Breast Cancer ICYMI

People whose treatment for cancer is delayed by even 1 month have a 6%-13% higher risk of dying, suggests research published online in the BMJ.

In light of the treatment delays resulting from the pandemic, Canadian and U.K. researchers carried out a review and analysis of relevant studies published between January 2000 and April 2020.

Included studies examined data on surgical interventions, systemic therapy, or radiotherapy for seven forms of cancer – bladder, breast, colon, rectum, lung, cervix, and head and neck. Delays were measured from diagnosis to the first treatment or from the completion of one treatment to the start of the next.

The search identified 34 suitable studies for 17 indications, with data from more than 1.2 million patients. The analysis identified a significant association between delay and increased mortality for 13 of the 17 indications (P < .05).

For surgery, there was a 6%-8% increase in the risk of death for every 4-week treatment delay. Estimates for systemic treatment varied (hazard ratio range, 1.01-1.28). Four-week delays in radiotherapy were for radical radiotherapy for head and neck cancer (HR, 1.09; 95% confidence interval, 1.05-1.14), adjuvant radiotherapy after breast-conserving surgery (HR, 0.98; 95% CI, 0.88-1.09), and cervical cancer adjuvant radiotherapy (HR, 1.23; 95% CI, 1.00-1.50).

Delays of up to 8 and 12 weeks further increased mortality. An 8-week delay in breast cancer surgery was linked to a 17% increased mortality, and a 12-week delay would increase mortality by 26%.

A surgical delay of 12 weeks for patients with breast cancer continuing for 1 year – which is likely to be the case as the pandemic continues – would lead to 1,400 excess deaths in the United Kingdom.

The authors said the results of this study could be used to guide policy making on the organization of cancer services, particularly as the pandemic continues and further delays are expected.

This article originally appeared on Univadis, part of the Medscape Professional Network.

People whose treatment for cancer is delayed by even 1 month have a 6%-13% higher risk of dying, suggests research published online in the BMJ.

In light of the treatment delays resulting from the pandemic, Canadian and U.K. researchers carried out a review and analysis of relevant studies published between January 2000 and April 2020.

Included studies examined data on surgical interventions, systemic therapy, or radiotherapy for seven forms of cancer – bladder, breast, colon, rectum, lung, cervix, and head and neck. Delays were measured from diagnosis to the first treatment or from the completion of one treatment to the start of the next.

The search identified 34 suitable studies for 17 indications, with data from more than 1.2 million patients. The analysis identified a significant association between delay and increased mortality for 13 of the 17 indications (P < .05).

For surgery, there was a 6%-8% increase in the risk of death for every 4-week treatment delay. Estimates for systemic treatment varied (hazard ratio range, 1.01-1.28). Four-week delays in radiotherapy were for radical radiotherapy for head and neck cancer (HR, 1.09; 95% confidence interval, 1.05-1.14), adjuvant radiotherapy after breast-conserving surgery (HR, 0.98; 95% CI, 0.88-1.09), and cervical cancer adjuvant radiotherapy (HR, 1.23; 95% CI, 1.00-1.50).

Delays of up to 8 and 12 weeks further increased mortality. An 8-week delay in breast cancer surgery was linked to a 17% increased mortality, and a 12-week delay would increase mortality by 26%.

A surgical delay of 12 weeks for patients with breast cancer continuing for 1 year – which is likely to be the case as the pandemic continues – would lead to 1,400 excess deaths in the United Kingdom.

The authors said the results of this study could be used to guide policy making on the organization of cancer services, particularly as the pandemic continues and further delays are expected.

This article originally appeared on Univadis, part of the Medscape Professional Network.

People whose treatment for cancer is delayed by even 1 month have a 6%-13% higher risk of dying, suggests research published online in the BMJ.

In light of the treatment delays resulting from the pandemic, Canadian and U.K. researchers carried out a review and analysis of relevant studies published between January 2000 and April 2020.

Included studies examined data on surgical interventions, systemic therapy, or radiotherapy for seven forms of cancer – bladder, breast, colon, rectum, lung, cervix, and head and neck. Delays were measured from diagnosis to the first treatment or from the completion of one treatment to the start of the next.

The search identified 34 suitable studies for 17 indications, with data from more than 1.2 million patients. The analysis identified a significant association between delay and increased mortality for 13 of the 17 indications (P < .05).

For surgery, there was a 6%-8% increase in the risk of death for every 4-week treatment delay. Estimates for systemic treatment varied (hazard ratio range, 1.01-1.28). Four-week delays in radiotherapy were for radical radiotherapy for head and neck cancer (HR, 1.09; 95% confidence interval, 1.05-1.14), adjuvant radiotherapy after breast-conserving surgery (HR, 0.98; 95% CI, 0.88-1.09), and cervical cancer adjuvant radiotherapy (HR, 1.23; 95% CI, 1.00-1.50).

Delays of up to 8 and 12 weeks further increased mortality. An 8-week delay in breast cancer surgery was linked to a 17% increased mortality, and a 12-week delay would increase mortality by 26%.

A surgical delay of 12 weeks for patients with breast cancer continuing for 1 year – which is likely to be the case as the pandemic continues – would lead to 1,400 excess deaths in the United Kingdom.

The authors said the results of this study could be used to guide policy making on the organization of cancer services, particularly as the pandemic continues and further delays are expected.

This article originally appeared on Univadis, part of the Medscape Professional Network.

The US Food and Drug Administration (FDA) approved the use of durvalumab for patients with unresectable stage III non-small cell lung cancer (NSCLC) whose disease has not progressed following concurrent platinum-based chemotherapy and radiation therapy (CRT).¹ After 2 randomized phase 3 studies in 2017 and 2018 showed significant progression-free and overall survival respectively,^2,3 durvalumab became a category 1 recommendation for the above indication per National Comprehensive Cancer Network (NCCN) guidelines.⁴ Adherence to guidelines have been shown to improve patient survival across several cancer types.^5-7 However, guideline adherence rates have been variable across health institutions. Therefore, further study is warranted to evaluate nonadherent practices with the goal of improving the quality of cancer care delivery.^8,9

Stage III NSCLC is associated with poor survival rates.¹⁰ Concurrent CRT remains the standard of care in patients with good performance status based on clinical trial populations.⁴ Lung cancer remains a disease of the elderly, with a median age at diagnosis of 70 years.¹¹ Discrepancies in the treatment of lung cancer in older adults can vary widely due to a lack of evidence surrounding the treatment in those who have comorbidities and poor performance status, widening the gap between clinical trial and real-world populations.¹¹

A recent review by Passaro and colleagues revealed that at least 11 pivotal randomized controlled trials have shown the activity of immune checkpoint inhibitors (ICI) in locally advanced and metastatic lung cancer. However, these studies have mostly excluded patients with a performance status of the Eastern Cooperative Oncology Group (ECOG) level ≥ 2.¹¹

Durvalumab is one of many new therapies to enter clinical practice to demonstrate survival benefit, but its use among veterans with stage III NSCLC in adherence with National Comprehensive Cancer Network (NCCN) guidelines was not robust at the Birmingham Veterans Affairs Medical Center (VAMC) in Alabama. Therefore, we decided to study the level of adherence and to identify barriers to conformity to the category 1 NCCN recommendations.

Methods

The Birmingham VAMC Outpatient Oncology Clinic billing data identified all individuals diagnosed with lung cancer treated between October 2017 and August 2019. Patients who did not have NSCLC that was stage III and unresectable were excluded from our study. Patients who did not receive a majority of their treatment at US Department of Veterans Affairs (VA) facilities were excluded as well. Each patient’s demographic, functional level, and tumor characteristics during the treatment planning phase and follow-up visits were obtained. Two investigators who evaluated health care provider documentation using the VA Computerized Patient Record System (CPRS) conducted chart reviews.

The primary outcomes were the proportion of patients who received concurrent CRT and the proportion who received durvalumab consolidation. Our chart review also categorized reasons for nonreceipt of concurrent CRT and subsequent durvalumab. Documented reasons for guideline discordancy were generated empirically and broadly. We noted if documentation was unclear and included reasons for why a veteran was not a candidate for CRT, the presence of toxicities associated with CRT, and a patient’s refusal for therapy despite medical advice. Descriptive data were analyzed for all clinical or demographic characteristics and outcomes.

This was considered an internal quality improvement initiative. As such, Birmingham VAMC did not require institutional review board approval for the study. The facility is accredited by the American College of Surgeons Commission on Cancer.

Results

A total of 41 veterans with stage III NSCLC were identified to have established care in the Birmingham VAMC Oncology Clinic between October 2017 and August 2019. Of these, 7 received the majority of their treatment from community-based non-VA facilities and 14 were not candidates for CRT and were excluded from this study.

The mean (SD) age of study participants was 70.0 (8.4) years (range, 57 to 92 years). Most of the study veterans (33; 97.1%) were male and 20 (58.8%) were African American (Table). Eighteen (53%) of study participants had clinical stage IIIa NSCLC; 19 (56%) showed a squamous subtype of NSCLC. A majority (53%) of the veterans studied were evaluated to be functionally fit with an ECOG status of 0 to 1, although documentation of ECOG status was lacking in 5 (14.7%) patients in the initial treatment planning visit records. It was unclear if performance status had been reevaluated and changes noted over the course of concurrent CRT.

CRT Patients

The relative distribution of veterans who underwent CRT for stage III NSCLC plus the reasons they did not receive guideline-based treatment with durvalumab is shown in the Figure. Fourteen patients (41%) were inappropriate candidates for CRT; the most common reason for this was their poor performance status upon initial evaluation and 3 patients (8.8%) in the study had extensive disease or were upstaged upon follow-up clinic visit.

Twenty (59%) veterans in the study initiated CRT. However, only 16 (47.1%) completed CRT. Those who dropped out of CRT did so because of toxicities that included various cytopenia, gastrointestinal toxicities due to radiation and/or chemotherapy, or failure to thrive.

Durvalumab Treatment

After initiation of CRT, 9 (26.5%) patients did not go on to receive durvalumab. Three patients (8.8%) suffered toxicities during CRT. One study patient was found to have a severe respiratory infection requiring intensive care unit admission. Another study patient was found to have a new sternal lesion on follow-up positron emission tomography. One declined because of a history of severe antineutrophil cytoplasmic antibodies vasculitis, which made durvalumab use unsafe. Three patients (8.8%) declined treatment with CRT or durvalumab because of personal preference. Documentation was unclear as to why durvalumab was prescribed to one patient who had completed CRT.

Discussion

NCCN guidelines on the use of durvalumab in NSCLC are based on the phase 3 PACIFIC placebo-controlled randomized clinical trial. This trial, which included only patients with documented performance status of ECOG 0 or 1, reported that grade 3 or 4 events occurred in 30.5% of patients randomized to consolidative durvalumab. Treatment was discontinued in 15.4% of patients due to adverse events.³

Our study examined consolidation therapy with durvalumab in patients with unresectable stage III NSCLC with an ECOG performance status of 0 to 1 who had not progressed after 2 or more cycles of definitive concurrent CRT.⁴ Patients with previous exposure to immunotherapy, a history of immunodeficiency, active infection, unresolved toxicity from CRT, autoimmune disease, and patients who received sequential CRT were excluded.² Surprisingly, the adherence rate to guidelines was close to 100% with appropriate documentation and justification of CRT initiation and durvalumab use. Five (14.7%) of veterans with unresectable stage III NSCLC did not have clear documentation of ECOG status on initial visit and only 1 veteran who completed CRT did not have clear documentation as to why durvalumab was not provided. Unfortunately, 23 (68.6%) veterans in the study were unable to receive durvalumab, a potentially disease-modifying drug; nearly one-third (10) of veterans were deemed poor candidates for concurrent CRT despite the fact that 52.9% (18) of veterans in the study had a documented ECOG of 0 or 1 on initial evaluation.

Clinical Trials vs Real World

The heterogeneity between anticipated study populations, those who were able to receive durvalumab in the PACIFIC trial, compared with our observed real-world veteran population, likely stems from the lack of information about how comorbidity and fitness can affect the choice of therapeutic intervention in patients with lung cancer.¹² In addition, older adults who participated in randomized controlled trials (RCTs) are not representative of the average older adult who presents to medical oncology clinics, making the application of guideline concordant care difficult.¹³

Similar real-world observations parallel to our analyses have confirmed, complemented and/or refuted findings of RCTs, and have helped impact the treatment of multiple acute and chronic conditions including influenza, cardiovascular disease, and diabetes.¹⁴

A component of socioeconomic barriers and access to supportive care played roles in the decisions of certain patients who chose not to undergo concurrent CRT despite medical advice. These 2 obstacles also affected the decision making for some in the study when considering the use of durvalumab (administered by a 60-minute IV infusion every 2 weeks for 1 year) per recommended guidelines.¹ These hurdles need further study in the context of their effect on quality of life and the difficulties generated by various social determinants of health.

Limitations

Study limitations included the biased and confounding factors previously described about retrospective and nonrandomized observational studies that are controlled for during RCTs.¹⁵ Electronic health record data may have been incorrectly collected resulting in missing or wrong data points that affect the validity of our conclusion. Recall bias with regard to documentation by health care providers describing reasons why CRT or durvalumab were not initiated or the patient’s ability to recall previous treatments and report ECOG status or toxicities also may have impacted our findings. Comorbidities and poor performance status, frequently occurring among veterans, negatively impact cancer treatment decisions and may result in a detection bias. For example, tobacco use, cardiovascular disease, including heart failure, and chronic obstructive pulmonary disease, are notoriously higher in the US veteran population when compared with civilian cohorts.^16-18 Also, veterans with poorly controlled depression and posttraumatic stress disorder resulting in functional impairment are a factor.¹⁹ Steps were taken to address some of these biases by performing repeat checks of tabulated data and employing 2 independent reviewers to evaluate all relevant clinical documentation, compare results, and reach a consensus.

Conlcusions

This retrospective analysis of adherence to category 1 NCCN guidelines for durvalumab use among patients at the Birmingham VAMC Oncology Clinic reinforced our practice and identified minor deficiencies in documentation that would impact future clinical visits. More importantly, it depicted the massive disparity in treatment candidacy among Birmingham veterans compared with clinical trial populations. Efforts will be made to address factors impacting a veteran’s candidacy for CRT and explore other variables such as socioeconomic barriers to treatment. Multiple complementary tools to assess patients’ frailty, such as the Charlson Comorbidity Index (CCI), are now being used for a variety of disorders including cancers. More robust data and standardization are needed to validate the use of these assessments in predicting response to immune checkpoint inhibitors.

Immune checkpoint inhibitors are currently being evaluated in stage III NSCLC studies and may be implemented as routine practice in the future.¹² It is important to distinguish fit from frail veterans with lung cancer for treatment selection. We would like to see the expansion of the eligibility criteria for clinical trials to include patients with a performance status of ECOG 2 in order for results to be truly generalizable to the real-world population. Our hope is that such work will improve not only the quality of lung cancer care, but also the quality of care across multiple tumor types.

The US Food and Drug Administration (FDA) approved the use of durvalumab for patients with unresectable stage III non-small cell lung cancer (NSCLC) whose disease has not progressed following concurrent platinum-based chemotherapy and radiation therapy (CRT).¹ After 2 randomized phase 3 studies in 2017 and 2018 showed significant progression-free and overall survival respectively,^2,3 durvalumab became a category 1 recommendation for the above indication per National Comprehensive Cancer Network (NCCN) guidelines.⁴ Adherence to guidelines have been shown to improve patient survival across several cancer types.^5-7 However, guideline adherence rates have been variable across health institutions. Therefore, further study is warranted to evaluate nonadherent practices with the goal of improving the quality of cancer care delivery.^8,9

Stage III NSCLC is associated with poor survival rates.¹⁰ Concurrent CRT remains the standard of care in patients with good performance status based on clinical trial populations.⁴ Lung cancer remains a disease of the elderly, with a median age at diagnosis of 70 years.¹¹ Discrepancies in the treatment of lung cancer in older adults can vary widely due to a lack of evidence surrounding the treatment in those who have comorbidities and poor performance status, widening the gap between clinical trial and real-world populations.¹¹

A recent review by Passaro and colleagues revealed that at least 11 pivotal randomized controlled trials have shown the activity of immune checkpoint inhibitors (ICI) in locally advanced and metastatic lung cancer. However, these studies have mostly excluded patients with a performance status of the Eastern Cooperative Oncology Group (ECOG) level ≥ 2.¹¹

Durvalumab is one of many new therapies to enter clinical practice to demonstrate survival benefit, but its use among veterans with stage III NSCLC in adherence with National Comprehensive Cancer Network (NCCN) guidelines was not robust at the Birmingham Veterans Affairs Medical Center (VAMC) in Alabama. Therefore, we decided to study the level of adherence and to identify barriers to conformity to the category 1 NCCN recommendations.

Methods

The Birmingham VAMC Outpatient Oncology Clinic billing data identified all individuals diagnosed with lung cancer treated between October 2017 and August 2019. Patients who did not have NSCLC that was stage III and unresectable were excluded from our study. Patients who did not receive a majority of their treatment at US Department of Veterans Affairs (VA) facilities were excluded as well. Each patient’s demographic, functional level, and tumor characteristics during the treatment planning phase and follow-up visits were obtained. Two investigators who evaluated health care provider documentation using the VA Computerized Patient Record System (CPRS) conducted chart reviews.

The primary outcomes were the proportion of patients who received concurrent CRT and the proportion who received durvalumab consolidation. Our chart review also categorized reasons for nonreceipt of concurrent CRT and subsequent durvalumab. Documented reasons for guideline discordancy were generated empirically and broadly. We noted if documentation was unclear and included reasons for why a veteran was not a candidate for CRT, the presence of toxicities associated with CRT, and a patient’s refusal for therapy despite medical advice. Descriptive data were analyzed for all clinical or demographic characteristics and outcomes.

This was considered an internal quality improvement initiative. As such, Birmingham VAMC did not require institutional review board approval for the study. The facility is accredited by the American College of Surgeons Commission on Cancer.

Results

A total of 41 veterans with stage III NSCLC were identified to have established care in the Birmingham VAMC Oncology Clinic between October 2017 and August 2019. Of these, 7 received the majority of their treatment from community-based non-VA facilities and 14 were not candidates for CRT and were excluded from this study.

The mean (SD) age of study participants was 70.0 (8.4) years (range, 57 to 92 years). Most of the study veterans (33; 97.1%) were male and 20 (58.8%) were African American (Table). Eighteen (53%) of study participants had clinical stage IIIa NSCLC; 19 (56%) showed a squamous subtype of NSCLC. A majority (53%) of the veterans studied were evaluated to be functionally fit with an ECOG status of 0 to 1, although documentation of ECOG status was lacking in 5 (14.7%) patients in the initial treatment planning visit records. It was unclear if performance status had been reevaluated and changes noted over the course of concurrent CRT.

CRT Patients

The relative distribution of veterans who underwent CRT for stage III NSCLC plus the reasons they did not receive guideline-based treatment with durvalumab is shown in the Figure. Fourteen patients (41%) were inappropriate candidates for CRT; the most common reason for this was their poor performance status upon initial evaluation and 3 patients (8.8%) in the study had extensive disease or were upstaged upon follow-up clinic visit.

Twenty (59%) veterans in the study initiated CRT. However, only 16 (47.1%) completed CRT. Those who dropped out of CRT did so because of toxicities that included various cytopenia, gastrointestinal toxicities due to radiation and/or chemotherapy, or failure to thrive.

Durvalumab Treatment

After initiation of CRT, 9 (26.5%) patients did not go on to receive durvalumab. Three patients (8.8%) suffered toxicities during CRT. One study patient was found to have a severe respiratory infection requiring intensive care unit admission. Another study patient was found to have a new sternal lesion on follow-up positron emission tomography. One declined because of a history of severe antineutrophil cytoplasmic antibodies vasculitis, which made durvalumab use unsafe. Three patients (8.8%) declined treatment with CRT or durvalumab because of personal preference. Documentation was unclear as to why durvalumab was prescribed to one patient who had completed CRT.

Discussion

NCCN guidelines on the use of durvalumab in NSCLC are based on the phase 3 PACIFIC placebo-controlled randomized clinical trial. This trial, which included only patients with documented performance status of ECOG 0 or 1, reported that grade 3 or 4 events occurred in 30.5% of patients randomized to consolidative durvalumab. Treatment was discontinued in 15.4% of patients due to adverse events.³

Our study examined consolidation therapy with durvalumab in patients with unresectable stage III NSCLC with an ECOG performance status of 0 to 1 who had not progressed after 2 or more cycles of definitive concurrent CRT.⁴ Patients with previous exposure to immunotherapy, a history of immunodeficiency, active infection, unresolved toxicity from CRT, autoimmune disease, and patients who received sequential CRT were excluded.² Surprisingly, the adherence rate to guidelines was close to 100% with appropriate documentation and justification of CRT initiation and durvalumab use. Five (14.7%) of veterans with unresectable stage III NSCLC did not have clear documentation of ECOG status on initial visit and only 1 veteran who completed CRT did not have clear documentation as to why durvalumab was not provided. Unfortunately, 23 (68.6%) veterans in the study were unable to receive durvalumab, a potentially disease-modifying drug; nearly one-third (10) of veterans were deemed poor candidates for concurrent CRT despite the fact that 52.9% (18) of veterans in the study had a documented ECOG of 0 or 1 on initial evaluation.

Clinical Trials vs Real World

The heterogeneity between anticipated study populations, those who were able to receive durvalumab in the PACIFIC trial, compared with our observed real-world veteran population, likely stems from the lack of information about how comorbidity and fitness can affect the choice of therapeutic intervention in patients with lung cancer.¹² In addition, older adults who participated in randomized controlled trials (RCTs) are not representative of the average older adult who presents to medical oncology clinics, making the application of guideline concordant care difficult.¹³

Similar real-world observations parallel to our analyses have confirmed, complemented and/or refuted findings of RCTs, and have helped impact the treatment of multiple acute and chronic conditions including influenza, cardiovascular disease, and diabetes.¹⁴

A component of socioeconomic barriers and access to supportive care played roles in the decisions of certain patients who chose not to undergo concurrent CRT despite medical advice. These 2 obstacles also affected the decision making for some in the study when considering the use of durvalumab (administered by a 60-minute IV infusion every 2 weeks for 1 year) per recommended guidelines.¹ These hurdles need further study in the context of their effect on quality of life and the difficulties generated by various social determinants of health.

Limitations

Study limitations included the biased and confounding factors previously described about retrospective and nonrandomized observational studies that are controlled for during RCTs.¹⁵ Electronic health record data may have been incorrectly collected resulting in missing or wrong data points that affect the validity of our conclusion. Recall bias with regard to documentation by health care providers describing reasons why CRT or durvalumab were not initiated or the patient’s ability to recall previous treatments and report ECOG status or toxicities also may have impacted our findings. Comorbidities and poor performance status, frequently occurring among veterans, negatively impact cancer treatment decisions and may result in a detection bias. For example, tobacco use, cardiovascular disease, including heart failure, and chronic obstructive pulmonary disease, are notoriously higher in the US veteran population when compared with civilian cohorts.^16-18 Also, veterans with poorly controlled depression and posttraumatic stress disorder resulting in functional impairment are a factor.¹⁹ Steps were taken to address some of these biases by performing repeat checks of tabulated data and employing 2 independent reviewers to evaluate all relevant clinical documentation, compare results, and reach a consensus.

Conlcusions

This retrospective analysis of adherence to category 1 NCCN guidelines for durvalumab use among patients at the Birmingham VAMC Oncology Clinic reinforced our practice and identified minor deficiencies in documentation that would impact future clinical visits. More importantly, it depicted the massive disparity in treatment candidacy among Birmingham veterans compared with clinical trial populations. Efforts will be made to address factors impacting a veteran’s candidacy for CRT and explore other variables such as socioeconomic barriers to treatment. Multiple complementary tools to assess patients’ frailty, such as the Charlson Comorbidity Index (CCI), are now being used for a variety of disorders including cancers. More robust data and standardization are needed to validate the use of these assessments in predicting response to immune checkpoint inhibitors.

Immune checkpoint inhibitors are currently being evaluated in stage III NSCLC studies and may be implemented as routine practice in the future.¹² It is important to distinguish fit from frail veterans with lung cancer for treatment selection. We would like to see the expansion of the eligibility criteria for clinical trials to include patients with a performance status of ECOG 2 in order for results to be truly generalizable to the real-world population. Our hope is that such work will improve not only the quality of lung cancer care, but also the quality of care across multiple tumor types.

The US Food and Drug Administration (FDA) approved the use of durvalumab for patients with unresectable stage III non-small cell lung cancer (NSCLC) whose disease has not progressed following concurrent platinum-based chemotherapy and radiation therapy (CRT).¹ After 2 randomized phase 3 studies in 2017 and 2018 showed significant progression-free and overall survival respectively,^2,3 durvalumab became a category 1 recommendation for the above indication per National Comprehensive Cancer Network (NCCN) guidelines.⁴ Adherence to guidelines have been shown to improve patient survival across several cancer types.^5-7 However, guideline adherence rates have been variable across health institutions. Therefore, further study is warranted to evaluate nonadherent practices with the goal of improving the quality of cancer care delivery.^8,9

Stage III NSCLC is associated with poor survival rates.¹⁰ Concurrent CRT remains the standard of care in patients with good performance status based on clinical trial populations.⁴ Lung cancer remains a disease of the elderly, with a median age at diagnosis of 70 years.¹¹ Discrepancies in the treatment of lung cancer in older adults can vary widely due to a lack of evidence surrounding the treatment in those who have comorbidities and poor performance status, widening the gap between clinical trial and real-world populations.¹¹

A recent review by Passaro and colleagues revealed that at least 11 pivotal randomized controlled trials have shown the activity of immune checkpoint inhibitors (ICI) in locally advanced and metastatic lung cancer. However, these studies have mostly excluded patients with a performance status of the Eastern Cooperative Oncology Group (ECOG) level ≥ 2.¹¹

Durvalumab is one of many new therapies to enter clinical practice to demonstrate survival benefit, but its use among veterans with stage III NSCLC in adherence with National Comprehensive Cancer Network (NCCN) guidelines was not robust at the Birmingham Veterans Affairs Medical Center (VAMC) in Alabama. Therefore, we decided to study the level of adherence and to identify barriers to conformity to the category 1 NCCN recommendations.

Methods

The Birmingham VAMC Outpatient Oncology Clinic billing data identified all individuals diagnosed with lung cancer treated between October 2017 and August 2019. Patients who did not have NSCLC that was stage III and unresectable were excluded from our study. Patients who did not receive a majority of their treatment at US Department of Veterans Affairs (VA) facilities were excluded as well. Each patient’s demographic, functional level, and tumor characteristics during the treatment planning phase and follow-up visits were obtained. Two investigators who evaluated health care provider documentation using the VA Computerized Patient Record System (CPRS) conducted chart reviews.

The primary outcomes were the proportion of patients who received concurrent CRT and the proportion who received durvalumab consolidation. Our chart review also categorized reasons for nonreceipt of concurrent CRT and subsequent durvalumab. Documented reasons for guideline discordancy were generated empirically and broadly. We noted if documentation was unclear and included reasons for why a veteran was not a candidate for CRT, the presence of toxicities associated with CRT, and a patient’s refusal for therapy despite medical advice. Descriptive data were analyzed for all clinical or demographic characteristics and outcomes.

This was considered an internal quality improvement initiative. As such, Birmingham VAMC did not require institutional review board approval for the study. The facility is accredited by the American College of Surgeons Commission on Cancer.

Results

A total of 41 veterans with stage III NSCLC were identified to have established care in the Birmingham VAMC Oncology Clinic between October 2017 and August 2019. Of these, 7 received the majority of their treatment from community-based non-VA facilities and 14 were not candidates for CRT and were excluded from this study.

The mean (SD) age of study participants was 70.0 (8.4) years (range, 57 to 92 years). Most of the study veterans (33; 97.1%) were male and 20 (58.8%) were African American (Table). Eighteen (53%) of study participants had clinical stage IIIa NSCLC; 19 (56%) showed a squamous subtype of NSCLC. A majority (53%) of the veterans studied were evaluated to be functionally fit with an ECOG status of 0 to 1, although documentation of ECOG status was lacking in 5 (14.7%) patients in the initial treatment planning visit records. It was unclear if performance status had been reevaluated and changes noted over the course of concurrent CRT.

CRT Patients

The relative distribution of veterans who underwent CRT for stage III NSCLC plus the reasons they did not receive guideline-based treatment with durvalumab is shown in the Figure. Fourteen patients (41%) were inappropriate candidates for CRT; the most common reason for this was their poor performance status upon initial evaluation and 3 patients (8.8%) in the study had extensive disease or were upstaged upon follow-up clinic visit.

Twenty (59%) veterans in the study initiated CRT. However, only 16 (47.1%) completed CRT. Those who dropped out of CRT did so because of toxicities that included various cytopenia, gastrointestinal toxicities due to radiation and/or chemotherapy, or failure to thrive.

Durvalumab Treatment

After initiation of CRT, 9 (26.5%) patients did not go on to receive durvalumab. Three patients (8.8%) suffered toxicities during CRT. One study patient was found to have a severe respiratory infection requiring intensive care unit admission. Another study patient was found to have a new sternal lesion on follow-up positron emission tomography. One declined because of a history of severe antineutrophil cytoplasmic antibodies vasculitis, which made durvalumab use unsafe. Three patients (8.8%) declined treatment with CRT or durvalumab because of personal preference. Documentation was unclear as to why durvalumab was prescribed to one patient who had completed CRT.

Discussion

NCCN guidelines on the use of durvalumab in NSCLC are based on the phase 3 PACIFIC placebo-controlled randomized clinical trial. This trial, which included only patients with documented performance status of ECOG 0 or 1, reported that grade 3 or 4 events occurred in 30.5% of patients randomized to consolidative durvalumab. Treatment was discontinued in 15.4% of patients due to adverse events.³

Our study examined consolidation therapy with durvalumab in patients with unresectable stage III NSCLC with an ECOG performance status of 0 to 1 who had not progressed after 2 or more cycles of definitive concurrent CRT.⁴ Patients with previous exposure to immunotherapy, a history of immunodeficiency, active infection, unresolved toxicity from CRT, autoimmune disease, and patients who received sequential CRT were excluded.² Surprisingly, the adherence rate to guidelines was close to 100% with appropriate documentation and justification of CRT initiation and durvalumab use. Five (14.7%) of veterans with unresectable stage III NSCLC did not have clear documentation of ECOG status on initial visit and only 1 veteran who completed CRT did not have clear documentation as to why durvalumab was not provided. Unfortunately, 23 (68.6%) veterans in the study were unable to receive durvalumab, a potentially disease-modifying drug; nearly one-third (10) of veterans were deemed poor candidates for concurrent CRT despite the fact that 52.9% (18) of veterans in the study had a documented ECOG of 0 or 1 on initial evaluation.

Clinical Trials vs Real World

The heterogeneity between anticipated study populations, those who were able to receive durvalumab in the PACIFIC trial, compared with our observed real-world veteran population, likely stems from the lack of information about how comorbidity and fitness can affect the choice of therapeutic intervention in patients with lung cancer.¹² In addition, older adults who participated in randomized controlled trials (RCTs) are not representative of the average older adult who presents to medical oncology clinics, making the application of guideline concordant care difficult.¹³

Similar real-world observations parallel to our analyses have confirmed, complemented and/or refuted findings of RCTs, and have helped impact the treatment of multiple acute and chronic conditions including influenza, cardiovascular disease, and diabetes.¹⁴

A component of socioeconomic barriers and access to supportive care played roles in the decisions of certain patients who chose not to undergo concurrent CRT despite medical advice. These 2 obstacles also affected the decision making for some in the study when considering the use of durvalumab (administered by a 60-minute IV infusion every 2 weeks for 1 year) per recommended guidelines.¹ These hurdles need further study in the context of their effect on quality of life and the difficulties generated by various social determinants of health.

Limitations

Study limitations included the biased and confounding factors previously described about retrospective and nonrandomized observational studies that are controlled for during RCTs.¹⁵ Electronic health record data may have been incorrectly collected resulting in missing or wrong data points that affect the validity of our conclusion. Recall bias with regard to documentation by health care providers describing reasons why CRT or durvalumab were not initiated or the patient’s ability to recall previous treatments and report ECOG status or toxicities also may have impacted our findings. Comorbidities and poor performance status, frequently occurring among veterans, negatively impact cancer treatment decisions and may result in a detection bias. For example, tobacco use, cardiovascular disease, including heart failure, and chronic obstructive pulmonary disease, are notoriously higher in the US veteran population when compared with civilian cohorts.^16-18 Also, veterans with poorly controlled depression and posttraumatic stress disorder resulting in functional impairment are a factor.¹⁹ Steps were taken to address some of these biases by performing repeat checks of tabulated data and employing 2 independent reviewers to evaluate all relevant clinical documentation, compare results, and reach a consensus.

Conlcusions

This retrospective analysis of adherence to category 1 NCCN guidelines for durvalumab use among patients at the Birmingham VAMC Oncology Clinic reinforced our practice and identified minor deficiencies in documentation that would impact future clinical visits. More importantly, it depicted the massive disparity in treatment candidacy among Birmingham veterans compared with clinical trial populations. Efforts will be made to address factors impacting a veteran’s candidacy for CRT and explore other variables such as socioeconomic barriers to treatment. Multiple complementary tools to assess patients’ frailty, such as the Charlson Comorbidity Index (CCI), are now being used for a variety of disorders including cancers. More robust data and standardization are needed to validate the use of these assessments in predicting response to immune checkpoint inhibitors.

Immune checkpoint inhibitors are currently being evaluated in stage III NSCLC studies and may be implemented as routine practice in the future.¹² It is important to distinguish fit from frail veterans with lung cancer for treatment selection. We would like to see the expansion of the eligibility criteria for clinical trials to include patients with a performance status of ECOG 2 in order for results to be truly generalizable to the real-world population. Our hope is that such work will improve not only the quality of lung cancer care, but also the quality of care across multiple tumor types.

It may be possible to diagnose Parkinson’s disease with a skin test, a new study suggests. For the study, researchers used a chemical assay to detect clumping of the protein alpha-synuclein, a hallmark of Parkinson’s disease, in autopsy skin samples taken from patients who had Parkinson’s disease confirmed by brain pathology and from controls without the disease. The test showed a high degree of sensitivity and specificity for the diagnosis of Parkinson’s disease.

The study was published online in Movement Disorders.

“This test has a lot of promise,” said senior author Anumantha Kanthasamy, PhD, professor of biomedical sciences at Iowa State University in Ames. “At present there are no peripheral biomarkers for Parkinson’s disease. The current diagnosis is just based on symptoms, and the symptoms can be similar to many other neurological diseases,” he added. “It can take many years to establish a correct diagnosis and the accuracy is low even with experienced neurologists.”

If the current results can be replicated in samples from live patients and in those with very early stages of Parkinson’s disease, a skin test could allow early diagnosis and the possibility of starting preventive treatments to slow disease progression before symptoms develop too severely, the researchers suggest.
 

Sensitive and specific test

The blinded study used a seeding assay – used previously to detect misfolded proteins in prion diseases – to analyze 50 skin samples provided by the Arizona Study of Aging and Neurodegenerative Disorders/Brain and Body Donation Program based at Banner Sun Health Research Institute in Sun City.

Half of the skin samples came from patients with Parkinson’s disease and half came from people without neurologic disease. The protein assay correctly diagnosed 24 out of 25 patients with Parkinson’s disease and only one of the 25 controls had the protein clumping.

“At present, the only way to definitely diagnose Parkinson’s disease is on autopsy – by the detection of alpha-synuclein clumps [Lewy bodies] in the brain,” commented Charles Adler, MD, professor of neurology at Mayo Clinic Arizona in Scottsdale and a coinvestigator of the study. “In our research, we have also seen clumping of alpha-synuclein in many other organs including submandibular gland, colon, skin, heart, and stomach, but in terms of access, the skin is probably the easiest source.”

In this study, “we found this seeding assay for alpha-synuclein clumps to be extremely sensitive and specific in the diagnosis of Parkinson’s disease,” he added. “This is very valuable data as we have samples from patients with autopsy-validated Parkinson’s disease.”
 

A reliable biomarker?

The researchers are now starting a study in living patients with funding from the National Institutes of Health in which they will repeat the process comparing skin samples from patients with clinically diagnosed Parkinson’s disease and controls.

“We need to know whether analyzing alpha-synuclein clumping in skin biopsies from live patients with Parkinson’s disease would serve as a reliable biomarker for disease progression. Will clumping of this protein in skin samples increase over time and does it correspond with disease progression?” Dr. Adler said.

In future they are also hoping to test individuals who have not yet developed Parkinson’s disease but may have some prodromal type symptoms and to test whether this assay could measure a treatment effect of drug therapy.

Dr. Adler noted that they are currently conducting an autopsy study of skin samples from individuals who did not have clinical Parkinson’s disease when alive but in whom Lewy bodies have been found postmortem.

“This suggests that the disease pathology starts before Parkinson’s symptoms develop, and in the future, if we can diagnose Parkinson’s disease earlier then we may be able to stop progression,” he said.

“There is a long list of compounds that have been studied to try and slow progression but haven’t shown benefits, but by the time patients develop symptoms they already have significant disease and [have] lost most of their dopamine neurons,” he added. “If we could backtrack by 10 years, then these drugs may well make a difference.”

Dr. Adler also noted that currently more advanced patients may undergo invasive procedures such as deep brain stimulation or surgery. “It is of utmost importance that they have an accurate diagnosis before being subjected to such procedures.”

In addition, he pointed out that an accurate test would help the drug development process. “It is vitally important to enroll patients with an accurate diagnosis in clinical trials of new drugs. At present, a large percentage of patients in these trials may not actually have Parkinson’s disease, which makes it very difficult to show a treatment effect.”
 

Important step, but preliminary

Commenting on the research, James Beck, PhD, chief scientific officer of the Parkinson’s Foundation, said the study “is an important step toward the creation of a new way to potentially diagnose Parkinson’s disease.”

But he cautioned that this is a preliminary study. “To really confirm the possibility of using this approach for diagnosing Parkinson’s disease, a larger study will be necessary. And it will be important to test this in a population with early disease – the most difficult group to accurately diagnose.”

Also commenting on the findings, Beate Ritz, MD, PhD, an epidemiologist at UCLA Fielding School of Public Health in Los Angeles, who is part of a team also working on ways to measure abnormal alpha-synuclein to diagnose Parkinson’s disease, described the current study of skin samples as “pretty nifty.”

“Their research shows clearly that they can distinguish between patients with Parkinson’s disease and controls in this way,” she said. “The big advantage of this study is that they have brain pathology, so they know exactly which individuals had Parkinson’s disease.”

Dr. Ritz is working with Gal Bitan, PhD, from the UCLA Brain Research Institute on a potential blood test to measure abnormal alpha-synuclein.

Dr. Ritz explained that it is not possible to measure alpha-synuclein pathology in regular blood samples as it is expressed normally in red blood cells, but they are measuring the protein and its more toxic phosphorylated form from exosomes, which contain the waste discarded by cells using technology that determines the origin of these exosomes.

“Alpha-synuclein itself is not a problem. It is the way it misfolds that causes toxicity and disrupts the workings of the cell,” Dr. Ritz added. “In Parkinson’s disease, it is particularly toxic to dopaminergic neurons, and in multiple system atrophy, it is toxic to glial cells, so if we can identify the source of the protein then that could be helpful.”

The study was funded by the National Institutes of Health and the US Army Medical Research Materiel Command. The study authors, Dr. Beck, and Dr. Ritz have disclosed no relevant financial relationships.
 

A version of this article originally appeared on Medscape.com.

It may be possible to diagnose Parkinson’s disease with a skin test, a new study suggests. For the study, researchers used a chemical assay to detect clumping of the protein alpha-synuclein, a hallmark of Parkinson’s disease, in autopsy skin samples taken from patients who had Parkinson’s disease confirmed by brain pathology and from controls without the disease. The test showed a high degree of sensitivity and specificity for the diagnosis of Parkinson’s disease.

The study was published online in Movement Disorders.

“This test has a lot of promise,” said senior author Anumantha Kanthasamy, PhD, professor of biomedical sciences at Iowa State University in Ames. “At present there are no peripheral biomarkers for Parkinson’s disease. The current diagnosis is just based on symptoms, and the symptoms can be similar to many other neurological diseases,” he added. “It can take many years to establish a correct diagnosis and the accuracy is low even with experienced neurologists.”

If the current results can be replicated in samples from live patients and in those with very early stages of Parkinson’s disease, a skin test could allow early diagnosis and the possibility of starting preventive treatments to slow disease progression before symptoms develop too severely, the researchers suggest.
 

Sensitive and specific test

The blinded study used a seeding assay – used previously to detect misfolded proteins in prion diseases – to analyze 50 skin samples provided by the Arizona Study of Aging and Neurodegenerative Disorders/Brain and Body Donation Program based at Banner Sun Health Research Institute in Sun City.

Half of the skin samples came from patients with Parkinson’s disease and half came from people without neurologic disease. The protein assay correctly diagnosed 24 out of 25 patients with Parkinson’s disease and only one of the 25 controls had the protein clumping.

“At present, the only way to definitely diagnose Parkinson’s disease is on autopsy – by the detection of alpha-synuclein clumps [Lewy bodies] in the brain,” commented Charles Adler, MD, professor of neurology at Mayo Clinic Arizona in Scottsdale and a coinvestigator of the study. “In our research, we have also seen clumping of alpha-synuclein in many other organs including submandibular gland, colon, skin, heart, and stomach, but in terms of access, the skin is probably the easiest source.”

In this study, “we found this seeding assay for alpha-synuclein clumps to be extremely sensitive and specific in the diagnosis of Parkinson’s disease,” he added. “This is very valuable data as we have samples from patients with autopsy-validated Parkinson’s disease.”
 

A reliable biomarker?

The researchers are now starting a study in living patients with funding from the National Institutes of Health in which they will repeat the process comparing skin samples from patients with clinically diagnosed Parkinson’s disease and controls.

“We need to know whether analyzing alpha-synuclein clumping in skin biopsies from live patients with Parkinson’s disease would serve as a reliable biomarker for disease progression. Will clumping of this protein in skin samples increase over time and does it correspond with disease progression?” Dr. Adler said.

In future they are also hoping to test individuals who have not yet developed Parkinson’s disease but may have some prodromal type symptoms and to test whether this assay could measure a treatment effect of drug therapy.

Dr. Adler noted that they are currently conducting an autopsy study of skin samples from individuals who did not have clinical Parkinson’s disease when alive but in whom Lewy bodies have been found postmortem.

“This suggests that the disease pathology starts before Parkinson’s symptoms develop, and in the future, if we can diagnose Parkinson’s disease earlier then we may be able to stop progression,” he said.

“There is a long list of compounds that have been studied to try and slow progression but haven’t shown benefits, but by the time patients develop symptoms they already have significant disease and [have] lost most of their dopamine neurons,” he added. “If we could backtrack by 10 years, then these drugs may well make a difference.”

Dr. Adler also noted that currently more advanced patients may undergo invasive procedures such as deep brain stimulation or surgery. “It is of utmost importance that they have an accurate diagnosis before being subjected to such procedures.”

In addition, he pointed out that an accurate test would help the drug development process. “It is vitally important to enroll patients with an accurate diagnosis in clinical trials of new drugs. At present, a large percentage of patients in these trials may not actually have Parkinson’s disease, which makes it very difficult to show a treatment effect.”
 

Important step, but preliminary

Commenting on the research, James Beck, PhD, chief scientific officer of the Parkinson’s Foundation, said the study “is an important step toward the creation of a new way to potentially diagnose Parkinson’s disease.”

But he cautioned that this is a preliminary study. “To really confirm the possibility of using this approach for diagnosing Parkinson’s disease, a larger study will be necessary. And it will be important to test this in a population with early disease – the most difficult group to accurately diagnose.”

Also commenting on the findings, Beate Ritz, MD, PhD, an epidemiologist at UCLA Fielding School of Public Health in Los Angeles, who is part of a team also working on ways to measure abnormal alpha-synuclein to diagnose Parkinson’s disease, described the current study of skin samples as “pretty nifty.”

“Their research shows clearly that they can distinguish between patients with Parkinson’s disease and controls in this way,” she said. “The big advantage of this study is that they have brain pathology, so they know exactly which individuals had Parkinson’s disease.”

Dr. Ritz is working with Gal Bitan, PhD, from the UCLA Brain Research Institute on a potential blood test to measure abnormal alpha-synuclein.

Dr. Ritz explained that it is not possible to measure alpha-synuclein pathology in regular blood samples as it is expressed normally in red blood cells, but they are measuring the protein and its more toxic phosphorylated form from exosomes, which contain the waste discarded by cells using technology that determines the origin of these exosomes.

“Alpha-synuclein itself is not a problem. It is the way it misfolds that causes toxicity and disrupts the workings of the cell,” Dr. Ritz added. “In Parkinson’s disease, it is particularly toxic to dopaminergic neurons, and in multiple system atrophy, it is toxic to glial cells, so if we can identify the source of the protein then that could be helpful.”

The study was funded by the National Institutes of Health and the US Army Medical Research Materiel Command. The study authors, Dr. Beck, and Dr. Ritz have disclosed no relevant financial relationships.
 

A version of this article originally appeared on Medscape.com.

It may be possible to diagnose Parkinson’s disease with a skin test, a new study suggests. For the study, researchers used a chemical assay to detect clumping of the protein alpha-synuclein, a hallmark of Parkinson’s disease, in autopsy skin samples taken from patients who had Parkinson’s disease confirmed by brain pathology and from controls without the disease. The test showed a high degree of sensitivity and specificity for the diagnosis of Parkinson’s disease.

The study was published online in Movement Disorders.

“This test has a lot of promise,” said senior author Anumantha Kanthasamy, PhD, professor of biomedical sciences at Iowa State University in Ames. “At present there are no peripheral biomarkers for Parkinson’s disease. The current diagnosis is just based on symptoms, and the symptoms can be similar to many other neurological diseases,” he added. “It can take many years to establish a correct diagnosis and the accuracy is low even with experienced neurologists.”

If the current results can be replicated in samples from live patients and in those with very early stages of Parkinson’s disease, a skin test could allow early diagnosis and the possibility of starting preventive treatments to slow disease progression before symptoms develop too severely, the researchers suggest.
 

Sensitive and specific test

The blinded study used a seeding assay – used previously to detect misfolded proteins in prion diseases – to analyze 50 skin samples provided by the Arizona Study of Aging and Neurodegenerative Disorders/Brain and Body Donation Program based at Banner Sun Health Research Institute in Sun City.

Half of the skin samples came from patients with Parkinson’s disease and half came from people without neurologic disease. The protein assay correctly diagnosed 24 out of 25 patients with Parkinson’s disease and only one of the 25 controls had the protein clumping.

“At present, the only way to definitely diagnose Parkinson’s disease is on autopsy – by the detection of alpha-synuclein clumps [Lewy bodies] in the brain,” commented Charles Adler, MD, professor of neurology at Mayo Clinic Arizona in Scottsdale and a coinvestigator of the study. “In our research, we have also seen clumping of alpha-synuclein in many other organs including submandibular gland, colon, skin, heart, and stomach, but in terms of access, the skin is probably the easiest source.”

In this study, “we found this seeding assay for alpha-synuclein clumps to be extremely sensitive and specific in the diagnosis of Parkinson’s disease,” he added. “This is very valuable data as we have samples from patients with autopsy-validated Parkinson’s disease.”
 

A reliable biomarker?

The researchers are now starting a study in living patients with funding from the National Institutes of Health in which they will repeat the process comparing skin samples from patients with clinically diagnosed Parkinson’s disease and controls.

“We need to know whether analyzing alpha-synuclein clumping in skin biopsies from live patients with Parkinson’s disease would serve as a reliable biomarker for disease progression. Will clumping of this protein in skin samples increase over time and does it correspond with disease progression?” Dr. Adler said.

In future they are also hoping to test individuals who have not yet developed Parkinson’s disease but may have some prodromal type symptoms and to test whether this assay could measure a treatment effect of drug therapy.

Dr. Adler noted that they are currently conducting an autopsy study of skin samples from individuals who did not have clinical Parkinson’s disease when alive but in whom Lewy bodies have been found postmortem.

“This suggests that the disease pathology starts before Parkinson’s symptoms develop, and in the future, if we can diagnose Parkinson’s disease earlier then we may be able to stop progression,” he said.

“There is a long list of compounds that have been studied to try and slow progression but haven’t shown benefits, but by the time patients develop symptoms they already have significant disease and [have] lost most of their dopamine neurons,” he added. “If we could backtrack by 10 years, then these drugs may well make a difference.”

Dr. Adler also noted that currently more advanced patients may undergo invasive procedures such as deep brain stimulation or surgery. “It is of utmost importance that they have an accurate diagnosis before being subjected to such procedures.”

In addition, he pointed out that an accurate test would help the drug development process. “It is vitally important to enroll patients with an accurate diagnosis in clinical trials of new drugs. At present, a large percentage of patients in these trials may not actually have Parkinson’s disease, which makes it very difficult to show a treatment effect.”
 

Important step, but preliminary

Commenting on the research, James Beck, PhD, chief scientific officer of the Parkinson’s Foundation, said the study “is an important step toward the creation of a new way to potentially diagnose Parkinson’s disease.”

But he cautioned that this is a preliminary study. “To really confirm the possibility of using this approach for diagnosing Parkinson’s disease, a larger study will be necessary. And it will be important to test this in a population with early disease – the most difficult group to accurately diagnose.”

Also commenting on the findings, Beate Ritz, MD, PhD, an epidemiologist at UCLA Fielding School of Public Health in Los Angeles, who is part of a team also working on ways to measure abnormal alpha-synuclein to diagnose Parkinson’s disease, described the current study of skin samples as “pretty nifty.”

“Their research shows clearly that they can distinguish between patients with Parkinson’s disease and controls in this way,” she said. “The big advantage of this study is that they have brain pathology, so they know exactly which individuals had Parkinson’s disease.”

Dr. Ritz is working with Gal Bitan, PhD, from the UCLA Brain Research Institute on a potential blood test to measure abnormal alpha-synuclein.

Dr. Ritz explained that it is not possible to measure alpha-synuclein pathology in regular blood samples as it is expressed normally in red blood cells, but they are measuring the protein and its more toxic phosphorylated form from exosomes, which contain the waste discarded by cells using technology that determines the origin of these exosomes.

“Alpha-synuclein itself is not a problem. It is the way it misfolds that causes toxicity and disrupts the workings of the cell,” Dr. Ritz added. “In Parkinson’s disease, it is particularly toxic to dopaminergic neurons, and in multiple system atrophy, it is toxic to glial cells, so if we can identify the source of the protein then that could be helpful.”

The study was funded by the National Institutes of Health and the US Army Medical Research Materiel Command. The study authors, Dr. Beck, and Dr. Ritz have disclosed no relevant financial relationships.
 

A version of this article originally appeared on Medscape.com.

A new, large study has confirmed that different types of hormone replacement therapy (HRT) are associated with an increased risk for breast cancer and has provided additional information on factors associated with that increased risk.

The study was published online on October 28 in The BMJ.

“The study confirms increased risk of breast cancer in patients taking HRT but shows that the magnitude of risk depends on a number of factors,” first author Yana Vinogradova, PhD, said in an interview. Dr. Vinogradova is a medical statistician at the University of Nottingham (England).

The study also suggests the risk may be lower than was estimated in a large meta-analysis of 24 trials that was published in 2019 in The Lancet. In that study, researchers suggested the risk for breast cancer with HRT was higher and persisted longer than had been thought.

This conclusion from the meta-analysis was widely reported in the lay press and led to the UK Medicine and Healthcare Products Regulatory Agency issuing a safety alert for HRT regarding breast cancer. Experts in the field questioned the alert and said it caused undue anxiety. The European Medicines Agency also issued a safety alert because of the study.

This new study was begun before publication of the meta-analysis. Although the results are broadly similar in suggesting increased risk for breast cancer with HRT use, findings from the new study suggest the risk is lower than had been estimated in the meta-analysis and that the risk diminishes more rapidly after stopping HRT than was suggested by the meta-analysis.

“The publicity surrounding publication of the meta-analysis highlighted unexpectedly high risks and led to a heightened level of concern in some quarters,” Dr. Vinogradova commented. “Our study, based on general population data, has not confirmed any such findings. In general, it showed lower levels of risk and clarified the variability of magnitude within them.”

Dr. Vinogradova said the discrepancy could be related to the fact that the studies were designed differently. The meta-analysis relied on results from 24 studies that were conducted around the world at different periods and included women of different ages and backgrounds. The studies in the meta-analysis used different methods, including questionnaires that relied on women’s memories and therefore could have been biased, she said.

In contrast, the new study analyzed EMR data collected prospectively by general practices in the United Kingdom. The data came from the QResearch and from the Clinical Practice Research Datalink (CPRD) databases, the two largest primary care databases in the United Kingdom, which were linked to hospital, mortality, and cancer registries.

Because this study used a “consistent design” and “consistent data sources,” these new results “are likely to be more accurate and reliable for assessing risks among HRT users,” Dr. Vinogradova commented.

This study used an observational design, so it cannot prove that HRT causes breast cancer. These results may better represent women in the general U.K. population, compared with the earlier meta-analysis, she added.

Commenting on the new study, Michael Jones, PhD, senior staff scientist in genetics and epidemiology at the Institute of Cancer Research, London, also emphasized that it was large and its data came from general practitioner medical records, “so the strong statistical associations are unlikely to be due to chance.

“The results of this study generally confirm what has been seen before and is well established – that the use of combined estrogen plus progestogen HRT is associated with increased risk of breast cancer, and this risk increases with duration of use. But reassuringly, after stopping HRT, the raised risk of breast cancer mostly returns to that seen in nonusers of HRT,” he said.

“It’s important to note that no one study should be considered in isolation,” he added. “Even though some risks were found to be slightly smaller than those reported in another meta-analysis of the worldwide epidemiological evidence recently published in 2019, women considering use of HRT should still follow advice given to them by their [general practitioners].”
 

Study details

In the study, researchers evaluated all types of HRT commonly prescribed in the United Kingdom over the past 20 years, including topical estrogen, vaginal pessaries, and creams. They grouped HRT use by recent (within the past 5 years) and past (5 or more years ago) and HRT duration as short term (less than 5 years) and long term (5 years or longer). Results were adjusted for a range of factors that could affect breast cancer risk, including lifestyle, smoking, alcohol consumption, other medical conditions, family history, and use of other prescribed drugs.

The analysis included 98,611 women aged 50-79 years who were first diagnosed with breast cancer between 1998 and 2019. These women were matched by age and general practice to 457,498 women who were not diagnosed with breast cancer over these years. HRT use was reported in 34% (33,703) of women with breast cancer and in 31% (134,391) of women without breast cancer.

Overall, the risk for breast cancer was increased with use of most HRT drugs (adjusted odds ratio, 1.21; 95% confidence, 1.19-1.23), compared with not using HRT drugs. The highest risk was tied to combined estrogen/progestogen HRT (adjusted OR, 1.26; 95% CI, 1.24-1.29). The lowest risk was tied to estrogen-only HRT (adjusted OR, 1.06; 95% CI, 1.03-1.10). Estrogen cream and vaginal estrogen were not associated with increased breast cancer risk.

In general, breast cancer risk was higher among recent HRT users and those receiving long-term therapy. HRT-associated breast cancer risk increased with age and declined after discontinuing treatment. Therapy of less than 1 year was not associated with increased breast cancer risk.

Women who had recently been receiving long-term combined estrogen/progestogen HRT had a 79% increased risk for breast cancer (adjusted OR, 1.79; 95% CI, 1.73-1.85), compared with never-users. Among recent long-term users of combined HRT, breast cancer risk was highest for norethisterone (adjusted OR, 1.88; 95% CI, 1.79-1.99) and lowest for dydrogesterone (adjusted OR, 1.24; 95% CI, 1.03-1.48). Women who had recently been receiving long-term estrogen-only HRT had a 15% increased risk for breast cancer compared to never-users (adjusted OR, 1.15; 95% CI, 1.09-1.21).

Among women who discontinued HRT 5 or more years ago, risk for breast cancer was no longer increased for long-term estrogen-only therapy and short-term estrogen/progestogen therapy. However, breast cancer risk remained elevated 5 years after discontinuing long-term estrogen/progestogen (adjusted OR, 1.16; 95% CI, 1.11-1.21).

HRT-associated risk for breast cancer increased with age across all durations of therapy.

Compared with never-use, recent long-term estrogen-only therapy was associated with zero extra breast cancer cases per 10,000 women-years among women aged 50-59 years and eight extra cases per 10,000 women-years among women aged 70-79.

Recent long-term estrogen/progestogen use was associated with 15 extra breast cancer cases among women aged 50-59 and 36 extra cases among women aged 70-79 per 10,000 women-years.

Past long-term estrogen/progestogen use was associated with zero extra breast cancer cases among women aged 50-59 and eight extra cases among women aged 70-79 per 10,000 women-years.

Summarizing, Dr. Vinogradova said the increased risk for breast cancer with HRT appears to be “relatively small, particularly for younger women and for any women who use HRT only for a restricted period.”

Decisions about whether to use HRT and which type to use should depend on symptom severity, patient factors, and suitability of other treatment options, she commented.

“Particularly for those women who our study has shown to be most at risk, these decisions should be made through discussions between the patient and her doctor,” she concluded. “We hope that the new and more detailed information provided by our study will facilitate such prescribing decisions.”

The study was partially funded by the School for Primary Care Research of the National Institute for Health Research, by Cancer Research UK, and by the Cancer Research UK Oxford Center. Dr. Vinogradova has disclosed no relevant financial relationships. Senior author Julia Hippisley-Cox is an unpaid director of QResearch and was a paid director of ClinRisk until 2019. The other authors have disclosed no relevant financial relationships.
 

A version of this story originally appeared on Medscape.com.

A new, large study has confirmed that different types of hormone replacement therapy (HRT) are associated with an increased risk for breast cancer and has provided additional information on factors associated with that increased risk.

The study was published online on October 28 in The BMJ.

“The study confirms increased risk of breast cancer in patients taking HRT but shows that the magnitude of risk depends on a number of factors,” first author Yana Vinogradova, PhD, said in an interview. Dr. Vinogradova is a medical statistician at the University of Nottingham (England).

The study also suggests the risk may be lower than was estimated in a large meta-analysis of 24 trials that was published in 2019 in The Lancet. In that study, researchers suggested the risk for breast cancer with HRT was higher and persisted longer than had been thought.

This conclusion from the meta-analysis was widely reported in the lay press and led to the UK Medicine and Healthcare Products Regulatory Agency issuing a safety alert for HRT regarding breast cancer. Experts in the field questioned the alert and said it caused undue anxiety. The European Medicines Agency also issued a safety alert because of the study.

This new study was begun before publication of the meta-analysis. Although the results are broadly similar in suggesting increased risk for breast cancer with HRT use, findings from the new study suggest the risk is lower than had been estimated in the meta-analysis and that the risk diminishes more rapidly after stopping HRT than was suggested by the meta-analysis.

“The publicity surrounding publication of the meta-analysis highlighted unexpectedly high risks and led to a heightened level of concern in some quarters,” Dr. Vinogradova commented. “Our study, based on general population data, has not confirmed any such findings. In general, it showed lower levels of risk and clarified the variability of magnitude within them.”

Dr. Vinogradova said the discrepancy could be related to the fact that the studies were designed differently. The meta-analysis relied on results from 24 studies that were conducted around the world at different periods and included women of different ages and backgrounds. The studies in the meta-analysis used different methods, including questionnaires that relied on women’s memories and therefore could have been biased, she said.

In contrast, the new study analyzed EMR data collected prospectively by general practices in the United Kingdom. The data came from the QResearch and from the Clinical Practice Research Datalink (CPRD) databases, the two largest primary care databases in the United Kingdom, which were linked to hospital, mortality, and cancer registries.

Because this study used a “consistent design” and “consistent data sources,” these new results “are likely to be more accurate and reliable for assessing risks among HRT users,” Dr. Vinogradova commented.

This study used an observational design, so it cannot prove that HRT causes breast cancer. These results may better represent women in the general U.K. population, compared with the earlier meta-analysis, she added.

Commenting on the new study, Michael Jones, PhD, senior staff scientist in genetics and epidemiology at the Institute of Cancer Research, London, also emphasized that it was large and its data came from general practitioner medical records, “so the strong statistical associations are unlikely to be due to chance.

“The results of this study generally confirm what has been seen before and is well established – that the use of combined estrogen plus progestogen HRT is associated with increased risk of breast cancer, and this risk increases with duration of use. But reassuringly, after stopping HRT, the raised risk of breast cancer mostly returns to that seen in nonusers of HRT,” he said.

“It’s important to note that no one study should be considered in isolation,” he added. “Even though some risks were found to be slightly smaller than those reported in another meta-analysis of the worldwide epidemiological evidence recently published in 2019, women considering use of HRT should still follow advice given to them by their [general practitioners].”
 

Study details

In the study, researchers evaluated all types of HRT commonly prescribed in the United Kingdom over the past 20 years, including topical estrogen, vaginal pessaries, and creams. They grouped HRT use by recent (within the past 5 years) and past (5 or more years ago) and HRT duration as short term (less than 5 years) and long term (5 years or longer). Results were adjusted for a range of factors that could affect breast cancer risk, including lifestyle, smoking, alcohol consumption, other medical conditions, family history, and use of other prescribed drugs.

The analysis included 98,611 women aged 50-79 years who were first diagnosed with breast cancer between 1998 and 2019. These women were matched by age and general practice to 457,498 women who were not diagnosed with breast cancer over these years. HRT use was reported in 34% (33,703) of women with breast cancer and in 31% (134,391) of women without breast cancer.

Overall, the risk for breast cancer was increased with use of most HRT drugs (adjusted odds ratio, 1.21; 95% confidence, 1.19-1.23), compared with not using HRT drugs. The highest risk was tied to combined estrogen/progestogen HRT (adjusted OR, 1.26; 95% CI, 1.24-1.29). The lowest risk was tied to estrogen-only HRT (adjusted OR, 1.06; 95% CI, 1.03-1.10). Estrogen cream and vaginal estrogen were not associated with increased breast cancer risk.

In general, breast cancer risk was higher among recent HRT users and those receiving long-term therapy. HRT-associated breast cancer risk increased with age and declined after discontinuing treatment. Therapy of less than 1 year was not associated with increased breast cancer risk.

Women who had recently been receiving long-term combined estrogen/progestogen HRT had a 79% increased risk for breast cancer (adjusted OR, 1.79; 95% CI, 1.73-1.85), compared with never-users. Among recent long-term users of combined HRT, breast cancer risk was highest for norethisterone (adjusted OR, 1.88; 95% CI, 1.79-1.99) and lowest for dydrogesterone (adjusted OR, 1.24; 95% CI, 1.03-1.48). Women who had recently been receiving long-term estrogen-only HRT had a 15% increased risk for breast cancer compared to never-users (adjusted OR, 1.15; 95% CI, 1.09-1.21).

Among women who discontinued HRT 5 or more years ago, risk for breast cancer was no longer increased for long-term estrogen-only therapy and short-term estrogen/progestogen therapy. However, breast cancer risk remained elevated 5 years after discontinuing long-term estrogen/progestogen (adjusted OR, 1.16; 95% CI, 1.11-1.21).

HRT-associated risk for breast cancer increased with age across all durations of therapy.

Compared with never-use, recent long-term estrogen-only therapy was associated with zero extra breast cancer cases per 10,000 women-years among women aged 50-59 years and eight extra cases per 10,000 women-years among women aged 70-79.

Recent long-term estrogen/progestogen use was associated with 15 extra breast cancer cases among women aged 50-59 and 36 extra cases among women aged 70-79 per 10,000 women-years.

Past long-term estrogen/progestogen use was associated with zero extra breast cancer cases among women aged 50-59 and eight extra cases among women aged 70-79 per 10,000 women-years.

Summarizing, Dr. Vinogradova said the increased risk for breast cancer with HRT appears to be “relatively small, particularly for younger women and for any women who use HRT only for a restricted period.”

Decisions about whether to use HRT and which type to use should depend on symptom severity, patient factors, and suitability of other treatment options, she commented.

“Particularly for those women who our study has shown to be most at risk, these decisions should be made through discussions between the patient and her doctor,” she concluded. “We hope that the new and more detailed information provided by our study will facilitate such prescribing decisions.”

The study was partially funded by the School for Primary Care Research of the National Institute for Health Research, by Cancer Research UK, and by the Cancer Research UK Oxford Center. Dr. Vinogradova has disclosed no relevant financial relationships. Senior author Julia Hippisley-Cox is an unpaid director of QResearch and was a paid director of ClinRisk until 2019. The other authors have disclosed no relevant financial relationships.
 

A version of this story originally appeared on Medscape.com.

A new, large study has confirmed that different types of hormone replacement therapy (HRT) are associated with an increased risk for breast cancer and has provided additional information on factors associated with that increased risk.

The study was published online on October 28 in The BMJ.

“The study confirms increased risk of breast cancer in patients taking HRT but shows that the magnitude of risk depends on a number of factors,” first author Yana Vinogradova, PhD, said in an interview. Dr. Vinogradova is a medical statistician at the University of Nottingham (England).

The study also suggests the risk may be lower than was estimated in a large meta-analysis of 24 trials that was published in 2019 in The Lancet. In that study, researchers suggested the risk for breast cancer with HRT was higher and persisted longer than had been thought.

This conclusion from the meta-analysis was widely reported in the lay press and led to the UK Medicine and Healthcare Products Regulatory Agency issuing a safety alert for HRT regarding breast cancer. Experts in the field questioned the alert and said it caused undue anxiety. The European Medicines Agency also issued a safety alert because of the study.

This new study was begun before publication of the meta-analysis. Although the results are broadly similar in suggesting increased risk for breast cancer with HRT use, findings from the new study suggest the risk is lower than had been estimated in the meta-analysis and that the risk diminishes more rapidly after stopping HRT than was suggested by the meta-analysis.

“The publicity surrounding publication of the meta-analysis highlighted unexpectedly high risks and led to a heightened level of concern in some quarters,” Dr. Vinogradova commented. “Our study, based on general population data, has not confirmed any such findings. In general, it showed lower levels of risk and clarified the variability of magnitude within them.”

Dr. Vinogradova said the discrepancy could be related to the fact that the studies were designed differently. The meta-analysis relied on results from 24 studies that were conducted around the world at different periods and included women of different ages and backgrounds. The studies in the meta-analysis used different methods, including questionnaires that relied on women’s memories and therefore could have been biased, she said.

In contrast, the new study analyzed EMR data collected prospectively by general practices in the United Kingdom. The data came from the QResearch and from the Clinical Practice Research Datalink (CPRD) databases, the two largest primary care databases in the United Kingdom, which were linked to hospital, mortality, and cancer registries.

Because this study used a “consistent design” and “consistent data sources,” these new results “are likely to be more accurate and reliable for assessing risks among HRT users,” Dr. Vinogradova commented.

This study used an observational design, so it cannot prove that HRT causes breast cancer. These results may better represent women in the general U.K. population, compared with the earlier meta-analysis, she added.

Commenting on the new study, Michael Jones, PhD, senior staff scientist in genetics and epidemiology at the Institute of Cancer Research, London, also emphasized that it was large and its data came from general practitioner medical records, “so the strong statistical associations are unlikely to be due to chance.

“The results of this study generally confirm what has been seen before and is well established – that the use of combined estrogen plus progestogen HRT is associated with increased risk of breast cancer, and this risk increases with duration of use. But reassuringly, after stopping HRT, the raised risk of breast cancer mostly returns to that seen in nonusers of HRT,” he said.

“It’s important to note that no one study should be considered in isolation,” he added. “Even though some risks were found to be slightly smaller than those reported in another meta-analysis of the worldwide epidemiological evidence recently published in 2019, women considering use of HRT should still follow advice given to them by their [general practitioners].”
 

Study details

In the study, researchers evaluated all types of HRT commonly prescribed in the United Kingdom over the past 20 years, including topical estrogen, vaginal pessaries, and creams. They grouped HRT use by recent (within the past 5 years) and past (5 or more years ago) and HRT duration as short term (less than 5 years) and long term (5 years or longer). Results were adjusted for a range of factors that could affect breast cancer risk, including lifestyle, smoking, alcohol consumption, other medical conditions, family history, and use of other prescribed drugs.

The analysis included 98,611 women aged 50-79 years who were first diagnosed with breast cancer between 1998 and 2019. These women were matched by age and general practice to 457,498 women who were not diagnosed with breast cancer over these years. HRT use was reported in 34% (33,703) of women with breast cancer and in 31% (134,391) of women without breast cancer.

Overall, the risk for breast cancer was increased with use of most HRT drugs (adjusted odds ratio, 1.21; 95% confidence, 1.19-1.23), compared with not using HRT drugs. The highest risk was tied to combined estrogen/progestogen HRT (adjusted OR, 1.26; 95% CI, 1.24-1.29). The lowest risk was tied to estrogen-only HRT (adjusted OR, 1.06; 95% CI, 1.03-1.10). Estrogen cream and vaginal estrogen were not associated with increased breast cancer risk.

In general, breast cancer risk was higher among recent HRT users and those receiving long-term therapy. HRT-associated breast cancer risk increased with age and declined after discontinuing treatment. Therapy of less than 1 year was not associated with increased breast cancer risk.

Women who had recently been receiving long-term combined estrogen/progestogen HRT had a 79% increased risk for breast cancer (adjusted OR, 1.79; 95% CI, 1.73-1.85), compared with never-users. Among recent long-term users of combined HRT, breast cancer risk was highest for norethisterone (adjusted OR, 1.88; 95% CI, 1.79-1.99) and lowest for dydrogesterone (adjusted OR, 1.24; 95% CI, 1.03-1.48). Women who had recently been receiving long-term estrogen-only HRT had a 15% increased risk for breast cancer compared to never-users (adjusted OR, 1.15; 95% CI, 1.09-1.21).

Among women who discontinued HRT 5 or more years ago, risk for breast cancer was no longer increased for long-term estrogen-only therapy and short-term estrogen/progestogen therapy. However, breast cancer risk remained elevated 5 years after discontinuing long-term estrogen/progestogen (adjusted OR, 1.16; 95% CI, 1.11-1.21).

HRT-associated risk for breast cancer increased with age across all durations of therapy.

Compared with never-use, recent long-term estrogen-only therapy was associated with zero extra breast cancer cases per 10,000 women-years among women aged 50-59 years and eight extra cases per 10,000 women-years among women aged 70-79.

Recent long-term estrogen/progestogen use was associated with 15 extra breast cancer cases among women aged 50-59 and 36 extra cases among women aged 70-79 per 10,000 women-years.

Past long-term estrogen/progestogen use was associated with zero extra breast cancer cases among women aged 50-59 and eight extra cases among women aged 70-79 per 10,000 women-years.

Summarizing, Dr. Vinogradova said the increased risk for breast cancer with HRT appears to be “relatively small, particularly for younger women and for any women who use HRT only for a restricted period.”

Decisions about whether to use HRT and which type to use should depend on symptom severity, patient factors, and suitability of other treatment options, she commented.

“Particularly for those women who our study has shown to be most at risk, these decisions should be made through discussions between the patient and her doctor,” she concluded. “We hope that the new and more detailed information provided by our study will facilitate such prescribing decisions.”

The study was partially funded by the School for Primary Care Research of the National Institute for Health Research, by Cancer Research UK, and by the Cancer Research UK Oxford Center. Dr. Vinogradova has disclosed no relevant financial relationships. Senior author Julia Hippisley-Cox is an unpaid director of QResearch and was a paid director of ClinRisk until 2019. The other authors have disclosed no relevant financial relationships.
 

A version of this story originally appeared on Medscape.com.

Stereotactic radiosurgery (SRS) should replace whole-brain radiotherapy (WBRT) as the new standard of care for patients with four or more brain metastases, say researchers who report results from a randomized trial conducted in patients with four to 15 brain metastases

“SRS was associated with reduced risk of neurocognitive deterioration compared to WBRT, as demonstrated by a constellation of neurocognitive tests, individually or by composite scores,” said lead author Jing Li, MD, PhD, associate professor of radiation oncology and codirector of the Brain Metastasis Clinic at the University of Texas MD Anderson Cancer Center, Houston.

She was speaking at the American Society for Radiation Oncology (ASTRO) 2020 Annual Meeting, which was held online this year because of the COVID pandemic.

“The results from this phase 3 randomized trial strongly support the use of SRS in patients with four to 15 brain metastases to better preserve cognitive function and to minimize interruption of systemic therapy, without compromising overall survival,” said Li.

SRS is already the standard of care for patients with one to three brain metastases. Two previous phase 3 randomized trials showed that SRS was better at preserving cognitive function without compromising overall survival in comparison to WBRT.

However, there has been some controversy over the use of SRS for patients with multiple brain metastases, commented study discussant Sue S. Yom, MD, PhD, a professor in the Departments of Radiation Oncology and Otolaryngology–Head and Neck Surgery, University of California, San Francisco.

This study has shown, “in a practice-changing manner, that giving SRS can improve the quality of life of patients with metastatic disease,” she said.

Up to 30% of cancer patients develop brain metastases. Historically, these have been associated with poor overall survival, in the range of 1 to 4 months.
 

Reduces cognitive decline

The new trial involved 72 patients with four to 15 untreated, nonmelanoma brain metastases (up to 20 lesions were allowed at the time of treatment); the median number of brain metastases was eight. Most (83%) of the trial participants were White, nearly half were aged 60 years or older, and 58% were women.

Patients were randomly assigned to receive either SRS (15–24 Gy per Radiation Therapy Oncology Group protocol 9005) or WBRT (30 Gy in 10 fractions). On the basis of previous research, 62% of patients in the WBRT arm were also given memantine, a dementia drug that can help preserve cognitive function.

All participants completed neurocognitive testing, including testing of learning, memory, attention span, executive function, verbal fluency, processing speed, and motor dexterity, at enrollment and longitudinally.

The primary endpoints were Hopkins Verbal Learning Test – Revised Total Recall (HVLT-R TR) score and local control at 4 months. Secondary endpoints included overall survival, distant brain failure, toxicity, and time to initiation of systemic therapy.

In the primary endpoint analysis, at 4 months, the HVLT-R TR standardized z-score increased by +0.21 (standard error [SE], 0.27) for patients who received SRS, but it declined by –0.74 (SE, 0.36) for WBRT-treated patients (P = .041). On the basis of Clinical Trial Battery Composite score, neurocognitive function of patients in the SRS arm improved on average +0.23 (SE, 0.14) but declined an average –0.73 (SE, 0.35) in the WBRT arm (P = .008).

Li pointed out that there was also a “clinically meaningful and statistically significant benefit” with SRS at 1 month (P = .033) and 6 months (P = .012).

A total of 69 patients (35 for SRS and 34 for WBRT) were evaluable for overall survival, which was similar between the groups (SRS median, 7.8 months; WBRT median, 8.9 months; P = .59). Treatment with SRS resulted in better local control rates (95% at 4 months with SRS and 86.7% with WBRT; P = .09), but the median time to distant brain failure was shorter (10.5 months for WBRT and 6.3 months for SRS; P = .37).

In her discussion of the study, Yom noted that overall survival time was similar in the two arms and that, numerically, it may have even been a little longer in the SRS group. “While it is true that they had more relapses in untreated portions of the brain, they lived as long or longer than those who received WBRT and had better cognitive function,” she noted

Yom also noted that of particular importance was the finding that SRS was associated with shorter interruptions of systemic therapy (time to systemic therapy: SRS, 1.7 weeks; WBRT, 4.1 weeks; P = .001). Patients with metastatic disease usually have cancer in locations other than the brain. They may be receiving some type of systemic therapy, which is interrupted with WBRT, Li commented.

Toxicities of grade 3 or higher were observed in four patients in the WBRT arm and two in the SRS arm. Radiographic evidence of radiation necrosis, a side effect associated with SRS, was observed in 17% patients in the SRS arm of the trial (4% of all treated lesions).

The trial was halted early owing to the publication of another phase 3 trial (NRG Oncology CC 001), which provided level 1 evidence for replacing standard WBRT with hippocampal-avoidance WBRT. Despite the early trial termination, Li concluded that these results “strongly support the use of SRS in patients with four to 15 brain metastases to better preserve cognitive function and to minimize interruption of systemic therapy, without compromising overall survival.”

Li has received research funding from BMS and Medtronic and honorarium from Novocure and Monteris.

This article first appeared on Medscape.com.

Stereotactic radiosurgery (SRS) should replace whole-brain radiotherapy (WBRT) as the new standard of care for patients with four or more brain metastases, say researchers who report results from a randomized trial conducted in patients with four to 15 brain metastases

“SRS was associated with reduced risk of neurocognitive deterioration compared to WBRT, as demonstrated by a constellation of neurocognitive tests, individually or by composite scores,” said lead author Jing Li, MD, PhD, associate professor of radiation oncology and codirector of the Brain Metastasis Clinic at the University of Texas MD Anderson Cancer Center, Houston.

She was speaking at the American Society for Radiation Oncology (ASTRO) 2020 Annual Meeting, which was held online this year because of the COVID pandemic.

“The results from this phase 3 randomized trial strongly support the use of SRS in patients with four to 15 brain metastases to better preserve cognitive function and to minimize interruption of systemic therapy, without compromising overall survival,” said Li.

SRS is already the standard of care for patients with one to three brain metastases. Two previous phase 3 randomized trials showed that SRS was better at preserving cognitive function without compromising overall survival in comparison to WBRT.

However, there has been some controversy over the use of SRS for patients with multiple brain metastases, commented study discussant Sue S. Yom, MD, PhD, a professor in the Departments of Radiation Oncology and Otolaryngology–Head and Neck Surgery, University of California, San Francisco.

This study has shown, “in a practice-changing manner, that giving SRS can improve the quality of life of patients with metastatic disease,” she said.

Up to 30% of cancer patients develop brain metastases. Historically, these have been associated with poor overall survival, in the range of 1 to 4 months.
 

Reduces cognitive decline

The new trial involved 72 patients with four to 15 untreated, nonmelanoma brain metastases (up to 20 lesions were allowed at the time of treatment); the median number of brain metastases was eight. Most (83%) of the trial participants were White, nearly half were aged 60 years or older, and 58% were women.

Patients were randomly assigned to receive either SRS (15–24 Gy per Radiation Therapy Oncology Group protocol 9005) or WBRT (30 Gy in 10 fractions). On the basis of previous research, 62% of patients in the WBRT arm were also given memantine, a dementia drug that can help preserve cognitive function.

All participants completed neurocognitive testing, including testing of learning, memory, attention span, executive function, verbal fluency, processing speed, and motor dexterity, at enrollment and longitudinally.

The primary endpoints were Hopkins Verbal Learning Test – Revised Total Recall (HVLT-R TR) score and local control at 4 months. Secondary endpoints included overall survival, distant brain failure, toxicity, and time to initiation of systemic therapy.

In the primary endpoint analysis, at 4 months, the HVLT-R TR standardized z-score increased by +0.21 (standard error [SE], 0.27) for patients who received SRS, but it declined by –0.74 (SE, 0.36) for WBRT-treated patients (P = .041). On the basis of Clinical Trial Battery Composite score, neurocognitive function of patients in the SRS arm improved on average +0.23 (SE, 0.14) but declined an average –0.73 (SE, 0.35) in the WBRT arm (P = .008).

Li pointed out that there was also a “clinically meaningful and statistically significant benefit” with SRS at 1 month (P = .033) and 6 months (P = .012).

A total of 69 patients (35 for SRS and 34 for WBRT) were evaluable for overall survival, which was similar between the groups (SRS median, 7.8 months; WBRT median, 8.9 months; P = .59). Treatment with SRS resulted in better local control rates (95% at 4 months with SRS and 86.7% with WBRT; P = .09), but the median time to distant brain failure was shorter (10.5 months for WBRT and 6.3 months for SRS; P = .37).

In her discussion of the study, Yom noted that overall survival time was similar in the two arms and that, numerically, it may have even been a little longer in the SRS group. “While it is true that they had more relapses in untreated portions of the brain, they lived as long or longer than those who received WBRT and had better cognitive function,” she noted

Yom also noted that of particular importance was the finding that SRS was associated with shorter interruptions of systemic therapy (time to systemic therapy: SRS, 1.7 weeks; WBRT, 4.1 weeks; P = .001). Patients with metastatic disease usually have cancer in locations other than the brain. They may be receiving some type of systemic therapy, which is interrupted with WBRT, Li commented.

Toxicities of grade 3 or higher were observed in four patients in the WBRT arm and two in the SRS arm. Radiographic evidence of radiation necrosis, a side effect associated with SRS, was observed in 17% patients in the SRS arm of the trial (4% of all treated lesions).

The trial was halted early owing to the publication of another phase 3 trial (NRG Oncology CC 001), which provided level 1 evidence for replacing standard WBRT with hippocampal-avoidance WBRT. Despite the early trial termination, Li concluded that these results “strongly support the use of SRS in patients with four to 15 brain metastases to better preserve cognitive function and to minimize interruption of systemic therapy, without compromising overall survival.”

Li has received research funding from BMS and Medtronic and honorarium from Novocure and Monteris.

This article first appeared on Medscape.com.

Stereotactic radiosurgery (SRS) should replace whole-brain radiotherapy (WBRT) as the new standard of care for patients with four or more brain metastases, say researchers who report results from a randomized trial conducted in patients with four to 15 brain metastases

“SRS was associated with reduced risk of neurocognitive deterioration compared to WBRT, as demonstrated by a constellation of neurocognitive tests, individually or by composite scores,” said lead author Jing Li, MD, PhD, associate professor of radiation oncology and codirector of the Brain Metastasis Clinic at the University of Texas MD Anderson Cancer Center, Houston.

She was speaking at the American Society for Radiation Oncology (ASTRO) 2020 Annual Meeting, which was held online this year because of the COVID pandemic.

“The results from this phase 3 randomized trial strongly support the use of SRS in patients with four to 15 brain metastases to better preserve cognitive function and to minimize interruption of systemic therapy, without compromising overall survival,” said Li.

SRS is already the standard of care for patients with one to three brain metastases. Two previous phase 3 randomized trials showed that SRS was better at preserving cognitive function without compromising overall survival in comparison to WBRT.

However, there has been some controversy over the use of SRS for patients with multiple brain metastases, commented study discussant Sue S. Yom, MD, PhD, a professor in the Departments of Radiation Oncology and Otolaryngology–Head and Neck Surgery, University of California, San Francisco.

This study has shown, “in a practice-changing manner, that giving SRS can improve the quality of life of patients with metastatic disease,” she said.

Up to 30% of cancer patients develop brain metastases. Historically, these have been associated with poor overall survival, in the range of 1 to 4 months.
 

Reduces cognitive decline

The new trial involved 72 patients with four to 15 untreated, nonmelanoma brain metastases (up to 20 lesions were allowed at the time of treatment); the median number of brain metastases was eight. Most (83%) of the trial participants were White, nearly half were aged 60 years or older, and 58% were women.

Patients were randomly assigned to receive either SRS (15–24 Gy per Radiation Therapy Oncology Group protocol 9005) or WBRT (30 Gy in 10 fractions). On the basis of previous research, 62% of patients in the WBRT arm were also given memantine, a dementia drug that can help preserve cognitive function.

All participants completed neurocognitive testing, including testing of learning, memory, attention span, executive function, verbal fluency, processing speed, and motor dexterity, at enrollment and longitudinally.

The primary endpoints were Hopkins Verbal Learning Test – Revised Total Recall (HVLT-R TR) score and local control at 4 months. Secondary endpoints included overall survival, distant brain failure, toxicity, and time to initiation of systemic therapy.

In the primary endpoint analysis, at 4 months, the HVLT-R TR standardized z-score increased by +0.21 (standard error [SE], 0.27) for patients who received SRS, but it declined by –0.74 (SE, 0.36) for WBRT-treated patients (P = .041). On the basis of Clinical Trial Battery Composite score, neurocognitive function of patients in the SRS arm improved on average +0.23 (SE, 0.14) but declined an average –0.73 (SE, 0.35) in the WBRT arm (P = .008).

Li pointed out that there was also a “clinically meaningful and statistically significant benefit” with SRS at 1 month (P = .033) and 6 months (P = .012).

A total of 69 patients (35 for SRS and 34 for WBRT) were evaluable for overall survival, which was similar between the groups (SRS median, 7.8 months; WBRT median, 8.9 months; P = .59). Treatment with SRS resulted in better local control rates (95% at 4 months with SRS and 86.7% with WBRT; P = .09), but the median time to distant brain failure was shorter (10.5 months for WBRT and 6.3 months for SRS; P = .37).

In her discussion of the study, Yom noted that overall survival time was similar in the two arms and that, numerically, it may have even been a little longer in the SRS group. “While it is true that they had more relapses in untreated portions of the brain, they lived as long or longer than those who received WBRT and had better cognitive function,” she noted

Yom also noted that of particular importance was the finding that SRS was associated with shorter interruptions of systemic therapy (time to systemic therapy: SRS, 1.7 weeks; WBRT, 4.1 weeks; P = .001). Patients with metastatic disease usually have cancer in locations other than the brain. They may be receiving some type of systemic therapy, which is interrupted with WBRT, Li commented.

Toxicities of grade 3 or higher were observed in four patients in the WBRT arm and two in the SRS arm. Radiographic evidence of radiation necrosis, a side effect associated with SRS, was observed in 17% patients in the SRS arm of the trial (4% of all treated lesions).

The trial was halted early owing to the publication of another phase 3 trial (NRG Oncology CC 001), which provided level 1 evidence for replacing standard WBRT with hippocampal-avoidance WBRT. Despite the early trial termination, Li concluded that these results “strongly support the use of SRS in patients with four to 15 brain metastases to better preserve cognitive function and to minimize interruption of systemic therapy, without compromising overall survival.”

Li has received research funding from BMS and Medtronic and honorarium from Novocure and Monteris.

This article first appeared on Medscape.com.

Sexual dysfunction is a common treatment-related problem observed across numerous cancer diagnoses, and a new survey finds that 87% of cancer survivors have had such problems.

However, most of them also reported that their oncologist had not formally discussed the topic, and female patients were particularly unlikely to be asked about sexual dysfunction.

“The main takeaway from our study is that sexual side effects following treatment are very common,” said lead author James Taylor, MD, MPH, chief resident in radiation oncology at the Sidney Kimmel Cancer Center at Thomas Jefferson University in Philadelphia, Pennsylvania.

“Nearly 9 in 10 patients reported some change after cancer treatment that negatively affected their sexual health,” he said.

Taylor was speaking at the American Society for Radiation Oncology (ASTRO) Annual Meeting, held virtually this year because of the pandemic.

“Negative effects on sexual health after cancer treatment are unfortunately very common,” he said. “This is not just patients treated with radiation but this includes chemotherapy, hormonal therapy, surgery, and other treatment modalities.”

Potential issues include physical complications such as erectile dysfunction with prostate cancer treatment or vaginal dryness with gynecological cancer treatment. One recent study found that one-third of men who had undergone treatment for prostate cancer reported that a subsequent lack of sexual function has had the greatest impact on their quality of life. Another study reported that nearly all patients with breast cancer taking endocrine therapy experience a high degree of sexual dysfunction, including vulvovaginal dryness and severe dyspareunia.
 

Not discussed, not warned

Taylor and colleagues developed a questionnaire with input from radiation oncologists, medical oncologists, and surgeons, which consisted of more than 25 questions and was specifically targeted at cancer survivors.

A total of 405 adults completed the electronic survey about their experiences with sexual side effects after cancer treatment (391 responses were eligible for analysis). Most of the respondents were women (81%), and the most common cancer types were breast (67%), prostate (16%), and endometrial (6%). Treatments included chemotherapy (78%), radiation therapy (54%), and hormone therapy (47%).

“The questionnaires were distributed at Thomas Jefferson and throughout social media,” said Taylor. “The responses from social media are important because it shows a broad representation of patients who are treated in multiple clinics across the United States.”

Most of the survivors who responded (n = 337, 87%) stated cancer treatment had impacted sexual function or desire, with 53.8% reporting body image distortion, 73.4% with dyspareunia, and 42.3% unable to achieve orgasm.

Only about one-quarter (27.9%) said they had been formally asked about their sexual health by their clinician.

“Only about 40% said that they have been preemptively warned that their sexual health may be affected by treatment,” said Taylor.

Women were far less likely to be asked about their sexual health by their provider. The survey showed that male respondents were twice as likely to say they had been asked about sexual health and counseled about the potential toxicity (53% vs 22%; P < .001), and a substantially higher percentage of men reported receiving a formal assessment tool such as a survey (32% vs 5%; P = .001) compared with female respondents.

Taylor noted that the survey demonstrated several things. “One is that sexual toxicity is exceedingly common, and number two, it identified a gender disparity,” he said. “But number 3, and I think that this is an important aspect of our study, is that the majority of respondents felt that they would like a standard questionnaire to initiate and guide a discussion on sexual health with their provider.”

The reason that aspect is very important, he emphasized, is that “we know metrics and questionnaires already exist, so this gives us an actionable intervention that we can distribute and help mitigate some of these disparities.”
 

Importance of being holistic

The results of the survey “highlight the importance of being holistic in our approach to patient survivorship,” commented Karen Winkfield, MD, PhD, associate professor of radiation oncology at Wake Forest University, Winston-Salem, North Carolina, and executive director of the Meharry-Vanderbilt Alliance, Nashville, Tennessee.

“We need to ask patients about all parts of their well-being, including sexual health,” Winkfield said. “Body dysmorphism can impact anyone, but especially patients who have had surgery or radiation,” she said, while chemotherapy can impact energy and libido and have other toxicities that impact sexual health.

“I encourage all oncologists to ask patients about their sexual health, and a standardized form that can be used across all sites will make this much easier,” Winkfield commented. “We owe it to our patients to treat them holistically.”

The authors have reported no relevant financial relationships.

This article first appeared on Medscape.com.

Sexual dysfunction is a common treatment-related problem observed across numerous cancer diagnoses, and a new survey finds that 87% of cancer survivors have had such problems.

However, most of them also reported that their oncologist had not formally discussed the topic, and female patients were particularly unlikely to be asked about sexual dysfunction.

“The main takeaway from our study is that sexual side effects following treatment are very common,” said lead author James Taylor, MD, MPH, chief resident in radiation oncology at the Sidney Kimmel Cancer Center at Thomas Jefferson University in Philadelphia, Pennsylvania.

“Nearly 9 in 10 patients reported some change after cancer treatment that negatively affected their sexual health,” he said.

Taylor was speaking at the American Society for Radiation Oncology (ASTRO) Annual Meeting, held virtually this year because of the pandemic.

“Negative effects on sexual health after cancer treatment are unfortunately very common,” he said. “This is not just patients treated with radiation but this includes chemotherapy, hormonal therapy, surgery, and other treatment modalities.”

Potential issues include physical complications such as erectile dysfunction with prostate cancer treatment or vaginal dryness with gynecological cancer treatment. One recent study found that one-third of men who had undergone treatment for prostate cancer reported that a subsequent lack of sexual function has had the greatest impact on their quality of life. Another study reported that nearly all patients with breast cancer taking endocrine therapy experience a high degree of sexual dysfunction, including vulvovaginal dryness and severe dyspareunia.
 

Not discussed, not warned

Taylor and colleagues developed a questionnaire with input from radiation oncologists, medical oncologists, and surgeons, which consisted of more than 25 questions and was specifically targeted at cancer survivors.

A total of 405 adults completed the electronic survey about their experiences with sexual side effects after cancer treatment (391 responses were eligible for analysis). Most of the respondents were women (81%), and the most common cancer types were breast (67%), prostate (16%), and endometrial (6%). Treatments included chemotherapy (78%), radiation therapy (54%), and hormone therapy (47%).

“The questionnaires were distributed at Thomas Jefferson and throughout social media,” said Taylor. “The responses from social media are important because it shows a broad representation of patients who are treated in multiple clinics across the United States.”

Most of the survivors who responded (n = 337, 87%) stated cancer treatment had impacted sexual function or desire, with 53.8% reporting body image distortion, 73.4% with dyspareunia, and 42.3% unable to achieve orgasm.

Only about one-quarter (27.9%) said they had been formally asked about their sexual health by their clinician.

“Only about 40% said that they have been preemptively warned that their sexual health may be affected by treatment,” said Taylor.

Women were far less likely to be asked about their sexual health by their provider. The survey showed that male respondents were twice as likely to say they had been asked about sexual health and counseled about the potential toxicity (53% vs 22%; P < .001), and a substantially higher percentage of men reported receiving a formal assessment tool such as a survey (32% vs 5%; P = .001) compared with female respondents.

Taylor noted that the survey demonstrated several things. “One is that sexual toxicity is exceedingly common, and number two, it identified a gender disparity,” he said. “But number 3, and I think that this is an important aspect of our study, is that the majority of respondents felt that they would like a standard questionnaire to initiate and guide a discussion on sexual health with their provider.”

The reason that aspect is very important, he emphasized, is that “we know metrics and questionnaires already exist, so this gives us an actionable intervention that we can distribute and help mitigate some of these disparities.”
 

Importance of being holistic

The results of the survey “highlight the importance of being holistic in our approach to patient survivorship,” commented Karen Winkfield, MD, PhD, associate professor of radiation oncology at Wake Forest University, Winston-Salem, North Carolina, and executive director of the Meharry-Vanderbilt Alliance, Nashville, Tennessee.

“We need to ask patients about all parts of their well-being, including sexual health,” Winkfield said. “Body dysmorphism can impact anyone, but especially patients who have had surgery or radiation,” she said, while chemotherapy can impact energy and libido and have other toxicities that impact sexual health.

“I encourage all oncologists to ask patients about their sexual health, and a standardized form that can be used across all sites will make this much easier,” Winkfield commented. “We owe it to our patients to treat them holistically.”

The authors have reported no relevant financial relationships.

This article first appeared on Medscape.com.

Sexual dysfunction is a common treatment-related problem observed across numerous cancer diagnoses, and a new survey finds that 87% of cancer survivors have had such problems.

However, most of them also reported that their oncologist had not formally discussed the topic, and female patients were particularly unlikely to be asked about sexual dysfunction.

“The main takeaway from our study is that sexual side effects following treatment are very common,” said lead author James Taylor, MD, MPH, chief resident in radiation oncology at the Sidney Kimmel Cancer Center at Thomas Jefferson University in Philadelphia, Pennsylvania.

“Nearly 9 in 10 patients reported some change after cancer treatment that negatively affected their sexual health,” he said.

Taylor was speaking at the American Society for Radiation Oncology (ASTRO) Annual Meeting, held virtually this year because of the pandemic.

“Negative effects on sexual health after cancer treatment are unfortunately very common,” he said. “This is not just patients treated with radiation but this includes chemotherapy, hormonal therapy, surgery, and other treatment modalities.”

Potential issues include physical complications such as erectile dysfunction with prostate cancer treatment or vaginal dryness with gynecological cancer treatment. One recent study found that one-third of men who had undergone treatment for prostate cancer reported that a subsequent lack of sexual function has had the greatest impact on their quality of life. Another study reported that nearly all patients with breast cancer taking endocrine therapy experience a high degree of sexual dysfunction, including vulvovaginal dryness and severe dyspareunia.
 

Not discussed, not warned

Taylor and colleagues developed a questionnaire with input from radiation oncologists, medical oncologists, and surgeons, which consisted of more than 25 questions and was specifically targeted at cancer survivors.

A total of 405 adults completed the electronic survey about their experiences with sexual side effects after cancer treatment (391 responses were eligible for analysis). Most of the respondents were women (81%), and the most common cancer types were breast (67%), prostate (16%), and endometrial (6%). Treatments included chemotherapy (78%), radiation therapy (54%), and hormone therapy (47%).

“The questionnaires were distributed at Thomas Jefferson and throughout social media,” said Taylor. “The responses from social media are important because it shows a broad representation of patients who are treated in multiple clinics across the United States.”

Most of the survivors who responded (n = 337, 87%) stated cancer treatment had impacted sexual function or desire, with 53.8% reporting body image distortion, 73.4% with dyspareunia, and 42.3% unable to achieve orgasm.

Only about one-quarter (27.9%) said they had been formally asked about their sexual health by their clinician.

“Only about 40% said that they have been preemptively warned that their sexual health may be affected by treatment,” said Taylor.

Women were far less likely to be asked about their sexual health by their provider. The survey showed that male respondents were twice as likely to say they had been asked about sexual health and counseled about the potential toxicity (53% vs 22%; P < .001), and a substantially higher percentage of men reported receiving a formal assessment tool such as a survey (32% vs 5%; P = .001) compared with female respondents.

Taylor noted that the survey demonstrated several things. “One is that sexual toxicity is exceedingly common, and number two, it identified a gender disparity,” he said. “But number 3, and I think that this is an important aspect of our study, is that the majority of respondents felt that they would like a standard questionnaire to initiate and guide a discussion on sexual health with their provider.”

The reason that aspect is very important, he emphasized, is that “we know metrics and questionnaires already exist, so this gives us an actionable intervention that we can distribute and help mitigate some of these disparities.”
 

Importance of being holistic

The results of the survey “highlight the importance of being holistic in our approach to patient survivorship,” commented Karen Winkfield, MD, PhD, associate professor of radiation oncology at Wake Forest University, Winston-Salem, North Carolina, and executive director of the Meharry-Vanderbilt Alliance, Nashville, Tennessee.

“We need to ask patients about all parts of their well-being, including sexual health,” Winkfield said. “Body dysmorphism can impact anyone, but especially patients who have had surgery or radiation,” she said, while chemotherapy can impact energy and libido and have other toxicities that impact sexual health.

“I encourage all oncologists to ask patients about their sexual health, and a standardized form that can be used across all sites will make this much easier,” Winkfield commented. “We owe it to our patients to treat them holistically.”

The authors have reported no relevant financial relationships.

This article first appeared on Medscape.com.

A national effort to perform genotype drug matching across cancer types shows the value of next-generation sequencing and provides a roadmap for future precision oncology trials, according to experts.

Massachusetts General Hospital

The effort is the National Cancer Institute Molecular Analysis for Therapy Choice (NCI-MATCH) trial. For this study, researchers performed next-generation sequencing on tumor biopsy specimens to identify therapeutically actionable molecular alterations in patients with “underexplored” cancer types.

The trial included 5,954 patients with cancers that had progressed on standard treatments or rare cancers for which there is no standard treatment. If actionable alterations were found in these patients, they could receive new drugs in development that showed promise in other clinical trials or drugs that were approved by the Food and Drug Administration to treat at least one cancer type.

Data newly reported in the Journal of Clinical Oncology showed that 37.6% of patients had alterations that could be matched to targeted drugs, and 17.8% of patients were assigned to targeted treatment. Multiple actionable tumor mutations were seen in 11.9% of specimens, and resistance-conferring mutations were seen in 71.3% of specimens.

“The bottom line from this report is that next-generation sequencing is an efficient way to identify both approved and promising investigational therapies. For this reason, it should be considered standard of care for patients with advanced cancers,” said study chair Keith T. Flaherty, MD, director of the Henri and Belinda Termeer Center for Targeted Therapy at Massachusetts General Hospital Cancer Center in Boston.

“This study sets the benchmark for the ‘actionability’ of next-generation sequencing,” Dr. Flaherty added. “We expect this number [of actionable alterations] will continue to rise steadily as further advances are made in the development of therapies that target some of the genetic alterations for which we could not offer treatment options in NCI-MATCH.”
 

Relapsed/refractory vs. primary tumors

The NCI-MATCH researchers focused on the most commonly found genetic alterations and performed biopsies at study entry to provide the most accurate picture of the genetic landscape of relapsed/refractory cancer patients. That makes this cohort distinct from The Cancer Genome Atlas (TCGA), a database of patients with mostly untreated primary tumors, and other published cohorts that include genetic analysis of primary tumors and biopsies from the time of initial metastatic recurrence.

The researchers compared the tumor gene makeup of NCI-MATCH and TCGA patients with seven cancer types – breast, bile duct, cervix, colorectal, lung, pancreas, and prostate.

ECOG-ACRIN Cancer Research Group

“Perhaps the biggest surprise was the relatively minimal change in the genetic alterations found in these relapsed/refractory patients, compared to primary tumors,” Dr. Flaherty said. “These findings suggest that it is very reasonable to perform next-generation sequencing at the time of initial metastatic cancer diagnosis and to rely on those findings for the purposes of considering FDA-approved therapies and clinical trial participation.”
 

Multiple alterations and resistance

The complex genetics of cancers has led researchers to explore combinations of targeted and other therapies to address multiple defects at the same time.

“Not surprisingly, the most common collision of multiple genetic alterations within the same tumor was in the commonly altered tumor suppressor genes: TP53, APC, and PTEN,” Dr. Flaherty said.

“An increasing body of evidence supports a role for loss-of-function alterations in these genes to confer resistance to many targeted therapies,” he added. “While we don’t have targeted therapies yet established to directly counter this form of therapeutic resistance, we hypothesize that various types of combination therapy may be able to indirectly undercut resistance and enhance the benefit of many targeted therapies.”

The NCI-MATCH researchers will continue to mine this large dataset to better understand the many small, genetically defined cancer subpopulations.

“We will continue to report the outcome of the individual treatment subprotocols, and combining this genetic analysis with those outcomes will likely inform the next clinical trials,” Dr. Flaherty said.
 

Actionable mutations make a difference

Precision oncology experts agree that NCI-MATCH results are impressive and add a fuller appreciation that actionable mutations make a clinical difference.

“This is a powerful, extremely well-designed study, a tour de force of collaborative science,” said Stephen Gruber, MD, PhD, director of the Center for Precision Medicine at City of Hope National Medical Center in Duarte, Calif.

“The future holds even more promise,” he added. “Our ability to interrogate the genomic landscape of cancer is improving rapidly. Tumor testing helps get the right drug to the right tumor faster than a guidelines-based approach from historical data of combination chemotherapy. This is a likely game changer for the way oncologists will practice in the future, especially as we learn more results of subset trials. The NCI-MATCH researchers have taken a laser-focused look at the current data, but we now know we can look far more comprehensively at genomic profiles of tumors.”

From the viewpoint of the practicing oncologist, co-occurring resistance mutations make a difference in defining what combinations are likely and, more importantly, less likely to be effective. “When we see two mutations and one is likely to confer resistance, we can make a choice to avoid a drug that is not likely to work,” Dr. Gruber said.

“The NCI-MATCH trial allows both approved and investigational agents, which expands the possibility of matching patients to newer agents. This is especially relevant if there are no FDA-approved drugs yet for some molecular aberrations,” said Lillian L. Siu, MD, a senior medical oncologist at the Princess Margaret Cancer Centre in Toronto. “This trial enables such evaluations under the auspice of a clinical trial to provide important knowledge.”

Both experts agree that in-depth biological interrogations of cancer will move the field of precision oncology forward. Dr. Gruber said that “studies have not yet fully addressed the power of germline genetic testing of DNA. Inherited susceptibility will drive therapeutic choices – for example, PARP inhibitors that access homologous recombination deficiency for breast, ovarian, and prostate cancer. We will learn more about treatment choices for those cancers.”

Dr. Siu added: “I truly believe that liquid biopsies [circulating tumor DNA] will help us perform target-drug matching in a less invasive way. We need to explore beyond the genome to look at the transcriptome, proteome, epigenome, and immunome, among others. It is likely that multiomic predictors are going to be able to identify more therapeutic options compared to single genomic predictors.”

Dr. Flaherty noted that all tumor samples from patients assigned to treatment are being subjected to whole-exome sequencing to further the discovery of the genetic features of responsive and nonresponsive tumors.

NCI-MATCH was funded by the National Cancer Institute. Dr. Flaherty disclosed relationships with Clovis Oncology, Loxo, X4 Pharma, and many other companies. His coauthors disclosed many conflicts as well. Dr. Gruber is cofounder of Brogent International. Dr. Siu disclosed relationships with Agios, Treadwell Therapeutics, Merck, Pfizer, and many other companies.

SOURCE: Flaherty KT et al. J Clin Oncol. 2020 Oct 13. doi: 10.1200/JCO.19.03010.

A national effort to perform genotype drug matching across cancer types shows the value of next-generation sequencing and provides a roadmap for future precision oncology trials, according to experts.

Massachusetts General Hospital

The effort is the National Cancer Institute Molecular Analysis for Therapy Choice (NCI-MATCH) trial. For this study, researchers performed next-generation sequencing on tumor biopsy specimens to identify therapeutically actionable molecular alterations in patients with “underexplored” cancer types.

The trial included 5,954 patients with cancers that had progressed on standard treatments or rare cancers for which there is no standard treatment. If actionable alterations were found in these patients, they could receive new drugs in development that showed promise in other clinical trials or drugs that were approved by the Food and Drug Administration to treat at least one cancer type.

Data newly reported in the Journal of Clinical Oncology showed that 37.6% of patients had alterations that could be matched to targeted drugs, and 17.8% of patients were assigned to targeted treatment. Multiple actionable tumor mutations were seen in 11.9% of specimens, and resistance-conferring mutations were seen in 71.3% of specimens.

“The bottom line from this report is that next-generation sequencing is an efficient way to identify both approved and promising investigational therapies. For this reason, it should be considered standard of care for patients with advanced cancers,” said study chair Keith T. Flaherty, MD, director of the Henri and Belinda Termeer Center for Targeted Therapy at Massachusetts General Hospital Cancer Center in Boston.

“This study sets the benchmark for the ‘actionability’ of next-generation sequencing,” Dr. Flaherty added. “We expect this number [of actionable alterations] will continue to rise steadily as further advances are made in the development of therapies that target some of the genetic alterations for which we could not offer treatment options in NCI-MATCH.”
 

Relapsed/refractory vs. primary tumors

The NCI-MATCH researchers focused on the most commonly found genetic alterations and performed biopsies at study entry to provide the most accurate picture of the genetic landscape of relapsed/refractory cancer patients. That makes this cohort distinct from The Cancer Genome Atlas (TCGA), a database of patients with mostly untreated primary tumors, and other published cohorts that include genetic analysis of primary tumors and biopsies from the time of initial metastatic recurrence.

The researchers compared the tumor gene makeup of NCI-MATCH and TCGA patients with seven cancer types – breast, bile duct, cervix, colorectal, lung, pancreas, and prostate.

ECOG-ACRIN Cancer Research Group

“Perhaps the biggest surprise was the relatively minimal change in the genetic alterations found in these relapsed/refractory patients, compared to primary tumors,” Dr. Flaherty said. “These findings suggest that it is very reasonable to perform next-generation sequencing at the time of initial metastatic cancer diagnosis and to rely on those findings for the purposes of considering FDA-approved therapies and clinical trial participation.”
 

Multiple alterations and resistance

The complex genetics of cancers has led researchers to explore combinations of targeted and other therapies to address multiple defects at the same time.

“Not surprisingly, the most common collision of multiple genetic alterations within the same tumor was in the commonly altered tumor suppressor genes: TP53, APC, and PTEN,” Dr. Flaherty said.

“An increasing body of evidence supports a role for loss-of-function alterations in these genes to confer resistance to many targeted therapies,” he added. “While we don’t have targeted therapies yet established to directly counter this form of therapeutic resistance, we hypothesize that various types of combination therapy may be able to indirectly undercut resistance and enhance the benefit of many targeted therapies.”

The NCI-MATCH researchers will continue to mine this large dataset to better understand the many small, genetically defined cancer subpopulations.

“We will continue to report the outcome of the individual treatment subprotocols, and combining this genetic analysis with those outcomes will likely inform the next clinical trials,” Dr. Flaherty said.
 

Actionable mutations make a difference

Precision oncology experts agree that NCI-MATCH results are impressive and add a fuller appreciation that actionable mutations make a clinical difference.

“This is a powerful, extremely well-designed study, a tour de force of collaborative science,” said Stephen Gruber, MD, PhD, director of the Center for Precision Medicine at City of Hope National Medical Center in Duarte, Calif.

“The future holds even more promise,” he added. “Our ability to interrogate the genomic landscape of cancer is improving rapidly. Tumor testing helps get the right drug to the right tumor faster than a guidelines-based approach from historical data of combination chemotherapy. This is a likely game changer for the way oncologists will practice in the future, especially as we learn more results of subset trials. The NCI-MATCH researchers have taken a laser-focused look at the current data, but we now know we can look far more comprehensively at genomic profiles of tumors.”

From the viewpoint of the practicing oncologist, co-occurring resistance mutations make a difference in defining what combinations are likely and, more importantly, less likely to be effective. “When we see two mutations and one is likely to confer resistance, we can make a choice to avoid a drug that is not likely to work,” Dr. Gruber said.

“The NCI-MATCH trial allows both approved and investigational agents, which expands the possibility of matching patients to newer agents. This is especially relevant if there are no FDA-approved drugs yet for some molecular aberrations,” said Lillian L. Siu, MD, a senior medical oncologist at the Princess Margaret Cancer Centre in Toronto. “This trial enables such evaluations under the auspice of a clinical trial to provide important knowledge.”

Both experts agree that in-depth biological interrogations of cancer will move the field of precision oncology forward. Dr. Gruber said that “studies have not yet fully addressed the power of germline genetic testing of DNA. Inherited susceptibility will drive therapeutic choices – for example, PARP inhibitors that access homologous recombination deficiency for breast, ovarian, and prostate cancer. We will learn more about treatment choices for those cancers.”

Dr. Siu added: “I truly believe that liquid biopsies [circulating tumor DNA] will help us perform target-drug matching in a less invasive way. We need to explore beyond the genome to look at the transcriptome, proteome, epigenome, and immunome, among others. It is likely that multiomic predictors are going to be able to identify more therapeutic options compared to single genomic predictors.”

Dr. Flaherty noted that all tumor samples from patients assigned to treatment are being subjected to whole-exome sequencing to further the discovery of the genetic features of responsive and nonresponsive tumors.

NCI-MATCH was funded by the National Cancer Institute. Dr. Flaherty disclosed relationships with Clovis Oncology, Loxo, X4 Pharma, and many other companies. His coauthors disclosed many conflicts as well. Dr. Gruber is cofounder of Brogent International. Dr. Siu disclosed relationships with Agios, Treadwell Therapeutics, Merck, Pfizer, and many other companies.

SOURCE: Flaherty KT et al. J Clin Oncol. 2020 Oct 13. doi: 10.1200/JCO.19.03010.

A national effort to perform genotype drug matching across cancer types shows the value of next-generation sequencing and provides a roadmap for future precision oncology trials, according to experts.

Massachusetts General Hospital

The effort is the National Cancer Institute Molecular Analysis for Therapy Choice (NCI-MATCH) trial. For this study, researchers performed next-generation sequencing on tumor biopsy specimens to identify therapeutically actionable molecular alterations in patients with “underexplored” cancer types.

The trial included 5,954 patients with cancers that had progressed on standard treatments or rare cancers for which there is no standard treatment. If actionable alterations were found in these patients, they could receive new drugs in development that showed promise in other clinical trials or drugs that were approved by the Food and Drug Administration to treat at least one cancer type.

Data newly reported in the Journal of Clinical Oncology showed that 37.6% of patients had alterations that could be matched to targeted drugs, and 17.8% of patients were assigned to targeted treatment. Multiple actionable tumor mutations were seen in 11.9% of specimens, and resistance-conferring mutations were seen in 71.3% of specimens.

“The bottom line from this report is that next-generation sequencing is an efficient way to identify both approved and promising investigational therapies. For this reason, it should be considered standard of care for patients with advanced cancers,” said study chair Keith T. Flaherty, MD, director of the Henri and Belinda Termeer Center for Targeted Therapy at Massachusetts General Hospital Cancer Center in Boston.

“This study sets the benchmark for the ‘actionability’ of next-generation sequencing,” Dr. Flaherty added. “We expect this number [of actionable alterations] will continue to rise steadily as further advances are made in the development of therapies that target some of the genetic alterations for which we could not offer treatment options in NCI-MATCH.”
 

Relapsed/refractory vs. primary tumors

The NCI-MATCH researchers focused on the most commonly found genetic alterations and performed biopsies at study entry to provide the most accurate picture of the genetic landscape of relapsed/refractory cancer patients. That makes this cohort distinct from The Cancer Genome Atlas (TCGA), a database of patients with mostly untreated primary tumors, and other published cohorts that include genetic analysis of primary tumors and biopsies from the time of initial metastatic recurrence.

The researchers compared the tumor gene makeup of NCI-MATCH and TCGA patients with seven cancer types – breast, bile duct, cervix, colorectal, lung, pancreas, and prostate.

ECOG-ACRIN Cancer Research Group

“Perhaps the biggest surprise was the relatively minimal change in the genetic alterations found in these relapsed/refractory patients, compared to primary tumors,” Dr. Flaherty said. “These findings suggest that it is very reasonable to perform next-generation sequencing at the time of initial metastatic cancer diagnosis and to rely on those findings for the purposes of considering FDA-approved therapies and clinical trial participation.”
 

Multiple alterations and resistance

The complex genetics of cancers has led researchers to explore combinations of targeted and other therapies to address multiple defects at the same time.

“Not surprisingly, the most common collision of multiple genetic alterations within the same tumor was in the commonly altered tumor suppressor genes: TP53, APC, and PTEN,” Dr. Flaherty said.

“An increasing body of evidence supports a role for loss-of-function alterations in these genes to confer resistance to many targeted therapies,” he added. “While we don’t have targeted therapies yet established to directly counter this form of therapeutic resistance, we hypothesize that various types of combination therapy may be able to indirectly undercut resistance and enhance the benefit of many targeted therapies.”

The NCI-MATCH researchers will continue to mine this large dataset to better understand the many small, genetically defined cancer subpopulations.

“We will continue to report the outcome of the individual treatment subprotocols, and combining this genetic analysis with those outcomes will likely inform the next clinical trials,” Dr. Flaherty said.
 

Actionable mutations make a difference

Precision oncology experts agree that NCI-MATCH results are impressive and add a fuller appreciation that actionable mutations make a clinical difference.

“This is a powerful, extremely well-designed study, a tour de force of collaborative science,” said Stephen Gruber, MD, PhD, director of the Center for Precision Medicine at City of Hope National Medical Center in Duarte, Calif.

“The future holds even more promise,” he added. “Our ability to interrogate the genomic landscape of cancer is improving rapidly. Tumor testing helps get the right drug to the right tumor faster than a guidelines-based approach from historical data of combination chemotherapy. This is a likely game changer for the way oncologists will practice in the future, especially as we learn more results of subset trials. The NCI-MATCH researchers have taken a laser-focused look at the current data, but we now know we can look far more comprehensively at genomic profiles of tumors.”

From the viewpoint of the practicing oncologist, co-occurring resistance mutations make a difference in defining what combinations are likely and, more importantly, less likely to be effective. “When we see two mutations and one is likely to confer resistance, we can make a choice to avoid a drug that is not likely to work,” Dr. Gruber said.

“The NCI-MATCH trial allows both approved and investigational agents, which expands the possibility of matching patients to newer agents. This is especially relevant if there are no FDA-approved drugs yet for some molecular aberrations,” said Lillian L. Siu, MD, a senior medical oncologist at the Princess Margaret Cancer Centre in Toronto. “This trial enables such evaluations under the auspice of a clinical trial to provide important knowledge.”

Both experts agree that in-depth biological interrogations of cancer will move the field of precision oncology forward. Dr. Gruber said that “studies have not yet fully addressed the power of germline genetic testing of DNA. Inherited susceptibility will drive therapeutic choices – for example, PARP inhibitors that access homologous recombination deficiency for breast, ovarian, and prostate cancer. We will learn more about treatment choices for those cancers.”

Dr. Siu added: “I truly believe that liquid biopsies [circulating tumor DNA] will help us perform target-drug matching in a less invasive way. We need to explore beyond the genome to look at the transcriptome, proteome, epigenome, and immunome, among others. It is likely that multiomic predictors are going to be able to identify more therapeutic options compared to single genomic predictors.”

Dr. Flaherty noted that all tumor samples from patients assigned to treatment are being subjected to whole-exome sequencing to further the discovery of the genetic features of responsive and nonresponsive tumors.

NCI-MATCH was funded by the National Cancer Institute. Dr. Flaherty disclosed relationships with Clovis Oncology, Loxo, X4 Pharma, and many other companies. His coauthors disclosed many conflicts as well. Dr. Gruber is cofounder of Brogent International. Dr. Siu disclosed relationships with Agios, Treadwell Therapeutics, Merck, Pfizer, and many other companies.

SOURCE: Flaherty KT et al. J Clin Oncol. 2020 Oct 13. doi: 10.1200/JCO.19.03010.

It’s not ready for the clinic, but new research suggests that angiotensin receptor II blockers (ARBs) widely used to treat hypertension may improve responses to cancer immunotherapy agents targeted against the programmed death-1/ligand-1 (PD-1/PD-L1) pathway.

That conclusion comes from an observational study of 597 patients with more than 3 dozen different cancer types treated in clinical trials at the US National Institutes of Health. Investigators found that both objective response rates and 3-year overall survival (OS) rates were significantly higher for patients treated with a PD-1/PD-L1 inhibitor who were on ARBs, compared with patients who weren’t taking the antihypertensive agents.

An association was also seen between higher ORR and OS rates for patients taking ACE inhibitors, but it was not statistically significant, reported Julius Strauss, MD, from the Center for Cancer Research at the National Cancer Institute in Bethesda, Md.

All study patients received PD-1/PD-L1 inhibitors, and the ORR for patients treated with ARBs was 33.8%, compared with 19.5% for those treated with ACE inhibitors, and 17% for those who took neither drug. The respective complete response (CR) rates were 11.3%, 3.7%, and 3.1%.

Strauss discussed the data during an online briefing prior to his presentation of the findings during the 32nd EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics, which is taking place virtually.

Several early studies have suggested that angiotensin II, in addition to its effect on blood pressure, can also affect cancer growth by leading to downstream production of two proteins: vascular endothelial growth factor (VEGF) and transforming growth factor–beta (TGF-beta), he explained.

“Both of these [proteins] have been linked to cancer growth and cancer resistance to immune system attack,” Strauss observed.

He also discussed the mechanics of possible effects. Angiotensin II increases VEGF and TGF-beta through binding to the AT1 receptor, but has the opposite effect when it binds to the AT2 receptor, resulting in a decrease in both of the growth factors, he added.

ACE inhibitors prevent the conversion of angiotensin I to angiotensin II, with the result being that the drugs indirectly block both the AT1 and AT2 receptors.

In contrast, ARBs block only the AT1 receptor and leave the AT2 counter-regulatory receptor alone, said Strauss.
 

More data, including on overall survival

Strauss and colleagues examined whether ACE inhibitors and/or ARBs could have an effect on the response to PD-1/PD-L1 immune checkpoint inhibitors delivered with or without other immunotherapies, such as anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) checkpoint inhibitors, or targeted agents such as tyrosine kinase inhibitors (TKIs).

They pooled data on 597 patients receiving PD-1/PD-L1 inhibitors in clinical trials for various cancers, including 71 receiving concomitant ARBs, 82 receiving an ACE inhibitor, and 444 who were not receiving either class of antihypertensives.

The above-mentioned improvement in ORR with ARBs compared with patients not receiving the drug was statistically significant (P = .001), as was the improvement in CR rates (P = .002). In contrast, neither ORR nor CR were significantly better with patients on ACE inhibitors compared with patients not taking these drugs.

In multiple regression analysis controlling for age, gender, body mass index (BMI), tumor type, and additional therapies given, the superior ORR and CR rates with ARBs remained (P = .039 and .002, respectively), while there continued to be no significant additional benefit with ACE inhibitors.

The median overall survival was 35.2 months for patients on ARBs, 26.2 months for those on ACE inhibitors, and 18.8 months for patients on neither drug. The respective 3-year OS rates were 48.1%, 37.2%, and 31.5%, with the difference between the ARB and no-drug groups being significant (P = .0078).

In regression analysis controlling for the factors mentioned before, the OS advantage with ARBs but not ACE inhibitors remained significant (P = .006 for ARBs, and .078 for ACE inhibitors).

Strauss emphasized that further study is needed to determine if AT1 blockade can improve outcomes when combined anti-PD-1/PD-L1-based therapy.

It might be reasonable for patients who are taking ACE inhibitors to control blood pressure and are also receiving immunotherapy with a PD-1/PD-L1 inhibitor to be switched to an ARB if it is deemed safe and if further research bears it out, said Strauss in response to a question from Medscape Medical News.
 

Hypothesis-generating study

Meeting cochair Emiliano Calvo, MD, PhD, from Hospital de Madrid Norte Sanchinarro in Madrid, who attended the media briefing but was not involved in the study, commented that hypothesis-generating research using drugs already on the market for other indications adds important value to cancer therapy.

James Gulley, MD, PhD, from the Center for Cancer Research at the NCI, also a meeting cochair, agreed with Calvo.

“Thinking about utilizing the data that already exists to really get hypothesis-generating questions, it also opens up the possibility for real-world data, real-world evidence from these big datasets from [electronic medical records] that we could really interrogate and understand what we might see and get these hypothesis-generating findings that we could then prospectively evaluate,” Gulley said.

The research was funded by the National Cancer Institute. Strauss and Gulley are National Cancer Institute employees. Calvo disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

It’s not ready for the clinic, but new research suggests that angiotensin receptor II blockers (ARBs) widely used to treat hypertension may improve responses to cancer immunotherapy agents targeted against the programmed death-1/ligand-1 (PD-1/PD-L1) pathway.

That conclusion comes from an observational study of 597 patients with more than 3 dozen different cancer types treated in clinical trials at the US National Institutes of Health. Investigators found that both objective response rates and 3-year overall survival (OS) rates were significantly higher for patients treated with a PD-1/PD-L1 inhibitor who were on ARBs, compared with patients who weren’t taking the antihypertensive agents.

An association was also seen between higher ORR and OS rates for patients taking ACE inhibitors, but it was not statistically significant, reported Julius Strauss, MD, from the Center for Cancer Research at the National Cancer Institute in Bethesda, Md.

All study patients received PD-1/PD-L1 inhibitors, and the ORR for patients treated with ARBs was 33.8%, compared with 19.5% for those treated with ACE inhibitors, and 17% for those who took neither drug. The respective complete response (CR) rates were 11.3%, 3.7%, and 3.1%.

Strauss discussed the data during an online briefing prior to his presentation of the findings during the 32nd EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics, which is taking place virtually.

Several early studies have suggested that angiotensin II, in addition to its effect on blood pressure, can also affect cancer growth by leading to downstream production of two proteins: vascular endothelial growth factor (VEGF) and transforming growth factor–beta (TGF-beta), he explained.

“Both of these [proteins] have been linked to cancer growth and cancer resistance to immune system attack,” Strauss observed.

He also discussed the mechanics of possible effects. Angiotensin II increases VEGF and TGF-beta through binding to the AT1 receptor, but has the opposite effect when it binds to the AT2 receptor, resulting in a decrease in both of the growth factors, he added.

ACE inhibitors prevent the conversion of angiotensin I to angiotensin II, with the result being that the drugs indirectly block both the AT1 and AT2 receptors.

In contrast, ARBs block only the AT1 receptor and leave the AT2 counter-regulatory receptor alone, said Strauss.
 

More data, including on overall survival

Strauss and colleagues examined whether ACE inhibitors and/or ARBs could have an effect on the response to PD-1/PD-L1 immune checkpoint inhibitors delivered with or without other immunotherapies, such as anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) checkpoint inhibitors, or targeted agents such as tyrosine kinase inhibitors (TKIs).

They pooled data on 597 patients receiving PD-1/PD-L1 inhibitors in clinical trials for various cancers, including 71 receiving concomitant ARBs, 82 receiving an ACE inhibitor, and 444 who were not receiving either class of antihypertensives.

The above-mentioned improvement in ORR with ARBs compared with patients not receiving the drug was statistically significant (P = .001), as was the improvement in CR rates (P = .002). In contrast, neither ORR nor CR were significantly better with patients on ACE inhibitors compared with patients not taking these drugs.

In multiple regression analysis controlling for age, gender, body mass index (BMI), tumor type, and additional therapies given, the superior ORR and CR rates with ARBs remained (P = .039 and .002, respectively), while there continued to be no significant additional benefit with ACE inhibitors.

The median overall survival was 35.2 months for patients on ARBs, 26.2 months for those on ACE inhibitors, and 18.8 months for patients on neither drug. The respective 3-year OS rates were 48.1%, 37.2%, and 31.5%, with the difference between the ARB and no-drug groups being significant (P = .0078).

In regression analysis controlling for the factors mentioned before, the OS advantage with ARBs but not ACE inhibitors remained significant (P = .006 for ARBs, and .078 for ACE inhibitors).

Strauss emphasized that further study is needed to determine if AT1 blockade can improve outcomes when combined anti-PD-1/PD-L1-based therapy.

It might be reasonable for patients who are taking ACE inhibitors to control blood pressure and are also receiving immunotherapy with a PD-1/PD-L1 inhibitor to be switched to an ARB if it is deemed safe and if further research bears it out, said Strauss in response to a question from Medscape Medical News.
 

Hypothesis-generating study

Meeting cochair Emiliano Calvo, MD, PhD, from Hospital de Madrid Norte Sanchinarro in Madrid, who attended the media briefing but was not involved in the study, commented that hypothesis-generating research using drugs already on the market for other indications adds important value to cancer therapy.

James Gulley, MD, PhD, from the Center for Cancer Research at the NCI, also a meeting cochair, agreed with Calvo.

“Thinking about utilizing the data that already exists to really get hypothesis-generating questions, it also opens up the possibility for real-world data, real-world evidence from these big datasets from [electronic medical records] that we could really interrogate and understand what we might see and get these hypothesis-generating findings that we could then prospectively evaluate,” Gulley said.

The research was funded by the National Cancer Institute. Strauss and Gulley are National Cancer Institute employees. Calvo disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

It’s not ready for the clinic, but new research suggests that angiotensin receptor II blockers (ARBs) widely used to treat hypertension may improve responses to cancer immunotherapy agents targeted against the programmed death-1/ligand-1 (PD-1/PD-L1) pathway.

That conclusion comes from an observational study of 597 patients with more than 3 dozen different cancer types treated in clinical trials at the US National Institutes of Health. Investigators found that both objective response rates and 3-year overall survival (OS) rates were significantly higher for patients treated with a PD-1/PD-L1 inhibitor who were on ARBs, compared with patients who weren’t taking the antihypertensive agents.

An association was also seen between higher ORR and OS rates for patients taking ACE inhibitors, but it was not statistically significant, reported Julius Strauss, MD, from the Center for Cancer Research at the National Cancer Institute in Bethesda, Md.

All study patients received PD-1/PD-L1 inhibitors, and the ORR for patients treated with ARBs was 33.8%, compared with 19.5% for those treated with ACE inhibitors, and 17% for those who took neither drug. The respective complete response (CR) rates were 11.3%, 3.7%, and 3.1%.

Strauss discussed the data during an online briefing prior to his presentation of the findings during the 32nd EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics, which is taking place virtually.

Several early studies have suggested that angiotensin II, in addition to its effect on blood pressure, can also affect cancer growth by leading to downstream production of two proteins: vascular endothelial growth factor (VEGF) and transforming growth factor–beta (TGF-beta), he explained.

“Both of these [proteins] have been linked to cancer growth and cancer resistance to immune system attack,” Strauss observed.

He also discussed the mechanics of possible effects. Angiotensin II increases VEGF and TGF-beta through binding to the AT1 receptor, but has the opposite effect when it binds to the AT2 receptor, resulting in a decrease in both of the growth factors, he added.

ACE inhibitors prevent the conversion of angiotensin I to angiotensin II, with the result being that the drugs indirectly block both the AT1 and AT2 receptors.

In contrast, ARBs block only the AT1 receptor and leave the AT2 counter-regulatory receptor alone, said Strauss.
 

More data, including on overall survival

Strauss and colleagues examined whether ACE inhibitors and/or ARBs could have an effect on the response to PD-1/PD-L1 immune checkpoint inhibitors delivered with or without other immunotherapies, such as anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) checkpoint inhibitors, or targeted agents such as tyrosine kinase inhibitors (TKIs).

They pooled data on 597 patients receiving PD-1/PD-L1 inhibitors in clinical trials for various cancers, including 71 receiving concomitant ARBs, 82 receiving an ACE inhibitor, and 444 who were not receiving either class of antihypertensives.

The above-mentioned improvement in ORR with ARBs compared with patients not receiving the drug was statistically significant (P = .001), as was the improvement in CR rates (P = .002). In contrast, neither ORR nor CR were significantly better with patients on ACE inhibitors compared with patients not taking these drugs.

In multiple regression analysis controlling for age, gender, body mass index (BMI), tumor type, and additional therapies given, the superior ORR and CR rates with ARBs remained (P = .039 and .002, respectively), while there continued to be no significant additional benefit with ACE inhibitors.

The median overall survival was 35.2 months for patients on ARBs, 26.2 months for those on ACE inhibitors, and 18.8 months for patients on neither drug. The respective 3-year OS rates were 48.1%, 37.2%, and 31.5%, with the difference between the ARB and no-drug groups being significant (P = .0078).

In regression analysis controlling for the factors mentioned before, the OS advantage with ARBs but not ACE inhibitors remained significant (P = .006 for ARBs, and .078 for ACE inhibitors).

Strauss emphasized that further study is needed to determine if AT1 blockade can improve outcomes when combined anti-PD-1/PD-L1-based therapy.

It might be reasonable for patients who are taking ACE inhibitors to control blood pressure and are also receiving immunotherapy with a PD-1/PD-L1 inhibitor to be switched to an ARB if it is deemed safe and if further research bears it out, said Strauss in response to a question from Medscape Medical News.
 

Hypothesis-generating study

Meeting cochair Emiliano Calvo, MD, PhD, from Hospital de Madrid Norte Sanchinarro in Madrid, who attended the media briefing but was not involved in the study, commented that hypothesis-generating research using drugs already on the market for other indications adds important value to cancer therapy.

James Gulley, MD, PhD, from the Center for Cancer Research at the NCI, also a meeting cochair, agreed with Calvo.

“Thinking about utilizing the data that already exists to really get hypothesis-generating questions, it also opens up the possibility for real-world data, real-world evidence from these big datasets from [electronic medical records] that we could really interrogate and understand what we might see and get these hypothesis-generating findings that we could then prospectively evaluate,” Gulley said.

The research was funded by the National Cancer Institute. Strauss and Gulley are National Cancer Institute employees. Calvo disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Sensitivity and area under the curve (AUC) analyses of thermography that is combined with diagnostic software demonstrate “the efficacy of the tool for breast cancer screening,” concludes an observational, comparative study from India published online Oct. 1 in JCO Global Oncology, a publication of the American Society of Clinical Oncology.

Siva Teja Kakileti of Niramai Health Analytix, Koramangala, Bangalore, India, and colleagues said that the product, Thermalytix, is potentially a good fit for low- and middle-income countries because it is portable and provides automated quantitative analysis of thermal images – and thus can be conducted by technicians with “minimal training.”

Conventional thermography involves manual interpretation of complex thermal images, which “often results in erroneous results owing to subjectivity,” said the study authors.

That manual interpretation of thermal images might involve looking at 200 color shades, which is “high cognitive overload for the thermographer,” explained Mr. Kakileti in an interview.

However, an American mammography expert who was approached for comment dismissed thermography – even with the new twist of software-aided diagnostic scoring by Thermalytix – as wholly inappropriate for the detection of early breast cancer, owing to inherent limitations.

“Thermal imaging of any type has no value in finding early breast cancer,” Daniel Kopans, MD, of Harvard University and Massachusetts General Hospital, both in Boston, said in an interview. He said that thermal imaging only detects heat on the skin and perhaps a few millimeters beneath the skin and thus misses deeper cancers, the heat from which is carried away by the vascular system.

The new study included 470 women who presented for breast screening at two centers in Bangalore, India. A total of 238 women had symptoms such as breast lump, nipple discharge, skin changes, or breast pain; the remaining 232 women were asymptomatic.

All participants underwent a Thermalytix test and one or more standard-of-care tests for breast cancer screening (such as mammography, ultrasonography, biopsy, fine-needle aspiration, or elastography). A total of 78 women, or 16.6% of the group overall, were diagnosed with a malignancy. For the overall group of 470 women, Thermalytix had a sensitivity of 91.02% (symptomatic, 89.85%; asymptomatic,100%) and a specificity of 82.39% (symptomatic, 69.04%; asymptomatic, 92.41%) in detection of breast malignancy. Thermalytix showed an overall AUC of 0.90, with an AUC of 0.82 for symptomatic and 0.98 for asymptomatic women.

The study authors characterized both the sensitivity and AUC as “high.”

The results from the study, which the authors characterized as preliminary, encouraged the study sponsor, Niramai, to start planning a large-scale, multicountry trial.

But Dr. Kopans, who serves as a consultant to DART, which produces digital breast tomosynthesis units in China, suggested that this research will be fruitless. “Thermal imaging seems to raise its head every few years since it is passive, but it does not work and is a waste of money,” Dr. Kopans reiterated.

“Its use can be dangerous by dissuading women from being screened with mammography, which has been proven to save lives,” he stressed.
 

Thermalytix compared with mammography

Investigators also compared screening results in the subset of 242 women who underwent both Thermalytix and mammography. Results showed that Thermalytix had a higher sensitivity than did mammography (91.23% vs. 85.96%), but mammography had a higher specificity than Thermalytix did (94.05% vs. 68.65%).

In the asymptomatic group who underwent both tests (n = 95), four cancers were detected, and Thermalytix demonstrated superior sensitivity than mammography (100% vs. 50%), Mr. Kakileti and colleagues state.
 

Thermalytix evaluates vascularity variations too

In the subset of 228 women who did not undergo mammography (owing to dense breasts, younger age, or other reasons), Thermalytix detected tumors in all but 3 of 21 patients who went on to be diagnosed with breast cancer. The authors state that, because their artificial intelligence–based analysis uses vascularity, as well as temperature variations on the skin, to complement hot-spot detection, it is able to detect small lesions.

In the current study, 24 malignant tumors were less than 2 cm in diameter, and Thermalytix was able to identify 17 of the tumors as positive, for a 71% sensitivity rate for T1 tumors. This compared with a 68% sensitivity rate for mammography for detecting the same T1 tumors. Thermalytix also showed promising results in women younger than 40 years, for whom screening mammography is not usually recommended. The automated test picked up all 11 tumors eventually diagnosed in this younger cohort.

“Thermalytix is a portable, noninvasive, radiation-free test that has shown promising results in this preliminary study,” the investigators wrote, “[and] it can be an affordable and scalable method of screening in remote areas,” they added.

“We believe that Thermalytix ... is poised to be a promising modality for breast cancer screening,” Mr. Kakileti and colleagues summarized.
 

The FDA warns about thermography in place of mammography

The US Food and Drug Administration fairly recently warned against the use of thermography as an alternative to mammography for breast cancer screening or diagnosis, noting that it has received reports that facilities where thermography is offered often provide false information about the technology that can mislead patients into believing that it is either an alternative to or a better option than mammography.

Dr. Kopans says that other groups have invested in thermography research. “The Israelis spent millions working on a similar approach that didn’t work,” he commented.

The new software from Thermalytix, which is derived from artificial intelligence, is a “gimmick,” says the Boston radiologist. “If the basic information is not there, a computer cannot find it,” he stated, referring to what he believes are deeper-tissue tumors that are inaccessible to heat-detecting technology.

Mr. Kakileti is an employee of Nirami Health Analytix and owns stock and has filed patents with the company. Other investigators are also employed by the same company or receive research and other funding or have patents filed by the company as well. Dr. Kopans serves as a consultant to DART, which produces digital breast tomosynthesis units in China.
 

A version of this article originally appeared on Medscape.com.

Sensitivity and area under the curve (AUC) analyses of thermography that is combined with diagnostic software demonstrate “the efficacy of the tool for breast cancer screening,” concludes an observational, comparative study from India published online Oct. 1 in JCO Global Oncology, a publication of the American Society of Clinical Oncology.

Siva Teja Kakileti of Niramai Health Analytix, Koramangala, Bangalore, India, and colleagues said that the product, Thermalytix, is potentially a good fit for low- and middle-income countries because it is portable and provides automated quantitative analysis of thermal images – and thus can be conducted by technicians with “minimal training.”

Conventional thermography involves manual interpretation of complex thermal images, which “often results in erroneous results owing to subjectivity,” said the study authors.

That manual interpretation of thermal images might involve looking at 200 color shades, which is “high cognitive overload for the thermographer,” explained Mr. Kakileti in an interview.

However, an American mammography expert who was approached for comment dismissed thermography – even with the new twist of software-aided diagnostic scoring by Thermalytix – as wholly inappropriate for the detection of early breast cancer, owing to inherent limitations.

“Thermal imaging of any type has no value in finding early breast cancer,” Daniel Kopans, MD, of Harvard University and Massachusetts General Hospital, both in Boston, said in an interview. He said that thermal imaging only detects heat on the skin and perhaps a few millimeters beneath the skin and thus misses deeper cancers, the heat from which is carried away by the vascular system.

The new study included 470 women who presented for breast screening at two centers in Bangalore, India. A total of 238 women had symptoms such as breast lump, nipple discharge, skin changes, or breast pain; the remaining 232 women were asymptomatic.

All participants underwent a Thermalytix test and one or more standard-of-care tests for breast cancer screening (such as mammography, ultrasonography, biopsy, fine-needle aspiration, or elastography). A total of 78 women, or 16.6% of the group overall, were diagnosed with a malignancy. For the overall group of 470 women, Thermalytix had a sensitivity of 91.02% (symptomatic, 89.85%; asymptomatic,100%) and a specificity of 82.39% (symptomatic, 69.04%; asymptomatic, 92.41%) in detection of breast malignancy. Thermalytix showed an overall AUC of 0.90, with an AUC of 0.82 for symptomatic and 0.98 for asymptomatic women.

The study authors characterized both the sensitivity and AUC as “high.”

The results from the study, which the authors characterized as preliminary, encouraged the study sponsor, Niramai, to start planning a large-scale, multicountry trial.

But Dr. Kopans, who serves as a consultant to DART, which produces digital breast tomosynthesis units in China, suggested that this research will be fruitless. “Thermal imaging seems to raise its head every few years since it is passive, but it does not work and is a waste of money,” Dr. Kopans reiterated.

“Its use can be dangerous by dissuading women from being screened with mammography, which has been proven to save lives,” he stressed.
 

Thermalytix compared with mammography

Investigators also compared screening results in the subset of 242 women who underwent both Thermalytix and mammography. Results showed that Thermalytix had a higher sensitivity than did mammography (91.23% vs. 85.96%), but mammography had a higher specificity than Thermalytix did (94.05% vs. 68.65%).

In the asymptomatic group who underwent both tests (n = 95), four cancers were detected, and Thermalytix demonstrated superior sensitivity than mammography (100% vs. 50%), Mr. Kakileti and colleagues state.
 

Thermalytix evaluates vascularity variations too

In the subset of 228 women who did not undergo mammography (owing to dense breasts, younger age, or other reasons), Thermalytix detected tumors in all but 3 of 21 patients who went on to be diagnosed with breast cancer. The authors state that, because their artificial intelligence–based analysis uses vascularity, as well as temperature variations on the skin, to complement hot-spot detection, it is able to detect small lesions.

In the current study, 24 malignant tumors were less than 2 cm in diameter, and Thermalytix was able to identify 17 of the tumors as positive, for a 71% sensitivity rate for T1 tumors. This compared with a 68% sensitivity rate for mammography for detecting the same T1 tumors. Thermalytix also showed promising results in women younger than 40 years, for whom screening mammography is not usually recommended. The automated test picked up all 11 tumors eventually diagnosed in this younger cohort.

“Thermalytix is a portable, noninvasive, radiation-free test that has shown promising results in this preliminary study,” the investigators wrote, “[and] it can be an affordable and scalable method of screening in remote areas,” they added.

“We believe that Thermalytix ... is poised to be a promising modality for breast cancer screening,” Mr. Kakileti and colleagues summarized.
 

The FDA warns about thermography in place of mammography

The US Food and Drug Administration fairly recently warned against the use of thermography as an alternative to mammography for breast cancer screening or diagnosis, noting that it has received reports that facilities where thermography is offered often provide false information about the technology that can mislead patients into believing that it is either an alternative to or a better option than mammography.

Dr. Kopans says that other groups have invested in thermography research. “The Israelis spent millions working on a similar approach that didn’t work,” he commented.

The new software from Thermalytix, which is derived from artificial intelligence, is a “gimmick,” says the Boston radiologist. “If the basic information is not there, a computer cannot find it,” he stated, referring to what he believes are deeper-tissue tumors that are inaccessible to heat-detecting technology.

Mr. Kakileti is an employee of Nirami Health Analytix and owns stock and has filed patents with the company. Other investigators are also employed by the same company or receive research and other funding or have patents filed by the company as well. Dr. Kopans serves as a consultant to DART, which produces digital breast tomosynthesis units in China.
 

A version of this article originally appeared on Medscape.com.

Sensitivity and area under the curve (AUC) analyses of thermography that is combined with diagnostic software demonstrate “the efficacy of the tool for breast cancer screening,” concludes an observational, comparative study from India published online Oct. 1 in JCO Global Oncology, a publication of the American Society of Clinical Oncology.

Siva Teja Kakileti of Niramai Health Analytix, Koramangala, Bangalore, India, and colleagues said that the product, Thermalytix, is potentially a good fit for low- and middle-income countries because it is portable and provides automated quantitative analysis of thermal images – and thus can be conducted by technicians with “minimal training.”

Conventional thermography involves manual interpretation of complex thermal images, which “often results in erroneous results owing to subjectivity,” said the study authors.

That manual interpretation of thermal images might involve looking at 200 color shades, which is “high cognitive overload for the thermographer,” explained Mr. Kakileti in an interview.

However, an American mammography expert who was approached for comment dismissed thermography – even with the new twist of software-aided diagnostic scoring by Thermalytix – as wholly inappropriate for the detection of early breast cancer, owing to inherent limitations.

“Thermal imaging of any type has no value in finding early breast cancer,” Daniel Kopans, MD, of Harvard University and Massachusetts General Hospital, both in Boston, said in an interview. He said that thermal imaging only detects heat on the skin and perhaps a few millimeters beneath the skin and thus misses deeper cancers, the heat from which is carried away by the vascular system.

The new study included 470 women who presented for breast screening at two centers in Bangalore, India. A total of 238 women had symptoms such as breast lump, nipple discharge, skin changes, or breast pain; the remaining 232 women were asymptomatic.

All participants underwent a Thermalytix test and one or more standard-of-care tests for breast cancer screening (such as mammography, ultrasonography, biopsy, fine-needle aspiration, or elastography). A total of 78 women, or 16.6% of the group overall, were diagnosed with a malignancy. For the overall group of 470 women, Thermalytix had a sensitivity of 91.02% (symptomatic, 89.85%; asymptomatic,100%) and a specificity of 82.39% (symptomatic, 69.04%; asymptomatic, 92.41%) in detection of breast malignancy. Thermalytix showed an overall AUC of 0.90, with an AUC of 0.82 for symptomatic and 0.98 for asymptomatic women.

The study authors characterized both the sensitivity and AUC as “high.”

The results from the study, which the authors characterized as preliminary, encouraged the study sponsor, Niramai, to start planning a large-scale, multicountry trial.

But Dr. Kopans, who serves as a consultant to DART, which produces digital breast tomosynthesis units in China, suggested that this research will be fruitless. “Thermal imaging seems to raise its head every few years since it is passive, but it does not work and is a waste of money,” Dr. Kopans reiterated.

“Its use can be dangerous by dissuading women from being screened with mammography, which has been proven to save lives,” he stressed.
 

Thermalytix compared with mammography

Investigators also compared screening results in the subset of 242 women who underwent both Thermalytix and mammography. Results showed that Thermalytix had a higher sensitivity than did mammography (91.23% vs. 85.96%), but mammography had a higher specificity than Thermalytix did (94.05% vs. 68.65%).

In the asymptomatic group who underwent both tests (n = 95), four cancers were detected, and Thermalytix demonstrated superior sensitivity than mammography (100% vs. 50%), Mr. Kakileti and colleagues state.
 

Thermalytix evaluates vascularity variations too

In the subset of 228 women who did not undergo mammography (owing to dense breasts, younger age, or other reasons), Thermalytix detected tumors in all but 3 of 21 patients who went on to be diagnosed with breast cancer. The authors state that, because their artificial intelligence–based analysis uses vascularity, as well as temperature variations on the skin, to complement hot-spot detection, it is able to detect small lesions.

In the current study, 24 malignant tumors were less than 2 cm in diameter, and Thermalytix was able to identify 17 of the tumors as positive, for a 71% sensitivity rate for T1 tumors. This compared with a 68% sensitivity rate for mammography for detecting the same T1 tumors. Thermalytix also showed promising results in women younger than 40 years, for whom screening mammography is not usually recommended. The automated test picked up all 11 tumors eventually diagnosed in this younger cohort.

“Thermalytix is a portable, noninvasive, radiation-free test that has shown promising results in this preliminary study,” the investigators wrote, “[and] it can be an affordable and scalable method of screening in remote areas,” they added.

“We believe that Thermalytix ... is poised to be a promising modality for breast cancer screening,” Mr. Kakileti and colleagues summarized.
 

The FDA warns about thermography in place of mammography

The US Food and Drug Administration fairly recently warned against the use of thermography as an alternative to mammography for breast cancer screening or diagnosis, noting that it has received reports that facilities where thermography is offered often provide false information about the technology that can mislead patients into believing that it is either an alternative to or a better option than mammography.

Dr. Kopans says that other groups have invested in thermography research. “The Israelis spent millions working on a similar approach that didn’t work,” he commented.

The new software from Thermalytix, which is derived from artificial intelligence, is a “gimmick,” says the Boston radiologist. “If the basic information is not there, a computer cannot find it,” he stated, referring to what he believes are deeper-tissue tumors that are inaccessible to heat-detecting technology.

Mr. Kakileti is an employee of Nirami Health Analytix and owns stock and has filed patents with the company. Other investigators are also employed by the same company or receive research and other funding or have patents filed by the company as well. Dr. Kopans serves as a consultant to DART, which produces digital breast tomosynthesis units in China.
 

A version of this article originally appeared on Medscape.com.

Canceled appointments, postponed surgeries, and delayed cancer diagnoses – all are a recipe for exhaustion for oncologists around the world, struggling to reach and treat their patients during the pandemic. Physicians and their teams felt the pain as COVID-19 took its initial march around the globe.

“We saw the distress of people with cancer who could no longer get to anyone on the phone. Their medical visit was usually canceled. Their radiotherapy session was postponed or modified, and chemotherapy postponed,” says Axel Kahn, MD, chairman of the board of directors of La Ligue Nationale Contre le Cancer (National League Against Cancer). “In the vast majority of cases, cancer treatment can be postponed or readjusted, without affecting the patient’s chances of survival, but there has been a lot of anxiety because the patients do not know that.”

The stay-at-home factor was one that played out across many months during the first wave.

“I believe that the ‘stay-home’ message that we transmitted was rigorously followed by patients who should have come to the emergency room much earlier and who, therefore, were admitted with a much more deteriorated general condition than in non-COVID-19 times,” says Benjamín Domingo Arrué, MD, from the department of medical oncology at Hospital Universitari i Politècnic La Fe in Valencia, Spain.

And in Brazil, some of the impact from the initial hit of COVID-19 on oncology is only now being felt, according to Laura Testa, MD, head of breast medical oncology, Instituto do Câncer do Estado de São Paulo.

“We are starting to see a lot of cancer cases that didn’t show up at the beginning of the pandemic, but now they are arriving to us already in advanced stages,” she said. “These patients need hospital care. If the situation worsens and goes back to what we saw at the peak of the curve, I fear the public system won’t be able to treat properly the oncology patients that need hospital care and the patients with cancer who also have COVID-19.”

But even as health care worker fatigue and concerns linger, oncologists say that what they have learned in the last 6 months has helped them prepare as COVID-19 cases increase and a second global wave kicks up.
 

Lessons from the first wave

In the United States, COVID-19 hit different regions at different times and to different degrees. One of the areas hit first was Seattle.

“We jumped on top of this, we were evidence based, we put things in place very, very quickly,” said Julie Gralow, MD, professor at the University of Washington and the Fred Hutchinson Cancer Research Center, both in Seattle.

“We did a really good job keeping COVID out of our cancer centers,” Dr. Gralow said. “We learned how to be super safe, and to keep symptomatic people out of the building, and to limit the extra people they could bring with them. It’s all about the number of contacts you have.”

The story was different, though, for oncologists in several other countries, and sometimes it varied immensely within each nation.

“We treated fewer patients with cancer during the first wave,” says Dirk Arnold, MD, medical director of the Asklepios Tumor Center Hamburg (Germany), in an interview. “In part, this was because staff were quarantined and because we had a completely different infrastructure in all of the hospitals. But also fewer patients with cancer came to the clinic at all. A lot of resources were directed toward COVID-19.” 

In Spain, telemedicine helped keep up with visits, but other areas felt the effect of COVID-19 patient loads.

“At least in the oncology department of our center, we have practically maintained 100% of visits, mostly by telephone,” says Dr. Arrué, “but the reality is that our country has not yet been prepared for telemedicine.”

Laura Mezquita, MD, of the department of medical oncology at Hospital Clinic de Barcelona, describes a more dramatic situation: “We have seen how some of our patients, especially with metastatic disease, have been dismissed for intensive care and life-support treatments, as well as specific treatments against COVID-19 (tocilizumab, remdesivir, etc.) due to the general health collapse of the former wave,” she said. She adds that specific oncologic populations, such as those with thoracic tumors, have been more affected.
 

Distress among oncologists 

Many oncologists are still feeling stressed and fatigued after the first wave, just as a second string of outbreaks is on its way. 

A survey presented at last month’s ESMO 2020 Congress found that, in July-August, moral distress was reported by one-third of the oncologists who responded, and more than half reported a feeling of exhaustion. 

“The tiredness and team exhaustion is noticeable,” said Dr. Arnold. “We recently had a task force discussion about what will happen when we have a second wave and how the department and our services will adapt. It was clear that those who were at the very front in the first wave had only a limited desire to do that again in the second wave.”

Another concern: COVID-19’s effect on staffing levels. 

“We have a population of young caregivers who are affected by the COVID-19 disease with an absenteeism rate that is quite unprecedented,” said Sophie Beaupère, general delegate of Unicancer since January.

She said that, in general, the absenteeism rate in the cancer centers averages 5%-6%, depending on the year. But that rate is now skyrocketing.
 

Stop-start cycle for surgery

As caregivers quarantined around the world, more than 10% of patients with cancer had treatment canceled or delayed during the first wave of the pandemic, according to another survey from ESMO, involving 109 oncologists from 18 countries.

Difficulties were reported for surgeries by 34% of the centers, but also difficulties with delivering chemotherapy (22% of centers), radiotherapy (13.7%), and therapy with checkpoint inhibitors (9.1%), monoclonal antibodies (9%), and oral targeted therapy (3.7%).

Stopping surgery is a real concern in France, noted Dr. Kahn, the National League Against Cancer chair. He says that in regions that were badly hit by COVID-19, “it was not possible to have access to the operating room for people who absolutely needed surgery; for example, patients with lung cancer that was still operable. Most of the recovery rooms were mobilized for resuscitation.”

There may be some solutions, suggested Thierry Breton, director general of the National Institute of Cancer in France. “We are getting prepared, with the health ministry, for a possible increase in hospital tension, which would lead to a situation where we would have to reschedule operations. Nationally, regionally, and locally, we are seeing how we can resume and prioritize surgeries that have not been done.”
 

Delays in cancer diagnosis

While COVID-19 affected treatment, many oncologists say the major impact of the first wave was a delay in diagnosing cancer. Some of this was a result of the suspension of cancer screening programs, but there was also fear among the general public about visiting clinics and hospitals during a pandemic.

“We didn’t do so well with cancer during the first wave here in the U.K.,” said Karol Sikora, PhD, MBBChir, professor of cancer medicine and founding dean at the University of Buckingham Medical School, London. “Cancer diagnostic pathways virtually stalled partly because patients didn’t seek help, but getting scans and biopsies was also very difficult. Even patients referred urgently under the ‘2-weeks-wait’ rule were turned down.” 

In France, “the delay in diagnosis is indisputable,” said Dr. Kahn. “About 50% of the cancer diagnoses one would expect during this period were missed.” 

“I am worried that there remains a major traffic jam that has not been caught up with, and, in the meantime, the health crisis is worsening,” he added.  

In Seattle, Dr. Gralow said the first COVID-19 wave had little impact on treatment for breast cancer, but it was in screening for breast cancer “where things really got messed up.”

“Even though we’ve been fully ramped up again,” she said, concerns remain. To ensure that screening mammography is maintained, “we have spaced out the visits to keep our waiting rooms less populated, with a longer time between using the machine so we can clean it. To do this, we have extended operating hours and are now opening on Saturday.

“So we’re actually at 100% of our capacity, but I’m really nervous, though, that a lot of people put off their screening mammogram and aren’t going to come in and get it.

“Not only did people get the message to stay home and not do nonessential things, but I think a lot of people lost their health insurance when they lost their jobs,” she said, and without health insurance, they are not covered for cancer screening.
 

Looking ahead, with a plan

Many oncologists agree that access to care can and must be improved – and there were some positive moves.

“Some regimens changed during the first months of the pandemic, and I don’t see them going back to the way they were anytime soon,” said Dr. Testa. “The changes/adaptations that were made to minimize the chance of SARS-CoV-2 infection are still in place and will go on for a while. In this context, telemedicine helped a lot. The pandemic forced the stakeholders to step up and put it in place in March. And now it’s here to stay.”

The experience gained in the last several months has driven preparation for the next wave.

“We are not going to see the disorganization that we saw during the first wave,” said Florence Joly, MD, PhD, head of medical oncology at the Centre François Baclesse in Caen, France. “The difference between now and earlier this year is that COVID diagnostic tests are available. That was one of the problems in the first wave. We had no way to diagnose.”

On the East Coast of the United States, medical oncologist Charu Aggarwal, MD, MPH, is also optimistic: “I think we’re at a place where we can manage.”

“I believe if there was going to be a new wave of COVID-19 cases we would be: better psychologically prepared and better organized,” said Dr. Aggarwal, assistant professor of medicine in the hematology-oncology division at the University of Pennsylvania, Philadelphia. “We already have experience with all of the tools, we have telemedicine available, we have screening protocols available, we have testing, we are already universally masking, everyone’s hand-washing, so I do think that means we would be okay.” 

Dr. Arnold agreed that “we are much better prepared than for the first wave, but … we have immense tasks in the area of patient management, the digitization of patient care, the clear allocation of resources when there is a second or third wave. In many areas of preparation, I believe, unfortunately, we are not as well positioned as we had actually hoped.” 

The first wave of COVID hit cancer services in the United Kingdom particularly hard: One modeling study suggested that delays in cancer referrals will lead to thousands of additional deaths and tens of thousands of life-years lost.

“Cancer services are working at near normal levels now, but they are still fragile and could be severely compromised again if the NHS [National Health Service] gets flooded by COVID patients,” said Dr. Sikora.

The second wave may be different. “Although the number of infections has increased, the hospitalizations have only risen a little. Let’s see what happens,” he said in an interview. Since then, however, infections have continued to rise, and there has been an increase in hospitalizations. New social distancing measures in the United Kingdom were put into place on Oct. 12, with the aim of protecting the NHS from overload.

Dr. Arrué describes it this way: “The reality is that the ‘second wave’ has left behind the initial grief and shock that both patients and health professionals experienced when faced with something that, until now, we had only seen in the movies.” The second wave has led to new restrictions – including a partial lockdown since the beginning of October.

Dr. Aggarwal says her department recently had a conference with Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, about the impact of COVID-19 on oncology.

“I asked him what advice he’d give oncologists, and he said to go back to as much screening as you were doing previously as quickly as possible. That’s what must be relayed to our oncologists in the community – and also to primary care physicians – because they are often the ones who are ordering and championing the screening efforts.”

This article was originated by Aude Lecrubier, Medscape French edition, and developed by Zosia Chustecka, Medscape Oncology. With additional reporting by Kate Johnson, freelance medical journalist, Claudia Gottschling for Medscape Germany, Leoleli Schwartz for Medscape em português, Tim Locke for Medscape United Kingdom, and Carla Nieto Martínez, freelance medical journalist for Medscape Spanish edition. 

This article first appeared on Medscape.com.

Canceled appointments, postponed surgeries, and delayed cancer diagnoses – all are a recipe for exhaustion for oncologists around the world, struggling to reach and treat their patients during the pandemic. Physicians and their teams felt the pain as COVID-19 took its initial march around the globe.

“We saw the distress of people with cancer who could no longer get to anyone on the phone. Their medical visit was usually canceled. Their radiotherapy session was postponed or modified, and chemotherapy postponed,” says Axel Kahn, MD, chairman of the board of directors of La Ligue Nationale Contre le Cancer (National League Against Cancer). “In the vast majority of cases, cancer treatment can be postponed or readjusted, without affecting the patient’s chances of survival, but there has been a lot of anxiety because the patients do not know that.”

The stay-at-home factor was one that played out across many months during the first wave.

“I believe that the ‘stay-home’ message that we transmitted was rigorously followed by patients who should have come to the emergency room much earlier and who, therefore, were admitted with a much more deteriorated general condition than in non-COVID-19 times,” says Benjamín Domingo Arrué, MD, from the department of medical oncology at Hospital Universitari i Politècnic La Fe in Valencia, Spain.

And in Brazil, some of the impact from the initial hit of COVID-19 on oncology is only now being felt, according to Laura Testa, MD, head of breast medical oncology, Instituto do Câncer do Estado de São Paulo.

“We are starting to see a lot of cancer cases that didn’t show up at the beginning of the pandemic, but now they are arriving to us already in advanced stages,” she said. “These patients need hospital care. If the situation worsens and goes back to what we saw at the peak of the curve, I fear the public system won’t be able to treat properly the oncology patients that need hospital care and the patients with cancer who also have COVID-19.”

But even as health care worker fatigue and concerns linger, oncologists say that what they have learned in the last 6 months has helped them prepare as COVID-19 cases increase and a second global wave kicks up.
 

Lessons from the first wave

In the United States, COVID-19 hit different regions at different times and to different degrees. One of the areas hit first was Seattle.

“We jumped on top of this, we were evidence based, we put things in place very, very quickly,” said Julie Gralow, MD, professor at the University of Washington and the Fred Hutchinson Cancer Research Center, both in Seattle.

“We did a really good job keeping COVID out of our cancer centers,” Dr. Gralow said. “We learned how to be super safe, and to keep symptomatic people out of the building, and to limit the extra people they could bring with them. It’s all about the number of contacts you have.”

The story was different, though, for oncologists in several other countries, and sometimes it varied immensely within each nation.

“We treated fewer patients with cancer during the first wave,” says Dirk Arnold, MD, medical director of the Asklepios Tumor Center Hamburg (Germany), in an interview. “In part, this was because staff were quarantined and because we had a completely different infrastructure in all of the hospitals. But also fewer patients with cancer came to the clinic at all. A lot of resources were directed toward COVID-19.” 

In Spain, telemedicine helped keep up with visits, but other areas felt the effect of COVID-19 patient loads.

“At least in the oncology department of our center, we have practically maintained 100% of visits, mostly by telephone,” says Dr. Arrué, “but the reality is that our country has not yet been prepared for telemedicine.”

Laura Mezquita, MD, of the department of medical oncology at Hospital Clinic de Barcelona, describes a more dramatic situation: “We have seen how some of our patients, especially with metastatic disease, have been dismissed for intensive care and life-support treatments, as well as specific treatments against COVID-19 (tocilizumab, remdesivir, etc.) due to the general health collapse of the former wave,” she said. She adds that specific oncologic populations, such as those with thoracic tumors, have been more affected.
 

Distress among oncologists 

Many oncologists are still feeling stressed and fatigued after the first wave, just as a second string of outbreaks is on its way. 

A survey presented at last month’s ESMO 2020 Congress found that, in July-August, moral distress was reported by one-third of the oncologists who responded, and more than half reported a feeling of exhaustion. 

“The tiredness and team exhaustion is noticeable,” said Dr. Arnold. “We recently had a task force discussion about what will happen when we have a second wave and how the department and our services will adapt. It was clear that those who were at the very front in the first wave had only a limited desire to do that again in the second wave.”

Another concern: COVID-19’s effect on staffing levels. 

“We have a population of young caregivers who are affected by the COVID-19 disease with an absenteeism rate that is quite unprecedented,” said Sophie Beaupère, general delegate of Unicancer since January.

She said that, in general, the absenteeism rate in the cancer centers averages 5%-6%, depending on the year. But that rate is now skyrocketing.
 

Stop-start cycle for surgery

As caregivers quarantined around the world, more than 10% of patients with cancer had treatment canceled or delayed during the first wave of the pandemic, according to another survey from ESMO, involving 109 oncologists from 18 countries.

Difficulties were reported for surgeries by 34% of the centers, but also difficulties with delivering chemotherapy (22% of centers), radiotherapy (13.7%), and therapy with checkpoint inhibitors (9.1%), monoclonal antibodies (9%), and oral targeted therapy (3.7%).

Stopping surgery is a real concern in France, noted Dr. Kahn, the National League Against Cancer chair. He says that in regions that were badly hit by COVID-19, “it was not possible to have access to the operating room for people who absolutely needed surgery; for example, patients with lung cancer that was still operable. Most of the recovery rooms were mobilized for resuscitation.”

There may be some solutions, suggested Thierry Breton, director general of the National Institute of Cancer in France. “We are getting prepared, with the health ministry, for a possible increase in hospital tension, which would lead to a situation where we would have to reschedule operations. Nationally, regionally, and locally, we are seeing how we can resume and prioritize surgeries that have not been done.”
 

Delays in cancer diagnosis

While COVID-19 affected treatment, many oncologists say the major impact of the first wave was a delay in diagnosing cancer. Some of this was a result of the suspension of cancer screening programs, but there was also fear among the general public about visiting clinics and hospitals during a pandemic.

“We didn’t do so well with cancer during the first wave here in the U.K.,” said Karol Sikora, PhD, MBBChir, professor of cancer medicine and founding dean at the University of Buckingham Medical School, London. “Cancer diagnostic pathways virtually stalled partly because patients didn’t seek help, but getting scans and biopsies was also very difficult. Even patients referred urgently under the ‘2-weeks-wait’ rule were turned down.” 

In France, “the delay in diagnosis is indisputable,” said Dr. Kahn. “About 50% of the cancer diagnoses one would expect during this period were missed.” 

“I am worried that there remains a major traffic jam that has not been caught up with, and, in the meantime, the health crisis is worsening,” he added.  

In Seattle, Dr. Gralow said the first COVID-19 wave had little impact on treatment for breast cancer, but it was in screening for breast cancer “where things really got messed up.”

“Even though we’ve been fully ramped up again,” she said, concerns remain. To ensure that screening mammography is maintained, “we have spaced out the visits to keep our waiting rooms less populated, with a longer time between using the machine so we can clean it. To do this, we have extended operating hours and are now opening on Saturday.

“So we’re actually at 100% of our capacity, but I’m really nervous, though, that a lot of people put off their screening mammogram and aren’t going to come in and get it.

“Not only did people get the message to stay home and not do nonessential things, but I think a lot of people lost their health insurance when they lost their jobs,” she said, and without health insurance, they are not covered for cancer screening.
 

Looking ahead, with a plan

Many oncologists agree that access to care can and must be improved – and there were some positive moves.

“Some regimens changed during the first months of the pandemic, and I don’t see them going back to the way they were anytime soon,” said Dr. Testa. “The changes/adaptations that were made to minimize the chance of SARS-CoV-2 infection are still in place and will go on for a while. In this context, telemedicine helped a lot. The pandemic forced the stakeholders to step up and put it in place in March. And now it’s here to stay.”

The experience gained in the last several months has driven preparation for the next wave.

“We are not going to see the disorganization that we saw during the first wave,” said Florence Joly, MD, PhD, head of medical oncology at the Centre François Baclesse in Caen, France. “The difference between now and earlier this year is that COVID diagnostic tests are available. That was one of the problems in the first wave. We had no way to diagnose.”

On the East Coast of the United States, medical oncologist Charu Aggarwal, MD, MPH, is also optimistic: “I think we’re at a place where we can manage.”

“I believe if there was going to be a new wave of COVID-19 cases we would be: better psychologically prepared and better organized,” said Dr. Aggarwal, assistant professor of medicine in the hematology-oncology division at the University of Pennsylvania, Philadelphia. “We already have experience with all of the tools, we have telemedicine available, we have screening protocols available, we have testing, we are already universally masking, everyone’s hand-washing, so I do think that means we would be okay.” 

Dr. Arnold agreed that “we are much better prepared than for the first wave, but … we have immense tasks in the area of patient management, the digitization of patient care, the clear allocation of resources when there is a second or third wave. In many areas of preparation, I believe, unfortunately, we are not as well positioned as we had actually hoped.” 

The first wave of COVID hit cancer services in the United Kingdom particularly hard: One modeling study suggested that delays in cancer referrals will lead to thousands of additional deaths and tens of thousands of life-years lost.

“Cancer services are working at near normal levels now, but they are still fragile and could be severely compromised again if the NHS [National Health Service] gets flooded by COVID patients,” said Dr. Sikora.

The second wave may be different. “Although the number of infections has increased, the hospitalizations have only risen a little. Let’s see what happens,” he said in an interview. Since then, however, infections have continued to rise, and there has been an increase in hospitalizations. New social distancing measures in the United Kingdom were put into place on Oct. 12, with the aim of protecting the NHS from overload.

Dr. Arrué describes it this way: “The reality is that the ‘second wave’ has left behind the initial grief and shock that both patients and health professionals experienced when faced with something that, until now, we had only seen in the movies.” The second wave has led to new restrictions – including a partial lockdown since the beginning of October.

Dr. Aggarwal says her department recently had a conference with Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, about the impact of COVID-19 on oncology.

“I asked him what advice he’d give oncologists, and he said to go back to as much screening as you were doing previously as quickly as possible. That’s what must be relayed to our oncologists in the community – and also to primary care physicians – because they are often the ones who are ordering and championing the screening efforts.”

This article was originated by Aude Lecrubier, Medscape French edition, and developed by Zosia Chustecka, Medscape Oncology. With additional reporting by Kate Johnson, freelance medical journalist, Claudia Gottschling for Medscape Germany, Leoleli Schwartz for Medscape em português, Tim Locke for Medscape United Kingdom, and Carla Nieto Martínez, freelance medical journalist for Medscape Spanish edition. 

This article first appeared on Medscape.com.

Canceled appointments, postponed surgeries, and delayed cancer diagnoses – all are a recipe for exhaustion for oncologists around the world, struggling to reach and treat their patients during the pandemic. Physicians and their teams felt the pain as COVID-19 took its initial march around the globe.

“We saw the distress of people with cancer who could no longer get to anyone on the phone. Their medical visit was usually canceled. Their radiotherapy session was postponed or modified, and chemotherapy postponed,” says Axel Kahn, MD, chairman of the board of directors of La Ligue Nationale Contre le Cancer (National League Against Cancer). “In the vast majority of cases, cancer treatment can be postponed or readjusted, without affecting the patient’s chances of survival, but there has been a lot of anxiety because the patients do not know that.”

The stay-at-home factor was one that played out across many months during the first wave.

“I believe that the ‘stay-home’ message that we transmitted was rigorously followed by patients who should have come to the emergency room much earlier and who, therefore, were admitted with a much more deteriorated general condition than in non-COVID-19 times,” says Benjamín Domingo Arrué, MD, from the department of medical oncology at Hospital Universitari i Politècnic La Fe in Valencia, Spain.

And in Brazil, some of the impact from the initial hit of COVID-19 on oncology is only now being felt, according to Laura Testa, MD, head of breast medical oncology, Instituto do Câncer do Estado de São Paulo.

“We are starting to see a lot of cancer cases that didn’t show up at the beginning of the pandemic, but now they are arriving to us already in advanced stages,” she said. “These patients need hospital care. If the situation worsens and goes back to what we saw at the peak of the curve, I fear the public system won’t be able to treat properly the oncology patients that need hospital care and the patients with cancer who also have COVID-19.”

But even as health care worker fatigue and concerns linger, oncologists say that what they have learned in the last 6 months has helped them prepare as COVID-19 cases increase and a second global wave kicks up.
 

Lessons from the first wave

In the United States, COVID-19 hit different regions at different times and to different degrees. One of the areas hit first was Seattle.

“We jumped on top of this, we were evidence based, we put things in place very, very quickly,” said Julie Gralow, MD, professor at the University of Washington and the Fred Hutchinson Cancer Research Center, both in Seattle.

“We did a really good job keeping COVID out of our cancer centers,” Dr. Gralow said. “We learned how to be super safe, and to keep symptomatic people out of the building, and to limit the extra people they could bring with them. It’s all about the number of contacts you have.”

The story was different, though, for oncologists in several other countries, and sometimes it varied immensely within each nation.

“We treated fewer patients with cancer during the first wave,” says Dirk Arnold, MD, medical director of the Asklepios Tumor Center Hamburg (Germany), in an interview. “In part, this was because staff were quarantined and because we had a completely different infrastructure in all of the hospitals. But also fewer patients with cancer came to the clinic at all. A lot of resources were directed toward COVID-19.” 

In Spain, telemedicine helped keep up with visits, but other areas felt the effect of COVID-19 patient loads.

“At least in the oncology department of our center, we have practically maintained 100% of visits, mostly by telephone,” says Dr. Arrué, “but the reality is that our country has not yet been prepared for telemedicine.”

Laura Mezquita, MD, of the department of medical oncology at Hospital Clinic de Barcelona, describes a more dramatic situation: “We have seen how some of our patients, especially with metastatic disease, have been dismissed for intensive care and life-support treatments, as well as specific treatments against COVID-19 (tocilizumab, remdesivir, etc.) due to the general health collapse of the former wave,” she said. She adds that specific oncologic populations, such as those with thoracic tumors, have been more affected.
 

Distress among oncologists 

Many oncologists are still feeling stressed and fatigued after the first wave, just as a second string of outbreaks is on its way. 

A survey presented at last month’s ESMO 2020 Congress found that, in July-August, moral distress was reported by one-third of the oncologists who responded, and more than half reported a feeling of exhaustion. 

“The tiredness and team exhaustion is noticeable,” said Dr. Arnold. “We recently had a task force discussion about what will happen when we have a second wave and how the department and our services will adapt. It was clear that those who were at the very front in the first wave had only a limited desire to do that again in the second wave.”

Another concern: COVID-19’s effect on staffing levels. 

“We have a population of young caregivers who are affected by the COVID-19 disease with an absenteeism rate that is quite unprecedented,” said Sophie Beaupère, general delegate of Unicancer since January.

She said that, in general, the absenteeism rate in the cancer centers averages 5%-6%, depending on the year. But that rate is now skyrocketing.
 

Stop-start cycle for surgery

As caregivers quarantined around the world, more than 10% of patients with cancer had treatment canceled or delayed during the first wave of the pandemic, according to another survey from ESMO, involving 109 oncologists from 18 countries.

Difficulties were reported for surgeries by 34% of the centers, but also difficulties with delivering chemotherapy (22% of centers), radiotherapy (13.7%), and therapy with checkpoint inhibitors (9.1%), monoclonal antibodies (9%), and oral targeted therapy (3.7%).

Stopping surgery is a real concern in France, noted Dr. Kahn, the National League Against Cancer chair. He says that in regions that were badly hit by COVID-19, “it was not possible to have access to the operating room for people who absolutely needed surgery; for example, patients with lung cancer that was still operable. Most of the recovery rooms were mobilized for resuscitation.”

There may be some solutions, suggested Thierry Breton, director general of the National Institute of Cancer in France. “We are getting prepared, with the health ministry, for a possible increase in hospital tension, which would lead to a situation where we would have to reschedule operations. Nationally, regionally, and locally, we are seeing how we can resume and prioritize surgeries that have not been done.”
 

Delays in cancer diagnosis

While COVID-19 affected treatment, many oncologists say the major impact of the first wave was a delay in diagnosing cancer. Some of this was a result of the suspension of cancer screening programs, but there was also fear among the general public about visiting clinics and hospitals during a pandemic.

“We didn’t do so well with cancer during the first wave here in the U.K.,” said Karol Sikora, PhD, MBBChir, professor of cancer medicine and founding dean at the University of Buckingham Medical School, London. “Cancer diagnostic pathways virtually stalled partly because patients didn’t seek help, but getting scans and biopsies was also very difficult. Even patients referred urgently under the ‘2-weeks-wait’ rule were turned down.” 

In France, “the delay in diagnosis is indisputable,” said Dr. Kahn. “About 50% of the cancer diagnoses one would expect during this period were missed.” 

“I am worried that there remains a major traffic jam that has not been caught up with, and, in the meantime, the health crisis is worsening,” he added.  

In Seattle, Dr. Gralow said the first COVID-19 wave had little impact on treatment for breast cancer, but it was in screening for breast cancer “where things really got messed up.”

“Even though we’ve been fully ramped up again,” she said, concerns remain. To ensure that screening mammography is maintained, “we have spaced out the visits to keep our waiting rooms less populated, with a longer time between using the machine so we can clean it. To do this, we have extended operating hours and are now opening on Saturday.

“So we’re actually at 100% of our capacity, but I’m really nervous, though, that a lot of people put off their screening mammogram and aren’t going to come in and get it.

“Not only did people get the message to stay home and not do nonessential things, but I think a lot of people lost their health insurance when they lost their jobs,” she said, and without health insurance, they are not covered for cancer screening.
 

Looking ahead, with a plan

Many oncologists agree that access to care can and must be improved – and there were some positive moves.

“Some regimens changed during the first months of the pandemic, and I don’t see them going back to the way they were anytime soon,” said Dr. Testa. “The changes/adaptations that were made to minimize the chance of SARS-CoV-2 infection are still in place and will go on for a while. In this context, telemedicine helped a lot. The pandemic forced the stakeholders to step up and put it in place in March. And now it’s here to stay.”

The experience gained in the last several months has driven preparation for the next wave.

“We are not going to see the disorganization that we saw during the first wave,” said Florence Joly, MD, PhD, head of medical oncology at the Centre François Baclesse in Caen, France. “The difference between now and earlier this year is that COVID diagnostic tests are available. That was one of the problems in the first wave. We had no way to diagnose.”

On the East Coast of the United States, medical oncologist Charu Aggarwal, MD, MPH, is also optimistic: “I think we’re at a place where we can manage.”

“I believe if there was going to be a new wave of COVID-19 cases we would be: better psychologically prepared and better organized,” said Dr. Aggarwal, assistant professor of medicine in the hematology-oncology division at the University of Pennsylvania, Philadelphia. “We already have experience with all of the tools, we have telemedicine available, we have screening protocols available, we have testing, we are already universally masking, everyone’s hand-washing, so I do think that means we would be okay.” 

Dr. Arnold agreed that “we are much better prepared than for the first wave, but … we have immense tasks in the area of patient management, the digitization of patient care, the clear allocation of resources when there is a second or third wave. In many areas of preparation, I believe, unfortunately, we are not as well positioned as we had actually hoped.” 

The first wave of COVID hit cancer services in the United Kingdom particularly hard: One modeling study suggested that delays in cancer referrals will lead to thousands of additional deaths and tens of thousands of life-years lost.

“Cancer services are working at near normal levels now, but they are still fragile and could be severely compromised again if the NHS [National Health Service] gets flooded by COVID patients,” said Dr. Sikora.

The second wave may be different. “Although the number of infections has increased, the hospitalizations have only risen a little. Let’s see what happens,” he said in an interview. Since then, however, infections have continued to rise, and there has been an increase in hospitalizations. New social distancing measures in the United Kingdom were put into place on Oct. 12, with the aim of protecting the NHS from overload.

Dr. Arrué describes it this way: “The reality is that the ‘second wave’ has left behind the initial grief and shock that both patients and health professionals experienced when faced with something that, until now, we had only seen in the movies.” The second wave has led to new restrictions – including a partial lockdown since the beginning of October.

Dr. Aggarwal says her department recently had a conference with Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, about the impact of COVID-19 on oncology.

“I asked him what advice he’d give oncologists, and he said to go back to as much screening as you were doing previously as quickly as possible. That’s what must be relayed to our oncologists in the community – and also to primary care physicians – because they are often the ones who are ordering and championing the screening efforts.”

This article was originated by Aude Lecrubier, Medscape French edition, and developed by Zosia Chustecka, Medscape Oncology. With additional reporting by Kate Johnson, freelance medical journalist, Claudia Gottschling for Medscape Germany, Leoleli Schwartz for Medscape em português, Tim Locke for Medscape United Kingdom, and Carla Nieto Martínez, freelance medical journalist for Medscape Spanish edition. 

This article first appeared on Medscape.com.