AVAHO

Mohs micrographic surgery (MMS) may be a viable alternative to wide margin excision (WME) in selected patients with early-stage invasive melanoma, according to a retrospective cohort study.

In the study, which was published in JAMA Dermatology, patients who underwent MMS had a “modest survival advantage” when compared with those who were treated with WME, the approach recommended for treatment of invasive melanoma without nodal or extralymphatic metastases in national guidelines, reported the investigators.

“We sought herein to investigate the association of the type of surgical excision – WME or MMS – with overall survival for cases of American Joint Committee on Cancer Cancer Staging Manual 8th edition (AJCC-8) stage I invasive melanoma,” wrote Shayan Cheraghlou, of Yale University, New Haven, Conn., and colleagues.

The researchers identified a total of 70,319 patients diagnosed with stage I invasive melanoma between Jan. 1, 2004, and Dec. 31, 2014. Data were collected from the National Cancer Database, including 3,234 (4.6%) and 67,085 (95.4%) patients who underwent MMS and WME, respectively. The median age of patients in the cohort was 57 years; 47.7% were female, and almost 97% were white.

In the survival analysis, the team adjusted for clinical and tumor-specific variables and conducted a matched analysis using propensity scores. The primary outcome measured was overall survival.

After analysis, the researchers found that MMS was associated with modestly better overall survival when compared with WME after adjustments (hazard ratio, 0.86; 95% confidence interval, 0.76-0.97). In the propensity score–matched analysis, a similar modest survival advantage was seen for patients who underwent MMS (hazard ratio, 0.82; 95% CI, 0.68-0.98).

“Significant differences in treatment practices based on the treatment facility were noted, with academic facilities more than twice as likely as nonacademic facilities to use MMS,” they wrote.

The researchers acknowledged a key limitation of the study was the use of a convenience sample, as opposed to a population-based sample. As a result, the generalizability of the findings may be limited to certain treatment facilities.

“These data suggest that MMS is an effective approach compared with WME for AJCC-8 stage I invasive melanoma,” they concluded.

No funding sources were reported. The authors reported having no conflicts of interest.

SOURCE: Cheraghlou S et al. JAMA Dermatol. 2019 Sep 25. doi: 10.1001/jamadermatol.2019.2890.

Mohs micrographic surgery (MMS) may be a viable alternative to wide margin excision (WME) in selected patients with early-stage invasive melanoma, according to a retrospective cohort study.

In the study, which was published in JAMA Dermatology, patients who underwent MMS had a “modest survival advantage” when compared with those who were treated with WME, the approach recommended for treatment of invasive melanoma without nodal or extralymphatic metastases in national guidelines, reported the investigators.

“We sought herein to investigate the association of the type of surgical excision – WME or MMS – with overall survival for cases of American Joint Committee on Cancer Cancer Staging Manual 8th edition (AJCC-8) stage I invasive melanoma,” wrote Shayan Cheraghlou, of Yale University, New Haven, Conn., and colleagues.

The researchers identified a total of 70,319 patients diagnosed with stage I invasive melanoma between Jan. 1, 2004, and Dec. 31, 2014. Data were collected from the National Cancer Database, including 3,234 (4.6%) and 67,085 (95.4%) patients who underwent MMS and WME, respectively. The median age of patients in the cohort was 57 years; 47.7% were female, and almost 97% were white.

In the survival analysis, the team adjusted for clinical and tumor-specific variables and conducted a matched analysis using propensity scores. The primary outcome measured was overall survival.

After analysis, the researchers found that MMS was associated with modestly better overall survival when compared with WME after adjustments (hazard ratio, 0.86; 95% confidence interval, 0.76-0.97). In the propensity score–matched analysis, a similar modest survival advantage was seen for patients who underwent MMS (hazard ratio, 0.82; 95% CI, 0.68-0.98).

“Significant differences in treatment practices based on the treatment facility were noted, with academic facilities more than twice as likely as nonacademic facilities to use MMS,” they wrote.

The researchers acknowledged a key limitation of the study was the use of a convenience sample, as opposed to a population-based sample. As a result, the generalizability of the findings may be limited to certain treatment facilities.

“These data suggest that MMS is an effective approach compared with WME for AJCC-8 stage I invasive melanoma,” they concluded.

No funding sources were reported. The authors reported having no conflicts of interest.

SOURCE: Cheraghlou S et al. JAMA Dermatol. 2019 Sep 25. doi: 10.1001/jamadermatol.2019.2890.

Mohs micrographic surgery (MMS) may be a viable alternative to wide margin excision (WME) in selected patients with early-stage invasive melanoma, according to a retrospective cohort study.

In the study, which was published in JAMA Dermatology, patients who underwent MMS had a “modest survival advantage” when compared with those who were treated with WME, the approach recommended for treatment of invasive melanoma without nodal or extralymphatic metastases in national guidelines, reported the investigators.

“We sought herein to investigate the association of the type of surgical excision – WME or MMS – with overall survival for cases of American Joint Committee on Cancer Cancer Staging Manual 8th edition (AJCC-8) stage I invasive melanoma,” wrote Shayan Cheraghlou, of Yale University, New Haven, Conn., and colleagues.

The researchers identified a total of 70,319 patients diagnosed with stage I invasive melanoma between Jan. 1, 2004, and Dec. 31, 2014. Data were collected from the National Cancer Database, including 3,234 (4.6%) and 67,085 (95.4%) patients who underwent MMS and WME, respectively. The median age of patients in the cohort was 57 years; 47.7% were female, and almost 97% were white.

In the survival analysis, the team adjusted for clinical and tumor-specific variables and conducted a matched analysis using propensity scores. The primary outcome measured was overall survival.

After analysis, the researchers found that MMS was associated with modestly better overall survival when compared with WME after adjustments (hazard ratio, 0.86; 95% confidence interval, 0.76-0.97). In the propensity score–matched analysis, a similar modest survival advantage was seen for patients who underwent MMS (hazard ratio, 0.82; 95% CI, 0.68-0.98).

“Significant differences in treatment practices based on the treatment facility were noted, with academic facilities more than twice as likely as nonacademic facilities to use MMS,” they wrote.

The researchers acknowledged a key limitation of the study was the use of a convenience sample, as opposed to a population-based sample. As a result, the generalizability of the findings may be limited to certain treatment facilities.

“These data suggest that MMS is an effective approach compared with WME for AJCC-8 stage I invasive melanoma,” they concluded.

No funding sources were reported. The authors reported having no conflicts of interest.

SOURCE: Cheraghlou S et al. JAMA Dermatol. 2019 Sep 25. doi: 10.1001/jamadermatol.2019.2890.

Breast cancer screening recommendations have evolved over the past decade. The new U.S. Preventive Services Take Force recommendations detailing screening for patients at increased risk of BRCA1/2 mutations have added another dimension to screening for breast and associated cancers for primary care physicians. BRCA1/2 genes are tumor-suppressor genes. Mutations in these genes place women at an increased risk for developing breast, ovarian, fallopian tube, and peritoneal cancer. Detection of BRCA1/2 mutations through genetic screening can provide patients with more information about their cancer risk and can lead to discussion of prophylactic therapies. This includes increased screening frequency, medical therapy, and surgical interventions.

New USPSTF recommendations address who is at an increased risk for BRCA1/2 mutations. They recommend using screening tools focusing on family history that primary care physicians can utilize to determine who should be referred for genetic counseling to discuss the risks and benefits of genetic screening. The following are the task force’s two primary recommendations:


The USPSTF recommends that primary care clinicians assess women with a personal or family history of breast, ovarian, tubal, or peritoneal cancer or who have an ancestry associated with BRCA1/2 gene mutations with an appropriate brief familial risk assessment tool. Women with a positive result on the risk assessment tool should receive genetic counseling and, if indicated after counseling, genetic testing. (B recommendation)


The USPSTF recommends against routine risk assessment, genetic counseling, or genetic testing for women whose personal or family history or ancestry is not associated with potentially harmful BRCA1/2 gene mutations. (D recommendation)


Breast cancer is the second leading cause of cancer and cancer death for women in the United States. Ovarian cancer ranks fifth in cancer deaths for women in the U.S. By age 70, women with BRCA1/2 mutations have a 45%-65% cumulative lifetime risk of developing breast cancer.

Mutations in BRCA1, specifically, are associated with a 39% lifetime risk for ovarian, fallopian tube, and peritoneal cancer. In contrast, mutations in BRCA2 are associated with a 10%-17% lifetime risk.

The USPSTF also underscores the increased prevalence of BRCA1/2 mutations in the Ashkenazi Jewish population. Three out of seven familial risk assessment tools inquire about Jewish ancestry. This is because the Ashkenazi Jewish population have a higher prevalence of three founder mutations in the BRCA1/2 gene. A member of this population has a 1 in 40 chance of carrying one of these three mutations, whereas the general population has a 1 in 300 chance.

The USPSTF recommends a multistep process of screening. The first step is taking a family history of cancer. For women who have a family history of breast, ovarian, tubal, or peritoneal cancer or a personal history of these cancers, a brief familial risk assessment tool should be used to determine the need for referral for in-depth genetic counseling to determine the need for genetic testing.

It is important to recognize that the validated tools recommended by the USPSTF are specific for genetic risk assessment. General breast cancer risk assessment tools, including the National Cancer Institute Breast Cancer Risk Assessment Tool, which is based on the Gail model, are not recommended.

The sensitivity of the tools recommended by the USPSTF range between 77% and 100%. A number of tools are given as an option with no one tool being better than the other. Perhaps the easiest to implement of the validated tools recommended is the Pedigree Assessment Tool. For this tool, points are assigned for every family member with breast or ovarian cancer as indicated in the table below.

The bottom line

USPSTF recommended that primary care physicians should use familial risk assessment tools to screen women for BRCA1/2 mutations. This includes women with a personal and/or family history of breast, ovarian, tubal, or peritoneal cancer or women with a family history of BRCA1/2 gene mutations. Patients who test positive through one of the suggested screening tools should be referred for genetic counseling. This could lead to genetic testing and subsequent prophylactic therapies and/or increased screenings if the patient so desires. It is of importance to note the USPSTF recommends against routine screening of BRCA1/2 gene mutations for women who do not meet the above requirements.

Reference

USPSTF Recommendation: Assessment, counseling, and testing for BRCA-related cancer. JAMA. 2019;322(7):652-65. doi: 10.1001/jama.2019.10987.
 

Dr. Style is a second-year resident in the Family Medicine Residency Program at Abington (Pa.) Jefferson Health. Dr. Skolnik is professor of family and community medicine at Jefferson Medical College, Philadelphia, and an associate director of the family medicine residency program at Abington Jefferson Health.

Breast cancer screening recommendations have evolved over the past decade. The new U.S. Preventive Services Take Force recommendations detailing screening for patients at increased risk of BRCA1/2 mutations have added another dimension to screening for breast and associated cancers for primary care physicians. BRCA1/2 genes are tumor-suppressor genes. Mutations in these genes place women at an increased risk for developing breast, ovarian, fallopian tube, and peritoneal cancer. Detection of BRCA1/2 mutations through genetic screening can provide patients with more information about their cancer risk and can lead to discussion of prophylactic therapies. This includes increased screening frequency, medical therapy, and surgical interventions.

New USPSTF recommendations address who is at an increased risk for BRCA1/2 mutations. They recommend using screening tools focusing on family history that primary care physicians can utilize to determine who should be referred for genetic counseling to discuss the risks and benefits of genetic screening. The following are the task force’s two primary recommendations:


The USPSTF recommends that primary care clinicians assess women with a personal or family history of breast, ovarian, tubal, or peritoneal cancer or who have an ancestry associated with BRCA1/2 gene mutations with an appropriate brief familial risk assessment tool. Women with a positive result on the risk assessment tool should receive genetic counseling and, if indicated after counseling, genetic testing. (B recommendation)


The USPSTF recommends against routine risk assessment, genetic counseling, or genetic testing for women whose personal or family history or ancestry is not associated with potentially harmful BRCA1/2 gene mutations. (D recommendation)


Breast cancer is the second leading cause of cancer and cancer death for women in the United States. Ovarian cancer ranks fifth in cancer deaths for women in the U.S. By age 70, women with BRCA1/2 mutations have a 45%-65% cumulative lifetime risk of developing breast cancer.

Mutations in BRCA1, specifically, are associated with a 39% lifetime risk for ovarian, fallopian tube, and peritoneal cancer. In contrast, mutations in BRCA2 are associated with a 10%-17% lifetime risk.

The USPSTF also underscores the increased prevalence of BRCA1/2 mutations in the Ashkenazi Jewish population. Three out of seven familial risk assessment tools inquire about Jewish ancestry. This is because the Ashkenazi Jewish population have a higher prevalence of three founder mutations in the BRCA1/2 gene. A member of this population has a 1 in 40 chance of carrying one of these three mutations, whereas the general population has a 1 in 300 chance.

The USPSTF recommends a multistep process of screening. The first step is taking a family history of cancer. For women who have a family history of breast, ovarian, tubal, or peritoneal cancer or a personal history of these cancers, a brief familial risk assessment tool should be used to determine the need for referral for in-depth genetic counseling to determine the need for genetic testing.

It is important to recognize that the validated tools recommended by the USPSTF are specific for genetic risk assessment. General breast cancer risk assessment tools, including the National Cancer Institute Breast Cancer Risk Assessment Tool, which is based on the Gail model, are not recommended.

The sensitivity of the tools recommended by the USPSTF range between 77% and 100%. A number of tools are given as an option with no one tool being better than the other. Perhaps the easiest to implement of the validated tools recommended is the Pedigree Assessment Tool. For this tool, points are assigned for every family member with breast or ovarian cancer as indicated in the table below.

The bottom line

USPSTF recommended that primary care physicians should use familial risk assessment tools to screen women for BRCA1/2 mutations. This includes women with a personal and/or family history of breast, ovarian, tubal, or peritoneal cancer or women with a family history of BRCA1/2 gene mutations. Patients who test positive through one of the suggested screening tools should be referred for genetic counseling. This could lead to genetic testing and subsequent prophylactic therapies and/or increased screenings if the patient so desires. It is of importance to note the USPSTF recommends against routine screening of BRCA1/2 gene mutations for women who do not meet the above requirements.

Reference

USPSTF Recommendation: Assessment, counseling, and testing for BRCA-related cancer. JAMA. 2019;322(7):652-65. doi: 10.1001/jama.2019.10987.
 

Dr. Style is a second-year resident in the Family Medicine Residency Program at Abington (Pa.) Jefferson Health. Dr. Skolnik is professor of family and community medicine at Jefferson Medical College, Philadelphia, and an associate director of the family medicine residency program at Abington Jefferson Health.

Breast cancer screening recommendations have evolved over the past decade. The new U.S. Preventive Services Take Force recommendations detailing screening for patients at increased risk of BRCA1/2 mutations have added another dimension to screening for breast and associated cancers for primary care physicians. BRCA1/2 genes are tumor-suppressor genes. Mutations in these genes place women at an increased risk for developing breast, ovarian, fallopian tube, and peritoneal cancer. Detection of BRCA1/2 mutations through genetic screening can provide patients with more information about their cancer risk and can lead to discussion of prophylactic therapies. This includes increased screening frequency, medical therapy, and surgical interventions.

New USPSTF recommendations address who is at an increased risk for BRCA1/2 mutations. They recommend using screening tools focusing on family history that primary care physicians can utilize to determine who should be referred for genetic counseling to discuss the risks and benefits of genetic screening. The following are the task force’s two primary recommendations:


The USPSTF recommends that primary care clinicians assess women with a personal or family history of breast, ovarian, tubal, or peritoneal cancer or who have an ancestry associated with BRCA1/2 gene mutations with an appropriate brief familial risk assessment tool. Women with a positive result on the risk assessment tool should receive genetic counseling and, if indicated after counseling, genetic testing. (B recommendation)


The USPSTF recommends against routine risk assessment, genetic counseling, or genetic testing for women whose personal or family history or ancestry is not associated with potentially harmful BRCA1/2 gene mutations. (D recommendation)


Breast cancer is the second leading cause of cancer and cancer death for women in the United States. Ovarian cancer ranks fifth in cancer deaths for women in the U.S. By age 70, women with BRCA1/2 mutations have a 45%-65% cumulative lifetime risk of developing breast cancer.

Mutations in BRCA1, specifically, are associated with a 39% lifetime risk for ovarian, fallopian tube, and peritoneal cancer. In contrast, mutations in BRCA2 are associated with a 10%-17% lifetime risk.

The USPSTF also underscores the increased prevalence of BRCA1/2 mutations in the Ashkenazi Jewish population. Three out of seven familial risk assessment tools inquire about Jewish ancestry. This is because the Ashkenazi Jewish population have a higher prevalence of three founder mutations in the BRCA1/2 gene. A member of this population has a 1 in 40 chance of carrying one of these three mutations, whereas the general population has a 1 in 300 chance.

The USPSTF recommends a multistep process of screening. The first step is taking a family history of cancer. For women who have a family history of breast, ovarian, tubal, or peritoneal cancer or a personal history of these cancers, a brief familial risk assessment tool should be used to determine the need for referral for in-depth genetic counseling to determine the need for genetic testing.

It is important to recognize that the validated tools recommended by the USPSTF are specific for genetic risk assessment. General breast cancer risk assessment tools, including the National Cancer Institute Breast Cancer Risk Assessment Tool, which is based on the Gail model, are not recommended.

The sensitivity of the tools recommended by the USPSTF range between 77% and 100%. A number of tools are given as an option with no one tool being better than the other. Perhaps the easiest to implement of the validated tools recommended is the Pedigree Assessment Tool. For this tool, points are assigned for every family member with breast or ovarian cancer as indicated in the table below.

The bottom line

USPSTF recommended that primary care physicians should use familial risk assessment tools to screen women for BRCA1/2 mutations. This includes women with a personal and/or family history of breast, ovarian, tubal, or peritoneal cancer or women with a family history of BRCA1/2 gene mutations. Patients who test positive through one of the suggested screening tools should be referred for genetic counseling. This could lead to genetic testing and subsequent prophylactic therapies and/or increased screenings if the patient so desires. It is of importance to note the USPSTF recommends against routine screening of BRCA1/2 gene mutations for women who do not meet the above requirements.

Reference

USPSTF Recommendation: Assessment, counseling, and testing for BRCA-related cancer. JAMA. 2019;322(7):652-65. doi: 10.1001/jama.2019.10987.
 

Dr. Style is a second-year resident in the Family Medicine Residency Program at Abington (Pa.) Jefferson Health. Dr. Skolnik is professor of family and community medicine at Jefferson Medical College, Philadelphia, and an associate director of the family medicine residency program at Abington Jefferson Health.

NEW ORLEANS – Patients tended to recall the benefits of lung cancer screening much more than the risks in a recent survey, underscoring the need for ongoing patient education beyond the initial shared decision-making encounter, a researcher said.

While about 9 in 10 patients recalled key information on the benefits, only about 4 in 10 recalled information on risks, according to Erin Hirsch, MSPH, of the Colorado School of Public Health in Aurora.

“This may mean we need ongoing clinician involvement or continued education about this important information, especially if the patients aren’t screening annually,” Ms. Hirsch said in a podium presentation at the annual meeting of the American College of Chest Physicians.

Even fewer patients could correctly recall eligibility criteria for lung cancer screening, which suggests “ongoing clinician involvement” is needed to identify appropriate patients, Hirsch added in her presentation.

Shared decision making about lung cancer screening, which is supposed to entail a balanced patient-provider conversation about eligibility, risks, and benefits, is required by the Centers for Medicare & Medicaid Services to cover the cost of lung cancer screening as a preventative service, Hirsch noted in her presentation.

However, it’s largely unknown to what extent patients due for an annual screening recall information that should have been imparted in that initial discussion.

“The gap in knowledge centers around the fact that shared decision making is only required for baseline scan, but screening is recommended on an annual basis,” she said.

To test patient recall, Hirsch and colleagues developed a knowledge survey including 34 questions about lung cancer screening eligibility, risks, and benefits. The surveys went out by mail or email to 228 patients who had a baseline screening CT scan 6-12 months earlier; a total of 53 complete responses were included in the analysis, which focused on seven key questions about benefit, risk, and eligibility.

Recall was “excellent” for the benefit questions, Ms. Hirsch said, with 91% of patients able to recall that a computed tomography (CT) scan is better at detecting a possible lung cancer than a chest x-ray, while 87% recalled that without screening lung cancer is often found at a later stage when cure is less likely.

By contrast, a “moderate” amount (40%) remembered that a CT scan can suggest the patient has lung cancer when in fact they do not, she said, and only 38% recalled that radiation exposure was one of the harms of lung cancer screening, she added.

Eligibility recall was “poor,” she added, with only 21% affirming that not all current and former smokers need to be screened for lung cancer. Just 8% recalled that 55 years is the age at which beginning lung cancer screening is recommended, and 4% knew that 30 is the minimum number of pack-years required to be eligible for screening.

While these results may have clinical implications, Ms. Hirsch acknowledged a number of limitations to this pilot study. Among those was the fact that the content of the initial shared decision-making conversation could not be assessed: “We assumed that the patients were exposed to the information asked about in the survey ahead of time, but we can’t say for sure if that was true,” she explained.

Ms. Hirsch and coauthors disclosed no relationships relevant to their study.

SOURCE: Hirsch E et al. CHEST 2019. Abstract, doi: 10.1016/j.chest.2019.08.107.

NEW ORLEANS – Patients tended to recall the benefits of lung cancer screening much more than the risks in a recent survey, underscoring the need for ongoing patient education beyond the initial shared decision-making encounter, a researcher said.

While about 9 in 10 patients recalled key information on the benefits, only about 4 in 10 recalled information on risks, according to Erin Hirsch, MSPH, of the Colorado School of Public Health in Aurora.

“This may mean we need ongoing clinician involvement or continued education about this important information, especially if the patients aren’t screening annually,” Ms. Hirsch said in a podium presentation at the annual meeting of the American College of Chest Physicians.

Even fewer patients could correctly recall eligibility criteria for lung cancer screening, which suggests “ongoing clinician involvement” is needed to identify appropriate patients, Hirsch added in her presentation.

Shared decision making about lung cancer screening, which is supposed to entail a balanced patient-provider conversation about eligibility, risks, and benefits, is required by the Centers for Medicare & Medicaid Services to cover the cost of lung cancer screening as a preventative service, Hirsch noted in her presentation.

However, it’s largely unknown to what extent patients due for an annual screening recall information that should have been imparted in that initial discussion.

“The gap in knowledge centers around the fact that shared decision making is only required for baseline scan, but screening is recommended on an annual basis,” she said.

To test patient recall, Hirsch and colleagues developed a knowledge survey including 34 questions about lung cancer screening eligibility, risks, and benefits. The surveys went out by mail or email to 228 patients who had a baseline screening CT scan 6-12 months earlier; a total of 53 complete responses were included in the analysis, which focused on seven key questions about benefit, risk, and eligibility.

Recall was “excellent” for the benefit questions, Ms. Hirsch said, with 91% of patients able to recall that a computed tomography (CT) scan is better at detecting a possible lung cancer than a chest x-ray, while 87% recalled that without screening lung cancer is often found at a later stage when cure is less likely.

By contrast, a “moderate” amount (40%) remembered that a CT scan can suggest the patient has lung cancer when in fact they do not, she said, and only 38% recalled that radiation exposure was one of the harms of lung cancer screening, she added.

Eligibility recall was “poor,” she added, with only 21% affirming that not all current and former smokers need to be screened for lung cancer. Just 8% recalled that 55 years is the age at which beginning lung cancer screening is recommended, and 4% knew that 30 is the minimum number of pack-years required to be eligible for screening.

While these results may have clinical implications, Ms. Hirsch acknowledged a number of limitations to this pilot study. Among those was the fact that the content of the initial shared decision-making conversation could not be assessed: “We assumed that the patients were exposed to the information asked about in the survey ahead of time, but we can’t say for sure if that was true,” she explained.

Ms. Hirsch and coauthors disclosed no relationships relevant to their study.

SOURCE: Hirsch E et al. CHEST 2019. Abstract, doi: 10.1016/j.chest.2019.08.107.

NEW ORLEANS – Patients tended to recall the benefits of lung cancer screening much more than the risks in a recent survey, underscoring the need for ongoing patient education beyond the initial shared decision-making encounter, a researcher said.

While about 9 in 10 patients recalled key information on the benefits, only about 4 in 10 recalled information on risks, according to Erin Hirsch, MSPH, of the Colorado School of Public Health in Aurora.

“This may mean we need ongoing clinician involvement or continued education about this important information, especially if the patients aren’t screening annually,” Ms. Hirsch said in a podium presentation at the annual meeting of the American College of Chest Physicians.

Even fewer patients could correctly recall eligibility criteria for lung cancer screening, which suggests “ongoing clinician involvement” is needed to identify appropriate patients, Hirsch added in her presentation.

Shared decision making about lung cancer screening, which is supposed to entail a balanced patient-provider conversation about eligibility, risks, and benefits, is required by the Centers for Medicare & Medicaid Services to cover the cost of lung cancer screening as a preventative service, Hirsch noted in her presentation.

However, it’s largely unknown to what extent patients due for an annual screening recall information that should have been imparted in that initial discussion.

“The gap in knowledge centers around the fact that shared decision making is only required for baseline scan, but screening is recommended on an annual basis,” she said.

To test patient recall, Hirsch and colleagues developed a knowledge survey including 34 questions about lung cancer screening eligibility, risks, and benefits. The surveys went out by mail or email to 228 patients who had a baseline screening CT scan 6-12 months earlier; a total of 53 complete responses were included in the analysis, which focused on seven key questions about benefit, risk, and eligibility.

Recall was “excellent” for the benefit questions, Ms. Hirsch said, with 91% of patients able to recall that a computed tomography (CT) scan is better at detecting a possible lung cancer than a chest x-ray, while 87% recalled that without screening lung cancer is often found at a later stage when cure is less likely.

By contrast, a “moderate” amount (40%) remembered that a CT scan can suggest the patient has lung cancer when in fact they do not, she said, and only 38% recalled that radiation exposure was one of the harms of lung cancer screening, she added.

Eligibility recall was “poor,” she added, with only 21% affirming that not all current and former smokers need to be screened for lung cancer. Just 8% recalled that 55 years is the age at which beginning lung cancer screening is recommended, and 4% knew that 30 is the minimum number of pack-years required to be eligible for screening.

While these results may have clinical implications, Ms. Hirsch acknowledged a number of limitations to this pilot study. Among those was the fact that the content of the initial shared decision-making conversation could not be assessed: “We assumed that the patients were exposed to the information asked about in the survey ahead of time, but we can’t say for sure if that was true,” she explained.

Ms. Hirsch and coauthors disclosed no relationships relevant to their study.

SOURCE: Hirsch E et al. CHEST 2019. Abstract, doi: 10.1016/j.chest.2019.08.107.

There is increasing evidence that exercise lowers the risk of developing cancer, improves survival after a cancer diagnosis, and helps ease related health outcomes. However, relatively few cancer patients meet current physical activity guidelines – often because it wasn’t recommended by their oncologist.

thinkstock

“Observed barriers to clinicians referring patients to exercise programming include lack of awareness of the potential value of exercise in cancer populations, uncertainty regarding the safety or suitability of exercise for a particular patient, lack of awareness regarding available programs to help facilitate exercise in cancer populations, need for education and skills development for making referrals, and a belief that referrals to exercise programming are not within the scope of practice for oncology clinicians,” Kathryn H. Schmitz, PhD, from Penn State University in Hershey and coauthors from the American College of Sports Medicine International Multidisciplinary Roundtable wrote in CA: A Cancer Journal for Clinicians.

Dr. Schmitz and colleagues proposed using the American College of Sports Medicine’s Exercise Is Medicine initiative to address this gap, with a focus on asking physicians to take an assess, revise, and refer approach to recommending exercise.

Noting that there is clear evidence that patients are more likely to exercise if their oncologist recommends that they do so, the authors said a clinician’s silence on the subject of exercise could be interpreted as “tacit approval to maintain inactivity.”

To assess a patient’s level of physical activity, the authors suggested asking patients how many days during the past week they had undertaken physical activity during which their heart beat faster or they breathed harder than normal for more than 30 minutes or how often they had undertaken activity to increase muscle strength.

If the patient can safely exercise without medical supervision, the authors recommend that clinicians advise patients to increase their physical activity to achieve current recommended levels. Clinicians can refer patients to community programs to help ramp up their activity.

However, for patients who may not be able to exercise safely on their own, the authors recommend referring them to an outpatient rehabiliation professional.

“Referral to appropriate and effective programs and follow-up with an assessment of progress (or lack thereof) at subsequent visits can serve as key transition points to change a patient’s behavior and affect their tolerance of or recovery from treatment,” they wrote.

The authors stressed that oncology clinicians were not expected to prescribe specific levels of exercise or to perform extensive screening and triage of patients based on their fitness.

“Oncology clinicians, however, play a vital role in telling the patient that it is important to exercise and pointing patients in the right direction to make that happen,” they wrote.

The American College of Sports Medicine International Multidisciplinary Roundtable was funded by the American College of Sports Medicine, the American Cancer Society, and other groups. Four authors declared grant support for participating in the study. One declared private industry funding unrelated to the study. No other conflicts of interest were declared.

[email protected]

SOURCE: Schmitz K et al. CA Cancer J Clin. 2019 Oct 16. doi: 10.3322/caac.21579.

There is increasing evidence that exercise lowers the risk of developing cancer, improves survival after a cancer diagnosis, and helps ease related health outcomes. However, relatively few cancer patients meet current physical activity guidelines – often because it wasn’t recommended by their oncologist.

thinkstock

“Observed barriers to clinicians referring patients to exercise programming include lack of awareness of the potential value of exercise in cancer populations, uncertainty regarding the safety or suitability of exercise for a particular patient, lack of awareness regarding available programs to help facilitate exercise in cancer populations, need for education and skills development for making referrals, and a belief that referrals to exercise programming are not within the scope of practice for oncology clinicians,” Kathryn H. Schmitz, PhD, from Penn State University in Hershey and coauthors from the American College of Sports Medicine International Multidisciplinary Roundtable wrote in CA: A Cancer Journal for Clinicians.

Dr. Schmitz and colleagues proposed using the American College of Sports Medicine’s Exercise Is Medicine initiative to address this gap, with a focus on asking physicians to take an assess, revise, and refer approach to recommending exercise.

Noting that there is clear evidence that patients are more likely to exercise if their oncologist recommends that they do so, the authors said a clinician’s silence on the subject of exercise could be interpreted as “tacit approval to maintain inactivity.”

To assess a patient’s level of physical activity, the authors suggested asking patients how many days during the past week they had undertaken physical activity during which their heart beat faster or they breathed harder than normal for more than 30 minutes or how often they had undertaken activity to increase muscle strength.

If the patient can safely exercise without medical supervision, the authors recommend that clinicians advise patients to increase their physical activity to achieve current recommended levels. Clinicians can refer patients to community programs to help ramp up their activity.

However, for patients who may not be able to exercise safely on their own, the authors recommend referring them to an outpatient rehabiliation professional.

“Referral to appropriate and effective programs and follow-up with an assessment of progress (or lack thereof) at subsequent visits can serve as key transition points to change a patient’s behavior and affect their tolerance of or recovery from treatment,” they wrote.

The authors stressed that oncology clinicians were not expected to prescribe specific levels of exercise or to perform extensive screening and triage of patients based on their fitness.

“Oncology clinicians, however, play a vital role in telling the patient that it is important to exercise and pointing patients in the right direction to make that happen,” they wrote.

The American College of Sports Medicine International Multidisciplinary Roundtable was funded by the American College of Sports Medicine, the American Cancer Society, and other groups. Four authors declared grant support for participating in the study. One declared private industry funding unrelated to the study. No other conflicts of interest were declared.

[email protected]

SOURCE: Schmitz K et al. CA Cancer J Clin. 2019 Oct 16. doi: 10.3322/caac.21579.

There is increasing evidence that exercise lowers the risk of developing cancer, improves survival after a cancer diagnosis, and helps ease related health outcomes. However, relatively few cancer patients meet current physical activity guidelines – often because it wasn’t recommended by their oncologist.

thinkstock

“Observed barriers to clinicians referring patients to exercise programming include lack of awareness of the potential value of exercise in cancer populations, uncertainty regarding the safety or suitability of exercise for a particular patient, lack of awareness regarding available programs to help facilitate exercise in cancer populations, need for education and skills development for making referrals, and a belief that referrals to exercise programming are not within the scope of practice for oncology clinicians,” Kathryn H. Schmitz, PhD, from Penn State University in Hershey and coauthors from the American College of Sports Medicine International Multidisciplinary Roundtable wrote in CA: A Cancer Journal for Clinicians.

Dr. Schmitz and colleagues proposed using the American College of Sports Medicine’s Exercise Is Medicine initiative to address this gap, with a focus on asking physicians to take an assess, revise, and refer approach to recommending exercise.

Noting that there is clear evidence that patients are more likely to exercise if their oncologist recommends that they do so, the authors said a clinician’s silence on the subject of exercise could be interpreted as “tacit approval to maintain inactivity.”

To assess a patient’s level of physical activity, the authors suggested asking patients how many days during the past week they had undertaken physical activity during which their heart beat faster or they breathed harder than normal for more than 30 minutes or how often they had undertaken activity to increase muscle strength.

If the patient can safely exercise without medical supervision, the authors recommend that clinicians advise patients to increase their physical activity to achieve current recommended levels. Clinicians can refer patients to community programs to help ramp up their activity.

However, for patients who may not be able to exercise safely on their own, the authors recommend referring them to an outpatient rehabiliation professional.

“Referral to appropriate and effective programs and follow-up with an assessment of progress (or lack thereof) at subsequent visits can serve as key transition points to change a patient’s behavior and affect their tolerance of or recovery from treatment,” they wrote.

The authors stressed that oncology clinicians were not expected to prescribe specific levels of exercise or to perform extensive screening and triage of patients based on their fitness.

“Oncology clinicians, however, play a vital role in telling the patient that it is important to exercise and pointing patients in the right direction to make that happen,” they wrote.

The American College of Sports Medicine International Multidisciplinary Roundtable was funded by the American College of Sports Medicine, the American Cancer Society, and other groups. Four authors declared grant support for participating in the study. One declared private industry funding unrelated to the study. No other conflicts of interest were declared.

[email protected]

SOURCE: Schmitz K et al. CA Cancer J Clin. 2019 Oct 16. doi: 10.3322/caac.21579.

Early-career researchers who are interested in studying mantle cell lymphoma can now apply for a $50,000 grant from the American Society of Clinical Oncology’s Conquer Cancer foundation.

The young investigator grant is for a 1-year period and the award is used to fund a project focused on clinical or translational research on the clinical biology, natural history, prevention, screening, diagnosis, therapy, or epidemiology of MCL.

The purpose of this annual award, according to ASCO, is to fund physicians during the transition from a fellowship program to a faculty appointment.

Eligible applicants must be physicians currently in the last 2 years of final subspecialty training and within 10 years of having obtained his or her medical degree. Additionally, applicants must be planning a research career in clinical oncology, with a focus on MCL.

The grant selection committee’s primary criteria include the significance and originality of the proposed study and hypothesis, the feasibility of the experiment and methodology, whether it has an appropriate and detailed statistical analysis plan, and if the research is patient oriented.

The application deadline is Jan. 7, 2020, and the award term is July 1, 2020–June 30, 2021.

Application instructions are available on the ASCO website.

[email protected]

Early-career researchers who are interested in studying mantle cell lymphoma can now apply for a $50,000 grant from the American Society of Clinical Oncology’s Conquer Cancer foundation.

The young investigator grant is for a 1-year period and the award is used to fund a project focused on clinical or translational research on the clinical biology, natural history, prevention, screening, diagnosis, therapy, or epidemiology of MCL.

The purpose of this annual award, according to ASCO, is to fund physicians during the transition from a fellowship program to a faculty appointment.

Eligible applicants must be physicians currently in the last 2 years of final subspecialty training and within 10 years of having obtained his or her medical degree. Additionally, applicants must be planning a research career in clinical oncology, with a focus on MCL.

The grant selection committee’s primary criteria include the significance and originality of the proposed study and hypothesis, the feasibility of the experiment and methodology, whether it has an appropriate and detailed statistical analysis plan, and if the research is patient oriented.

The application deadline is Jan. 7, 2020, and the award term is July 1, 2020–June 30, 2021.

Application instructions are available on the ASCO website.

[email protected]

Early-career researchers who are interested in studying mantle cell lymphoma can now apply for a $50,000 grant from the American Society of Clinical Oncology’s Conquer Cancer foundation.

The young investigator grant is for a 1-year period and the award is used to fund a project focused on clinical or translational research on the clinical biology, natural history, prevention, screening, diagnosis, therapy, or epidemiology of MCL.

The purpose of this annual award, according to ASCO, is to fund physicians during the transition from a fellowship program to a faculty appointment.

Eligible applicants must be physicians currently in the last 2 years of final subspecialty training and within 10 years of having obtained his or her medical degree. Additionally, applicants must be planning a research career in clinical oncology, with a focus on MCL.

The grant selection committee’s primary criteria include the significance and originality of the proposed study and hypothesis, the feasibility of the experiment and methodology, whether it has an appropriate and detailed statistical analysis plan, and if the research is patient oriented.

The application deadline is Jan. 7, 2020, and the award term is July 1, 2020–June 30, 2021.

Application instructions are available on the ASCO website.

[email protected]

Among patients with human epidermal growth factor receptor 2–positive (HER2+) breast cancer, adding trastuzumab to adjuvant chemotherapy reduces risk of recurrence for at least 10 years, according to investigators.

The benefit of trastuzumab was greater among patients with hormone receptor–positive (HR+) disease than those with HR– disease until the 5-year timepoint, after which HR status had no significant impact on recurrence rates, reported lead author Saranya Chumsri, MD, of the Mayo Clinic in Jacksonville, Fla., and colleagues. This finding echoes a pattern similar to that of HER2– breast cancer, in which patients with HR+ disease have relatively consistent risk of recurrence over time, whereas patients with HR– disease have an early risk of recurrence that decreases after 5 years.

“To the best of our knowledge, this analysis is the first to address the risk of late relapses in subsets of HER2+ breast cancer patients who were treated with adjuvant trastuzumab,” the investigators wrote. Their report is in Journal of Clinical Oncology.

They drew data from 3,177 patients with HER2+ breast cancer who were involved in two phase 3 studies: the North Central Cancer Treatment Group N9831 and National Surgical Adjuvant Breast and Bowel Project B-31 trials. Patients involved in the analysis received either standard adjuvant chemotherapy with cyclophosphamide and doxorubicin followed by weekly paclitaxel or the same chemotherapy regimen plus concurrent trastuzumab. The primary outcome was recurrence-free survival, which was defined as time from randomization until local, regional, or distant recurrence of breast cancer or breast cancer–related death. Kaplan-Meier estimates were performed to determine recurrence-free survival, while Cox proportional hazards regression models were used to determine factors that predicted relapse.

Including a median follow-up of 8 years across all patients, the analysis showed that those with HR+ breast cancer had a significantly higher estimated rate of recurrence-free survival than that of those with HR– disease after 5 years (81.49% vs. 74.65%) and 10 years (73.84% vs. 69.22%). Overall, a comparable level of benefit was derived from adding trastuzumab regardless of HR status (interaction P = .87). However, during the first 5 years, HR positivity predicted greater benefit from adding trastuzumab, as patients with HR+ disease had a 40% lower risk of relapse than that of those with HR– disease (hazard ratio, 0.60; P less than .001). Between years 5 and 10, the statistical significance of HR status faded (P = .12), suggesting that HR status is not a predictor of long-term recurrence.

“Given concerning adverse effects and potentially smaller benefit of extended adjuvant endocrine therapy, particularly in patients with N0 or N1 disease, our findings highlight the need to develop better risk prediction models and biomarkers to identify which patients have sufficient risk for late relapse to warrant the use of extended endocrine therapy in HER2+ breast cancer,” the investigators concluded.

The study was funded by the National Institutes of Health, the Breast Cancer Research Foundation, Bankhead-Coley Research Program, the DONNA Foundation, and Genentech. Dr. Chumsri disclosed a financial relationship with Merck. Coauthors disclosed ties with Merck, Novartis, Genentech, and NanoString Technologies.

SOURCE: Chumsri et al. J Clin Oncol. 2019 Oct 17. doi: 10.1200/JCO.19.00443.

Among patients with human epidermal growth factor receptor 2–positive (HER2+) breast cancer, adding trastuzumab to adjuvant chemotherapy reduces risk of recurrence for at least 10 years, according to investigators.

The benefit of trastuzumab was greater among patients with hormone receptor–positive (HR+) disease than those with HR– disease until the 5-year timepoint, after which HR status had no significant impact on recurrence rates, reported lead author Saranya Chumsri, MD, of the Mayo Clinic in Jacksonville, Fla., and colleagues. This finding echoes a pattern similar to that of HER2– breast cancer, in which patients with HR+ disease have relatively consistent risk of recurrence over time, whereas patients with HR– disease have an early risk of recurrence that decreases after 5 years.

“To the best of our knowledge, this analysis is the first to address the risk of late relapses in subsets of HER2+ breast cancer patients who were treated with adjuvant trastuzumab,” the investigators wrote. Their report is in Journal of Clinical Oncology.

They drew data from 3,177 patients with HER2+ breast cancer who were involved in two phase 3 studies: the North Central Cancer Treatment Group N9831 and National Surgical Adjuvant Breast and Bowel Project B-31 trials. Patients involved in the analysis received either standard adjuvant chemotherapy with cyclophosphamide and doxorubicin followed by weekly paclitaxel or the same chemotherapy regimen plus concurrent trastuzumab. The primary outcome was recurrence-free survival, which was defined as time from randomization until local, regional, or distant recurrence of breast cancer or breast cancer–related death. Kaplan-Meier estimates were performed to determine recurrence-free survival, while Cox proportional hazards regression models were used to determine factors that predicted relapse.

Including a median follow-up of 8 years across all patients, the analysis showed that those with HR+ breast cancer had a significantly higher estimated rate of recurrence-free survival than that of those with HR– disease after 5 years (81.49% vs. 74.65%) and 10 years (73.84% vs. 69.22%). Overall, a comparable level of benefit was derived from adding trastuzumab regardless of HR status (interaction P = .87). However, during the first 5 years, HR positivity predicted greater benefit from adding trastuzumab, as patients with HR+ disease had a 40% lower risk of relapse than that of those with HR– disease (hazard ratio, 0.60; P less than .001). Between years 5 and 10, the statistical significance of HR status faded (P = .12), suggesting that HR status is not a predictor of long-term recurrence.

“Given concerning adverse effects and potentially smaller benefit of extended adjuvant endocrine therapy, particularly in patients with N0 or N1 disease, our findings highlight the need to develop better risk prediction models and biomarkers to identify which patients have sufficient risk for late relapse to warrant the use of extended endocrine therapy in HER2+ breast cancer,” the investigators concluded.

The study was funded by the National Institutes of Health, the Breast Cancer Research Foundation, Bankhead-Coley Research Program, the DONNA Foundation, and Genentech. Dr. Chumsri disclosed a financial relationship with Merck. Coauthors disclosed ties with Merck, Novartis, Genentech, and NanoString Technologies.

SOURCE: Chumsri et al. J Clin Oncol. 2019 Oct 17. doi: 10.1200/JCO.19.00443.

Among patients with human epidermal growth factor receptor 2–positive (HER2+) breast cancer, adding trastuzumab to adjuvant chemotherapy reduces risk of recurrence for at least 10 years, according to investigators.

The benefit of trastuzumab was greater among patients with hormone receptor–positive (HR+) disease than those with HR– disease until the 5-year timepoint, after which HR status had no significant impact on recurrence rates, reported lead author Saranya Chumsri, MD, of the Mayo Clinic in Jacksonville, Fla., and colleagues. This finding echoes a pattern similar to that of HER2– breast cancer, in which patients with HR+ disease have relatively consistent risk of recurrence over time, whereas patients with HR– disease have an early risk of recurrence that decreases after 5 years.

“To the best of our knowledge, this analysis is the first to address the risk of late relapses in subsets of HER2+ breast cancer patients who were treated with adjuvant trastuzumab,” the investigators wrote. Their report is in Journal of Clinical Oncology.

They drew data from 3,177 patients with HER2+ breast cancer who were involved in two phase 3 studies: the North Central Cancer Treatment Group N9831 and National Surgical Adjuvant Breast and Bowel Project B-31 trials. Patients involved in the analysis received either standard adjuvant chemotherapy with cyclophosphamide and doxorubicin followed by weekly paclitaxel or the same chemotherapy regimen plus concurrent trastuzumab. The primary outcome was recurrence-free survival, which was defined as time from randomization until local, regional, or distant recurrence of breast cancer or breast cancer–related death. Kaplan-Meier estimates were performed to determine recurrence-free survival, while Cox proportional hazards regression models were used to determine factors that predicted relapse.

Including a median follow-up of 8 years across all patients, the analysis showed that those with HR+ breast cancer had a significantly higher estimated rate of recurrence-free survival than that of those with HR– disease after 5 years (81.49% vs. 74.65%) and 10 years (73.84% vs. 69.22%). Overall, a comparable level of benefit was derived from adding trastuzumab regardless of HR status (interaction P = .87). However, during the first 5 years, HR positivity predicted greater benefit from adding trastuzumab, as patients with HR+ disease had a 40% lower risk of relapse than that of those with HR– disease (hazard ratio, 0.60; P less than .001). Between years 5 and 10, the statistical significance of HR status faded (P = .12), suggesting that HR status is not a predictor of long-term recurrence.

“Given concerning adverse effects and potentially smaller benefit of extended adjuvant endocrine therapy, particularly in patients with N0 or N1 disease, our findings highlight the need to develop better risk prediction models and biomarkers to identify which patients have sufficient risk for late relapse to warrant the use of extended endocrine therapy in HER2+ breast cancer,” the investigators concluded.

The study was funded by the National Institutes of Health, the Breast Cancer Research Foundation, Bankhead-Coley Research Program, the DONNA Foundation, and Genentech. Dr. Chumsri disclosed a financial relationship with Merck. Coauthors disclosed ties with Merck, Novartis, Genentech, and NanoString Technologies.

SOURCE: Chumsri et al. J Clin Oncol. 2019 Oct 17. doi: 10.1200/JCO.19.00443.

A pooled analysis suggests adverse cytogenetics are a key factor negatively impacting outcomes in patients with NPM1^mut/FLT3-ITD^neg/low acute myeloid leukemia (AML).

National Institutes of Health/Wikimedia Commons/Public Domain

In patients with adverse chromosomal abnormalities, NPM1 mutational status was found not to confer a favorable outcome. The findings suggest cytogenetic risk outweighs molecular risk in patients with NPM1 mutations and the FLT3-ITD^neg/low genotype.

“Patients carrying adverse-risk cytogenetics shared a virtually identical unfavorable outcome, regardless of whether the otherwise beneficial NPM1^mut/FLT3-ITD^neg/low status was present. The type of the adverse chromosomal abnormality did not seem to influence this effect, although low numbers might obscure detection of heterogeneity among individual aberrations,” Linus Angenendt, MD, of University Hospital Munster (Germany) and colleagues, wrote in the Journal of Clinical Oncology.

The researchers retrospectively analyzed 2,426 patients with NPM1^mut/FLT3-ITD^neg/low AML. Of these, 17.6% had an abnormal karyotype, and 3.4% had adverse-risk chromosomal aberrations.

Prior to analysis, individual patient data were pooled from nine international AML study group registries or treatment centers.

After analysis, the researchers found that adverse cytogenetics were associated with inferior complete remission rates (66.3%), compared with in patients with normal karyotype or intermediate-risk cytogenetic abnormalities (87.7% and 86.0%, respectively; P less than .001). The complete remission rates for the NPM1^mut/FLT3-ITD^neg/low AML adverse cytogenetics group was similar to patients with NPM1^wt/FLT3-ITD^neg/low and adverse cytogenetic abnormalities (66.3% vs. 57.5%).

Five-year event-free survival rates and overall survival rates were also lower in patients with NPM1^mut/FLT3-ITD^neg/low AML and adverse cytogenetics, compared with patients with normal karyotype or intermediate-risk cytogenetic abnormalities (P less than .001).

“Even though the combination of an NPM1 mutation with these abnormalities is rare, the prognostic effect of adverse cytogenetics in NPM1^mut AML has important implications for postremission treatment decisions, in particular, the current recommendation that patients who are NPM1^mut/FLT3-ITD^neg/low not receive allogeneic hematopoietic stem cell transplantation (HSCT), given their presumed low risk of relapse might be altered if the adverse karyotype increased the risk,” they wrote.

The type of chromosomal aberration did not appear to impact this effect, but the small sample size may have hindered the ability to detect a difference between different abnormalities, the researchers noted.

One key limitation of the study was the retrospective design. As a result, in patients with an abnormal karyotype, some genetic analyses could have been underutilized.

“These results demand additional validation within prospective trials,” the researchers concluded.

The study was funded by the University of Munster Medical School, the German Research Foundation, the French government, the Ministry of Health of the Czech Republic, and others. The authors reported financial affiliations with numerous pharmaceutical companies.

SOURCE: Angenendt L et al. J Clin Oncol. 2019 Oct 10;37(29):2632-42.

A pooled analysis suggests adverse cytogenetics are a key factor negatively impacting outcomes in patients with NPM1^mut/FLT3-ITD^neg/low acute myeloid leukemia (AML).

National Institutes of Health/Wikimedia Commons/Public Domain

In patients with adverse chromosomal abnormalities, NPM1 mutational status was found not to confer a favorable outcome. The findings suggest cytogenetic risk outweighs molecular risk in patients with NPM1 mutations and the FLT3-ITD^neg/low genotype.

“Patients carrying adverse-risk cytogenetics shared a virtually identical unfavorable outcome, regardless of whether the otherwise beneficial NPM1^mut/FLT3-ITD^neg/low status was present. The type of the adverse chromosomal abnormality did not seem to influence this effect, although low numbers might obscure detection of heterogeneity among individual aberrations,” Linus Angenendt, MD, of University Hospital Munster (Germany) and colleagues, wrote in the Journal of Clinical Oncology.

The researchers retrospectively analyzed 2,426 patients with NPM1^mut/FLT3-ITD^neg/low AML. Of these, 17.6% had an abnormal karyotype, and 3.4% had adverse-risk chromosomal aberrations.

Prior to analysis, individual patient data were pooled from nine international AML study group registries or treatment centers.

After analysis, the researchers found that adverse cytogenetics were associated with inferior complete remission rates (66.3%), compared with in patients with normal karyotype or intermediate-risk cytogenetic abnormalities (87.7% and 86.0%, respectively; P less than .001). The complete remission rates for the NPM1^mut/FLT3-ITD^neg/low AML adverse cytogenetics group was similar to patients with NPM1^wt/FLT3-ITD^neg/low and adverse cytogenetic abnormalities (66.3% vs. 57.5%).

Five-year event-free survival rates and overall survival rates were also lower in patients with NPM1^mut/FLT3-ITD^neg/low AML and adverse cytogenetics, compared with patients with normal karyotype or intermediate-risk cytogenetic abnormalities (P less than .001).

“Even though the combination of an NPM1 mutation with these abnormalities is rare, the prognostic effect of adverse cytogenetics in NPM1^mut AML has important implications for postremission treatment decisions, in particular, the current recommendation that patients who are NPM1^mut/FLT3-ITD^neg/low not receive allogeneic hematopoietic stem cell transplantation (HSCT), given their presumed low risk of relapse might be altered if the adverse karyotype increased the risk,” they wrote.

The type of chromosomal aberration did not appear to impact this effect, but the small sample size may have hindered the ability to detect a difference between different abnormalities, the researchers noted.

One key limitation of the study was the retrospective design. As a result, in patients with an abnormal karyotype, some genetic analyses could have been underutilized.

“These results demand additional validation within prospective trials,” the researchers concluded.

The study was funded by the University of Munster Medical School, the German Research Foundation, the French government, the Ministry of Health of the Czech Republic, and others. The authors reported financial affiliations with numerous pharmaceutical companies.

SOURCE: Angenendt L et al. J Clin Oncol. 2019 Oct 10;37(29):2632-42.

A pooled analysis suggests adverse cytogenetics are a key factor negatively impacting outcomes in patients with NPM1^mut/FLT3-ITD^neg/low acute myeloid leukemia (AML).

National Institutes of Health/Wikimedia Commons/Public Domain

In patients with adverse chromosomal abnormalities, NPM1 mutational status was found not to confer a favorable outcome. The findings suggest cytogenetic risk outweighs molecular risk in patients with NPM1 mutations and the FLT3-ITD^neg/low genotype.

“Patients carrying adverse-risk cytogenetics shared a virtually identical unfavorable outcome, regardless of whether the otherwise beneficial NPM1^mut/FLT3-ITD^neg/low status was present. The type of the adverse chromosomal abnormality did not seem to influence this effect, although low numbers might obscure detection of heterogeneity among individual aberrations,” Linus Angenendt, MD, of University Hospital Munster (Germany) and colleagues, wrote in the Journal of Clinical Oncology.

The researchers retrospectively analyzed 2,426 patients with NPM1^mut/FLT3-ITD^neg/low AML. Of these, 17.6% had an abnormal karyotype, and 3.4% had adverse-risk chromosomal aberrations.

Prior to analysis, individual patient data were pooled from nine international AML study group registries or treatment centers.

After analysis, the researchers found that adverse cytogenetics were associated with inferior complete remission rates (66.3%), compared with in patients with normal karyotype or intermediate-risk cytogenetic abnormalities (87.7% and 86.0%, respectively; P less than .001). The complete remission rates for the NPM1^mut/FLT3-ITD^neg/low AML adverse cytogenetics group was similar to patients with NPM1^wt/FLT3-ITD^neg/low and adverse cytogenetic abnormalities (66.3% vs. 57.5%).

Five-year event-free survival rates and overall survival rates were also lower in patients with NPM1^mut/FLT3-ITD^neg/low AML and adverse cytogenetics, compared with patients with normal karyotype or intermediate-risk cytogenetic abnormalities (P less than .001).

“Even though the combination of an NPM1 mutation with these abnormalities is rare, the prognostic effect of adverse cytogenetics in NPM1^mut AML has important implications for postremission treatment decisions, in particular, the current recommendation that patients who are NPM1^mut/FLT3-ITD^neg/low not receive allogeneic hematopoietic stem cell transplantation (HSCT), given their presumed low risk of relapse might be altered if the adverse karyotype increased the risk,” they wrote.

The type of chromosomal aberration did not appear to impact this effect, but the small sample size may have hindered the ability to detect a difference between different abnormalities, the researchers noted.

One key limitation of the study was the retrospective design. As a result, in patients with an abnormal karyotype, some genetic analyses could have been underutilized.

“These results demand additional validation within prospective trials,” the researchers concluded.

The study was funded by the University of Munster Medical School, the German Research Foundation, the French government, the Ministry of Health of the Czech Republic, and others. The authors reported financial affiliations with numerous pharmaceutical companies.

SOURCE: Angenendt L et al. J Clin Oncol. 2019 Oct 10;37(29):2632-42.

BARCELONA – Checkpoint inhibition with nivolumab led to a clinically meaningful, but not statistically significant, improvement in overall survival, compared with sorafenib for the first-line treatment of advanced hepatocellular carcinoma (HCC) in the phase 3 CheckMate 459 study.

Median overall survival (OS), the primary study endpoint, was 16.4 months in 371 patients randomized to receive the programmed death-1 (PD-1) inhibitor nivolumab, and 14.7 months in 372 patients who received the tyrosine kinase inhibitor sorafenib – the current standard for advanced HCC therapy (hazard ratio, 0.85; P = .0752), Thomas Yau, MD, reported at the European Society for Medical Oncology Congress.

The median OS seen with nivolumab is the longest ever reported in a first-line phase 3 HCC trial, but the difference between the arms did not meet the predefined threshold for statistical significance (HR, 0.84 and P = .419). However, clinical benefit was observed across predefined subgroups of patients, including those with hepatitis infection and those with vascular invasion and/or extrahepatic spread, said Dr. Yau of the University of Hong Kong.

The overall response rates (ORR) were 15% and 7% in the nivolumab and sorafenib arms, with 14 and 5 patients in each group experiencing a complete response (CR), respectively, he said.

At 12 and 24 months, the OS rates in the groups were 59.7% vs. 55.1%, and 36.5% vs. 33.1%, respectively. Median progression-free survival (PFS) was similar in the groups, at 3.7 and 3.8 months, respectively, and analysis by baseline tumor programmed death-ligand 1 (PD-L1) expression showed that ORR was 28% vs. 9% with PD-L1 expression of 1% or greater in the groups, respectively, and 12% vs. 7% among those with PD-L1 expression less than 1%.

Additionally, nivolumab had a more tolerable safety profile; grade 3/4 treatment-related adverse events were reported in 22% and 49% of patients in the groups, respectively, and led to discontinuation in 4% and 8%, respectively. No new safety signals were observed, Dr. Yau said.

Participants in the multicenter study were systemic therapy–naive adults with advanced disease. They were randomized 1:1 to receive intravenous nivolumab at a dose of 240 mg every 2 weeks or oral sorafenib at a dose of 400 mg twice daily, and were followed for at least 22.8 months.

“These results are important in the treatment of hepatocellular carcinoma, as there have been no significant advances over sorafenib in the first-line setting in more than a decade,” Dr. Yau said in an ESMO press release. “HCC is often diagnosed in the advanced stage, where effective treatment options are limited. The encouraging efficacy and favorable safety profile seen with nivolumab demonstrates the potential benefit of immunotherapy as a first-line treatment for patients with this aggressive cancer.”

He further noted that the OS benefit seen in this study is “particularly impactful considering the high frequency of subsequent use of systemic therapy, including immunotherapy, in the sorafenib arm,” and that the OS impact is bolstered by patient-reported outcomes suggesting improved quality of life in the nivolumab arm.

Nevertheless, the fact that CheckMate 459 did not meet its primary OS endpoint means the findings are unlikely to change the current standard of care, according to Angela Lamarca, MD, PhD, consultant medical oncologist and honorary senior lecturer at the Christie NHS Foundation Trust, University of Manchester (England).

She added, however, that the findings do underscore a potential role for immunotherapy in the first-line treatment of advanced HCC and noted that the clinically meaningful improvement in response rates with nivolumab, along with the checkpoint inhibitor’s favorable safety profile in this study, raise the possibility of its selection in this setting.

“In a hypothetical scenario in which both options ... were available and reimbursed, and if quality of life was shown to be better with nivolumab ... clinicians and patients may favor the option with a more tolerable safety profile,” she said in the press release.

She added, however, that at this point conclusions should be made cautiously and the high cost of immunotherapy should be considered.

Dr. Lamarca also highlighted the finding that patients with high PD-L1 expression had an increased response rate only in the nivolumab arm. This suggests a potential role for PD-L1 expression as a predictive biomarker in advanced HCC, but more research is needed to better understand how to select patients for immunotherapy, she said, adding that the lack of a reliable biomarker may have contributed to the study’s failure to show improved OS with nivolumab.

“In addition, the study design with a ‘high’ predefined threshold of statistical significance is generating confusion in the community, with potentially beneficial therapies generating statistically negative studies,” she noted.

CheckMate 459 was funded by Bristol-Myers Squibb. Dr. Yau is an advisor and/or consultant to Bristol-Myers Squibb, and reported honoraria from the company to his institution. Dr. Lamarca reported honoraria, consultation fees, travel funding, and/or education funding from Eisai, Nutricia, Ipsen, Pfizer, Bayer, AAA, Sirtex, Delcath, Novartis, and Mylan, as well as participation in company-sponsored speaker bureaus for Pfizer, Ipsen, Merck, and Incyte.

SOURCE: Yau T et al. ESMO 2019, Abstract LBA38-PR
 

BARCELONA – Checkpoint inhibition with nivolumab led to a clinically meaningful, but not statistically significant, improvement in overall survival, compared with sorafenib for the first-line treatment of advanced hepatocellular carcinoma (HCC) in the phase 3 CheckMate 459 study.

Median overall survival (OS), the primary study endpoint, was 16.4 months in 371 patients randomized to receive the programmed death-1 (PD-1) inhibitor nivolumab, and 14.7 months in 372 patients who received the tyrosine kinase inhibitor sorafenib – the current standard for advanced HCC therapy (hazard ratio, 0.85; P = .0752), Thomas Yau, MD, reported at the European Society for Medical Oncology Congress.

The median OS seen with nivolumab is the longest ever reported in a first-line phase 3 HCC trial, but the difference between the arms did not meet the predefined threshold for statistical significance (HR, 0.84 and P = .419). However, clinical benefit was observed across predefined subgroups of patients, including those with hepatitis infection and those with vascular invasion and/or extrahepatic spread, said Dr. Yau of the University of Hong Kong.

The overall response rates (ORR) were 15% and 7% in the nivolumab and sorafenib arms, with 14 and 5 patients in each group experiencing a complete response (CR), respectively, he said.

At 12 and 24 months, the OS rates in the groups were 59.7% vs. 55.1%, and 36.5% vs. 33.1%, respectively. Median progression-free survival (PFS) was similar in the groups, at 3.7 and 3.8 months, respectively, and analysis by baseline tumor programmed death-ligand 1 (PD-L1) expression showed that ORR was 28% vs. 9% with PD-L1 expression of 1% or greater in the groups, respectively, and 12% vs. 7% among those with PD-L1 expression less than 1%.

Additionally, nivolumab had a more tolerable safety profile; grade 3/4 treatment-related adverse events were reported in 22% and 49% of patients in the groups, respectively, and led to discontinuation in 4% and 8%, respectively. No new safety signals were observed, Dr. Yau said.

Participants in the multicenter study were systemic therapy–naive adults with advanced disease. They were randomized 1:1 to receive intravenous nivolumab at a dose of 240 mg every 2 weeks or oral sorafenib at a dose of 400 mg twice daily, and were followed for at least 22.8 months.

“These results are important in the treatment of hepatocellular carcinoma, as there have been no significant advances over sorafenib in the first-line setting in more than a decade,” Dr. Yau said in an ESMO press release. “HCC is often diagnosed in the advanced stage, where effective treatment options are limited. The encouraging efficacy and favorable safety profile seen with nivolumab demonstrates the potential benefit of immunotherapy as a first-line treatment for patients with this aggressive cancer.”

He further noted that the OS benefit seen in this study is “particularly impactful considering the high frequency of subsequent use of systemic therapy, including immunotherapy, in the sorafenib arm,” and that the OS impact is bolstered by patient-reported outcomes suggesting improved quality of life in the nivolumab arm.

Nevertheless, the fact that CheckMate 459 did not meet its primary OS endpoint means the findings are unlikely to change the current standard of care, according to Angela Lamarca, MD, PhD, consultant medical oncologist and honorary senior lecturer at the Christie NHS Foundation Trust, University of Manchester (England).

She added, however, that the findings do underscore a potential role for immunotherapy in the first-line treatment of advanced HCC and noted that the clinically meaningful improvement in response rates with nivolumab, along with the checkpoint inhibitor’s favorable safety profile in this study, raise the possibility of its selection in this setting.

“In a hypothetical scenario in which both options ... were available and reimbursed, and if quality of life was shown to be better with nivolumab ... clinicians and patients may favor the option with a more tolerable safety profile,” she said in the press release.

She added, however, that at this point conclusions should be made cautiously and the high cost of immunotherapy should be considered.

Dr. Lamarca also highlighted the finding that patients with high PD-L1 expression had an increased response rate only in the nivolumab arm. This suggests a potential role for PD-L1 expression as a predictive biomarker in advanced HCC, but more research is needed to better understand how to select patients for immunotherapy, she said, adding that the lack of a reliable biomarker may have contributed to the study’s failure to show improved OS with nivolumab.

“In addition, the study design with a ‘high’ predefined threshold of statistical significance is generating confusion in the community, with potentially beneficial therapies generating statistically negative studies,” she noted.

CheckMate 459 was funded by Bristol-Myers Squibb. Dr. Yau is an advisor and/or consultant to Bristol-Myers Squibb, and reported honoraria from the company to his institution. Dr. Lamarca reported honoraria, consultation fees, travel funding, and/or education funding from Eisai, Nutricia, Ipsen, Pfizer, Bayer, AAA, Sirtex, Delcath, Novartis, and Mylan, as well as participation in company-sponsored speaker bureaus for Pfizer, Ipsen, Merck, and Incyte.

SOURCE: Yau T et al. ESMO 2019, Abstract LBA38-PR
 

BARCELONA – Checkpoint inhibition with nivolumab led to a clinically meaningful, but not statistically significant, improvement in overall survival, compared with sorafenib for the first-line treatment of advanced hepatocellular carcinoma (HCC) in the phase 3 CheckMate 459 study.

Median overall survival (OS), the primary study endpoint, was 16.4 months in 371 patients randomized to receive the programmed death-1 (PD-1) inhibitor nivolumab, and 14.7 months in 372 patients who received the tyrosine kinase inhibitor sorafenib – the current standard for advanced HCC therapy (hazard ratio, 0.85; P = .0752), Thomas Yau, MD, reported at the European Society for Medical Oncology Congress.

The median OS seen with nivolumab is the longest ever reported in a first-line phase 3 HCC trial, but the difference between the arms did not meet the predefined threshold for statistical significance (HR, 0.84 and P = .419). However, clinical benefit was observed across predefined subgroups of patients, including those with hepatitis infection and those with vascular invasion and/or extrahepatic spread, said Dr. Yau of the University of Hong Kong.

The overall response rates (ORR) were 15% and 7% in the nivolumab and sorafenib arms, with 14 and 5 patients in each group experiencing a complete response (CR), respectively, he said.

At 12 and 24 months, the OS rates in the groups were 59.7% vs. 55.1%, and 36.5% vs. 33.1%, respectively. Median progression-free survival (PFS) was similar in the groups, at 3.7 and 3.8 months, respectively, and analysis by baseline tumor programmed death-ligand 1 (PD-L1) expression showed that ORR was 28% vs. 9% with PD-L1 expression of 1% or greater in the groups, respectively, and 12% vs. 7% among those with PD-L1 expression less than 1%.

Additionally, nivolumab had a more tolerable safety profile; grade 3/4 treatment-related adverse events were reported in 22% and 49% of patients in the groups, respectively, and led to discontinuation in 4% and 8%, respectively. No new safety signals were observed, Dr. Yau said.

Participants in the multicenter study were systemic therapy–naive adults with advanced disease. They were randomized 1:1 to receive intravenous nivolumab at a dose of 240 mg every 2 weeks or oral sorafenib at a dose of 400 mg twice daily, and were followed for at least 22.8 months.

“These results are important in the treatment of hepatocellular carcinoma, as there have been no significant advances over sorafenib in the first-line setting in more than a decade,” Dr. Yau said in an ESMO press release. “HCC is often diagnosed in the advanced stage, where effective treatment options are limited. The encouraging efficacy and favorable safety profile seen with nivolumab demonstrates the potential benefit of immunotherapy as a first-line treatment for patients with this aggressive cancer.”

He further noted that the OS benefit seen in this study is “particularly impactful considering the high frequency of subsequent use of systemic therapy, including immunotherapy, in the sorafenib arm,” and that the OS impact is bolstered by patient-reported outcomes suggesting improved quality of life in the nivolumab arm.

Nevertheless, the fact that CheckMate 459 did not meet its primary OS endpoint means the findings are unlikely to change the current standard of care, according to Angela Lamarca, MD, PhD, consultant medical oncologist and honorary senior lecturer at the Christie NHS Foundation Trust, University of Manchester (England).

She added, however, that the findings do underscore a potential role for immunotherapy in the first-line treatment of advanced HCC and noted that the clinically meaningful improvement in response rates with nivolumab, along with the checkpoint inhibitor’s favorable safety profile in this study, raise the possibility of its selection in this setting.

“In a hypothetical scenario in which both options ... were available and reimbursed, and if quality of life was shown to be better with nivolumab ... clinicians and patients may favor the option with a more tolerable safety profile,” she said in the press release.

She added, however, that at this point conclusions should be made cautiously and the high cost of immunotherapy should be considered.

Dr. Lamarca also highlighted the finding that patients with high PD-L1 expression had an increased response rate only in the nivolumab arm. This suggests a potential role for PD-L1 expression as a predictive biomarker in advanced HCC, but more research is needed to better understand how to select patients for immunotherapy, she said, adding that the lack of a reliable biomarker may have contributed to the study’s failure to show improved OS with nivolumab.

“In addition, the study design with a ‘high’ predefined threshold of statistical significance is generating confusion in the community, with potentially beneficial therapies generating statistically negative studies,” she noted.

CheckMate 459 was funded by Bristol-Myers Squibb. Dr. Yau is an advisor and/or consultant to Bristol-Myers Squibb, and reported honoraria from the company to his institution. Dr. Lamarca reported honoraria, consultation fees, travel funding, and/or education funding from Eisai, Nutricia, Ipsen, Pfizer, Bayer, AAA, Sirtex, Delcath, Novartis, and Mylan, as well as participation in company-sponsored speaker bureaus for Pfizer, Ipsen, Merck, and Incyte.

SOURCE: Yau T et al. ESMO 2019, Abstract LBA38-PR
 

Patients 50-79 years old with a demonstrably low risk of developing the disease within 15 years probably don’t need to be screened for colorectal cancer. But if their risk of disease is at least 3% over 15 years, patients should be screened, Lise M. Helsingen, MD, and colleagues wrote in BMJ (2019;367:l5515 doi: 10.1136/bmj.l5515).

For these patients, “We suggest screening with one of the four screening options: fecal immunochemical test (FIT) every year, FIT every 2 years, a single sigmoidoscopy, or a single colonoscopy,” wrote Dr. Helsingen of the University of Oslo, and her team.

She chaired a 22-member international panel that developed a collaborative effort from the MAGIC research and innovation program as a part of the BMJ Rapid Recommendations project. The team reviewed 12 research papers comprising almost 1.4 million patients from Denmark, Italy, the Netherlands, Norway, Poland, Spain, Sweden, the United Kingdom, and the United States. Follow-up ranged from 0 to 19.5 years for colorectal cancer incidence and up to 30 years for mortality.

Because of the dearth of relevant data in some studies, however, the projected outcomes had to be simulated, with benefits and harms calculations based on 100% screening adherence. However, the team noted, it’s impossible to achieve complete adherence. Most studies of colorectal screening don’t exceed a 50% adherence level.

“All the modeling data are of low certainty. It is a useful indication, but there is a high chance that new evidence will show a smaller or larger benefit, which in turn may alter these recommendations.”

Compared with no screening, all four screening models reduced the risk of colorectal cancer mortality to a similar level.

• FIT every year, 59%.
• FIT every 2 years, 50%.
• Single sigmoidoscopy, 52%.
• Single colonoscopy, 67%.

Screening had less of an impact on reducing the incidence of colorectal cancer:

• FIT every 2 years, 0.05%.
• FIT every year, 0.15%.
• Single sigmoidoscopy, 27%.
• Single colonoscopy, 34%.

The panel also assessed potential harms. Among almost 1 million patients, the colonoscopy-related mortality rate was 0.03 per 1,000 procedures. The perforation rate was 0.8 per 1,000 colonoscopies after a positive fecal test, and 1.4 per 1,000 screened with sigmoidoscopy. The bleeding rate was 1.9 per 1,000 colonoscopies performed after a positive fecal test, and 3-4 per 1,000 screened with sigmoidoscopy.

Successful implementation of these recommendations hinges on accurate risk assessment, however. The team recommended the QCancer platform as “one of the best performing models for both men and women.”

The calculator includes age, sex, ethnicity, smoking status, alcohol use, family history of gastrointestinal cancer, personal history of other cancers, diabetes, ulcerative colitis, colonic polyps, and body mass index.

“We suggest this model because it is available as an online calculator; includes only risk factors available in routine health care; has been validated in a population separate from the derivation population; has reasonable discriminatory ability; and has a good fit between predicted and observed outcomes. In addition, it is the only online risk calculator we know of that predicts risk over a 15-year time horizon.”

The team stressed that their recommendations can’t be applied to all patients. Because evidence for both screening recommendations was weak – largely because of the dearth of supporting data – patients and physicians should cocreate a personalized screening plan.

“Several factors influence individuals’ decisions whether to be screened, even when they are presented with the same information,” the authors said. These include variation in an individual’s values and preferences, a close balance of benefits versus harms and burdens, and personal preference.

“Some individuals may value a minimally invasive test such as FIT, and the possibility of invasive screening with colonoscopy might put them off screening altogether. Those who most value preventing colorectal cancer or avoiding repeated testing are likely to choose sigmoidoscopy or colonoscopy.”

The authors had no financial conflicts of interest.

SOURCE: BMJ 2019;367:l5515. doi: 10.1136/bmj.l5515.

Patients 50-79 years old with a demonstrably low risk of developing the disease within 15 years probably don’t need to be screened for colorectal cancer. But if their risk of disease is at least 3% over 15 years, patients should be screened, Lise M. Helsingen, MD, and colleagues wrote in BMJ (2019;367:l5515 doi: 10.1136/bmj.l5515).

For these patients, “We suggest screening with one of the four screening options: fecal immunochemical test (FIT) every year, FIT every 2 years, a single sigmoidoscopy, or a single colonoscopy,” wrote Dr. Helsingen of the University of Oslo, and her team.

She chaired a 22-member international panel that developed a collaborative effort from the MAGIC research and innovation program as a part of the BMJ Rapid Recommendations project. The team reviewed 12 research papers comprising almost 1.4 million patients from Denmark, Italy, the Netherlands, Norway, Poland, Spain, Sweden, the United Kingdom, and the United States. Follow-up ranged from 0 to 19.5 years for colorectal cancer incidence and up to 30 years for mortality.

Because of the dearth of relevant data in some studies, however, the projected outcomes had to be simulated, with benefits and harms calculations based on 100% screening adherence. However, the team noted, it’s impossible to achieve complete adherence. Most studies of colorectal screening don’t exceed a 50% adherence level.

“All the modeling data are of low certainty. It is a useful indication, but there is a high chance that new evidence will show a smaller or larger benefit, which in turn may alter these recommendations.”

Compared with no screening, all four screening models reduced the risk of colorectal cancer mortality to a similar level.

• FIT every year, 59%.
• FIT every 2 years, 50%.
• Single sigmoidoscopy, 52%.
• Single colonoscopy, 67%.

Screening had less of an impact on reducing the incidence of colorectal cancer:

• FIT every 2 years, 0.05%.
• FIT every year, 0.15%.
• Single sigmoidoscopy, 27%.
• Single colonoscopy, 34%.

The panel also assessed potential harms. Among almost 1 million patients, the colonoscopy-related mortality rate was 0.03 per 1,000 procedures. The perforation rate was 0.8 per 1,000 colonoscopies after a positive fecal test, and 1.4 per 1,000 screened with sigmoidoscopy. The bleeding rate was 1.9 per 1,000 colonoscopies performed after a positive fecal test, and 3-4 per 1,000 screened with sigmoidoscopy.

Successful implementation of these recommendations hinges on accurate risk assessment, however. The team recommended the QCancer platform as “one of the best performing models for both men and women.”

The calculator includes age, sex, ethnicity, smoking status, alcohol use, family history of gastrointestinal cancer, personal history of other cancers, diabetes, ulcerative colitis, colonic polyps, and body mass index.

“We suggest this model because it is available as an online calculator; includes only risk factors available in routine health care; has been validated in a population separate from the derivation population; has reasonable discriminatory ability; and has a good fit between predicted and observed outcomes. In addition, it is the only online risk calculator we know of that predicts risk over a 15-year time horizon.”

The team stressed that their recommendations can’t be applied to all patients. Because evidence for both screening recommendations was weak – largely because of the dearth of supporting data – patients and physicians should cocreate a personalized screening plan.

“Several factors influence individuals’ decisions whether to be screened, even when they are presented with the same information,” the authors said. These include variation in an individual’s values and preferences, a close balance of benefits versus harms and burdens, and personal preference.

“Some individuals may value a minimally invasive test such as FIT, and the possibility of invasive screening with colonoscopy might put them off screening altogether. Those who most value preventing colorectal cancer or avoiding repeated testing are likely to choose sigmoidoscopy or colonoscopy.”

The authors had no financial conflicts of interest.

SOURCE: BMJ 2019;367:l5515. doi: 10.1136/bmj.l5515.

Patients 50-79 years old with a demonstrably low risk of developing the disease within 15 years probably don’t need to be screened for colorectal cancer. But if their risk of disease is at least 3% over 15 years, patients should be screened, Lise M. Helsingen, MD, and colleagues wrote in BMJ (2019;367:l5515 doi: 10.1136/bmj.l5515).

For these patients, “We suggest screening with one of the four screening options: fecal immunochemical test (FIT) every year, FIT every 2 years, a single sigmoidoscopy, or a single colonoscopy,” wrote Dr. Helsingen of the University of Oslo, and her team.

She chaired a 22-member international panel that developed a collaborative effort from the MAGIC research and innovation program as a part of the BMJ Rapid Recommendations project. The team reviewed 12 research papers comprising almost 1.4 million patients from Denmark, Italy, the Netherlands, Norway, Poland, Spain, Sweden, the United Kingdom, and the United States. Follow-up ranged from 0 to 19.5 years for colorectal cancer incidence and up to 30 years for mortality.

Because of the dearth of relevant data in some studies, however, the projected outcomes had to be simulated, with benefits and harms calculations based on 100% screening adherence. However, the team noted, it’s impossible to achieve complete adherence. Most studies of colorectal screening don’t exceed a 50% adherence level.

“All the modeling data are of low certainty. It is a useful indication, but there is a high chance that new evidence will show a smaller or larger benefit, which in turn may alter these recommendations.”

Compared with no screening, all four screening models reduced the risk of colorectal cancer mortality to a similar level.

• FIT every year, 59%.
• FIT every 2 years, 50%.
• Single sigmoidoscopy, 52%.
• Single colonoscopy, 67%.

Screening had less of an impact on reducing the incidence of colorectal cancer:

• FIT every 2 years, 0.05%.
• FIT every year, 0.15%.
• Single sigmoidoscopy, 27%.
• Single colonoscopy, 34%.

The panel also assessed potential harms. Among almost 1 million patients, the colonoscopy-related mortality rate was 0.03 per 1,000 procedures. The perforation rate was 0.8 per 1,000 colonoscopies after a positive fecal test, and 1.4 per 1,000 screened with sigmoidoscopy. The bleeding rate was 1.9 per 1,000 colonoscopies performed after a positive fecal test, and 3-4 per 1,000 screened with sigmoidoscopy.

Successful implementation of these recommendations hinges on accurate risk assessment, however. The team recommended the QCancer platform as “one of the best performing models for both men and women.”

The calculator includes age, sex, ethnicity, smoking status, alcohol use, family history of gastrointestinal cancer, personal history of other cancers, diabetes, ulcerative colitis, colonic polyps, and body mass index.

“We suggest this model because it is available as an online calculator; includes only risk factors available in routine health care; has been validated in a population separate from the derivation population; has reasonable discriminatory ability; and has a good fit between predicted and observed outcomes. In addition, it is the only online risk calculator we know of that predicts risk over a 15-year time horizon.”

The team stressed that their recommendations can’t be applied to all patients. Because evidence for both screening recommendations was weak – largely because of the dearth of supporting data – patients and physicians should cocreate a personalized screening plan.

“Several factors influence individuals’ decisions whether to be screened, even when they are presented with the same information,” the authors said. These include variation in an individual’s values and preferences, a close balance of benefits versus harms and burdens, and personal preference.

“Some individuals may value a minimally invasive test such as FIT, and the possibility of invasive screening with colonoscopy might put them off screening altogether. Those who most value preventing colorectal cancer or avoiding repeated testing are likely to choose sigmoidoscopy or colonoscopy.”

The authors had no financial conflicts of interest.

SOURCE: BMJ 2019;367:l5515. doi: 10.1136/bmj.l5515.

MINNEAPOLIS -- Medical professionals within the US Department of Veterans Affairs (VA) can’t prescribe cannabis or certify patients to be able to get it. VA pharmacists can’t dispense it. Still, “we’re asked about it plenty,” a hospice and palliative care specialist told colleagues, at the annual meeting of the Association of VA Hematology/Oncology (AVAHO).

That brings up a big question, said Michael Stellini, MD, MS, FACP, FAAHPM, of Wayne State University, Karmanos Cancer Center, and the John D. Dingell VA Medical Center, in Detroit Michigan: “Should sick people be smoking pot?”

Even the question itself isn’t a simple one to answer since smoking isn’t the only way to consume cannabis for medical purposes. And figuring out the best advice is difficult. As Dr. Stellini said, there’s plenty of uncertainty about crucial cannabis topics like safety and benefits.

Dr. Stellini offered a number of facts and tips about cannabis in medicine.

Understand ‘qualifying conditions’ in your state

In states with legal medical marijuana, he said, physicians do not prescribe marijuana. However, they may certify that patients are eligible to get the drug for medical purposes if they meet certain qualifications.

A typical list of qualifying conditions includes diseases such as cancer, glaucoma, HIV/AIDS and Crohn’s disease. Qualifying conditions also tend to include treatments for severe diseases that produce wasting syndrome, severe and chronic pain, severe nausea, seizures and severe and persistent muscle spasm.

In Michigan, where Dr. Stellini practices, a panel in 2018 approved a long list of added qualifying conditions such as chronic pain, obsessive compulsive disorder and arthritis. But the panel rejected other conditions such as anxiety, asthma, panic attacks and schizophrenia.

Vaporizers are an alternative to joints, but...

Vaporizers are commonly used as an alternative to smoking marijuana joints, Dr. Stellini said, and they don’t significantly release tars or much if any carbon monoxide. While research is limited, he said, use of vaporizers hasn’t been linked to more lung cancer or chronic obstructive pulmonary disease.

“Vaping” is another option, but it’s been linked to dozens of deaths and hundreds of cases of illness in recent weeks. Many patients have reported using products that contain THC, a component of marijuana.

Other delivery methods exist

Marijuana can be ingested in liquid and solid food. “But edibles can have a slow onset of action compared to vaporizing or smoking,” Dr. Stellini said. “You might over-indulge. When users get to their steady state, they might have some adverse effects [AEs].”

Marijuana still has risks

Cannabis use has a long list of well-known AEs linked to the THC component. The most common are drowsiness, fatigue, dizziness, dry mouth, anxiety, cognitive effects, cough, and nausea, Dr. Stellini said. More serious AEs such as psychosis have been reported.

And, of course, users of cannabis with THC get high if they use enough.

A 2017 National Academies of Sciences, Engineering and Medicine report linked cannabis use to a higher risk of motor vehicle accidents. Still, Dr. Stellini said, “it’s relatively safe with respect to mortality, especially compared to opioids.”¹

Risk of use in cancer may be low

Research suggest that patients with cancer use cannabis as much as other people and perhaps even more, Dr. Stellini said. But are they facing any extra risks? In general, he said, it doesn’t appear that way.

Cannabis seems to be safe when used with chemotherapy, he said, and drug-drug interactions in cancer appear to be rare. Some studies have suggested that cannabinoids—a component of marijuana—may be an effective treatment for chemotherapy-induced peripheral neuropathy.

However, he said, 1 study has raised a red flag about a possible interaction with cancer immunotherapy. Researchers found evidence that patients who used cannabis had lower tumor response rates to nivolomab for advanced melanoma, non-small cell lung cancer, and renal clear cell carcinoma. However, survival wasn’t affected.²

Meanwhile, he said, there’s no strong evidence that cannabis is a useful treatment for cancer, he said, although it’s worth investigating.

Cannabidiol is the hot new product

Cannabidiol, also known as CBD, has become hugely popular, Dr. Stellini said. It is derived from hemp and doesn’t cause a “buzz” like cannabis.

Due to lack of regulation, he said, buyers should beware. And, he said, CBD has multiple EAs. Standard doses can cause drowsiness, fatigue, dizziness, dry mouth, hypotension and lightheadedness.

Dr. Stellini reports no relevant disclosures.

MINNEAPOLIS -- Medical professionals within the US Department of Veterans Affairs (VA) can’t prescribe cannabis or certify patients to be able to get it. VA pharmacists can’t dispense it. Still, “we’re asked about it plenty,” a hospice and palliative care specialist told colleagues, at the annual meeting of the Association of VA Hematology/Oncology (AVAHO).

That brings up a big question, said Michael Stellini, MD, MS, FACP, FAAHPM, of Wayne State University, Karmanos Cancer Center, and the John D. Dingell VA Medical Center, in Detroit Michigan: “Should sick people be smoking pot?”

Even the question itself isn’t a simple one to answer since smoking isn’t the only way to consume cannabis for medical purposes. And figuring out the best advice is difficult. As Dr. Stellini said, there’s plenty of uncertainty about crucial cannabis topics like safety and benefits.

Dr. Stellini offered a number of facts and tips about cannabis in medicine.

Understand ‘qualifying conditions’ in your state

In states with legal medical marijuana, he said, physicians do not prescribe marijuana. However, they may certify that patients are eligible to get the drug for medical purposes if they meet certain qualifications.

A typical list of qualifying conditions includes diseases such as cancer, glaucoma, HIV/AIDS and Crohn’s disease. Qualifying conditions also tend to include treatments for severe diseases that produce wasting syndrome, severe and chronic pain, severe nausea, seizures and severe and persistent muscle spasm.

In Michigan, where Dr. Stellini practices, a panel in 2018 approved a long list of added qualifying conditions such as chronic pain, obsessive compulsive disorder and arthritis. But the panel rejected other conditions such as anxiety, asthma, panic attacks and schizophrenia.

Vaporizers are an alternative to joints, but...

Vaporizers are commonly used as an alternative to smoking marijuana joints, Dr. Stellini said, and they don’t significantly release tars or much if any carbon monoxide. While research is limited, he said, use of vaporizers hasn’t been linked to more lung cancer or chronic obstructive pulmonary disease.

“Vaping” is another option, but it’s been linked to dozens of deaths and hundreds of cases of illness in recent weeks. Many patients have reported using products that contain THC, a component of marijuana.

Other delivery methods exist

Marijuana can be ingested in liquid and solid food. “But edibles can have a slow onset of action compared to vaporizing or smoking,” Dr. Stellini said. “You might over-indulge. When users get to their steady state, they might have some adverse effects [AEs].”

Marijuana still has risks

Cannabis use has a long list of well-known AEs linked to the THC component. The most common are drowsiness, fatigue, dizziness, dry mouth, anxiety, cognitive effects, cough, and nausea, Dr. Stellini said. More serious AEs such as psychosis have been reported.

And, of course, users of cannabis with THC get high if they use enough.

A 2017 National Academies of Sciences, Engineering and Medicine report linked cannabis use to a higher risk of motor vehicle accidents. Still, Dr. Stellini said, “it’s relatively safe with respect to mortality, especially compared to opioids.”¹

Risk of use in cancer may be low

Research suggest that patients with cancer use cannabis as much as other people and perhaps even more, Dr. Stellini said. But are they facing any extra risks? In general, he said, it doesn’t appear that way.

Cannabis seems to be safe when used with chemotherapy, he said, and drug-drug interactions in cancer appear to be rare. Some studies have suggested that cannabinoids—a component of marijuana—may be an effective treatment for chemotherapy-induced peripheral neuropathy.

However, he said, 1 study has raised a red flag about a possible interaction with cancer immunotherapy. Researchers found evidence that patients who used cannabis had lower tumor response rates to nivolomab for advanced melanoma, non-small cell lung cancer, and renal clear cell carcinoma. However, survival wasn’t affected.²

Meanwhile, he said, there’s no strong evidence that cannabis is a useful treatment for cancer, he said, although it’s worth investigating.

Cannabidiol is the hot new product

Cannabidiol, also known as CBD, has become hugely popular, Dr. Stellini said. It is derived from hemp and doesn’t cause a “buzz” like cannabis.

Due to lack of regulation, he said, buyers should beware. And, he said, CBD has multiple EAs. Standard doses can cause drowsiness, fatigue, dizziness, dry mouth, hypotension and lightheadedness.

Dr. Stellini reports no relevant disclosures.

MINNEAPOLIS -- Medical professionals within the US Department of Veterans Affairs (VA) can’t prescribe cannabis or certify patients to be able to get it. VA pharmacists can’t dispense it. Still, “we’re asked about it plenty,” a hospice and palliative care specialist told colleagues, at the annual meeting of the Association of VA Hematology/Oncology (AVAHO).

That brings up a big question, said Michael Stellini, MD, MS, FACP, FAAHPM, of Wayne State University, Karmanos Cancer Center, and the John D. Dingell VA Medical Center, in Detroit Michigan: “Should sick people be smoking pot?”

Even the question itself isn’t a simple one to answer since smoking isn’t the only way to consume cannabis for medical purposes. And figuring out the best advice is difficult. As Dr. Stellini said, there’s plenty of uncertainty about crucial cannabis topics like safety and benefits.

Dr. Stellini offered a number of facts and tips about cannabis in medicine.

Understand ‘qualifying conditions’ in your state

In states with legal medical marijuana, he said, physicians do not prescribe marijuana. However, they may certify that patients are eligible to get the drug for medical purposes if they meet certain qualifications.

A typical list of qualifying conditions includes diseases such as cancer, glaucoma, HIV/AIDS and Crohn’s disease. Qualifying conditions also tend to include treatments for severe diseases that produce wasting syndrome, severe and chronic pain, severe nausea, seizures and severe and persistent muscle spasm.

In Michigan, where Dr. Stellini practices, a panel in 2018 approved a long list of added qualifying conditions such as chronic pain, obsessive compulsive disorder and arthritis. But the panel rejected other conditions such as anxiety, asthma, panic attacks and schizophrenia.

Vaporizers are an alternative to joints, but...

Vaporizers are commonly used as an alternative to smoking marijuana joints, Dr. Stellini said, and they don’t significantly release tars or much if any carbon monoxide. While research is limited, he said, use of vaporizers hasn’t been linked to more lung cancer or chronic obstructive pulmonary disease.

“Vaping” is another option, but it’s been linked to dozens of deaths and hundreds of cases of illness in recent weeks. Many patients have reported using products that contain THC, a component of marijuana.

Other delivery methods exist

Marijuana can be ingested in liquid and solid food. “But edibles can have a slow onset of action compared to vaporizing or smoking,” Dr. Stellini said. “You might over-indulge. When users get to their steady state, they might have some adverse effects [AEs].”

Marijuana still has risks

Cannabis use has a long list of well-known AEs linked to the THC component. The most common are drowsiness, fatigue, dizziness, dry mouth, anxiety, cognitive effects, cough, and nausea, Dr. Stellini said. More serious AEs such as psychosis have been reported.

And, of course, users of cannabis with THC get high if they use enough.

A 2017 National Academies of Sciences, Engineering and Medicine report linked cannabis use to a higher risk of motor vehicle accidents. Still, Dr. Stellini said, “it’s relatively safe with respect to mortality, especially compared to opioids.”¹

Risk of use in cancer may be low

Research suggest that patients with cancer use cannabis as much as other people and perhaps even more, Dr. Stellini said. But are they facing any extra risks? In general, he said, it doesn’t appear that way.

Cannabis seems to be safe when used with chemotherapy, he said, and drug-drug interactions in cancer appear to be rare. Some studies have suggested that cannabinoids—a component of marijuana—may be an effective treatment for chemotherapy-induced peripheral neuropathy.

However, he said, 1 study has raised a red flag about a possible interaction with cancer immunotherapy. Researchers found evidence that patients who used cannabis had lower tumor response rates to nivolomab for advanced melanoma, non-small cell lung cancer, and renal clear cell carcinoma. However, survival wasn’t affected.²

Meanwhile, he said, there’s no strong evidence that cannabis is a useful treatment for cancer, he said, although it’s worth investigating.

Cannabidiol is the hot new product

Cannabidiol, also known as CBD, has become hugely popular, Dr. Stellini said. It is derived from hemp and doesn’t cause a “buzz” like cannabis.

Due to lack of regulation, he said, buyers should beware. And, he said, CBD has multiple EAs. Standard doses can cause drowsiness, fatigue, dizziness, dry mouth, hypotension and lightheadedness.

Dr. Stellini reports no relevant disclosures.