AVAHO

Recently updated colorectal cancer (CRC) screening guidance from the American College of Physicians is raising concerns among some specialists.

The ACP’s clinical guidance, published in Annals of Internal Medicine, called for CRC screenings to start at age 50 in average-risk individuals who are asymptomatic. This recommendation, however, conflicts with guidelines from the American Cancer Society and the U.S. Preventive Services Task Force, which, in 2021, officially lowered the recommended initial age of screening to 45.

Following the ACP’s announcement, several professional organizations, such as the American College of Radiology, criticized the new guidelines, calling them “a step backward” and warning they may hinder recent gains against CRC.

Some physicians believe the discordance will confuse patients and lead to varying referral practices among primary care physicians. And while insurers will likely continue to pay for screening procedures based on the USPSTF guidelines, which dictate insurance coverage, some physicians worry that insurers could create additional roadblocks for CRC screening coverage, such as requiring prior authorization.

“We’re in a conflicted space on this issue as a country,” said John L. Marshall, MD, a GI oncologist and director of The Ruesch Center for the Cure of GI Cancers at Georgetown University, Washington.

Ultimately, the physician community wants an inexpensive screening test that’s effective at preventing cancer and deaths, but the evidence thus far doesn’t necessarily support colonoscopy as that test, said Dr. Marshall, also chief medical officer for Lombardi Comprehensive Cancer Center.

Although colonoscopy can prevent CRC by removing precancerous polyps and can reduce deaths from cancer, it has not been shown to lower all-cause mortality, Dr. Marshall explained. A recent meta-analysis, for example, found that, aside from sigmoidoscopy for colon cancer screening, no other cancer screening modalities meaningfully changed life expectancy.

“That’s why we’re struggling,” Dr. Marshall said. “We’re emotionally invested in having screening available to younger people because we’re seeing colon cancer in younger people. So, we want it to move earlier, but it’s expensive and it’s invasive.”
 

Docs debate differing guidance

The new ACP guidance, based on a critical review of existing guidelines, evidence, and modeling studies, argues that the potential harms of screening average-risk individuals under age 50 may outweigh the potential benefits.

The benefits of screening, of course, include identifying and removing precancerous lesions or localized cancer, while the potential harms include false positives that may lead to unnecessary additional tests, treatments, and costs. More invasive screening procedures, such as colonoscopy, can also come with their own risks, including serious bleeding and perforation.

For colonoscopy, for instance, the ACP team determined that starting screening at age 45 vs. 50 could prevent three additional CRC cases per 1,000 individuals screened (58 vs. 61) and one CRC death (27 vs. 28) over the recommended screening time frame. On the flip side, screening starting at age 45 could increase the incidence of gastrointestinal or cardiovascular events (14 vs. 16).

“Even if we assumed the modeling study had no limitations and accepted the results at face value, we would conclude that the small estimated benefits and harms roughly balance each other out, resulting in an inadequate net benefit to warrant CRC screening in average-risk adults aged 45 to 49 years,” Amir Qaseem, MD, PhD, and ACP coauthors write.

Family physician Kenny Lin, MD, MPH, believes the updated ACP guidelines are reasonable, and points out the ACP is not the first group to disagree with the USPSTF’s recommendations.

“I think the [ACP] guidelines make a lot of sense,” said Dr. Lin, who practices in Lancaster, Pa. The American Academy of Family Physicians “also did not endorse the recommendations to start screenings at 45.” In its 2021 updated guidance, the AAFP recommended screening for CRC starting at age 50, concluding there was “insufficient evidence to assess the benefits and harms of screening” in the 45 to 49 population.

However, Jason R. Woloski, MD, a family physician based in Wilkes-Barre, Pa., expressed concern that the differing guidelines will confuse patients as well as present challenges for primary care physicians.

“I feel like we took the last couple of years convincing people that earlier is better,” said Dr. Woloski, an associate professor of family medicine at Geisinger Commonwealth School of Medicine, Scranton, Pa. “It can send a mixed message to a patient after we’ve been stressing the importance of earlier [screening], and then saying, ‘Maybe we got it wrong; maybe we were okay the first time.’ ”

Mark A. Lewis, MD, a GI oncologist, had a similar initial reaction upon hearing about the updated guidelines: “The lack of synchronization across groups is going to create confusion among patients.”

Although he could not say definitively whether the recommendations will affect GI oncologists, because he only sees patients with advanced CRC, he does see the demands in primary care and gastroenterology shifting.

“I think the much bigger impact will be on primary care physicians and gastroenterologists,” said Dr. Lewis, director of gastrointestinal oncology at Intermountain Healthcare in Murray, Utah. “My best guess is that the procedural burden on the latter will be mitigated by more stool testing ordered by primary care physicians. Patients may understandably prefer the convenience and lack of invasiveness of home-based fecal testing, but a positive FIT [fecal immunochemical test] without a follow-up scope is an incomplete screening.”

Dr. Marshall, however, had a different take. He does not envision the updated guidelines having much of a practical impact on physician practice. Most of the country is already not receiving proper colon cancer screenings, he said. Research shows more than 40% of Americans skip standard CRC screenings. Even anecdotally, he noted, friends in their 60s come to him and admit they haven’t had a colonoscopy yet.
 

Potential impact on patient outcomes, costs

Beyond mixed messaging, some experts worry that pushing CRC screening later could mean cancers are caught later, when they’re more advanced.

Finding cancers earlier, when they are easier and less expensive to treat, make earlier CRC screenings worthwhile, Dr. Woloski explained.

Dr. Lewis sees earlier screening as a way to stop a tumor from progressing before it can really pick up steam.

“To me the biggest advantage of colonoscopy is the interruption of the adenoma-to-carcinoma sequence, whereby a polyp that is completely removed cannot become an invasive adenocarcinoma,” Dr. Lewis said. “We’ve also had evidence for well over a decade that flexible sigmoidoscopy, which doesn’t come close to visualizing the entire colon, can confer a survival benefit.”

Another concern is the potential effect on insurance coverage.

Medicare and other insurers use USPSTF guidelines to make coverage decisions. However, because of this mixed message, Dr. Woloski questioned whether there would be more challenges regarding insurance coverage. “Does it mean primary care doctors are going to have to preauthorize a lot of these screenings even if you have shared decision-making with the patient?” he asked.

When it comes to screening referrals, Douglas A. Corley, MD, PhD, a gastroenterologist at Kaiser Permanente in northern California, said it’s critical for primary care physicians to educate patients about the differing views on screening benefits and harms as well as the different screening options.

“Given the different opinions, it is important to let people in this age group know that screening is an option recommended by some groups,” Dr. Corley said. “Colorectal cancer screening is very effective for decreasing the risk for death from colorectal cancer, which is the second leading cause of cancer death in the United States. Making sure all eligible people know this is an option provides the best way for patients to have an informed choice.”

Dr. Lin has already begun talking with patients about the differing recommendations. He said it’s helpful to simplify the issue and focus the conversation on what patients value most. For more assertive patients whose priority is finding every possible cancer early, starting screenings at age 45 may be reasonable, he said, whereas other patients may not find the process or possible side effects worth it.

“And then you have the middle group that decides, ‘Yes, I want to start at 45, but I want the fecal test. I don’t want to just jump into colonoscopy.’ ” Dr. Lin said. “That would be kind of a compromise where you’d be starting screening earlier, but not subjecting yourself to something that has more potential for harms.”

Dr. Woloski said he plans to continue making referrals based on the USPSTF recommendations.

“With every screening, it is about informed decision-making with the patient, but I think for now, since USPSTF still supports the earlier screening, I will probably stick with offering it earlier,” he said.

But when deciding on the appropriate timing for evaluating CRC, the most important distinction is between screening and diagnosis, Dr. Lewis added.

“The former is only appropriate in patients who are truly asymptomatic and who are truly average-risk,” he said. “The latter is critical in any patient with symptoms. I cannot count the number of times I have seen blood in the stool discounted as hemorrhoids without even an exam, digital rectal, or scope, to demonstrate that hemorrhoids are present and the culprit for blood loss.”

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

Recently updated colorectal cancer (CRC) screening guidance from the American College of Physicians is raising concerns among some specialists.

The ACP’s clinical guidance, published in Annals of Internal Medicine, called for CRC screenings to start at age 50 in average-risk individuals who are asymptomatic. This recommendation, however, conflicts with guidelines from the American Cancer Society and the U.S. Preventive Services Task Force, which, in 2021, officially lowered the recommended initial age of screening to 45.

Following the ACP’s announcement, several professional organizations, such as the American College of Radiology, criticized the new guidelines, calling them “a step backward” and warning they may hinder recent gains against CRC.

Some physicians believe the discordance will confuse patients and lead to varying referral practices among primary care physicians. And while insurers will likely continue to pay for screening procedures based on the USPSTF guidelines, which dictate insurance coverage, some physicians worry that insurers could create additional roadblocks for CRC screening coverage, such as requiring prior authorization.

“We’re in a conflicted space on this issue as a country,” said John L. Marshall, MD, a GI oncologist and director of The Ruesch Center for the Cure of GI Cancers at Georgetown University, Washington.

Ultimately, the physician community wants an inexpensive screening test that’s effective at preventing cancer and deaths, but the evidence thus far doesn’t necessarily support colonoscopy as that test, said Dr. Marshall, also chief medical officer for Lombardi Comprehensive Cancer Center.

Although colonoscopy can prevent CRC by removing precancerous polyps and can reduce deaths from cancer, it has not been shown to lower all-cause mortality, Dr. Marshall explained. A recent meta-analysis, for example, found that, aside from sigmoidoscopy for colon cancer screening, no other cancer screening modalities meaningfully changed life expectancy.

“That’s why we’re struggling,” Dr. Marshall said. “We’re emotionally invested in having screening available to younger people because we’re seeing colon cancer in younger people. So, we want it to move earlier, but it’s expensive and it’s invasive.”
 

Docs debate differing guidance

The new ACP guidance, based on a critical review of existing guidelines, evidence, and modeling studies, argues that the potential harms of screening average-risk individuals under age 50 may outweigh the potential benefits.

The benefits of screening, of course, include identifying and removing precancerous lesions or localized cancer, while the potential harms include false positives that may lead to unnecessary additional tests, treatments, and costs. More invasive screening procedures, such as colonoscopy, can also come with their own risks, including serious bleeding and perforation.

For colonoscopy, for instance, the ACP team determined that starting screening at age 45 vs. 50 could prevent three additional CRC cases per 1,000 individuals screened (58 vs. 61) and one CRC death (27 vs. 28) over the recommended screening time frame. On the flip side, screening starting at age 45 could increase the incidence of gastrointestinal or cardiovascular events (14 vs. 16).

“Even if we assumed the modeling study had no limitations and accepted the results at face value, we would conclude that the small estimated benefits and harms roughly balance each other out, resulting in an inadequate net benefit to warrant CRC screening in average-risk adults aged 45 to 49 years,” Amir Qaseem, MD, PhD, and ACP coauthors write.

Family physician Kenny Lin, MD, MPH, believes the updated ACP guidelines are reasonable, and points out the ACP is not the first group to disagree with the USPSTF’s recommendations.

“I think the [ACP] guidelines make a lot of sense,” said Dr. Lin, who practices in Lancaster, Pa. The American Academy of Family Physicians “also did not endorse the recommendations to start screenings at 45.” In its 2021 updated guidance, the AAFP recommended screening for CRC starting at age 50, concluding there was “insufficient evidence to assess the benefits and harms of screening” in the 45 to 49 population.

However, Jason R. Woloski, MD, a family physician based in Wilkes-Barre, Pa., expressed concern that the differing guidelines will confuse patients as well as present challenges for primary care physicians.

“I feel like we took the last couple of years convincing people that earlier is better,” said Dr. Woloski, an associate professor of family medicine at Geisinger Commonwealth School of Medicine, Scranton, Pa. “It can send a mixed message to a patient after we’ve been stressing the importance of earlier [screening], and then saying, ‘Maybe we got it wrong; maybe we were okay the first time.’ ”

Mark A. Lewis, MD, a GI oncologist, had a similar initial reaction upon hearing about the updated guidelines: “The lack of synchronization across groups is going to create confusion among patients.”

Although he could not say definitively whether the recommendations will affect GI oncologists, because he only sees patients with advanced CRC, he does see the demands in primary care and gastroenterology shifting.

“I think the much bigger impact will be on primary care physicians and gastroenterologists,” said Dr. Lewis, director of gastrointestinal oncology at Intermountain Healthcare in Murray, Utah. “My best guess is that the procedural burden on the latter will be mitigated by more stool testing ordered by primary care physicians. Patients may understandably prefer the convenience and lack of invasiveness of home-based fecal testing, but a positive FIT [fecal immunochemical test] without a follow-up scope is an incomplete screening.”

Dr. Marshall, however, had a different take. He does not envision the updated guidelines having much of a practical impact on physician practice. Most of the country is already not receiving proper colon cancer screenings, he said. Research shows more than 40% of Americans skip standard CRC screenings. Even anecdotally, he noted, friends in their 60s come to him and admit they haven’t had a colonoscopy yet.
 

Potential impact on patient outcomes, costs

Beyond mixed messaging, some experts worry that pushing CRC screening later could mean cancers are caught later, when they’re more advanced.

Finding cancers earlier, when they are easier and less expensive to treat, make earlier CRC screenings worthwhile, Dr. Woloski explained.

Dr. Lewis sees earlier screening as a way to stop a tumor from progressing before it can really pick up steam.

“To me the biggest advantage of colonoscopy is the interruption of the adenoma-to-carcinoma sequence, whereby a polyp that is completely removed cannot become an invasive adenocarcinoma,” Dr. Lewis said. “We’ve also had evidence for well over a decade that flexible sigmoidoscopy, which doesn’t come close to visualizing the entire colon, can confer a survival benefit.”

Another concern is the potential effect on insurance coverage.

Medicare and other insurers use USPSTF guidelines to make coverage decisions. However, because of this mixed message, Dr. Woloski questioned whether there would be more challenges regarding insurance coverage. “Does it mean primary care doctors are going to have to preauthorize a lot of these screenings even if you have shared decision-making with the patient?” he asked.

When it comes to screening referrals, Douglas A. Corley, MD, PhD, a gastroenterologist at Kaiser Permanente in northern California, said it’s critical for primary care physicians to educate patients about the differing views on screening benefits and harms as well as the different screening options.

“Given the different opinions, it is important to let people in this age group know that screening is an option recommended by some groups,” Dr. Corley said. “Colorectal cancer screening is very effective for decreasing the risk for death from colorectal cancer, which is the second leading cause of cancer death in the United States. Making sure all eligible people know this is an option provides the best way for patients to have an informed choice.”

Dr. Lin has already begun talking with patients about the differing recommendations. He said it’s helpful to simplify the issue and focus the conversation on what patients value most. For more assertive patients whose priority is finding every possible cancer early, starting screenings at age 45 may be reasonable, he said, whereas other patients may not find the process or possible side effects worth it.

“And then you have the middle group that decides, ‘Yes, I want to start at 45, but I want the fecal test. I don’t want to just jump into colonoscopy.’ ” Dr. Lin said. “That would be kind of a compromise where you’d be starting screening earlier, but not subjecting yourself to something that has more potential for harms.”

Dr. Woloski said he plans to continue making referrals based on the USPSTF recommendations.

“With every screening, it is about informed decision-making with the patient, but I think for now, since USPSTF still supports the earlier screening, I will probably stick with offering it earlier,” he said.

But when deciding on the appropriate timing for evaluating CRC, the most important distinction is between screening and diagnosis, Dr. Lewis added.

“The former is only appropriate in patients who are truly asymptomatic and who are truly average-risk,” he said. “The latter is critical in any patient with symptoms. I cannot count the number of times I have seen blood in the stool discounted as hemorrhoids without even an exam, digital rectal, or scope, to demonstrate that hemorrhoids are present and the culprit for blood loss.”

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

Recently updated colorectal cancer (CRC) screening guidance from the American College of Physicians is raising concerns among some specialists.

The ACP’s clinical guidance, published in Annals of Internal Medicine, called for CRC screenings to start at age 50 in average-risk individuals who are asymptomatic. This recommendation, however, conflicts with guidelines from the American Cancer Society and the U.S. Preventive Services Task Force, which, in 2021, officially lowered the recommended initial age of screening to 45.

Following the ACP’s announcement, several professional organizations, such as the American College of Radiology, criticized the new guidelines, calling them “a step backward” and warning they may hinder recent gains against CRC.

Some physicians believe the discordance will confuse patients and lead to varying referral practices among primary care physicians. And while insurers will likely continue to pay for screening procedures based on the USPSTF guidelines, which dictate insurance coverage, some physicians worry that insurers could create additional roadblocks for CRC screening coverage, such as requiring prior authorization.

“We’re in a conflicted space on this issue as a country,” said John L. Marshall, MD, a GI oncologist and director of The Ruesch Center for the Cure of GI Cancers at Georgetown University, Washington.

Ultimately, the physician community wants an inexpensive screening test that’s effective at preventing cancer and deaths, but the evidence thus far doesn’t necessarily support colonoscopy as that test, said Dr. Marshall, also chief medical officer for Lombardi Comprehensive Cancer Center.

Although colonoscopy can prevent CRC by removing precancerous polyps and can reduce deaths from cancer, it has not been shown to lower all-cause mortality, Dr. Marshall explained. A recent meta-analysis, for example, found that, aside from sigmoidoscopy for colon cancer screening, no other cancer screening modalities meaningfully changed life expectancy.

“That’s why we’re struggling,” Dr. Marshall said. “We’re emotionally invested in having screening available to younger people because we’re seeing colon cancer in younger people. So, we want it to move earlier, but it’s expensive and it’s invasive.”
 

Docs debate differing guidance

The new ACP guidance, based on a critical review of existing guidelines, evidence, and modeling studies, argues that the potential harms of screening average-risk individuals under age 50 may outweigh the potential benefits.

The benefits of screening, of course, include identifying and removing precancerous lesions or localized cancer, while the potential harms include false positives that may lead to unnecessary additional tests, treatments, and costs. More invasive screening procedures, such as colonoscopy, can also come with their own risks, including serious bleeding and perforation.

For colonoscopy, for instance, the ACP team determined that starting screening at age 45 vs. 50 could prevent three additional CRC cases per 1,000 individuals screened (58 vs. 61) and one CRC death (27 vs. 28) over the recommended screening time frame. On the flip side, screening starting at age 45 could increase the incidence of gastrointestinal or cardiovascular events (14 vs. 16).

“Even if we assumed the modeling study had no limitations and accepted the results at face value, we would conclude that the small estimated benefits and harms roughly balance each other out, resulting in an inadequate net benefit to warrant CRC screening in average-risk adults aged 45 to 49 years,” Amir Qaseem, MD, PhD, and ACP coauthors write.

Family physician Kenny Lin, MD, MPH, believes the updated ACP guidelines are reasonable, and points out the ACP is not the first group to disagree with the USPSTF’s recommendations.

“I think the [ACP] guidelines make a lot of sense,” said Dr. Lin, who practices in Lancaster, Pa. The American Academy of Family Physicians “also did not endorse the recommendations to start screenings at 45.” In its 2021 updated guidance, the AAFP recommended screening for CRC starting at age 50, concluding there was “insufficient evidence to assess the benefits and harms of screening” in the 45 to 49 population.

However, Jason R. Woloski, MD, a family physician based in Wilkes-Barre, Pa., expressed concern that the differing guidelines will confuse patients as well as present challenges for primary care physicians.

“I feel like we took the last couple of years convincing people that earlier is better,” said Dr. Woloski, an associate professor of family medicine at Geisinger Commonwealth School of Medicine, Scranton, Pa. “It can send a mixed message to a patient after we’ve been stressing the importance of earlier [screening], and then saying, ‘Maybe we got it wrong; maybe we were okay the first time.’ ”

Mark A. Lewis, MD, a GI oncologist, had a similar initial reaction upon hearing about the updated guidelines: “The lack of synchronization across groups is going to create confusion among patients.”

Although he could not say definitively whether the recommendations will affect GI oncologists, because he only sees patients with advanced CRC, he does see the demands in primary care and gastroenterology shifting.

“I think the much bigger impact will be on primary care physicians and gastroenterologists,” said Dr. Lewis, director of gastrointestinal oncology at Intermountain Healthcare in Murray, Utah. “My best guess is that the procedural burden on the latter will be mitigated by more stool testing ordered by primary care physicians. Patients may understandably prefer the convenience and lack of invasiveness of home-based fecal testing, but a positive FIT [fecal immunochemical test] without a follow-up scope is an incomplete screening.”

Dr. Marshall, however, had a different take. He does not envision the updated guidelines having much of a practical impact on physician practice. Most of the country is already not receiving proper colon cancer screenings, he said. Research shows more than 40% of Americans skip standard CRC screenings. Even anecdotally, he noted, friends in their 60s come to him and admit they haven’t had a colonoscopy yet.
 

Potential impact on patient outcomes, costs

Beyond mixed messaging, some experts worry that pushing CRC screening later could mean cancers are caught later, when they’re more advanced.

Finding cancers earlier, when they are easier and less expensive to treat, make earlier CRC screenings worthwhile, Dr. Woloski explained.

Dr. Lewis sees earlier screening as a way to stop a tumor from progressing before it can really pick up steam.

“To me the biggest advantage of colonoscopy is the interruption of the adenoma-to-carcinoma sequence, whereby a polyp that is completely removed cannot become an invasive adenocarcinoma,” Dr. Lewis said. “We’ve also had evidence for well over a decade that flexible sigmoidoscopy, which doesn’t come close to visualizing the entire colon, can confer a survival benefit.”

Another concern is the potential effect on insurance coverage.

Medicare and other insurers use USPSTF guidelines to make coverage decisions. However, because of this mixed message, Dr. Woloski questioned whether there would be more challenges regarding insurance coverage. “Does it mean primary care doctors are going to have to preauthorize a lot of these screenings even if you have shared decision-making with the patient?” he asked.

When it comes to screening referrals, Douglas A. Corley, MD, PhD, a gastroenterologist at Kaiser Permanente in northern California, said it’s critical for primary care physicians to educate patients about the differing views on screening benefits and harms as well as the different screening options.

“Given the different opinions, it is important to let people in this age group know that screening is an option recommended by some groups,” Dr. Corley said. “Colorectal cancer screening is very effective for decreasing the risk for death from colorectal cancer, which is the second leading cause of cancer death in the United States. Making sure all eligible people know this is an option provides the best way for patients to have an informed choice.”

Dr. Lin has already begun talking with patients about the differing recommendations. He said it’s helpful to simplify the issue and focus the conversation on what patients value most. For more assertive patients whose priority is finding every possible cancer early, starting screenings at age 45 may be reasonable, he said, whereas other patients may not find the process or possible side effects worth it.

“And then you have the middle group that decides, ‘Yes, I want to start at 45, but I want the fecal test. I don’t want to just jump into colonoscopy.’ ” Dr. Lin said. “That would be kind of a compromise where you’d be starting screening earlier, but not subjecting yourself to something that has more potential for harms.”

Dr. Woloski said he plans to continue making referrals based on the USPSTF recommendations.

“With every screening, it is about informed decision-making with the patient, but I think for now, since USPSTF still supports the earlier screening, I will probably stick with offering it earlier,” he said.

But when deciding on the appropriate timing for evaluating CRC, the most important distinction is between screening and diagnosis, Dr. Lewis added.

“The former is only appropriate in patients who are truly asymptomatic and who are truly average-risk,” he said. “The latter is critical in any patient with symptoms. I cannot count the number of times I have seen blood in the stool discounted as hemorrhoids without even an exam, digital rectal, or scope, to demonstrate that hemorrhoids are present and the culprit for blood loss.”

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

TOPLINE:

An artificial intelligence (AI) model shows potential for detecting early-stage, “hidden” pancreatic cancer on scans of asymptomatic individuals, paving the way for surgical intervention and cure, new research suggests.

METHODOLOGY:

• The researchers utilized a diverse dataset of 3,014 CT scans: 1,105 diagnostic CT scans with pancreatic ductal adenocarcinoma (PDA) and 1,909 control CT scans.
• Of the total, 696 diagnostic CT scans with PDA and 1,080 control CT scans were used as an AI model training subset, and 409 CT scans with PDA and 829 control CT scans were used as an intramural hold-out test subset.
• The model was also tested on a simulated cohort that evaluated the risk for PDA in new-onset diabetes; multicenter public datasets (194 CT scans with PDA and 80 controls); and a cohort of 100 prediagnostic CT scans, incidentally acquired 3-36 months prior to PDA being diagnosed, and 134 controls.

TAKEAWAY:

• The model correctly classified 360 CT scans with PDA (88%) and 783 control CT scans (94%) in the intramural test subset. The mean accuracy was 0.92, the area under the receiver operating characteristic curve was 0.97, sensitivity was 0.88, and specificity was 0.95.
• On heat maps, activation areas overlapped with the tumor in 350 of 360 CT scans (97%).
• Performance was high across tumor stages, with sensitivities of 0.80, 0.87, 0.95, and 1.0 on T1 through T4 stages, respectively. Performance was comparable for hypodense versus isodense tumors (sensitivity of 0.90 vs. 0.82, respectively), patient demographics, CT slice thicknesses, and vendors.
• Findings were generalizable on both the simulated cohort (accuracy, 0.95; area under the ROC curve, 0.97) and public datasets (accuracy, 0.86; AUROC, 0.9).
• Occult PDA was detected on prediagnostic CT scans at a median 475 days before clinical diagnosis. Accuracy was 0.84, AUROC was 0.91, sensitivity was 0.75, and specificity was 0.9.

IN PRACTICE:

“Artificial intelligence model could mitigate the inadequacies of imaging and the diagnostic errors in interpretation, which often contribute to delayed diagnosis of pancreas cancer. In combination with emerging blood-based biomarkers, such a model could be evaluated to screen for sporadic cancer in ongoing trials of high-risk cohorts such as the Early Detection Initiative (NCT04662879).”

SOURCE:

Panagiotis Korfiatis, PhD, of Mayo Clinic, Rochester, Minn., led the study, which was published online in Gastroenterology.

LIMITATIONS:

The retrospective design is prone to selection bias. Results are presented dichotomously as either cancer or control. These are preliminary insights, and prospective clinical trials that incorporate epidemiological risk factors and emerging blood-based biomarkers are needed to further evaluate the model’s performance.

DISCLOSURES:

The research was supported by the National Cancer Institute, the Centene Charitable Foundation, and the Champions for Hope Pancreatic Cancer Research Program of the Funk Zitiello Foundation. One author received an institutional research grant from Sofie Biosciences and Clovis Oncology, is on the BlueStar Genomics advisory board (ad hoc), and is a consultant for Bayer Healthcare, Candel Therapeutics, and UWorld. The remaining authors reported no relevant financial relationships.

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

TOPLINE:

An artificial intelligence (AI) model shows potential for detecting early-stage, “hidden” pancreatic cancer on scans of asymptomatic individuals, paving the way for surgical intervention and cure, new research suggests.

METHODOLOGY:

• The researchers utilized a diverse dataset of 3,014 CT scans: 1,105 diagnostic CT scans with pancreatic ductal adenocarcinoma (PDA) and 1,909 control CT scans.
• Of the total, 696 diagnostic CT scans with PDA and 1,080 control CT scans were used as an AI model training subset, and 409 CT scans with PDA and 829 control CT scans were used as an intramural hold-out test subset.
• The model was also tested on a simulated cohort that evaluated the risk for PDA in new-onset diabetes; multicenter public datasets (194 CT scans with PDA and 80 controls); and a cohort of 100 prediagnostic CT scans, incidentally acquired 3-36 months prior to PDA being diagnosed, and 134 controls.

TAKEAWAY:

• The model correctly classified 360 CT scans with PDA (88%) and 783 control CT scans (94%) in the intramural test subset. The mean accuracy was 0.92, the area under the receiver operating characteristic curve was 0.97, sensitivity was 0.88, and specificity was 0.95.
• On heat maps, activation areas overlapped with the tumor in 350 of 360 CT scans (97%).
• Performance was high across tumor stages, with sensitivities of 0.80, 0.87, 0.95, and 1.0 on T1 through T4 stages, respectively. Performance was comparable for hypodense versus isodense tumors (sensitivity of 0.90 vs. 0.82, respectively), patient demographics, CT slice thicknesses, and vendors.
• Findings were generalizable on both the simulated cohort (accuracy, 0.95; area under the ROC curve, 0.97) and public datasets (accuracy, 0.86; AUROC, 0.9).
• Occult PDA was detected on prediagnostic CT scans at a median 475 days before clinical diagnosis. Accuracy was 0.84, AUROC was 0.91, sensitivity was 0.75, and specificity was 0.9.

IN PRACTICE:

“Artificial intelligence model could mitigate the inadequacies of imaging and the diagnostic errors in interpretation, which often contribute to delayed diagnosis of pancreas cancer. In combination with emerging blood-based biomarkers, such a model could be evaluated to screen for sporadic cancer in ongoing trials of high-risk cohorts such as the Early Detection Initiative (NCT04662879).”

SOURCE:

Panagiotis Korfiatis, PhD, of Mayo Clinic, Rochester, Minn., led the study, which was published online in Gastroenterology.

LIMITATIONS:

The retrospective design is prone to selection bias. Results are presented dichotomously as either cancer or control. These are preliminary insights, and prospective clinical trials that incorporate epidemiological risk factors and emerging blood-based biomarkers are needed to further evaluate the model’s performance.

DISCLOSURES:

The research was supported by the National Cancer Institute, the Centene Charitable Foundation, and the Champions for Hope Pancreatic Cancer Research Program of the Funk Zitiello Foundation. One author received an institutional research grant from Sofie Biosciences and Clovis Oncology, is on the BlueStar Genomics advisory board (ad hoc), and is a consultant for Bayer Healthcare, Candel Therapeutics, and UWorld. The remaining authors reported no relevant financial relationships.

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

TOPLINE:

An artificial intelligence (AI) model shows potential for detecting early-stage, “hidden” pancreatic cancer on scans of asymptomatic individuals, paving the way for surgical intervention and cure, new research suggests.

METHODOLOGY:

• The researchers utilized a diverse dataset of 3,014 CT scans: 1,105 diagnostic CT scans with pancreatic ductal adenocarcinoma (PDA) and 1,909 control CT scans.
• Of the total, 696 diagnostic CT scans with PDA and 1,080 control CT scans were used as an AI model training subset, and 409 CT scans with PDA and 829 control CT scans were used as an intramural hold-out test subset.
• The model was also tested on a simulated cohort that evaluated the risk for PDA in new-onset diabetes; multicenter public datasets (194 CT scans with PDA and 80 controls); and a cohort of 100 prediagnostic CT scans, incidentally acquired 3-36 months prior to PDA being diagnosed, and 134 controls.

TAKEAWAY:

• The model correctly classified 360 CT scans with PDA (88%) and 783 control CT scans (94%) in the intramural test subset. The mean accuracy was 0.92, the area under the receiver operating characteristic curve was 0.97, sensitivity was 0.88, and specificity was 0.95.
• On heat maps, activation areas overlapped with the tumor in 350 of 360 CT scans (97%).
• Performance was high across tumor stages, with sensitivities of 0.80, 0.87, 0.95, and 1.0 on T1 through T4 stages, respectively. Performance was comparable for hypodense versus isodense tumors (sensitivity of 0.90 vs. 0.82, respectively), patient demographics, CT slice thicknesses, and vendors.
• Findings were generalizable on both the simulated cohort (accuracy, 0.95; area under the ROC curve, 0.97) and public datasets (accuracy, 0.86; AUROC, 0.9).
• Occult PDA was detected on prediagnostic CT scans at a median 475 days before clinical diagnosis. Accuracy was 0.84, AUROC was 0.91, sensitivity was 0.75, and specificity was 0.9.

IN PRACTICE:

“Artificial intelligence model could mitigate the inadequacies of imaging and the diagnostic errors in interpretation, which often contribute to delayed diagnosis of pancreas cancer. In combination with emerging blood-based biomarkers, such a model could be evaluated to screen for sporadic cancer in ongoing trials of high-risk cohorts such as the Early Detection Initiative (NCT04662879).”

SOURCE:

Panagiotis Korfiatis, PhD, of Mayo Clinic, Rochester, Minn., led the study, which was published online in Gastroenterology.

LIMITATIONS:

The retrospective design is prone to selection bias. Results are presented dichotomously as either cancer or control. These are preliminary insights, and prospective clinical trials that incorporate epidemiological risk factors and emerging blood-based biomarkers are needed to further evaluate the model’s performance.

DISCLOSURES:

The research was supported by the National Cancer Institute, the Centene Charitable Foundation, and the Champions for Hope Pancreatic Cancer Research Program of the Funk Zitiello Foundation. One author received an institutional research grant from Sofie Biosciences and Clovis Oncology, is on the BlueStar Genomics advisory board (ad hoc), and is a consultant for Bayer Healthcare, Candel Therapeutics, and UWorld. The remaining authors reported no relevant financial relationships.

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

This transcript has been edited for clarity.

Fatima Cardoso, MD: Today we will be discussing breast cancer in male patients. To join me in this discussion, I have Sharon Giordano and Oliver Bogler. I will ask, to start, that we briefly introduce ourselves.

I’m Fatima Cardoso. I’m a medical oncologist based in Lisbon, Portugal. I have had a special interest in this topic for a couple of years. Sharon?

Sharon H. Giordano, MD, MPH, FASCO: I’m Sharon Giordano. I practice at the University of Texas MD Anderson Cancer Center. I’m also a medical oncologist and treat most of the male breast cancer patients that are seen here.

Oliver Bogler, PhD: I’m Oliver Bogler. I’m a cancer biologist by background and an 11-year survivor of breast cancer. Dr. Giordano was my oncologist during the active phase of my treatment. It’s great to be here with you.

Special considerations surrounding male patients

• Dr. Cardoso: Sharon, when you are treating breast cancer in a male patient, what specific considerations do you have?
• Dr. Giordano: As we all know, breast cancer in men is a rare disease. It makes up about 1 in 1,000 cases of breast cancer. I think that one of the major challenges in treating the disease is we just don’t have the same to support our treatments as we do for women.

Often, what we need to do and what we end up doing is extrapolating as much as possible from clinical trials that were conducted in female patients with breast cancer. I think that’s one of the major challenges we face in treating the disease. There have been international efforts to try to put together standardized treatment approaches.

For example, ASCO has created guidelines for the management of male breast cancer. NCCN also has a special page on considerations for treatment of men with breast cancer. I would encourage people to look at those resources if questions do come up on the topic.

Dr. Cardoso: Perhaps we can also mention that the latest clinical trials fortunately have been allowing for male patients to be included, which is very important so that we can start having some data on the new drugs. I think that’s also relevant.

Dr. Giordano: That’s a great point because, historically, most of the trials explicitly excluded men. I don’t know if it was intentional or they just wrote the trials saying “women with breast cancer,” because that’s what most people thought of. I think it’s a great effort by the FDA and by investigators to make sure now that men are included in the trials. That will help build our evidence base.

Dr. Cardoso: Oliver, 11 years ago, you faced the diagnosis and you went through this. Can you speak a little bit about this challenge of going through what is considered a rare disease, but also a disease that is very much associated with the female gender traditionally?

Dr. Bogler: Gladly. For me, it was particularly odd because my wife, at the time that I was diagnosed, was a 5-year survivor of breast cancer. It took me some time to even think that the lump I felt might be the same disease. That seemed very unlikely, statistically, and also odd.

I have to say that I was protected from much of the fish-out-of-water experience that many men have because I both worked and was treated at MD Anderson, where Dr Giordano has a large practice, so my colleagues and my friends were not surprised that a man could get this disease.

Many of the patients I met had that experience, difficulty convincing their primary care physician or even their first-line oncologist that this could be the case. I just want to connect to what you both said, which is that 10 years ago, inclusion of men in clinical trials was not standard. It is a fantastic development to see that because unless we include men, we won’t learn about that type of breast cancer.

Dr. Cardoso: Even if only a few are entering each trial, at least it allows us to see if the drug behaves the same way or if there is any strange behavior of the drug in a male patient. It’s already one step forward. You were going to mention something, Sharon?

Dr. Giordano: I was going to say that, anecdotally, I’ve heard the experience that Oliver referred to, of many men feeling not so much uncomfortable with the diagnosis – although that does happen – but not having an obvious fit within the health care system.

For example, going to get their mammogram as part of their diagnostic workup and whoever might be taking them back saying, “Oh, no, this is Mrs. Jones, not Mr.,” and trying to argue with them that it’s not really meant for them. I had a patient – and this guy had a great sense of humor – who had a biopsy done and the instructions were to place this pink, floral ice pack inside your bra.

Even the materials that we have are gender specific. I think those things all together can certainly contribute to a man feeling like a fish out of water.

Dr. Cardoso: Actually, I fought in my institution because they wanted to call the Breast and Gynecology Unit the Women’s Unit. I said that there is no way you can call it the Women’s Unit because we have male patients. There are small things that we can do in our institutions to try to decrease the stigma and to make it less awkward for a man to be in a waiting room that says Women’s Clinic or something similar to that.

The importance of a support system

Dr. Cardoso: I wanted Oliver, perhaps, to mention experiences that you may have heard from other men. Some men do not feel that comfortable speaking about the disease. Also, some of them do not feel comfortable after treatment to go to the beach, to show the scar, and to show what happens after you have radiation.

Some men actually take it quite heavily, psychologically speaking. Have you encountered some of these men?

Dr. Bogler: Definitely. I think it leads to men not accessing the support opportunities – their family, their friends, or the support groups – and staying away from those because of this feeling of not wanting to share about it. That can be damaging. Cancer treatment is usually a tough road for most people, and the long-term consequences of hormone therapy – most men have hormone-driven disease – can be significant. I agree with you.

I participated in the male breast cancer SCAR Project by David Jay, a famous photographer. One of the high points of my life has been appearing in The New York Times topless, right after my radiation treatment, showing my scar. There are quite a few of us out there who’ve done that.

I’ll just mention in passing the Male Breast Cancer Global Alliance, which is a patient support supergroup, if you will. We’ve got a symposium coming up in November. That’s a great place for men who are early in the stage of their disease, or at any stage, to connect to others who are facing this issue.

Dr. Cardoso: They can also find specific information. This is a really good website where you can find information. One of the most important topics that I’ve heard from my patients is, “I never thought that I could have this disease. I never heard that men could have breast cancer as well.” Information is very crucial.

I believe that if you are well informed, you will also be less scared of the disease. Sources of reliable information are really crucial for patients. Since you mentioned the SCAR Project, we have a similar project here in Portugal that really called attention to the disease. It was very visual and really interesting.
 

Discussions during and after treatment

Dr. Cardoso: I wanted to say something, and I don’t know if both of you would agree. I think only recently surgeons have started to pay attention to the way they operate on men with breast cancer, and even in considering techniques of breast conservation and oncoplastic surgery. I had the feeling, looking at those photos, that some years ago, it wouldn’t have mattered how they do with the mastectomy scar just because it was a man. This was biased, right?

Just because it was a man, there was no need to pay attention to the aesthetic outcome. That is wrong, in my perspective. I’m very happy to see that now there are surgeons considering other types of breast surgery to conserve as much as possible the aesthetic outcome.

Dr. Bogler: I have to say that I was offered reconstruction at MD Anderson. I declined it. It wasn’t that big a part of my body image. When I raised this issue at home, my kids, who were quite young at the time, just suggested, “Well, Dad, why don’t you just wear a swim shirt?” They came up with a very practical solution for this issue.

I agree with you that it should be an option. I was also offered a nipple tattoo. I have yet to take that up, but maybe one day.

Dr. Cardoso: I’m not sure that we need to go into reconstruction. It also depends on whether a man has gynecomastia, if it’s going to be very asymmetric. There are other techniques to do, and depending on the size of the tumor, we can also do breast conservation, which we have done here in a couple of patients.

It’s quite an interesting approach where, for example, a skin-sparing mastectomy would be less aggressive, let’s say. Sharon?

Dr. Giordano: I completely agree. I’ve noticed increasing attention to the issue over the years that I’ve been in practice. I do think that it’s more front-and-center when the surgeons are having discussions with the patients now.

Also, although it’s still a minority, some do choose to have reconstructive surgery; some have more extensive surgeries, and some maybe have nipple reconstruction or a nipple tattoo. In a few men, like you mentioned, who are somewhat asymmetric, it actually can make a difference even when they’re dressed.

For many men, it’s more that they want to take off their shirt to play basketball or go swimming, and to decrease the feeling of awkwardness or like they have to make an explanation for why they have a nipple missing and a scar across their chest.
 

Biological aspects of male patients

Dr. Cardoso: Let’s switch gears now to the management, and before that, the biology. Oliver, with your other hat of biology, speak a little bit on what we know so far – whether it is exactly the same disease or there are biological specific characteristics of breast cancer in men.

Dr. Bogler: I should preface this by saying that I spent my career studying brain tumors. That was clearly a mistake.

Dr. Cardoso: It starts with a B. ...

Dr. Bogler: It starts with a B, but it’s the wrong part of the body. The reality is that we don’t really know that much fundamental biology yet, though the picture is changing and it has changed in recent years. Part of the reason is we don’t have many of the tools that we’ve had for the female disease for many years, particularly laboratory models.

On the genetic and transcriptomics front, there has been some really good activity. There was a comprehensive systematic review by Professor Val Speirs from the University of Aberdeen earlier this year that summarized much of the recent data. It showed that there are a handful of molecular hallmarks of the male disease, compared with the female disease, that are worth exploring.

Interestingly enough, one of them is the androgen receptor. It does beg the question of whether hormone-driven disease might not show up quite differently in males and females, where the hormone picture is a little different. I think there’s increasing evidence that there’s information out there to go after.

I will say that I was treated by Dr. Giordano and her colleagues very much like a woman would have been with my disease, and actually, very similarly to my wife. I’ve done well with it, so I would say, in most cases, the current standard of care is very effective but it falls a little short of personalized medicine, particularly when it comes to the hormone component.

Dr. Cardoso: Sharon?

Dr. Giordano: I would add that when I think about it as a clinician, although there’s a large amount of overlap and many similarities, when we’re treating men with breast cancer, almost all of the men have hormone receptor–positive disease, which I think Oliver mentioned earlier. We’re really thinking about endocrine therapy as one of the mainstays of treatment.

Obviously, as he also mentioned, it’s a different biologic background of hormones in a male vs. a female patient. There’s reason to think that some of those treatments could differ. In general, the subtypes are a little bit different. We see very, very few cases of triple-negative breast cancer in men. I think I’ve seen only one or two in my career. The ones I remember were probably radiation induced. They were cancer survivors who’d had chest-wall radiation for previous diseases. Those patients are very uncommon.

We also tend to see that the histology patterns are a little bit different. We tend to see more ductal cancers in men than we do in women as a relative proportion.

One thing that I always try to remember is that the risk for BRCA mutations or underlying germline genetic mutations is higher in men than in women. Just having a diagnosis of male breast cancer is an indication to consider genetic testing or meet with a genetic counselor to look for a BRCA1 or BRCA2 mutation.

Now, most men will not have that. Only roughly 10% of male patients, or maybe a little less, will have a BRCA2 mutation; for BRCA1, it’s more like only 1% or 2%. They’re not that common. Certainly, male breast cancer is recognized as being associated with the BRCA mutations.

Dr. Cardoso: If I have to give a take-home message in terms of biology, it would be that if there is a diagnosis of hormone receptor–negative or HER2-positive disease in a male patient, I would ask for a confirmation of the diagnosis. It’s not that it cannot exist, but it’s so rare that it’s worthwhile to confirm.

You mentioned that triple-negative disease is less than 1%, at about 0.5%, and HER2-positive disease is about 9%-10%. I think it will be very important to keep this in mind and confirm the biology if you have a different diagnosis than ER-positive, HER2-negative. Unfortunately, I received some cases where this was not done, and in fact, it ended up being a technical problem. People can receive the wrong treatment based on that.

Dr. Giordano: I’ve also seen that happen when it’s a metastasis to the breast rather than a primary breast cancer. I completely agree. That’s an excellent point. 

Management approaches

Dr. Cardoso: Let’s go now to management and focus on early breast cancer first. Sharon, what are your main take-home messages for a professional who doesn’t see this very often? What does someone need to remember when they manage a male patient who has early breast cancer?

Dr. Giordano: In general, in terms of chemotherapy, we essentially use the same guidelines as we do for women. Most of the male patients will have tumors that are hormone receptor positive. For endocrine therapy, we typically rely on tamoxifen as the standard of care for adjuvant endocrine treatment for breast cancer.

There are some data suggesting that there can be some efficacy of aromatase inhibitors as single agents. In general, and extrapolated from some population-based registry data, the outcomes for men treated with single-agent aromatase inhibitors don’t tend to be as good as for those treated with tamoxifen.

I know that these are not randomized data so there are all the caveats of that, but the best information we have suggests that tamoxifen appears to likely be more effective. Typically, we stay with tamoxifen. If, for some reason, a man cannot tolerate tamoxifen or has a contraindication, then we could use a GnRH agonist along with an aromatase inhibitor.

Dr. Cardoso: I would like to mention that, because it’s ER-positive, HER2-negative disease most of the time, there will be the question as to whether we can use genomic tests. I think it is important that people know that we have much less data regarding the use of Oncotype DX, MammaPrint, or any of the genomic tests in male patients.

We have some data on the distribution of, for example, Oncotype DX or MammaPrint scores. Whether we can use these tests for the decision of chemotherapy, we don’t have much data on that. I’ve seen many people making exactly the same decisions as with female patients, but that’s not really based on very strong evidence.

Dr. Giordano: It’s hard to know what to do with that. There are prognostic data on Oncotype, so the higher-risk tumors do seem to have a worse outcome than the lower-score tumors. You’re right, though; I don’t think we have any predictive information to really show that the Oncotype DX score predicts benefit to chemotherapy.

Having said that, I will sometimes order the test in my practice. If somebody comes back with a score of 5 or a very low-risk score, I will use that in my decision-making.

Dr. Cardoso: There is something we didn’t exactly mention in the diagnosis that may be important. We discussed most men not knowing that they can have breast cancer, and Oliver, you mentioned that sometimes the first-line physicians can think that very often. Usually, we have late diagnosis and that means a higher tumor burden.

Sometimes we have to go to chemotherapy because of locally advanced or very positive axillas and not really because of the biology. That’s one of the reasons to go for chemotherapy in this setting, right?

Dr. Bogler: Yes. I remember that conversation with you, Dr. Giordano. I asked you whether I should do one of these tests. You said, “Don’t worry about it. At stage III, you’re going to have chemo anyway.”

Dr. Cardoso: The problem of these rare diagnoses is the not thinking about it, even from the health professional side, and then having the diagnosis quite late that will demand chemotherapy use.

To clarify to everybody, in terms of distinguishing luminal A–like, luminal B–like, and what that implies in a male patient, we really don’t know if it’s the same as in a female. There have been some very interesting studies from our Nordic country colleagues showing that maybe the subtyping is different. There is likely a male-specific subtype that does not exist in female breast cancer and that probably behaves differently. We still have a large amount of research to do to understand that.

Is there anything else you would like to mention about early breast cancer management?

Dr. Bogler: One of the things that’s probably underexplored is adherence to tamoxifen therapy in men. I do know anecdotally that this is the discussion among men because of the impact on quality of life. I do worry that sometimes men perhaps make the wrong choice, and I think that’s an opportunity for more research. Again, if there were alternative therapies that were perhaps a little less impactful on things like libido, that might be an advance in the field.

Dr. Cardoso: We have been seeing more studies on the issue of quality of life. Noncompliance is also an issue in female patients. We have to acknowledge that. Not everybody is able to keep taking the treatments. Interestingly, when there is a relapse and people had stopped taking the tamoxifen, most of them say, “I stopped because I had not understood exactly how important it is.”

We come back to the importance of explaining that it is the most crucial treatment for this subtype of breast cancer. Again, information is really key.

Sometimes I also use the argument with my patients that the alternative is even worse because if you use an aromatase inhibitor, and you have to use an LHRH agonist, then the implications for your sexual life are even worse. That’s how I try to convince them to stay on tamoxifen.

Let’s finalize with a couple of words on metastatic breast cancer in male patients. Sharon, I’ll start with you again. Is there any difference in the management if you have a patient with metastatic, ER-positive, HER2-negative disease? How do you treat? How do you sequence the available therapies? Is it different from the female patient?

Dr. Giordano: I’d say that, big picture, it’s quite similar. Again, most of the men have hormone receptor–positive disease, so really, the mainstay of treatment and the first treatments are going to be endocrine therapies. We’ll sequence through the endocrine therapies like we do in women. When using aromatase inhibitors, I typically would add a GnRH agonist to that, and I have had that be a very successful therapy, along now with the CDK inhibitors that are also approved.

I don’t think the studies of CDK inhibitors included male patients, but at least palbociclib actually was approved in the United States, based on some real-world evidence of its efficacy. Anecdotally, again, in my clinical practice, that tends to be a really powerful combination of leuprolide, an aromatase inhibitor, and a CDK inhibitor.

I think there’s less information about drugs like fulvestrant, whether that would benefit from combination with a GnRH agonist or whether those should be given as single agents. We just don’t really know. We have a few case series out there.

Similar to the early breast cancer setting, I think it’s really important to remember to check for BRCA1 and BRCA2 mutations. PARP inhibitors could be a part of the treatment plan if those underlying germline mutations are found. Generally, we’re following a similar sequence of endocrine therapies and then, eventually, chemotherapy.

Dr. Cardoso: Maybe, Oliver, you’re also seeing that one consistent finding in the biology study is the importance of the AKT/PI3K/mTOR pathway in male patients with breast cancer, because we now have at least two classes of agents to tackle this pathway. Again, anecdotally – we’re not talking about trials – I’ve been seeing quite interesting responses, for example, to everolimus combined with endocrine therapy.

We have a little less experience with the PI3K inhibitor, but that’s just because of accessibility to the drug. I think this combination is also something to keep in mind that can be quite effective in these patients.

Dr. Bogler: I agree. Those findings are exciting in the context of dealing with something as difficult as metastatic breast cancer. It’s good to know that there’s some information coming and opportunities and options, hopefully, down the road for men facing that problem.

Dr. Cardoso: Sharon, although small numbers, in these cases where there is HER2-positive disease, you would also use the new anti-HER2 agents and more or less the same sequence, right?

Dr. Giordano: Absolutely. It’s not particularly data driven, but yes, I would. If it’s a HER2-positive tumor, I would use the same HER2-targeted therapies that are used for women with breast cancer.

Working toward a balance in patient care

Dr. Cardoso: I would like to add something for all of us to be united in the fight. I don’t know if it happens in the U.S., but in many countries, access to these new agents for male patients is very difficult because of the approval and the labeling. This is why I’m always fighting with those who are proposing that the labeling, again, says “women with breast cancer.”

It is really important that we keep on lobbying and pushing for the labeling to say “patients with breast cancer” so that nobody can withhold access to these new therapies because of gender. In the U.S., maybe you don’t have this problem. There are many European countries where men cannot access, for example, fulvestrant because it has been approved for women with breast cancer.

Dr. Giordano: Thankfully, I have not faced that issue very often. I’ve had occasional issues with getting GnRH agonists approved. Generally, in the U.S., if I provide, for example, the NCCN guideline recommendations, most insurers will cover it. I think it’s often just lack of knowledge.

Dr. Cardoso: It’s something to keep working hard on because for the old drugs that were approved with the wording that still said “women,” we have to keep fighting for accessibility.

I think we had a really nice discussion. I’m going to give you an opportunity for any last words that you want to say on this topic. Perhaps we’ll start with you, Sharon, and we’ll leave the very last word to Oliver.

Dr. Giordano: I would just emphasize the importance of doing research in this area. Hopefully, we will be able to get clinical trials. There are reasons to think that endocrine therapies may behave differently in men and women. We need to continue to work together as a community to collect the data so that we can ultimately improve the outcomes for our patients.

Dr. Bogler: I would echo what you just said, Dr. Giordano. I would like to express my gratitude to both of you. Dr. Giordano, you have a huge practice of men at MD Anderson. You took care of me and many other people I know.

Dr. Cardoso, you are a pioneer of a big registry trial that I am privileged to be working on, trying to gather data on men. You’re both pioneers in this field of working on behalf of people like me. I’m just very grateful for what you do.

Dr. Giordano: Thank you.

Dr. Cardoso: Thank you both for accepting this invitation. We hope that everybody takes more interest in this field. Who knows? Maybe we can find enough funds to run a specific trial for male patients with breast cancer.

Dr. Cardoso is director of the breast unit at Champalimaud Clinical Centre/Champalimaud Foundation, Lisbon. Dr. Giordano is professor of breast medical oncology and chair of health services research at the University of Texas MD Anderson Cancer Center, Houston. Dr. Bogler is a cancer biologist at the Randolph (Vt.) Center. Dr. Cardoso reported conflicts of interest with numerous pharmaceutical companies; Dr. Giordano and Dr. Bogler reported no conflicts of interest.

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

This transcript has been edited for clarity.

Fatima Cardoso, MD: Today we will be discussing breast cancer in male patients. To join me in this discussion, I have Sharon Giordano and Oliver Bogler. I will ask, to start, that we briefly introduce ourselves.

I’m Fatima Cardoso. I’m a medical oncologist based in Lisbon, Portugal. I have had a special interest in this topic for a couple of years. Sharon?

Sharon H. Giordano, MD, MPH, FASCO: I’m Sharon Giordano. I practice at the University of Texas MD Anderson Cancer Center. I’m also a medical oncologist and treat most of the male breast cancer patients that are seen here.

Oliver Bogler, PhD: I’m Oliver Bogler. I’m a cancer biologist by background and an 11-year survivor of breast cancer. Dr. Giordano was my oncologist during the active phase of my treatment. It’s great to be here with you.

Special considerations surrounding male patients

• Dr. Cardoso: Sharon, when you are treating breast cancer in a male patient, what specific considerations do you have?
• Dr. Giordano: As we all know, breast cancer in men is a rare disease. It makes up about 1 in 1,000 cases of breast cancer. I think that one of the major challenges in treating the disease is we just don’t have the same to support our treatments as we do for women.

Often, what we need to do and what we end up doing is extrapolating as much as possible from clinical trials that were conducted in female patients with breast cancer. I think that’s one of the major challenges we face in treating the disease. There have been international efforts to try to put together standardized treatment approaches.

For example, ASCO has created guidelines for the management of male breast cancer. NCCN also has a special page on considerations for treatment of men with breast cancer. I would encourage people to look at those resources if questions do come up on the topic.

Dr. Cardoso: Perhaps we can also mention that the latest clinical trials fortunately have been allowing for male patients to be included, which is very important so that we can start having some data on the new drugs. I think that’s also relevant.

Dr. Giordano: That’s a great point because, historically, most of the trials explicitly excluded men. I don’t know if it was intentional or they just wrote the trials saying “women with breast cancer,” because that’s what most people thought of. I think it’s a great effort by the FDA and by investigators to make sure now that men are included in the trials. That will help build our evidence base.

Dr. Cardoso: Oliver, 11 years ago, you faced the diagnosis and you went through this. Can you speak a little bit about this challenge of going through what is considered a rare disease, but also a disease that is very much associated with the female gender traditionally?

Dr. Bogler: Gladly. For me, it was particularly odd because my wife, at the time that I was diagnosed, was a 5-year survivor of breast cancer. It took me some time to even think that the lump I felt might be the same disease. That seemed very unlikely, statistically, and also odd.

I have to say that I was protected from much of the fish-out-of-water experience that many men have because I both worked and was treated at MD Anderson, where Dr Giordano has a large practice, so my colleagues and my friends were not surprised that a man could get this disease.

Many of the patients I met had that experience, difficulty convincing their primary care physician or even their first-line oncologist that this could be the case. I just want to connect to what you both said, which is that 10 years ago, inclusion of men in clinical trials was not standard. It is a fantastic development to see that because unless we include men, we won’t learn about that type of breast cancer.

Dr. Cardoso: Even if only a few are entering each trial, at least it allows us to see if the drug behaves the same way or if there is any strange behavior of the drug in a male patient. It’s already one step forward. You were going to mention something, Sharon?

Dr. Giordano: I was going to say that, anecdotally, I’ve heard the experience that Oliver referred to, of many men feeling not so much uncomfortable with the diagnosis – although that does happen – but not having an obvious fit within the health care system.

For example, going to get their mammogram as part of their diagnostic workup and whoever might be taking them back saying, “Oh, no, this is Mrs. Jones, not Mr.,” and trying to argue with them that it’s not really meant for them. I had a patient – and this guy had a great sense of humor – who had a biopsy done and the instructions were to place this pink, floral ice pack inside your bra.

Even the materials that we have are gender specific. I think those things all together can certainly contribute to a man feeling like a fish out of water.

Dr. Cardoso: Actually, I fought in my institution because they wanted to call the Breast and Gynecology Unit the Women’s Unit. I said that there is no way you can call it the Women’s Unit because we have male patients. There are small things that we can do in our institutions to try to decrease the stigma and to make it less awkward for a man to be in a waiting room that says Women’s Clinic or something similar to that.

The importance of a support system

Dr. Cardoso: I wanted Oliver, perhaps, to mention experiences that you may have heard from other men. Some men do not feel that comfortable speaking about the disease. Also, some of them do not feel comfortable after treatment to go to the beach, to show the scar, and to show what happens after you have radiation.

Some men actually take it quite heavily, psychologically speaking. Have you encountered some of these men?

Dr. Bogler: Definitely. I think it leads to men not accessing the support opportunities – their family, their friends, or the support groups – and staying away from those because of this feeling of not wanting to share about it. That can be damaging. Cancer treatment is usually a tough road for most people, and the long-term consequences of hormone therapy – most men have hormone-driven disease – can be significant. I agree with you.

I participated in the male breast cancer SCAR Project by David Jay, a famous photographer. One of the high points of my life has been appearing in The New York Times topless, right after my radiation treatment, showing my scar. There are quite a few of us out there who’ve done that.

I’ll just mention in passing the Male Breast Cancer Global Alliance, which is a patient support supergroup, if you will. We’ve got a symposium coming up in November. That’s a great place for men who are early in the stage of their disease, or at any stage, to connect to others who are facing this issue.

Dr. Cardoso: They can also find specific information. This is a really good website where you can find information. One of the most important topics that I’ve heard from my patients is, “I never thought that I could have this disease. I never heard that men could have breast cancer as well.” Information is very crucial.

I believe that if you are well informed, you will also be less scared of the disease. Sources of reliable information are really crucial for patients. Since you mentioned the SCAR Project, we have a similar project here in Portugal that really called attention to the disease. It was very visual and really interesting.
 

Discussions during and after treatment

Dr. Cardoso: I wanted to say something, and I don’t know if both of you would agree. I think only recently surgeons have started to pay attention to the way they operate on men with breast cancer, and even in considering techniques of breast conservation and oncoplastic surgery. I had the feeling, looking at those photos, that some years ago, it wouldn’t have mattered how they do with the mastectomy scar just because it was a man. This was biased, right?

Just because it was a man, there was no need to pay attention to the aesthetic outcome. That is wrong, in my perspective. I’m very happy to see that now there are surgeons considering other types of breast surgery to conserve as much as possible the aesthetic outcome.

Dr. Bogler: I have to say that I was offered reconstruction at MD Anderson. I declined it. It wasn’t that big a part of my body image. When I raised this issue at home, my kids, who were quite young at the time, just suggested, “Well, Dad, why don’t you just wear a swim shirt?” They came up with a very practical solution for this issue.

I agree with you that it should be an option. I was also offered a nipple tattoo. I have yet to take that up, but maybe one day.

Dr. Cardoso: I’m not sure that we need to go into reconstruction. It also depends on whether a man has gynecomastia, if it’s going to be very asymmetric. There are other techniques to do, and depending on the size of the tumor, we can also do breast conservation, which we have done here in a couple of patients.

It’s quite an interesting approach where, for example, a skin-sparing mastectomy would be less aggressive, let’s say. Sharon?

Dr. Giordano: I completely agree. I’ve noticed increasing attention to the issue over the years that I’ve been in practice. I do think that it’s more front-and-center when the surgeons are having discussions with the patients now.

Also, although it’s still a minority, some do choose to have reconstructive surgery; some have more extensive surgeries, and some maybe have nipple reconstruction or a nipple tattoo. In a few men, like you mentioned, who are somewhat asymmetric, it actually can make a difference even when they’re dressed.

For many men, it’s more that they want to take off their shirt to play basketball or go swimming, and to decrease the feeling of awkwardness or like they have to make an explanation for why they have a nipple missing and a scar across their chest.
 

Biological aspects of male patients

Dr. Cardoso: Let’s switch gears now to the management, and before that, the biology. Oliver, with your other hat of biology, speak a little bit on what we know so far – whether it is exactly the same disease or there are biological specific characteristics of breast cancer in men.

Dr. Bogler: I should preface this by saying that I spent my career studying brain tumors. That was clearly a mistake.

Dr. Cardoso: It starts with a B. ...

Dr. Bogler: It starts with a B, but it’s the wrong part of the body. The reality is that we don’t really know that much fundamental biology yet, though the picture is changing and it has changed in recent years. Part of the reason is we don’t have many of the tools that we’ve had for the female disease for many years, particularly laboratory models.

On the genetic and transcriptomics front, there has been some really good activity. There was a comprehensive systematic review by Professor Val Speirs from the University of Aberdeen earlier this year that summarized much of the recent data. It showed that there are a handful of molecular hallmarks of the male disease, compared with the female disease, that are worth exploring.

Interestingly enough, one of them is the androgen receptor. It does beg the question of whether hormone-driven disease might not show up quite differently in males and females, where the hormone picture is a little different. I think there’s increasing evidence that there’s information out there to go after.

I will say that I was treated by Dr. Giordano and her colleagues very much like a woman would have been with my disease, and actually, very similarly to my wife. I’ve done well with it, so I would say, in most cases, the current standard of care is very effective but it falls a little short of personalized medicine, particularly when it comes to the hormone component.

Dr. Cardoso: Sharon?

Dr. Giordano: I would add that when I think about it as a clinician, although there’s a large amount of overlap and many similarities, when we’re treating men with breast cancer, almost all of the men have hormone receptor–positive disease, which I think Oliver mentioned earlier. We’re really thinking about endocrine therapy as one of the mainstays of treatment.

Obviously, as he also mentioned, it’s a different biologic background of hormones in a male vs. a female patient. There’s reason to think that some of those treatments could differ. In general, the subtypes are a little bit different. We see very, very few cases of triple-negative breast cancer in men. I think I’ve seen only one or two in my career. The ones I remember were probably radiation induced. They were cancer survivors who’d had chest-wall radiation for previous diseases. Those patients are very uncommon.

We also tend to see that the histology patterns are a little bit different. We tend to see more ductal cancers in men than we do in women as a relative proportion.

One thing that I always try to remember is that the risk for BRCA mutations or underlying germline genetic mutations is higher in men than in women. Just having a diagnosis of male breast cancer is an indication to consider genetic testing or meet with a genetic counselor to look for a BRCA1 or BRCA2 mutation.

Now, most men will not have that. Only roughly 10% of male patients, or maybe a little less, will have a BRCA2 mutation; for BRCA1, it’s more like only 1% or 2%. They’re not that common. Certainly, male breast cancer is recognized as being associated with the BRCA mutations.

Dr. Cardoso: If I have to give a take-home message in terms of biology, it would be that if there is a diagnosis of hormone receptor–negative or HER2-positive disease in a male patient, I would ask for a confirmation of the diagnosis. It’s not that it cannot exist, but it’s so rare that it’s worthwhile to confirm.

You mentioned that triple-negative disease is less than 1%, at about 0.5%, and HER2-positive disease is about 9%-10%. I think it will be very important to keep this in mind and confirm the biology if you have a different diagnosis than ER-positive, HER2-negative. Unfortunately, I received some cases where this was not done, and in fact, it ended up being a technical problem. People can receive the wrong treatment based on that.

Dr. Giordano: I’ve also seen that happen when it’s a metastasis to the breast rather than a primary breast cancer. I completely agree. That’s an excellent point. 

Management approaches

Dr. Cardoso: Let’s go now to management and focus on early breast cancer first. Sharon, what are your main take-home messages for a professional who doesn’t see this very often? What does someone need to remember when they manage a male patient who has early breast cancer?

Dr. Giordano: In general, in terms of chemotherapy, we essentially use the same guidelines as we do for women. Most of the male patients will have tumors that are hormone receptor positive. For endocrine therapy, we typically rely on tamoxifen as the standard of care for adjuvant endocrine treatment for breast cancer.

There are some data suggesting that there can be some efficacy of aromatase inhibitors as single agents. In general, and extrapolated from some population-based registry data, the outcomes for men treated with single-agent aromatase inhibitors don’t tend to be as good as for those treated with tamoxifen.

I know that these are not randomized data so there are all the caveats of that, but the best information we have suggests that tamoxifen appears to likely be more effective. Typically, we stay with tamoxifen. If, for some reason, a man cannot tolerate tamoxifen or has a contraindication, then we could use a GnRH agonist along with an aromatase inhibitor.

Dr. Cardoso: I would like to mention that, because it’s ER-positive, HER2-negative disease most of the time, there will be the question as to whether we can use genomic tests. I think it is important that people know that we have much less data regarding the use of Oncotype DX, MammaPrint, or any of the genomic tests in male patients.

We have some data on the distribution of, for example, Oncotype DX or MammaPrint scores. Whether we can use these tests for the decision of chemotherapy, we don’t have much data on that. I’ve seen many people making exactly the same decisions as with female patients, but that’s not really based on very strong evidence.

Dr. Giordano: It’s hard to know what to do with that. There are prognostic data on Oncotype, so the higher-risk tumors do seem to have a worse outcome than the lower-score tumors. You’re right, though; I don’t think we have any predictive information to really show that the Oncotype DX score predicts benefit to chemotherapy.

Having said that, I will sometimes order the test in my practice. If somebody comes back with a score of 5 or a very low-risk score, I will use that in my decision-making.

Dr. Cardoso: There is something we didn’t exactly mention in the diagnosis that may be important. We discussed most men not knowing that they can have breast cancer, and Oliver, you mentioned that sometimes the first-line physicians can think that very often. Usually, we have late diagnosis and that means a higher tumor burden.

Sometimes we have to go to chemotherapy because of locally advanced or very positive axillas and not really because of the biology. That’s one of the reasons to go for chemotherapy in this setting, right?

Dr. Bogler: Yes. I remember that conversation with you, Dr. Giordano. I asked you whether I should do one of these tests. You said, “Don’t worry about it. At stage III, you’re going to have chemo anyway.”

Dr. Cardoso: The problem of these rare diagnoses is the not thinking about it, even from the health professional side, and then having the diagnosis quite late that will demand chemotherapy use.

To clarify to everybody, in terms of distinguishing luminal A–like, luminal B–like, and what that implies in a male patient, we really don’t know if it’s the same as in a female. There have been some very interesting studies from our Nordic country colleagues showing that maybe the subtyping is different. There is likely a male-specific subtype that does not exist in female breast cancer and that probably behaves differently. We still have a large amount of research to do to understand that.

Is there anything else you would like to mention about early breast cancer management?

Dr. Bogler: One of the things that’s probably underexplored is adherence to tamoxifen therapy in men. I do know anecdotally that this is the discussion among men because of the impact on quality of life. I do worry that sometimes men perhaps make the wrong choice, and I think that’s an opportunity for more research. Again, if there were alternative therapies that were perhaps a little less impactful on things like libido, that might be an advance in the field.

Dr. Cardoso: We have been seeing more studies on the issue of quality of life. Noncompliance is also an issue in female patients. We have to acknowledge that. Not everybody is able to keep taking the treatments. Interestingly, when there is a relapse and people had stopped taking the tamoxifen, most of them say, “I stopped because I had not understood exactly how important it is.”

We come back to the importance of explaining that it is the most crucial treatment for this subtype of breast cancer. Again, information is really key.

Sometimes I also use the argument with my patients that the alternative is even worse because if you use an aromatase inhibitor, and you have to use an LHRH agonist, then the implications for your sexual life are even worse. That’s how I try to convince them to stay on tamoxifen.

Let’s finalize with a couple of words on metastatic breast cancer in male patients. Sharon, I’ll start with you again. Is there any difference in the management if you have a patient with metastatic, ER-positive, HER2-negative disease? How do you treat? How do you sequence the available therapies? Is it different from the female patient?

Dr. Giordano: I’d say that, big picture, it’s quite similar. Again, most of the men have hormone receptor–positive disease, so really, the mainstay of treatment and the first treatments are going to be endocrine therapies. We’ll sequence through the endocrine therapies like we do in women. When using aromatase inhibitors, I typically would add a GnRH agonist to that, and I have had that be a very successful therapy, along now with the CDK inhibitors that are also approved.

I don’t think the studies of CDK inhibitors included male patients, but at least palbociclib actually was approved in the United States, based on some real-world evidence of its efficacy. Anecdotally, again, in my clinical practice, that tends to be a really powerful combination of leuprolide, an aromatase inhibitor, and a CDK inhibitor.

I think there’s less information about drugs like fulvestrant, whether that would benefit from combination with a GnRH agonist or whether those should be given as single agents. We just don’t really know. We have a few case series out there.

Similar to the early breast cancer setting, I think it’s really important to remember to check for BRCA1 and BRCA2 mutations. PARP inhibitors could be a part of the treatment plan if those underlying germline mutations are found. Generally, we’re following a similar sequence of endocrine therapies and then, eventually, chemotherapy.

Dr. Cardoso: Maybe, Oliver, you’re also seeing that one consistent finding in the biology study is the importance of the AKT/PI3K/mTOR pathway in male patients with breast cancer, because we now have at least two classes of agents to tackle this pathway. Again, anecdotally – we’re not talking about trials – I’ve been seeing quite interesting responses, for example, to everolimus combined with endocrine therapy.

We have a little less experience with the PI3K inhibitor, but that’s just because of accessibility to the drug. I think this combination is also something to keep in mind that can be quite effective in these patients.

Dr. Bogler: I agree. Those findings are exciting in the context of dealing with something as difficult as metastatic breast cancer. It’s good to know that there’s some information coming and opportunities and options, hopefully, down the road for men facing that problem.

Dr. Cardoso: Sharon, although small numbers, in these cases where there is HER2-positive disease, you would also use the new anti-HER2 agents and more or less the same sequence, right?

Dr. Giordano: Absolutely. It’s not particularly data driven, but yes, I would. If it’s a HER2-positive tumor, I would use the same HER2-targeted therapies that are used for women with breast cancer.

Working toward a balance in patient care

Dr. Cardoso: I would like to add something for all of us to be united in the fight. I don’t know if it happens in the U.S., but in many countries, access to these new agents for male patients is very difficult because of the approval and the labeling. This is why I’m always fighting with those who are proposing that the labeling, again, says “women with breast cancer.”

It is really important that we keep on lobbying and pushing for the labeling to say “patients with breast cancer” so that nobody can withhold access to these new therapies because of gender. In the U.S., maybe you don’t have this problem. There are many European countries where men cannot access, for example, fulvestrant because it has been approved for women with breast cancer.

Dr. Giordano: Thankfully, I have not faced that issue very often. I’ve had occasional issues with getting GnRH agonists approved. Generally, in the U.S., if I provide, for example, the NCCN guideline recommendations, most insurers will cover it. I think it’s often just lack of knowledge.

Dr. Cardoso: It’s something to keep working hard on because for the old drugs that were approved with the wording that still said “women,” we have to keep fighting for accessibility.

I think we had a really nice discussion. I’m going to give you an opportunity for any last words that you want to say on this topic. Perhaps we’ll start with you, Sharon, and we’ll leave the very last word to Oliver.

Dr. Giordano: I would just emphasize the importance of doing research in this area. Hopefully, we will be able to get clinical trials. There are reasons to think that endocrine therapies may behave differently in men and women. We need to continue to work together as a community to collect the data so that we can ultimately improve the outcomes for our patients.

Dr. Bogler: I would echo what you just said, Dr. Giordano. I would like to express my gratitude to both of you. Dr. Giordano, you have a huge practice of men at MD Anderson. You took care of me and many other people I know.

Dr. Cardoso, you are a pioneer of a big registry trial that I am privileged to be working on, trying to gather data on men. You’re both pioneers in this field of working on behalf of people like me. I’m just very grateful for what you do.

Dr. Giordano: Thank you.

Dr. Cardoso: Thank you both for accepting this invitation. We hope that everybody takes more interest in this field. Who knows? Maybe we can find enough funds to run a specific trial for male patients with breast cancer.

Dr. Cardoso is director of the breast unit at Champalimaud Clinical Centre/Champalimaud Foundation, Lisbon. Dr. Giordano is professor of breast medical oncology and chair of health services research at the University of Texas MD Anderson Cancer Center, Houston. Dr. Bogler is a cancer biologist at the Randolph (Vt.) Center. Dr. Cardoso reported conflicts of interest with numerous pharmaceutical companies; Dr. Giordano and Dr. Bogler reported no conflicts of interest.

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

This transcript has been edited for clarity.

Fatima Cardoso, MD: Today we will be discussing breast cancer in male patients. To join me in this discussion, I have Sharon Giordano and Oliver Bogler. I will ask, to start, that we briefly introduce ourselves.

I’m Fatima Cardoso. I’m a medical oncologist based in Lisbon, Portugal. I have had a special interest in this topic for a couple of years. Sharon?

Sharon H. Giordano, MD, MPH, FASCO: I’m Sharon Giordano. I practice at the University of Texas MD Anderson Cancer Center. I’m also a medical oncologist and treat most of the male breast cancer patients that are seen here.

Oliver Bogler, PhD: I’m Oliver Bogler. I’m a cancer biologist by background and an 11-year survivor of breast cancer. Dr. Giordano was my oncologist during the active phase of my treatment. It’s great to be here with you.

Special considerations surrounding male patients

• Dr. Cardoso: Sharon, when you are treating breast cancer in a male patient, what specific considerations do you have?
• Dr. Giordano: As we all know, breast cancer in men is a rare disease. It makes up about 1 in 1,000 cases of breast cancer. I think that one of the major challenges in treating the disease is we just don’t have the same to support our treatments as we do for women.

Often, what we need to do and what we end up doing is extrapolating as much as possible from clinical trials that were conducted in female patients with breast cancer. I think that’s one of the major challenges we face in treating the disease. There have been international efforts to try to put together standardized treatment approaches.

For example, ASCO has created guidelines for the management of male breast cancer. NCCN also has a special page on considerations for treatment of men with breast cancer. I would encourage people to look at those resources if questions do come up on the topic.

Dr. Cardoso: Perhaps we can also mention that the latest clinical trials fortunately have been allowing for male patients to be included, which is very important so that we can start having some data on the new drugs. I think that’s also relevant.

Dr. Giordano: That’s a great point because, historically, most of the trials explicitly excluded men. I don’t know if it was intentional or they just wrote the trials saying “women with breast cancer,” because that’s what most people thought of. I think it’s a great effort by the FDA and by investigators to make sure now that men are included in the trials. That will help build our evidence base.

Dr. Cardoso: Oliver, 11 years ago, you faced the diagnosis and you went through this. Can you speak a little bit about this challenge of going through what is considered a rare disease, but also a disease that is very much associated with the female gender traditionally?

Dr. Bogler: Gladly. For me, it was particularly odd because my wife, at the time that I was diagnosed, was a 5-year survivor of breast cancer. It took me some time to even think that the lump I felt might be the same disease. That seemed very unlikely, statistically, and also odd.

I have to say that I was protected from much of the fish-out-of-water experience that many men have because I both worked and was treated at MD Anderson, where Dr Giordano has a large practice, so my colleagues and my friends were not surprised that a man could get this disease.

Many of the patients I met had that experience, difficulty convincing their primary care physician or even their first-line oncologist that this could be the case. I just want to connect to what you both said, which is that 10 years ago, inclusion of men in clinical trials was not standard. It is a fantastic development to see that because unless we include men, we won’t learn about that type of breast cancer.

Dr. Cardoso: Even if only a few are entering each trial, at least it allows us to see if the drug behaves the same way or if there is any strange behavior of the drug in a male patient. It’s already one step forward. You were going to mention something, Sharon?

Dr. Giordano: I was going to say that, anecdotally, I’ve heard the experience that Oliver referred to, of many men feeling not so much uncomfortable with the diagnosis – although that does happen – but not having an obvious fit within the health care system.

For example, going to get their mammogram as part of their diagnostic workup and whoever might be taking them back saying, “Oh, no, this is Mrs. Jones, not Mr.,” and trying to argue with them that it’s not really meant for them. I had a patient – and this guy had a great sense of humor – who had a biopsy done and the instructions were to place this pink, floral ice pack inside your bra.

Even the materials that we have are gender specific. I think those things all together can certainly contribute to a man feeling like a fish out of water.

Dr. Cardoso: Actually, I fought in my institution because they wanted to call the Breast and Gynecology Unit the Women’s Unit. I said that there is no way you can call it the Women’s Unit because we have male patients. There are small things that we can do in our institutions to try to decrease the stigma and to make it less awkward for a man to be in a waiting room that says Women’s Clinic or something similar to that.

The importance of a support system

Dr. Cardoso: I wanted Oliver, perhaps, to mention experiences that you may have heard from other men. Some men do not feel that comfortable speaking about the disease. Also, some of them do not feel comfortable after treatment to go to the beach, to show the scar, and to show what happens after you have radiation.

Some men actually take it quite heavily, psychologically speaking. Have you encountered some of these men?

Dr. Bogler: Definitely. I think it leads to men not accessing the support opportunities – their family, their friends, or the support groups – and staying away from those because of this feeling of not wanting to share about it. That can be damaging. Cancer treatment is usually a tough road for most people, and the long-term consequences of hormone therapy – most men have hormone-driven disease – can be significant. I agree with you.

I participated in the male breast cancer SCAR Project by David Jay, a famous photographer. One of the high points of my life has been appearing in The New York Times topless, right after my radiation treatment, showing my scar. There are quite a few of us out there who’ve done that.

I’ll just mention in passing the Male Breast Cancer Global Alliance, which is a patient support supergroup, if you will. We’ve got a symposium coming up in November. That’s a great place for men who are early in the stage of their disease, or at any stage, to connect to others who are facing this issue.

Dr. Cardoso: They can also find specific information. This is a really good website where you can find information. One of the most important topics that I’ve heard from my patients is, “I never thought that I could have this disease. I never heard that men could have breast cancer as well.” Information is very crucial.

I believe that if you are well informed, you will also be less scared of the disease. Sources of reliable information are really crucial for patients. Since you mentioned the SCAR Project, we have a similar project here in Portugal that really called attention to the disease. It was very visual and really interesting.
 

Discussions during and after treatment

Dr. Cardoso: I wanted to say something, and I don’t know if both of you would agree. I think only recently surgeons have started to pay attention to the way they operate on men with breast cancer, and even in considering techniques of breast conservation and oncoplastic surgery. I had the feeling, looking at those photos, that some years ago, it wouldn’t have mattered how they do with the mastectomy scar just because it was a man. This was biased, right?

Just because it was a man, there was no need to pay attention to the aesthetic outcome. That is wrong, in my perspective. I’m very happy to see that now there are surgeons considering other types of breast surgery to conserve as much as possible the aesthetic outcome.

Dr. Bogler: I have to say that I was offered reconstruction at MD Anderson. I declined it. It wasn’t that big a part of my body image. When I raised this issue at home, my kids, who were quite young at the time, just suggested, “Well, Dad, why don’t you just wear a swim shirt?” They came up with a very practical solution for this issue.

I agree with you that it should be an option. I was also offered a nipple tattoo. I have yet to take that up, but maybe one day.

Dr. Cardoso: I’m not sure that we need to go into reconstruction. It also depends on whether a man has gynecomastia, if it’s going to be very asymmetric. There are other techniques to do, and depending on the size of the tumor, we can also do breast conservation, which we have done here in a couple of patients.

It’s quite an interesting approach where, for example, a skin-sparing mastectomy would be less aggressive, let’s say. Sharon?

Dr. Giordano: I completely agree. I’ve noticed increasing attention to the issue over the years that I’ve been in practice. I do think that it’s more front-and-center when the surgeons are having discussions with the patients now.

Also, although it’s still a minority, some do choose to have reconstructive surgery; some have more extensive surgeries, and some maybe have nipple reconstruction or a nipple tattoo. In a few men, like you mentioned, who are somewhat asymmetric, it actually can make a difference even when they’re dressed.

For many men, it’s more that they want to take off their shirt to play basketball or go swimming, and to decrease the feeling of awkwardness or like they have to make an explanation for why they have a nipple missing and a scar across their chest.
 

Biological aspects of male patients

Dr. Cardoso: Let’s switch gears now to the management, and before that, the biology. Oliver, with your other hat of biology, speak a little bit on what we know so far – whether it is exactly the same disease or there are biological specific characteristics of breast cancer in men.

Dr. Bogler: I should preface this by saying that I spent my career studying brain tumors. That was clearly a mistake.

Dr. Cardoso: It starts with a B. ...

Dr. Bogler: It starts with a B, but it’s the wrong part of the body. The reality is that we don’t really know that much fundamental biology yet, though the picture is changing and it has changed in recent years. Part of the reason is we don’t have many of the tools that we’ve had for the female disease for many years, particularly laboratory models.

On the genetic and transcriptomics front, there has been some really good activity. There was a comprehensive systematic review by Professor Val Speirs from the University of Aberdeen earlier this year that summarized much of the recent data. It showed that there are a handful of molecular hallmarks of the male disease, compared with the female disease, that are worth exploring.

Interestingly enough, one of them is the androgen receptor. It does beg the question of whether hormone-driven disease might not show up quite differently in males and females, where the hormone picture is a little different. I think there’s increasing evidence that there’s information out there to go after.

I will say that I was treated by Dr. Giordano and her colleagues very much like a woman would have been with my disease, and actually, very similarly to my wife. I’ve done well with it, so I would say, in most cases, the current standard of care is very effective but it falls a little short of personalized medicine, particularly when it comes to the hormone component.

Dr. Cardoso: Sharon?

Dr. Giordano: I would add that when I think about it as a clinician, although there’s a large amount of overlap and many similarities, when we’re treating men with breast cancer, almost all of the men have hormone receptor–positive disease, which I think Oliver mentioned earlier. We’re really thinking about endocrine therapy as one of the mainstays of treatment.

Obviously, as he also mentioned, it’s a different biologic background of hormones in a male vs. a female patient. There’s reason to think that some of those treatments could differ. In general, the subtypes are a little bit different. We see very, very few cases of triple-negative breast cancer in men. I think I’ve seen only one or two in my career. The ones I remember were probably radiation induced. They were cancer survivors who’d had chest-wall radiation for previous diseases. Those patients are very uncommon.

We also tend to see that the histology patterns are a little bit different. We tend to see more ductal cancers in men than we do in women as a relative proportion.

One thing that I always try to remember is that the risk for BRCA mutations or underlying germline genetic mutations is higher in men than in women. Just having a diagnosis of male breast cancer is an indication to consider genetic testing or meet with a genetic counselor to look for a BRCA1 or BRCA2 mutation.

Now, most men will not have that. Only roughly 10% of male patients, or maybe a little less, will have a BRCA2 mutation; for BRCA1, it’s more like only 1% or 2%. They’re not that common. Certainly, male breast cancer is recognized as being associated with the BRCA mutations.

Dr. Cardoso: If I have to give a take-home message in terms of biology, it would be that if there is a diagnosis of hormone receptor–negative or HER2-positive disease in a male patient, I would ask for a confirmation of the diagnosis. It’s not that it cannot exist, but it’s so rare that it’s worthwhile to confirm.

You mentioned that triple-negative disease is less than 1%, at about 0.5%, and HER2-positive disease is about 9%-10%. I think it will be very important to keep this in mind and confirm the biology if you have a different diagnosis than ER-positive, HER2-negative. Unfortunately, I received some cases where this was not done, and in fact, it ended up being a technical problem. People can receive the wrong treatment based on that.

Dr. Giordano: I’ve also seen that happen when it’s a metastasis to the breast rather than a primary breast cancer. I completely agree. That’s an excellent point. 

Management approaches

Dr. Cardoso: Let’s go now to management and focus on early breast cancer first. Sharon, what are your main take-home messages for a professional who doesn’t see this very often? What does someone need to remember when they manage a male patient who has early breast cancer?

Dr. Giordano: In general, in terms of chemotherapy, we essentially use the same guidelines as we do for women. Most of the male patients will have tumors that are hormone receptor positive. For endocrine therapy, we typically rely on tamoxifen as the standard of care for adjuvant endocrine treatment for breast cancer.

There are some data suggesting that there can be some efficacy of aromatase inhibitors as single agents. In general, and extrapolated from some population-based registry data, the outcomes for men treated with single-agent aromatase inhibitors don’t tend to be as good as for those treated with tamoxifen.

I know that these are not randomized data so there are all the caveats of that, but the best information we have suggests that tamoxifen appears to likely be more effective. Typically, we stay with tamoxifen. If, for some reason, a man cannot tolerate tamoxifen or has a contraindication, then we could use a GnRH agonist along with an aromatase inhibitor.

Dr. Cardoso: I would like to mention that, because it’s ER-positive, HER2-negative disease most of the time, there will be the question as to whether we can use genomic tests. I think it is important that people know that we have much less data regarding the use of Oncotype DX, MammaPrint, or any of the genomic tests in male patients.

We have some data on the distribution of, for example, Oncotype DX or MammaPrint scores. Whether we can use these tests for the decision of chemotherapy, we don’t have much data on that. I’ve seen many people making exactly the same decisions as with female patients, but that’s not really based on very strong evidence.

Dr. Giordano: It’s hard to know what to do with that. There are prognostic data on Oncotype, so the higher-risk tumors do seem to have a worse outcome than the lower-score tumors. You’re right, though; I don’t think we have any predictive information to really show that the Oncotype DX score predicts benefit to chemotherapy.

Having said that, I will sometimes order the test in my practice. If somebody comes back with a score of 5 or a very low-risk score, I will use that in my decision-making.

Dr. Cardoso: There is something we didn’t exactly mention in the diagnosis that may be important. We discussed most men not knowing that they can have breast cancer, and Oliver, you mentioned that sometimes the first-line physicians can think that very often. Usually, we have late diagnosis and that means a higher tumor burden.

Sometimes we have to go to chemotherapy because of locally advanced or very positive axillas and not really because of the biology. That’s one of the reasons to go for chemotherapy in this setting, right?

Dr. Bogler: Yes. I remember that conversation with you, Dr. Giordano. I asked you whether I should do one of these tests. You said, “Don’t worry about it. At stage III, you’re going to have chemo anyway.”

Dr. Cardoso: The problem of these rare diagnoses is the not thinking about it, even from the health professional side, and then having the diagnosis quite late that will demand chemotherapy use.

To clarify to everybody, in terms of distinguishing luminal A–like, luminal B–like, and what that implies in a male patient, we really don’t know if it’s the same as in a female. There have been some very interesting studies from our Nordic country colleagues showing that maybe the subtyping is different. There is likely a male-specific subtype that does not exist in female breast cancer and that probably behaves differently. We still have a large amount of research to do to understand that.

Is there anything else you would like to mention about early breast cancer management?

Dr. Bogler: One of the things that’s probably underexplored is adherence to tamoxifen therapy in men. I do know anecdotally that this is the discussion among men because of the impact on quality of life. I do worry that sometimes men perhaps make the wrong choice, and I think that’s an opportunity for more research. Again, if there were alternative therapies that were perhaps a little less impactful on things like libido, that might be an advance in the field.

Dr. Cardoso: We have been seeing more studies on the issue of quality of life. Noncompliance is also an issue in female patients. We have to acknowledge that. Not everybody is able to keep taking the treatments. Interestingly, when there is a relapse and people had stopped taking the tamoxifen, most of them say, “I stopped because I had not understood exactly how important it is.”

We come back to the importance of explaining that it is the most crucial treatment for this subtype of breast cancer. Again, information is really key.

Sometimes I also use the argument with my patients that the alternative is even worse because if you use an aromatase inhibitor, and you have to use an LHRH agonist, then the implications for your sexual life are even worse. That’s how I try to convince them to stay on tamoxifen.

Let’s finalize with a couple of words on metastatic breast cancer in male patients. Sharon, I’ll start with you again. Is there any difference in the management if you have a patient with metastatic, ER-positive, HER2-negative disease? How do you treat? How do you sequence the available therapies? Is it different from the female patient?

Dr. Giordano: I’d say that, big picture, it’s quite similar. Again, most of the men have hormone receptor–positive disease, so really, the mainstay of treatment and the first treatments are going to be endocrine therapies. We’ll sequence through the endocrine therapies like we do in women. When using aromatase inhibitors, I typically would add a GnRH agonist to that, and I have had that be a very successful therapy, along now with the CDK inhibitors that are also approved.

I don’t think the studies of CDK inhibitors included male patients, but at least palbociclib actually was approved in the United States, based on some real-world evidence of its efficacy. Anecdotally, again, in my clinical practice, that tends to be a really powerful combination of leuprolide, an aromatase inhibitor, and a CDK inhibitor.

I think there’s less information about drugs like fulvestrant, whether that would benefit from combination with a GnRH agonist or whether those should be given as single agents. We just don’t really know. We have a few case series out there.

Similar to the early breast cancer setting, I think it’s really important to remember to check for BRCA1 and BRCA2 mutations. PARP inhibitors could be a part of the treatment plan if those underlying germline mutations are found. Generally, we’re following a similar sequence of endocrine therapies and then, eventually, chemotherapy.

Dr. Cardoso: Maybe, Oliver, you’re also seeing that one consistent finding in the biology study is the importance of the AKT/PI3K/mTOR pathway in male patients with breast cancer, because we now have at least two classes of agents to tackle this pathway. Again, anecdotally – we’re not talking about trials – I’ve been seeing quite interesting responses, for example, to everolimus combined with endocrine therapy.

We have a little less experience with the PI3K inhibitor, but that’s just because of accessibility to the drug. I think this combination is also something to keep in mind that can be quite effective in these patients.

Dr. Bogler: I agree. Those findings are exciting in the context of dealing with something as difficult as metastatic breast cancer. It’s good to know that there’s some information coming and opportunities and options, hopefully, down the road for men facing that problem.

Dr. Cardoso: Sharon, although small numbers, in these cases where there is HER2-positive disease, you would also use the new anti-HER2 agents and more or less the same sequence, right?

Dr. Giordano: Absolutely. It’s not particularly data driven, but yes, I would. If it’s a HER2-positive tumor, I would use the same HER2-targeted therapies that are used for women with breast cancer.

Working toward a balance in patient care

Dr. Cardoso: I would like to add something for all of us to be united in the fight. I don’t know if it happens in the U.S., but in many countries, access to these new agents for male patients is very difficult because of the approval and the labeling. This is why I’m always fighting with those who are proposing that the labeling, again, says “women with breast cancer.”

It is really important that we keep on lobbying and pushing for the labeling to say “patients with breast cancer” so that nobody can withhold access to these new therapies because of gender. In the U.S., maybe you don’t have this problem. There are many European countries where men cannot access, for example, fulvestrant because it has been approved for women with breast cancer.

Dr. Giordano: Thankfully, I have not faced that issue very often. I’ve had occasional issues with getting GnRH agonists approved. Generally, in the U.S., if I provide, for example, the NCCN guideline recommendations, most insurers will cover it. I think it’s often just lack of knowledge.

Dr. Cardoso: It’s something to keep working hard on because for the old drugs that were approved with the wording that still said “women,” we have to keep fighting for accessibility.

I think we had a really nice discussion. I’m going to give you an opportunity for any last words that you want to say on this topic. Perhaps we’ll start with you, Sharon, and we’ll leave the very last word to Oliver.

Dr. Giordano: I would just emphasize the importance of doing research in this area. Hopefully, we will be able to get clinical trials. There are reasons to think that endocrine therapies may behave differently in men and women. We need to continue to work together as a community to collect the data so that we can ultimately improve the outcomes for our patients.

Dr. Bogler: I would echo what you just said, Dr. Giordano. I would like to express my gratitude to both of you. Dr. Giordano, you have a huge practice of men at MD Anderson. You took care of me and many other people I know.

Dr. Cardoso, you are a pioneer of a big registry trial that I am privileged to be working on, trying to gather data on men. You’re both pioneers in this field of working on behalf of people like me. I’m just very grateful for what you do.

Dr. Giordano: Thank you.

Dr. Cardoso: Thank you both for accepting this invitation. We hope that everybody takes more interest in this field. Who knows? Maybe we can find enough funds to run a specific trial for male patients with breast cancer.

Dr. Cardoso is director of the breast unit at Champalimaud Clinical Centre/Champalimaud Foundation, Lisbon. Dr. Giordano is professor of breast medical oncology and chair of health services research at the University of Texas MD Anderson Cancer Center, Houston. Dr. Bogler is a cancer biologist at the Randolph (Vt.) Center. Dr. Cardoso reported conflicts of interest with numerous pharmaceutical companies; Dr. Giordano and Dr. Bogler reported no conflicts of interest.

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

A novel DNA test system that assesses a person’s genetic predisposition for certain cancers – the first of its kind granted marketing authorization by the Food and Drug Administration – may become a valuable new public health tool.

The Common Hereditary Cancers Panel (Invitae) was approved late September following FDA review under the De Novo process, a regulatory pathway for new types of low- to moderate-risk devices.

Jezperklauzen/ThinkStock

Validation of the prescription-only in vitro test was based on assessments of more than 9,000 clinical samples, which demonstrated accuracy of at least 99% for all tested variants in 47 genes known to be associated with an increased risk of developing certain cancers, including breast, ovarian, uterine, prostate, colorectal, gastric, pancreatic as well as melanoma.
 

How the test system works

Next-generation sequencing assesses germline human genomic DNA extracted from a single blood sample collected at the point of care, such as a doctor’s office, and is sent to a laboratory for analysis.

Specifically, the system aims to detect substitutions, small insertion and deletion alterations, and copy number variants in the panel of 47 targeted genes.

This technology “can provide an important public health tool that offers individuals more information about their health, including possible predisposition for certain cancers,” Jeff Shuren, MD, JD, director of the FDA’s Center for Devices and Radiological health, explained in an FDA press release announcing the marketing authorization.

Clinical interpretation is based on evidence from the published literature, prediction programs, public databases, and Invitae’s own variants database, the FDA statement explained.
 

What the test can do

Not only can the Common Hereditary Cancer Panel identify genetic variants that increase an individual’s risk of certain cancers, the panel can also help identify potential cancer-related hereditary variants in patients already diagnosed with cancer.

The most clinically significant genes the test system can detect include BRCA1 and BRCA2, which have known associations with hereditary breast and ovarian cancer syndrome; Lynch syndrome–associated genes including MLH1, MSH2, MSH6, PMS2, and EPCAM; CDH1, which is largely associated with hereditary diffuse gastric cancer and lobular breast cancer; and STK11, which is associated with Peutz-Jeghers syndrome.

“Patients should speak with a health care professional, such as a genetic counselor, to discuss any personal/family history of cancer, as such information can be helpful in interpreting test results,” the FDA advised.
 

What the test can’t do

The test is not intended to identify or evaluate all known genes tied to a person’s potential predisposition for cancer. The test is also not intended for cancer screening or prenatal testing. 

For these reasons, and because genetics are not the only factor associated with developing cancer, negative test results could lead to misunderstanding among some patients about their cancer risk.

“Results are intended to be interpreted within the context of additional laboratory results, family history, and clinical findings,” the company wrote in a statement.
 

Test safety

Risks associated with the test include the possibility of false positive and false negative results and the potential for people to misunderstand what the results mean about their risk for cancer.

A false sense of assurance after a false negative result might, for instance, lead patients to forgo recommended surveillance or clinical management, whereas false positive test results could lead to inappropriate decision-making and undesirable consequences.

“These risks are mitigated by the analytical performance validation, clinical validation, and appropriate labeling of this test,” the agency explained.

Along with the De Novo authorization, the FDA is establishing special controls to define requirements for these tests. For instance, accuracy must be 99% or higher for positive agreement and at least 99.9% for negative agreement with a validated, independent method.
 

Public health implications

The information gleaned from this tool can “help guide physicians to provide appropriate monitoring and potential therapy, based on discovered variants,” Dr. Shuren said.

The marketing authorization of Invitae’s test established a new regulatory category, which “means that subsequent devices of the same type with the same intended use may go through FDA’s 510(k) premarket process,” the FDA explained.

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

A novel DNA test system that assesses a person’s genetic predisposition for certain cancers – the first of its kind granted marketing authorization by the Food and Drug Administration – may become a valuable new public health tool.

The Common Hereditary Cancers Panel (Invitae) was approved late September following FDA review under the De Novo process, a regulatory pathway for new types of low- to moderate-risk devices.

Jezperklauzen/ThinkStock

Validation of the prescription-only in vitro test was based on assessments of more than 9,000 clinical samples, which demonstrated accuracy of at least 99% for all tested variants in 47 genes known to be associated with an increased risk of developing certain cancers, including breast, ovarian, uterine, prostate, colorectal, gastric, pancreatic as well as melanoma.
 

How the test system works

Next-generation sequencing assesses germline human genomic DNA extracted from a single blood sample collected at the point of care, such as a doctor’s office, and is sent to a laboratory for analysis.

Specifically, the system aims to detect substitutions, small insertion and deletion alterations, and copy number variants in the panel of 47 targeted genes.

This technology “can provide an important public health tool that offers individuals more information about their health, including possible predisposition for certain cancers,” Jeff Shuren, MD, JD, director of the FDA’s Center for Devices and Radiological health, explained in an FDA press release announcing the marketing authorization.

Clinical interpretation is based on evidence from the published literature, prediction programs, public databases, and Invitae’s own variants database, the FDA statement explained.
 

What the test can do

Not only can the Common Hereditary Cancer Panel identify genetic variants that increase an individual’s risk of certain cancers, the panel can also help identify potential cancer-related hereditary variants in patients already diagnosed with cancer.

The most clinically significant genes the test system can detect include BRCA1 and BRCA2, which have known associations with hereditary breast and ovarian cancer syndrome; Lynch syndrome–associated genes including MLH1, MSH2, MSH6, PMS2, and EPCAM; CDH1, which is largely associated with hereditary diffuse gastric cancer and lobular breast cancer; and STK11, which is associated with Peutz-Jeghers syndrome.

“Patients should speak with a health care professional, such as a genetic counselor, to discuss any personal/family history of cancer, as such information can be helpful in interpreting test results,” the FDA advised.
 

What the test can’t do

The test is not intended to identify or evaluate all known genes tied to a person’s potential predisposition for cancer. The test is also not intended for cancer screening or prenatal testing. 

For these reasons, and because genetics are not the only factor associated with developing cancer, negative test results could lead to misunderstanding among some patients about their cancer risk.

“Results are intended to be interpreted within the context of additional laboratory results, family history, and clinical findings,” the company wrote in a statement.
 

Test safety

Risks associated with the test include the possibility of false positive and false negative results and the potential for people to misunderstand what the results mean about their risk for cancer.

A false sense of assurance after a false negative result might, for instance, lead patients to forgo recommended surveillance or clinical management, whereas false positive test results could lead to inappropriate decision-making and undesirable consequences.

“These risks are mitigated by the analytical performance validation, clinical validation, and appropriate labeling of this test,” the agency explained.

Along with the De Novo authorization, the FDA is establishing special controls to define requirements for these tests. For instance, accuracy must be 99% or higher for positive agreement and at least 99.9% for negative agreement with a validated, independent method.
 

Public health implications

The information gleaned from this tool can “help guide physicians to provide appropriate monitoring and potential therapy, based on discovered variants,” Dr. Shuren said.

The marketing authorization of Invitae’s test established a new regulatory category, which “means that subsequent devices of the same type with the same intended use may go through FDA’s 510(k) premarket process,” the FDA explained.

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

A novel DNA test system that assesses a person’s genetic predisposition for certain cancers – the first of its kind granted marketing authorization by the Food and Drug Administration – may become a valuable new public health tool.

The Common Hereditary Cancers Panel (Invitae) was approved late September following FDA review under the De Novo process, a regulatory pathway for new types of low- to moderate-risk devices.

Jezperklauzen/ThinkStock

Validation of the prescription-only in vitro test was based on assessments of more than 9,000 clinical samples, which demonstrated accuracy of at least 99% for all tested variants in 47 genes known to be associated with an increased risk of developing certain cancers, including breast, ovarian, uterine, prostate, colorectal, gastric, pancreatic as well as melanoma.
 

How the test system works

Next-generation sequencing assesses germline human genomic DNA extracted from a single blood sample collected at the point of care, such as a doctor’s office, and is sent to a laboratory for analysis.

Specifically, the system aims to detect substitutions, small insertion and deletion alterations, and copy number variants in the panel of 47 targeted genes.

This technology “can provide an important public health tool that offers individuals more information about their health, including possible predisposition for certain cancers,” Jeff Shuren, MD, JD, director of the FDA’s Center for Devices and Radiological health, explained in an FDA press release announcing the marketing authorization.

Clinical interpretation is based on evidence from the published literature, prediction programs, public databases, and Invitae’s own variants database, the FDA statement explained.
 

What the test can do

Not only can the Common Hereditary Cancer Panel identify genetic variants that increase an individual’s risk of certain cancers, the panel can also help identify potential cancer-related hereditary variants in patients already diagnosed with cancer.

The most clinically significant genes the test system can detect include BRCA1 and BRCA2, which have known associations with hereditary breast and ovarian cancer syndrome; Lynch syndrome–associated genes including MLH1, MSH2, MSH6, PMS2, and EPCAM; CDH1, which is largely associated with hereditary diffuse gastric cancer and lobular breast cancer; and STK11, which is associated with Peutz-Jeghers syndrome.

“Patients should speak with a health care professional, such as a genetic counselor, to discuss any personal/family history of cancer, as such information can be helpful in interpreting test results,” the FDA advised.
 

What the test can’t do

The test is not intended to identify or evaluate all known genes tied to a person’s potential predisposition for cancer. The test is also not intended for cancer screening or prenatal testing. 

For these reasons, and because genetics are not the only factor associated with developing cancer, negative test results could lead to misunderstanding among some patients about their cancer risk.

“Results are intended to be interpreted within the context of additional laboratory results, family history, and clinical findings,” the company wrote in a statement.
 

Test safety

Risks associated with the test include the possibility of false positive and false negative results and the potential for people to misunderstand what the results mean about their risk for cancer.

A false sense of assurance after a false negative result might, for instance, lead patients to forgo recommended surveillance or clinical management, whereas false positive test results could lead to inappropriate decision-making and undesirable consequences.

“These risks are mitigated by the analytical performance validation, clinical validation, and appropriate labeling of this test,” the agency explained.

Along with the De Novo authorization, the FDA is establishing special controls to define requirements for these tests. For instance, accuracy must be 99% or higher for positive agreement and at least 99.9% for negative agreement with a validated, independent method.
 

Public health implications

The information gleaned from this tool can “help guide physicians to provide appropriate monitoring and potential therapy, based on discovered variants,” Dr. Shuren said.

The marketing authorization of Invitae’s test established a new regulatory category, which “means that subsequent devices of the same type with the same intended use may go through FDA’s 510(k) premarket process,” the FDA explained.

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

CHICAGO—A new report offers a picture of patients seeking care for breast and gynecological cancers within the US Department of Veterans Affairs (VA) health care system: They are somewhat younger than their counterparts in the general population, and those with breast cancer are much more likely to be men.

            It is not clear whether these numbers are purely a reflection of the unique population within the VA or whether there is a more complicated explanation. Researchers also found that more than half of those with newly diagnosed breast, cervical, and ovarian cancers lived in the South compared with few (8%-13%) who lived in the Northeast.

The study findings were released in a poster at the 2023 annual meeting of the Association of VA Hematology/Oncology. Sarah Colonna, MD, study coauthor and medical director of breast oncology for the national VA, said in an interview that it is important to understand statistics regarding breast and gynecological cancer within the VA, especially as the system focuses more on patients with the conditions. And, she said, the wave of women who joined the military in recent decades are getting older and more likely to need oncology care. “We know women veterans are coming: They’re aging, and they’re going to get cancer.”

Colonna and colleagues examined statistics from the VA Corporate Data Warehouse to determine how many veterans were newly diagnosed with breast, uterine, ovarian, cervical, and vulvovaginal cancer in 2021 and 2022. The researchers compared their findings with 2020 statistics about the general population from the SEER database.

Within the VA, there were 3304 cases of breast cancer (mean age, 59 years; range, 23-99; mean body mass index [BMI], 31), 344 cases of cervical cancer (mean age, 46 years; range, 22-90; mean BMI, 29), 177 cases of ovarian cancer (mean age, 57 years; range, 24-80; mean BMI, 29), 365 cases of uterine cancer (mean age, 60 years; range, 24-85; mean BMI, 35), and 32 cases of vaginal/vulvar cancer (mean age, 56 years; range, 24-75; mean BMI, 31).

In contrast, the mean ages at diagnosis for the general population were slightly higher at 63 years for breast cancer, 50 years for cervical cancer, 63 years for ovarian cancer, and 63 years for uterine cancer. Vaginal/vulvar cancer was a bit of an outlier at mean age 69 years for the general population vs 56 years for the VA population; however, the number of cases in the latter group was quite low at 32 patients.

Overall, gynecological cancers were diagnosed at an average age of 55 years among the VA population vs 61 years among the general population. Men made up 11% of breast cancer cases in the VA vs 1% in the general population. “Of course, we have 10 times the proportion of men than in the outside,” said Colonna, an oncologist with the Huntsman Cancer Institute/Wahlen VA Medical Center in Utah. That may explain the difference, “but nobody knows for sure,” she said.

Patients Within the VA with the following cancers were more likely to be Black veterans than in the general population: breast, 30% vs 12%; cervical, 20% vs 14%; ovarian, 28% vs 10%; uterine, 25% vs 12%; and vaginal/vulvar, 44% vs 10%. This could reflect the fact that 30% of women treated within the VA are Black women vs 12% in the general population, Colonna said. Unfortunately, she said, “black women with breast cancer, tend to do really poorly. They tend to get it young, and they tend to die.”

As for the geographic distribution of cases, Colonna said it represents the high numbers of veterans who live in the South, suggesting that more VA oncology resources may be needed there.

In an interview, Aditi Hazra, PhD, MPH, an assistant professor of medicine at Harvard Medical School, said the new analysis is “very valuable”: “Women are a growing proportion of the veterans who serve, and we need more data to understand the risk factors and incidents of disease in this population.” Hazra said the next step will be to control the data for risk factors and “tease out what is driving the rates in the VA.”

There is no study funding, and the authors have no disclosures. Dr. Hazra discloses that she works for the VA and has collaborated with one of the study authors. 

CHICAGO—A new report offers a picture of patients seeking care for breast and gynecological cancers within the US Department of Veterans Affairs (VA) health care system: They are somewhat younger than their counterparts in the general population, and those with breast cancer are much more likely to be men.

            It is not clear whether these numbers are purely a reflection of the unique population within the VA or whether there is a more complicated explanation. Researchers also found that more than half of those with newly diagnosed breast, cervical, and ovarian cancers lived in the South compared with few (8%-13%) who lived in the Northeast.

The study findings were released in a poster at the 2023 annual meeting of the Association of VA Hematology/Oncology. Sarah Colonna, MD, study coauthor and medical director of breast oncology for the national VA, said in an interview that it is important to understand statistics regarding breast and gynecological cancer within the VA, especially as the system focuses more on patients with the conditions. And, she said, the wave of women who joined the military in recent decades are getting older and more likely to need oncology care. “We know women veterans are coming: They’re aging, and they’re going to get cancer.”

Colonna and colleagues examined statistics from the VA Corporate Data Warehouse to determine how many veterans were newly diagnosed with breast, uterine, ovarian, cervical, and vulvovaginal cancer in 2021 and 2022. The researchers compared their findings with 2020 statistics about the general population from the SEER database.

Within the VA, there were 3304 cases of breast cancer (mean age, 59 years; range, 23-99; mean body mass index [BMI], 31), 344 cases of cervical cancer (mean age, 46 years; range, 22-90; mean BMI, 29), 177 cases of ovarian cancer (mean age, 57 years; range, 24-80; mean BMI, 29), 365 cases of uterine cancer (mean age, 60 years; range, 24-85; mean BMI, 35), and 32 cases of vaginal/vulvar cancer (mean age, 56 years; range, 24-75; mean BMI, 31).

In contrast, the mean ages at diagnosis for the general population were slightly higher at 63 years for breast cancer, 50 years for cervical cancer, 63 years for ovarian cancer, and 63 years for uterine cancer. Vaginal/vulvar cancer was a bit of an outlier at mean age 69 years for the general population vs 56 years for the VA population; however, the number of cases in the latter group was quite low at 32 patients.

Overall, gynecological cancers were diagnosed at an average age of 55 years among the VA population vs 61 years among the general population. Men made up 11% of breast cancer cases in the VA vs 1% in the general population. “Of course, we have 10 times the proportion of men than in the outside,” said Colonna, an oncologist with the Huntsman Cancer Institute/Wahlen VA Medical Center in Utah. That may explain the difference, “but nobody knows for sure,” she said.

Patients Within the VA with the following cancers were more likely to be Black veterans than in the general population: breast, 30% vs 12%; cervical, 20% vs 14%; ovarian, 28% vs 10%; uterine, 25% vs 12%; and vaginal/vulvar, 44% vs 10%. This could reflect the fact that 30% of women treated within the VA are Black women vs 12% in the general population, Colonna said. Unfortunately, she said, “black women with breast cancer, tend to do really poorly. They tend to get it young, and they tend to die.”

As for the geographic distribution of cases, Colonna said it represents the high numbers of veterans who live in the South, suggesting that more VA oncology resources may be needed there.

In an interview, Aditi Hazra, PhD, MPH, an assistant professor of medicine at Harvard Medical School, said the new analysis is “very valuable”: “Women are a growing proportion of the veterans who serve, and we need more data to understand the risk factors and incidents of disease in this population.” Hazra said the next step will be to control the data for risk factors and “tease out what is driving the rates in the VA.”

There is no study funding, and the authors have no disclosures. Dr. Hazra discloses that she works for the VA and has collaborated with one of the study authors. 

CHICAGO—A new report offers a picture of patients seeking care for breast and gynecological cancers within the US Department of Veterans Affairs (VA) health care system: They are somewhat younger than their counterparts in the general population, and those with breast cancer are much more likely to be men.

            It is not clear whether these numbers are purely a reflection of the unique population within the VA or whether there is a more complicated explanation. Researchers also found that more than half of those with newly diagnosed breast, cervical, and ovarian cancers lived in the South compared with few (8%-13%) who lived in the Northeast.

The study findings were released in a poster at the 2023 annual meeting of the Association of VA Hematology/Oncology. Sarah Colonna, MD, study coauthor and medical director of breast oncology for the national VA, said in an interview that it is important to understand statistics regarding breast and gynecological cancer within the VA, especially as the system focuses more on patients with the conditions. And, she said, the wave of women who joined the military in recent decades are getting older and more likely to need oncology care. “We know women veterans are coming: They’re aging, and they’re going to get cancer.”

Colonna and colleagues examined statistics from the VA Corporate Data Warehouse to determine how many veterans were newly diagnosed with breast, uterine, ovarian, cervical, and vulvovaginal cancer in 2021 and 2022. The researchers compared their findings with 2020 statistics about the general population from the SEER database.

Within the VA, there were 3304 cases of breast cancer (mean age, 59 years; range, 23-99; mean body mass index [BMI], 31), 344 cases of cervical cancer (mean age, 46 years; range, 22-90; mean BMI, 29), 177 cases of ovarian cancer (mean age, 57 years; range, 24-80; mean BMI, 29), 365 cases of uterine cancer (mean age, 60 years; range, 24-85; mean BMI, 35), and 32 cases of vaginal/vulvar cancer (mean age, 56 years; range, 24-75; mean BMI, 31).

In contrast, the mean ages at diagnosis for the general population were slightly higher at 63 years for breast cancer, 50 years for cervical cancer, 63 years for ovarian cancer, and 63 years for uterine cancer. Vaginal/vulvar cancer was a bit of an outlier at mean age 69 years for the general population vs 56 years for the VA population; however, the number of cases in the latter group was quite low at 32 patients.

Overall, gynecological cancers were diagnosed at an average age of 55 years among the VA population vs 61 years among the general population. Men made up 11% of breast cancer cases in the VA vs 1% in the general population. “Of course, we have 10 times the proportion of men than in the outside,” said Colonna, an oncologist with the Huntsman Cancer Institute/Wahlen VA Medical Center in Utah. That may explain the difference, “but nobody knows for sure,” she said.

Patients Within the VA with the following cancers were more likely to be Black veterans than in the general population: breast, 30% vs 12%; cervical, 20% vs 14%; ovarian, 28% vs 10%; uterine, 25% vs 12%; and vaginal/vulvar, 44% vs 10%. This could reflect the fact that 30% of women treated within the VA are Black women vs 12% in the general population, Colonna said. Unfortunately, she said, “black women with breast cancer, tend to do really poorly. They tend to get it young, and they tend to die.”

As for the geographic distribution of cases, Colonna said it represents the high numbers of veterans who live in the South, suggesting that more VA oncology resources may be needed there.

In an interview, Aditi Hazra, PhD, MPH, an assistant professor of medicine at Harvard Medical School, said the new analysis is “very valuable”: “Women are a growing proportion of the veterans who serve, and we need more data to understand the risk factors and incidents of disease in this population.” Hazra said the next step will be to control the data for risk factors and “tease out what is driving the rates in the VA.”

There is no study funding, and the authors have no disclosures. Dr. Hazra discloses that she works for the VA and has collaborated with one of the study authors. 

Screening for cancer is only half the battle: Patients often fail to complete recommended follow-up and additional testing after an abnormal result, leaving them at risk, according to authors of a new study published in the Journal of the American Medical Association.

Results from the clustered, randomized clinical trial indicate that systems-based interventions, such as automating reminders in electronic health records (EHRs), outreach in the form of phone calls or letters, and assistance with barriers to health care, such as housing insecurity, can increase the number of patients who complete appropriate diagnostic follow-up after an abnormal result.

Patients who received an EHR reminder, outreach call or letter, and additional calls to screen for and assist with nine barriers to health care – housing insecurity, food insecurity, paying for basic utilities, family caregiving, legal issues, transportation, financial compensation for treatment, education, and employment – completed follow-up within 120 days of study enrollment at a rate of 31.4%. The follow-up rate was 31% for those who received only an EHR reminder and outreach, 22.7% for those who received only an EHR reminder, and 22.9% for those who received usual care.

“The benefits of cancer screening won’t be fully realized without systems to ensure timely follow-up of abnormal results,” said Anna Tosteson, ScD, director of the Dartmouth Institute for Health Policy and Clinical Practice in Lebanon, N.H., a coauthor of the study.

Current payment incentives and quality-of-care indicators focus on getting people in for screening but should also address completion of screening – meaning timely and appropriate follow-up of results that could be indicative of cancer, Dr. Tosteson said.

“There’s a disconnect if you have screening rates that are high but once people have an abnormal result, which is potentially one step closer to a cancer diagnosis, there are no systems in place to help clinicians track them,” said study coauthor Jennifer Haas, MD, director of the Center for Primary Care Research at Massachusetts General Hospital in Boston.

In a 2016 study, researchers found that follow-up rates after abnormal cancer screenings varied widely. While 95.6% of patients with abnormal breast cancer screenings underwent timely follow-up testing, only 68.1% of patients with colorectal abnormalities and 44.8% of patients with cervical abnormalities did so.

Researchers for the new study used guideline recommendations and specialist input to create automated EHR algorithms that determined a follow-up period and diagnostic test.

They put the algorithm into practice with 11,980 patients who were part of 44 primary care practices within three health networks between August 2020 and December 2021. All patients had received abnormal test results for colorectal, breast, cervical, or lung cancer in varying risk categories.

All patients received usual care from their providers, which consisted of a “hodgepodge of whatever their clinic usually does,” Dr. Haas said. Without standards and systems in place for follow-up, the burden of testing and tracking patients with abnormal results typically falls on the primary care provider.

The researchers intervened only when patients were overdue for completion of follow-up. They then staggered the interventions sequentially.

All study participants received an automated, algorithm-triggered EHR reminder for follow-up in their patient portal along with routine health maintenance reminders. To view the reminder, patients had to log into their portal. Participants in the outreach and outreach and navigation groups also received a phone call, an EHR message, or a physical letter 2 weeks after receiving an EHR notification if they hadn’t completed follow-up. Research assistants performed the outreach after having been prompted by the algorithm.

After another 4 weeks, those in the EHR, outreach, and navigation group received a call from a patient navigator who helped them address nine barriers to health care, chiefly by providing them with referrals to free resources.

Among patients who received navigation, outcomes were not significantly better than among those who received EHR and outreach, indicating social determinants of health did not significantly affect the population studied or that the modest approach to navigation and the resources provided were insufficient, Dr. Haas said.

The complexity of an automated platform that encompasses many types of cancers, test results, and other data elements could prove difficult to apply in settings with less infrastructure, said Steven Atlas, MD, MPH, director of the Practice-Based Research and Quality Improvement Network in the division of general internal medicine at Mass General.

“I think there’s a role for the federal government to take on these initiatives,” Dr. Atlas said. Government intervention could help create “national IT systems to create standards for creating code for what an abnormal result is and how it should be followed,” he said.

While interventions improved patient follow-up, the overall rates were still low.

“What concerns me is that despite the various interventions implemented to encourage and support patients to return for follow-up testing, over 60% of patients still did not return for the recommended testing,” said Joann G. Elmore, MD, MPH, professor of medicine at the University of California, Los Angeles. Dr. Elmore was not involved with the study.

The research took place during the COVID-19 pandemic, which may have reduced follow-up, the study authors wrote. Still, given that previous research has shown that follow-up tends to be low, the rates highlight “the need to understand factors associated with not completing follow-up that go beyond reminder effort,” they wrote. These include a need for patient education about the meaning of test results and what follow-up procedures involve.

The study was supported by the National Cancer Institute and the American Cancer Society. The authors have disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Screening for cancer is only half the battle: Patients often fail to complete recommended follow-up and additional testing after an abnormal result, leaving them at risk, according to authors of a new study published in the Journal of the American Medical Association.

Results from the clustered, randomized clinical trial indicate that systems-based interventions, such as automating reminders in electronic health records (EHRs), outreach in the form of phone calls or letters, and assistance with barriers to health care, such as housing insecurity, can increase the number of patients who complete appropriate diagnostic follow-up after an abnormal result.

Patients who received an EHR reminder, outreach call or letter, and additional calls to screen for and assist with nine barriers to health care – housing insecurity, food insecurity, paying for basic utilities, family caregiving, legal issues, transportation, financial compensation for treatment, education, and employment – completed follow-up within 120 days of study enrollment at a rate of 31.4%. The follow-up rate was 31% for those who received only an EHR reminder and outreach, 22.7% for those who received only an EHR reminder, and 22.9% for those who received usual care.

“The benefits of cancer screening won’t be fully realized without systems to ensure timely follow-up of abnormal results,” said Anna Tosteson, ScD, director of the Dartmouth Institute for Health Policy and Clinical Practice in Lebanon, N.H., a coauthor of the study.

Current payment incentives and quality-of-care indicators focus on getting people in for screening but should also address completion of screening – meaning timely and appropriate follow-up of results that could be indicative of cancer, Dr. Tosteson said.

“There’s a disconnect if you have screening rates that are high but once people have an abnormal result, which is potentially one step closer to a cancer diagnosis, there are no systems in place to help clinicians track them,” said study coauthor Jennifer Haas, MD, director of the Center for Primary Care Research at Massachusetts General Hospital in Boston.

In a 2016 study, researchers found that follow-up rates after abnormal cancer screenings varied widely. While 95.6% of patients with abnormal breast cancer screenings underwent timely follow-up testing, only 68.1% of patients with colorectal abnormalities and 44.8% of patients with cervical abnormalities did so.

Researchers for the new study used guideline recommendations and specialist input to create automated EHR algorithms that determined a follow-up period and diagnostic test.

They put the algorithm into practice with 11,980 patients who were part of 44 primary care practices within three health networks between August 2020 and December 2021. All patients had received abnormal test results for colorectal, breast, cervical, or lung cancer in varying risk categories.

All patients received usual care from their providers, which consisted of a “hodgepodge of whatever their clinic usually does,” Dr. Haas said. Without standards and systems in place for follow-up, the burden of testing and tracking patients with abnormal results typically falls on the primary care provider.

The researchers intervened only when patients were overdue for completion of follow-up. They then staggered the interventions sequentially.

All study participants received an automated, algorithm-triggered EHR reminder for follow-up in their patient portal along with routine health maintenance reminders. To view the reminder, patients had to log into their portal. Participants in the outreach and outreach and navigation groups also received a phone call, an EHR message, or a physical letter 2 weeks after receiving an EHR notification if they hadn’t completed follow-up. Research assistants performed the outreach after having been prompted by the algorithm.

After another 4 weeks, those in the EHR, outreach, and navigation group received a call from a patient navigator who helped them address nine barriers to health care, chiefly by providing them with referrals to free resources.

Among patients who received navigation, outcomes were not significantly better than among those who received EHR and outreach, indicating social determinants of health did not significantly affect the population studied or that the modest approach to navigation and the resources provided were insufficient, Dr. Haas said.

The complexity of an automated platform that encompasses many types of cancers, test results, and other data elements could prove difficult to apply in settings with less infrastructure, said Steven Atlas, MD, MPH, director of the Practice-Based Research and Quality Improvement Network in the division of general internal medicine at Mass General.

“I think there’s a role for the federal government to take on these initiatives,” Dr. Atlas said. Government intervention could help create “national IT systems to create standards for creating code for what an abnormal result is and how it should be followed,” he said.

While interventions improved patient follow-up, the overall rates were still low.

“What concerns me is that despite the various interventions implemented to encourage and support patients to return for follow-up testing, over 60% of patients still did not return for the recommended testing,” said Joann G. Elmore, MD, MPH, professor of medicine at the University of California, Los Angeles. Dr. Elmore was not involved with the study.

The research took place during the COVID-19 pandemic, which may have reduced follow-up, the study authors wrote. Still, given that previous research has shown that follow-up tends to be low, the rates highlight “the need to understand factors associated with not completing follow-up that go beyond reminder effort,” they wrote. These include a need for patient education about the meaning of test results and what follow-up procedures involve.

The study was supported by the National Cancer Institute and the American Cancer Society. The authors have disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Screening for cancer is only half the battle: Patients often fail to complete recommended follow-up and additional testing after an abnormal result, leaving them at risk, according to authors of a new study published in the Journal of the American Medical Association.

Results from the clustered, randomized clinical trial indicate that systems-based interventions, such as automating reminders in electronic health records (EHRs), outreach in the form of phone calls or letters, and assistance with barriers to health care, such as housing insecurity, can increase the number of patients who complete appropriate diagnostic follow-up after an abnormal result.

Patients who received an EHR reminder, outreach call or letter, and additional calls to screen for and assist with nine barriers to health care – housing insecurity, food insecurity, paying for basic utilities, family caregiving, legal issues, transportation, financial compensation for treatment, education, and employment – completed follow-up within 120 days of study enrollment at a rate of 31.4%. The follow-up rate was 31% for those who received only an EHR reminder and outreach, 22.7% for those who received only an EHR reminder, and 22.9% for those who received usual care.

“The benefits of cancer screening won’t be fully realized without systems to ensure timely follow-up of abnormal results,” said Anna Tosteson, ScD, director of the Dartmouth Institute for Health Policy and Clinical Practice in Lebanon, N.H., a coauthor of the study.

Current payment incentives and quality-of-care indicators focus on getting people in for screening but should also address completion of screening – meaning timely and appropriate follow-up of results that could be indicative of cancer, Dr. Tosteson said.

“There’s a disconnect if you have screening rates that are high but once people have an abnormal result, which is potentially one step closer to a cancer diagnosis, there are no systems in place to help clinicians track them,” said study coauthor Jennifer Haas, MD, director of the Center for Primary Care Research at Massachusetts General Hospital in Boston.

In a 2016 study, researchers found that follow-up rates after abnormal cancer screenings varied widely. While 95.6% of patients with abnormal breast cancer screenings underwent timely follow-up testing, only 68.1% of patients with colorectal abnormalities and 44.8% of patients with cervical abnormalities did so.

Researchers for the new study used guideline recommendations and specialist input to create automated EHR algorithms that determined a follow-up period and diagnostic test.

They put the algorithm into practice with 11,980 patients who were part of 44 primary care practices within three health networks between August 2020 and December 2021. All patients had received abnormal test results for colorectal, breast, cervical, or lung cancer in varying risk categories.

All patients received usual care from their providers, which consisted of a “hodgepodge of whatever their clinic usually does,” Dr. Haas said. Without standards and systems in place for follow-up, the burden of testing and tracking patients with abnormal results typically falls on the primary care provider.

The researchers intervened only when patients were overdue for completion of follow-up. They then staggered the interventions sequentially.

All study participants received an automated, algorithm-triggered EHR reminder for follow-up in their patient portal along with routine health maintenance reminders. To view the reminder, patients had to log into their portal. Participants in the outreach and outreach and navigation groups also received a phone call, an EHR message, or a physical letter 2 weeks after receiving an EHR notification if they hadn’t completed follow-up. Research assistants performed the outreach after having been prompted by the algorithm.

After another 4 weeks, those in the EHR, outreach, and navigation group received a call from a patient navigator who helped them address nine barriers to health care, chiefly by providing them with referrals to free resources.

Among patients who received navigation, outcomes were not significantly better than among those who received EHR and outreach, indicating social determinants of health did not significantly affect the population studied or that the modest approach to navigation and the resources provided were insufficient, Dr. Haas said.

The complexity of an automated platform that encompasses many types of cancers, test results, and other data elements could prove difficult to apply in settings with less infrastructure, said Steven Atlas, MD, MPH, director of the Practice-Based Research and Quality Improvement Network in the division of general internal medicine at Mass General.

“I think there’s a role for the federal government to take on these initiatives,” Dr. Atlas said. Government intervention could help create “national IT systems to create standards for creating code for what an abnormal result is and how it should be followed,” he said.

While interventions improved patient follow-up, the overall rates were still low.

“What concerns me is that despite the various interventions implemented to encourage and support patients to return for follow-up testing, over 60% of patients still did not return for the recommended testing,” said Joann G. Elmore, MD, MPH, professor of medicine at the University of California, Los Angeles. Dr. Elmore was not involved with the study.

The research took place during the COVID-19 pandemic, which may have reduced follow-up, the study authors wrote. Still, given that previous research has shown that follow-up tends to be low, the rates highlight “the need to understand factors associated with not completing follow-up that go beyond reminder effort,” they wrote. These include a need for patient education about the meaning of test results and what follow-up procedures involve.

The study was supported by the National Cancer Institute and the American Cancer Society. The authors have disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Opposition to the current American Board of Internal Medicine’s (ABIM’s) Maintenance of Certification (MOC) process continues to gain momentum, with the latest condemnation coming from the American Society of Hematology (ASH).

ASH president Robert A. Brodsky, MD, sent a letter to ABIM’s President and Chief Executive Officer Richard Baron, MD, highlighting hematologists’ concerns about the MOC process and outlining immediate actions ABIM should take.

“ASH continues to support the importance of lifelong learning for hematologists via a program that is evidence-based, relevant to one’s practice, and transparent; however, these three basic requirements are not met by the current ABIM MOC program,” Dr. Brodsky stated in the Sept. 27 letter to Baron.

Dr. Brodsky highlighted, for instance, the fact that the Longitudinal Knowledge Assessment – the alternative to the 10-year exam – “does not reflect real life practice, nor does it target each individual’s scope of practice.” Dr. Brodsky added that, according to members of ASH, the assessment is also “creating high levels of stress and contributing to burnout.”

The letter from Dr. Brodsky urged ABIM to “establish a new MOC program” that does not involve high-stakes assessments, reduces the number of Longitudinal Knowledge Assessment questions physicians receive, and eliminates redundancy between the MOC requirement to have a current license and the requirement to report continued medical education to ABIM.

The ABIM shared a copy of the letter in a Sept. 28 blog post defending the MOC process, highlighting past collaboration with ASH that “has led to meaningful enhancements to the [MOC] program” and committing to “continue to listen to and learn from the physician community going forward.”

The recent backlash against the MOC process stemmed from a petition demanding an end to the MOC. The petition was launched in July by hematologist-oncologist Aaron Goodman, MD, from the University of California, San Diego, who has been a vocal critic of the MOC process.

The criticism largely centered around the high costs and the “complex and time-consuming process that poses significant challenges to practicing physicians,” Dr. Goodman wrote in the petition, which has garnered more than 20,700 signatures.

In August, the Society for Cardiovascular Angiography and Interventions (SCAI) published “SCAI Position on ABIM Revocation of Certification for Not Participating in MOC.” The Electrophysiology Advocacy Foundation and the Heart Rhythm Society (HRS) issued statements pushing back on the MOC as well.

On Sept. 21, the SCAI, HRS, American College of Cardiology, and the Heart Failure Society of America went a step further and announced plans to create a new certification process that is independent of the ABIM MOC system.

The American Society of Clinical Oncology (ASCO) is now also surveying members about their MOC experience. A Sept. 26 announcement encouraged recipients to check their inboxes for a link to an anonymous MOC Experience Questionnaire before Oct. 12 and thanked respondents for their “engagement as ASCO works to address this critical issue for the oncology community.”

After ASH sent its letter to ABIM, Dr. Goodman applauded the society’s stance in a post on his X (formerly Twitter) account. Vincent Rajkumar, MD, a hematologist at the Mayo Clinic in Rochester, Minn., commented on ABIM’s response to ASH’s letter via X, noting, “If I were @ASH_hematology leadership, I would take ABIM response as disrespectful. A hasty response within a day is not a sign of good faith.”

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

Opposition to the current American Board of Internal Medicine’s (ABIM’s) Maintenance of Certification (MOC) process continues to gain momentum, with the latest condemnation coming from the American Society of Hematology (ASH).

ASH president Robert A. Brodsky, MD, sent a letter to ABIM’s President and Chief Executive Officer Richard Baron, MD, highlighting hematologists’ concerns about the MOC process and outlining immediate actions ABIM should take.

“ASH continues to support the importance of lifelong learning for hematologists via a program that is evidence-based, relevant to one’s practice, and transparent; however, these three basic requirements are not met by the current ABIM MOC program,” Dr. Brodsky stated in the Sept. 27 letter to Baron.

Dr. Brodsky highlighted, for instance, the fact that the Longitudinal Knowledge Assessment – the alternative to the 10-year exam – “does not reflect real life practice, nor does it target each individual’s scope of practice.” Dr. Brodsky added that, according to members of ASH, the assessment is also “creating high levels of stress and contributing to burnout.”

The letter from Dr. Brodsky urged ABIM to “establish a new MOC program” that does not involve high-stakes assessments, reduces the number of Longitudinal Knowledge Assessment questions physicians receive, and eliminates redundancy between the MOC requirement to have a current license and the requirement to report continued medical education to ABIM.

The ABIM shared a copy of the letter in a Sept. 28 blog post defending the MOC process, highlighting past collaboration with ASH that “has led to meaningful enhancements to the [MOC] program” and committing to “continue to listen to and learn from the physician community going forward.”

The recent backlash against the MOC process stemmed from a petition demanding an end to the MOC. The petition was launched in July by hematologist-oncologist Aaron Goodman, MD, from the University of California, San Diego, who has been a vocal critic of the MOC process.

The criticism largely centered around the high costs and the “complex and time-consuming process that poses significant challenges to practicing physicians,” Dr. Goodman wrote in the petition, which has garnered more than 20,700 signatures.

In August, the Society for Cardiovascular Angiography and Interventions (SCAI) published “SCAI Position on ABIM Revocation of Certification for Not Participating in MOC.” The Electrophysiology Advocacy Foundation and the Heart Rhythm Society (HRS) issued statements pushing back on the MOC as well.

On Sept. 21, the SCAI, HRS, American College of Cardiology, and the Heart Failure Society of America went a step further and announced plans to create a new certification process that is independent of the ABIM MOC system.

The American Society of Clinical Oncology (ASCO) is now also surveying members about their MOC experience. A Sept. 26 announcement encouraged recipients to check their inboxes for a link to an anonymous MOC Experience Questionnaire before Oct. 12 and thanked respondents for their “engagement as ASCO works to address this critical issue for the oncology community.”

After ASH sent its letter to ABIM, Dr. Goodman applauded the society’s stance in a post on his X (formerly Twitter) account. Vincent Rajkumar, MD, a hematologist at the Mayo Clinic in Rochester, Minn., commented on ABIM’s response to ASH’s letter via X, noting, “If I were @ASH_hematology leadership, I would take ABIM response as disrespectful. A hasty response within a day is not a sign of good faith.”

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

Opposition to the current American Board of Internal Medicine’s (ABIM’s) Maintenance of Certification (MOC) process continues to gain momentum, with the latest condemnation coming from the American Society of Hematology (ASH).

ASH president Robert A. Brodsky, MD, sent a letter to ABIM’s President and Chief Executive Officer Richard Baron, MD, highlighting hematologists’ concerns about the MOC process and outlining immediate actions ABIM should take.

“ASH continues to support the importance of lifelong learning for hematologists via a program that is evidence-based, relevant to one’s practice, and transparent; however, these three basic requirements are not met by the current ABIM MOC program,” Dr. Brodsky stated in the Sept. 27 letter to Baron.

Dr. Brodsky highlighted, for instance, the fact that the Longitudinal Knowledge Assessment – the alternative to the 10-year exam – “does not reflect real life practice, nor does it target each individual’s scope of practice.” Dr. Brodsky added that, according to members of ASH, the assessment is also “creating high levels of stress and contributing to burnout.”

The letter from Dr. Brodsky urged ABIM to “establish a new MOC program” that does not involve high-stakes assessments, reduces the number of Longitudinal Knowledge Assessment questions physicians receive, and eliminates redundancy between the MOC requirement to have a current license and the requirement to report continued medical education to ABIM.

The ABIM shared a copy of the letter in a Sept. 28 blog post defending the MOC process, highlighting past collaboration with ASH that “has led to meaningful enhancements to the [MOC] program” and committing to “continue to listen to and learn from the physician community going forward.”

The recent backlash against the MOC process stemmed from a petition demanding an end to the MOC. The petition was launched in July by hematologist-oncologist Aaron Goodman, MD, from the University of California, San Diego, who has been a vocal critic of the MOC process.

The criticism largely centered around the high costs and the “complex and time-consuming process that poses significant challenges to practicing physicians,” Dr. Goodman wrote in the petition, which has garnered more than 20,700 signatures.

In August, the Society for Cardiovascular Angiography and Interventions (SCAI) published “SCAI Position on ABIM Revocation of Certification for Not Participating in MOC.” The Electrophysiology Advocacy Foundation and the Heart Rhythm Society (HRS) issued statements pushing back on the MOC as well.

On Sept. 21, the SCAI, HRS, American College of Cardiology, and the Heart Failure Society of America went a step further and announced plans to create a new certification process that is independent of the ABIM MOC system.

The American Society of Clinical Oncology (ASCO) is now also surveying members about their MOC experience. A Sept. 26 announcement encouraged recipients to check their inboxes for a link to an anonymous MOC Experience Questionnaire before Oct. 12 and thanked respondents for their “engagement as ASCO works to address this critical issue for the oncology community.”

After ASH sent its letter to ABIM, Dr. Goodman applauded the society’s stance in a post on his X (formerly Twitter) account. Vincent Rajkumar, MD, a hematologist at the Mayo Clinic in Rochester, Minn., commented on ABIM’s response to ASH’s letter via X, noting, “If I were @ASH_hematology leadership, I would take ABIM response as disrespectful. A hasty response within a day is not a sign of good faith.”

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

WASHINGTON – Transgender female veterans are more likely to have thyroid cancer at rates comparable with cisgender women rather than cisgender men. Experts urge a cautious interpretation of these recent study results.

“In our clinic of about 50 transgender women, we noticed that we had two diagnosed cases of thyroid cancer in a year,” first author John Christensen, MD, of UC Davis Health, division of endocrinology, diabetes & metabolism, Sacramento, said in an interivew. He presented their findings at the annual meeting of the American Thyroid Association.

Comparatively, the thyroid cancer prevalence among cisgender male veterans is estimated at about 0.19%; the rate among all those assigned male at birth in the general population is 0.13%, whereas the rate among those assigned female at birth, which has historically been higher for all thyroid cancer subtypes, is 0.44%, according to U.S. cancer statistics for 2020 from the National Cancer Institute.

“About one-third of our [veteran] patients had been receiving estrogen for an average of over 3 years before diagnosis, which could suggest estrogen gender‐affirming hormone therapy [GAHT] may be a potentially important risk factor,” Dr. Christensen said.

Sustained use of external estrogen, especially in cisgender women undergoing fertility treatments, has been linked to an increased risk for thyroid cancer. This is because it can lead to an increase in estrogen receptors in cancerous cells. But experts caution that many other factors also come into play.

“There is definitely an implication that if you give extra estrogen to someone assigned female at birth, you may have an increased risk of thyroid cancer,” Dr. Christensen said. “So, it would stand to reason that even in those who are not assigned female at birth, there may be a risk from exogenous estrogen that may lead to an increased risk of thyroid cancer down the line.”

To investigate the issue in a larger population, Dr. Christensen and colleagues evaluated data from the comprehensive, nationwide Veterans Affairs Informatics and Computing Infrastructure database, including approximately 9 million veterans who had outpatient visits between December 2017 and January 2022.

Of the veterans, 9,988 were determined to likely be transgender women, based on either having an ICD-10 diagnosis code for gender dysphoria or being assigned male at birth and having received an estrogen or estradiol prescription.

Of those patients, 76 had an ICD-10 code indicating thyroid cancer and 34 had verification of the thyroid cancer on chart review, representing a prevalence of 0.34% among transgender female veterans.

The average age at thyroid cancer diagnosis among the veterans was 53.8 years, and 29.4% (10 of 34) of those patients had extrathyroidal disease at the time of their thyroid cancer diagnosis. The median body mass index, available for 26 patients, was 32, which is indicative of obesity.

In terms of the patients’ thyroid cancer subtypes, 22 were papillary cancer, 5 were a follicular variant of papillary cancer, 5 were both papillary and follicular cancer, 4 were follicular cancer, 3 were a Hürthle cell variant of follicular cancer, and one was unknown.

Among 11 (32.3%) of the 34 veterans receiving estrogen GAHT at diagnosis, treatment began an average of 3.38 years prior to diagnosis at variable doses and using various routes of administration.

About half of the patients had a history of smoking; however, Dr. Christensen noted that the role of smoking as being a risk factor in estrogenic cancers has been debated. Though most patients were obese, obesity is both very common and not well established in terms of its quantitative impact on the risk for cancer development.

With the small size of the thyroid cancer cohort and omissions in the medical record among the study’s important limitations, Dr. Christensen urged a cautious interpretation of the findings.

“We are certainly suspicious that GAHT may be associated with an increased risk of thyroid cancer, but I would characterize the trends in our data as being potentially suggestive or hypothesis generating – not conclusive,” he added. “I would hate for any transgender women reading this to stop taking GAHT without talking to their doctors first.”

Commenting on the issue, Maurice Garcia, MD, a clinical associate professor of urology and director of the transgender surgery and health program at Cedars-Sinai Medical Center, Los Angeles, said that any definitive evidence of an increase in cancer risk among transgender people is lacking.

“With an estimated 1.5 [million] to 1.6 million people in the U.S. who are transgender, with many of them receiving GAHT, we haven’t observed a bump or high incidence of any kind of cancer among these people so far,” he said.

“There’s certainly a high potential that hormone therapy, whether it’s feminizing or masculinizing hormone therapy, can affect an individual’s cancer risk,” he added. “But we don’t know of any [definitive evidence] yet of an increase, and, there’s also even the question of whether there could be an opposite effect.”

Regarding the thyroid cancer data, Dr. Garcia agreed that the preliminary nature of the study is a key limitation. “It’s hard to tell if these were comparable groups, or whether those in the transgender group came in with higher risk factors for thyroid cancer.

“Until more statistical analysis is done, I think all that can be said is that it’s speculative.”

Dr. Garcia, who coauthored a review on cancer screening for transgender individuals, underscored that, despite a lack of data suggesting that transgender patients need cancer screening any more than their matched cisgender counterparts, “the point is that we cannot forget to screen them at all.”

Dr. Christensen and Dr. Garcia had no disclosures to report.

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

WASHINGTON – Transgender female veterans are more likely to have thyroid cancer at rates comparable with cisgender women rather than cisgender men. Experts urge a cautious interpretation of these recent study results.

“In our clinic of about 50 transgender women, we noticed that we had two diagnosed cases of thyroid cancer in a year,” first author John Christensen, MD, of UC Davis Health, division of endocrinology, diabetes & metabolism, Sacramento, said in an interivew. He presented their findings at the annual meeting of the American Thyroid Association.

Comparatively, the thyroid cancer prevalence among cisgender male veterans is estimated at about 0.19%; the rate among all those assigned male at birth in the general population is 0.13%, whereas the rate among those assigned female at birth, which has historically been higher for all thyroid cancer subtypes, is 0.44%, according to U.S. cancer statistics for 2020 from the National Cancer Institute.

“About one-third of our [veteran] patients had been receiving estrogen for an average of over 3 years before diagnosis, which could suggest estrogen gender‐affirming hormone therapy [GAHT] may be a potentially important risk factor,” Dr. Christensen said.

Sustained use of external estrogen, especially in cisgender women undergoing fertility treatments, has been linked to an increased risk for thyroid cancer. This is because it can lead to an increase in estrogen receptors in cancerous cells. But experts caution that many other factors also come into play.

“There is definitely an implication that if you give extra estrogen to someone assigned female at birth, you may have an increased risk of thyroid cancer,” Dr. Christensen said. “So, it would stand to reason that even in those who are not assigned female at birth, there may be a risk from exogenous estrogen that may lead to an increased risk of thyroid cancer down the line.”

To investigate the issue in a larger population, Dr. Christensen and colleagues evaluated data from the comprehensive, nationwide Veterans Affairs Informatics and Computing Infrastructure database, including approximately 9 million veterans who had outpatient visits between December 2017 and January 2022.

Of the veterans, 9,988 were determined to likely be transgender women, based on either having an ICD-10 diagnosis code for gender dysphoria or being assigned male at birth and having received an estrogen or estradiol prescription.

Of those patients, 76 had an ICD-10 code indicating thyroid cancer and 34 had verification of the thyroid cancer on chart review, representing a prevalence of 0.34% among transgender female veterans.

The average age at thyroid cancer diagnosis among the veterans was 53.8 years, and 29.4% (10 of 34) of those patients had extrathyroidal disease at the time of their thyroid cancer diagnosis. The median body mass index, available for 26 patients, was 32, which is indicative of obesity.

In terms of the patients’ thyroid cancer subtypes, 22 were papillary cancer, 5 were a follicular variant of papillary cancer, 5 were both papillary and follicular cancer, 4 were follicular cancer, 3 were a Hürthle cell variant of follicular cancer, and one was unknown.

Among 11 (32.3%) of the 34 veterans receiving estrogen GAHT at diagnosis, treatment began an average of 3.38 years prior to diagnosis at variable doses and using various routes of administration.

About half of the patients had a history of smoking; however, Dr. Christensen noted that the role of smoking as being a risk factor in estrogenic cancers has been debated. Though most patients were obese, obesity is both very common and not well established in terms of its quantitative impact on the risk for cancer development.

With the small size of the thyroid cancer cohort and omissions in the medical record among the study’s important limitations, Dr. Christensen urged a cautious interpretation of the findings.

“We are certainly suspicious that GAHT may be associated with an increased risk of thyroid cancer, but I would characterize the trends in our data as being potentially suggestive or hypothesis generating – not conclusive,” he added. “I would hate for any transgender women reading this to stop taking GAHT without talking to their doctors first.”

Commenting on the issue, Maurice Garcia, MD, a clinical associate professor of urology and director of the transgender surgery and health program at Cedars-Sinai Medical Center, Los Angeles, said that any definitive evidence of an increase in cancer risk among transgender people is lacking.

“With an estimated 1.5 [million] to 1.6 million people in the U.S. who are transgender, with many of them receiving GAHT, we haven’t observed a bump or high incidence of any kind of cancer among these people so far,” he said.

“There’s certainly a high potential that hormone therapy, whether it’s feminizing or masculinizing hormone therapy, can affect an individual’s cancer risk,” he added. “But we don’t know of any [definitive evidence] yet of an increase, and, there’s also even the question of whether there could be an opposite effect.”

Regarding the thyroid cancer data, Dr. Garcia agreed that the preliminary nature of the study is a key limitation. “It’s hard to tell if these were comparable groups, or whether those in the transgender group came in with higher risk factors for thyroid cancer.

“Until more statistical analysis is done, I think all that can be said is that it’s speculative.”

Dr. Garcia, who coauthored a review on cancer screening for transgender individuals, underscored that, despite a lack of data suggesting that transgender patients need cancer screening any more than their matched cisgender counterparts, “the point is that we cannot forget to screen them at all.”

Dr. Christensen and Dr. Garcia had no disclosures to report.

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

WASHINGTON – Transgender female veterans are more likely to have thyroid cancer at rates comparable with cisgender women rather than cisgender men. Experts urge a cautious interpretation of these recent study results.

“In our clinic of about 50 transgender women, we noticed that we had two diagnosed cases of thyroid cancer in a year,” first author John Christensen, MD, of UC Davis Health, division of endocrinology, diabetes & metabolism, Sacramento, said in an interivew. He presented their findings at the annual meeting of the American Thyroid Association.

Comparatively, the thyroid cancer prevalence among cisgender male veterans is estimated at about 0.19%; the rate among all those assigned male at birth in the general population is 0.13%, whereas the rate among those assigned female at birth, which has historically been higher for all thyroid cancer subtypes, is 0.44%, according to U.S. cancer statistics for 2020 from the National Cancer Institute.

“About one-third of our [veteran] patients had been receiving estrogen for an average of over 3 years before diagnosis, which could suggest estrogen gender‐affirming hormone therapy [GAHT] may be a potentially important risk factor,” Dr. Christensen said.

Sustained use of external estrogen, especially in cisgender women undergoing fertility treatments, has been linked to an increased risk for thyroid cancer. This is because it can lead to an increase in estrogen receptors in cancerous cells. But experts caution that many other factors also come into play.

“There is definitely an implication that if you give extra estrogen to someone assigned female at birth, you may have an increased risk of thyroid cancer,” Dr. Christensen said. “So, it would stand to reason that even in those who are not assigned female at birth, there may be a risk from exogenous estrogen that may lead to an increased risk of thyroid cancer down the line.”

To investigate the issue in a larger population, Dr. Christensen and colleagues evaluated data from the comprehensive, nationwide Veterans Affairs Informatics and Computing Infrastructure database, including approximately 9 million veterans who had outpatient visits between December 2017 and January 2022.

Of the veterans, 9,988 were determined to likely be transgender women, based on either having an ICD-10 diagnosis code for gender dysphoria or being assigned male at birth and having received an estrogen or estradiol prescription.

Of those patients, 76 had an ICD-10 code indicating thyroid cancer and 34 had verification of the thyroid cancer on chart review, representing a prevalence of 0.34% among transgender female veterans.

The average age at thyroid cancer diagnosis among the veterans was 53.8 years, and 29.4% (10 of 34) of those patients had extrathyroidal disease at the time of their thyroid cancer diagnosis. The median body mass index, available for 26 patients, was 32, which is indicative of obesity.

In terms of the patients’ thyroid cancer subtypes, 22 were papillary cancer, 5 were a follicular variant of papillary cancer, 5 were both papillary and follicular cancer, 4 were follicular cancer, 3 were a Hürthle cell variant of follicular cancer, and one was unknown.

Among 11 (32.3%) of the 34 veterans receiving estrogen GAHT at diagnosis, treatment began an average of 3.38 years prior to diagnosis at variable doses and using various routes of administration.

About half of the patients had a history of smoking; however, Dr. Christensen noted that the role of smoking as being a risk factor in estrogenic cancers has been debated. Though most patients were obese, obesity is both very common and not well established in terms of its quantitative impact on the risk for cancer development.

With the small size of the thyroid cancer cohort and omissions in the medical record among the study’s important limitations, Dr. Christensen urged a cautious interpretation of the findings.

“We are certainly suspicious that GAHT may be associated with an increased risk of thyroid cancer, but I would characterize the trends in our data as being potentially suggestive or hypothesis generating – not conclusive,” he added. “I would hate for any transgender women reading this to stop taking GAHT without talking to their doctors first.”

Commenting on the issue, Maurice Garcia, MD, a clinical associate professor of urology and director of the transgender surgery and health program at Cedars-Sinai Medical Center, Los Angeles, said that any definitive evidence of an increase in cancer risk among transgender people is lacking.

“With an estimated 1.5 [million] to 1.6 million people in the U.S. who are transgender, with many of them receiving GAHT, we haven’t observed a bump or high incidence of any kind of cancer among these people so far,” he said.

“There’s certainly a high potential that hormone therapy, whether it’s feminizing or masculinizing hormone therapy, can affect an individual’s cancer risk,” he added. “But we don’t know of any [definitive evidence] yet of an increase, and, there’s also even the question of whether there could be an opposite effect.”

Regarding the thyroid cancer data, Dr. Garcia agreed that the preliminary nature of the study is a key limitation. “It’s hard to tell if these were comparable groups, or whether those in the transgender group came in with higher risk factors for thyroid cancer.

“Until more statistical analysis is done, I think all that can be said is that it’s speculative.”

Dr. Garcia, who coauthored a review on cancer screening for transgender individuals, underscored that, despite a lack of data suggesting that transgender patients need cancer screening any more than their matched cisgender counterparts, “the point is that we cannot forget to screen them at all.”

Dr. Christensen and Dr. Garcia had no disclosures to report.

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

SAN DIEGO – Patients with limited-stage small cell lung cancer (LS-SCLC) had improved overall survival and progression-free survival when they received higher-dose thoracic radiotherapy instead of the standard treatment, according to a new multicenter, open-label, randomized phase III trial.

Among 224 patients in China, aged 18-70, those randomly assigned to receive volumetric-modulated arc radiotherapy of high-dose, hypofractionated thoracic radiotherapy of 54 Gy in 30 fractions had a much higher median overall survival (62.4 months) than those who received the standard dose of 45 Gy in 30 fractions (43.1 months, P = .001), reported Jiayi Yu, PhD, of Beijing University Cancer Hospital and Institute and colleagues at the annual meeting of the American Society for Radiation Oncology.

Median progression-free survival was also higher in the 54 Gy group (30.5 months vs. 16.7 months in the 45 Gy group, P = .044).

Kristin Higgins, MD, of Winship Cancer Institute of Emory University, Atlanta, provided perspective at the ASTRO session following Dr. Yu’s presentation. She noted that the study population is quite different than that of LS-SCLC patients in the United States, where patients are often older and more likely to have a history of smoking.

“We need more technical details to understand how to deliver this regimen in clinical practice, and it may not be applicable for all patients,” she said. Still, she added that “a key takeaway here is that optimizing the radiotherapy component of treatment is very important.”

Both groups received chemotherapy. “Higher-dose thoracic radiation therapy concurrently with chemotherapy is an alternative therapeutic option,” Dr. Yu said at an ASTRO presentation.

As Dr. Yu noted, twice-daily thoracic radiotherapy of 45 Gy in 30 fractions and concurrent chemotherapy has been the standard treatment for LS-SCLC for the last 20 years. Trials failed to show benefits for once-daily 66-Gy (33 fractions) or 70-Gy treatment (35 fractions), but a phase 2 trial published in 2023 did indicate that twice-daily treatment of 60 Gy (40 fractions) improved survival without boosting side effects.

For the new study, researchers tracked 224 patients from 2017 to 2021 who were previously untreated or had received specific chemotherapy treatments and had ECOG performance status scores of 0 or 1; 108 patients were randomly assigned to the 54-Gy arm and 116 to the 45-Gy arm. All were recruited at 16 public hospitals in China.

The median age in the two groups were 60 in the 54-Gy arm and 62 in the 45-Gy arm; the percentages of women were similar (45.4% and 45.7%, respectively). Most were current or former smokers (62.0% and 61.2%, respectively).

The researchers closed the trial in April 2021 because of the survival benefit in the 54-Gy arm, and patients were tracked through January 2023 for a median 45 months.

Nearly three-quarters of patients in the 54-Gy arm survived to 2 years (77.7%) vs. 53.4% in the 45-Gy arm, a 41% reduction in risk of death. Adverse events were similar between the groups, with 1 reported treatment-related death (myocardial infarction), in the 54-Gy group.

In an interview, Kenneth Rosenzweig, MD, chairman of the department of radiation oncology at Icahn School of Medicine at Mount Sinai, New York, praised the study. It’s “no surprise” that higher radiation doses are well-tolerated since “our ability to shield normal tissue has improved” over the years, said Dr. Rosenzweig, who served as a moderator of the ASTRO session where the research was presented.

However, he cautioned that hypofractionation is still “intense” and may not be appropriate for certain patients. And he added that some clinics may not be set up to provide twice-daily treatments.

Information about study funding was not provided. The study authors have no disclosures. Dr. Higgins discloses relationships with AstraZeneca and Regeneron (advisory board), Jazz (funded research), and Janssen and Picture Health (consulting). Dr. Rosenzweig has no disclosures.

SAN DIEGO – Patients with limited-stage small cell lung cancer (LS-SCLC) had improved overall survival and progression-free survival when they received higher-dose thoracic radiotherapy instead of the standard treatment, according to a new multicenter, open-label, randomized phase III trial.

Among 224 patients in China, aged 18-70, those randomly assigned to receive volumetric-modulated arc radiotherapy of high-dose, hypofractionated thoracic radiotherapy of 54 Gy in 30 fractions had a much higher median overall survival (62.4 months) than those who received the standard dose of 45 Gy in 30 fractions (43.1 months, P = .001), reported Jiayi Yu, PhD, of Beijing University Cancer Hospital and Institute and colleagues at the annual meeting of the American Society for Radiation Oncology.

Median progression-free survival was also higher in the 54 Gy group (30.5 months vs. 16.7 months in the 45 Gy group, P = .044).

Kristin Higgins, MD, of Winship Cancer Institute of Emory University, Atlanta, provided perspective at the ASTRO session following Dr. Yu’s presentation. She noted that the study population is quite different than that of LS-SCLC patients in the United States, where patients are often older and more likely to have a history of smoking.

“We need more technical details to understand how to deliver this regimen in clinical practice, and it may not be applicable for all patients,” she said. Still, she added that “a key takeaway here is that optimizing the radiotherapy component of treatment is very important.”

Both groups received chemotherapy. “Higher-dose thoracic radiation therapy concurrently with chemotherapy is an alternative therapeutic option,” Dr. Yu said at an ASTRO presentation.

As Dr. Yu noted, twice-daily thoracic radiotherapy of 45 Gy in 30 fractions and concurrent chemotherapy has been the standard treatment for LS-SCLC for the last 20 years. Trials failed to show benefits for once-daily 66-Gy (33 fractions) or 70-Gy treatment (35 fractions), but a phase 2 trial published in 2023 did indicate that twice-daily treatment of 60 Gy (40 fractions) improved survival without boosting side effects.

For the new study, researchers tracked 224 patients from 2017 to 2021 who were previously untreated or had received specific chemotherapy treatments and had ECOG performance status scores of 0 or 1; 108 patients were randomly assigned to the 54-Gy arm and 116 to the 45-Gy arm. All were recruited at 16 public hospitals in China.

The median age in the two groups were 60 in the 54-Gy arm and 62 in the 45-Gy arm; the percentages of women were similar (45.4% and 45.7%, respectively). Most were current or former smokers (62.0% and 61.2%, respectively).

The researchers closed the trial in April 2021 because of the survival benefit in the 54-Gy arm, and patients were tracked through January 2023 for a median 45 months.

Nearly three-quarters of patients in the 54-Gy arm survived to 2 years (77.7%) vs. 53.4% in the 45-Gy arm, a 41% reduction in risk of death. Adverse events were similar between the groups, with 1 reported treatment-related death (myocardial infarction), in the 54-Gy group.

In an interview, Kenneth Rosenzweig, MD, chairman of the department of radiation oncology at Icahn School of Medicine at Mount Sinai, New York, praised the study. It’s “no surprise” that higher radiation doses are well-tolerated since “our ability to shield normal tissue has improved” over the years, said Dr. Rosenzweig, who served as a moderator of the ASTRO session where the research was presented.

However, he cautioned that hypofractionation is still “intense” and may not be appropriate for certain patients. And he added that some clinics may not be set up to provide twice-daily treatments.

Information about study funding was not provided. The study authors have no disclosures. Dr. Higgins discloses relationships with AstraZeneca and Regeneron (advisory board), Jazz (funded research), and Janssen and Picture Health (consulting). Dr. Rosenzweig has no disclosures.

SAN DIEGO – Patients with limited-stage small cell lung cancer (LS-SCLC) had improved overall survival and progression-free survival when they received higher-dose thoracic radiotherapy instead of the standard treatment, according to a new multicenter, open-label, randomized phase III trial.

Among 224 patients in China, aged 18-70, those randomly assigned to receive volumetric-modulated arc radiotherapy of high-dose, hypofractionated thoracic radiotherapy of 54 Gy in 30 fractions had a much higher median overall survival (62.4 months) than those who received the standard dose of 45 Gy in 30 fractions (43.1 months, P = .001), reported Jiayi Yu, PhD, of Beijing University Cancer Hospital and Institute and colleagues at the annual meeting of the American Society for Radiation Oncology.

Median progression-free survival was also higher in the 54 Gy group (30.5 months vs. 16.7 months in the 45 Gy group, P = .044).

Kristin Higgins, MD, of Winship Cancer Institute of Emory University, Atlanta, provided perspective at the ASTRO session following Dr. Yu’s presentation. She noted that the study population is quite different than that of LS-SCLC patients in the United States, where patients are often older and more likely to have a history of smoking.

“We need more technical details to understand how to deliver this regimen in clinical practice, and it may not be applicable for all patients,” she said. Still, she added that “a key takeaway here is that optimizing the radiotherapy component of treatment is very important.”

Both groups received chemotherapy. “Higher-dose thoracic radiation therapy concurrently with chemotherapy is an alternative therapeutic option,” Dr. Yu said at an ASTRO presentation.

As Dr. Yu noted, twice-daily thoracic radiotherapy of 45 Gy in 30 fractions and concurrent chemotherapy has been the standard treatment for LS-SCLC for the last 20 years. Trials failed to show benefits for once-daily 66-Gy (33 fractions) or 70-Gy treatment (35 fractions), but a phase 2 trial published in 2023 did indicate that twice-daily treatment of 60 Gy (40 fractions) improved survival without boosting side effects.

For the new study, researchers tracked 224 patients from 2017 to 2021 who were previously untreated or had received specific chemotherapy treatments and had ECOG performance status scores of 0 or 1; 108 patients were randomly assigned to the 54-Gy arm and 116 to the 45-Gy arm. All were recruited at 16 public hospitals in China.

The median age in the two groups were 60 in the 54-Gy arm and 62 in the 45-Gy arm; the percentages of women were similar (45.4% and 45.7%, respectively). Most were current or former smokers (62.0% and 61.2%, respectively).

The researchers closed the trial in April 2021 because of the survival benefit in the 54-Gy arm, and patients were tracked through January 2023 for a median 45 months.

Nearly three-quarters of patients in the 54-Gy arm survived to 2 years (77.7%) vs. 53.4% in the 45-Gy arm, a 41% reduction in risk of death. Adverse events were similar between the groups, with 1 reported treatment-related death (myocardial infarction), in the 54-Gy group.

In an interview, Kenneth Rosenzweig, MD, chairman of the department of radiation oncology at Icahn School of Medicine at Mount Sinai, New York, praised the study. It’s “no surprise” that higher radiation doses are well-tolerated since “our ability to shield normal tissue has improved” over the years, said Dr. Rosenzweig, who served as a moderator of the ASTRO session where the research was presented.

However, he cautioned that hypofractionation is still “intense” and may not be appropriate for certain patients. And he added that some clinics may not be set up to provide twice-daily treatments.

Information about study funding was not provided. The study authors have no disclosures. Dr. Higgins discloses relationships with AstraZeneca and Regeneron (advisory board), Jazz (funded research), and Janssen and Picture Health (consulting). Dr. Rosenzweig has no disclosures.

For patients with up to 10 brain metastases from small cell lung cancer (SCLC), stereotactic radiosurgery was associated with less cognitive impairment than whole-brain radiation therapy (WBRT) without compromising overall survival, results of the randomized ENCEPHALON (ARO 2018-9) trial suggest.

Among 56 patients with one to 10 SCLC brain metastases, 24% of those who received WBRT demonstrated significant declines in memory function 3 months after treatment, compared with 7% of patients whose metastases were treated with stereotactic radiosurgery alone. Preliminary data showed no significant differences in overall survival between the treatment groups at 6 months of follow-up, Denise Bernhardt, MD, from the Technical University of Munich, reported at the American Society of Radiation Oncology (ASTRO) annual meeting.

“We propose stereotactic radiosurgery should be an option for patients with up to 10 brain metastases in small cell lung cancer,” Dr. Bernhardt said during her presentation.

Vinai Gondi, MD, who was not involved in the study, said that the primary results from the trial – while limited by the study’s small size and missing data – are notable.

Patients with brain metastases from most cancer types typically receive stereotactic radiosurgery but WBRT has remained the standard of care to control brain metastases among patients with SCLC.

“This is the first prospective trial of radiosurgery versus whole-brain radiotherapy for small cell lung cancer brain metastases, and it’s important to recognize how important this is,” said Dr. Gondi, director of Radiation Oncology and codirector of the Brain Tumor Center at Northwestern Medicine Cancer Center, Warrenville, Ill.

Prior trials that have asked the same question did not include SCLC because many of those patients received prophylactic cranial irradiation, Dr. Gondi explained. Prophylactic cranial irradiation, however, has been on the decline among patients with brain metastases from SCLC, following a study from Japan showing no difference in survival among those who received the therapy and those followed with observation as well as evidence demonstrating significant toxicities associated with the technique.

Now “with the declining use of prophylactic cranial irradiation, the emergence of brain metastases is increasing significantly in volume in the small cell lung cancer population,” said Dr. Gondi, who is principal investigator on a phase 3 trial exploring stereotactic radiosurgery versus WBRT in a similar patient population.

In a previous retrospective trial), Dr. Bernhardt and colleagues found that first-line stereotactic radiosurgery did not compromise survival, compared with WBRT, but patients receiving stereotactic radiosurgery did have a higher risk for intracranial failure.

In the current study, the investigators compared the neurocognitive responses in patients with brain metastases from SCLC treated with stereotactic radiosurgery or WBRT.

Enrolled patients had histologically confirmed extensive disease with up to 10 metastatic brain lesions and had not previously received either therapeutic or prophylactic brain irradiation. After stratifying patients by synchronous versus metachronous disease, 56 patients were randomly assigned to either WBRT, at a total dose of 30 Gy delivered in 10 fractions, or to stereotactic radiosurgery with 20 Gy, 18 Gy, or fractionated stereotactic radiosurgery with 30 Gy in 5 Gy fractions for lesions larger than 3 cm.

The primary endpoint was neurocognition after radiation therapy as defined by a decline from baseline of at least five points on the Hopkins Verbal Learning Test-Revised (HVLT-R) total recall subscale at 3 months. Secondary endpoints included survival outcomes, additional neurocognitive assessments of motor skills, executive function, attention, memory, and processing as well as quality-of-life measures.

The investigators expected a high rate of study dropout and planned their statistical analysis accordingly, using a method for estimating the likely values of missing data based on observed data.

Among 26 patients who eventually underwent stereotactic radiosurgery, 18 did not meet the primary endpoint and 2 (7%) demonstrated declines on the HVLT-R subscale of 5 or more points. Data for the remaining 6 patients were missing.

Among the 25 who underwent WBRT, 13 did not meet the primary endpoint and 6 (24%) demonstrated declines of at least 5 points. Data for 6 of the remaining patients were missing.

Although more patients in the WBRT arm had significant declines in neurocognitive function, the difference between the groups was not significant, due to the high proportion of study dropouts – approximately one-fourth of patients in each arm. But the analysis suggested that the neuroprotective effect of stereotactic radiosurgery was notable, Dr. Bernhardt said.

At 6 months, the team also found no significant difference in the survival probability between the treatment groups (P = .36). The median time to death was 124 days among patients who received stereotactic radiosurgery and 131 days among patients who received WBRT. 

Dr. Gondi said the data from ENCEPHALON, while promising, need to be carefully scrutinized because of the small sample sizes and the possibility for unintended bias.

ARO 2018-9 is an investigator-initiated trial funded by Accuray. Dr. Bernhardt disclosed consulting actives, fees, travel expenses, and research funding from Accuray and others. Dr. Gondi disclosed honoraria from UpToDate.

A version of this article appeared on Medscape.com.

For patients with up to 10 brain metastases from small cell lung cancer (SCLC), stereotactic radiosurgery was associated with less cognitive impairment than whole-brain radiation therapy (WBRT) without compromising overall survival, results of the randomized ENCEPHALON (ARO 2018-9) trial suggest.

Among 56 patients with one to 10 SCLC brain metastases, 24% of those who received WBRT demonstrated significant declines in memory function 3 months after treatment, compared with 7% of patients whose metastases were treated with stereotactic radiosurgery alone. Preliminary data showed no significant differences in overall survival between the treatment groups at 6 months of follow-up, Denise Bernhardt, MD, from the Technical University of Munich, reported at the American Society of Radiation Oncology (ASTRO) annual meeting.

“We propose stereotactic radiosurgery should be an option for patients with up to 10 brain metastases in small cell lung cancer,” Dr. Bernhardt said during her presentation.

Vinai Gondi, MD, who was not involved in the study, said that the primary results from the trial – while limited by the study’s small size and missing data – are notable.

Patients with brain metastases from most cancer types typically receive stereotactic radiosurgery but WBRT has remained the standard of care to control brain metastases among patients with SCLC.

“This is the first prospective trial of radiosurgery versus whole-brain radiotherapy for small cell lung cancer brain metastases, and it’s important to recognize how important this is,” said Dr. Gondi, director of Radiation Oncology and codirector of the Brain Tumor Center at Northwestern Medicine Cancer Center, Warrenville, Ill.

Prior trials that have asked the same question did not include SCLC because many of those patients received prophylactic cranial irradiation, Dr. Gondi explained. Prophylactic cranial irradiation, however, has been on the decline among patients with brain metastases from SCLC, following a study from Japan showing no difference in survival among those who received the therapy and those followed with observation as well as evidence demonstrating significant toxicities associated with the technique.

Now “with the declining use of prophylactic cranial irradiation, the emergence of brain metastases is increasing significantly in volume in the small cell lung cancer population,” said Dr. Gondi, who is principal investigator on a phase 3 trial exploring stereotactic radiosurgery versus WBRT in a similar patient population.

In a previous retrospective trial), Dr. Bernhardt and colleagues found that first-line stereotactic radiosurgery did not compromise survival, compared with WBRT, but patients receiving stereotactic radiosurgery did have a higher risk for intracranial failure.

In the current study, the investigators compared the neurocognitive responses in patients with brain metastases from SCLC treated with stereotactic radiosurgery or WBRT.

Enrolled patients had histologically confirmed extensive disease with up to 10 metastatic brain lesions and had not previously received either therapeutic or prophylactic brain irradiation. After stratifying patients by synchronous versus metachronous disease, 56 patients were randomly assigned to either WBRT, at a total dose of 30 Gy delivered in 10 fractions, or to stereotactic radiosurgery with 20 Gy, 18 Gy, or fractionated stereotactic radiosurgery with 30 Gy in 5 Gy fractions for lesions larger than 3 cm.

The primary endpoint was neurocognition after radiation therapy as defined by a decline from baseline of at least five points on the Hopkins Verbal Learning Test-Revised (HVLT-R) total recall subscale at 3 months. Secondary endpoints included survival outcomes, additional neurocognitive assessments of motor skills, executive function, attention, memory, and processing as well as quality-of-life measures.

The investigators expected a high rate of study dropout and planned their statistical analysis accordingly, using a method for estimating the likely values of missing data based on observed data.

Among 26 patients who eventually underwent stereotactic radiosurgery, 18 did not meet the primary endpoint and 2 (7%) demonstrated declines on the HVLT-R subscale of 5 or more points. Data for the remaining 6 patients were missing.

Among the 25 who underwent WBRT, 13 did not meet the primary endpoint and 6 (24%) demonstrated declines of at least 5 points. Data for 6 of the remaining patients were missing.

Although more patients in the WBRT arm had significant declines in neurocognitive function, the difference between the groups was not significant, due to the high proportion of study dropouts – approximately one-fourth of patients in each arm. But the analysis suggested that the neuroprotective effect of stereotactic radiosurgery was notable, Dr. Bernhardt said.

At 6 months, the team also found no significant difference in the survival probability between the treatment groups (P = .36). The median time to death was 124 days among patients who received stereotactic radiosurgery and 131 days among patients who received WBRT. 

Dr. Gondi said the data from ENCEPHALON, while promising, need to be carefully scrutinized because of the small sample sizes and the possibility for unintended bias.

ARO 2018-9 is an investigator-initiated trial funded by Accuray. Dr. Bernhardt disclosed consulting actives, fees, travel expenses, and research funding from Accuray and others. Dr. Gondi disclosed honoraria from UpToDate.

A version of this article appeared on Medscape.com.

For patients with up to 10 brain metastases from small cell lung cancer (SCLC), stereotactic radiosurgery was associated with less cognitive impairment than whole-brain radiation therapy (WBRT) without compromising overall survival, results of the randomized ENCEPHALON (ARO 2018-9) trial suggest.

Among 56 patients with one to 10 SCLC brain metastases, 24% of those who received WBRT demonstrated significant declines in memory function 3 months after treatment, compared with 7% of patients whose metastases were treated with stereotactic radiosurgery alone. Preliminary data showed no significant differences in overall survival between the treatment groups at 6 months of follow-up, Denise Bernhardt, MD, from the Technical University of Munich, reported at the American Society of Radiation Oncology (ASTRO) annual meeting.

“We propose stereotactic radiosurgery should be an option for patients with up to 10 brain metastases in small cell lung cancer,” Dr. Bernhardt said during her presentation.

Vinai Gondi, MD, who was not involved in the study, said that the primary results from the trial – while limited by the study’s small size and missing data – are notable.

Patients with brain metastases from most cancer types typically receive stereotactic radiosurgery but WBRT has remained the standard of care to control brain metastases among patients with SCLC.

“This is the first prospective trial of radiosurgery versus whole-brain radiotherapy for small cell lung cancer brain metastases, and it’s important to recognize how important this is,” said Dr. Gondi, director of Radiation Oncology and codirector of the Brain Tumor Center at Northwestern Medicine Cancer Center, Warrenville, Ill.

Prior trials that have asked the same question did not include SCLC because many of those patients received prophylactic cranial irradiation, Dr. Gondi explained. Prophylactic cranial irradiation, however, has been on the decline among patients with brain metastases from SCLC, following a study from Japan showing no difference in survival among those who received the therapy and those followed with observation as well as evidence demonstrating significant toxicities associated with the technique.

Now “with the declining use of prophylactic cranial irradiation, the emergence of brain metastases is increasing significantly in volume in the small cell lung cancer population,” said Dr. Gondi, who is principal investigator on a phase 3 trial exploring stereotactic radiosurgery versus WBRT in a similar patient population.

In a previous retrospective trial), Dr. Bernhardt and colleagues found that first-line stereotactic radiosurgery did not compromise survival, compared with WBRT, but patients receiving stereotactic radiosurgery did have a higher risk for intracranial failure.

In the current study, the investigators compared the neurocognitive responses in patients with brain metastases from SCLC treated with stereotactic radiosurgery or WBRT.

Enrolled patients had histologically confirmed extensive disease with up to 10 metastatic brain lesions and had not previously received either therapeutic or prophylactic brain irradiation. After stratifying patients by synchronous versus metachronous disease, 56 patients were randomly assigned to either WBRT, at a total dose of 30 Gy delivered in 10 fractions, or to stereotactic radiosurgery with 20 Gy, 18 Gy, or fractionated stereotactic radiosurgery with 30 Gy in 5 Gy fractions for lesions larger than 3 cm.

The primary endpoint was neurocognition after radiation therapy as defined by a decline from baseline of at least five points on the Hopkins Verbal Learning Test-Revised (HVLT-R) total recall subscale at 3 months. Secondary endpoints included survival outcomes, additional neurocognitive assessments of motor skills, executive function, attention, memory, and processing as well as quality-of-life measures.

The investigators expected a high rate of study dropout and planned their statistical analysis accordingly, using a method for estimating the likely values of missing data based on observed data.

Among 26 patients who eventually underwent stereotactic radiosurgery, 18 did not meet the primary endpoint and 2 (7%) demonstrated declines on the HVLT-R subscale of 5 or more points. Data for the remaining 6 patients were missing.

Among the 25 who underwent WBRT, 13 did not meet the primary endpoint and 6 (24%) demonstrated declines of at least 5 points. Data for 6 of the remaining patients were missing.

Although more patients in the WBRT arm had significant declines in neurocognitive function, the difference between the groups was not significant, due to the high proportion of study dropouts – approximately one-fourth of patients in each arm. But the analysis suggested that the neuroprotective effect of stereotactic radiosurgery was notable, Dr. Bernhardt said.

At 6 months, the team also found no significant difference in the survival probability between the treatment groups (P = .36). The median time to death was 124 days among patients who received stereotactic radiosurgery and 131 days among patients who received WBRT. 

Dr. Gondi said the data from ENCEPHALON, while promising, need to be carefully scrutinized because of the small sample sizes and the possibility for unintended bias.

ARO 2018-9 is an investigator-initiated trial funded by Accuray. Dr. Bernhardt disclosed consulting actives, fees, travel expenses, and research funding from Accuray and others. Dr. Gondi disclosed honoraria from UpToDate.

A version of this article appeared on Medscape.com.