaluated to determine whether these factors had an impact on risk status.
Results
The JJP and DC VAMCs screened 103 women veterans between 2015 and 2018. Four patients were excluded for nonveteran (spousal) status, leaving 99 women veterans with a mean age of 54 years. The most common self-reported races were Black (60%), non-Hispanic White (14%), and Hispanic or Latino (13%) (Table 1).
Women veterans in our study were nearly 3-times more likely than the general population were to receive a high-risk Gail Score/BCRAT (35% vs 13%, respectively).50,51 Of this subset, 46% had breast biopsies, and 86% had a positive family history. Thirty-one percent of Black women in our study were high risk, while nationally, 8.2 to 13.3% of Black women aged 50 to 59 years are considered high risk.50,51 Of the Black high-risk group with a high Gail/BCRAT score, 94% had a positive family history, and 33% had a history of breast biopsy (Table 2).
Of the 35 high-risk patients 26 (74%) patients accepted consultations for chemoprevention and 5 (19%) started chemoprevention. Of this high-risk group, 13 (37%) patients were referred for genetic counseling (Table 3).44 The prevalence of PTSD was present in 31% of high-risk women and 29% of the cohort (Figure).The lifestyle questions indicated that, among all participants, 79% had an overweight or obese body mass index; 58% exercised weekly; 51% consumed alcohol; 14% were smokers; and 21% consumed 3 to 4 servings of fruits/vegetables daily.
Discussion
Breast cancer is the most common cancer in women.52 The number of women with breast cancer in the VHA has more than tripled from 1995 to 2012.1 The lifetime risk of developing breast cancer in the general population is about 13%.50 This rate can be affected by risk factors including age, hormone exposure, family history, radiation exposure, and lifestyle factors, such as weight and alcohol use.6,52-56 In the United States, invasive breast cancer affects 1 in 8 women.50,52,57
Our screened population showed nearly 3 times as many women veterans were at an increased risk for breast cancer when compared with historical averages in US women. This difference may be based on a high rate of prior breast biopsies or positive family history, although a provocative study using the Surveillance, Epidemiology, and End Results database showed military women to have higher rates of breast cancer as well.9 Historically, Blacks are vastly understudied in clinical research with only 5% representation on a national level.5,58 The urban locations of both pilot sites (Washington, DC and Bronx, NY) allowed for the inclusion of minority patients in our study. We found that the rates of breast cancer in Black women veterans to be higher than seen nationally, possibly prompting further screening initiatives for this understudied population.
Our pilot study’s chemoprevention utilization (19%) was double the < 10% seen in the national population.33-35 The presence of a knowledgeable breast health practitioner to recruit study participants and offer personalized counseling to women veterans is a likely factor in overcoming barriers to chemopreventive acceptance. These participants may have been motivated to seek care for their high-risk status given a strong family history and prior breast biopsies.
Interestingly, a 3-fold higher PTSD rate was seen in this pilot population (29%) when compared with PTSD rates in the general female population (7-10%) and still one-third higher than the general population of women veterans (20%).45-47 Mental health, anxiety, and PTSD have been barriers to patients who sought treatment and have been implicated in poor adherence to medical advice.48,49 Cancer screening can induce anxiety in patients, and it may be amplified in patients with PTSD. It was remarkable that although adherence with screening recommendations is decreased when PTSD is present, our patient population demonstrated a higher rate of screening adherence.
Women who are seen at the VA often use multiple clinical specialties, and their EMR can be accessed across VA medical centers nationwide. Therefore, identifying women veterans who meet screening criteria is easily attainable within the VA.
When comparing high-risk with average risk women, the lifestyle results (BMI, smoking history, exercise and consumption of fruits, vegetables and alcohol) were essentially the same. Lifestyle factors were similar to national population rates and were unlikely to impact risk levels.
Limitations
Study limitations included a high number of self-referrals and the large percentage of patients with a family history of breast cancer, making them more likely to seek screening. The higher-than-average risk of breast cancer may be driven by a high rate of breast biopsies and a strong family history. Lifestyle metrics could not be accurately compared to other national assessments of lifestyle factors due to the difference in data points that we used or the format of our questions.
Conclusions
As the number of women veterans increases and the incidence of breast cancer in women veterans rise, chemoprevention options should follow national guidelines. To our knowledge, this is the only oncology study with 60% Black women veterans. This study had a higher participation rate for Black women veterans than is typically seen in national research studies and shows the VA to be a germane source for further understanding of an understudied population that may benefit from increased screening for breast cancer.
A team-based, multidisciplinary model that meets the unique healthcare needs of women veterans results in a patient-centric delivery of care for assessing breast cancer risk status and prevention options. This model can be replicated nationally by directing primary care physicians and women’s health practitioners to a risk-assessment questionnaire and referring high-risk women for appropriate preventative care. Given that these results show chemoprevention adherence rates doubled those seen nationally, perhaps techniques used within this VA pilot study may be adapted to decrease breast cancer incidence nationally.
Since the rate of PTSD among women veterans is triple the national average, we would expect adherence rates to be lower in our patient cohort. However, the multidisciplinary approach we used in this study (eg, 1:1 consultation with oncologist; genetic counseling referrals; mental health support available), may have improved adherence rates. Perhaps the high rates of PTSD seen in the VA patient population can be a useful way to explore patient adherence rates in those with mental illness and medical conditions.
Future research with a larger cohort may lead to greater insight into the correlation between PTSD and adherence to treatment. Exploring the connection between breast cancer, epigenetics, and specific military service-related exposures could be an area of analysis among this veteran population exhibiting increased breast cancer rates. VAMCs are situated in rural, suburban, and urban locations across the United States and offers a diverse socioeconomic and ethnic patient population for inclusion in clinical investigations. Women veterans make up a small subpopulation of women in the United States, but it is worth considering VA patients as an untapped resource for research collaboration.
Acknowledgements
The authors thank Steven Sanchez and Marissa Vallette, PhD, Breast Health Research Group. This research project was approved by the James J. Peters VA Medical Center Quality Executive Committee and the Washington, DC VA Medical Center Institutional Review Board. This work was supported by the US Department of Veterans Affairs. This work did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.
Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the US Government, or any of its agencies.
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37. Goss PE, Ingle JN, Alés-Martínez JE, et al. Exemestane for breast-cancer prevention in postmenopausal women [published correction appears in N Engl J Med. 2011 Oct 6;365(14):1361]. N Engl J Med. 2011;364(25):2381-2391. doi:10.1056/NEJMoa1103507
38. Kmietowicz Z. Five in six women reject drugs that could reduce their risk of breast cancer. BMJ. 2015;351:h6650. Published 2015 Dec 8. doi:10.1136/bmj.h6650
39. Nelson HD, Fu R, Griffin JC, Nygren P, Smith ME, Humphrey L. Systematic review: comparative effectiveness of medications to reduce risk for primary breast cancer. Ann Intern Med. 2009;151(10):703-235. doi:10.7326/0003-4819-151-10-200911170-00147
40. Dahabreh IJ, Wieland LS, Adam GP, Halladay C, Lau J, Trikalinos TA. Core needle and open surgery biopsy for diagnosis of breast lesions: an update to the 2009 report. Published September 2014. Accessed April 12, 2021. https://www.ncbi.nlm.nih.gov/books/NBK246878
41. National Cancer Institute. Genetics of breast and ovarian cancer (PDQ)—health profession version. Updated February 12, 2021. Accessed April 12, 2021. http://www.cancer.gov/cancertopics/pdq/genetics/breast-and-ovarian/HealthProfessional
42. US Department of Health and Human Services. National Institutes of Health, National Institute of Environmental Health Sciences The sister study. Accessed April 12, 2021. https://sisterstudy.niehs.nih.gov/english/NIEHS.htm
43. Tutt A, Ashworth A. Can genetic testing guide treatment in breast cancer?. Eur J Cancer. 2008;44(18):2774-2780. doi:10.1016/j.ejca.2008.10.009
44. Katz SJ, Ward KC, Hamilton AS, et al. Gaps in receipt of clinically indicated genetic counseling after diagnosis of breast cancer. J Clin Oncol. 2018;36(12):1218-1224. doi:10.1200/JCO.2017.76.2369
45. US Department of Veterans Affairs. PTSD: National Center for PTSD. How common is PTSD in adults? Updated October 17, 2019. Accessed April 12, 2021. https://www.ptsd.va.gov/understand/common/common_adults.asp
46. US Department of Veterans Affairs. PTSD: National Center for PTSD. How common is PTSD in women? Updated October 16, 2019. Accessed April 12, 2021. https://www.ptsd.va.gov/understand/common/common_women.asp
47. US Department of Veterans Affairs. PTSD: National Center for PTSD. How common is PTSD in veterans? Updated September 24, 2018. Accessed April 12, 2021. https://www.ptsd.va.gov/understand/common/common_veterans.asp
48. Lindberg NM, Wellisch D. Anxiety and compliance among women at high risk for breast cancer. Ann Behav Med. 2001;23(4):298-303. doi:10.1207/S15324796ABM2304_9
49. DiMatteo MR, Lepper HS, Croghan TW. Depression is a risk factor for noncompliance with medical treatment: meta-analysis of the effects of anxiety and depression on patient adherence. Arch Intern Med. 2000;160(14):2101-2107. doi:10.1001/archinte.160.14.2101
50. Centers for Disease Control and Prevention. MMWR appendix: breast cancer rates among black women and white women. Updated October 13, 2016. Accessed April 12, 2021. https://www.cdc.gov/cancer/breast/statistics/trends_invasive.htm
51. Richardson LC, Henley SJ, Miller JW, Massetti G, Thomas CC. Patterns and trends in age-specific black-white differences in breast cancer incidence and mortality - United States, 1999-2014. MMWR Morb Mortal Wkly Rep. 2016;65(40):1093-1098. Published 2016 Oct 14. doi:10.15585/mmwr.mm6540a1
52. Brody JG, Moysich KB, Humblet O, Attfield KR, Beehler GP, Rudel RA. Environmental pollutants and breast cancer: epidemiologic studies. Cancer. 2007;109(12 Suppl):2667-2711. doi:10.1002/cncr.22655
53. Brophy JT, Keith MM, Watterson A, et al. Breast cancer risk in relation to occupations with exposure to carcinogens and endocrine disruptors: a Canadian case-control study. Environ Health. 2012;11:87. Published 2012 Nov 19. doi:10.1186/1476-069X-11-87
54. Labrèche F, Goldberg MS, Valois MF, Nadon L. Postmenopausal breast cancer and occupational exposures. Occup Environ Med. 2010;67(4):263-269. doi:10.1136/oem.2009.049817
55. National Institute of Environmental Health Sciences, Interagency Breast Cancer & Environmental Research Coordinating Committee. Breast cancer and the environment: prioritizing prevention. Updated March 8, 2013. Accessed April 12, 2021. https://www.niehs.nih.gov/about/boards/ibcercc/index.cfm
56. Gail MH, Costantino JP, Pee D, et al. Projecting individualized absolute invasive breast cancer risk in African American women [published correction appears in J Natl Cancer Inst. 2008 Aug 6;100(15):1118] [published correction appears in J Natl Cancer Inst. 2008 Mar 5;100(5):373]. J Natl Cancer Inst. 2007;99(23):1782-1792. doi:10.1093/jnci/djm223
57. Corbie-Smith G, Thomas SB, Williams MV, Moody-Ayers S. Attitudes and beliefs of African Americans toward participation in medical research. J Gen Intern Med. 1999;14(9):537-546. doi:10.1046/j.1525-1497.1999.07048.x
58. Braunstein JB, Sherber NS, Schulman SP, Ding EL, Powe NR. Race, medical researcher distrust, perceived harm, and willingness to participate in cardiovascular prevention trials. Medicine (Baltimore). 2008;87(1):1-9. doi:10.1097/MD.0b013e3181625d78
The number of women seeking care from the Veterans Health Administration (VHA) is increasing.1 In 2015, there were 2 million women veterans in the United States, which is 9.4% of the total veteran population. This group is expected to increase at an average of about 18,000 women per year for the next 10 years.2 The percentage of women veterans who are US Department of Veterans Affairs (VA) users aged 45 to 64 years rose 46% from 2000 to 2015.1,3-4 It is estimated that 15% of veterans who used VA services in 2020 were women.1 Nineteen percent of women veterans are Black.1 The median age of women veterans in 2015 was 50 years.5 Breast cancer is the leading cancer affecting female veterans, and data suggest they have an increased risk of breast cancer based on unique service-related exposures.1,6-9
In the US, about 10 million women are eligible for breast cancer preventive therapy, including, but not limited to, medications, surgery, or lifestyle changes.10 Secondary prevention options include change in surveillance that can reduce their risk or identify cancer at an earlier stage when treatment is more effective. The United States Preventive Services Task Force, the National Comprehensive Cancer Network, the American Society for Clinical Oncology, the National Institute for Health and Care Excellence, and the Oncology Nursing Society recommend screening women aged ≥ 35 years to assess breast cancer risk.11-18 If a woman is at increased risk, she may be a candidate for chemoprevention, prozphylactic surgery, and possibly an enhanced screening regimen.
Urban and minority women are an understudied population. Most veterans (75%) live in urban or suburban settings.19,20 Urban veteran women constitute an important potential study population.
Chemoprevention measures have been underused because of factors involving both women and their health care providers. A large proportion of women are unaware of their higher risk status due to lack of adequate screening and risk assessment.21,22 In addition to patient lack of awareness of their high-risk status, primary care physicians are also reluctant to prescribe chemopreventive agents due to a lack of comfort or familiarity with the risks and benefits.23-26 The STAR2015, BCPT2005, IBIS2014, MAP3 2011, IBIS-I 2014, and IBIS II 2014 studies clearly demonstrate a 49 to 62% reduction in risk for women using chemoprevention such as selective estrogen receptor modulators or aromatase inhibitors, respectively.27-32 Yet only 4 to 9% of high-risk women not enrolled in a clinical trial are using chemoprevention.33-39
The possibility of developing breast cancer also may be increased because of a positive family history or being a member of a family in which there is a known susceptibility gene mutation.40 Based on these risk factors, women may be eligible for tailored follow-up and genetic counseling.41-44
Nationally, 7 to 10% of the civilian US population will experience posttraumatic stress disorder (PTSD).45 The rates are remarkably higher for women veterans, with roughly 20% diagnosed with PTSD.46,47 Anxiety and PTSD have been implicated in poor adherence to medical advice.48,49
In 2014, a national VA multidisciplinary group focused on breast cancer prevention, detection, treatment, and research to address breast health in the growing population of women veterans. High-risk breast cancer screenings are not routinely carried out by the VA in primary care, women’s health, or oncology services. Furthermore, the recording of screening questionnaire results was not synchronized until a standard questionnaire was created and approved as a template by this group in the VA electronic medical record (EMR) in 2015.
Several prediction models can identify which women are at an increased risk of developing breast cancer. The most commonly used risk assessment model, the Gail breast cancer risk assessment tool (BCRAT), has been refined to include women of additional ethnicities (https://www.cancer.gov/bcrisktool).
This pilot project was launched to identify an effective manner to screen women veterans regarding their risk of developing breast cancer and refer them for chemoprevention education or genetic counseling as appropriate.
Methods
A high-risk breast cancer screening questionnaire based on the Gail BCRAT and including lifestyle questions was developed and included as a note template in the VA EMR. The James J. Peters VA Medical Center, Bronx, NY (JJPVAMC) and the Washington DC VA Medical Center (DCVAMC) ran a pilot study between 2015 and 2018 using this breast cancer screening questionnaire to collect data from women veterans. Quality Executive Committee and institutional review board approvals were granted respectively.
Eligibility criteria included women aged ≥ 35 years with no personal history of breast cancer. Most patients were self-referred, but participants also were recruited during VA Breast Cancer Awareness month events, health fairs, or at informational tables in the hospital lobbies. After completing the 20 multiple choice questionnaire with a study team member, either in person or over the phone, a 5-year and lifetime risk of invasive breast cancer was calculated using the Gail BCRAT. A woman is considered high risk and eligible for chemoprevention if her 5-year risk is > 1.66% or her lifetime risk is ≥ 20%. Eligibility for genetic counseling is based on the Breast Cancer Referral Screening Tool, which includes a personal or family history of breast or ovarian cancer and Jewish ancestry.
All patients were notified of their average or high risk status by a clinician. Those who were deemed to be average risk received a follow-up letter in the mail with instructions (eg, to follow-up with a yearly mammogram). Those who were deemed to be high risk for developing breast cancer were asked to come in for an appointment with the study principal investigator (a VA oncologist/breast cancer specialist) to discuss prevention options, further screening, or referrals to genetic counseling. Depending on a patient’s other health factors, a woman at high risk for developing breast cancer also may be a candidate for chemoprevention with tamoxifen, raloxifene, exemestane, anastrozole, or letrozole.
Data on the participant’s lifestyle, including exercise, diet, and smoking, were evaluated to determine whether these factors had an impact on risk status.
Results
The JJP and DC VAMCs screened 103 women veterans between 2015 and 2018. Four patients were excluded for nonveteran (spousal) status, leaving 99 women veterans with a mean age of 54 years. The most common self-reported races were Black (60%), non-Hispanic White (14%), and Hispanic or Latino (13%) (Table 1).
Women veterans in our study were nearly 3-times more likely than the general population were to receive a high-risk Gail Score/BCRAT (35% vs 13%, respectively).50,51 Of this subset, 46% had breast biopsies, and 86% had a positive family history. Thirty-one percent of Black women in our study were high risk, while nationally, 8.2 to 13.3% of Black women aged 50 to 59 years are considered high risk.50,51 Of the Black high-risk group with a high Gail/BCRAT score, 94% had a positive family history, and 33% had a history of breast biopsy (Table 2).
Of the 35 high-risk patients 26 (74%) patients accepted consultations for chemoprevention and 5 (19%) started chemoprevention. Of this high-risk group, 13 (37%) patients were referred for genetic counseling (Table 3).44 The prevalence of PTSD was present in 31% of high-risk women and 29% of the cohort (Figure).The lifestyle questions indicated that, among all participants, 79% had an overweight or obese body mass index; 58% exercised weekly; 51% consumed alcohol; 14% were smokers; and 21% consumed 3 to 4 servings of fruits/vegetables daily.
Discussion
Breast cancer is the most common cancer in women.52 The number of women with breast cancer in the VHA has more than tripled from 1995 to 2012.1 The lifetime risk of developing breast cancer in the general population is about 13%.50 This rate can be affected by risk factors including age, hormone exposure, family history, radiation exposure, and lifestyle factors, such as weight and alcohol use.6,52-56 In the United States, invasive breast cancer affects 1 in 8 women.50,52,57
Our screened population showed nearly 3 times as many women veterans were at an increased risk for breast cancer when compared with historical averages in US women. This difference may be based on a high rate of prior breast biopsies or positive family history, although a provocative study using the Surveillance, Epidemiology, and End Results database showed military women to have higher rates of breast cancer as well.9 Historically, Blacks are vastly understudied in clinical research with only 5% representation on a national level.5,58 The urban locations of both pilot sites (Washington, DC and Bronx, NY) allowed for the inclusion of minority patients in our study. We found that the rates of breast cancer in Black women veterans to be higher than seen nationally, possibly prompting further screening initiatives for this understudied population.
Our pilot study’s chemoprevention utilization (19%) was double the < 10% seen in the national population.33-35 The presence of a knowledgeable breast health practitioner to recruit study participants and offer personalized counseling to women veterans is a likely factor in overcoming barriers to chemopreventive acceptance. These participants may have been motivated to seek care for their high-risk status given a strong family history and prior breast biopsies.
Interestingly, a 3-fold higher PTSD rate was seen in this pilot population (29%) when compared with PTSD rates in the general female population (7-10%) and still one-third higher than the general population of women veterans (20%).45-47 Mental health, anxiety, and PTSD have been barriers to patients who sought treatment and have been implicated in poor adherence to medical advice.48,49 Cancer screening can induce anxiety in patients, and it may be amplified in patients with PTSD. It was remarkable that although adherence with screening recommendations is decreased when PTSD is present, our patient population demonstrated a higher rate of screening adherence.
Women who are seen at the VA often use multiple clinical specialties, and their EMR can be accessed across VA medical centers nationwide. Therefore, identifying women veterans who meet screening criteria is easily attainable within the VA.
When comparing high-risk with average risk women, the lifestyle results (BMI, smoking history, exercise and consumption of fruits, vegetables and alcohol) were essentially the same. Lifestyle factors were similar to national population rates and were unlikely to impact risk levels.
Limitations
Study limitations included a high number of self-referrals and the large percentage of patients with a family history of breast cancer, making them more likely to seek screening. The higher-than-average risk of breast cancer may be driven by a high rate of breast biopsies and a strong family history. Lifestyle metrics could not be accurately compared to other national assessments of lifestyle factors due to the difference in data points that we used or the format of our questions.
Conclusions
As the number of women veterans increases and the incidence of breast cancer in women veterans rise, chemoprevention options should follow national guidelines. To our knowledge, this is the only oncology study with 60% Black women veterans. This study had a higher participation rate for Black women veterans than is typically seen in national research studies and shows the VA to be a germane source for further understanding of an understudied population that may benefit from increased screening for breast cancer.
A team-based, multidisciplinary model that meets the unique healthcare needs of women veterans results in a patient-centric delivery of care for assessing breast cancer risk status and prevention options. This model can be replicated nationally by directing primary care physicians and women’s health practitioners to a risk-assessment questionnaire and referring high-risk women for appropriate preventative care. Given that these results show chemoprevention adherence rates doubled those seen nationally, perhaps techniques used within this VA pilot study may be adapted to decrease breast cancer incidence nationally.
Since the rate of PTSD among women veterans is triple the national average, we would expect adherence rates to be lower in our patient cohort. However, the multidisciplinary approach we used in this study (eg, 1:1 consultation with oncologist; genetic counseling referrals; mental health support available), may have improved adherence rates. Perhaps the high rates of PTSD seen in the VA patient population can be a useful way to explore patient adherence rates in those with mental illness and medical conditions.
Future research with a larger cohort may lead to greater insight into the correlation between PTSD and adherence to treatment. Exploring the connection between breast cancer, epigenetics, and specific military service-related exposures could be an area of analysis among this veteran population exhibiting increased breast cancer rates. VAMCs are situated in rural, suburban, and urban locations across the United States and offers a diverse socioeconomic and ethnic patient population for inclusion in clinical investigations. Women veterans make up a small subpopulation of women in the United States, but it is worth considering VA patients as an untapped resource for research collaboration.
Acknowledgements
The authors thank Steven Sanchez and Marissa Vallette, PhD, Breast Health Research Group. This research project was approved by the James J. Peters VA Medical Center Quality Executive Committee and the Washington, DC VA Medical Center Institutional Review Board. This work was supported by the US Department of Veterans Affairs. This work did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.
Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the US Government, or any of its agencies.
The number of women seeking care from the Veterans Health Administration (VHA) is increasing.1 In 2015, there were 2 million women veterans in the United States, which is 9.4% of the total veteran population. This group is expected to increase at an average of about 18,000 women per year for the next 10 years.2 The percentage of women veterans who are US Department of Veterans Affairs (VA) users aged 45 to 64 years rose 46% from 2000 to 2015.1,3-4 It is estimated that 15% of veterans who used VA services in 2020 were women.1 Nineteen percent of women veterans are Black.1 The median age of women veterans in 2015 was 50 years.5 Breast cancer is the leading cancer affecting female veterans, and data suggest they have an increased risk of breast cancer based on unique service-related exposures.1,6-9
In the US, about 10 million women are eligible for breast cancer preventive therapy, including, but not limited to, medications, surgery, or lifestyle changes.10 Secondary prevention options include change in surveillance that can reduce their risk or identify cancer at an earlier stage when treatment is more effective. The United States Preventive Services Task Force, the National Comprehensive Cancer Network, the American Society for Clinical Oncology, the National Institute for Health and Care Excellence, and the Oncology Nursing Society recommend screening women aged ≥ 35 years to assess breast cancer risk.11-18 If a woman is at increased risk, she may be a candidate for chemoprevention, prozphylactic surgery, and possibly an enhanced screening regimen.
Urban and minority women are an understudied population. Most veterans (75%) live in urban or suburban settings.19,20 Urban veteran women constitute an important potential study population.
Chemoprevention measures have been underused because of factors involving both women and their health care providers. A large proportion of women are unaware of their higher risk status due to lack of adequate screening and risk assessment.21,22 In addition to patient lack of awareness of their high-risk status, primary care physicians are also reluctant to prescribe chemopreventive agents due to a lack of comfort or familiarity with the risks and benefits.23-26 The STAR2015, BCPT2005, IBIS2014, MAP3 2011, IBIS-I 2014, and IBIS II 2014 studies clearly demonstrate a 49 to 62% reduction in risk for women using chemoprevention such as selective estrogen receptor modulators or aromatase inhibitors, respectively.27-32 Yet only 4 to 9% of high-risk women not enrolled in a clinical trial are using chemoprevention.33-39
The possibility of developing breast cancer also may be increased because of a positive family history or being a member of a family in which there is a known susceptibility gene mutation.40 Based on these risk factors, women may be eligible for tailored follow-up and genetic counseling.41-44
Nationally, 7 to 10% of the civilian US population will experience posttraumatic stress disorder (PTSD).45 The rates are remarkably higher for women veterans, with roughly 20% diagnosed with PTSD.46,47 Anxiety and PTSD have been implicated in poor adherence to medical advice.48,49
In 2014, a national VA multidisciplinary group focused on breast cancer prevention, detection, treatment, and research to address breast health in the growing population of women veterans. High-risk breast cancer screenings are not routinely carried out by the VA in primary care, women’s health, or oncology services. Furthermore, the recording of screening questionnaire results was not synchronized until a standard questionnaire was created and approved as a template by this group in the VA electronic medical record (EMR) in 2015.
Several prediction models can identify which women are at an increased risk of developing breast cancer. The most commonly used risk assessment model, the Gail breast cancer risk assessment tool (BCRAT), has been refined to include women of additional ethnicities (https://www.cancer.gov/bcrisktool).
This pilot project was launched to identify an effective manner to screen women veterans regarding their risk of developing breast cancer and refer them for chemoprevention education or genetic counseling as appropriate.
Methods
A high-risk breast cancer screening questionnaire based on the Gail BCRAT and including lifestyle questions was developed and included as a note template in the VA EMR. The James J. Peters VA Medical Center, Bronx, NY (JJPVAMC) and the Washington DC VA Medical Center (DCVAMC) ran a pilot study between 2015 and 2018 using this breast cancer screening questionnaire to collect data from women veterans. Quality Executive Committee and institutional review board approvals were granted respectively.
Eligibility criteria included women aged ≥ 35 years with no personal history of breast cancer. Most patients were self-referred, but participants also were recruited during VA Breast Cancer Awareness month events, health fairs, or at informational tables in the hospital lobbies. After completing the 20 multiple choice questionnaire with a study team member, either in person or over the phone, a 5-year and lifetime risk of invasive breast cancer was calculated using the Gail BCRAT. A woman is considered high risk and eligible for chemoprevention if her 5-year risk is > 1.66% or her lifetime risk is ≥ 20%. Eligibility for genetic counseling is based on the Breast Cancer Referral Screening Tool, which includes a personal or family history of breast or ovarian cancer and Jewish ancestry.
All patients were notified of their average or high risk status by a clinician. Those who were deemed to be average risk received a follow-up letter in the mail with instructions (eg, to follow-up with a yearly mammogram). Those who were deemed to be high risk for developing breast cancer were asked to come in for an appointment with the study principal investigator (a VA oncologist/breast cancer specialist) to discuss prevention options, further screening, or referrals to genetic counseling. Depending on a patient’s other health factors, a woman at high risk for developing breast cancer also may be a candidate for chemoprevention with tamoxifen, raloxifene, exemestane, anastrozole, or letrozole.
Data on the participant’s lifestyle, including exercise, diet, and smoking, were evaluated to determine whether these factors had an impact on risk status.
Results
The JJP and DC VAMCs screened 103 women veterans between 2015 and 2018. Four patients were excluded for nonveteran (spousal) status, leaving 99 women veterans with a mean age of 54 years. The most common self-reported races were Black (60%), non-Hispanic White (14%), and Hispanic or Latino (13%) (Table 1).
Women veterans in our study were nearly 3-times more likely than the general population were to receive a high-risk Gail Score/BCRAT (35% vs 13%, respectively).50,51 Of this subset, 46% had breast biopsies, and 86% had a positive family history. Thirty-one percent of Black women in our study were high risk, while nationally, 8.2 to 13.3% of Black women aged 50 to 59 years are considered high risk.50,51 Of the Black high-risk group with a high Gail/BCRAT score, 94% had a positive family history, and 33% had a history of breast biopsy (Table 2).
Of the 35 high-risk patients 26 (74%) patients accepted consultations for chemoprevention and 5 (19%) started chemoprevention. Of this high-risk group, 13 (37%) patients were referred for genetic counseling (Table 3).44 The prevalence of PTSD was present in 31% of high-risk women and 29% of the cohort (Figure).The lifestyle questions indicated that, among all participants, 79% had an overweight or obese body mass index; 58% exercised weekly; 51% consumed alcohol; 14% were smokers; and 21% consumed 3 to 4 servings of fruits/vegetables daily.
Discussion
Breast cancer is the most common cancer in women.52 The number of women with breast cancer in the VHA has more than tripled from 1995 to 2012.1 The lifetime risk of developing breast cancer in the general population is about 13%.50 This rate can be affected by risk factors including age, hormone exposure, family history, radiation exposure, and lifestyle factors, such as weight and alcohol use.6,52-56 In the United States, invasive breast cancer affects 1 in 8 women.50,52,57
Our screened population showed nearly 3 times as many women veterans were at an increased risk for breast cancer when compared with historical averages in US women. This difference may be based on a high rate of prior breast biopsies or positive family history, although a provocative study using the Surveillance, Epidemiology, and End Results database showed military women to have higher rates of breast cancer as well.9 Historically, Blacks are vastly understudied in clinical research with only 5% representation on a national level.5,58 The urban locations of both pilot sites (Washington, DC and Bronx, NY) allowed for the inclusion of minority patients in our study. We found that the rates of breast cancer in Black women veterans to be higher than seen nationally, possibly prompting further screening initiatives for this understudied population.
Our pilot study’s chemoprevention utilization (19%) was double the < 10% seen in the national population.33-35 The presence of a knowledgeable breast health practitioner to recruit study participants and offer personalized counseling to women veterans is a likely factor in overcoming barriers to chemopreventive acceptance. These participants may have been motivated to seek care for their high-risk status given a strong family history and prior breast biopsies.
Interestingly, a 3-fold higher PTSD rate was seen in this pilot population (29%) when compared with PTSD rates in the general female population (7-10%) and still one-third higher than the general population of women veterans (20%).45-47 Mental health, anxiety, and PTSD have been barriers to patients who sought treatment and have been implicated in poor adherence to medical advice.48,49 Cancer screening can induce anxiety in patients, and it may be amplified in patients with PTSD. It was remarkable that although adherence with screening recommendations is decreased when PTSD is present, our patient population demonstrated a higher rate of screening adherence.
Women who are seen at the VA often use multiple clinical specialties, and their EMR can be accessed across VA medical centers nationwide. Therefore, identifying women veterans who meet screening criteria is easily attainable within the VA.
When comparing high-risk with average risk women, the lifestyle results (BMI, smoking history, exercise and consumption of fruits, vegetables and alcohol) were essentially the same. Lifestyle factors were similar to national population rates and were unlikely to impact risk levels.
Limitations
Study limitations included a high number of self-referrals and the large percentage of patients with a family history of breast cancer, making them more likely to seek screening. The higher-than-average risk of breast cancer may be driven by a high rate of breast biopsies and a strong family history. Lifestyle metrics could not be accurately compared to other national assessments of lifestyle factors due to the difference in data points that we used or the format of our questions.
Conclusions
As the number of women veterans increases and the incidence of breast cancer in women veterans rise, chemoprevention options should follow national guidelines. To our knowledge, this is the only oncology study with 60% Black women veterans. This study had a higher participation rate for Black women veterans than is typically seen in national research studies and shows the VA to be a germane source for further understanding of an understudied population that may benefit from increased screening for breast cancer.
A team-based, multidisciplinary model that meets the unique healthcare needs of women veterans results in a patient-centric delivery of care for assessing breast cancer risk status and prevention options. This model can be replicated nationally by directing primary care physicians and women’s health practitioners to a risk-assessment questionnaire and referring high-risk women for appropriate preventative care. Given that these results show chemoprevention adherence rates doubled those seen nationally, perhaps techniques used within this VA pilot study may be adapted to decrease breast cancer incidence nationally.
Since the rate of PTSD among women veterans is triple the national average, we would expect adherence rates to be lower in our patient cohort. However, the multidisciplinary approach we used in this study (eg, 1:1 consultation with oncologist; genetic counseling referrals; mental health support available), may have improved adherence rates. Perhaps the high rates of PTSD seen in the VA patient population can be a useful way to explore patient adherence rates in those with mental illness and medical conditions.
Future research with a larger cohort may lead to greater insight into the correlation between PTSD and adherence to treatment. Exploring the connection between breast cancer, epigenetics, and specific military service-related exposures could be an area of analysis among this veteran population exhibiting increased breast cancer rates. VAMCs are situated in rural, suburban, and urban locations across the United States and offers a diverse socioeconomic and ethnic patient population for inclusion in clinical investigations. Women veterans make up a small subpopulation of women in the United States, but it is worth considering VA patients as an untapped resource for research collaboration.
Acknowledgements
The authors thank Steven Sanchez and Marissa Vallette, PhD, Breast Health Research Group. This research project was approved by the James J. Peters VA Medical Center Quality Executive Committee and the Washington, DC VA Medical Center Institutional Review Board. This work was supported by the US Department of Veterans Affairs. This work did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.
Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the US Government, or any of its agencies.
1. US Department of Veterans Affairs. National Center for Veterans Analysis and Statistics. The past, present and future of women veterans. Published February 2017. Accessed April 28, 2021. https://www.va.gov/vetdata/docs/specialreports/women_veterans_2015_final.pdf.
2. Frayne SM, Carney DV, Bastian L, et al. The VA Women’s Health Practice-Based Research Network: amplifying women veterans’ voices in VA research. J Gen Intern Med. 2013;28 Suppl 2(Suppl 2):S504-S509. doi:10.1007/s11606-013-2476-3
3. US Department of Veterans Affairs, Veterans Health Administration, Women’s Health Evaluation Initiative, Women Veterans Health Strategic Health Care Group. Sourcebook: women veterans in the Veterans Health Administration. Volume 1: Sociodemographic characteristics and use of VHA care. Published December 2010. Accessed April 12, 2021. https://www.va.gov/vhapublications/ViewPublication.asp?pub_ID=2455
4. Bean-Mayberry B, Yano EM, Bayliss N, Navratil J, Weisman CS, Scholle SH. Federally funded comprehensive women’s health centers: leading innovation in women’s healthcare delivery. J Womens Health (Larchmt). 2007;16(9):1281-1290. doi:10.1089/jwh.2006.0284
5. US Department of Veterans Affairs. National Center for Veterans Analysis and Statistics.VA utilization profile FY 2016. Published November 2017. Accessed April 12, 2021. https://www.va.gov/vetdata/docs/QuickFacts/VA_Utilization_Profile.PDF
6. Ekenga CC, Parks CG, Sandler DP. Chemical exposures in the workplace and breast cancer risk: a prospective cohort study. Int J Cancer. 2015;137(7):1765-1774. doi:10.1002/ijc.29545
7. Rennix CP, Quinn MM, Amoroso PJ, Eisen EA, Wegman DH. Risk of breast cancer among enlisted Army women occupationally exposed to volatile organic compounds. Am J Ind Med. 2005;48(3):157-167. doi:10.1002/ajim.20201
8. Ritz B. Cancer mortality among workers exposed to chemicals during uranium processing. J Occup Environ Med. 1999;41(7):556-566. doi:10.1097/00043764-199907000-00004
9. Zhu K, Devesa SS, Wu H, et al. Cancer incidence in the U.S. military population: comparison with rates from the SEER program. Cancer Epidemiol Biomarkers Prev. 2009;18(6):1740-1745. doi:10.1158/1055-9965.EPI-09-0041
10. Freedman AN, Yu B, Gail MH, et al. Benefit/risk assessment for breast cancer chemoprevention with raloxifene or tamoxifen for women age 50 years or older [published correction appears in J Clin Oncol. 2013 Nov 10;31(32):4167]. J Clin Oncol. 2011;29(17):2327-2333. doi:10.1200/JCO.2010.33.0258
11. Greene, H. Cancer prevention, screening and early detection. In: Gobel BH, Triest-Robertson S, Vogel WH, eds. Advanced Oncology Nursing Certification Review and Resource Manual. 3rd ed. Oncology Nursing Society; 2016:1-34. https://www.ons.org/sites/default/files/publication_pdfs/2%20ADVPrac%20chapter%201.pdf
12. National Comprehensive Cancer Network. NCCN Breast Cancer Risk Reduction. Version 1.2021 NCCN Clinical Practice Guidelines in Oncology. Updated March 24, 2021 Accessed April 12, 2021. https://www.nccn.org/professionals/physician_gls/pdf/breast_risk.pdf
13. US Preventive Services Task Force. Breast cancer: Medications use to reduce risk. Updated September 3, 2019. Accessed April 12, 2021. https://www.uspreventiveservicestaskforce.org/uspstf/recommendation/breast-cancer-medications-for-risk-reduction
14. Moyer VA; U.S. Preventive Services Task Force. Medications to decrease the risk for breast cancer in women: recommendations from the U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2013;159(10):698-708. doi:10.7326/0003-4819-159-10-201311190-00717
15. Boucher JE. Chemoprevention: an overview of pharmacologic agents and nursing considerations. Clin J Oncol Nurs. 2018;22(3):350-353. doi:10.1188/18.CJON.350-353
16. Nichols HB, Stürmer T, Lee VS, et al. Breast cancer chemoprevention in an integrated health care setting. JCO Clin Cancer Inform. 2017;1:1-12. doi:10.1200/CCI.16.00059
17. Bevers TB, Helvie M, Bonaccio E, et al. Breast cancer screening and diagnosis, Version 3.2018, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2018;16(11):1362-1389. doi:10.6004/jnccn.2018.0083
18. Visvanathan K, Hurley P, Bantug E, et al. Use of pharmacologic interventions for breast cancer risk reduction: American Society of Clinical Oncology clinical practice guideline [published correction appears in J Clin Oncol. 2013 Dec 1;31(34):4383]. J Clin Oncol. 2013;31(23):2942-2962. doi:10.1200/JCO.2013.49.3122
19. Sealy-Jefferson S, Roseland ME, Cote ML, et al. rural-urban residence and stage at breast cancer diagnosis among postmenopausal women: The Women’s Health Initiative. J Womens Health (Larchmt). 2019;28(2):276-283. doi:10.1089/jwh.2017.6884
20. Holder KA. Veterans in rural America: 2011-2015. Published January 25, 2017. Accessed April 12, 2021. https://www.census.gov/library/publications/2017/acs/acs-36.html
21. Owens WL, Gallagher TJ, Kincheloe MJ, Ruetten VL. Implementation in a large health system of a program to identify women at high risk for breast cancer. J Oncol Pract. 2011;7(2):85-88. doi:10.1200/JOP.2010.000107
2. Pivot X, Viguier J, Touboul C, et al. Breast cancer screening controversy: too much or not enough?. Eur J Cancer Prev. 2015;24 Suppl:S73-S76. doi:10.1097/CEJ.0000000000000145
23. Bidassie B, Kovach A, Vallette MA, et al. Breast Cancer risk assessment and chemoprevention use among veterans affairs primary care providers: a national online survey. Mil Med. 2020;185(3-4):512-518. doi:10.1093/milmed/usz291
24. Brewster AM, Davidson NE, McCaskill-Stevens W. Chemoprevention for breast cancer: overcoming barriers to treatment. Am Soc Clin Oncol Educ Book. 2012;85-90. doi:10.14694/EdBook_AM.2012.32.152
25. Meyskens FL Jr, Curt GA, Brenner DE, et al. Regulatory approval of cancer risk-reducing (chemopreventive) drugs: moving what we have learned into the clinic. Cancer Prev Res (Phila). 2011;4(3):311-323. doi:10.1158/1940-6207.CAPR-09-0014
26. Tice JA, Kerlikowske K. Screening and prevention of breast cancer in primary care. Prim Care. 2009;36(3):533-558. doi:10.1016/j.pop.2009.04.003
27. Vogel VG. Selective estrogen receptor modulators and aromatase inhibitors for breast cancer chemoprevention. Curr Drug Targets. 2011;12(13):1874-1887. doi:10.2174/138945011798184164
28. Vogel VG, Costantino JP, Wickerham DL, et al. Effects of tamoxifen vs raloxifene on the risk of developing invasive breast cancer and other disease outcomes: the NSABP Study of Tamoxifen and Raloxifene (STAR) P-2 trial [published correction appears in JAMA. 2006 Dec 27;296(24):2926] [published correction appears in JAMA. 2007 Sep 5;298(9):973]. JAMA. 2006;295(23):2727-2741. doi:10.1001/jama.295.23.joc60074
29. Pruthi S, Heisey RE, Bevers TB. Chemoprevention for breast cancer. Ann Surg Oncol. 2015;22(10):3230-3235. doi:10.1245/s10434-015-4715-9
30. Cuzick J, Sestak I, Forbes JF, et al. Anastrozole for prevention of breast cancer in high-risk postmenopausal women (IBIS-II): an international, double-blind, randomised placebo-controlled trial [published correction appears in Lancet. 2014 Mar 22;383(9922):1040] [published correction appears in Lancet. 2017 Mar 11;389(10073):1010]. Lancet. 2014;383(9922):1041-1048. doi:10.1016/S0140-6736(13)62292-8
31. Bozovic-Spasojevic I, Azambuja E, McCaskill-Stevens W, Dinh P, Cardoso F. Chemoprevention for breast cancer. Cancer Treat Rev. 2012;38(5):329-339. doi:10.1016/j.ctrv.2011.07.005
32. Gabriel EM, Jatoi I. Breast cancer chemoprevention. Expert Rev Anticancer Ther. 2012;12(2):223-228. doi:10.1586/era.11.206
33. Crew KD, Albain KS, Hershman DL, Unger JM, Lo SS. How do we increase uptake of tamoxifen and other anti-estrogens for breast cancer prevention?. NPJ Breast Cancer. 2017;3:20. Published 2017 May 19. doi:10.1038/s41523-017-0021-y
34. Ropka ME, Keim J, Philbrick JT. Patient decisions about breast cancer chemoprevention: a systematic review and meta-analysis. J Clin Oncol. 2010;28(18):3090-3095. doi:10.1200/JCO.2009.27.8077
35. Smith SG, Sestak I, Forster A, et al. Factors affecting uptake and adherence to breast cancer chemoprevention: a systematic review and meta-analysis. Ann Oncol. 2016;27(4):575-590. doi:10.1093/annonc/mdv590
36. Grann VR, Patel PR, Jacobson JS, et al. Comparative effectiveness of screening and prevention strategies among BRCA1/2-affected mutation carriers. Breast Cancer Res Treat. 2011 Feb;125(3):837-847. doi:10.1007/s10549-010-1043-4
37. Goss PE, Ingle JN, Alés-Martínez JE, et al. Exemestane for breast-cancer prevention in postmenopausal women [published correction appears in N Engl J Med. 2011 Oct 6;365(14):1361]. N Engl J Med. 2011;364(25):2381-2391. doi:10.1056/NEJMoa1103507
38. Kmietowicz Z. Five in six women reject drugs that could reduce their risk of breast cancer. BMJ. 2015;351:h6650. Published 2015 Dec 8. doi:10.1136/bmj.h6650
39. Nelson HD, Fu R, Griffin JC, Nygren P, Smith ME, Humphrey L. Systematic review: comparative effectiveness of medications to reduce risk for primary breast cancer. Ann Intern Med. 2009;151(10):703-235. doi:10.7326/0003-4819-151-10-200911170-00147
40. Dahabreh IJ, Wieland LS, Adam GP, Halladay C, Lau J, Trikalinos TA. Core needle and open surgery biopsy for diagnosis of breast lesions: an update to the 2009 report. Published September 2014. Accessed April 12, 2021. https://www.ncbi.nlm.nih.gov/books/NBK246878
41. National Cancer Institute. Genetics of breast and ovarian cancer (PDQ)—health profession version. Updated February 12, 2021. Accessed April 12, 2021. http://www.cancer.gov/cancertopics/pdq/genetics/breast-and-ovarian/HealthProfessional
42. US Department of Health and Human Services. National Institutes of Health, National Institute of Environmental Health Sciences The sister study. Accessed April 12, 2021. https://sisterstudy.niehs.nih.gov/english/NIEHS.htm
43. Tutt A, Ashworth A. Can genetic testing guide treatment in breast cancer?. Eur J Cancer. 2008;44(18):2774-2780. doi:10.1016/j.ejca.2008.10.009
44. Katz SJ, Ward KC, Hamilton AS, et al. Gaps in receipt of clinically indicated genetic counseling after diagnosis of breast cancer. J Clin Oncol. 2018;36(12):1218-1224. doi:10.1200/JCO.2017.76.2369
45. US Department of Veterans Affairs. PTSD: National Center for PTSD. How common is PTSD in adults? Updated October 17, 2019. Accessed April 12, 2021. https://www.ptsd.va.gov/understand/common/common_adults.asp
46. US Department of Veterans Affairs. PTSD: National Center for PTSD. How common is PTSD in women? Updated October 16, 2019. Accessed April 12, 2021. https://www.ptsd.va.gov/understand/common/common_women.asp
47. US Department of Veterans Affairs. PTSD: National Center for PTSD. How common is PTSD in veterans? Updated September 24, 2018. Accessed April 12, 2021. https://www.ptsd.va.gov/understand/common/common_veterans.asp
48. Lindberg NM, Wellisch D. Anxiety and compliance among women at high risk for breast cancer. Ann Behav Med. 2001;23(4):298-303. doi:10.1207/S15324796ABM2304_9
49. DiMatteo MR, Lepper HS, Croghan TW. Depression is a risk factor for noncompliance with medical treatment: meta-analysis of the effects of anxiety and depression on patient adherence. Arch Intern Med. 2000;160(14):2101-2107. doi:10.1001/archinte.160.14.2101
50. Centers for Disease Control and Prevention. MMWR appendix: breast cancer rates among black women and white women. Updated October 13, 2016. Accessed April 12, 2021. https://www.cdc.gov/cancer/breast/statistics/trends_invasive.htm
51. Richardson LC, Henley SJ, Miller JW, Massetti G, Thomas CC. Patterns and trends in age-specific black-white differences in breast cancer incidence and mortality - United States, 1999-2014. MMWR Morb Mortal Wkly Rep. 2016;65(40):1093-1098. Published 2016 Oct 14. doi:10.15585/mmwr.mm6540a1
52. Brody JG, Moysich KB, Humblet O, Attfield KR, Beehler GP, Rudel RA. Environmental pollutants and breast cancer: epidemiologic studies. Cancer. 2007;109(12 Suppl):2667-2711. doi:10.1002/cncr.22655
53. Brophy JT, Keith MM, Watterson A, et al. Breast cancer risk in relation to occupations with exposure to carcinogens and endocrine disruptors: a Canadian case-control study. Environ Health. 2012;11:87. Published 2012 Nov 19. doi:10.1186/1476-069X-11-87
54. Labrèche F, Goldberg MS, Valois MF, Nadon L. Postmenopausal breast cancer and occupational exposures. Occup Environ Med. 2010;67(4):263-269. doi:10.1136/oem.2009.049817
55. National Institute of Environmental Health Sciences, Interagency Breast Cancer & Environmental Research Coordinating Committee. Breast cancer and the environment: prioritizing prevention. Updated March 8, 2013. Accessed April 12, 2021. https://www.niehs.nih.gov/about/boards/ibcercc/index.cfm
56. Gail MH, Costantino JP, Pee D, et al. Projecting individualized absolute invasive breast cancer risk in African American women [published correction appears in J Natl Cancer Inst. 2008 Aug 6;100(15):1118] [published correction appears in J Natl Cancer Inst. 2008 Mar 5;100(5):373]. J Natl Cancer Inst. 2007;99(23):1782-1792. doi:10.1093/jnci/djm223
57. Corbie-Smith G, Thomas SB, Williams MV, Moody-Ayers S. Attitudes and beliefs of African Americans toward participation in medical research. J Gen Intern Med. 1999;14(9):537-546. doi:10.1046/j.1525-1497.1999.07048.x
58. Braunstein JB, Sherber NS, Schulman SP, Ding EL, Powe NR. Race, medical researcher distrust, perceived harm, and willingness to participate in cardiovascular prevention trials. Medicine (Baltimore). 2008;87(1):1-9. doi:10.1097/MD.0b013e3181625d78
1. US Department of Veterans Affairs. National Center for Veterans Analysis and Statistics. The past, present and future of women veterans. Published February 2017. Accessed April 28, 2021. https://www.va.gov/vetdata/docs/specialreports/women_veterans_2015_final.pdf.
2. Frayne SM, Carney DV, Bastian L, et al. The VA Women’s Health Practice-Based Research Network: amplifying women veterans’ voices in VA research. J Gen Intern Med. 2013;28 Suppl 2(Suppl 2):S504-S509. doi:10.1007/s11606-013-2476-3
3. US Department of Veterans Affairs, Veterans Health Administration, Women’s Health Evaluation Initiative, Women Veterans Health Strategic Health Care Group. Sourcebook: women veterans in the Veterans Health Administration. Volume 1: Sociodemographic characteristics and use of VHA care. Published December 2010. Accessed April 12, 2021. https://www.va.gov/vhapublications/ViewPublication.asp?pub_ID=2455
4. Bean-Mayberry B, Yano EM, Bayliss N, Navratil J, Weisman CS, Scholle SH. Federally funded comprehensive women’s health centers: leading innovation in women’s healthcare delivery. J Womens Health (Larchmt). 2007;16(9):1281-1290. doi:10.1089/jwh.2006.0284
5. US Department of Veterans Affairs. National Center for Veterans Analysis and Statistics.VA utilization profile FY 2016. Published November 2017. Accessed April 12, 2021. https://www.va.gov/vetdata/docs/QuickFacts/VA_Utilization_Profile.PDF
6. Ekenga CC, Parks CG, Sandler DP. Chemical exposures in the workplace and breast cancer risk: a prospective cohort study. Int J Cancer. 2015;137(7):1765-1774. doi:10.1002/ijc.29545
7. Rennix CP, Quinn MM, Amoroso PJ, Eisen EA, Wegman DH. Risk of breast cancer among enlisted Army women occupationally exposed to volatile organic compounds. Am J Ind Med. 2005;48(3):157-167. doi:10.1002/ajim.20201
8. Ritz B. Cancer mortality among workers exposed to chemicals during uranium processing. J Occup Environ Med. 1999;41(7):556-566. doi:10.1097/00043764-199907000-00004
9. Zhu K, Devesa SS, Wu H, et al. Cancer incidence in the U.S. military population: comparison with rates from the SEER program. Cancer Epidemiol Biomarkers Prev. 2009;18(6):1740-1745. doi:10.1158/1055-9965.EPI-09-0041
10. Freedman AN, Yu B, Gail MH, et al. Benefit/risk assessment for breast cancer chemoprevention with raloxifene or tamoxifen for women age 50 years or older [published correction appears in J Clin Oncol. 2013 Nov 10;31(32):4167]. J Clin Oncol. 2011;29(17):2327-2333. doi:10.1200/JCO.2010.33.0258
11. Greene, H. Cancer prevention, screening and early detection. In: Gobel BH, Triest-Robertson S, Vogel WH, eds. Advanced Oncology Nursing Certification Review and Resource Manual. 3rd ed. Oncology Nursing Society; 2016:1-34. https://www.ons.org/sites/default/files/publication_pdfs/2%20ADVPrac%20chapter%201.pdf
12. National Comprehensive Cancer Network. NCCN Breast Cancer Risk Reduction. Version 1.2021 NCCN Clinical Practice Guidelines in Oncology. Updated March 24, 2021 Accessed April 12, 2021. https://www.nccn.org/professionals/physician_gls/pdf/breast_risk.pdf
13. US Preventive Services Task Force. Breast cancer: Medications use to reduce risk. Updated September 3, 2019. Accessed April 12, 2021. https://www.uspreventiveservicestaskforce.org/uspstf/recommendation/breast-cancer-medications-for-risk-reduction
14. Moyer VA; U.S. Preventive Services Task Force. Medications to decrease the risk for breast cancer in women: recommendations from the U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2013;159(10):698-708. doi:10.7326/0003-4819-159-10-201311190-00717
15. Boucher JE. Chemoprevention: an overview of pharmacologic agents and nursing considerations. Clin J Oncol Nurs. 2018;22(3):350-353. doi:10.1188/18.CJON.350-353
16. Nichols HB, Stürmer T, Lee VS, et al. Breast cancer chemoprevention in an integrated health care setting. JCO Clin Cancer Inform. 2017;1:1-12. doi:10.1200/CCI.16.00059
17. Bevers TB, Helvie M, Bonaccio E, et al. Breast cancer screening and diagnosis, Version 3.2018, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2018;16(11):1362-1389. doi:10.6004/jnccn.2018.0083
18. Visvanathan K, Hurley P, Bantug E, et al. Use of pharmacologic interventions for breast cancer risk reduction: American Society of Clinical Oncology clinical practice guideline [published correction appears in J Clin Oncol. 2013 Dec 1;31(34):4383]. J Clin Oncol. 2013;31(23):2942-2962. doi:10.1200/JCO.2013.49.3122
19. Sealy-Jefferson S, Roseland ME, Cote ML, et al. rural-urban residence and stage at breast cancer diagnosis among postmenopausal women: The Women’s Health Initiative. J Womens Health (Larchmt). 2019;28(2):276-283. doi:10.1089/jwh.2017.6884
20. Holder KA. Veterans in rural America: 2011-2015. Published January 25, 2017. Accessed April 12, 2021. https://www.census.gov/library/publications/2017/acs/acs-36.html
21. Owens WL, Gallagher TJ, Kincheloe MJ, Ruetten VL. Implementation in a large health system of a program to identify women at high risk for breast cancer. J Oncol Pract. 2011;7(2):85-88. doi:10.1200/JOP.2010.000107
2. Pivot X, Viguier J, Touboul C, et al. Breast cancer screening controversy: too much or not enough?. Eur J Cancer Prev. 2015;24 Suppl:S73-S76. doi:10.1097/CEJ.0000000000000145
23. Bidassie B, Kovach A, Vallette MA, et al. Breast Cancer risk assessment and chemoprevention use among veterans affairs primary care providers: a national online survey. Mil Med. 2020;185(3-4):512-518. doi:10.1093/milmed/usz291
24. Brewster AM, Davidson NE, McCaskill-Stevens W. Chemoprevention for breast cancer: overcoming barriers to treatment. Am Soc Clin Oncol Educ Book. 2012;85-90. doi:10.14694/EdBook_AM.2012.32.152
25. Meyskens FL Jr, Curt GA, Brenner DE, et al. Regulatory approval of cancer risk-reducing (chemopreventive) drugs: moving what we have learned into the clinic. Cancer Prev Res (Phila). 2011;4(3):311-323. doi:10.1158/1940-6207.CAPR-09-0014
26. Tice JA, Kerlikowske K. Screening and prevention of breast cancer in primary care. Prim Care. 2009;36(3):533-558. doi:10.1016/j.pop.2009.04.003
27. Vogel VG. Selective estrogen receptor modulators and aromatase inhibitors for breast cancer chemoprevention. Curr Drug Targets. 2011;12(13):1874-1887. doi:10.2174/138945011798184164
28. Vogel VG, Costantino JP, Wickerham DL, et al. Effects of tamoxifen vs raloxifene on the risk of developing invasive breast cancer and other disease outcomes: the NSABP Study of Tamoxifen and Raloxifene (STAR) P-2 trial [published correction appears in JAMA. 2006 Dec 27;296(24):2926] [published correction appears in JAMA. 2007 Sep 5;298(9):973]. JAMA. 2006;295(23):2727-2741. doi:10.1001/jama.295.23.joc60074
29. Pruthi S, Heisey RE, Bevers TB. Chemoprevention for breast cancer. Ann Surg Oncol. 2015;22(10):3230-3235. doi:10.1245/s10434-015-4715-9
30. Cuzick J, Sestak I, Forbes JF, et al. Anastrozole for prevention of breast cancer in high-risk postmenopausal women (IBIS-II): an international, double-blind, randomised placebo-controlled trial [published correction appears in Lancet. 2014 Mar 22;383(9922):1040] [published correction appears in Lancet. 2017 Mar 11;389(10073):1010]. Lancet. 2014;383(9922):1041-1048. doi:10.1016/S0140-6736(13)62292-8
31. Bozovic-Spasojevic I, Azambuja E, McCaskill-Stevens W, Dinh P, Cardoso F. Chemoprevention for breast cancer. Cancer Treat Rev. 2012;38(5):329-339. doi:10.1016/j.ctrv.2011.07.005
32. Gabriel EM, Jatoi I. Breast cancer chemoprevention. Expert Rev Anticancer Ther. 2012;12(2):223-228. doi:10.1586/era.11.206
33. Crew KD, Albain KS, Hershman DL, Unger JM, Lo SS. How do we increase uptake of tamoxifen and other anti-estrogens for breast cancer prevention?. NPJ Breast Cancer. 2017;3:20. Published 2017 May 19. doi:10.1038/s41523-017-0021-y
34. Ropka ME, Keim J, Philbrick JT. Patient decisions about breast cancer chemoprevention: a systematic review and meta-analysis. J Clin Oncol. 2010;28(18):3090-3095. doi:10.1200/JCO.2009.27.8077
35. Smith SG, Sestak I, Forster A, et al. Factors affecting uptake and adherence to breast cancer chemoprevention: a systematic review and meta-analysis. Ann Oncol. 2016;27(4):575-590. doi:10.1093/annonc/mdv590
36. Grann VR, Patel PR, Jacobson JS, et al. Comparative effectiveness of screening and prevention strategies among BRCA1/2-affected mutation carriers. Breast Cancer Res Treat. 2011 Feb;125(3):837-847. doi:10.1007/s10549-010-1043-4
37. Goss PE, Ingle JN, Alés-Martínez JE, et al. Exemestane for breast-cancer prevention in postmenopausal women [published correction appears in N Engl J Med. 2011 Oct 6;365(14):1361]. N Engl J Med. 2011;364(25):2381-2391. doi:10.1056/NEJMoa1103507
38. Kmietowicz Z. Five in six women reject drugs that could reduce their risk of breast cancer. BMJ. 2015;351:h6650. Published 2015 Dec 8. doi:10.1136/bmj.h6650
39. Nelson HD, Fu R, Griffin JC, Nygren P, Smith ME, Humphrey L. Systematic review: comparative effectiveness of medications to reduce risk for primary breast cancer. Ann Intern Med. 2009;151(10):703-235. doi:10.7326/0003-4819-151-10-200911170-00147
40. Dahabreh IJ, Wieland LS, Adam GP, Halladay C, Lau J, Trikalinos TA. Core needle and open surgery biopsy for diagnosis of breast lesions: an update to the 2009 report. Published September 2014. Accessed April 12, 2021. https://www.ncbi.nlm.nih.gov/books/NBK246878
41. National Cancer Institute. Genetics of breast and ovarian cancer (PDQ)—health profession version. Updated February 12, 2021. Accessed April 12, 2021. http://www.cancer.gov/cancertopics/pdq/genetics/breast-and-ovarian/HealthProfessional
42. US Department of Health and Human Services. National Institutes of Health, National Institute of Environmental Health Sciences The sister study. Accessed April 12, 2021. https://sisterstudy.niehs.nih.gov/english/NIEHS.htm
43. Tutt A, Ashworth A. Can genetic testing guide treatment in breast cancer?. Eur J Cancer. 2008;44(18):2774-2780. doi:10.1016/j.ejca.2008.10.009
44. Katz SJ, Ward KC, Hamilton AS, et al. Gaps in receipt of clinically indicated genetic counseling after diagnosis of breast cancer. J Clin Oncol. 2018;36(12):1218-1224. doi:10.1200/JCO.2017.76.2369
45. US Department of Veterans Affairs. PTSD: National Center for PTSD. How common is PTSD in adults? Updated October 17, 2019. Accessed April 12, 2021. https://www.ptsd.va.gov/understand/common/common_adults.asp
46. US Department of Veterans Affairs. PTSD: National Center for PTSD. How common is PTSD in women? Updated October 16, 2019. Accessed April 12, 2021. https://www.ptsd.va.gov/understand/common/common_women.asp
47. US Department of Veterans Affairs. PTSD: National Center for PTSD. How common is PTSD in veterans? Updated September 24, 2018. Accessed April 12, 2021. https://www.ptsd.va.gov/understand/common/common_veterans.asp
48. Lindberg NM, Wellisch D. Anxiety and compliance among women at high risk for breast cancer. Ann Behav Med. 2001;23(4):298-303. doi:10.1207/S15324796ABM2304_9
49. DiMatteo MR, Lepper HS, Croghan TW. Depression is a risk factor for noncompliance with medical treatment: meta-analysis of the effects of anxiety and depression on patient adherence. Arch Intern Med. 2000;160(14):2101-2107. doi:10.1001/archinte.160.14.2101
50. Centers for Disease Control and Prevention. MMWR appendix: breast cancer rates among black women and white women. Updated October 13, 2016. Accessed April 12, 2021. https://www.cdc.gov/cancer/breast/statistics/trends_invasive.htm
51. Richardson LC, Henley SJ, Miller JW, Massetti G, Thomas CC. Patterns and trends in age-specific black-white differences in breast cancer incidence and mortality - United States, 1999-2014. MMWR Morb Mortal Wkly Rep. 2016;65(40):1093-1098. Published 2016 Oct 14. doi:10.15585/mmwr.mm6540a1
52. Brody JG, Moysich KB, Humblet O, Attfield KR, Beehler GP, Rudel RA. Environmental pollutants and breast cancer: epidemiologic studies. Cancer. 2007;109(12 Suppl):2667-2711. doi:10.1002/cncr.22655
53. Brophy JT, Keith MM, Watterson A, et al. Breast cancer risk in relation to occupations with exposure to carcinogens and endocrine disruptors: a Canadian case-control study. Environ Health. 2012;11:87. Published 2012 Nov 19. doi:10.1186/1476-069X-11-87
54. Labrèche F, Goldberg MS, Valois MF, Nadon L. Postmenopausal breast cancer and occupational exposures. Occup Environ Med. 2010;67(4):263-269. doi:10.1136/oem.2009.049817
55. National Institute of Environmental Health Sciences, Interagency Breast Cancer & Environmental Research Coordinating Committee. Breast cancer and the environment: prioritizing prevention. Updated March 8, 2013. Accessed April 12, 2021. https://www.niehs.nih.gov/about/boards/ibcercc/index.cfm
56. Gail MH, Costantino JP, Pee D, et al. Projecting individualized absolute invasive breast cancer risk in African American women [published correction appears in J Natl Cancer Inst. 2008 Aug 6;100(15):1118] [published correction appears in J Natl Cancer Inst. 2008 Mar 5;100(5):373]. J Natl Cancer Inst. 2007;99(23):1782-1792. doi:10.1093/jnci/djm223
57. Corbie-Smith G, Thomas SB, Williams MV, Moody-Ayers S. Attitudes and beliefs of African Americans toward participation in medical research. J Gen Intern Med. 1999;14(9):537-546. doi:10.1046/j.1525-1497.1999.07048.x
58. Braunstein JB, Sherber NS, Schulman SP, Ding EL, Powe NR. Race, medical researcher distrust, perceived harm, and willingness to participate in cardiovascular prevention trials. Medicine (Baltimore). 2008;87(1):1-9. doi:10.1097/MD.0b013e3181625d78
Study supports intensifying chemoradiotherapy for head and neck cancer
Of the 16 treatment options compared and ranked, HFCRT topped the list for overall survival, event-free survival, locoregional control, and cancer-specific death.
The results also suggested that taxane-based induction chemotherapy followed by locoregional therapy, especially with concomitant chemotherapy, “is another good option in selected patients with a good performance status and minor comorbidities,” according to investigator Claire Petit, MD, PhD, of Centre hospitalier de l’Université de Montréal in Canada, and colleagues.
The investigators concluded that further intensifying chemoradiotherapy with these approaches “could improve outcomes over chemoradiotherapy.”
The findings, published in The Lancet Oncology, “could help to guide clinical decision-making in locally advanced head and neck cancer with a high risk of locoregional failure, especially human papillomavirus–negative tumours,” the authors wrote.
However, Jared Weiss, MD, of the University of North Carolina, Chapel Hill, cautioned that this “study is an individual patient data network meta-analysis, not a randomized controlled trial. As the authors note, it can help frame existing data but cannot define standard of care.”
Still, “it does support the efficacy of two commonly considered intensification strategies for high-risk patients – hyperfractionation of the radiation and the addition of preceding induction chemotherapy. Both of these intensifications substantially increase the time commitment from the patient, and many patients find this unacceptable. But, for select patients, hyperfractionation and induction chemotherapy have a role and may be considered for patients at high risk of treatment failure,” Dr. Weiss said.
Study details
The goal of this study was to find the best option among many chemoradiation approaches for head and neck cancer. The investigators pulled together and reanalyzed individual patient data from recently updated meta-analyses.
The current analysis included 115 randomized trials that enrolled patients between Jan. 1, 1980, and April 30, 2012. This encompassed 28,978 patients with 20,579 progression events and 19,253 deaths over a median follow-up of 6.6 years.
Treatments were ranked by P score, with higher scores indicating more effective therapies.
For overall survival, HFCRT had a P score of 97%. The hazard ratio (HR) was 0.63 for the comparison with locoregional therapy alone (surgery, radiotherapy, or both). The absolute benefit at 5 years, compared with locoregional therapy alone, was 16.7% with HFCRT.
The P score for the second most effective treatment option – induction chemotherapy with taxane, cisplatin, and fluorouracil followed by locoregional therapy (ICTaxPF-LRT) – was 89%, with a hazard ratio of 0.69 and an absolute benefit at 5 years of 13.4%, versus locoregional therapy.
The HR of HFCRT versus the accepted standard of care worldwide – locoregional therapy with concomitant platinum-based chemotherapy and radiotherapy (CLRTP) – was 0.82 in favor of HFCRT for overall survival and 0.80 for event-free survival.
For overall survival, the P score for CLRTP was 78%. Three other treatment options had a better P score than CLRTP but not a better HR (0.77). These included ICTaxPF-LRT (P score, 89%; HR, 0.69), accelerated radiotherapy with concomitant chemotherapy (P score, 82%; HR, 0.75), and ICTaxPF-LRT followed by CLRTP (P score, 80%; HR, 0.75).
In the end, the investigators found “superiority of HFCRT over other treatments,” but noted it can be difficult to implement HFCRT in the era of intensity-modulated radiotherapy for head and neck cancer. Even so, HFCRT “could be considered as an option for tertiary centres with a high throughput of patients,” the investigators wrote.
The team noted that one of the limitations of this study is that cancer care has improved substantially since the very earliest trials that were included in the analysis. This introduces potential confounders, including that patients in older trials might have been understaged so that even an experimental local therapy would have been less effective.
Toxicity wasn’t part of this analysis but must be taken into account when making therapeutic decisions, “especially because HFCRT and induction chemotherapy based on taxane, cisplatin, and fluorouracil are known to be toxic,” the investigators wrote.
This research was funded by the French Institut National du Cancer, French Ligue Nationale Contre le Cancer, and Fondation ARC. The authors disclosed relationships with numerous companies, including AbbVie, Lilly, and Merck. Dr. Weiss did not report any relevant conflicts.
Of the 16 treatment options compared and ranked, HFCRT topped the list for overall survival, event-free survival, locoregional control, and cancer-specific death.
The results also suggested that taxane-based induction chemotherapy followed by locoregional therapy, especially with concomitant chemotherapy, “is another good option in selected patients with a good performance status and minor comorbidities,” according to investigator Claire Petit, MD, PhD, of Centre hospitalier de l’Université de Montréal in Canada, and colleagues.
The investigators concluded that further intensifying chemoradiotherapy with these approaches “could improve outcomes over chemoradiotherapy.”
The findings, published in The Lancet Oncology, “could help to guide clinical decision-making in locally advanced head and neck cancer with a high risk of locoregional failure, especially human papillomavirus–negative tumours,” the authors wrote.
However, Jared Weiss, MD, of the University of North Carolina, Chapel Hill, cautioned that this “study is an individual patient data network meta-analysis, not a randomized controlled trial. As the authors note, it can help frame existing data but cannot define standard of care.”
Still, “it does support the efficacy of two commonly considered intensification strategies for high-risk patients – hyperfractionation of the radiation and the addition of preceding induction chemotherapy. Both of these intensifications substantially increase the time commitment from the patient, and many patients find this unacceptable. But, for select patients, hyperfractionation and induction chemotherapy have a role and may be considered for patients at high risk of treatment failure,” Dr. Weiss said.
Study details
The goal of this study was to find the best option among many chemoradiation approaches for head and neck cancer. The investigators pulled together and reanalyzed individual patient data from recently updated meta-analyses.
The current analysis included 115 randomized trials that enrolled patients between Jan. 1, 1980, and April 30, 2012. This encompassed 28,978 patients with 20,579 progression events and 19,253 deaths over a median follow-up of 6.6 years.
Treatments were ranked by P score, with higher scores indicating more effective therapies.
For overall survival, HFCRT had a P score of 97%. The hazard ratio (HR) was 0.63 for the comparison with locoregional therapy alone (surgery, radiotherapy, or both). The absolute benefit at 5 years, compared with locoregional therapy alone, was 16.7% with HFCRT.
The P score for the second most effective treatment option – induction chemotherapy with taxane, cisplatin, and fluorouracil followed by locoregional therapy (ICTaxPF-LRT) – was 89%, with a hazard ratio of 0.69 and an absolute benefit at 5 years of 13.4%, versus locoregional therapy.
The HR of HFCRT versus the accepted standard of care worldwide – locoregional therapy with concomitant platinum-based chemotherapy and radiotherapy (CLRTP) – was 0.82 in favor of HFCRT for overall survival and 0.80 for event-free survival.
For overall survival, the P score for CLRTP was 78%. Three other treatment options had a better P score than CLRTP but not a better HR (0.77). These included ICTaxPF-LRT (P score, 89%; HR, 0.69), accelerated radiotherapy with concomitant chemotherapy (P score, 82%; HR, 0.75), and ICTaxPF-LRT followed by CLRTP (P score, 80%; HR, 0.75).
In the end, the investigators found “superiority of HFCRT over other treatments,” but noted it can be difficult to implement HFCRT in the era of intensity-modulated radiotherapy for head and neck cancer. Even so, HFCRT “could be considered as an option for tertiary centres with a high throughput of patients,” the investigators wrote.
The team noted that one of the limitations of this study is that cancer care has improved substantially since the very earliest trials that were included in the analysis. This introduces potential confounders, including that patients in older trials might have been understaged so that even an experimental local therapy would have been less effective.
Toxicity wasn’t part of this analysis but must be taken into account when making therapeutic decisions, “especially because HFCRT and induction chemotherapy based on taxane, cisplatin, and fluorouracil are known to be toxic,” the investigators wrote.
This research was funded by the French Institut National du Cancer, French Ligue Nationale Contre le Cancer, and Fondation ARC. The authors disclosed relationships with numerous companies, including AbbVie, Lilly, and Merck. Dr. Weiss did not report any relevant conflicts.
Of the 16 treatment options compared and ranked, HFCRT topped the list for overall survival, event-free survival, locoregional control, and cancer-specific death.
The results also suggested that taxane-based induction chemotherapy followed by locoregional therapy, especially with concomitant chemotherapy, “is another good option in selected patients with a good performance status and minor comorbidities,” according to investigator Claire Petit, MD, PhD, of Centre hospitalier de l’Université de Montréal in Canada, and colleagues.
The investigators concluded that further intensifying chemoradiotherapy with these approaches “could improve outcomes over chemoradiotherapy.”
The findings, published in The Lancet Oncology, “could help to guide clinical decision-making in locally advanced head and neck cancer with a high risk of locoregional failure, especially human papillomavirus–negative tumours,” the authors wrote.
However, Jared Weiss, MD, of the University of North Carolina, Chapel Hill, cautioned that this “study is an individual patient data network meta-analysis, not a randomized controlled trial. As the authors note, it can help frame existing data but cannot define standard of care.”
Still, “it does support the efficacy of two commonly considered intensification strategies for high-risk patients – hyperfractionation of the radiation and the addition of preceding induction chemotherapy. Both of these intensifications substantially increase the time commitment from the patient, and many patients find this unacceptable. But, for select patients, hyperfractionation and induction chemotherapy have a role and may be considered for patients at high risk of treatment failure,” Dr. Weiss said.
Study details
The goal of this study was to find the best option among many chemoradiation approaches for head and neck cancer. The investigators pulled together and reanalyzed individual patient data from recently updated meta-analyses.
The current analysis included 115 randomized trials that enrolled patients between Jan. 1, 1980, and April 30, 2012. This encompassed 28,978 patients with 20,579 progression events and 19,253 deaths over a median follow-up of 6.6 years.
Treatments were ranked by P score, with higher scores indicating more effective therapies.
For overall survival, HFCRT had a P score of 97%. The hazard ratio (HR) was 0.63 for the comparison with locoregional therapy alone (surgery, radiotherapy, or both). The absolute benefit at 5 years, compared with locoregional therapy alone, was 16.7% with HFCRT.
The P score for the second most effective treatment option – induction chemotherapy with taxane, cisplatin, and fluorouracil followed by locoregional therapy (ICTaxPF-LRT) – was 89%, with a hazard ratio of 0.69 and an absolute benefit at 5 years of 13.4%, versus locoregional therapy.
The HR of HFCRT versus the accepted standard of care worldwide – locoregional therapy with concomitant platinum-based chemotherapy and radiotherapy (CLRTP) – was 0.82 in favor of HFCRT for overall survival and 0.80 for event-free survival.
For overall survival, the P score for CLRTP was 78%. Three other treatment options had a better P score than CLRTP but not a better HR (0.77). These included ICTaxPF-LRT (P score, 89%; HR, 0.69), accelerated radiotherapy with concomitant chemotherapy (P score, 82%; HR, 0.75), and ICTaxPF-LRT followed by CLRTP (P score, 80%; HR, 0.75).
In the end, the investigators found “superiority of HFCRT over other treatments,” but noted it can be difficult to implement HFCRT in the era of intensity-modulated radiotherapy for head and neck cancer. Even so, HFCRT “could be considered as an option for tertiary centres with a high throughput of patients,” the investigators wrote.
The team noted that one of the limitations of this study is that cancer care has improved substantially since the very earliest trials that were included in the analysis. This introduces potential confounders, including that patients in older trials might have been understaged so that even an experimental local therapy would have been less effective.
Toxicity wasn’t part of this analysis but must be taken into account when making therapeutic decisions, “especially because HFCRT and induction chemotherapy based on taxane, cisplatin, and fluorouracil are known to be toxic,” the investigators wrote.
This research was funded by the French Institut National du Cancer, French Ligue Nationale Contre le Cancer, and Fondation ARC. The authors disclosed relationships with numerous companies, including AbbVie, Lilly, and Merck. Dr. Weiss did not report any relevant conflicts.
FROM THE LANCET ONCOLOGY
Possible obesity effect detected in cancer death rates
“By integrating 20 years of cancer mortality data, we demonstrated that trends in obesity-associated cancer mortality showed signs of recent deceleration, consistent with recent findings for heart disease mortality,” Christy L. Avery, PhD, and associates wrote in JAMA Network Open.
Improvements in mortality related to heart disease slowed after 2011, a phenomenon that has been associated with rising obesity rates. The age-adjusted mortality rate (AAMR) declined at an average of 3.8 deaths per 100,000 persons from 1999 to 2011 but only 0.7 deaths per 100,000 from 2011 to 2018, based on data from the Centers for Disease Control and Prevention’s Wide-Ranging Online Data for Epidemiologic Research (WONDER).
To understand trends in cancer mortality and their possible connection with obesity, data for 1999-2018 from the WONDER database were divided into obesity-associated and non–obesity-associated categories and compared with heart disease mortality, they explained. The database included more than 50 million deaths that matched inclusion criteria.
The analysis showed there was difference between obesity-associated and non–obesity-associated cancers that was obscured when all cancer deaths were considered together. The average annual change in AAMR for obesity-associated cancers slowed from –1.19 deaths per 100,000 in 1999-2011 to –0.83 in 2011-2018, Dr. Avery and associates reported.
For non–obesity-associated cancers, the annual change in AAMR increased from –1.62 per 100,000 for 1999-2011 to –2.29 for 2011-2018, following the trend for all cancers: –1.48 per 100,000 during 1999-2011 and –1.77 in 2011-2018, they said.
“The largest mortality decreases were observed for melanoma of the skin and lung cancer, two cancers not associated with obesity. For obesity-associated cancers, stable or increasing mortality rates have been observed for liver and pancreatic cancer among both men and women as well as for uterine cancer among women,” the investigators wrote.
Demographically, however, the slowing improvement in mortality for obesity-associated cancers did not follow the trend for heart disease. The deceleration for cancer was more pronounced for women and for non-Hispanic Whites and not seen at all in non-Hispanic Asian/Pacific Islander individuals. “For heart disease, evidence of a deceleration was consistent across sex, race, and ethnicity,” they said.
There are “longstanding disparities in obesity” among various populations in the United States, and the recent trend of obesity occurring earlier in life may be having an effect. “Whether the findings of decelerating mortality rates potentially signal a changing profile of cancer and heart disease mortality as the consequences of the obesity epidemic are realized remains to be seen,” they concluded.
The investigators reported receiving grants from the National Institutes of Health during the conduct of the study, but no other disclosures were reported.
“By integrating 20 years of cancer mortality data, we demonstrated that trends in obesity-associated cancer mortality showed signs of recent deceleration, consistent with recent findings for heart disease mortality,” Christy L. Avery, PhD, and associates wrote in JAMA Network Open.
Improvements in mortality related to heart disease slowed after 2011, a phenomenon that has been associated with rising obesity rates. The age-adjusted mortality rate (AAMR) declined at an average of 3.8 deaths per 100,000 persons from 1999 to 2011 but only 0.7 deaths per 100,000 from 2011 to 2018, based on data from the Centers for Disease Control and Prevention’s Wide-Ranging Online Data for Epidemiologic Research (WONDER).
To understand trends in cancer mortality and their possible connection with obesity, data for 1999-2018 from the WONDER database were divided into obesity-associated and non–obesity-associated categories and compared with heart disease mortality, they explained. The database included more than 50 million deaths that matched inclusion criteria.
The analysis showed there was difference between obesity-associated and non–obesity-associated cancers that was obscured when all cancer deaths were considered together. The average annual change in AAMR for obesity-associated cancers slowed from –1.19 deaths per 100,000 in 1999-2011 to –0.83 in 2011-2018, Dr. Avery and associates reported.
For non–obesity-associated cancers, the annual change in AAMR increased from –1.62 per 100,000 for 1999-2011 to –2.29 for 2011-2018, following the trend for all cancers: –1.48 per 100,000 during 1999-2011 and –1.77 in 2011-2018, they said.
“The largest mortality decreases were observed for melanoma of the skin and lung cancer, two cancers not associated with obesity. For obesity-associated cancers, stable or increasing mortality rates have been observed for liver and pancreatic cancer among both men and women as well as for uterine cancer among women,” the investigators wrote.
Demographically, however, the slowing improvement in mortality for obesity-associated cancers did not follow the trend for heart disease. The deceleration for cancer was more pronounced for women and for non-Hispanic Whites and not seen at all in non-Hispanic Asian/Pacific Islander individuals. “For heart disease, evidence of a deceleration was consistent across sex, race, and ethnicity,” they said.
There are “longstanding disparities in obesity” among various populations in the United States, and the recent trend of obesity occurring earlier in life may be having an effect. “Whether the findings of decelerating mortality rates potentially signal a changing profile of cancer and heart disease mortality as the consequences of the obesity epidemic are realized remains to be seen,” they concluded.
The investigators reported receiving grants from the National Institutes of Health during the conduct of the study, but no other disclosures were reported.
“By integrating 20 years of cancer mortality data, we demonstrated that trends in obesity-associated cancer mortality showed signs of recent deceleration, consistent with recent findings for heart disease mortality,” Christy L. Avery, PhD, and associates wrote in JAMA Network Open.
Improvements in mortality related to heart disease slowed after 2011, a phenomenon that has been associated with rising obesity rates. The age-adjusted mortality rate (AAMR) declined at an average of 3.8 deaths per 100,000 persons from 1999 to 2011 but only 0.7 deaths per 100,000 from 2011 to 2018, based on data from the Centers for Disease Control and Prevention’s Wide-Ranging Online Data for Epidemiologic Research (WONDER).
To understand trends in cancer mortality and their possible connection with obesity, data for 1999-2018 from the WONDER database were divided into obesity-associated and non–obesity-associated categories and compared with heart disease mortality, they explained. The database included more than 50 million deaths that matched inclusion criteria.
The analysis showed there was difference between obesity-associated and non–obesity-associated cancers that was obscured when all cancer deaths were considered together. The average annual change in AAMR for obesity-associated cancers slowed from –1.19 deaths per 100,000 in 1999-2011 to –0.83 in 2011-2018, Dr. Avery and associates reported.
For non–obesity-associated cancers, the annual change in AAMR increased from –1.62 per 100,000 for 1999-2011 to –2.29 for 2011-2018, following the trend for all cancers: –1.48 per 100,000 during 1999-2011 and –1.77 in 2011-2018, they said.
“The largest mortality decreases were observed for melanoma of the skin and lung cancer, two cancers not associated with obesity. For obesity-associated cancers, stable or increasing mortality rates have been observed for liver and pancreatic cancer among both men and women as well as for uterine cancer among women,” the investigators wrote.
Demographically, however, the slowing improvement in mortality for obesity-associated cancers did not follow the trend for heart disease. The deceleration for cancer was more pronounced for women and for non-Hispanic Whites and not seen at all in non-Hispanic Asian/Pacific Islander individuals. “For heart disease, evidence of a deceleration was consistent across sex, race, and ethnicity,” they said.
There are “longstanding disparities in obesity” among various populations in the United States, and the recent trend of obesity occurring earlier in life may be having an effect. “Whether the findings of decelerating mortality rates potentially signal a changing profile of cancer and heart disease mortality as the consequences of the obesity epidemic are realized remains to be seen,” they concluded.
The investigators reported receiving grants from the National Institutes of Health during the conduct of the study, but no other disclosures were reported.
FROM JAMA NETWORK OPEN
FDA okays upfront pembro for advanced HER2+ gastric cancer
The checkpoint inhibitor is to be used in conjunction with trastuzumab (Herceptin) and fluoropyrimidine- and platinum-containing chemotherapy.
Previously, pembrolizumab was approved as a single agent for these cancers for patients whose tumors express PD-L1 and whose disease progressed after two or more lines of treatment that included chemotherapy and HER2-targeted therapy.
The new approval comes about a year after the FDA’s first-ever approval of a checkpoint inhibitor (nivolumab [Opdivo] in combination with chemotherapies) for the frontline treatment of gastric cancers, as reported by this news organization.
The new approval is based on interim data from the first 264 patients of the ongoing KEYNOTE-811 trial, a randomized, double-blind, placebo-controlled trial involving patients with HER2-positive advanced gastric or GEJ adenocarcinoma who had not previously received systemic therapy for their metastatic disease.
Patients were randomly assigned (1:1) to receive either pembrolizumab at 200 mg or placebo every 3 weeks in combination with trastuzumab and either fluorouracil plus cisplatin or capecitabine plus oxaliplatin.
The overall response rate, which is the primary outcome, was 74% in the pembrolizumab arm and 52% in the placebo arm (one-sided P < .0001).
The median duration of response was 10.6 months in the pembrolizumab arm and 9.5 months in the placebo arm.
The adverse-reaction profile for patients receiving pembrolizumab is consistent with the known pembrolizumab safety profile, the FDA said in a statement.
The recommended pembrolizumab dose in this setting is 200 mg every 3 weeks or 400 mg every 6 weeks.
The FDA’s review, which was granted priority status, used the Real-Time Oncology Review pilot program, which allows streamlined data submission prior to the filing of the full clinical application, and Assessment Aid, a voluntary submission that facilitates the FDA’s assessment.
A version of this article first appeared on Medscape.com.
The checkpoint inhibitor is to be used in conjunction with trastuzumab (Herceptin) and fluoropyrimidine- and platinum-containing chemotherapy.
Previously, pembrolizumab was approved as a single agent for these cancers for patients whose tumors express PD-L1 and whose disease progressed after two or more lines of treatment that included chemotherapy and HER2-targeted therapy.
The new approval comes about a year after the FDA’s first-ever approval of a checkpoint inhibitor (nivolumab [Opdivo] in combination with chemotherapies) for the frontline treatment of gastric cancers, as reported by this news organization.
The new approval is based on interim data from the first 264 patients of the ongoing KEYNOTE-811 trial, a randomized, double-blind, placebo-controlled trial involving patients with HER2-positive advanced gastric or GEJ adenocarcinoma who had not previously received systemic therapy for their metastatic disease.
Patients were randomly assigned (1:1) to receive either pembrolizumab at 200 mg or placebo every 3 weeks in combination with trastuzumab and either fluorouracil plus cisplatin or capecitabine plus oxaliplatin.
The overall response rate, which is the primary outcome, was 74% in the pembrolizumab arm and 52% in the placebo arm (one-sided P < .0001).
The median duration of response was 10.6 months in the pembrolizumab arm and 9.5 months in the placebo arm.
The adverse-reaction profile for patients receiving pembrolizumab is consistent with the known pembrolizumab safety profile, the FDA said in a statement.
The recommended pembrolizumab dose in this setting is 200 mg every 3 weeks or 400 mg every 6 weeks.
The FDA’s review, which was granted priority status, used the Real-Time Oncology Review pilot program, which allows streamlined data submission prior to the filing of the full clinical application, and Assessment Aid, a voluntary submission that facilitates the FDA’s assessment.
A version of this article first appeared on Medscape.com.
The checkpoint inhibitor is to be used in conjunction with trastuzumab (Herceptin) and fluoropyrimidine- and platinum-containing chemotherapy.
Previously, pembrolizumab was approved as a single agent for these cancers for patients whose tumors express PD-L1 and whose disease progressed after two or more lines of treatment that included chemotherapy and HER2-targeted therapy.
The new approval comes about a year after the FDA’s first-ever approval of a checkpoint inhibitor (nivolumab [Opdivo] in combination with chemotherapies) for the frontline treatment of gastric cancers, as reported by this news organization.
The new approval is based on interim data from the first 264 patients of the ongoing KEYNOTE-811 trial, a randomized, double-blind, placebo-controlled trial involving patients with HER2-positive advanced gastric or GEJ adenocarcinoma who had not previously received systemic therapy for their metastatic disease.
Patients were randomly assigned (1:1) to receive either pembrolizumab at 200 mg or placebo every 3 weeks in combination with trastuzumab and either fluorouracil plus cisplatin or capecitabine plus oxaliplatin.
The overall response rate, which is the primary outcome, was 74% in the pembrolizumab arm and 52% in the placebo arm (one-sided P < .0001).
The median duration of response was 10.6 months in the pembrolizumab arm and 9.5 months in the placebo arm.
The adverse-reaction profile for patients receiving pembrolizumab is consistent with the known pembrolizumab safety profile, the FDA said in a statement.
The recommended pembrolizumab dose in this setting is 200 mg every 3 weeks or 400 mg every 6 weeks.
The FDA’s review, which was granted priority status, used the Real-Time Oncology Review pilot program, which allows streamlined data submission prior to the filing of the full clinical application, and Assessment Aid, a voluntary submission that facilitates the FDA’s assessment.
A version of this article first appeared on Medscape.com.
COVID-19 impact on breast cancer: Upfront endocrine Rx increased
The use of neoadjuvant endocrine therapy (NET) increased significantly during the first 8 months of the COVID-19 pandemic for women with estrogen receptor–positive (ER+) breast cancer. These patients would normally undergo surgery first, but because of operating room restrictions, those surgeries were delayed because of the pandemic, according to a new study.
“We hypothesized that by offering a nontoxic therapy, we would be able to ‘hold over’ patients until such time when personal protective equipment supplies were renewed and we could get into the operating room,” lead author Lee Wilke, MD, professor of surgery, University of Wisconsin, Madison, said in an interview.
“And while a small number of women with ER+ tumors get NET anyway, we found over one-third of patients with ER+ breast cancer were treated with NET due to COVID-19 during the first 8 months of last year,” she said.
“One year later, 31% of the same patient population is still getting NET,” she added.
The study was presented during the online annual meeting of the American Society of Breast Surgeons (ASBrS).
COVID-specific registry
Dr. Wilke believes that this study presents an accurate snapshot of changes in treatment caused by the pandemic.
She and her colleagues compared data collected in the ASBrS Mastery Program registry to data collected in an embedded but separate COVID-19 segment. The data were for the period from March 1 to Oct. 28, 2020.
Almost three-quarters of the surgeons who entered patients into the COVID-19 segment were from urban areas; 95% reported stopping mammographic screening during part of this period.
The preliminary analysis focused on data collected from 2,476 patients in the COVID-19 segment and 2,303 patients within the Mastery registry.
For patients with ER+/HER2- breast cancer, NET was described as a usual approach in 6.5% of patients in the COVID-19 registry. In the Mastery registry, 7.8% of patients received NET.
Compared with surgery first/usual practice, which served as the reference, older patients were more likely to receive NET first because of the COVID-19 pandemic than younger patients, and they were more likely to receive NET first if they lived in the Northeast or the Southeast compared to other regions of the United States. Dr. Wilke pointed out that the Northeast and the Southeast were hardest hit by COVID-19 early on in the pandemic.
Genomic testing was carried out in a small subgroup of patients; 24% of those patients underwent testing on the core biopsy specimen because of COVID-19, the investigators noted. Genomic testing on a core biopsy specimen helps determine whether it’s feasible to forgo chemotherapy and use NET instead or whether the patient should proceed directly to surgery. The authors noted that almost 11% of patients required a change in the usual surgical approach because of COVID-19. Such changes were made primarily to avoid hospitalizations during the early phase of the pandemic for patients who were to undergo mastectomy or reconstruction.
“Patients who needed standard approaches still got them,” Dr. Wilke emphasized in a statement. For example, women with aggressive triple-negative and HER2+ tumors were treated with neoadjuvant chemotherapy, she added. “However, NET is a very good approach for a moderate subset of patients, and we think we will see it being used more often in the U.S. now,” Dr. Wilke observed.
“But especially early during the pandemic, these revised treatments were necessary because access to hospital ORs was limited or unavailable, so our algorithmic-based treatment guidelines allowed us to offer high-quality, evidence-based care fine-tuned for a patient’s specific cancer profile,” she affirmed.
Dr. Wilke has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The use of neoadjuvant endocrine therapy (NET) increased significantly during the first 8 months of the COVID-19 pandemic for women with estrogen receptor–positive (ER+) breast cancer. These patients would normally undergo surgery first, but because of operating room restrictions, those surgeries were delayed because of the pandemic, according to a new study.
“We hypothesized that by offering a nontoxic therapy, we would be able to ‘hold over’ patients until such time when personal protective equipment supplies were renewed and we could get into the operating room,” lead author Lee Wilke, MD, professor of surgery, University of Wisconsin, Madison, said in an interview.
“And while a small number of women with ER+ tumors get NET anyway, we found over one-third of patients with ER+ breast cancer were treated with NET due to COVID-19 during the first 8 months of last year,” she said.
“One year later, 31% of the same patient population is still getting NET,” she added.
The study was presented during the online annual meeting of the American Society of Breast Surgeons (ASBrS).
COVID-specific registry
Dr. Wilke believes that this study presents an accurate snapshot of changes in treatment caused by the pandemic.
She and her colleagues compared data collected in the ASBrS Mastery Program registry to data collected in an embedded but separate COVID-19 segment. The data were for the period from March 1 to Oct. 28, 2020.
Almost three-quarters of the surgeons who entered patients into the COVID-19 segment were from urban areas; 95% reported stopping mammographic screening during part of this period.
The preliminary analysis focused on data collected from 2,476 patients in the COVID-19 segment and 2,303 patients within the Mastery registry.
For patients with ER+/HER2- breast cancer, NET was described as a usual approach in 6.5% of patients in the COVID-19 registry. In the Mastery registry, 7.8% of patients received NET.
Compared with surgery first/usual practice, which served as the reference, older patients were more likely to receive NET first because of the COVID-19 pandemic than younger patients, and they were more likely to receive NET first if they lived in the Northeast or the Southeast compared to other regions of the United States. Dr. Wilke pointed out that the Northeast and the Southeast were hardest hit by COVID-19 early on in the pandemic.
Genomic testing was carried out in a small subgroup of patients; 24% of those patients underwent testing on the core biopsy specimen because of COVID-19, the investigators noted. Genomic testing on a core biopsy specimen helps determine whether it’s feasible to forgo chemotherapy and use NET instead or whether the patient should proceed directly to surgery. The authors noted that almost 11% of patients required a change in the usual surgical approach because of COVID-19. Such changes were made primarily to avoid hospitalizations during the early phase of the pandemic for patients who were to undergo mastectomy or reconstruction.
“Patients who needed standard approaches still got them,” Dr. Wilke emphasized in a statement. For example, women with aggressive triple-negative and HER2+ tumors were treated with neoadjuvant chemotherapy, she added. “However, NET is a very good approach for a moderate subset of patients, and we think we will see it being used more often in the U.S. now,” Dr. Wilke observed.
“But especially early during the pandemic, these revised treatments were necessary because access to hospital ORs was limited or unavailable, so our algorithmic-based treatment guidelines allowed us to offer high-quality, evidence-based care fine-tuned for a patient’s specific cancer profile,” she affirmed.
Dr. Wilke has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The use of neoadjuvant endocrine therapy (NET) increased significantly during the first 8 months of the COVID-19 pandemic for women with estrogen receptor–positive (ER+) breast cancer. These patients would normally undergo surgery first, but because of operating room restrictions, those surgeries were delayed because of the pandemic, according to a new study.
“We hypothesized that by offering a nontoxic therapy, we would be able to ‘hold over’ patients until such time when personal protective equipment supplies were renewed and we could get into the operating room,” lead author Lee Wilke, MD, professor of surgery, University of Wisconsin, Madison, said in an interview.
“And while a small number of women with ER+ tumors get NET anyway, we found over one-third of patients with ER+ breast cancer were treated with NET due to COVID-19 during the first 8 months of last year,” she said.
“One year later, 31% of the same patient population is still getting NET,” she added.
The study was presented during the online annual meeting of the American Society of Breast Surgeons (ASBrS).
COVID-specific registry
Dr. Wilke believes that this study presents an accurate snapshot of changes in treatment caused by the pandemic.
She and her colleagues compared data collected in the ASBrS Mastery Program registry to data collected in an embedded but separate COVID-19 segment. The data were for the period from March 1 to Oct. 28, 2020.
Almost three-quarters of the surgeons who entered patients into the COVID-19 segment were from urban areas; 95% reported stopping mammographic screening during part of this period.
The preliminary analysis focused on data collected from 2,476 patients in the COVID-19 segment and 2,303 patients within the Mastery registry.
For patients with ER+/HER2- breast cancer, NET was described as a usual approach in 6.5% of patients in the COVID-19 registry. In the Mastery registry, 7.8% of patients received NET.
Compared with surgery first/usual practice, which served as the reference, older patients were more likely to receive NET first because of the COVID-19 pandemic than younger patients, and they were more likely to receive NET first if they lived in the Northeast or the Southeast compared to other regions of the United States. Dr. Wilke pointed out that the Northeast and the Southeast were hardest hit by COVID-19 early on in the pandemic.
Genomic testing was carried out in a small subgroup of patients; 24% of those patients underwent testing on the core biopsy specimen because of COVID-19, the investigators noted. Genomic testing on a core biopsy specimen helps determine whether it’s feasible to forgo chemotherapy and use NET instead or whether the patient should proceed directly to surgery. The authors noted that almost 11% of patients required a change in the usual surgical approach because of COVID-19. Such changes were made primarily to avoid hospitalizations during the early phase of the pandemic for patients who were to undergo mastectomy or reconstruction.
“Patients who needed standard approaches still got them,” Dr. Wilke emphasized in a statement. For example, women with aggressive triple-negative and HER2+ tumors were treated with neoadjuvant chemotherapy, she added. “However, NET is a very good approach for a moderate subset of patients, and we think we will see it being used more often in the U.S. now,” Dr. Wilke observed.
“But especially early during the pandemic, these revised treatments were necessary because access to hospital ORs was limited or unavailable, so our algorithmic-based treatment guidelines allowed us to offer high-quality, evidence-based care fine-tuned for a patient’s specific cancer profile,” she affirmed.
Dr. Wilke has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Checkpoint inhibitor skin side effects more common in women
Overall, 62.4% of the 93 women in the review and 48.6% of the 142 men experienced confirmed skin reactions, for an odds ratio (OR) of 2.11 for women compared with men (P = .01).
“Clinicians should consider these results in counseling female patients regarding an elevated risk of dermatologic adverse events” when taking checkpoint inhibitors, said investigators led by Harvard University medical student Jordan Said, who presented the results at the American Academy of Dermatology Virtual Meeting Experience.
Autoimmune-like adverse events are common with checkpoint inhibitors. Dermatologic side effects occur in about half of people receiving monotherapy and more than that among patients receiving combination therapy.
Skin reactions can include psoriasiform dermatitis, lichenoid reactions, vitiligo, and bullous pemphigoid and may require hospitalization and prolonged steroid treatment.
Not much is known about risk factors for these reactions. A higher incidence among women has been previously reported. A 2019 study found a higher risk for pneumonitis and endocrinopathy, including hypophysitis, among women who underwent treatment for non–small cell lung cancer or metastatic melanoma.
The 2019 study found that the risk was higher among premenopausal women than postmenopausal women, which led some to suggest that estrogen may play a role.
The results of the Dana Farber review argue against that notion. In their review, the investigators found that the risk was similarly elevated among the 27 premenopausal women (OR, 1.97; P = .40) and the 66 postmenopausal women (OR, 2.17, P = .05). In the study, women who were aged 52 years or older at the start of treatment were considered to be postmenopausal.
“This suggests that factors beyond sex hormones are likely contributory” to the difference in risk between men and women. It’s known that women are at higher risk for autoimmune disease overall, which might be related to the increased odds of autoimmune-like reactions, and it may be that sex-related differences in innate and adoptive immunity are at work, Mr. Said noted.
When asked for comment, Douglas Johnson, MD, assistant professor of hematology/oncology at Vanderbilt University, Nashville, Tenn., said that although some studies have reported a greater risk for side effects among women, others have not. “Additional research is needed to determine the interactions between sex and effects of immune checkpoint inhibitors, as well as many other possible triggers of immune-related adverse events,” he said.
“Continued work in this area will be so important to help determine how to best counsel women and to ensure early recognition and intervention for dermatologic side effects,” said Bernice Kwong, MD, director of the Supportive Dermato-Oncology Program at Stanford (Calif.) University.
The patients in the review were treated from 2011 to 2016 and underwent at least monthly evaluations by their medical teams. They were taking either nivolumab, pembrolizumab, or ipilimumab or a nivolumab/ipilimumab combination.
The median age of the men in the study was 65 years; the median age of women was 60 years. Almost 98% of the participants were White. The majority received one to three infusions, most commonly with pembrolizumab monotherapy.
No funding for the study was reported. Mr. Said has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Overall, 62.4% of the 93 women in the review and 48.6% of the 142 men experienced confirmed skin reactions, for an odds ratio (OR) of 2.11 for women compared with men (P = .01).
“Clinicians should consider these results in counseling female patients regarding an elevated risk of dermatologic adverse events” when taking checkpoint inhibitors, said investigators led by Harvard University medical student Jordan Said, who presented the results at the American Academy of Dermatology Virtual Meeting Experience.
Autoimmune-like adverse events are common with checkpoint inhibitors. Dermatologic side effects occur in about half of people receiving monotherapy and more than that among patients receiving combination therapy.
Skin reactions can include psoriasiform dermatitis, lichenoid reactions, vitiligo, and bullous pemphigoid and may require hospitalization and prolonged steroid treatment.
Not much is known about risk factors for these reactions. A higher incidence among women has been previously reported. A 2019 study found a higher risk for pneumonitis and endocrinopathy, including hypophysitis, among women who underwent treatment for non–small cell lung cancer or metastatic melanoma.
The 2019 study found that the risk was higher among premenopausal women than postmenopausal women, which led some to suggest that estrogen may play a role.
The results of the Dana Farber review argue against that notion. In their review, the investigators found that the risk was similarly elevated among the 27 premenopausal women (OR, 1.97; P = .40) and the 66 postmenopausal women (OR, 2.17, P = .05). In the study, women who were aged 52 years or older at the start of treatment were considered to be postmenopausal.
“This suggests that factors beyond sex hormones are likely contributory” to the difference in risk between men and women. It’s known that women are at higher risk for autoimmune disease overall, which might be related to the increased odds of autoimmune-like reactions, and it may be that sex-related differences in innate and adoptive immunity are at work, Mr. Said noted.
When asked for comment, Douglas Johnson, MD, assistant professor of hematology/oncology at Vanderbilt University, Nashville, Tenn., said that although some studies have reported a greater risk for side effects among women, others have not. “Additional research is needed to determine the interactions between sex and effects of immune checkpoint inhibitors, as well as many other possible triggers of immune-related adverse events,” he said.
“Continued work in this area will be so important to help determine how to best counsel women and to ensure early recognition and intervention for dermatologic side effects,” said Bernice Kwong, MD, director of the Supportive Dermato-Oncology Program at Stanford (Calif.) University.
The patients in the review were treated from 2011 to 2016 and underwent at least monthly evaluations by their medical teams. They were taking either nivolumab, pembrolizumab, or ipilimumab or a nivolumab/ipilimumab combination.
The median age of the men in the study was 65 years; the median age of women was 60 years. Almost 98% of the participants were White. The majority received one to three infusions, most commonly with pembrolizumab monotherapy.
No funding for the study was reported. Mr. Said has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Overall, 62.4% of the 93 women in the review and 48.6% of the 142 men experienced confirmed skin reactions, for an odds ratio (OR) of 2.11 for women compared with men (P = .01).
“Clinicians should consider these results in counseling female patients regarding an elevated risk of dermatologic adverse events” when taking checkpoint inhibitors, said investigators led by Harvard University medical student Jordan Said, who presented the results at the American Academy of Dermatology Virtual Meeting Experience.
Autoimmune-like adverse events are common with checkpoint inhibitors. Dermatologic side effects occur in about half of people receiving monotherapy and more than that among patients receiving combination therapy.
Skin reactions can include psoriasiform dermatitis, lichenoid reactions, vitiligo, and bullous pemphigoid and may require hospitalization and prolonged steroid treatment.
Not much is known about risk factors for these reactions. A higher incidence among women has been previously reported. A 2019 study found a higher risk for pneumonitis and endocrinopathy, including hypophysitis, among women who underwent treatment for non–small cell lung cancer or metastatic melanoma.
The 2019 study found that the risk was higher among premenopausal women than postmenopausal women, which led some to suggest that estrogen may play a role.
The results of the Dana Farber review argue against that notion. In their review, the investigators found that the risk was similarly elevated among the 27 premenopausal women (OR, 1.97; P = .40) and the 66 postmenopausal women (OR, 2.17, P = .05). In the study, women who were aged 52 years or older at the start of treatment were considered to be postmenopausal.
“This suggests that factors beyond sex hormones are likely contributory” to the difference in risk between men and women. It’s known that women are at higher risk for autoimmune disease overall, which might be related to the increased odds of autoimmune-like reactions, and it may be that sex-related differences in innate and adoptive immunity are at work, Mr. Said noted.
When asked for comment, Douglas Johnson, MD, assistant professor of hematology/oncology at Vanderbilt University, Nashville, Tenn., said that although some studies have reported a greater risk for side effects among women, others have not. “Additional research is needed to determine the interactions between sex and effects of immune checkpoint inhibitors, as well as many other possible triggers of immune-related adverse events,” he said.
“Continued work in this area will be so important to help determine how to best counsel women and to ensure early recognition and intervention for dermatologic side effects,” said Bernice Kwong, MD, director of the Supportive Dermato-Oncology Program at Stanford (Calif.) University.
The patients in the review were treated from 2011 to 2016 and underwent at least monthly evaluations by their medical teams. They were taking either nivolumab, pembrolizumab, or ipilimumab or a nivolumab/ipilimumab combination.
The median age of the men in the study was 65 years; the median age of women was 60 years. Almost 98% of the participants were White. The majority received one to three infusions, most commonly with pembrolizumab monotherapy.
No funding for the study was reported. Mr. Said has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Formal geriatric assessment should be routine
a geriatric oncologist said during a presentation at the American College of Physicians annual Internal Medicine meeting.
A 2020 ASCO survey, which the speaker, Grant R. Williams, MD, coauthored, found that 9 out of 10 community oncologists assessed at least some older patients differently than younger patients. But only 1 out of 3 did so in a formal manner, Dr. Williams, director of the cancer and aging program at the University of Alabama at Birmingham, said during presentation at virtual meeting.
In most cases, informal geriatric assessment considers only the tip of the ‘geriatric oncology iceberg,’ including chronological age, performance status, tumor characteristics, and organ function, Dr. Williams noted.
In contrast, formal geriatric assessment dives deeper, measuring a series of additional outcome-associated factors: polypharmacy, comorbidities, falls, psychosocial dysfunction, social support, sarcopenia, nutritional deficits, cognitive impairment, and functional issues.
“All these other factors under the surface are critically important to developing a personalized and individualized cancer treatment plan for older adults,” Dr. Williams said.
He went on to explain that elderly cancer patients can be sorted into three broad categories: fit, vulnerable, and frail. Fit and frail patients are relatively easy to identify, but most elderly patients fall into the vulnerable category, Dr. Williams noted.
“It’s really more challenging to identify those individuals across the spectrum than those at the extremes,” Dr. Williams said, noting that formal geriatric assessment can detect problems not found routinely.
Formal geriatric assessment’s value
Geriatric assessment can be used for risk modeling and making life-expectancy calculations. It can also be used as an interventional tool, guiding cancer treatment selection, he said. Furthermore, it can open doors to general health interventions, such as occupational therapy, to reduce fall risk.
Beneficial interventions identified by geriatric assessment have been shown to improve function, reduce chemotherapy toxicities, improve quality of life, and extend survival, Dr. Williams noted.
Formal geriatric assessment may be particularly useful for primary care providers considering referral to an oncologist, he said.
“I think performing a geriatric assessment [prior to referral] would be a great idea. And that’s twofold: Even before you send them to the oncologist, it gives you an idea of how they may tolerate treatment, and frankly, it may give you an idea that they don’t need a referral to the oncologist if they’re particularly frail,” noted Dr. Williams.
Alternatives to formal assessments
When asked how providers can incorporate formal assessments into a busy day at the clinic, Dr. Williams encouraged the use of abbreviated formal assessments, then adding further testing if needed.
“Given known time and support staff restraints, modified geriatric assessment tools have been developed that are either mostly or completely patient-reported,” he said in an interview, referring to the Cancer and Aging Research Group (CARG) Geriatric Assessment and the Cancer and Aging Resilience Evaluation (CARE), respectively.
“[These assessments] can easily be completed before clinical visits or while in the waiting room,” Dr. Williams noted. “The additional objective tests, such as Timed Up and Go, and Mental Status Exam, can be completed if deemed necessary based on these initial assessments.”
Martine Extermann, MD, PhD, provided her suggestions in an interview for what physicians can do to get better outcomes for this patient group.
“The secret of successful anti-cancer treatment in an older person is to be proactive with supportive care,” said Dr. Extermann, leader of the senior adult oncology program at H. Lee Moffitt Cancer Center & Research Institute, Tampa, Fla. “You have to really plan ahead, identify the support gaps, identify the potential problems, and prevent them thoroughly. The upfront work of good patient evaluation will save you a lot of trouble down the line,” she added.
Ms. Extermann also mentioned the challenges to providing care to geriatric patients with cancer, including a lack of financial incentive for physicians to specialize in geriatrics.
Gerontology remains a practice gap
Oncologists who don’t perform geriatric assessments are probably missing more than they think, Dr. Extermann said in an interview.
“Many oncologists don’t fully realize the importance of [geriatric assessment] yet,” Dr. Extermann said. “They kind of think that their internal medicine training will carry through, and they’ll be able to identify everything; actually, we know very well we miss half of what is found by geriatric assessment clinically.”
Gerontology remains a practice gap, Dr. Extermann said, not only within oncology, but across specialties.
“One of the big problems with the U.S. health care system is we don’t have enough geriatricians, and the reason we don’t have enough geriatricians is because we don’t pay them,” she said.
“Geriatrics is the only specialty where you do more training to be paid less, because Medicare doesn’t reimburse geriatric assessment, [and] it doesn’t reimburse geriatric consultation. [This] doesn’t motivate universities to create geriatric clinics and geriatric programs because they will lose money, basically, doing that. If we want to really solve the problem, we have to solve the reimbursement problem up front,” she explained.
Dr. Williams disclosed financial relationships with Carevive Health Systems, Cardinal Health, the National Cancer Institute, and the American Cancer Society. Dr. Extermann reported no conflicts of interest.
a geriatric oncologist said during a presentation at the American College of Physicians annual Internal Medicine meeting.
A 2020 ASCO survey, which the speaker, Grant R. Williams, MD, coauthored, found that 9 out of 10 community oncologists assessed at least some older patients differently than younger patients. But only 1 out of 3 did so in a formal manner, Dr. Williams, director of the cancer and aging program at the University of Alabama at Birmingham, said during presentation at virtual meeting.
In most cases, informal geriatric assessment considers only the tip of the ‘geriatric oncology iceberg,’ including chronological age, performance status, tumor characteristics, and organ function, Dr. Williams noted.
In contrast, formal geriatric assessment dives deeper, measuring a series of additional outcome-associated factors: polypharmacy, comorbidities, falls, psychosocial dysfunction, social support, sarcopenia, nutritional deficits, cognitive impairment, and functional issues.
“All these other factors under the surface are critically important to developing a personalized and individualized cancer treatment plan for older adults,” Dr. Williams said.
He went on to explain that elderly cancer patients can be sorted into three broad categories: fit, vulnerable, and frail. Fit and frail patients are relatively easy to identify, but most elderly patients fall into the vulnerable category, Dr. Williams noted.
“It’s really more challenging to identify those individuals across the spectrum than those at the extremes,” Dr. Williams said, noting that formal geriatric assessment can detect problems not found routinely.
Formal geriatric assessment’s value
Geriatric assessment can be used for risk modeling and making life-expectancy calculations. It can also be used as an interventional tool, guiding cancer treatment selection, he said. Furthermore, it can open doors to general health interventions, such as occupational therapy, to reduce fall risk.
Beneficial interventions identified by geriatric assessment have been shown to improve function, reduce chemotherapy toxicities, improve quality of life, and extend survival, Dr. Williams noted.
Formal geriatric assessment may be particularly useful for primary care providers considering referral to an oncologist, he said.
“I think performing a geriatric assessment [prior to referral] would be a great idea. And that’s twofold: Even before you send them to the oncologist, it gives you an idea of how they may tolerate treatment, and frankly, it may give you an idea that they don’t need a referral to the oncologist if they’re particularly frail,” noted Dr. Williams.
Alternatives to formal assessments
When asked how providers can incorporate formal assessments into a busy day at the clinic, Dr. Williams encouraged the use of abbreviated formal assessments, then adding further testing if needed.
“Given known time and support staff restraints, modified geriatric assessment tools have been developed that are either mostly or completely patient-reported,” he said in an interview, referring to the Cancer and Aging Research Group (CARG) Geriatric Assessment and the Cancer and Aging Resilience Evaluation (CARE), respectively.
“[These assessments] can easily be completed before clinical visits or while in the waiting room,” Dr. Williams noted. “The additional objective tests, such as Timed Up and Go, and Mental Status Exam, can be completed if deemed necessary based on these initial assessments.”
Martine Extermann, MD, PhD, provided her suggestions in an interview for what physicians can do to get better outcomes for this patient group.
“The secret of successful anti-cancer treatment in an older person is to be proactive with supportive care,” said Dr. Extermann, leader of the senior adult oncology program at H. Lee Moffitt Cancer Center & Research Institute, Tampa, Fla. “You have to really plan ahead, identify the support gaps, identify the potential problems, and prevent them thoroughly. The upfront work of good patient evaluation will save you a lot of trouble down the line,” she added.
Ms. Extermann also mentioned the challenges to providing care to geriatric patients with cancer, including a lack of financial incentive for physicians to specialize in geriatrics.
Gerontology remains a practice gap
Oncologists who don’t perform geriatric assessments are probably missing more than they think, Dr. Extermann said in an interview.
“Many oncologists don’t fully realize the importance of [geriatric assessment] yet,” Dr. Extermann said. “They kind of think that their internal medicine training will carry through, and they’ll be able to identify everything; actually, we know very well we miss half of what is found by geriatric assessment clinically.”
Gerontology remains a practice gap, Dr. Extermann said, not only within oncology, but across specialties.
“One of the big problems with the U.S. health care system is we don’t have enough geriatricians, and the reason we don’t have enough geriatricians is because we don’t pay them,” she said.
“Geriatrics is the only specialty where you do more training to be paid less, because Medicare doesn’t reimburse geriatric assessment, [and] it doesn’t reimburse geriatric consultation. [This] doesn’t motivate universities to create geriatric clinics and geriatric programs because they will lose money, basically, doing that. If we want to really solve the problem, we have to solve the reimbursement problem up front,” she explained.
Dr. Williams disclosed financial relationships with Carevive Health Systems, Cardinal Health, the National Cancer Institute, and the American Cancer Society. Dr. Extermann reported no conflicts of interest.
a geriatric oncologist said during a presentation at the American College of Physicians annual Internal Medicine meeting.
A 2020 ASCO survey, which the speaker, Grant R. Williams, MD, coauthored, found that 9 out of 10 community oncologists assessed at least some older patients differently than younger patients. But only 1 out of 3 did so in a formal manner, Dr. Williams, director of the cancer and aging program at the University of Alabama at Birmingham, said during presentation at virtual meeting.
In most cases, informal geriatric assessment considers only the tip of the ‘geriatric oncology iceberg,’ including chronological age, performance status, tumor characteristics, and organ function, Dr. Williams noted.
In contrast, formal geriatric assessment dives deeper, measuring a series of additional outcome-associated factors: polypharmacy, comorbidities, falls, psychosocial dysfunction, social support, sarcopenia, nutritional deficits, cognitive impairment, and functional issues.
“All these other factors under the surface are critically important to developing a personalized and individualized cancer treatment plan for older adults,” Dr. Williams said.
He went on to explain that elderly cancer patients can be sorted into three broad categories: fit, vulnerable, and frail. Fit and frail patients are relatively easy to identify, but most elderly patients fall into the vulnerable category, Dr. Williams noted.
“It’s really more challenging to identify those individuals across the spectrum than those at the extremes,” Dr. Williams said, noting that formal geriatric assessment can detect problems not found routinely.
Formal geriatric assessment’s value
Geriatric assessment can be used for risk modeling and making life-expectancy calculations. It can also be used as an interventional tool, guiding cancer treatment selection, he said. Furthermore, it can open doors to general health interventions, such as occupational therapy, to reduce fall risk.
Beneficial interventions identified by geriatric assessment have been shown to improve function, reduce chemotherapy toxicities, improve quality of life, and extend survival, Dr. Williams noted.
Formal geriatric assessment may be particularly useful for primary care providers considering referral to an oncologist, he said.
“I think performing a geriatric assessment [prior to referral] would be a great idea. And that’s twofold: Even before you send them to the oncologist, it gives you an idea of how they may tolerate treatment, and frankly, it may give you an idea that they don’t need a referral to the oncologist if they’re particularly frail,” noted Dr. Williams.
Alternatives to formal assessments
When asked how providers can incorporate formal assessments into a busy day at the clinic, Dr. Williams encouraged the use of abbreviated formal assessments, then adding further testing if needed.
“Given known time and support staff restraints, modified geriatric assessment tools have been developed that are either mostly or completely patient-reported,” he said in an interview, referring to the Cancer and Aging Research Group (CARG) Geriatric Assessment and the Cancer and Aging Resilience Evaluation (CARE), respectively.
“[These assessments] can easily be completed before clinical visits or while in the waiting room,” Dr. Williams noted. “The additional objective tests, such as Timed Up and Go, and Mental Status Exam, can be completed if deemed necessary based on these initial assessments.”
Martine Extermann, MD, PhD, provided her suggestions in an interview for what physicians can do to get better outcomes for this patient group.
“The secret of successful anti-cancer treatment in an older person is to be proactive with supportive care,” said Dr. Extermann, leader of the senior adult oncology program at H. Lee Moffitt Cancer Center & Research Institute, Tampa, Fla. “You have to really plan ahead, identify the support gaps, identify the potential problems, and prevent them thoroughly. The upfront work of good patient evaluation will save you a lot of trouble down the line,” she added.
Ms. Extermann also mentioned the challenges to providing care to geriatric patients with cancer, including a lack of financial incentive for physicians to specialize in geriatrics.
Gerontology remains a practice gap
Oncologists who don’t perform geriatric assessments are probably missing more than they think, Dr. Extermann said in an interview.
“Many oncologists don’t fully realize the importance of [geriatric assessment] yet,” Dr. Extermann said. “They kind of think that their internal medicine training will carry through, and they’ll be able to identify everything; actually, we know very well we miss half of what is found by geriatric assessment clinically.”
Gerontology remains a practice gap, Dr. Extermann said, not only within oncology, but across specialties.
“One of the big problems with the U.S. health care system is we don’t have enough geriatricians, and the reason we don’t have enough geriatricians is because we don’t pay them,” she said.
“Geriatrics is the only specialty where you do more training to be paid less, because Medicare doesn’t reimburse geriatric assessment, [and] it doesn’t reimburse geriatric consultation. [This] doesn’t motivate universities to create geriatric clinics and geriatric programs because they will lose money, basically, doing that. If we want to really solve the problem, we have to solve the reimbursement problem up front,” she explained.
Dr. Williams disclosed financial relationships with Carevive Health Systems, Cardinal Health, the National Cancer Institute, and the American Cancer Society. Dr. Extermann reported no conflicts of interest.
FROM INTERNAL MEDICINE 2021
The power and promise of social media in oncology
Mark A. Lewis, MD, explained to the COSMO meeting audience how storytelling on social media can educate and engage patients, advocates, and professional colleagues – advancing knowledge, dispelling misinformation, and promoting clinical research.
Dr. Lewis, an oncologist at Intermountain Healthcare in Salt Lake City, reflected on the bifid roles of oncologists as scientists engaged in life-long learning and humanists who can internalize and appreciate the unique character and circumstances of their patients.
Patients who have serious illnesses are necessarily aggregated by statistics. However, in an essay published in 2011, Dr. Lewis noted that “each individual patient partakes in a unique, irreproducible experiment where n = 1” (J Clin Oncol. 2011 Aug 1;29[22]:3103-4).
Dr. Lewis highlighted the duality of individual data points on a survival curve as descriptors of common disease trajectories and treatment effects. However, those data points also conceal important narratives regarding the most highly valued aspects of the doctor-patient relationship and the impact of cancer treatment on patients’ lives.
In referring to the futuristic essay “Ars Brevis,” Dr. Lewis contrasted the humanism of oncology specialists in the present day with the fictional image of data-regurgitating robots programmed to maximize the efficiency of each patient encounter (J Clin Oncol. 2013 May 10;31[14]:1792-4).
Dr. Lewis reminded attendees that to practice medicine without using both “head and heart” undermines the inherent nature of medical care.
Unfortunately, that perspective may not match the public perception of oncologists. Dr. Lewis described his experience of typing “oncologists are” into an Internet search engine and seeing the auto-complete function prompt words such as “criminals,” “evil,” “murderers,” and “confused.”
Obviously, it is hard to establish a trusting patient-doctor relationship if that is the prima facie perception of the oncology specialty.
Dispelling myths and creating community via social media
A primary goal of consultation with a newly-diagnosed cancer patient is for the patient to feel that the oncologist will be there to take care of them, regardless of what the future holds.
Dr. Lewis has found that social media can potentially extend that feeling to a global community of patients, caregivers, and others seeking information relevant to a cancer diagnosis. He believes that oncologists have an opportunity to dispel myths and fears by being attentive to the real-life concerns of patients.
Dr. Lewis took advantage of this opportunity when he underwent a Whipple procedure (pancreaticoduodenectomy) for a pancreatic neuroendocrine tumor. He and the hospital’s media services staff “live-tweeted” his surgery and recovery.
With those tweets, Dr. Lewis demystified each step of a major surgical procedure. From messages he received on social media, Dr. Lewis knows he made the decision to have a Whipple procedure more acceptable to other patients.
His personal medical experience notwithstanding, Dr. Lewis acknowledged that every patient’s circumstances are unique.
Oncologists cannot possibly empathize with every circumstance. However, when they show sensitivity to personal elements of the cancer experience, they shed light on the complicated role they play in patient care and can facilitate good decision-making among patients across the globe.
Social media for professional development and patient care
The publication of his 2011 essay was gratifying for Dr. Lewis, but the finite number of comments he received thereafter illustrated the rather limited audience that traditional academic publications have and the laborious process for subsequent interaction (J Clin Oncol. 2011 Aug 1;29[22]:3103-4).
First as an observer and later as a participant on social media, Dr. Lewis appreciated that teaching points and publications can be amplified by global distribution and the potential for informal bidirectional communication.
Social media platforms enable physicians to connect with a larger audience through participative communication, in which users develop, share, and react to content (N Engl J Med. 2009 Aug 13;361[7]:649-51).
Dr. Lewis reflected on how oncologists are challenged to sort through the thousands of oncology-focused publications annually. Through social media, one can see the studies on which the experts are commenting and appreciate the nuances that contextualize the results. Focused interactions with renowned doctors, at regular intervals, require little formality.
Online journal clubs enable the sharing of ideas, opinions, multimedia resources, and references across institutional and international borders (J Gen Intern Med. 2014 Oct;29[10]:1317-8).
Social media in oncology: Accomplishments and promise
The development of broadband Internet, wireless connectivity, and social media for peer-to-peer and general communication are among the major technological advances that have transformed medical communication.
As an organization, COSMO aims to describe, understand, and improve the use of social media to increase the penetration of evidence-based guidelines and research insights into clinical practice (Future Oncol. 2017 Jun;13[15]:1281-5).
At the inaugural COSMO meeting, areas of progress since COSMO’s inception in 2015 were highlighted, including:
- The involvement of cancer professionals and advocates in multiple distinctive platforms.
- The development of hashtag libraries to aggregate interest groups and topics.
- The refinement of strategies for engaging advocates with attention to inclusiveness.
- A steady trajectory of growth in tweeting at scientific conferences.
An overarching theme of the COSMO meeting was “authenticity,” a virtue that is easy to admire but requires conscious, consistent effort to achieve.
Disclosure of conflicts of interest and avoiding using social media simply as a recruitment tool for clinical trials are basic components of accurate self-representation.
In addition, Dr. Lewis advocated for sharing personal experiences in a component of social media posts so oncologists can show humanity as a feature of their professional online identity and inherent nature.
Dr. Lewis disclosed consultancy with Medscape/WebMD, which are owned by the same parent company as MDedge. He also disclosed relationships with Foundation Medicine, Natera, Exelixis, QED, HalioDX, and Ipsen.
Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.
Mark A. Lewis, MD, explained to the COSMO meeting audience how storytelling on social media can educate and engage patients, advocates, and professional colleagues – advancing knowledge, dispelling misinformation, and promoting clinical research.
Dr. Lewis, an oncologist at Intermountain Healthcare in Salt Lake City, reflected on the bifid roles of oncologists as scientists engaged in life-long learning and humanists who can internalize and appreciate the unique character and circumstances of their patients.
Patients who have serious illnesses are necessarily aggregated by statistics. However, in an essay published in 2011, Dr. Lewis noted that “each individual patient partakes in a unique, irreproducible experiment where n = 1” (J Clin Oncol. 2011 Aug 1;29[22]:3103-4).
Dr. Lewis highlighted the duality of individual data points on a survival curve as descriptors of common disease trajectories and treatment effects. However, those data points also conceal important narratives regarding the most highly valued aspects of the doctor-patient relationship and the impact of cancer treatment on patients’ lives.
In referring to the futuristic essay “Ars Brevis,” Dr. Lewis contrasted the humanism of oncology specialists in the present day with the fictional image of data-regurgitating robots programmed to maximize the efficiency of each patient encounter (J Clin Oncol. 2013 May 10;31[14]:1792-4).
Dr. Lewis reminded attendees that to practice medicine without using both “head and heart” undermines the inherent nature of medical care.
Unfortunately, that perspective may not match the public perception of oncologists. Dr. Lewis described his experience of typing “oncologists are” into an Internet search engine and seeing the auto-complete function prompt words such as “criminals,” “evil,” “murderers,” and “confused.”
Obviously, it is hard to establish a trusting patient-doctor relationship if that is the prima facie perception of the oncology specialty.
Dispelling myths and creating community via social media
A primary goal of consultation with a newly-diagnosed cancer patient is for the patient to feel that the oncologist will be there to take care of them, regardless of what the future holds.
Dr. Lewis has found that social media can potentially extend that feeling to a global community of patients, caregivers, and others seeking information relevant to a cancer diagnosis. He believes that oncologists have an opportunity to dispel myths and fears by being attentive to the real-life concerns of patients.
Dr. Lewis took advantage of this opportunity when he underwent a Whipple procedure (pancreaticoduodenectomy) for a pancreatic neuroendocrine tumor. He and the hospital’s media services staff “live-tweeted” his surgery and recovery.
With those tweets, Dr. Lewis demystified each step of a major surgical procedure. From messages he received on social media, Dr. Lewis knows he made the decision to have a Whipple procedure more acceptable to other patients.
His personal medical experience notwithstanding, Dr. Lewis acknowledged that every patient’s circumstances are unique.
Oncologists cannot possibly empathize with every circumstance. However, when they show sensitivity to personal elements of the cancer experience, they shed light on the complicated role they play in patient care and can facilitate good decision-making among patients across the globe.
Social media for professional development and patient care
The publication of his 2011 essay was gratifying for Dr. Lewis, but the finite number of comments he received thereafter illustrated the rather limited audience that traditional academic publications have and the laborious process for subsequent interaction (J Clin Oncol. 2011 Aug 1;29[22]:3103-4).
First as an observer and later as a participant on social media, Dr. Lewis appreciated that teaching points and publications can be amplified by global distribution and the potential for informal bidirectional communication.
Social media platforms enable physicians to connect with a larger audience through participative communication, in which users develop, share, and react to content (N Engl J Med. 2009 Aug 13;361[7]:649-51).
Dr. Lewis reflected on how oncologists are challenged to sort through the thousands of oncology-focused publications annually. Through social media, one can see the studies on which the experts are commenting and appreciate the nuances that contextualize the results. Focused interactions with renowned doctors, at regular intervals, require little formality.
Online journal clubs enable the sharing of ideas, opinions, multimedia resources, and references across institutional and international borders (J Gen Intern Med. 2014 Oct;29[10]:1317-8).
Social media in oncology: Accomplishments and promise
The development of broadband Internet, wireless connectivity, and social media for peer-to-peer and general communication are among the major technological advances that have transformed medical communication.
As an organization, COSMO aims to describe, understand, and improve the use of social media to increase the penetration of evidence-based guidelines and research insights into clinical practice (Future Oncol. 2017 Jun;13[15]:1281-5).
At the inaugural COSMO meeting, areas of progress since COSMO’s inception in 2015 were highlighted, including:
- The involvement of cancer professionals and advocates in multiple distinctive platforms.
- The development of hashtag libraries to aggregate interest groups and topics.
- The refinement of strategies for engaging advocates with attention to inclusiveness.
- A steady trajectory of growth in tweeting at scientific conferences.
An overarching theme of the COSMO meeting was “authenticity,” a virtue that is easy to admire but requires conscious, consistent effort to achieve.
Disclosure of conflicts of interest and avoiding using social media simply as a recruitment tool for clinical trials are basic components of accurate self-representation.
In addition, Dr. Lewis advocated for sharing personal experiences in a component of social media posts so oncologists can show humanity as a feature of their professional online identity and inherent nature.
Dr. Lewis disclosed consultancy with Medscape/WebMD, which are owned by the same parent company as MDedge. He also disclosed relationships with Foundation Medicine, Natera, Exelixis, QED, HalioDX, and Ipsen.
Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.
Mark A. Lewis, MD, explained to the COSMO meeting audience how storytelling on social media can educate and engage patients, advocates, and professional colleagues – advancing knowledge, dispelling misinformation, and promoting clinical research.
Dr. Lewis, an oncologist at Intermountain Healthcare in Salt Lake City, reflected on the bifid roles of oncologists as scientists engaged in life-long learning and humanists who can internalize and appreciate the unique character and circumstances of their patients.
Patients who have serious illnesses are necessarily aggregated by statistics. However, in an essay published in 2011, Dr. Lewis noted that “each individual patient partakes in a unique, irreproducible experiment where n = 1” (J Clin Oncol. 2011 Aug 1;29[22]:3103-4).
Dr. Lewis highlighted the duality of individual data points on a survival curve as descriptors of common disease trajectories and treatment effects. However, those data points also conceal important narratives regarding the most highly valued aspects of the doctor-patient relationship and the impact of cancer treatment on patients’ lives.
In referring to the futuristic essay “Ars Brevis,” Dr. Lewis contrasted the humanism of oncology specialists in the present day with the fictional image of data-regurgitating robots programmed to maximize the efficiency of each patient encounter (J Clin Oncol. 2013 May 10;31[14]:1792-4).
Dr. Lewis reminded attendees that to practice medicine without using both “head and heart” undermines the inherent nature of medical care.
Unfortunately, that perspective may not match the public perception of oncologists. Dr. Lewis described his experience of typing “oncologists are” into an Internet search engine and seeing the auto-complete function prompt words such as “criminals,” “evil,” “murderers,” and “confused.”
Obviously, it is hard to establish a trusting patient-doctor relationship if that is the prima facie perception of the oncology specialty.
Dispelling myths and creating community via social media
A primary goal of consultation with a newly-diagnosed cancer patient is for the patient to feel that the oncologist will be there to take care of them, regardless of what the future holds.
Dr. Lewis has found that social media can potentially extend that feeling to a global community of patients, caregivers, and others seeking information relevant to a cancer diagnosis. He believes that oncologists have an opportunity to dispel myths and fears by being attentive to the real-life concerns of patients.
Dr. Lewis took advantage of this opportunity when he underwent a Whipple procedure (pancreaticoduodenectomy) for a pancreatic neuroendocrine tumor. He and the hospital’s media services staff “live-tweeted” his surgery and recovery.
With those tweets, Dr. Lewis demystified each step of a major surgical procedure. From messages he received on social media, Dr. Lewis knows he made the decision to have a Whipple procedure more acceptable to other patients.
His personal medical experience notwithstanding, Dr. Lewis acknowledged that every patient’s circumstances are unique.
Oncologists cannot possibly empathize with every circumstance. However, when they show sensitivity to personal elements of the cancer experience, they shed light on the complicated role they play in patient care and can facilitate good decision-making among patients across the globe.
Social media for professional development and patient care
The publication of his 2011 essay was gratifying for Dr. Lewis, but the finite number of comments he received thereafter illustrated the rather limited audience that traditional academic publications have and the laborious process for subsequent interaction (J Clin Oncol. 2011 Aug 1;29[22]:3103-4).
First as an observer and later as a participant on social media, Dr. Lewis appreciated that teaching points and publications can be amplified by global distribution and the potential for informal bidirectional communication.
Social media platforms enable physicians to connect with a larger audience through participative communication, in which users develop, share, and react to content (N Engl J Med. 2009 Aug 13;361[7]:649-51).
Dr. Lewis reflected on how oncologists are challenged to sort through the thousands of oncology-focused publications annually. Through social media, one can see the studies on which the experts are commenting and appreciate the nuances that contextualize the results. Focused interactions with renowned doctors, at regular intervals, require little formality.
Online journal clubs enable the sharing of ideas, opinions, multimedia resources, and references across institutional and international borders (J Gen Intern Med. 2014 Oct;29[10]:1317-8).
Social media in oncology: Accomplishments and promise
The development of broadband Internet, wireless connectivity, and social media for peer-to-peer and general communication are among the major technological advances that have transformed medical communication.
As an organization, COSMO aims to describe, understand, and improve the use of social media to increase the penetration of evidence-based guidelines and research insights into clinical practice (Future Oncol. 2017 Jun;13[15]:1281-5).
At the inaugural COSMO meeting, areas of progress since COSMO’s inception in 2015 were highlighted, including:
- The involvement of cancer professionals and advocates in multiple distinctive platforms.
- The development of hashtag libraries to aggregate interest groups and topics.
- The refinement of strategies for engaging advocates with attention to inclusiveness.
- A steady trajectory of growth in tweeting at scientific conferences.
An overarching theme of the COSMO meeting was “authenticity,” a virtue that is easy to admire but requires conscious, consistent effort to achieve.
Disclosure of conflicts of interest and avoiding using social media simply as a recruitment tool for clinical trials are basic components of accurate self-representation.
In addition, Dr. Lewis advocated for sharing personal experiences in a component of social media posts so oncologists can show humanity as a feature of their professional online identity and inherent nature.
Dr. Lewis disclosed consultancy with Medscape/WebMD, which are owned by the same parent company as MDedge. He also disclosed relationships with Foundation Medicine, Natera, Exelixis, QED, HalioDX, and Ipsen.
Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.
FROM COSMO 2021
For cervical cancer screening, any strategy is acceptable
Cytology testing every 3 years, cytology/human papillomavirus cotesting every 5 years, and primary HPV testing every 5 years are similarly effective at reducing cervical cancer risk, said Rachel P. Brook, MD, of the University of California, Los Angeles Health Iris Cantor Women’s Health Center, during a presentation at the annual meeting of the American College of Physicians.
“The most important thing a primary care provider can do is to screen with whatever test is most accessible,” Dr. Brook said in an interview. She also noted that access to screening remains a pressing concern, particularly among underrepresented groups and women in rural areas. Even when women can access testing, follow-up after abnormal results can be inadequate, leading to increased risk of cervical cancer mortality.
To address some of these shortcomings, Dr. Brook provided an overview of current guidelines and appropriate responses to abnormal test results.
First, during her presentation, she noted that guideline recommendations do not apply to patients with additional risk factors, including a compromised immune system, HIV infection, previous treatment of cervical cancer or a high-grade cancerous lesion, or in utero exposure to diethylstilbestrol.
“This is very important,” Dr. Brook said during her presentation. “They should receive individualized care due to their above average risk of cervical cancer.”
Among women with average risk, both the USPSTF 2018 guideline and the ACS 2020 guideline recommend against screening women aged less than 21 years.
In a major change to the most recent ACS guideline, screening women aged 21-24 years is no longer recommended, in contrast with the USPSTF guideline, which still calls for cytology every 3 years for this age group. This recommendation by the USPSTF extends to women aged 25-29 years, a group for which the ACS recommends primary HPV testing every 5 years, cytology/HPV cotesting every 5 years, or cytology testing every 3 years. For both organizations, any of these three testing methods is recommended for women aged 30-65 years, followed by discontinuation of testing after 65 years, given adequate prior screening.
“For all these recommendations and guidelines, they’re pertinent to patients regardless of HPV vaccination status,” Dr. Brook said. But she added that increased rates of HPV vaccination may affect future screening guidelines, as vaccinated patients are more likely to have false positive cytology results because of low-risk HPV strains. This trend may steer future recommendations toward primary HPV testing, Dr. Brook said.
Presently, for applicable age groups, the ACS guideline favors HPV testing alone over cytology alone or cotesting, whereas the USPSTF guideline offers no preference between the three testing strategies.
Primary HPV vs. cytology testing
Dr. Brook said a single negative HPV test provides more than 95% assurance that a patient will not develop cervical cancer or a cancer precursor within the next 5 years. One negative HPV test offers similar reliability to about 3 negative cytology tests.
Switching to a 5-year testing cycle may be unsettling for patients who are used to getting a Pap test every year, but having a conversation about test accuracy can help assuage patient concerns, she said.
Still, Dr. Brook emphasized that any of the three testing strategies is ultimately acceptable.
“The take-home message here is – truly – that any of the recommended screening options will greatly reduce cervical cancer risk,” Dr. Brook said. “So, screen. And if there is any confusion or concern with your patients about which [screening strategy to use], just help them decide on any of the three. But please screen.”
Self-swabbing could improve screening in certain groups
To improve screening rates, particularly for women with poor access and those averse to a speculum exam, Dr. Brook highlighted self-swabbing primary HPV tests, which may soon be available. While no self-swabbing HPV tests are yet approved by the Food and Drug Administration, they offer a 76% sensitivity rate for cervical intraepithelial neoplasia grade 2, and a rate of 85% for CIN3, compared with 91% for physician-collected samples.
Regardless of the exact HPV test, Dr. Brook advised appropriate reflex testing.
“We need to make sure all primary HPV screening tests positive for types other than HPV-16 or -18 will require additional reflex triage testing with cytology,” Dr. Brook said in interview. “If not – if a woman has a primary HPV screening test that is positive and I cannot perform reflex cytology – I have to bring her back for an additional test and speculum exam to get cytology, which is an unnecessary burden to the patient, and also increases testing.”
Kathy L. MacLaughlin, MD, associate professor of family medicine at Mayo Clinic, Rochester, Minn., said this is one drawback to self-swabbing tests in an interview.
“If there is a positive HPV result [with a self-swabbing test], the patient will need to have a clinic appointment for Pap collection [if one of the ‘other’ 12 HPV types are identified], or be referred for a colposcopy [if HPV types 16 or 18 are identified],” Dr. MacLaughlin said. “There need to be plans in place for access to those services.”
Incidentally, it may be women who face barriers to access that need self-swabbing HPV tests the most, according to Dr. MacLaughlin.
“I think there is significant potential to improve screening rates among never-screened and underscreened women and those are the groups for whom this makes the most sense,” she said. “I don’t think anyone is suggesting that women who have the means and interest in scheduling a face-to-face visit for clinician-collected screening switch to self-screening, but it is a promising option [once FDA approved] for reaching other women and reducing disparities in screening rates.”
Dr. MacLaughlin suggested that self-screening programs could operate outside of normal business hours in a variety of settings, such as homes, community centers, and churches.
Until self-screening is an option, Dr. MacLaughlin agreed with Dr. Brook that any of the three testing strategies is suitable for screening, and recommended that primary care providers seize the opportunities presented to them.
“Individual primary care providers can improve screening rates by offering to update cervical cancer screening at a clinic appointment even if that was not the primary indication for the visit, especially for women who are long overdue,” Dr. MacLaughlin said. “If there is just no time to fit in the screening or the patient declines, then order a return visit and have the patient stop at the appointment desk as they leave.”
“I recognize we are asked to fit in more and more in less time, but I’ve found this to be effective when I have capacity in the clinic day to offer it,” she added.
Dr. Brook and Dr. MacLaughlin reported no conflicts of interest.
Cytology testing every 3 years, cytology/human papillomavirus cotesting every 5 years, and primary HPV testing every 5 years are similarly effective at reducing cervical cancer risk, said Rachel P. Brook, MD, of the University of California, Los Angeles Health Iris Cantor Women’s Health Center, during a presentation at the annual meeting of the American College of Physicians.
“The most important thing a primary care provider can do is to screen with whatever test is most accessible,” Dr. Brook said in an interview. She also noted that access to screening remains a pressing concern, particularly among underrepresented groups and women in rural areas. Even when women can access testing, follow-up after abnormal results can be inadequate, leading to increased risk of cervical cancer mortality.
To address some of these shortcomings, Dr. Brook provided an overview of current guidelines and appropriate responses to abnormal test results.
First, during her presentation, she noted that guideline recommendations do not apply to patients with additional risk factors, including a compromised immune system, HIV infection, previous treatment of cervical cancer or a high-grade cancerous lesion, or in utero exposure to diethylstilbestrol.
“This is very important,” Dr. Brook said during her presentation. “They should receive individualized care due to their above average risk of cervical cancer.”
Among women with average risk, both the USPSTF 2018 guideline and the ACS 2020 guideline recommend against screening women aged less than 21 years.
In a major change to the most recent ACS guideline, screening women aged 21-24 years is no longer recommended, in contrast with the USPSTF guideline, which still calls for cytology every 3 years for this age group. This recommendation by the USPSTF extends to women aged 25-29 years, a group for which the ACS recommends primary HPV testing every 5 years, cytology/HPV cotesting every 5 years, or cytology testing every 3 years. For both organizations, any of these three testing methods is recommended for women aged 30-65 years, followed by discontinuation of testing after 65 years, given adequate prior screening.
“For all these recommendations and guidelines, they’re pertinent to patients regardless of HPV vaccination status,” Dr. Brook said. But she added that increased rates of HPV vaccination may affect future screening guidelines, as vaccinated patients are more likely to have false positive cytology results because of low-risk HPV strains. This trend may steer future recommendations toward primary HPV testing, Dr. Brook said.
Presently, for applicable age groups, the ACS guideline favors HPV testing alone over cytology alone or cotesting, whereas the USPSTF guideline offers no preference between the three testing strategies.
Primary HPV vs. cytology testing
Dr. Brook said a single negative HPV test provides more than 95% assurance that a patient will not develop cervical cancer or a cancer precursor within the next 5 years. One negative HPV test offers similar reliability to about 3 negative cytology tests.
Switching to a 5-year testing cycle may be unsettling for patients who are used to getting a Pap test every year, but having a conversation about test accuracy can help assuage patient concerns, she said.
Still, Dr. Brook emphasized that any of the three testing strategies is ultimately acceptable.
“The take-home message here is – truly – that any of the recommended screening options will greatly reduce cervical cancer risk,” Dr. Brook said. “So, screen. And if there is any confusion or concern with your patients about which [screening strategy to use], just help them decide on any of the three. But please screen.”
Self-swabbing could improve screening in certain groups
To improve screening rates, particularly for women with poor access and those averse to a speculum exam, Dr. Brook highlighted self-swabbing primary HPV tests, which may soon be available. While no self-swabbing HPV tests are yet approved by the Food and Drug Administration, they offer a 76% sensitivity rate for cervical intraepithelial neoplasia grade 2, and a rate of 85% for CIN3, compared with 91% for physician-collected samples.
Regardless of the exact HPV test, Dr. Brook advised appropriate reflex testing.
“We need to make sure all primary HPV screening tests positive for types other than HPV-16 or -18 will require additional reflex triage testing with cytology,” Dr. Brook said in interview. “If not – if a woman has a primary HPV screening test that is positive and I cannot perform reflex cytology – I have to bring her back for an additional test and speculum exam to get cytology, which is an unnecessary burden to the patient, and also increases testing.”
Kathy L. MacLaughlin, MD, associate professor of family medicine at Mayo Clinic, Rochester, Minn., said this is one drawback to self-swabbing tests in an interview.
“If there is a positive HPV result [with a self-swabbing test], the patient will need to have a clinic appointment for Pap collection [if one of the ‘other’ 12 HPV types are identified], or be referred for a colposcopy [if HPV types 16 or 18 are identified],” Dr. MacLaughlin said. “There need to be plans in place for access to those services.”
Incidentally, it may be women who face barriers to access that need self-swabbing HPV tests the most, according to Dr. MacLaughlin.
“I think there is significant potential to improve screening rates among never-screened and underscreened women and those are the groups for whom this makes the most sense,” she said. “I don’t think anyone is suggesting that women who have the means and interest in scheduling a face-to-face visit for clinician-collected screening switch to self-screening, but it is a promising option [once FDA approved] for reaching other women and reducing disparities in screening rates.”
Dr. MacLaughlin suggested that self-screening programs could operate outside of normal business hours in a variety of settings, such as homes, community centers, and churches.
Until self-screening is an option, Dr. MacLaughlin agreed with Dr. Brook that any of the three testing strategies is suitable for screening, and recommended that primary care providers seize the opportunities presented to them.
“Individual primary care providers can improve screening rates by offering to update cervical cancer screening at a clinic appointment even if that was not the primary indication for the visit, especially for women who are long overdue,” Dr. MacLaughlin said. “If there is just no time to fit in the screening or the patient declines, then order a return visit and have the patient stop at the appointment desk as they leave.”
“I recognize we are asked to fit in more and more in less time, but I’ve found this to be effective when I have capacity in the clinic day to offer it,” she added.
Dr. Brook and Dr. MacLaughlin reported no conflicts of interest.
Cytology testing every 3 years, cytology/human papillomavirus cotesting every 5 years, and primary HPV testing every 5 years are similarly effective at reducing cervical cancer risk, said Rachel P. Brook, MD, of the University of California, Los Angeles Health Iris Cantor Women’s Health Center, during a presentation at the annual meeting of the American College of Physicians.
“The most important thing a primary care provider can do is to screen with whatever test is most accessible,” Dr. Brook said in an interview. She also noted that access to screening remains a pressing concern, particularly among underrepresented groups and women in rural areas. Even when women can access testing, follow-up after abnormal results can be inadequate, leading to increased risk of cervical cancer mortality.
To address some of these shortcomings, Dr. Brook provided an overview of current guidelines and appropriate responses to abnormal test results.
First, during her presentation, she noted that guideline recommendations do not apply to patients with additional risk factors, including a compromised immune system, HIV infection, previous treatment of cervical cancer or a high-grade cancerous lesion, or in utero exposure to diethylstilbestrol.
“This is very important,” Dr. Brook said during her presentation. “They should receive individualized care due to their above average risk of cervical cancer.”
Among women with average risk, both the USPSTF 2018 guideline and the ACS 2020 guideline recommend against screening women aged less than 21 years.
In a major change to the most recent ACS guideline, screening women aged 21-24 years is no longer recommended, in contrast with the USPSTF guideline, which still calls for cytology every 3 years for this age group. This recommendation by the USPSTF extends to women aged 25-29 years, a group for which the ACS recommends primary HPV testing every 5 years, cytology/HPV cotesting every 5 years, or cytology testing every 3 years. For both organizations, any of these three testing methods is recommended for women aged 30-65 years, followed by discontinuation of testing after 65 years, given adequate prior screening.
“For all these recommendations and guidelines, they’re pertinent to patients regardless of HPV vaccination status,” Dr. Brook said. But she added that increased rates of HPV vaccination may affect future screening guidelines, as vaccinated patients are more likely to have false positive cytology results because of low-risk HPV strains. This trend may steer future recommendations toward primary HPV testing, Dr. Brook said.
Presently, for applicable age groups, the ACS guideline favors HPV testing alone over cytology alone or cotesting, whereas the USPSTF guideline offers no preference between the three testing strategies.
Primary HPV vs. cytology testing
Dr. Brook said a single negative HPV test provides more than 95% assurance that a patient will not develop cervical cancer or a cancer precursor within the next 5 years. One negative HPV test offers similar reliability to about 3 negative cytology tests.
Switching to a 5-year testing cycle may be unsettling for patients who are used to getting a Pap test every year, but having a conversation about test accuracy can help assuage patient concerns, she said.
Still, Dr. Brook emphasized that any of the three testing strategies is ultimately acceptable.
“The take-home message here is – truly – that any of the recommended screening options will greatly reduce cervical cancer risk,” Dr. Brook said. “So, screen. And if there is any confusion or concern with your patients about which [screening strategy to use], just help them decide on any of the three. But please screen.”
Self-swabbing could improve screening in certain groups
To improve screening rates, particularly for women with poor access and those averse to a speculum exam, Dr. Brook highlighted self-swabbing primary HPV tests, which may soon be available. While no self-swabbing HPV tests are yet approved by the Food and Drug Administration, they offer a 76% sensitivity rate for cervical intraepithelial neoplasia grade 2, and a rate of 85% for CIN3, compared with 91% for physician-collected samples.
Regardless of the exact HPV test, Dr. Brook advised appropriate reflex testing.
“We need to make sure all primary HPV screening tests positive for types other than HPV-16 or -18 will require additional reflex triage testing with cytology,” Dr. Brook said in interview. “If not – if a woman has a primary HPV screening test that is positive and I cannot perform reflex cytology – I have to bring her back for an additional test and speculum exam to get cytology, which is an unnecessary burden to the patient, and also increases testing.”
Kathy L. MacLaughlin, MD, associate professor of family medicine at Mayo Clinic, Rochester, Minn., said this is one drawback to self-swabbing tests in an interview.
“If there is a positive HPV result [with a self-swabbing test], the patient will need to have a clinic appointment for Pap collection [if one of the ‘other’ 12 HPV types are identified], or be referred for a colposcopy [if HPV types 16 or 18 are identified],” Dr. MacLaughlin said. “There need to be plans in place for access to those services.”
Incidentally, it may be women who face barriers to access that need self-swabbing HPV tests the most, according to Dr. MacLaughlin.
“I think there is significant potential to improve screening rates among never-screened and underscreened women and those are the groups for whom this makes the most sense,” she said. “I don’t think anyone is suggesting that women who have the means and interest in scheduling a face-to-face visit for clinician-collected screening switch to self-screening, but it is a promising option [once FDA approved] for reaching other women and reducing disparities in screening rates.”
Dr. MacLaughlin suggested that self-screening programs could operate outside of normal business hours in a variety of settings, such as homes, community centers, and churches.
Until self-screening is an option, Dr. MacLaughlin agreed with Dr. Brook that any of the three testing strategies is suitable for screening, and recommended that primary care providers seize the opportunities presented to them.
“Individual primary care providers can improve screening rates by offering to update cervical cancer screening at a clinic appointment even if that was not the primary indication for the visit, especially for women who are long overdue,” Dr. MacLaughlin said. “If there is just no time to fit in the screening or the patient declines, then order a return visit and have the patient stop at the appointment desk as they leave.”
“I recognize we are asked to fit in more and more in less time, but I’ve found this to be effective when I have capacity in the clinic day to offer it,” she added.
Dr. Brook and Dr. MacLaughlin reported no conflicts of interest.
FROM INTERNAL MEDICINE 2021