AVAHO

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.

SAN DIEGO – With just five fractions of stereotactic body radiation therapy (SBRT), men with low- or intermediate-risk prostate cancer can have 5-year disease control as good as that provided by conventional external-beam radiation therapy delivered at higher doses in 20-39 fractions, according to new data from the phase 3 randomized PACE-B trial.

Overall, the 5-year event-free survival rates were 95.8% among patients who received SBRT and 94.6% among those who had conventional radiation. The incidence of adverse events was also low in both groups, with no significant differences observed between the trial arms.

The similar event-free survival and toxicity profiles in both groups provide more support for SBRT, which treats prostate cancer with larger radiation fractions over a shorter time period.

“I think we can also say now with a high level of confidence that SBRT can be considered a new standard of care for low and favorable intermediate-risk prostate cancer,” said Nicholas van As, MD, MB, from the Royal Marsden NHS Foundation Trust and Institute of Cancer Research in London, who presented efficacy and safety results from the noninferiority trial at the American Society for Radiation Oncology (ASTRO) annual meeting. SBRT is more convenient for patients and more cost-effective for health care providers, Dr. Van As added.

Invited discussant Alejandro Berlin, MD, MSc, from Princess Margaret Cancer Centre and the University of Toronto, agreed “that this should be a standard of care for low and favorable intermediate-risk prostate cancer,” an option already endorsed by relevant guidelines.

But, Dr. Berlin noted, SBRT requires careful attention to technique to achieve the desired results. Further research will be needed to identify and potentially reduce variability among radiation oncology practice regarding margins, dosimetry goals, dose heterogeneity, treatment schedules, and other factors, he said.
 

An international trial

PACE-B is one of three branches of a multi-center collaboration among 37 radiation therapy centers in the United Kingdom, Ireland, and Canada.

In the trial, investigators enrolled 874 patients with T1c or T2c prostate cancer, Gleason score of 3+4 or less, prostate-specific antigen (PSA) level no higher than 20 ng/mL, MRI staging, and no prior androgen deprivation therapy. Investigators then randomly assigned them on a 1:1 basis to receive either conventional radiation (n = 441) or SBRT (n = 433).

At the start of the trial, patients who were assigned to the conventional radiation group received 78 Gy in 39 fractions over 4-8 weeks. However, after results from the CHHiP trial, which showed that a 60-Gy, 20-fraction regimen was not inferior to a 74-Gy, 37-fraction regimen, the PACE-B investigators modified the protocol to 62 Gy delivered in 20 fractions.

Patients assigned to SBRT received 36.25 Gy divided into give fractions delivered over 1-2 weeks, with 40 Gy to the clinical target volume.

The primary outcome was noninferiority of SBRT, measured as whether patients remained free of biochemical clinical failure. Biochemical clinical failure was defined as evidence that the cancer was returning, such as an increase in PSA levels or distant metastases or death from prostate cancer.

At a median follow-up of 73.1 months, 5-year event-free survival rates were 94.6% for patients who received conventional radiation therapy and 95.8% for patients who received SBRT, meeting the prespecified criteria for noninferiority of SBRT (P = .007).

Freedom from biochemical and clinical failure, the trial’s primary endpoint, “was significantly better on both arms than our original power calculation, where we expected control rates of approximately 85%,” Dr. Van As said in an ASTRO plenary session.

Toxicity rates were also low in both study arms. The rate of grade 2 or greater urogenital side effects at 5 years was 5.5% in the SBRT arm and 3.2% in the conventional therapy arm. Grade 2 or greater gastrointestinal side effects occurred in only two patients, one in each study arm.

Given the findings, “I think it’s now imperative that our surgeons discuss this data with their patients before they perform prostatectomies,” Dr. Van As said.

Neha Vapiwala, MD, president-elect of ASTRO who moderated a media briefing where Dr. Van As summarized the PACE-B data, commented that “this study was conducted very rigorously, with excellent quality assurance.”

The study also highlights that clinicians in the United States have considerable catching up to do, said Dr. Vapiwala, from the Hospital of the University of Pennsylvania, Philadelphia.

In the United States, “we are way behind our colleagues on the other side of the pond,” she said. “We are way behind in our uptake of ultra-hypofractionated radiation [such as SBRT], and I do believe that some of that comes from the lack of feeling comfortable with the techniques that are needed and the expertise that is needed.”

PACE-B was funded by Accuray. Dr. Van As disclosed research grants from the company and consulting fees from Varian. Dr. Berlin reported no conflict of interest relevant to the study. Dr. Vapiwala has disclosed a consulting or advisory role with Bayer.

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

SAN DIEGO – With just five fractions of stereotactic body radiation therapy (SBRT), men with low- or intermediate-risk prostate cancer can have 5-year disease control as good as that provided by conventional external-beam radiation therapy delivered at higher doses in 20-39 fractions, according to new data from the phase 3 randomized PACE-B trial.

Overall, the 5-year event-free survival rates were 95.8% among patients who received SBRT and 94.6% among those who had conventional radiation. The incidence of adverse events was also low in both groups, with no significant differences observed between the trial arms.

The similar event-free survival and toxicity profiles in both groups provide more support for SBRT, which treats prostate cancer with larger radiation fractions over a shorter time period.

“I think we can also say now with a high level of confidence that SBRT can be considered a new standard of care for low and favorable intermediate-risk prostate cancer,” said Nicholas van As, MD, MB, from the Royal Marsden NHS Foundation Trust and Institute of Cancer Research in London, who presented efficacy and safety results from the noninferiority trial at the American Society for Radiation Oncology (ASTRO) annual meeting. SBRT is more convenient for patients and more cost-effective for health care providers, Dr. Van As added.

Invited discussant Alejandro Berlin, MD, MSc, from Princess Margaret Cancer Centre and the University of Toronto, agreed “that this should be a standard of care for low and favorable intermediate-risk prostate cancer,” an option already endorsed by relevant guidelines.

But, Dr. Berlin noted, SBRT requires careful attention to technique to achieve the desired results. Further research will be needed to identify and potentially reduce variability among radiation oncology practice regarding margins, dosimetry goals, dose heterogeneity, treatment schedules, and other factors, he said.
 

An international trial

PACE-B is one of three branches of a multi-center collaboration among 37 radiation therapy centers in the United Kingdom, Ireland, and Canada.

In the trial, investigators enrolled 874 patients with T1c or T2c prostate cancer, Gleason score of 3+4 or less, prostate-specific antigen (PSA) level no higher than 20 ng/mL, MRI staging, and no prior androgen deprivation therapy. Investigators then randomly assigned them on a 1:1 basis to receive either conventional radiation (n = 441) or SBRT (n = 433).

At the start of the trial, patients who were assigned to the conventional radiation group received 78 Gy in 39 fractions over 4-8 weeks. However, after results from the CHHiP trial, which showed that a 60-Gy, 20-fraction regimen was not inferior to a 74-Gy, 37-fraction regimen, the PACE-B investigators modified the protocol to 62 Gy delivered in 20 fractions.

Patients assigned to SBRT received 36.25 Gy divided into give fractions delivered over 1-2 weeks, with 40 Gy to the clinical target volume.

The primary outcome was noninferiority of SBRT, measured as whether patients remained free of biochemical clinical failure. Biochemical clinical failure was defined as evidence that the cancer was returning, such as an increase in PSA levels or distant metastases or death from prostate cancer.

At a median follow-up of 73.1 months, 5-year event-free survival rates were 94.6% for patients who received conventional radiation therapy and 95.8% for patients who received SBRT, meeting the prespecified criteria for noninferiority of SBRT (P = .007).

Freedom from biochemical and clinical failure, the trial’s primary endpoint, “was significantly better on both arms than our original power calculation, where we expected control rates of approximately 85%,” Dr. Van As said in an ASTRO plenary session.

Toxicity rates were also low in both study arms. The rate of grade 2 or greater urogenital side effects at 5 years was 5.5% in the SBRT arm and 3.2% in the conventional therapy arm. Grade 2 or greater gastrointestinal side effects occurred in only two patients, one in each study arm.

Given the findings, “I think it’s now imperative that our surgeons discuss this data with their patients before they perform prostatectomies,” Dr. Van As said.

Neha Vapiwala, MD, president-elect of ASTRO who moderated a media briefing where Dr. Van As summarized the PACE-B data, commented that “this study was conducted very rigorously, with excellent quality assurance.”

The study also highlights that clinicians in the United States have considerable catching up to do, said Dr. Vapiwala, from the Hospital of the University of Pennsylvania, Philadelphia.

In the United States, “we are way behind our colleagues on the other side of the pond,” she said. “We are way behind in our uptake of ultra-hypofractionated radiation [such as SBRT], and I do believe that some of that comes from the lack of feeling comfortable with the techniques that are needed and the expertise that is needed.”

PACE-B was funded by Accuray. Dr. Van As disclosed research grants from the company and consulting fees from Varian. Dr. Berlin reported no conflict of interest relevant to the study. Dr. Vapiwala has disclosed a consulting or advisory role with Bayer.

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

SAN DIEGO – With just five fractions of stereotactic body radiation therapy (SBRT), men with low- or intermediate-risk prostate cancer can have 5-year disease control as good as that provided by conventional external-beam radiation therapy delivered at higher doses in 20-39 fractions, according to new data from the phase 3 randomized PACE-B trial.

Overall, the 5-year event-free survival rates were 95.8% among patients who received SBRT and 94.6% among those who had conventional radiation. The incidence of adverse events was also low in both groups, with no significant differences observed between the trial arms.

The similar event-free survival and toxicity profiles in both groups provide more support for SBRT, which treats prostate cancer with larger radiation fractions over a shorter time period.

“I think we can also say now with a high level of confidence that SBRT can be considered a new standard of care for low and favorable intermediate-risk prostate cancer,” said Nicholas van As, MD, MB, from the Royal Marsden NHS Foundation Trust and Institute of Cancer Research in London, who presented efficacy and safety results from the noninferiority trial at the American Society for Radiation Oncology (ASTRO) annual meeting. SBRT is more convenient for patients and more cost-effective for health care providers, Dr. Van As added.

Invited discussant Alejandro Berlin, MD, MSc, from Princess Margaret Cancer Centre and the University of Toronto, agreed “that this should be a standard of care for low and favorable intermediate-risk prostate cancer,” an option already endorsed by relevant guidelines.

But, Dr. Berlin noted, SBRT requires careful attention to technique to achieve the desired results. Further research will be needed to identify and potentially reduce variability among radiation oncology practice regarding margins, dosimetry goals, dose heterogeneity, treatment schedules, and other factors, he said.
 

An international trial

PACE-B is one of three branches of a multi-center collaboration among 37 radiation therapy centers in the United Kingdom, Ireland, and Canada.

In the trial, investigators enrolled 874 patients with T1c or T2c prostate cancer, Gleason score of 3+4 or less, prostate-specific antigen (PSA) level no higher than 20 ng/mL, MRI staging, and no prior androgen deprivation therapy. Investigators then randomly assigned them on a 1:1 basis to receive either conventional radiation (n = 441) or SBRT (n = 433).

At the start of the trial, patients who were assigned to the conventional radiation group received 78 Gy in 39 fractions over 4-8 weeks. However, after results from the CHHiP trial, which showed that a 60-Gy, 20-fraction regimen was not inferior to a 74-Gy, 37-fraction regimen, the PACE-B investigators modified the protocol to 62 Gy delivered in 20 fractions.

Patients assigned to SBRT received 36.25 Gy divided into give fractions delivered over 1-2 weeks, with 40 Gy to the clinical target volume.

The primary outcome was noninferiority of SBRT, measured as whether patients remained free of biochemical clinical failure. Biochemical clinical failure was defined as evidence that the cancer was returning, such as an increase in PSA levels or distant metastases or death from prostate cancer.

At a median follow-up of 73.1 months, 5-year event-free survival rates were 94.6% for patients who received conventional radiation therapy and 95.8% for patients who received SBRT, meeting the prespecified criteria for noninferiority of SBRT (P = .007).

Freedom from biochemical and clinical failure, the trial’s primary endpoint, “was significantly better on both arms than our original power calculation, where we expected control rates of approximately 85%,” Dr. Van As said in an ASTRO plenary session.

Toxicity rates were also low in both study arms. The rate of grade 2 or greater urogenital side effects at 5 years was 5.5% in the SBRT arm and 3.2% in the conventional therapy arm. Grade 2 or greater gastrointestinal side effects occurred in only two patients, one in each study arm.

Given the findings, “I think it’s now imperative that our surgeons discuss this data with their patients before they perform prostatectomies,” Dr. Van As said.

Neha Vapiwala, MD, president-elect of ASTRO who moderated a media briefing where Dr. Van As summarized the PACE-B data, commented that “this study was conducted very rigorously, with excellent quality assurance.”

The study also highlights that clinicians in the United States have considerable catching up to do, said Dr. Vapiwala, from the Hospital of the University of Pennsylvania, Philadelphia.

In the United States, “we are way behind our colleagues on the other side of the pond,” she said. “We are way behind in our uptake of ultra-hypofractionated radiation [such as SBRT], and I do believe that some of that comes from the lack of feeling comfortable with the techniques that are needed and the expertise that is needed.”

PACE-B was funded by Accuray. Dr. Van As disclosed research grants from the company and consulting fees from Varian. Dr. Berlin reported no conflict of interest relevant to the study. Dr. Vapiwala has disclosed a consulting or advisory role with Bayer.

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

SAN DIEGO – Women with breast cancer who underwent postmastectomy breast reconstruction benefited from shorter bursts of higher-dose radiation, compared with the standard therapy, according to a new prospective, randomized study.

Side effects and physical well-being scores were similar among 400 women who received the two treatment regimens, and outcomes were similar or slightly better in the higher-dose group, reported Rinaa Punglia, MD, MPH, an associate professor of radiation oncology at Dana-Farber Brigham Cancer Center in Boston and colleagues at the annual meeting of the American Society for Radiation Oncology. In a press statement, Dr. Punglia noted that the outcomes weren’t as impressive as researchers had hoped, but it’s positive that higher doses didn’t cause more side effects.

The use of the higher-dose approach, known as hypofractionation, “resulted in fewer treatment breaks and less financial toxicity” vs. conventional fractionation, Dr. Punglia said at a news briefing. The findings of the FABREC study “support the use of hypofractionated postmastectomy radiation for patients with basic reconstruction.”

According to Dr. Punglia, “postmastectomy radiation therapy is indicated for almost one-third of mastectomy patients and improves the lives of patients who are at an elevated risk for recurrence.” However, “the addition of radiation therapy greatly increases the risk of reconstruction complications.”

The typical radiation treatment period is 5-6 weeks in these patients, a major hardship for patients that can take them away from their families for extended periods of time. The researchers sought to understand whether another approach – hypofractionation over 3-4 weeks – is a better option. The strategy is widely used after breast-conserving surgery, she said, and has been linked to similar cancer outcomes, improved quality of life, and improved breast appearance.

From 2018 to 2021, the researchers recruited 400 patients with stage 0-III breast cancer who were treated with mastectomy and immediately underwent implant-based reconstruction (median age = 47.0, 23-79). None had tumors growing into the chest wall or skin.

The patients, spread nationwide across 16 institutions, were randomized to receive conventional fractionation (n = 201, 25 fractions, 5 days a week for 5 weeks of 200 cGy) or hypofractionation (n=199, 16 fractions, 5 days a week, for about 3 weeks of 266 cGy).

The researchers tracked 385 patients over a median follow-up of 40.4 months. There was no statistically significant difference in distant recurrence (12 in conventional fractionation arm, 11 in hypofractionation arm), death (2 in each arm), local recurrence (1 in each arm), or toxicity in the chest wall area (20 in conventional fractionation arm, 19 in hypofractionation arm). Changes in physical well-being scores, the primary endpoint, were similar after controlling for age.

“We found that younger patients randomized to hypofractionation were less bothered by side effects of treatment at 6 months relative to their counterparts who received conventional fractionation,” Dr. Punglia said.

Treatment breaks were more common in the conventional fractionation arm (7.7%, mean = 3.3 days) vs. the hypofractionation arm (2.7%, mean = 2.8 days, P = .03).

Among 51 patients who took unpaid time off work, those who underwent hypofractionation took fewer mean days off (73.7 days vs. 125.8 days for conventional fractionation, P = .046).

The study is the first of its kind to compare conventional fractionation to hypofractionation in this population in a randomized, phase III study, Dr. Punglia said.

At the news briefing, an independent expert – Lori Pierce, MD, a professor of radiation oncology at the University of Michigan – said the new study is a “game changer.”

The findings about the benefits of hypofractionation “will potentially impact thousands of women,” said Dr. Pierce, former president of the American Society of Clinical Oncology. The shorter course of radiation is more convenient for patients, she said, and reduces hardship.

“Without a doubt, these results should be discussed with all patients who have had mastectomy and implant-based reconstruction,” she said.

In an interview, Bruce G. Haffty, MD, MS, professor and chair of Radiation Oncology at Rutgers Cancer Institute of New Jersey, said the study adds to existing data suggesting that shorter courses of therapy “are probably OK.” The new findings “give people a little more confidence that [short courses are] safe in terms of well-being and toxicity.”

However, the follow-up in the trial is relatively short, he said, and longer-term research will be needed to change the standard of care in these patients. “It’ll be an evolving story over the next 5-10 years,” he said.

The study was funded by the Patient-Centered Outcomes Research Institute. Dr. Punglia has no disclosures; disclosures for other authors were not provided. Disclosure information for Dr. Pierce was not provided. Dr. Haffty is an investigator in a similar study called RT CHARM.

SAN DIEGO – Women with breast cancer who underwent postmastectomy breast reconstruction benefited from shorter bursts of higher-dose radiation, compared with the standard therapy, according to a new prospective, randomized study.

Side effects and physical well-being scores were similar among 400 women who received the two treatment regimens, and outcomes were similar or slightly better in the higher-dose group, reported Rinaa Punglia, MD, MPH, an associate professor of radiation oncology at Dana-Farber Brigham Cancer Center in Boston and colleagues at the annual meeting of the American Society for Radiation Oncology. In a press statement, Dr. Punglia noted that the outcomes weren’t as impressive as researchers had hoped, but it’s positive that higher doses didn’t cause more side effects.

The use of the higher-dose approach, known as hypofractionation, “resulted in fewer treatment breaks and less financial toxicity” vs. conventional fractionation, Dr. Punglia said at a news briefing. The findings of the FABREC study “support the use of hypofractionated postmastectomy radiation for patients with basic reconstruction.”

According to Dr. Punglia, “postmastectomy radiation therapy is indicated for almost one-third of mastectomy patients and improves the lives of patients who are at an elevated risk for recurrence.” However, “the addition of radiation therapy greatly increases the risk of reconstruction complications.”

The typical radiation treatment period is 5-6 weeks in these patients, a major hardship for patients that can take them away from their families for extended periods of time. The researchers sought to understand whether another approach – hypofractionation over 3-4 weeks – is a better option. The strategy is widely used after breast-conserving surgery, she said, and has been linked to similar cancer outcomes, improved quality of life, and improved breast appearance.

From 2018 to 2021, the researchers recruited 400 patients with stage 0-III breast cancer who were treated with mastectomy and immediately underwent implant-based reconstruction (median age = 47.0, 23-79). None had tumors growing into the chest wall or skin.

The patients, spread nationwide across 16 institutions, were randomized to receive conventional fractionation (n = 201, 25 fractions, 5 days a week for 5 weeks of 200 cGy) or hypofractionation (n=199, 16 fractions, 5 days a week, for about 3 weeks of 266 cGy).

The researchers tracked 385 patients over a median follow-up of 40.4 months. There was no statistically significant difference in distant recurrence (12 in conventional fractionation arm, 11 in hypofractionation arm), death (2 in each arm), local recurrence (1 in each arm), or toxicity in the chest wall area (20 in conventional fractionation arm, 19 in hypofractionation arm). Changes in physical well-being scores, the primary endpoint, were similar after controlling for age.

“We found that younger patients randomized to hypofractionation were less bothered by side effects of treatment at 6 months relative to their counterparts who received conventional fractionation,” Dr. Punglia said.

Treatment breaks were more common in the conventional fractionation arm (7.7%, mean = 3.3 days) vs. the hypofractionation arm (2.7%, mean = 2.8 days, P = .03).

Among 51 patients who took unpaid time off work, those who underwent hypofractionation took fewer mean days off (73.7 days vs. 125.8 days for conventional fractionation, P = .046).

The study is the first of its kind to compare conventional fractionation to hypofractionation in this population in a randomized, phase III study, Dr. Punglia said.

At the news briefing, an independent expert – Lori Pierce, MD, a professor of radiation oncology at the University of Michigan – said the new study is a “game changer.”

The findings about the benefits of hypofractionation “will potentially impact thousands of women,” said Dr. Pierce, former president of the American Society of Clinical Oncology. The shorter course of radiation is more convenient for patients, she said, and reduces hardship.

“Without a doubt, these results should be discussed with all patients who have had mastectomy and implant-based reconstruction,” she said.

In an interview, Bruce G. Haffty, MD, MS, professor and chair of Radiation Oncology at Rutgers Cancer Institute of New Jersey, said the study adds to existing data suggesting that shorter courses of therapy “are probably OK.” The new findings “give people a little more confidence that [short courses are] safe in terms of well-being and toxicity.”

However, the follow-up in the trial is relatively short, he said, and longer-term research will be needed to change the standard of care in these patients. “It’ll be an evolving story over the next 5-10 years,” he said.

The study was funded by the Patient-Centered Outcomes Research Institute. Dr. Punglia has no disclosures; disclosures for other authors were not provided. Disclosure information for Dr. Pierce was not provided. Dr. Haffty is an investigator in a similar study called RT CHARM.

SAN DIEGO – Women with breast cancer who underwent postmastectomy breast reconstruction benefited from shorter bursts of higher-dose radiation, compared with the standard therapy, according to a new prospective, randomized study.

Side effects and physical well-being scores were similar among 400 women who received the two treatment regimens, and outcomes were similar or slightly better in the higher-dose group, reported Rinaa Punglia, MD, MPH, an associate professor of radiation oncology at Dana-Farber Brigham Cancer Center in Boston and colleagues at the annual meeting of the American Society for Radiation Oncology. In a press statement, Dr. Punglia noted that the outcomes weren’t as impressive as researchers had hoped, but it’s positive that higher doses didn’t cause more side effects.

The use of the higher-dose approach, known as hypofractionation, “resulted in fewer treatment breaks and less financial toxicity” vs. conventional fractionation, Dr. Punglia said at a news briefing. The findings of the FABREC study “support the use of hypofractionated postmastectomy radiation for patients with basic reconstruction.”

According to Dr. Punglia, “postmastectomy radiation therapy is indicated for almost one-third of mastectomy patients and improves the lives of patients who are at an elevated risk for recurrence.” However, “the addition of radiation therapy greatly increases the risk of reconstruction complications.”

The typical radiation treatment period is 5-6 weeks in these patients, a major hardship for patients that can take them away from their families for extended periods of time. The researchers sought to understand whether another approach – hypofractionation over 3-4 weeks – is a better option. The strategy is widely used after breast-conserving surgery, she said, and has been linked to similar cancer outcomes, improved quality of life, and improved breast appearance.

From 2018 to 2021, the researchers recruited 400 patients with stage 0-III breast cancer who were treated with mastectomy and immediately underwent implant-based reconstruction (median age = 47.0, 23-79). None had tumors growing into the chest wall or skin.

The patients, spread nationwide across 16 institutions, were randomized to receive conventional fractionation (n = 201, 25 fractions, 5 days a week for 5 weeks of 200 cGy) or hypofractionation (n=199, 16 fractions, 5 days a week, for about 3 weeks of 266 cGy).

The researchers tracked 385 patients over a median follow-up of 40.4 months. There was no statistically significant difference in distant recurrence (12 in conventional fractionation arm, 11 in hypofractionation arm), death (2 in each arm), local recurrence (1 in each arm), or toxicity in the chest wall area (20 in conventional fractionation arm, 19 in hypofractionation arm). Changes in physical well-being scores, the primary endpoint, were similar after controlling for age.

“We found that younger patients randomized to hypofractionation were less bothered by side effects of treatment at 6 months relative to their counterparts who received conventional fractionation,” Dr. Punglia said.

Treatment breaks were more common in the conventional fractionation arm (7.7%, mean = 3.3 days) vs. the hypofractionation arm (2.7%, mean = 2.8 days, P = .03).

Among 51 patients who took unpaid time off work, those who underwent hypofractionation took fewer mean days off (73.7 days vs. 125.8 days for conventional fractionation, P = .046).

The study is the first of its kind to compare conventional fractionation to hypofractionation in this population in a randomized, phase III study, Dr. Punglia said.

At the news briefing, an independent expert – Lori Pierce, MD, a professor of radiation oncology at the University of Michigan – said the new study is a “game changer.”

The findings about the benefits of hypofractionation “will potentially impact thousands of women,” said Dr. Pierce, former president of the American Society of Clinical Oncology. The shorter course of radiation is more convenient for patients, she said, and reduces hardship.

“Without a doubt, these results should be discussed with all patients who have had mastectomy and implant-based reconstruction,” she said.

In an interview, Bruce G. Haffty, MD, MS, professor and chair of Radiation Oncology at Rutgers Cancer Institute of New Jersey, said the study adds to existing data suggesting that shorter courses of therapy “are probably OK.” The new findings “give people a little more confidence that [short courses are] safe in terms of well-being and toxicity.”

However, the follow-up in the trial is relatively short, he said, and longer-term research will be needed to change the standard of care in these patients. “It’ll be an evolving story over the next 5-10 years,” he said.

The study was funded by the Patient-Centered Outcomes Research Institute. Dr. Punglia has no disclosures; disclosures for other authors were not provided. Disclosure information for Dr. Pierce was not provided. Dr. Haffty is an investigator in a similar study called RT CHARM.

Multicancer early-detection blood (MCED) tests are the focus of intensive development. What techniques do these tests use? What potential do they show? Suzette Delaloge, MD, MSc, oncologist, breast cancer specialist, and director of the individualized cancer prevention program (Interception) at the Gustave Roussy Institute in Villejuif, France, looks into these “liquid biopsies” and shares her reservations about their potential marketing, especially to the organized care plans.

Question: What are the general principles underpinning these MCED tests?

Suzette Delaloge, MD, MSc: Despite their specificities, the general idea is to detect certain cancer markers in various body fluids (blood, urine, saliva, etc.), for example, molecules released by cancer cells (cytokines, inflammatory proteins, leptin, etc.) or distinctive features of the DNA in tumor cells. In blood, these molecules can be found in plasma or in serum. In urine, it’s more about detecting kidney, bladder, and urinary tract cancers.

Q: What sort of time frame are we looking at for these MCED tests to be used in routine practice?

Dr. Delaloge: They first appeared around 10 years ago. Development of these tests has intensified in recent years. There are numerous research laboratories, both public and private, that are developing different early-detection tests for cancer.

Some of these development processes are about to come to an end and are expected to be in regular, concrete use within 5-10 years. For the most advanced developments, the main biologic material researched and analyzed is DNA from cancer cells. We all have fragments of DNA from dead cells in our plasma (apoptosis), but cancer cells release more of these than others, and most importantly, their DNA has distinctive characteristics. The idea is to develop tests capable of detecting these characteristics.

Liquid biopsies based on genomic biomarkers could make MCED a reality, especially for cancers for which there is no standard screening process. But at this stage of the research, there are limitations, including low sensitivity for detecting stage I cancers in validation studies and an increased risk for overdiagnosis.

Q: What specific set of characteristics are the most advanced approaches based on?

Dr. Delaloge: They’re based on the analysis of DNA methylation, a biological process by which CH3 methyl groups are added to the DNA molecule and that determines gene expression. This phenomenon differs depending on whether the cell is cancerous. Among the tests currently under development making use of this specific characteristic is the Galleri test, which is the most advanced of them all.

A previous British National Health Service study, SYMPLIFY, which was published in 2023 by researchers at the University of Oxford, was conducted in symptomatic patients attending a health center. It offers promising results in a diagnostic situation. It has nothing at all to do with screening here. A large, randomized English study, NHS-Galleri, is underway, this time involving the general population, with the aim of assessing the potential benefit of the same test as screening in 140,000 people between ages 50 and 77 years.

In the SYMPLIFY study, which was carried out in symptomatic patients attending a health center, the Galleri MCED test had a positive predictive value of 75.5%, a negative predictive value of 97.6%, a sensitivity of 66.3%, and a specificity of 98.4%. Sensitivity increased with age and cancer stage from 24.2% at stage I to 95.3% at stage IV. For cases for which a cancer signal was detected in patients with cancer, the prediction of the original site of the cancer by the MCED test was accurate in 85.2% of cases. This large-scale prospective evaluation of an MCED diagnostic test confirms its feasibility in a symptomatic population but is not yet sufficiently accurate to “confirm or rule out the presence of cancer.” According to the authors, “in cases in which the MCED test detects a cancer signal in this context, the probability of a diagnosis of cancer being made is considerably higher and may identify cancers at sites other than those suspected during the initial referral phase, thus reducing delays in diagnosis.” A negative test means a lower likelihood of cancer but not so low that proper investigation can be ruled out. Further tests will be needed to optimize use of a negative predictive value.

Q: Does MCED testing concern all types of cancer?

Dr. Delaloge: The Galleri test is based on full profiling of DNA methylation. This allows for early diagnosis of cancer even before it can be seen on imaging tests. The issue with these tests is that they aren’t that good at early diagnosis of the most common types of cancer (breast, colorectal, cervical, etc.) for which we already have more efficient means such as the fecal immunochemical test for colorectal cancer, mammography, HPV testing, and so on.

These blood tests would thus not be aimed at replacing routine screening but rather at screening asymptomatic individuals or those with nonspecific signs for cancers for which we have few or no screening measures and which are on the rise, such as deep tumors and cancer diagnosed at a late stage, namely pancreas, bile duct, ovarian, esophageal, lung, stomach, etc.

The results from the studies published are promising, but others are underway to confirm the benefit of these MCEDs. The challenge is to identify cancer at an early stage, at a stage where it will be easier to cure the patient and control its growth using treatments that are less onerous for the patient and that have fewer aftereffects but not at the expense of a massive increase in overdiagnosis, as seen with prostate-specific antigen levels in prostate cancer a few years ago!

Q: What would be the focus of these MCED tests?

Dr. Delaloge: We must be alert to the risk for the market development of MCED tests. For now, they are mostly, especially the Galleri test, developed in the general population to screen for types of cancer that could not be detected in any other way but also because it’s the most financially beneficial situation. The designers want to position themselves in the general population, regardless of whether this means they’ll have to test hundreds of people to find one for whom the test is beneficial. What’s more, developing tests in isolation, without considering their place in ad hoc treatment pathways, is not realistic. It’s likely that some of these tests will be marketed within the next 10 years, but the health care systems destined to receive them are not remotely ready to do so.

Q: An even more recent publication, from late July 2023, is even more exciting in relation to early detection of lung cancer using circulating DNA sequencing. What are your thoughts on it?

Dr. Delaloge: Initially overtaken by other technologies in favor of MCED approaches, DNA sequencing as a technique to detect somatic mutations seems to have reentered the competition with this new-generation research. The authors published some very interesting results, especially for stage I lung cancer with a very high sensitivity of 75%. [Editor’s note: A machine-learning model using genome-wide mutational profiles combined with other features and followed by CT imaging detected more than 90% of patients with lung cancer, including those with stage I and II disease.]

This research illustrates the difficulty of providing high performance while covering a broad range of cancers. Here, the good results mainly concern lung cancer. Researchers and health care authorities must be alert to ensuring that MCED tests prove themselves in terms of sensitivity and specificity in responding to a medical need and in their impact on specific mortality. This craze for MCED tests must not hinder the development of “single-cancer” technologies that may be much better for detecting specific cancers. This recent publication is interesting in this respect, because this sequencing test seems to be particularly good at detecting lung cancer.

Q: Another approach used in MCED tests is based on analyzing the size of DNA fragments in the blood. Can you explain how this works?

Dr. Delaloge: When cancer is not present, the size of DNA fragments in cells is much more homogeneous. Here also, the benefit of MCED based on this technique rests on the very early detection of cancers that are less common than those for which we already have good screening methods available.

Other approaches, still at the experimental stage, detect certain proteins, certain inflammatory molecules, RNA, etc. But for many researchers, the future will involve pairing tests on the basis of circulating DNA in the blood with the detection of specific molecules indicating the presence of cancer to obtain early screening tests that are even more effective or that possibly even allow us to identify an appropriate treatment at an early stage.

The development of a simple test based on a blood draw that allows us to screen early for all cancers and that would replace all current screening measures is, therefore, not imminent, although it could potentially be on the horizon in years to come. Alongside this, an important issue is the benefit of cancer screening in the general population vs. in a targeted population with a specific risk. The latter option is in development but requires an individualized screening pathway based on blood testing and current screening methods: imaging, etc. It also depends on an individual’s cancer risk profile such as age, personal and family medical history, genetic predisposition, and so on.

According to recent modeling, these multicancer tests could theoretically prevent a minimum of 2,000 deaths from cancer per 100,000 people between ages 50 and 79 years screened per year (17% fewer deaths from cancer per year).

This article was translated from the Medscape French Edition. A version appeared on Medscape.com.

Multicancer early-detection blood (MCED) tests are the focus of intensive development. What techniques do these tests use? What potential do they show? Suzette Delaloge, MD, MSc, oncologist, breast cancer specialist, and director of the individualized cancer prevention program (Interception) at the Gustave Roussy Institute in Villejuif, France, looks into these “liquid biopsies” and shares her reservations about their potential marketing, especially to the organized care plans.

Question: What are the general principles underpinning these MCED tests?

Suzette Delaloge, MD, MSc: Despite their specificities, the general idea is to detect certain cancer markers in various body fluids (blood, urine, saliva, etc.), for example, molecules released by cancer cells (cytokines, inflammatory proteins, leptin, etc.) or distinctive features of the DNA in tumor cells. In blood, these molecules can be found in plasma or in serum. In urine, it’s more about detecting kidney, bladder, and urinary tract cancers.

Q: What sort of time frame are we looking at for these MCED tests to be used in routine practice?

Dr. Delaloge: They first appeared around 10 years ago. Development of these tests has intensified in recent years. There are numerous research laboratories, both public and private, that are developing different early-detection tests for cancer.

Some of these development processes are about to come to an end and are expected to be in regular, concrete use within 5-10 years. For the most advanced developments, the main biologic material researched and analyzed is DNA from cancer cells. We all have fragments of DNA from dead cells in our plasma (apoptosis), but cancer cells release more of these than others, and most importantly, their DNA has distinctive characteristics. The idea is to develop tests capable of detecting these characteristics.

Liquid biopsies based on genomic biomarkers could make MCED a reality, especially for cancers for which there is no standard screening process. But at this stage of the research, there are limitations, including low sensitivity for detecting stage I cancers in validation studies and an increased risk for overdiagnosis.

Q: What specific set of characteristics are the most advanced approaches based on?

Dr. Delaloge: They’re based on the analysis of DNA methylation, a biological process by which CH3 methyl groups are added to the DNA molecule and that determines gene expression. This phenomenon differs depending on whether the cell is cancerous. Among the tests currently under development making use of this specific characteristic is the Galleri test, which is the most advanced of them all.

A previous British National Health Service study, SYMPLIFY, which was published in 2023 by researchers at the University of Oxford, was conducted in symptomatic patients attending a health center. It offers promising results in a diagnostic situation. It has nothing at all to do with screening here. A large, randomized English study, NHS-Galleri, is underway, this time involving the general population, with the aim of assessing the potential benefit of the same test as screening in 140,000 people between ages 50 and 77 years.

In the SYMPLIFY study, which was carried out in symptomatic patients attending a health center, the Galleri MCED test had a positive predictive value of 75.5%, a negative predictive value of 97.6%, a sensitivity of 66.3%, and a specificity of 98.4%. Sensitivity increased with age and cancer stage from 24.2% at stage I to 95.3% at stage IV. For cases for which a cancer signal was detected in patients with cancer, the prediction of the original site of the cancer by the MCED test was accurate in 85.2% of cases. This large-scale prospective evaluation of an MCED diagnostic test confirms its feasibility in a symptomatic population but is not yet sufficiently accurate to “confirm or rule out the presence of cancer.” According to the authors, “in cases in which the MCED test detects a cancer signal in this context, the probability of a diagnosis of cancer being made is considerably higher and may identify cancers at sites other than those suspected during the initial referral phase, thus reducing delays in diagnosis.” A negative test means a lower likelihood of cancer but not so low that proper investigation can be ruled out. Further tests will be needed to optimize use of a negative predictive value.

Q: Does MCED testing concern all types of cancer?

Dr. Delaloge: The Galleri test is based on full profiling of DNA methylation. This allows for early diagnosis of cancer even before it can be seen on imaging tests. The issue with these tests is that they aren’t that good at early diagnosis of the most common types of cancer (breast, colorectal, cervical, etc.) for which we already have more efficient means such as the fecal immunochemical test for colorectal cancer, mammography, HPV testing, and so on.

These blood tests would thus not be aimed at replacing routine screening but rather at screening asymptomatic individuals or those with nonspecific signs for cancers for which we have few or no screening measures and which are on the rise, such as deep tumors and cancer diagnosed at a late stage, namely pancreas, bile duct, ovarian, esophageal, lung, stomach, etc.

The results from the studies published are promising, but others are underway to confirm the benefit of these MCEDs. The challenge is to identify cancer at an early stage, at a stage where it will be easier to cure the patient and control its growth using treatments that are less onerous for the patient and that have fewer aftereffects but not at the expense of a massive increase in overdiagnosis, as seen with prostate-specific antigen levels in prostate cancer a few years ago!

Q: What would be the focus of these MCED tests?

Dr. Delaloge: We must be alert to the risk for the market development of MCED tests. For now, they are mostly, especially the Galleri test, developed in the general population to screen for types of cancer that could not be detected in any other way but also because it’s the most financially beneficial situation. The designers want to position themselves in the general population, regardless of whether this means they’ll have to test hundreds of people to find one for whom the test is beneficial. What’s more, developing tests in isolation, without considering their place in ad hoc treatment pathways, is not realistic. It’s likely that some of these tests will be marketed within the next 10 years, but the health care systems destined to receive them are not remotely ready to do so.

Q: An even more recent publication, from late July 2023, is even more exciting in relation to early detection of lung cancer using circulating DNA sequencing. What are your thoughts on it?

Dr. Delaloge: Initially overtaken by other technologies in favor of MCED approaches, DNA sequencing as a technique to detect somatic mutations seems to have reentered the competition with this new-generation research. The authors published some very interesting results, especially for stage I lung cancer with a very high sensitivity of 75%. [Editor’s note: A machine-learning model using genome-wide mutational profiles combined with other features and followed by CT imaging detected more than 90% of patients with lung cancer, including those with stage I and II disease.]

This research illustrates the difficulty of providing high performance while covering a broad range of cancers. Here, the good results mainly concern lung cancer. Researchers and health care authorities must be alert to ensuring that MCED tests prove themselves in terms of sensitivity and specificity in responding to a medical need and in their impact on specific mortality. This craze for MCED tests must not hinder the development of “single-cancer” technologies that may be much better for detecting specific cancers. This recent publication is interesting in this respect, because this sequencing test seems to be particularly good at detecting lung cancer.

Q: Another approach used in MCED tests is based on analyzing the size of DNA fragments in the blood. Can you explain how this works?

Dr. Delaloge: When cancer is not present, the size of DNA fragments in cells is much more homogeneous. Here also, the benefit of MCED based on this technique rests on the very early detection of cancers that are less common than those for which we already have good screening methods available.

Other approaches, still at the experimental stage, detect certain proteins, certain inflammatory molecules, RNA, etc. But for many researchers, the future will involve pairing tests on the basis of circulating DNA in the blood with the detection of specific molecules indicating the presence of cancer to obtain early screening tests that are even more effective or that possibly even allow us to identify an appropriate treatment at an early stage.

The development of a simple test based on a blood draw that allows us to screen early for all cancers and that would replace all current screening measures is, therefore, not imminent, although it could potentially be on the horizon in years to come. Alongside this, an important issue is the benefit of cancer screening in the general population vs. in a targeted population with a specific risk. The latter option is in development but requires an individualized screening pathway based on blood testing and current screening methods: imaging, etc. It also depends on an individual’s cancer risk profile such as age, personal and family medical history, genetic predisposition, and so on.

According to recent modeling, these multicancer tests could theoretically prevent a minimum of 2,000 deaths from cancer per 100,000 people between ages 50 and 79 years screened per year (17% fewer deaths from cancer per year).

This article was translated from the Medscape French Edition. A version appeared on Medscape.com.

Multicancer early-detection blood (MCED) tests are the focus of intensive development. What techniques do these tests use? What potential do they show? Suzette Delaloge, MD, MSc, oncologist, breast cancer specialist, and director of the individualized cancer prevention program (Interception) at the Gustave Roussy Institute in Villejuif, France, looks into these “liquid biopsies” and shares her reservations about their potential marketing, especially to the organized care plans.

Question: What are the general principles underpinning these MCED tests?

Suzette Delaloge, MD, MSc: Despite their specificities, the general idea is to detect certain cancer markers in various body fluids (blood, urine, saliva, etc.), for example, molecules released by cancer cells (cytokines, inflammatory proteins, leptin, etc.) or distinctive features of the DNA in tumor cells. In blood, these molecules can be found in plasma or in serum. In urine, it’s more about detecting kidney, bladder, and urinary tract cancers.

Q: What sort of time frame are we looking at for these MCED tests to be used in routine practice?

Dr. Delaloge: They first appeared around 10 years ago. Development of these tests has intensified in recent years. There are numerous research laboratories, both public and private, that are developing different early-detection tests for cancer.

Some of these development processes are about to come to an end and are expected to be in regular, concrete use within 5-10 years. For the most advanced developments, the main biologic material researched and analyzed is DNA from cancer cells. We all have fragments of DNA from dead cells in our plasma (apoptosis), but cancer cells release more of these than others, and most importantly, their DNA has distinctive characteristics. The idea is to develop tests capable of detecting these characteristics.

Liquid biopsies based on genomic biomarkers could make MCED a reality, especially for cancers for which there is no standard screening process. But at this stage of the research, there are limitations, including low sensitivity for detecting stage I cancers in validation studies and an increased risk for overdiagnosis.

Q: What specific set of characteristics are the most advanced approaches based on?

Dr. Delaloge: They’re based on the analysis of DNA methylation, a biological process by which CH3 methyl groups are added to the DNA molecule and that determines gene expression. This phenomenon differs depending on whether the cell is cancerous. Among the tests currently under development making use of this specific characteristic is the Galleri test, which is the most advanced of them all.

A previous British National Health Service study, SYMPLIFY, which was published in 2023 by researchers at the University of Oxford, was conducted in symptomatic patients attending a health center. It offers promising results in a diagnostic situation. It has nothing at all to do with screening here. A large, randomized English study, NHS-Galleri, is underway, this time involving the general population, with the aim of assessing the potential benefit of the same test as screening in 140,000 people between ages 50 and 77 years.

In the SYMPLIFY study, which was carried out in symptomatic patients attending a health center, the Galleri MCED test had a positive predictive value of 75.5%, a negative predictive value of 97.6%, a sensitivity of 66.3%, and a specificity of 98.4%. Sensitivity increased with age and cancer stage from 24.2% at stage I to 95.3% at stage IV. For cases for which a cancer signal was detected in patients with cancer, the prediction of the original site of the cancer by the MCED test was accurate in 85.2% of cases. This large-scale prospective evaluation of an MCED diagnostic test confirms its feasibility in a symptomatic population but is not yet sufficiently accurate to “confirm or rule out the presence of cancer.” According to the authors, “in cases in which the MCED test detects a cancer signal in this context, the probability of a diagnosis of cancer being made is considerably higher and may identify cancers at sites other than those suspected during the initial referral phase, thus reducing delays in diagnosis.” A negative test means a lower likelihood of cancer but not so low that proper investigation can be ruled out. Further tests will be needed to optimize use of a negative predictive value.

Q: Does MCED testing concern all types of cancer?

Dr. Delaloge: The Galleri test is based on full profiling of DNA methylation. This allows for early diagnosis of cancer even before it can be seen on imaging tests. The issue with these tests is that they aren’t that good at early diagnosis of the most common types of cancer (breast, colorectal, cervical, etc.) for which we already have more efficient means such as the fecal immunochemical test for colorectal cancer, mammography, HPV testing, and so on.

These blood tests would thus not be aimed at replacing routine screening but rather at screening asymptomatic individuals or those with nonspecific signs for cancers for which we have few or no screening measures and which are on the rise, such as deep tumors and cancer diagnosed at a late stage, namely pancreas, bile duct, ovarian, esophageal, lung, stomach, etc.

The results from the studies published are promising, but others are underway to confirm the benefit of these MCEDs. The challenge is to identify cancer at an early stage, at a stage where it will be easier to cure the patient and control its growth using treatments that are less onerous for the patient and that have fewer aftereffects but not at the expense of a massive increase in overdiagnosis, as seen with prostate-specific antigen levels in prostate cancer a few years ago!

Q: What would be the focus of these MCED tests?

Dr. Delaloge: We must be alert to the risk for the market development of MCED tests. For now, they are mostly, especially the Galleri test, developed in the general population to screen for types of cancer that could not be detected in any other way but also because it’s the most financially beneficial situation. The designers want to position themselves in the general population, regardless of whether this means they’ll have to test hundreds of people to find one for whom the test is beneficial. What’s more, developing tests in isolation, without considering their place in ad hoc treatment pathways, is not realistic. It’s likely that some of these tests will be marketed within the next 10 years, but the health care systems destined to receive them are not remotely ready to do so.

Q: An even more recent publication, from late July 2023, is even more exciting in relation to early detection of lung cancer using circulating DNA sequencing. What are your thoughts on it?

Dr. Delaloge: Initially overtaken by other technologies in favor of MCED approaches, DNA sequencing as a technique to detect somatic mutations seems to have reentered the competition with this new-generation research. The authors published some very interesting results, especially for stage I lung cancer with a very high sensitivity of 75%. [Editor’s note: A machine-learning model using genome-wide mutational profiles combined with other features and followed by CT imaging detected more than 90% of patients with lung cancer, including those with stage I and II disease.]

This research illustrates the difficulty of providing high performance while covering a broad range of cancers. Here, the good results mainly concern lung cancer. Researchers and health care authorities must be alert to ensuring that MCED tests prove themselves in terms of sensitivity and specificity in responding to a medical need and in their impact on specific mortality. This craze for MCED tests must not hinder the development of “single-cancer” technologies that may be much better for detecting specific cancers. This recent publication is interesting in this respect, because this sequencing test seems to be particularly good at detecting lung cancer.

Q: Another approach used in MCED tests is based on analyzing the size of DNA fragments in the blood. Can you explain how this works?

Dr. Delaloge: When cancer is not present, the size of DNA fragments in cells is much more homogeneous. Here also, the benefit of MCED based on this technique rests on the very early detection of cancers that are less common than those for which we already have good screening methods available.

Other approaches, still at the experimental stage, detect certain proteins, certain inflammatory molecules, RNA, etc. But for many researchers, the future will involve pairing tests on the basis of circulating DNA in the blood with the detection of specific molecules indicating the presence of cancer to obtain early screening tests that are even more effective or that possibly even allow us to identify an appropriate treatment at an early stage.

The development of a simple test based on a blood draw that allows us to screen early for all cancers and that would replace all current screening measures is, therefore, not imminent, although it could potentially be on the horizon in years to come. Alongside this, an important issue is the benefit of cancer screening in the general population vs. in a targeted population with a specific risk. The latter option is in development but requires an individualized screening pathway based on blood testing and current screening methods: imaging, etc. It also depends on an individual’s cancer risk profile such as age, personal and family medical history, genetic predisposition, and so on.

According to recent modeling, these multicancer tests could theoretically prevent a minimum of 2,000 deaths from cancer per 100,000 people between ages 50 and 79 years screened per year (17% fewer deaths from cancer per year).

This article was translated from the Medscape French Edition. A version appeared on Medscape.com.

The updated draft recommendation from the U.S. Preventive Services Task Force that would lower the recommended start age for routine screening mammograms by a decade for all average-risk women is not justified, experts argue in a “dissenting view” published in the New England Journal of Medicine.

The proposed change would affect more than 20 million U.S. women, and it’s “hard to see any potential benefits associated with lowering the starting age,” coauthor Steven Woloshin, MD, with Dartmouth Cancer Center, Lebanon, N.H., said in an NEJM podcast.

Back in May, when USPSTF released the draft recommendation, task force member John Wong, MD, with Tufts Medical Center, Boston, said in an interview, “It is now clear that screening every other year starting at age 40 has the potential to save about 20% more lives among all women.”

But, according to Dr. Woloshin, there is no recent evidence that mortality from breast cancer is increasing in young women.

In fact, the United States has seen a steady decrease in breast cancer mortality, especially among younger women. Breast cancer mortality among women under 50 “has been cut in half over the past 30 years,” Dr. Woloshin and coauthors explained.

Another wrinkle: The task force did not base its recent recommendation on randomized trial data. In fact, there have been no new randomized trials of screening mammography for women in their 40s since 2016. Instead, the task force relied on statistical models to “estimate what might happen if the starting age were lowered,” Dr. Woloshin and colleagues said.

Relying on a statistical model, however, “is problematic because it has some very optimistic assumptions about the benefit of mammography,” Dr. Woloshin said in the podcast. For instance, the models assume that screening mammography reduces breast cancer mortality by about 25%.

That 25% reduction is “far greater than what’s reported in the meta-analyses of the available randomized trials,” Dr. Woloshin explained. The meta-analyses report about a 16% reduction for all the trials combined and an estimated 13% for trials at low risk of bias. But “even these meta-analyses are likely to overstate the effect of screening since the trials were done before the major advances in treatment.”

In their own calculations, Dr. Woloshin and colleagues found that lowering the screening age to 40 came with a small potential benefit and a substantial risk for harm.

Combing data from the National Cancer Institute, the team reported that the risk for death for women in their 40s from any cause over the next 10 years was about 3% whether or not they received their biennial mammogram.

The risk for death from breast cancer in that time was 0.23% with mammograms – about 2 in every 1,000 women – and 0.31% without. “That’s 1 less breast cancer death per 1,000 women screened for 10 years,” Dr. Woloshin said.

Put another way, with mammography screening, “the chance of not dying from breast cancer over the next 10 years increases from 99.7% to 99.8%,” Dr. Woloshin said.

The benefit is arguably small, while the harms appear quite significant, Dr. Woloshin said. About 36% of women who begin screening at age 40 would have at least one false alarm over 10 years, and almost 7% would have a false alarm requiring a biopsy in that time frame.
 

Ease or exacerbate racial disparity?

Another argument that the USPSTF highlighted for lowering the screening age: Research indicates that Black women get breast cancer at younger ages and are more likely to die of the disease, compared with White women.

Dr. Woloshin and coauthors, however, also took issue with the view that lowering the screening age could reduce disparities between Black and White women.

“There’s no question that there are substantial differences between Black and White women in terms of breast cancer mortality, but there’s actually very little disparity in breast cancer screening – about 60% of Black and White women in their 40s are screened regularly in the United States,” Dr. Woloshin explained in the podcast.

Therefore, it’s “really hard to imagine” how recommending the same intervention to both groups could possibly reduce the disparity, he said.

“The disparity is not a reflection of screening. It reflects differences in cancer biology,” he added. “Black women are at higher risk for more aggressive, fast-growing cancers that are less likely to be caught by screening and unfortunately are less likely to benefit from treatment.”

Earlier screening would also not address the problems facing poor women, who tend to be disproportionately Black, such as lower quality of available medical services, follow-up delays after abnormal scans, treatment delays, and less use of adjuvant therapy, Dr. Woloshin cautioned.

In Dr. Woloshin’s view, lowering the screening age, which broadens the eligible population, may actually “exacerbate problems contributing to disparity by diverting resources toward expanded screening rather than doing what we know works by ensuring that high-quality treatments are more readily accessible to poor women with breast cancer.”
 

Reconsider the change?

Because task force recommendations are so influential, Dr. Woloshin and colleagues worry that mammography screening for women in their 40s will probably become a performance measure.

“Our concern is that, rather than fostering informed decisions, clinicians and practices are going to be judged and rewarded and punished based on compliance with this quality metric,” Dr. Woloshin said.

That’s a problem, he noted, “because women should be able to make the decision for themselves rather than having this be a public health imperative, which is imposed by physicians and practices who are incentivized to meet a quality metric.”

The hope, said Dr. Woloshin, is that this prospective piece will help influence the task force to “reconsider the recommendation, because we think that the bottom line is that their models are insufficient to support a new imperative. The benefits are really limited, and there are really common and important harms for healthy women.”

The comment period for the draft recommendation is now closed, and a final decision from the task force is forthcoming.

The research had no funding. Dr. Woloshin has no relevant disclosures.

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

The updated draft recommendation from the U.S. Preventive Services Task Force that would lower the recommended start age for routine screening mammograms by a decade for all average-risk women is not justified, experts argue in a “dissenting view” published in the New England Journal of Medicine.

The proposed change would affect more than 20 million U.S. women, and it’s “hard to see any potential benefits associated with lowering the starting age,” coauthor Steven Woloshin, MD, with Dartmouth Cancer Center, Lebanon, N.H., said in an NEJM podcast.

Back in May, when USPSTF released the draft recommendation, task force member John Wong, MD, with Tufts Medical Center, Boston, said in an interview, “It is now clear that screening every other year starting at age 40 has the potential to save about 20% more lives among all women.”

But, according to Dr. Woloshin, there is no recent evidence that mortality from breast cancer is increasing in young women.

In fact, the United States has seen a steady decrease in breast cancer mortality, especially among younger women. Breast cancer mortality among women under 50 “has been cut in half over the past 30 years,” Dr. Woloshin and coauthors explained.

Another wrinkle: The task force did not base its recent recommendation on randomized trial data. In fact, there have been no new randomized trials of screening mammography for women in their 40s since 2016. Instead, the task force relied on statistical models to “estimate what might happen if the starting age were lowered,” Dr. Woloshin and colleagues said.

Relying on a statistical model, however, “is problematic because it has some very optimistic assumptions about the benefit of mammography,” Dr. Woloshin said in the podcast. For instance, the models assume that screening mammography reduces breast cancer mortality by about 25%.

That 25% reduction is “far greater than what’s reported in the meta-analyses of the available randomized trials,” Dr. Woloshin explained. The meta-analyses report about a 16% reduction for all the trials combined and an estimated 13% for trials at low risk of bias. But “even these meta-analyses are likely to overstate the effect of screening since the trials were done before the major advances in treatment.”

In their own calculations, Dr. Woloshin and colleagues found that lowering the screening age to 40 came with a small potential benefit and a substantial risk for harm.

Combing data from the National Cancer Institute, the team reported that the risk for death for women in their 40s from any cause over the next 10 years was about 3% whether or not they received their biennial mammogram.

The risk for death from breast cancer in that time was 0.23% with mammograms – about 2 in every 1,000 women – and 0.31% without. “That’s 1 less breast cancer death per 1,000 women screened for 10 years,” Dr. Woloshin said.

Put another way, with mammography screening, “the chance of not dying from breast cancer over the next 10 years increases from 99.7% to 99.8%,” Dr. Woloshin said.

The benefit is arguably small, while the harms appear quite significant, Dr. Woloshin said. About 36% of women who begin screening at age 40 would have at least one false alarm over 10 years, and almost 7% would have a false alarm requiring a biopsy in that time frame.
 

Ease or exacerbate racial disparity?

Another argument that the USPSTF highlighted for lowering the screening age: Research indicates that Black women get breast cancer at younger ages and are more likely to die of the disease, compared with White women.

Dr. Woloshin and coauthors, however, also took issue with the view that lowering the screening age could reduce disparities between Black and White women.

“There’s no question that there are substantial differences between Black and White women in terms of breast cancer mortality, but there’s actually very little disparity in breast cancer screening – about 60% of Black and White women in their 40s are screened regularly in the United States,” Dr. Woloshin explained in the podcast.

Therefore, it’s “really hard to imagine” how recommending the same intervention to both groups could possibly reduce the disparity, he said.

“The disparity is not a reflection of screening. It reflects differences in cancer biology,” he added. “Black women are at higher risk for more aggressive, fast-growing cancers that are less likely to be caught by screening and unfortunately are less likely to benefit from treatment.”

Earlier screening would also not address the problems facing poor women, who tend to be disproportionately Black, such as lower quality of available medical services, follow-up delays after abnormal scans, treatment delays, and less use of adjuvant therapy, Dr. Woloshin cautioned.

In Dr. Woloshin’s view, lowering the screening age, which broadens the eligible population, may actually “exacerbate problems contributing to disparity by diverting resources toward expanded screening rather than doing what we know works by ensuring that high-quality treatments are more readily accessible to poor women with breast cancer.”
 

Reconsider the change?

Because task force recommendations are so influential, Dr. Woloshin and colleagues worry that mammography screening for women in their 40s will probably become a performance measure.

“Our concern is that, rather than fostering informed decisions, clinicians and practices are going to be judged and rewarded and punished based on compliance with this quality metric,” Dr. Woloshin said.

That’s a problem, he noted, “because women should be able to make the decision for themselves rather than having this be a public health imperative, which is imposed by physicians and practices who are incentivized to meet a quality metric.”

The hope, said Dr. Woloshin, is that this prospective piece will help influence the task force to “reconsider the recommendation, because we think that the bottom line is that their models are insufficient to support a new imperative. The benefits are really limited, and there are really common and important harms for healthy women.”

The comment period for the draft recommendation is now closed, and a final decision from the task force is forthcoming.

The research had no funding. Dr. Woloshin has no relevant disclosures.

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

The updated draft recommendation from the U.S. Preventive Services Task Force that would lower the recommended start age for routine screening mammograms by a decade for all average-risk women is not justified, experts argue in a “dissenting view” published in the New England Journal of Medicine.

The proposed change would affect more than 20 million U.S. women, and it’s “hard to see any potential benefits associated with lowering the starting age,” coauthor Steven Woloshin, MD, with Dartmouth Cancer Center, Lebanon, N.H., said in an NEJM podcast.

Back in May, when USPSTF released the draft recommendation, task force member John Wong, MD, with Tufts Medical Center, Boston, said in an interview, “It is now clear that screening every other year starting at age 40 has the potential to save about 20% more lives among all women.”

But, according to Dr. Woloshin, there is no recent evidence that mortality from breast cancer is increasing in young women.

In fact, the United States has seen a steady decrease in breast cancer mortality, especially among younger women. Breast cancer mortality among women under 50 “has been cut in half over the past 30 years,” Dr. Woloshin and coauthors explained.

Another wrinkle: The task force did not base its recent recommendation on randomized trial data. In fact, there have been no new randomized trials of screening mammography for women in their 40s since 2016. Instead, the task force relied on statistical models to “estimate what might happen if the starting age were lowered,” Dr. Woloshin and colleagues said.

Relying on a statistical model, however, “is problematic because it has some very optimistic assumptions about the benefit of mammography,” Dr. Woloshin said in the podcast. For instance, the models assume that screening mammography reduces breast cancer mortality by about 25%.

That 25% reduction is “far greater than what’s reported in the meta-analyses of the available randomized trials,” Dr. Woloshin explained. The meta-analyses report about a 16% reduction for all the trials combined and an estimated 13% for trials at low risk of bias. But “even these meta-analyses are likely to overstate the effect of screening since the trials were done before the major advances in treatment.”

In their own calculations, Dr. Woloshin and colleagues found that lowering the screening age to 40 came with a small potential benefit and a substantial risk for harm.

Combing data from the National Cancer Institute, the team reported that the risk for death for women in their 40s from any cause over the next 10 years was about 3% whether or not they received their biennial mammogram.

The risk for death from breast cancer in that time was 0.23% with mammograms – about 2 in every 1,000 women – and 0.31% without. “That’s 1 less breast cancer death per 1,000 women screened for 10 years,” Dr. Woloshin said.

Put another way, with mammography screening, “the chance of not dying from breast cancer over the next 10 years increases from 99.7% to 99.8%,” Dr. Woloshin said.

The benefit is arguably small, while the harms appear quite significant, Dr. Woloshin said. About 36% of women who begin screening at age 40 would have at least one false alarm over 10 years, and almost 7% would have a false alarm requiring a biopsy in that time frame.
 

Ease or exacerbate racial disparity?

Another argument that the USPSTF highlighted for lowering the screening age: Research indicates that Black women get breast cancer at younger ages and are more likely to die of the disease, compared with White women.

Dr. Woloshin and coauthors, however, also took issue with the view that lowering the screening age could reduce disparities between Black and White women.

“There’s no question that there are substantial differences between Black and White women in terms of breast cancer mortality, but there’s actually very little disparity in breast cancer screening – about 60% of Black and White women in their 40s are screened regularly in the United States,” Dr. Woloshin explained in the podcast.

Therefore, it’s “really hard to imagine” how recommending the same intervention to both groups could possibly reduce the disparity, he said.

“The disparity is not a reflection of screening. It reflects differences in cancer biology,” he added. “Black women are at higher risk for more aggressive, fast-growing cancers that are less likely to be caught by screening and unfortunately are less likely to benefit from treatment.”

Earlier screening would also not address the problems facing poor women, who tend to be disproportionately Black, such as lower quality of available medical services, follow-up delays after abnormal scans, treatment delays, and less use of adjuvant therapy, Dr. Woloshin cautioned.

In Dr. Woloshin’s view, lowering the screening age, which broadens the eligible population, may actually “exacerbate problems contributing to disparity by diverting resources toward expanded screening rather than doing what we know works by ensuring that high-quality treatments are more readily accessible to poor women with breast cancer.”
 

Reconsider the change?

Because task force recommendations are so influential, Dr. Woloshin and colleagues worry that mammography screening for women in their 40s will probably become a performance measure.

“Our concern is that, rather than fostering informed decisions, clinicians and practices are going to be judged and rewarded and punished based on compliance with this quality metric,” Dr. Woloshin said.

That’s a problem, he noted, “because women should be able to make the decision for themselves rather than having this be a public health imperative, which is imposed by physicians and practices who are incentivized to meet a quality metric.”

The hope, said Dr. Woloshin, is that this prospective piece will help influence the task force to “reconsider the recommendation, because we think that the bottom line is that their models are insufficient to support a new imperative. The benefits are really limited, and there are really common and important harms for healthy women.”

The comment period for the draft recommendation is now closed, and a final decision from the task force is forthcoming.

The research had no funding. Dr. Woloshin has no relevant disclosures.

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

CHICAGO – The US Department of Veterans Affairs (VA) top medical officer told the Association of VA Hematology/Oncology (AVAHO) oncology members that they are at the forefront of the agency’s push to expand care for veterans who may have been injured by exposure to hazardous materials on the job.

“All of you are playing a critical role in implementing the PACT Act, the signature legislative achievement of the Biden administration,” said Shereef Elnahal, MD, MBA, the VA Under Secretary for Health, in a keynote address at the 2023 annual meeting of AVAHO. “But more importantly, if we do our jobs right, it could be the largest expansion of veterans’ benefits in the history of this country. That requires us to have the capacity to deliver care to so many more individuals.”

The VA has provided more than 4.1 million free toxic exposure screenings to veterans since President Biden signed the PACT Act (The Sergeant First Class Heath Robinson Honoring our Promise to Address Comprehensive Toxics Act) in August 2022. The legislation prioritizes claims for cancer, terminal illnesses, and homelessness, and the White House says it has allowed the Veterans Health Administration and the Veterans Benefits Administration to grow at the fastest rates in 2 decades. 

“Almost every type of solid tumor is now considered a presumptive condition associated with burden of exposure to veterans deployed anywhere in Central Command, either in the Persian Gulf War or the post-9/11 conflicts,” said Under Secretary Elnahal, who was confirmed in his job by the Senate in July 2022. 

Implementing the PACT Act “requires all of us to make investments and further strengthen our system’s care for oncology,” he said. It is also crucial, to reduce “leakage into the community,” referring to veterans who leave the VA for private care. “I know for a fact that the care that veterans get when they have oncology services available in our direct-care system within VA is better. That's not a contention. That is proven by different peer-reviewed studies over the years. And I think that comparison is only intensifying when it comes to how much better evidence-based care our veterans receive at the hands of all of you across the country.”

Elnahal highlighted the development of a “2-way” cancer registry that will allow the National Institute and the VA to exchange cancer diagnosis and treatment data with state registries. “This will give the VA access to critical data in a complete way—to what veterans have experienced, especially veterans who are getting parts of their care in one place and parts of their care in a different place.”

On the data front, he also noted that “the PACT Act also requires us to research the future and determine the next set of presumptive conditions that are related to the hazards of serving our country. It requires that we have robust data sets to be able to gain those insights.”
More globally, Elnahal said the VA can play a crucial role in the Cancer Moonshot Program: “We can win the race, and VA can contribute asymmetrically to that race, to make cancer a chronic condition.”

He highlighted efforts within the VA to battle cancer such as programs to reduce disparities, boost cancer screening, treat rural veterans via a national teleoncology service, and implement the Close to Me program to bring infusion services to veterans in isolated regions.

But Elnahal’s presentation was not entirely rosy. He warned that 40% of veterans are being served outside the VA. “That's sort of a rule-of-thumb threshold when you start looking more like a payer than a provider.”

He also noted that while the VA hired 54,000 people in just the past year—6.2% growth—it takes a long time to bring workers on board. “That’s why I'm holding every single leader in our system accountable for reducing onboarding times by at least a month,” he said. The AVAHO audience enthusiastically applauded.

CHICAGO – The US Department of Veterans Affairs (VA) top medical officer told the Association of VA Hematology/Oncology (AVAHO) oncology members that they are at the forefront of the agency’s push to expand care for veterans who may have been injured by exposure to hazardous materials on the job.

“All of you are playing a critical role in implementing the PACT Act, the signature legislative achievement of the Biden administration,” said Shereef Elnahal, MD, MBA, the VA Under Secretary for Health, in a keynote address at the 2023 annual meeting of AVAHO. “But more importantly, if we do our jobs right, it could be the largest expansion of veterans’ benefits in the history of this country. That requires us to have the capacity to deliver care to so many more individuals.”

The VA has provided more than 4.1 million free toxic exposure screenings to veterans since President Biden signed the PACT Act (The Sergeant First Class Heath Robinson Honoring our Promise to Address Comprehensive Toxics Act) in August 2022. The legislation prioritizes claims for cancer, terminal illnesses, and homelessness, and the White House says it has allowed the Veterans Health Administration and the Veterans Benefits Administration to grow at the fastest rates in 2 decades. 

“Almost every type of solid tumor is now considered a presumptive condition associated with burden of exposure to veterans deployed anywhere in Central Command, either in the Persian Gulf War or the post-9/11 conflicts,” said Under Secretary Elnahal, who was confirmed in his job by the Senate in July 2022. 

Implementing the PACT Act “requires all of us to make investments and further strengthen our system’s care for oncology,” he said. It is also crucial, to reduce “leakage into the community,” referring to veterans who leave the VA for private care. “I know for a fact that the care that veterans get when they have oncology services available in our direct-care system within VA is better. That's not a contention. That is proven by different peer-reviewed studies over the years. And I think that comparison is only intensifying when it comes to how much better evidence-based care our veterans receive at the hands of all of you across the country.”

Elnahal highlighted the development of a “2-way” cancer registry that will allow the National Institute and the VA to exchange cancer diagnosis and treatment data with state registries. “This will give the VA access to critical data in a complete way—to what veterans have experienced, especially veterans who are getting parts of their care in one place and parts of their care in a different place.”

On the data front, he also noted that “the PACT Act also requires us to research the future and determine the next set of presumptive conditions that are related to the hazards of serving our country. It requires that we have robust data sets to be able to gain those insights.”
More globally, Elnahal said the VA can play a crucial role in the Cancer Moonshot Program: “We can win the race, and VA can contribute asymmetrically to that race, to make cancer a chronic condition.”

He highlighted efforts within the VA to battle cancer such as programs to reduce disparities, boost cancer screening, treat rural veterans via a national teleoncology service, and implement the Close to Me program to bring infusion services to veterans in isolated regions.

But Elnahal’s presentation was not entirely rosy. He warned that 40% of veterans are being served outside the VA. “That's sort of a rule-of-thumb threshold when you start looking more like a payer than a provider.”

He also noted that while the VA hired 54,000 people in just the past year—6.2% growth—it takes a long time to bring workers on board. “That’s why I'm holding every single leader in our system accountable for reducing onboarding times by at least a month,” he said. The AVAHO audience enthusiastically applauded.

CHICAGO – The US Department of Veterans Affairs (VA) top medical officer told the Association of VA Hematology/Oncology (AVAHO) oncology members that they are at the forefront of the agency’s push to expand care for veterans who may have been injured by exposure to hazardous materials on the job.

“All of you are playing a critical role in implementing the PACT Act, the signature legislative achievement of the Biden administration,” said Shereef Elnahal, MD, MBA, the VA Under Secretary for Health, in a keynote address at the 2023 annual meeting of AVAHO. “But more importantly, if we do our jobs right, it could be the largest expansion of veterans’ benefits in the history of this country. That requires us to have the capacity to deliver care to so many more individuals.”

The VA has provided more than 4.1 million free toxic exposure screenings to veterans since President Biden signed the PACT Act (The Sergeant First Class Heath Robinson Honoring our Promise to Address Comprehensive Toxics Act) in August 2022. The legislation prioritizes claims for cancer, terminal illnesses, and homelessness, and the White House says it has allowed the Veterans Health Administration and the Veterans Benefits Administration to grow at the fastest rates in 2 decades. 

“Almost every type of solid tumor is now considered a presumptive condition associated with burden of exposure to veterans deployed anywhere in Central Command, either in the Persian Gulf War or the post-9/11 conflicts,” said Under Secretary Elnahal, who was confirmed in his job by the Senate in July 2022. 

Implementing the PACT Act “requires all of us to make investments and further strengthen our system’s care for oncology,” he said. It is also crucial, to reduce “leakage into the community,” referring to veterans who leave the VA for private care. “I know for a fact that the care that veterans get when they have oncology services available in our direct-care system within VA is better. That's not a contention. That is proven by different peer-reviewed studies over the years. And I think that comparison is only intensifying when it comes to how much better evidence-based care our veterans receive at the hands of all of you across the country.”

Elnahal highlighted the development of a “2-way” cancer registry that will allow the National Institute and the VA to exchange cancer diagnosis and treatment data with state registries. “This will give the VA access to critical data in a complete way—to what veterans have experienced, especially veterans who are getting parts of their care in one place and parts of their care in a different place.”

On the data front, he also noted that “the PACT Act also requires us to research the future and determine the next set of presumptive conditions that are related to the hazards of serving our country. It requires that we have robust data sets to be able to gain those insights.”
More globally, Elnahal said the VA can play a crucial role in the Cancer Moonshot Program: “We can win the race, and VA can contribute asymmetrically to that race, to make cancer a chronic condition.”

He highlighted efforts within the VA to battle cancer such as programs to reduce disparities, boost cancer screening, treat rural veterans via a national teleoncology service, and implement the Close to Me program to bring infusion services to veterans in isolated regions.

But Elnahal’s presentation was not entirely rosy. He warned that 40% of veterans are being served outside the VA. “That's sort of a rule-of-thumb threshold when you start looking more like a payer than a provider.”

He also noted that while the VA hired 54,000 people in just the past year—6.2% growth—it takes a long time to bring workers on board. “That’s why I'm holding every single leader in our system accountable for reducing onboarding times by at least a month,” he said. The AVAHO audience enthusiastically applauded.

WASHINGTON – Adding the PD-1 inhibitor pembrolizumab to the established combination of dabrafenib and trametinib (DT) significantly improves survival outcomes in BRAF V600E-mutated anaplastic thyroid cancer - particularly when administered in a neoadjuvant fashion, prior to surgery. Overall survival rates in the study exceeded 5 years.

“The very long median overall survival in the study’s neoadjuvant group is quite remarkable for a group of patients who used to have a very poor prognosis,” senior author Maria E. Cabanillas, MD, associate professor in the department of endocrine neoplasia and hormonal disorders at the University of Texas MD Anderson Cancer Center in Houston, said in an interview.

“This median overall survival definitely exceeds any other treatments thus far in BRAF-mutated anaplastic thyroid cancer.”

The research was presented at the annual meeting of the American Thyroid Association.

Anaplastic thyroid cancer, though rare, is the most aggressive form of thyroid cancer. It accounts for just 1% of the cancers but causes about 50% of thyroid cancer mortality.

The historical median overall survival is 5-6 months.

With research in recent years showing that as many as 40% of anaplastic thyroid cancers harbor BRAF V600E mutations, the door has opened for potential benefits with the combination of the BRAF inhibitor dabrafenib with the MEK-inhibitor drug trametinib.

The treatment combination was shown in research that included the phase 2 ROAR trial to yield important responses. It was approved by the Food and Drug Administration in 2018 for locally advanced or metastatic BRAF V600E-mutant anaplastic thyroid cancer, as well as other cancers.

However, a key caveat of DT is that patients eventually develop resistance mutations, leading to disease progression.

To overcome the problem, Dr. Cabanillas and her team found two key strategies that show promise – the addition of immunotherapy, such as pembrolizumab to DT, and the use of a neoadjuvant approach, with surgery performed after an initial response to the triplet therapy.
 

Triple therapy showed highly favorable results

In a study presented at the 2022 ATA annual meeting, researchers reported on the triple therapy of BRAF/MEK inhibitors vemurafenib and cobimetinib plus immunotherapy with atezolizumab. Results were highly favorable, with an overall response rate of 72% and an impressive 2-year survival of 67%.

However, a major limitation was that the study lacked a control arm. In the current study, the addition of pembrolizumab to DT was compared with DT alone. The investigators also sought to determine the survival benefits of a neoadjuvant strategy.

For the study, first author Sarah Hamidi, MD, also of the MD Anderson Cancer Center, and her colleagues identified 94 patients with BRAF-mutated anaplastic thyroid cancer who were treated either with first‐line DT or DT plus pembrolizumab between 2014 and 2023, either outside of a trial or in a reported clinical trial.

The study compared three treatment regimens – DT alone (n = 23), DT with pembrolizumab added before or after disease progression (n = 48), and DT with neoadjuvant pembrolizumab added prior to or after surgery (n = 23).

There were no significant differences in baseline characteristics between the groups. Metastatic disease was present at the start of treatment among 87.0% of the DT group, 79.2% of the pembrolizumab group prior to or after disease progression, and 65.2% of the neoadjuvant pembrolizumab group.

The median follow-up of the three groups was 102 months, 28 months, and 42 months, respectively. The median overall survival was 9 months with DT alone, vs. 17 months with DT plus pembrolizumab before or after progression and 63 months with neoadjuvant pembrolizumab plus DT (P < .001).

The 12- and 24-month survival rates with DT alone were 33.7% and 28.9%, respectively; for DT plus pembrolizumab before or after progression, the rates were 60.2% and 36.5%; and for neoadjuvant pembrolizumab plus DT, the rates were 80.7% and 74.5%.

In an analysis that did not include the neoadjuvant group, median progression-free survival was significantly longer with DT plus pembrolizumab as an initial treatment (11.0 months) compared with DT alone (4.0 months; P  =  .049).

A subanalysis that evaluated the timing of the addition of pembrolizumab to DT before or after disease progression showed no significant differences between the two in median overall survival (17 months vs. 16 months; P = .554).

“This is valuable information, especially for centers where pembrolizumab cannot be easily obtained as a first-line therapy for anaplastic thyroid cancer,” Dr. Hamidi said in presenting the findings.

She noted, however, that the results should be interpreted with caution, given the small number of patients who received pembrolizumab before progression (n = 34) and especially after progression (n = 14).

In terms of safety, there were no grade 5 adverse events (AEs); 32.4% of patients experienced immune‐related AEs, most frequently, colitis and hepatitis.
 

Therapies “improve survival”

Overall, the results are important, Dr. Cabanillas said.

The results are “very exciting when you think about the fact that 10 years ago, patients with anaplastic thyroid cancer had a median overall survival measured in months, and now we see that those with a BRAF mutation have a real chance at survival when managed appropriately from the start,” she told this news organization.

She noted that a key caveat is the study’s retrospective nature. Other important considerations are that pembrolizumab adds toxicity as well as cost, and it is largely used off label in anaplastic thyroid cancer.

Nevertheless, “it does feel like there needs to be a call to action in the guidelines for this disease so that it includes neoadjuvant DT or DT plus pembrolizumab as the primary treatment of patients with BRAF-mutated anaplastic thyroid cancer because the initial treatment is critical here,” Dr. Cabanillas said.

She added that a phase 2 trial with neoadjuvant DT plus pembrolizumab is ongoing. Enrollment is expected to be completed soon.

Commenting on the findings, Sarimar Agosto Salgado, MD, of the department of head and neck – endocrine oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Fla., who was a comoderator of the session, said the results are encouraging.

“These findings are promising because they open the landscape of options of therapies that we can provide these patients,” she said in an interview.

“Anaplastic thyroid cancer has been a disease with a very short survival despite aggressive therapies, but we are seeing that not only have these therapies been able to improve survival but also patients’ quality of life.”

Particularly encouraging is how quickly the therapies can work, Dr. Salgado added.

“Many times when patients present to the clinic, the rapid response to these systemic therapies can even [allow them to avoid] having a tracheostomy, and we’re also seeing that some of these patients are able to go from unresectable disease to resectable disease, and then by having the main tumor out, their survival improves.

“So, this is definitely a big ray of hope for these patients.”

Dr. Cabanillas has received research funding from Merck. Dr. Hamidi has disclosed no relevant financial relationships. Dr. Salgado has relationships with Lilly and Exelixis.
 

A version of this article appeared on Medscape.com.

WASHINGTON – Adding the PD-1 inhibitor pembrolizumab to the established combination of dabrafenib and trametinib (DT) significantly improves survival outcomes in BRAF V600E-mutated anaplastic thyroid cancer - particularly when administered in a neoadjuvant fashion, prior to surgery. Overall survival rates in the study exceeded 5 years.

“The very long median overall survival in the study’s neoadjuvant group is quite remarkable for a group of patients who used to have a very poor prognosis,” senior author Maria E. Cabanillas, MD, associate professor in the department of endocrine neoplasia and hormonal disorders at the University of Texas MD Anderson Cancer Center in Houston, said in an interview.

“This median overall survival definitely exceeds any other treatments thus far in BRAF-mutated anaplastic thyroid cancer.”

The research was presented at the annual meeting of the American Thyroid Association.

Anaplastic thyroid cancer, though rare, is the most aggressive form of thyroid cancer. It accounts for just 1% of the cancers but causes about 50% of thyroid cancer mortality.

The historical median overall survival is 5-6 months.

With research in recent years showing that as many as 40% of anaplastic thyroid cancers harbor BRAF V600E mutations, the door has opened for potential benefits with the combination of the BRAF inhibitor dabrafenib with the MEK-inhibitor drug trametinib.

The treatment combination was shown in research that included the phase 2 ROAR trial to yield important responses. It was approved by the Food and Drug Administration in 2018 for locally advanced or metastatic BRAF V600E-mutant anaplastic thyroid cancer, as well as other cancers.

However, a key caveat of DT is that patients eventually develop resistance mutations, leading to disease progression.

To overcome the problem, Dr. Cabanillas and her team found two key strategies that show promise – the addition of immunotherapy, such as pembrolizumab to DT, and the use of a neoadjuvant approach, with surgery performed after an initial response to the triplet therapy.
 

Triple therapy showed highly favorable results

In a study presented at the 2022 ATA annual meeting, researchers reported on the triple therapy of BRAF/MEK inhibitors vemurafenib and cobimetinib plus immunotherapy with atezolizumab. Results were highly favorable, with an overall response rate of 72% and an impressive 2-year survival of 67%.

However, a major limitation was that the study lacked a control arm. In the current study, the addition of pembrolizumab to DT was compared with DT alone. The investigators also sought to determine the survival benefits of a neoadjuvant strategy.

For the study, first author Sarah Hamidi, MD, also of the MD Anderson Cancer Center, and her colleagues identified 94 patients with BRAF-mutated anaplastic thyroid cancer who were treated either with first‐line DT or DT plus pembrolizumab between 2014 and 2023, either outside of a trial or in a reported clinical trial.

The study compared three treatment regimens – DT alone (n = 23), DT with pembrolizumab added before or after disease progression (n = 48), and DT with neoadjuvant pembrolizumab added prior to or after surgery (n = 23).

There were no significant differences in baseline characteristics between the groups. Metastatic disease was present at the start of treatment among 87.0% of the DT group, 79.2% of the pembrolizumab group prior to or after disease progression, and 65.2% of the neoadjuvant pembrolizumab group.

The median follow-up of the three groups was 102 months, 28 months, and 42 months, respectively. The median overall survival was 9 months with DT alone, vs. 17 months with DT plus pembrolizumab before or after progression and 63 months with neoadjuvant pembrolizumab plus DT (P < .001).

The 12- and 24-month survival rates with DT alone were 33.7% and 28.9%, respectively; for DT plus pembrolizumab before or after progression, the rates were 60.2% and 36.5%; and for neoadjuvant pembrolizumab plus DT, the rates were 80.7% and 74.5%.

In an analysis that did not include the neoadjuvant group, median progression-free survival was significantly longer with DT plus pembrolizumab as an initial treatment (11.0 months) compared with DT alone (4.0 months; P  =  .049).

A subanalysis that evaluated the timing of the addition of pembrolizumab to DT before or after disease progression showed no significant differences between the two in median overall survival (17 months vs. 16 months; P = .554).

“This is valuable information, especially for centers where pembrolizumab cannot be easily obtained as a first-line therapy for anaplastic thyroid cancer,” Dr. Hamidi said in presenting the findings.

She noted, however, that the results should be interpreted with caution, given the small number of patients who received pembrolizumab before progression (n = 34) and especially after progression (n = 14).

In terms of safety, there were no grade 5 adverse events (AEs); 32.4% of patients experienced immune‐related AEs, most frequently, colitis and hepatitis.
 

Therapies “improve survival”

Overall, the results are important, Dr. Cabanillas said.

The results are “very exciting when you think about the fact that 10 years ago, patients with anaplastic thyroid cancer had a median overall survival measured in months, and now we see that those with a BRAF mutation have a real chance at survival when managed appropriately from the start,” she told this news organization.

She noted that a key caveat is the study’s retrospective nature. Other important considerations are that pembrolizumab adds toxicity as well as cost, and it is largely used off label in anaplastic thyroid cancer.

Nevertheless, “it does feel like there needs to be a call to action in the guidelines for this disease so that it includes neoadjuvant DT or DT plus pembrolizumab as the primary treatment of patients with BRAF-mutated anaplastic thyroid cancer because the initial treatment is critical here,” Dr. Cabanillas said.

She added that a phase 2 trial with neoadjuvant DT plus pembrolizumab is ongoing. Enrollment is expected to be completed soon.

Commenting on the findings, Sarimar Agosto Salgado, MD, of the department of head and neck – endocrine oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Fla., who was a comoderator of the session, said the results are encouraging.

“These findings are promising because they open the landscape of options of therapies that we can provide these patients,” she said in an interview.

“Anaplastic thyroid cancer has been a disease with a very short survival despite aggressive therapies, but we are seeing that not only have these therapies been able to improve survival but also patients’ quality of life.”

Particularly encouraging is how quickly the therapies can work, Dr. Salgado added.

“Many times when patients present to the clinic, the rapid response to these systemic therapies can even [allow them to avoid] having a tracheostomy, and we’re also seeing that some of these patients are able to go from unresectable disease to resectable disease, and then by having the main tumor out, their survival improves.

“So, this is definitely a big ray of hope for these patients.”

Dr. Cabanillas has received research funding from Merck. Dr. Hamidi has disclosed no relevant financial relationships. Dr. Salgado has relationships with Lilly and Exelixis.
 

A version of this article appeared on Medscape.com.

WASHINGTON – Adding the PD-1 inhibitor pembrolizumab to the established combination of dabrafenib and trametinib (DT) significantly improves survival outcomes in BRAF V600E-mutated anaplastic thyroid cancer - particularly when administered in a neoadjuvant fashion, prior to surgery. Overall survival rates in the study exceeded 5 years.

“The very long median overall survival in the study’s neoadjuvant group is quite remarkable for a group of patients who used to have a very poor prognosis,” senior author Maria E. Cabanillas, MD, associate professor in the department of endocrine neoplasia and hormonal disorders at the University of Texas MD Anderson Cancer Center in Houston, said in an interview.

“This median overall survival definitely exceeds any other treatments thus far in BRAF-mutated anaplastic thyroid cancer.”

The research was presented at the annual meeting of the American Thyroid Association.

Anaplastic thyroid cancer, though rare, is the most aggressive form of thyroid cancer. It accounts for just 1% of the cancers but causes about 50% of thyroid cancer mortality.

The historical median overall survival is 5-6 months.

With research in recent years showing that as many as 40% of anaplastic thyroid cancers harbor BRAF V600E mutations, the door has opened for potential benefits with the combination of the BRAF inhibitor dabrafenib with the MEK-inhibitor drug trametinib.

The treatment combination was shown in research that included the phase 2 ROAR trial to yield important responses. It was approved by the Food and Drug Administration in 2018 for locally advanced or metastatic BRAF V600E-mutant anaplastic thyroid cancer, as well as other cancers.

However, a key caveat of DT is that patients eventually develop resistance mutations, leading to disease progression.

To overcome the problem, Dr. Cabanillas and her team found two key strategies that show promise – the addition of immunotherapy, such as pembrolizumab to DT, and the use of a neoadjuvant approach, with surgery performed after an initial response to the triplet therapy.
 

Triple therapy showed highly favorable results

In a study presented at the 2022 ATA annual meeting, researchers reported on the triple therapy of BRAF/MEK inhibitors vemurafenib and cobimetinib plus immunotherapy with atezolizumab. Results were highly favorable, with an overall response rate of 72% and an impressive 2-year survival of 67%.

However, a major limitation was that the study lacked a control arm. In the current study, the addition of pembrolizumab to DT was compared with DT alone. The investigators also sought to determine the survival benefits of a neoadjuvant strategy.

For the study, first author Sarah Hamidi, MD, also of the MD Anderson Cancer Center, and her colleagues identified 94 patients with BRAF-mutated anaplastic thyroid cancer who were treated either with first‐line DT or DT plus pembrolizumab between 2014 and 2023, either outside of a trial or in a reported clinical trial.

The study compared three treatment regimens – DT alone (n = 23), DT with pembrolizumab added before or after disease progression (n = 48), and DT with neoadjuvant pembrolizumab added prior to or after surgery (n = 23).

There were no significant differences in baseline characteristics between the groups. Metastatic disease was present at the start of treatment among 87.0% of the DT group, 79.2% of the pembrolizumab group prior to or after disease progression, and 65.2% of the neoadjuvant pembrolizumab group.

The median follow-up of the three groups was 102 months, 28 months, and 42 months, respectively. The median overall survival was 9 months with DT alone, vs. 17 months with DT plus pembrolizumab before or after progression and 63 months with neoadjuvant pembrolizumab plus DT (P < .001).

The 12- and 24-month survival rates with DT alone were 33.7% and 28.9%, respectively; for DT plus pembrolizumab before or after progression, the rates were 60.2% and 36.5%; and for neoadjuvant pembrolizumab plus DT, the rates were 80.7% and 74.5%.

In an analysis that did not include the neoadjuvant group, median progression-free survival was significantly longer with DT plus pembrolizumab as an initial treatment (11.0 months) compared with DT alone (4.0 months; P  =  .049).

A subanalysis that evaluated the timing of the addition of pembrolizumab to DT before or after disease progression showed no significant differences between the two in median overall survival (17 months vs. 16 months; P = .554).

“This is valuable information, especially for centers where pembrolizumab cannot be easily obtained as a first-line therapy for anaplastic thyroid cancer,” Dr. Hamidi said in presenting the findings.

She noted, however, that the results should be interpreted with caution, given the small number of patients who received pembrolizumab before progression (n = 34) and especially after progression (n = 14).

In terms of safety, there were no grade 5 adverse events (AEs); 32.4% of patients experienced immune‐related AEs, most frequently, colitis and hepatitis.
 

Therapies “improve survival”

Overall, the results are important, Dr. Cabanillas said.

The results are “very exciting when you think about the fact that 10 years ago, patients with anaplastic thyroid cancer had a median overall survival measured in months, and now we see that those with a BRAF mutation have a real chance at survival when managed appropriately from the start,” she told this news organization.

She noted that a key caveat is the study’s retrospective nature. Other important considerations are that pembrolizumab adds toxicity as well as cost, and it is largely used off label in anaplastic thyroid cancer.

Nevertheless, “it does feel like there needs to be a call to action in the guidelines for this disease so that it includes neoadjuvant DT or DT plus pembrolizumab as the primary treatment of patients with BRAF-mutated anaplastic thyroid cancer because the initial treatment is critical here,” Dr. Cabanillas said.

She added that a phase 2 trial with neoadjuvant DT plus pembrolizumab is ongoing. Enrollment is expected to be completed soon.

Commenting on the findings, Sarimar Agosto Salgado, MD, of the department of head and neck – endocrine oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Fla., who was a comoderator of the session, said the results are encouraging.

“These findings are promising because they open the landscape of options of therapies that we can provide these patients,” she said in an interview.

“Anaplastic thyroid cancer has been a disease with a very short survival despite aggressive therapies, but we are seeing that not only have these therapies been able to improve survival but also patients’ quality of life.”

Particularly encouraging is how quickly the therapies can work, Dr. Salgado added.

“Many times when patients present to the clinic, the rapid response to these systemic therapies can even [allow them to avoid] having a tracheostomy, and we’re also seeing that some of these patients are able to go from unresectable disease to resectable disease, and then by having the main tumor out, their survival improves.

“So, this is definitely a big ray of hope for these patients.”

Dr. Cabanillas has received research funding from Merck. Dr. Hamidi has disclosed no relevant financial relationships. Dr. Salgado has relationships with Lilly and Exelixis.
 

A version of this article appeared on Medscape.com.