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Reports Find Room for Improvement in VA Suicide-Risk Screening
About 18 veterans die by suicide daily, and while many received health care services in the year prior to their death, half did not receive a mental health diagnosis.
To address this, the Veterans Health Administration (VHA) has updated or initiated programs and policies aimed at identifying at-risk veterans. Since May 2018, the VHA introduced the Suicide Risk Identification Strategy (Risk ID) program, which includes screening patients using the Columbia-Suicide Severity Rating Scale (C-SSRS). Positive screenings call for a licensed independent clinician to document a comprehensive suicide risk evaluation.
Despite these measures, challenges persist in implementation and effectiveness, outlined in reports issue by the VA Office of Inspector General (OIG) during the Biden Administration. Michael Missal, who had served as VA Inspector General since 2016 was recently dismissed by President Trump.
Risk ID
The OIG report surveyed 137 facilities regarding Risk ID processes, training, and monitoring. Findings from that review revealed gaps in training: suicide prevention training does not adequately address Risk ID requirements, leaving staff unprepared to conduct screenings and evaluations. Although the VHA has developed additional training related to Risk ID, the training is not required and the VHA does not monitor staff training completion.
The VHA requires annual screening for all patients and has established a screening clinical reminder in patients’ electronic health records. Despite this, the national screening metric remained below 60% in 2023. Conversely, same-day evaluations after positive screenings reached 82%, though this metric excludes patients who were not screened. In 2024, the VHA added Risk ID evaluation metrics to leadership performance plans, aiming to clarify standards and promote adherence.
Mental Health Treatment Coordinators
A second OIG investigation from December 2024 reviewed VHA requirements related to suicide risk identification processes and also evaluated national compliance with mental health treatment coordinator (MHTC) role requirements.
Suicide risks peaks after discharge from mental health units, with 40% of suicidal behaviors occurring within 90 days. The VHA requires suicide risk screening within 24 hours of discharge and safety plans for high-risk patients using the C-SSRS, but the OIG found adherence issues. In a review of 200 patients discharged between October 2019 and September 2020, staff failed to complete the required screening for 27% of patients and safety plans for 12% of patients.
The VHA also requires clinicians to develop a safety plan with patients who recently attempted suicide or expressed suicidal ideation, are at risk of suicide prior to mental health unit discharge, or are determined to be at “high or intermediate acute or chronic risk” of suicide. For those patients, staff must flag the electronic health record.
OIG also found that over half of surveyed patients with an assigned MHTC were not able to identify the MHTC or another VHA staff member to contact for help with care. One-third of assigned MHTCs did not participate in patients’ transitions from inpatient to outpatient care. Despite the VHA no longer requiring 7-day follow-up appointments as of 2023, the OIG emphasized the need for guidance on scheduling postdischarge mental health appointments to promote engagement.
Consistent with VHA’s discontinuation of a required 7-day follow-up appointment, the OIG recognizes that postdischarge follow-up appointments are most effectively scheduled in consideration of a patient’s treatment needs, preferences, and availability rather than an arbitrary timeliness expectation. Patients flagged as high-risk must attend 4 mental health visits within 30 days of discharge. However, the OIG found that only 48% met this requirement, while 34% attended 1 to 3 appointments, and 18% attended none. Among surveyed patients, self-motivation and encouragement from family or friends were key drivers of attendance.
The OIG concluded that failures in suicide risk identification and care coordination could lead to underestimated suicide risk, overestimated discharge readiness, and unmitigated risks. Inadequate safety planning may also leave patients ill-equipped to manage crises. While the VHA has updated guidelines for MHTC involvement, these measures have not significantly improved continuity of care.
About 18 veterans die by suicide daily, and while many received health care services in the year prior to their death, half did not receive a mental health diagnosis.
To address this, the Veterans Health Administration (VHA) has updated or initiated programs and policies aimed at identifying at-risk veterans. Since May 2018, the VHA introduced the Suicide Risk Identification Strategy (Risk ID) program, which includes screening patients using the Columbia-Suicide Severity Rating Scale (C-SSRS). Positive screenings call for a licensed independent clinician to document a comprehensive suicide risk evaluation.
Despite these measures, challenges persist in implementation and effectiveness, outlined in reports issue by the VA Office of Inspector General (OIG) during the Biden Administration. Michael Missal, who had served as VA Inspector General since 2016 was recently dismissed by President Trump.
Risk ID
The OIG report surveyed 137 facilities regarding Risk ID processes, training, and monitoring. Findings from that review revealed gaps in training: suicide prevention training does not adequately address Risk ID requirements, leaving staff unprepared to conduct screenings and evaluations. Although the VHA has developed additional training related to Risk ID, the training is not required and the VHA does not monitor staff training completion.
The VHA requires annual screening for all patients and has established a screening clinical reminder in patients’ electronic health records. Despite this, the national screening metric remained below 60% in 2023. Conversely, same-day evaluations after positive screenings reached 82%, though this metric excludes patients who were not screened. In 2024, the VHA added Risk ID evaluation metrics to leadership performance plans, aiming to clarify standards and promote adherence.
Mental Health Treatment Coordinators
A second OIG investigation from December 2024 reviewed VHA requirements related to suicide risk identification processes and also evaluated national compliance with mental health treatment coordinator (MHTC) role requirements.
Suicide risks peaks after discharge from mental health units, with 40% of suicidal behaviors occurring within 90 days. The VHA requires suicide risk screening within 24 hours of discharge and safety plans for high-risk patients using the C-SSRS, but the OIG found adherence issues. In a review of 200 patients discharged between October 2019 and September 2020, staff failed to complete the required screening for 27% of patients and safety plans for 12% of patients.
The VHA also requires clinicians to develop a safety plan with patients who recently attempted suicide or expressed suicidal ideation, are at risk of suicide prior to mental health unit discharge, or are determined to be at “high or intermediate acute or chronic risk” of suicide. For those patients, staff must flag the electronic health record.
OIG also found that over half of surveyed patients with an assigned MHTC were not able to identify the MHTC or another VHA staff member to contact for help with care. One-third of assigned MHTCs did not participate in patients’ transitions from inpatient to outpatient care. Despite the VHA no longer requiring 7-day follow-up appointments as of 2023, the OIG emphasized the need for guidance on scheduling postdischarge mental health appointments to promote engagement.
Consistent with VHA’s discontinuation of a required 7-day follow-up appointment, the OIG recognizes that postdischarge follow-up appointments are most effectively scheduled in consideration of a patient’s treatment needs, preferences, and availability rather than an arbitrary timeliness expectation. Patients flagged as high-risk must attend 4 mental health visits within 30 days of discharge. However, the OIG found that only 48% met this requirement, while 34% attended 1 to 3 appointments, and 18% attended none. Among surveyed patients, self-motivation and encouragement from family or friends were key drivers of attendance.
The OIG concluded that failures in suicide risk identification and care coordination could lead to underestimated suicide risk, overestimated discharge readiness, and unmitigated risks. Inadequate safety planning may also leave patients ill-equipped to manage crises. While the VHA has updated guidelines for MHTC involvement, these measures have not significantly improved continuity of care.
About 18 veterans die by suicide daily, and while many received health care services in the year prior to their death, half did not receive a mental health diagnosis.
To address this, the Veterans Health Administration (VHA) has updated or initiated programs and policies aimed at identifying at-risk veterans. Since May 2018, the VHA introduced the Suicide Risk Identification Strategy (Risk ID) program, which includes screening patients using the Columbia-Suicide Severity Rating Scale (C-SSRS). Positive screenings call for a licensed independent clinician to document a comprehensive suicide risk evaluation.
Despite these measures, challenges persist in implementation and effectiveness, outlined in reports issue by the VA Office of Inspector General (OIG) during the Biden Administration. Michael Missal, who had served as VA Inspector General since 2016 was recently dismissed by President Trump.
Risk ID
The OIG report surveyed 137 facilities regarding Risk ID processes, training, and monitoring. Findings from that review revealed gaps in training: suicide prevention training does not adequately address Risk ID requirements, leaving staff unprepared to conduct screenings and evaluations. Although the VHA has developed additional training related to Risk ID, the training is not required and the VHA does not monitor staff training completion.
The VHA requires annual screening for all patients and has established a screening clinical reminder in patients’ electronic health records. Despite this, the national screening metric remained below 60% in 2023. Conversely, same-day evaluations after positive screenings reached 82%, though this metric excludes patients who were not screened. In 2024, the VHA added Risk ID evaluation metrics to leadership performance plans, aiming to clarify standards and promote adherence.
Mental Health Treatment Coordinators
A second OIG investigation from December 2024 reviewed VHA requirements related to suicide risk identification processes and also evaluated national compliance with mental health treatment coordinator (MHTC) role requirements.
Suicide risks peaks after discharge from mental health units, with 40% of suicidal behaviors occurring within 90 days. The VHA requires suicide risk screening within 24 hours of discharge and safety plans for high-risk patients using the C-SSRS, but the OIG found adherence issues. In a review of 200 patients discharged between October 2019 and September 2020, staff failed to complete the required screening for 27% of patients and safety plans for 12% of patients.
The VHA also requires clinicians to develop a safety plan with patients who recently attempted suicide or expressed suicidal ideation, are at risk of suicide prior to mental health unit discharge, or are determined to be at “high or intermediate acute or chronic risk” of suicide. For those patients, staff must flag the electronic health record.
OIG also found that over half of surveyed patients with an assigned MHTC were not able to identify the MHTC or another VHA staff member to contact for help with care. One-third of assigned MHTCs did not participate in patients’ transitions from inpatient to outpatient care. Despite the VHA no longer requiring 7-day follow-up appointments as of 2023, the OIG emphasized the need for guidance on scheduling postdischarge mental health appointments to promote engagement.
Consistent with VHA’s discontinuation of a required 7-day follow-up appointment, the OIG recognizes that postdischarge follow-up appointments are most effectively scheduled in consideration of a patient’s treatment needs, preferences, and availability rather than an arbitrary timeliness expectation. Patients flagged as high-risk must attend 4 mental health visits within 30 days of discharge. However, the OIG found that only 48% met this requirement, while 34% attended 1 to 3 appointments, and 18% attended none. Among surveyed patients, self-motivation and encouragement from family or friends were key drivers of attendance.
The OIG concluded that failures in suicide risk identification and care coordination could lead to underestimated suicide risk, overestimated discharge readiness, and unmitigated risks. Inadequate safety planning may also leave patients ill-equipped to manage crises. While the VHA has updated guidelines for MHTC involvement, these measures have not significantly improved continuity of care.
Promising New Blood Test for Colorectal Cancer Screening
, the largest study of any blood-based CRC screening test.
With continued optimization, this blood test “may provide a convenient, effective option for colorectal cancer screening in the intended use population,” said Aasma Shaukat, MD, MPH, AGAF, with New York University Grossman School of Medicine in New York City.
CRC screening rates remain suboptimal, with nearly 40% of eligible adults in the United States not up to date with screening, noted Shaukat, who presented the study results at the American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium 2025 in San Francisco.
Blood-based testing offers a promising complementary approach that may boost patient adherence among unscreened individuals, she added.
The study evaluated the clinical performance of the investigational blood-based screening test in 27,010 adults aged ≥ 45 years at average-risk for CRC. Patients with no personal history of cancer, colorectal adenoma, or inflammatory bowel disease, as well as no family history of CRC or hereditary gastrointestinal cancer syndromes were eligible for the study.
Participants had blood drawn before bowel preparation for colonoscopy, and the blood test results were measured against colonoscopy findings.
The primary endpoints included sensitivity for CRC, specificity for advanced colorectal neoplasia, and negative and positive predictive value for advanced colorectal neoplasia. A secondary endpoint was sensitivity for advanced precancerous lesions.
The blood-based screening test met all primary endpoints, with a sensitivity for CRC of 79.2% and a specificity for advanced colorectal neoplasia of 91.5%, Shaukat reported at a conference briefing. Negative predictive value for advanced colorectal neoplasia was 90.8%, though the positive predictive value was only 15.5% and sensitivity for advanced precancerous lesions, a secondary endpoint, was 12.5%.
Similar results were achieved in a prespecified analysis in which performance of the blood test was weighted to match US census data for sex and age distributions. Sensitivity for CRC was 81.1%, specificity was 90.4%, and negative predictive value for advanced colorectal neoplasia was 90.5%; but the positive predictive value was 15.5%, and the sensitivity for advanced precancerous lesions was 13.7%.
This type of analysis provides “a snapshot of how [the test] would perform in the US population,” Shaukat explained, adding that the sensitivity for CRC and advanced precursor lesions was “lower than expected and will continue to be optimized in future research and development.”
It will also be important to determine when the test should be repeated and how often and to look at the determinants around cost and comparative effectiveness, she said. Modeling and other outcome studies — which will be forthcoming in the future years — could help shed some light on these questions.
Briefing moderator Julie Gralow, MD, ASCO chief medical officer, said it will be important to compare how this new blood test compares with Guardant Health’s Shield CRC blood test that was approved in 2024. Although there’s no study directly comparing the new blood test to Shield, data from the ECLIPSE study reported that Shield had 83% sensitivity for CRC and 90% specificity for advanced neoplasia, but only 13% sensitivity for advanced precancerous lesions — which appears similar, so far, to findings reported for the new blood test.
But any screening is better than no screening, and with further study, this blood test may “add another tool to our toolkit,” said Pamela Kunz, MD, director of the Center for Gastrointestinal Cancers at Smilow Cancer Hospital and Yale Cancer Center, New Haven, Connecticut, who spoke at the briefing. Kunz said she is eager to see some of the future work optimizing the sensitivity and subsequent analyses that look at differences by race and ethnicity.
The study had no specific funding. Shaukat consults for Freenome Holdings and Iterative Health. Kunz declared ties with Ipsen, Novartis, Genentech/Roche, Amgen, Crinetics Pharmaceuticals, Natera, HUTCHMED, and ITM Isotope Technologies Munich. Gralow declared consulting or advisory roles with Genentech/Roche.
A version of this article appeared on Medscape.com .
, the largest study of any blood-based CRC screening test.
With continued optimization, this blood test “may provide a convenient, effective option for colorectal cancer screening in the intended use population,” said Aasma Shaukat, MD, MPH, AGAF, with New York University Grossman School of Medicine in New York City.
CRC screening rates remain suboptimal, with nearly 40% of eligible adults in the United States not up to date with screening, noted Shaukat, who presented the study results at the American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium 2025 in San Francisco.
Blood-based testing offers a promising complementary approach that may boost patient adherence among unscreened individuals, she added.
The study evaluated the clinical performance of the investigational blood-based screening test in 27,010 adults aged ≥ 45 years at average-risk for CRC. Patients with no personal history of cancer, colorectal adenoma, or inflammatory bowel disease, as well as no family history of CRC or hereditary gastrointestinal cancer syndromes were eligible for the study.
Participants had blood drawn before bowel preparation for colonoscopy, and the blood test results were measured against colonoscopy findings.
The primary endpoints included sensitivity for CRC, specificity for advanced colorectal neoplasia, and negative and positive predictive value for advanced colorectal neoplasia. A secondary endpoint was sensitivity for advanced precancerous lesions.
The blood-based screening test met all primary endpoints, with a sensitivity for CRC of 79.2% and a specificity for advanced colorectal neoplasia of 91.5%, Shaukat reported at a conference briefing. Negative predictive value for advanced colorectal neoplasia was 90.8%, though the positive predictive value was only 15.5% and sensitivity for advanced precancerous lesions, a secondary endpoint, was 12.5%.
Similar results were achieved in a prespecified analysis in which performance of the blood test was weighted to match US census data for sex and age distributions. Sensitivity for CRC was 81.1%, specificity was 90.4%, and negative predictive value for advanced colorectal neoplasia was 90.5%; but the positive predictive value was 15.5%, and the sensitivity for advanced precancerous lesions was 13.7%.
This type of analysis provides “a snapshot of how [the test] would perform in the US population,” Shaukat explained, adding that the sensitivity for CRC and advanced precursor lesions was “lower than expected and will continue to be optimized in future research and development.”
It will also be important to determine when the test should be repeated and how often and to look at the determinants around cost and comparative effectiveness, she said. Modeling and other outcome studies — which will be forthcoming in the future years — could help shed some light on these questions.
Briefing moderator Julie Gralow, MD, ASCO chief medical officer, said it will be important to compare how this new blood test compares with Guardant Health’s Shield CRC blood test that was approved in 2024. Although there’s no study directly comparing the new blood test to Shield, data from the ECLIPSE study reported that Shield had 83% sensitivity for CRC and 90% specificity for advanced neoplasia, but only 13% sensitivity for advanced precancerous lesions — which appears similar, so far, to findings reported for the new blood test.
But any screening is better than no screening, and with further study, this blood test may “add another tool to our toolkit,” said Pamela Kunz, MD, director of the Center for Gastrointestinal Cancers at Smilow Cancer Hospital and Yale Cancer Center, New Haven, Connecticut, who spoke at the briefing. Kunz said she is eager to see some of the future work optimizing the sensitivity and subsequent analyses that look at differences by race and ethnicity.
The study had no specific funding. Shaukat consults for Freenome Holdings and Iterative Health. Kunz declared ties with Ipsen, Novartis, Genentech/Roche, Amgen, Crinetics Pharmaceuticals, Natera, HUTCHMED, and ITM Isotope Technologies Munich. Gralow declared consulting or advisory roles with Genentech/Roche.
A version of this article appeared on Medscape.com .
, the largest study of any blood-based CRC screening test.
With continued optimization, this blood test “may provide a convenient, effective option for colorectal cancer screening in the intended use population,” said Aasma Shaukat, MD, MPH, AGAF, with New York University Grossman School of Medicine in New York City.
CRC screening rates remain suboptimal, with nearly 40% of eligible adults in the United States not up to date with screening, noted Shaukat, who presented the study results at the American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium 2025 in San Francisco.
Blood-based testing offers a promising complementary approach that may boost patient adherence among unscreened individuals, she added.
The study evaluated the clinical performance of the investigational blood-based screening test in 27,010 adults aged ≥ 45 years at average-risk for CRC. Patients with no personal history of cancer, colorectal adenoma, or inflammatory bowel disease, as well as no family history of CRC or hereditary gastrointestinal cancer syndromes were eligible for the study.
Participants had blood drawn before bowel preparation for colonoscopy, and the blood test results were measured against colonoscopy findings.
The primary endpoints included sensitivity for CRC, specificity for advanced colorectal neoplasia, and negative and positive predictive value for advanced colorectal neoplasia. A secondary endpoint was sensitivity for advanced precancerous lesions.
The blood-based screening test met all primary endpoints, with a sensitivity for CRC of 79.2% and a specificity for advanced colorectal neoplasia of 91.5%, Shaukat reported at a conference briefing. Negative predictive value for advanced colorectal neoplasia was 90.8%, though the positive predictive value was only 15.5% and sensitivity for advanced precancerous lesions, a secondary endpoint, was 12.5%.
Similar results were achieved in a prespecified analysis in which performance of the blood test was weighted to match US census data for sex and age distributions. Sensitivity for CRC was 81.1%, specificity was 90.4%, and negative predictive value for advanced colorectal neoplasia was 90.5%; but the positive predictive value was 15.5%, and the sensitivity for advanced precancerous lesions was 13.7%.
This type of analysis provides “a snapshot of how [the test] would perform in the US population,” Shaukat explained, adding that the sensitivity for CRC and advanced precursor lesions was “lower than expected and will continue to be optimized in future research and development.”
It will also be important to determine when the test should be repeated and how often and to look at the determinants around cost and comparative effectiveness, she said. Modeling and other outcome studies — which will be forthcoming in the future years — could help shed some light on these questions.
Briefing moderator Julie Gralow, MD, ASCO chief medical officer, said it will be important to compare how this new blood test compares with Guardant Health’s Shield CRC blood test that was approved in 2024. Although there’s no study directly comparing the new blood test to Shield, data from the ECLIPSE study reported that Shield had 83% sensitivity for CRC and 90% specificity for advanced neoplasia, but only 13% sensitivity for advanced precancerous lesions — which appears similar, so far, to findings reported for the new blood test.
But any screening is better than no screening, and with further study, this blood test may “add another tool to our toolkit,” said Pamela Kunz, MD, director of the Center for Gastrointestinal Cancers at Smilow Cancer Hospital and Yale Cancer Center, New Haven, Connecticut, who spoke at the briefing. Kunz said she is eager to see some of the future work optimizing the sensitivity and subsequent analyses that look at differences by race and ethnicity.
The study had no specific funding. Shaukat consults for Freenome Holdings and Iterative Health. Kunz declared ties with Ipsen, Novartis, Genentech/Roche, Amgen, Crinetics Pharmaceuticals, Natera, HUTCHMED, and ITM Isotope Technologies Munich. Gralow declared consulting or advisory roles with Genentech/Roche.
A version of this article appeared on Medscape.com .
FROM ASCO GI 2025
Low-Dose Aspirin Cuts CRC Recurrence
according to findings from the phase 3 ALASCCA trial.
These results stress “the importance of upfront genomic testing” in patients with CRC, said Anna Martling, MD, PhD, from Karolinska Institutet, Stockholm, Sweden, who reported the findings at the American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium 2025 in San Francisco.
This is the first trial to show that mutations in the PI3K signaling pathway, beyond PIK3CA alterations, predict aspirin response, “expanding the targetable patient population substantially,” Martling added. Genetic mutations along the PI3K signaling pathway are found in about 30% of CRCs.
While aspirin as chemoprevention in CRC has been studied, data confirming its effectiveness as well as uptake of this approach in practice have been lacking, explained ASCO expert commenter Pamela Kunz, MD, with Smilow Cancer Hospital and Yale Cancer Center, New Haven, Connecticut.
“It’s really clear that this is a practice-changing study,” said Kunz. The findings indicate that this approach “checks all of the boxes: It’s effective, it’s low risk, it’s inexpensive, and it’s easy to administer.”
The trial included 626 patients (median age, 66 years; 52% women) with stages II-III colon cancer (67%) or stages I-III rectal cancer (33%) across 33 hospitals in Sweden, Denmark, Finland, and Norway.
Patients were stratified into two groups based on specific PI3K pathway alterations Group A (n = 314) included patients with PIK3CA mutations in exon 9 and/or 20, and group B (n = 312) included those with other PI3K pathway mutations, including PIK3CA mutations outside exon 9/20, or mutations in PIK3R1 or PTEN genes.
Participants in both groups were randomly allocated 1:1 to 160 mg/d of aspirin or placebo for 3 years. The primary outcome was CRC recurrence; disease-free survival was a secondary outcome.
Compared with placebo, aspirin reduced the risk for recurrence by 51% (hazard ratio [HR], 0.49) in patients with PIK3CA mutations, with a 3-year recurrence rate of 7.7% in those taking aspirin vs 14.1% in the placebo group.
“Interestingly,” Martling noted, in the exploratory arm that included other mutations along the PIK3 pathway beyond PIK3CA (Group B), the effect was even stronger. Patients in this group had a 58% (HR, 0.42) lower risk for recurrence than those in the placebo group, with a 3-year recurrence rate of 7.7% in the aspirin group vs 16.8% recurrence rate in the placebo group.
Aspirin also had a disease-free survival benefit in both groups, but it was significant only in group B.
While the study was not specifically designed for subgroup analysis, the benefit of aspirin was observed in all subgroups examined, including men and women with colon or rectal cancer, those who did and did not receive neoadjuvant or adjuvant treatment, and those with stages I-III disease.
The incidence of adverse events was as expected and severe side effects associated with 160 mg/d aspirin were rare, Martling said.
Both Martling and Kunz predicted that these findings will change clinical practice. “I anticipate that we’ll be seeing adoption of this [strategy],” Kunz said.
This study received funding from the Swedish Research Council, Swedish Cancer Society, ALF (a regional agreement on medical training and clinical research between the Stockholm County Council and Karolinska Institutet), and the Stockholm Cancer Society. Martling disclosed various relationships with Bactiguard, Smartcella, CarpoNovum and Pfizer. Kunz disclosed relationships with Bristol-Myers Squibb, Novartis and TayzeBio.
A version of this article appeared on Medscape.com .
according to findings from the phase 3 ALASCCA trial.
These results stress “the importance of upfront genomic testing” in patients with CRC, said Anna Martling, MD, PhD, from Karolinska Institutet, Stockholm, Sweden, who reported the findings at the American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium 2025 in San Francisco.
This is the first trial to show that mutations in the PI3K signaling pathway, beyond PIK3CA alterations, predict aspirin response, “expanding the targetable patient population substantially,” Martling added. Genetic mutations along the PI3K signaling pathway are found in about 30% of CRCs.
While aspirin as chemoprevention in CRC has been studied, data confirming its effectiveness as well as uptake of this approach in practice have been lacking, explained ASCO expert commenter Pamela Kunz, MD, with Smilow Cancer Hospital and Yale Cancer Center, New Haven, Connecticut.
“It’s really clear that this is a practice-changing study,” said Kunz. The findings indicate that this approach “checks all of the boxes: It’s effective, it’s low risk, it’s inexpensive, and it’s easy to administer.”
The trial included 626 patients (median age, 66 years; 52% women) with stages II-III colon cancer (67%) or stages I-III rectal cancer (33%) across 33 hospitals in Sweden, Denmark, Finland, and Norway.
Patients were stratified into two groups based on specific PI3K pathway alterations Group A (n = 314) included patients with PIK3CA mutations in exon 9 and/or 20, and group B (n = 312) included those with other PI3K pathway mutations, including PIK3CA mutations outside exon 9/20, or mutations in PIK3R1 or PTEN genes.
Participants in both groups were randomly allocated 1:1 to 160 mg/d of aspirin or placebo for 3 years. The primary outcome was CRC recurrence; disease-free survival was a secondary outcome.
Compared with placebo, aspirin reduced the risk for recurrence by 51% (hazard ratio [HR], 0.49) in patients with PIK3CA mutations, with a 3-year recurrence rate of 7.7% in those taking aspirin vs 14.1% in the placebo group.
“Interestingly,” Martling noted, in the exploratory arm that included other mutations along the PIK3 pathway beyond PIK3CA (Group B), the effect was even stronger. Patients in this group had a 58% (HR, 0.42) lower risk for recurrence than those in the placebo group, with a 3-year recurrence rate of 7.7% in the aspirin group vs 16.8% recurrence rate in the placebo group.
Aspirin also had a disease-free survival benefit in both groups, but it was significant only in group B.
While the study was not specifically designed for subgroup analysis, the benefit of aspirin was observed in all subgroups examined, including men and women with colon or rectal cancer, those who did and did not receive neoadjuvant or adjuvant treatment, and those with stages I-III disease.
The incidence of adverse events was as expected and severe side effects associated with 160 mg/d aspirin were rare, Martling said.
Both Martling and Kunz predicted that these findings will change clinical practice. “I anticipate that we’ll be seeing adoption of this [strategy],” Kunz said.
This study received funding from the Swedish Research Council, Swedish Cancer Society, ALF (a regional agreement on medical training and clinical research between the Stockholm County Council and Karolinska Institutet), and the Stockholm Cancer Society. Martling disclosed various relationships with Bactiguard, Smartcella, CarpoNovum and Pfizer. Kunz disclosed relationships with Bristol-Myers Squibb, Novartis and TayzeBio.
A version of this article appeared on Medscape.com .
according to findings from the phase 3 ALASCCA trial.
These results stress “the importance of upfront genomic testing” in patients with CRC, said Anna Martling, MD, PhD, from Karolinska Institutet, Stockholm, Sweden, who reported the findings at the American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium 2025 in San Francisco.
This is the first trial to show that mutations in the PI3K signaling pathway, beyond PIK3CA alterations, predict aspirin response, “expanding the targetable patient population substantially,” Martling added. Genetic mutations along the PI3K signaling pathway are found in about 30% of CRCs.
While aspirin as chemoprevention in CRC has been studied, data confirming its effectiveness as well as uptake of this approach in practice have been lacking, explained ASCO expert commenter Pamela Kunz, MD, with Smilow Cancer Hospital and Yale Cancer Center, New Haven, Connecticut.
“It’s really clear that this is a practice-changing study,” said Kunz. The findings indicate that this approach “checks all of the boxes: It’s effective, it’s low risk, it’s inexpensive, and it’s easy to administer.”
The trial included 626 patients (median age, 66 years; 52% women) with stages II-III colon cancer (67%) or stages I-III rectal cancer (33%) across 33 hospitals in Sweden, Denmark, Finland, and Norway.
Patients were stratified into two groups based on specific PI3K pathway alterations Group A (n = 314) included patients with PIK3CA mutations in exon 9 and/or 20, and group B (n = 312) included those with other PI3K pathway mutations, including PIK3CA mutations outside exon 9/20, or mutations in PIK3R1 or PTEN genes.
Participants in both groups were randomly allocated 1:1 to 160 mg/d of aspirin or placebo for 3 years. The primary outcome was CRC recurrence; disease-free survival was a secondary outcome.
Compared with placebo, aspirin reduced the risk for recurrence by 51% (hazard ratio [HR], 0.49) in patients with PIK3CA mutations, with a 3-year recurrence rate of 7.7% in those taking aspirin vs 14.1% in the placebo group.
“Interestingly,” Martling noted, in the exploratory arm that included other mutations along the PIK3 pathway beyond PIK3CA (Group B), the effect was even stronger. Patients in this group had a 58% (HR, 0.42) lower risk for recurrence than those in the placebo group, with a 3-year recurrence rate of 7.7% in the aspirin group vs 16.8% recurrence rate in the placebo group.
Aspirin also had a disease-free survival benefit in both groups, but it was significant only in group B.
While the study was not specifically designed for subgroup analysis, the benefit of aspirin was observed in all subgroups examined, including men and women with colon or rectal cancer, those who did and did not receive neoadjuvant or adjuvant treatment, and those with stages I-III disease.
The incidence of adverse events was as expected and severe side effects associated with 160 mg/d aspirin were rare, Martling said.
Both Martling and Kunz predicted that these findings will change clinical practice. “I anticipate that we’ll be seeing adoption of this [strategy],” Kunz said.
This study received funding from the Swedish Research Council, Swedish Cancer Society, ALF (a regional agreement on medical training and clinical research between the Stockholm County Council and Karolinska Institutet), and the Stockholm Cancer Society. Martling disclosed various relationships with Bactiguard, Smartcella, CarpoNovum and Pfizer. Kunz disclosed relationships with Bristol-Myers Squibb, Novartis and TayzeBio.
A version of this article appeared on Medscape.com .
FROM ASCO GI 2025
Women Researchers Remain Underrepresented in Pharma-Sponsored IBD Presentations
A recent study found that The study was published in Gastroenterology and also appeared concurrently in Clinical Gastroenterology and Hepatology .
Indeed, among gastrointestinal (GI) subspecialties, IBD was selected by 26.5% of all women GI physicians, compared with 18.9% of all their male counterparts, according to a 2021 study.
Thus, conference organizers and pharmaceutical companies should promote speaker diversity by seeking out women presenters, according to a group led by Maria A. Quintero, MD, of the Division of Gastroenterology at the Leonard Miller School of Medicine at the University of Miami, Florida.
“Seeing more women IBD leaders at the podium will inspire other women to engage in IBD clinical research,” Quintero and associates wrote.
In addition, women investigators should be included at every stage of the study process in industry-sponsored research, both as principal investigators and members of steering committees involved in study design, the authors said. Training more women clinical trial investigators in the IBD setting is another way forward.
In another recommendation, pharmaceutical companies need to be more transparent about the way first and senior authors on IBD studies are chosen because in the past the principal investigator who enrolled the most patients became the first author of the study. “That is no longer the case. However, it remains unclear whether all investigators have an equal opportunity to be the first or senior author,” Quintero and associates wrote.
The Study
The investigators analyzed IBD abstracts of presentations at five conferences for two large GI meetings, Digestive Disease Week (DDW) and United European Gastroenterology (UEG) in the period 2021-2023.
They asked whether women investigators were as likely as their male counterparts to present abstracts based on results from industry-supported clinical trials. As a point of comparison, they also looked for possible gender differences in invited-speaker vs investigator-initiated IBD sessions. To do this, they examined all IBD-related abstracts from the two meetings, identified the lead author of each oral presentation, and divided them into women or men. They also assessed whether the presentation was pharma-sponsored, investigator-initiated, or presented by an invited speaker.
Among the study findings:
- Across categories there were 178 invited lectures, 336 investigator-submitted presentations, and 150 industry-supported presentations for UEG (2021, 2022, and 2023) and DDW (2022 and 2023).
- The gender gap for men vs women was significant for industry-supported oral presentations (78.7% vs 21.3%; P < .0001) and for invited lectures (67.4% vs 32.6%; P < .0001) — but not for investigator-submitted abstracts (49.7% vs 50.3%; P = .91).
- The gender gap for industry-supported abstracts, however, was significantly larger than for investigator-submitted abstracts (57.3% vs 0.6%; P < .0001) and larger than for invited lectures (57.3% vs 34.9%; P = .09).
- The gender gap for invited lectures was significantly larger than for investigator-submitted oral presentations (34.9% vs 0.6%; P = .0009).
Why the Discordance?
This disparity may be due to the paucity of women investigators on steering committees for clinical trials. “Although the number of women doing IBD research continues to increase, then number of women senior investigators is still smaller than the number of men senior investigators,” the researchers wrote. “Ideally, there would be transparency in terms of the metrics used by pharma to choose who will be a presenting author and more intentional recruitment of women investigators to steering committees.”
Commenting on the study but not involved in it, internist Shannon M. Ruzycki, MD, MPH, an assistant professor in the Cumming School of Medicine at the University of Calgary Medical Centre in Alberta, Canada, said the findings are not surprising. “In nearly every setting where gender differences are studied in academic medicine, women are found to be disadvantaged compared to men. These differences are not attributable to skill, merit, or career attainment, but rather appear to be arbitrary and due to biases. They add up across time and likely contribute to the larger differences we see between men and women in promotion, compensation, and awards.”
Ruzycki, lead author of a study of women presenters at medical conferences, noted that differences in gender representation in academia, academic medicine, and clinical trials are similar “because the underlying causes are similar.” On the positive side, she added, conference planning committees are using strategies to reduce bias in how presenters are selected by masking the names and/or institutions of those are submitting abstracts and are being more intentional in inviting a diverse panel of qualified speakers.
“However, one strategy alone is unlikely to address such an insidious problem that affects all parts of selection,” she said. “For example, if pharmaceutical companies believe that men presenters are seen as more authoritative or knowledgeable than women presenters, they will select men to be the first author on submitted abstracts which could deprive these opportunities for deserving women candidates.”
Ruzycki attributed the imbalance to systems (academia, medicine, science) designed by men who lack empathy for the experiences of women. “In the same way you can never really understand how exhausting it is to be a parent until you become a parent or how challenging it can be to have a physical disability until you break a leg and have to navigate the world on crutches, it is really challenging for men to understand how cold and hostile these settings can be for women.”
Many of the things that make conferences, academia, and medicine so challenging for women have straightforward solutions, however, Ruzycki added. Onsite childcare, scrubs that fit women, operating room equipment that is ergonomic for women surgeons — even more washroom stalls would help. “If only we listened and cared about things that didn’t directly impact us.”
This study was supported by the 2023 Travel Grant from the International Organization for the Study of Inflammatory Bowel Diseases. One coauthor serves as a consultant or on advisory boards for AbbVie, Amgen, Bristol Myers Squibb, Celsius Therapeutics, Eli Lilly, Gilead Sciences, Janssen Pharmaceuticals, and Pfizer Pharmaceutical. She is a teacher, lecturer, and speaker for Janssen and Takeda Pharmaceuticals. The remaining authors disclosed no conflicts. Ruzycki had no relevant conflicts of interest to declare.
A version of this article appeared on Medscape.com.
A recent study found that The study was published in Gastroenterology and also appeared concurrently in Clinical Gastroenterology and Hepatology .
Indeed, among gastrointestinal (GI) subspecialties, IBD was selected by 26.5% of all women GI physicians, compared with 18.9% of all their male counterparts, according to a 2021 study.
Thus, conference organizers and pharmaceutical companies should promote speaker diversity by seeking out women presenters, according to a group led by Maria A. Quintero, MD, of the Division of Gastroenterology at the Leonard Miller School of Medicine at the University of Miami, Florida.
“Seeing more women IBD leaders at the podium will inspire other women to engage in IBD clinical research,” Quintero and associates wrote.
In addition, women investigators should be included at every stage of the study process in industry-sponsored research, both as principal investigators and members of steering committees involved in study design, the authors said. Training more women clinical trial investigators in the IBD setting is another way forward.
In another recommendation, pharmaceutical companies need to be more transparent about the way first and senior authors on IBD studies are chosen because in the past the principal investigator who enrolled the most patients became the first author of the study. “That is no longer the case. However, it remains unclear whether all investigators have an equal opportunity to be the first or senior author,” Quintero and associates wrote.
The Study
The investigators analyzed IBD abstracts of presentations at five conferences for two large GI meetings, Digestive Disease Week (DDW) and United European Gastroenterology (UEG) in the period 2021-2023.
They asked whether women investigators were as likely as their male counterparts to present abstracts based on results from industry-supported clinical trials. As a point of comparison, they also looked for possible gender differences in invited-speaker vs investigator-initiated IBD sessions. To do this, they examined all IBD-related abstracts from the two meetings, identified the lead author of each oral presentation, and divided them into women or men. They also assessed whether the presentation was pharma-sponsored, investigator-initiated, or presented by an invited speaker.
Among the study findings:
- Across categories there were 178 invited lectures, 336 investigator-submitted presentations, and 150 industry-supported presentations for UEG (2021, 2022, and 2023) and DDW (2022 and 2023).
- The gender gap for men vs women was significant for industry-supported oral presentations (78.7% vs 21.3%; P < .0001) and for invited lectures (67.4% vs 32.6%; P < .0001) — but not for investigator-submitted abstracts (49.7% vs 50.3%; P = .91).
- The gender gap for industry-supported abstracts, however, was significantly larger than for investigator-submitted abstracts (57.3% vs 0.6%; P < .0001) and larger than for invited lectures (57.3% vs 34.9%; P = .09).
- The gender gap for invited lectures was significantly larger than for investigator-submitted oral presentations (34.9% vs 0.6%; P = .0009).
Why the Discordance?
This disparity may be due to the paucity of women investigators on steering committees for clinical trials. “Although the number of women doing IBD research continues to increase, then number of women senior investigators is still smaller than the number of men senior investigators,” the researchers wrote. “Ideally, there would be transparency in terms of the metrics used by pharma to choose who will be a presenting author and more intentional recruitment of women investigators to steering committees.”
Commenting on the study but not involved in it, internist Shannon M. Ruzycki, MD, MPH, an assistant professor in the Cumming School of Medicine at the University of Calgary Medical Centre in Alberta, Canada, said the findings are not surprising. “In nearly every setting where gender differences are studied in academic medicine, women are found to be disadvantaged compared to men. These differences are not attributable to skill, merit, or career attainment, but rather appear to be arbitrary and due to biases. They add up across time and likely contribute to the larger differences we see between men and women in promotion, compensation, and awards.”
Ruzycki, lead author of a study of women presenters at medical conferences, noted that differences in gender representation in academia, academic medicine, and clinical trials are similar “because the underlying causes are similar.” On the positive side, she added, conference planning committees are using strategies to reduce bias in how presenters are selected by masking the names and/or institutions of those are submitting abstracts and are being more intentional in inviting a diverse panel of qualified speakers.
“However, one strategy alone is unlikely to address such an insidious problem that affects all parts of selection,” she said. “For example, if pharmaceutical companies believe that men presenters are seen as more authoritative or knowledgeable than women presenters, they will select men to be the first author on submitted abstracts which could deprive these opportunities for deserving women candidates.”
Ruzycki attributed the imbalance to systems (academia, medicine, science) designed by men who lack empathy for the experiences of women. “In the same way you can never really understand how exhausting it is to be a parent until you become a parent or how challenging it can be to have a physical disability until you break a leg and have to navigate the world on crutches, it is really challenging for men to understand how cold and hostile these settings can be for women.”
Many of the things that make conferences, academia, and medicine so challenging for women have straightforward solutions, however, Ruzycki added. Onsite childcare, scrubs that fit women, operating room equipment that is ergonomic for women surgeons — even more washroom stalls would help. “If only we listened and cared about things that didn’t directly impact us.”
This study was supported by the 2023 Travel Grant from the International Organization for the Study of Inflammatory Bowel Diseases. One coauthor serves as a consultant or on advisory boards for AbbVie, Amgen, Bristol Myers Squibb, Celsius Therapeutics, Eli Lilly, Gilead Sciences, Janssen Pharmaceuticals, and Pfizer Pharmaceutical. She is a teacher, lecturer, and speaker for Janssen and Takeda Pharmaceuticals. The remaining authors disclosed no conflicts. Ruzycki had no relevant conflicts of interest to declare.
A version of this article appeared on Medscape.com.
A recent study found that The study was published in Gastroenterology and also appeared concurrently in Clinical Gastroenterology and Hepatology .
Indeed, among gastrointestinal (GI) subspecialties, IBD was selected by 26.5% of all women GI physicians, compared with 18.9% of all their male counterparts, according to a 2021 study.
Thus, conference organizers and pharmaceutical companies should promote speaker diversity by seeking out women presenters, according to a group led by Maria A. Quintero, MD, of the Division of Gastroenterology at the Leonard Miller School of Medicine at the University of Miami, Florida.
“Seeing more women IBD leaders at the podium will inspire other women to engage in IBD clinical research,” Quintero and associates wrote.
In addition, women investigators should be included at every stage of the study process in industry-sponsored research, both as principal investigators and members of steering committees involved in study design, the authors said. Training more women clinical trial investigators in the IBD setting is another way forward.
In another recommendation, pharmaceutical companies need to be more transparent about the way first and senior authors on IBD studies are chosen because in the past the principal investigator who enrolled the most patients became the first author of the study. “That is no longer the case. However, it remains unclear whether all investigators have an equal opportunity to be the first or senior author,” Quintero and associates wrote.
The Study
The investigators analyzed IBD abstracts of presentations at five conferences for two large GI meetings, Digestive Disease Week (DDW) and United European Gastroenterology (UEG) in the period 2021-2023.
They asked whether women investigators were as likely as their male counterparts to present abstracts based on results from industry-supported clinical trials. As a point of comparison, they also looked for possible gender differences in invited-speaker vs investigator-initiated IBD sessions. To do this, they examined all IBD-related abstracts from the two meetings, identified the lead author of each oral presentation, and divided them into women or men. They also assessed whether the presentation was pharma-sponsored, investigator-initiated, or presented by an invited speaker.
Among the study findings:
- Across categories there were 178 invited lectures, 336 investigator-submitted presentations, and 150 industry-supported presentations for UEG (2021, 2022, and 2023) and DDW (2022 and 2023).
- The gender gap for men vs women was significant for industry-supported oral presentations (78.7% vs 21.3%; P < .0001) and for invited lectures (67.4% vs 32.6%; P < .0001) — but not for investigator-submitted abstracts (49.7% vs 50.3%; P = .91).
- The gender gap for industry-supported abstracts, however, was significantly larger than for investigator-submitted abstracts (57.3% vs 0.6%; P < .0001) and larger than for invited lectures (57.3% vs 34.9%; P = .09).
- The gender gap for invited lectures was significantly larger than for investigator-submitted oral presentations (34.9% vs 0.6%; P = .0009).
Why the Discordance?
This disparity may be due to the paucity of women investigators on steering committees for clinical trials. “Although the number of women doing IBD research continues to increase, then number of women senior investigators is still smaller than the number of men senior investigators,” the researchers wrote. “Ideally, there would be transparency in terms of the metrics used by pharma to choose who will be a presenting author and more intentional recruitment of women investigators to steering committees.”
Commenting on the study but not involved in it, internist Shannon M. Ruzycki, MD, MPH, an assistant professor in the Cumming School of Medicine at the University of Calgary Medical Centre in Alberta, Canada, said the findings are not surprising. “In nearly every setting where gender differences are studied in academic medicine, women are found to be disadvantaged compared to men. These differences are not attributable to skill, merit, or career attainment, but rather appear to be arbitrary and due to biases. They add up across time and likely contribute to the larger differences we see between men and women in promotion, compensation, and awards.”
Ruzycki, lead author of a study of women presenters at medical conferences, noted that differences in gender representation in academia, academic medicine, and clinical trials are similar “because the underlying causes are similar.” On the positive side, she added, conference planning committees are using strategies to reduce bias in how presenters are selected by masking the names and/or institutions of those are submitting abstracts and are being more intentional in inviting a diverse panel of qualified speakers.
“However, one strategy alone is unlikely to address such an insidious problem that affects all parts of selection,” she said. “For example, if pharmaceutical companies believe that men presenters are seen as more authoritative or knowledgeable than women presenters, they will select men to be the first author on submitted abstracts which could deprive these opportunities for deserving women candidates.”
Ruzycki attributed the imbalance to systems (academia, medicine, science) designed by men who lack empathy for the experiences of women. “In the same way you can never really understand how exhausting it is to be a parent until you become a parent or how challenging it can be to have a physical disability until you break a leg and have to navigate the world on crutches, it is really challenging for men to understand how cold and hostile these settings can be for women.”
Many of the things that make conferences, academia, and medicine so challenging for women have straightforward solutions, however, Ruzycki added. Onsite childcare, scrubs that fit women, operating room equipment that is ergonomic for women surgeons — even more washroom stalls would help. “If only we listened and cared about things that didn’t directly impact us.”
This study was supported by the 2023 Travel Grant from the International Organization for the Study of Inflammatory Bowel Diseases. One coauthor serves as a consultant or on advisory boards for AbbVie, Amgen, Bristol Myers Squibb, Celsius Therapeutics, Eli Lilly, Gilead Sciences, Janssen Pharmaceuticals, and Pfizer Pharmaceutical. She is a teacher, lecturer, and speaker for Janssen and Takeda Pharmaceuticals. The remaining authors disclosed no conflicts. Ruzycki had no relevant conflicts of interest to declare.
A version of this article appeared on Medscape.com.
FROM GASTROENTEROLOGY
New Guideline on EoE Reflects Over a Decade of Advances in Diagnosis and Management
according to a new clinical guideline from the American College of Gastroenterology (ACG).
As an update to the 2013 version, the guideline covers paradigm-shifting changes in EoE knowledge about risk factors, pathogenesis, validated outcome metrics, new nomenclature, and pediatric-specific considerations.
“There have been multiple advances across diagnosis, treatment, monitoring, and other aspects of EoE management in the decade since the last ACG guidelines and in the 5 years since the last AGA [American Gastroenterological Association] guidelines, including new drug approvals globally for EoE,” said lead author Evan Dellon, MD, AGAF, professor of gastroenterology and hepatology and director of the Center for Esophageal Diseases and Swallowing at the University of North Carolina School of Medicine, Chapel Hill.
“The guidelines aimed to provide practical and evidence-based recommendations that could be implemented in daily practice, as well as to provide advice on a number of aspects of diagnosis and management of EoE where there might not be a definitive evidence base, but where clinical questions commonly arise,” he said.
The update was published online in The American Journal of Gastroenterology.
EoE Diagnosis
EoE is a chronic allergen-induced, type 2 immune-mediated disease of the esophagus, which is characterized by symptoms of esophageal dysfunction (such as dysphagia and food impaction) and an eosinophilic predominant infiltrate in the esophagus, the authors wrote.
A diagnosis should be based on the presence of esophageal dysfunction symptoms and at least 15 eosinophils per high-power field on esophageal biopsy, particularly after ruling out non-EoE disorders. A critical change from the 2013 guideline eliminates the requirement of a PPI trial for diagnosis.
Endoscopic evaluation is critical for diagnosis, assessing treatment response, and long-term monitoring, the authors wrote. The guideline advises using the EoE endoscopic reference score (EREFS) to characterize endoscopic findings, a recommendation that was also endorsed in 2022 guidelines by the American Society for Gastrointestinal Endoscopy. EREFS classifies five key EoE features, including edema, rings, exudates, furrows, and strictures, by severity.
To assess for histologic features of EoE, at least six esophageal biopsies should be taken from at least two esophageal levels (such as proximal/mid and distal halves), specifically targeted in areas of furrows or exudates.
In addition, peak eosinophil counts should be quantified on esophageal biopsies from every endoscopy performed for EoE, which will help with subsequent management and monitoring.
As new research expands on the role of mast cells, T cells, basophils, NK cells, and fibroblasts in EoE, the authors postulate that using the EoE histologic scoring system may become more relevant in the future, particularly around findings such as persistent basal zone hyperplasia or lamina propria fibrosis as drivers of ongoing symptoms when eosinophil counts decline.
A Better Understanding of Pathogenesis
“While EoE is considered a relatively new disease, there has been a concerted effort by researchers and clinicians to work together, in partnership with patients, to better understand the basic disease pathogenesis and develop the best treatment approaches,” said Marc Rothenberg, MD, PhD, director of allergy and immunology at Cincinnati Children’s Hospital Medical Center, Ohio. Rothenberg wasn’t involved with the update.
“A lot of progress has been made since the initial thought that esophageal eosinophilia was a ramification of acid reflux disease,” said Rothenberg, the founding director and a principal investigator of the Consortium of Eosinophilic Gastrointestinal Disease Researchers.
“We now understand that the esophagus is an immune-responsive organ and that food allergies can be manifested as EoE. Investment in science is paying off as the basic disease pathoetiology has been uncovered, and this has led to successful strategies for disease intervention, including precision therapy.”
When treating EoE, the goals include improving patient symptoms and quality of life, improving endoscopic and histologic findings, normalizing growth and development in children, maintaining nutrition, and preventing complications such as food impaction or perforation.
This means addressing both the inflammatory and fibrostenotic aspects of the disease, the authors wrote. Pharmacologic or dietary therapies can treat the inflammatory component and may lead to esophageal improvements, whereas esophageal dilation can treat strictures and luminal narrowing. Notably, treatment choices should be individualized based on disease characteristics and patient preferences.
In general, PPIs are suggested as treatment, even beyond reflux symptoms. In EoE, PPIs can decrease eotaxin-3 cytokines that recruit eosinophils to the esophagus, improve esophageal barrier function, and maintain esophageal epithelial transcriptional homeostasis. Although potassium-competitive acid blocker medications have been studied in EoE, data remains limited. H2 receptor blockers don’t appear to be effective for EoE.
Swallowed topical corticosteroids have shown histologic efficacy, the authors reported, particularly in recent phase 3 trials of budesonide oral suspension (BOS) and budesonide orodispersible tablet (BOT). BOS was approved for EoE by the Food and Drug Administration (FDA) in 2024, and BOT was approved for EoE by the European Medicines Agency in 2018.
In terms of dietary elimination, a range of options appear to be effective for patients, including the six-food elimination diet, which has been studied most. However, less restrictive or step-up approaches (such as four-food elimination or one-food elimination of milk) may be better for patients, the authors wrote. Ultimately, the “optimal” choice is one that patients and families can adhere to and have the resources to complete.
In addition, they noted that allergy test-directed elimination diets aren’t currently recommended because EoE has delayed hypersensitivity, so skin prick, patch, or serum Ig allergy tests tend to have limited success in predicting EoE food triggers.
In terms of biologic treatments, dupilumab is recommended for ages 12 years or older who don’t respond to PPI therapy, as well as suggested for ages 1-11 years based on previous clinical trial data. The FDA approved the use of dupilumab for ages 1-11 years in February 2024.
In this update, the authors declined to make recommendations about other biologics such as cendakimab, benralizumab, lirentelimab, mepolizumab, or reslizumab. They also advised against using omaluzumab as a treatment for EoE.
“This new 2025 guideline summarizes and synthesizes key studies in support of proton pump inhibitors, topical steroids, dietary therapy, and biologics for EoE. Additionally, the guidelines are clinically relevant in providing practical suggestions (such as medication dosing) and expert opinions on key concepts in managing EoE,” said Joy Weiling Chang, MD, assistant professor of gastroenterology at the University of Michigan, Ann Arbor, who specializes in patient-physician preferences and decision-making in EoE care.
“It’s an exciting time to take care of patients with EoE with many new therapies, but the rapidly evolving options can be overwhelming,” said Chang, who wasn’t involved with the update. “Since there are no clinical effectiveness studies between the various treatments, and therapies can differ so much (with delivery and daily use, monitoring, cost), electing EoE treatment is an ideal opportunity for shared decision-making. Equipped with these clinical guidelines, clinicians can be empowered to elicit and consider patient preferences and values in the management of this chronic disease.”
The authors received no specific funding for this update. Dellon and Rothenberg reported receiving research funding and consultant roles with numerous pharmaceutical companies and organizations. Chang reported no relevant disclosures.
A version of this article appeared on Medscape.com.
according to a new clinical guideline from the American College of Gastroenterology (ACG).
As an update to the 2013 version, the guideline covers paradigm-shifting changes in EoE knowledge about risk factors, pathogenesis, validated outcome metrics, new nomenclature, and pediatric-specific considerations.
“There have been multiple advances across diagnosis, treatment, monitoring, and other aspects of EoE management in the decade since the last ACG guidelines and in the 5 years since the last AGA [American Gastroenterological Association] guidelines, including new drug approvals globally for EoE,” said lead author Evan Dellon, MD, AGAF, professor of gastroenterology and hepatology and director of the Center for Esophageal Diseases and Swallowing at the University of North Carolina School of Medicine, Chapel Hill.
“The guidelines aimed to provide practical and evidence-based recommendations that could be implemented in daily practice, as well as to provide advice on a number of aspects of diagnosis and management of EoE where there might not be a definitive evidence base, but where clinical questions commonly arise,” he said.
The update was published online in The American Journal of Gastroenterology.
EoE Diagnosis
EoE is a chronic allergen-induced, type 2 immune-mediated disease of the esophagus, which is characterized by symptoms of esophageal dysfunction (such as dysphagia and food impaction) and an eosinophilic predominant infiltrate in the esophagus, the authors wrote.
A diagnosis should be based on the presence of esophageal dysfunction symptoms and at least 15 eosinophils per high-power field on esophageal biopsy, particularly after ruling out non-EoE disorders. A critical change from the 2013 guideline eliminates the requirement of a PPI trial for diagnosis.
Endoscopic evaluation is critical for diagnosis, assessing treatment response, and long-term monitoring, the authors wrote. The guideline advises using the EoE endoscopic reference score (EREFS) to characterize endoscopic findings, a recommendation that was also endorsed in 2022 guidelines by the American Society for Gastrointestinal Endoscopy. EREFS classifies five key EoE features, including edema, rings, exudates, furrows, and strictures, by severity.
To assess for histologic features of EoE, at least six esophageal biopsies should be taken from at least two esophageal levels (such as proximal/mid and distal halves), specifically targeted in areas of furrows or exudates.
In addition, peak eosinophil counts should be quantified on esophageal biopsies from every endoscopy performed for EoE, which will help with subsequent management and monitoring.
As new research expands on the role of mast cells, T cells, basophils, NK cells, and fibroblasts in EoE, the authors postulate that using the EoE histologic scoring system may become more relevant in the future, particularly around findings such as persistent basal zone hyperplasia or lamina propria fibrosis as drivers of ongoing symptoms when eosinophil counts decline.
A Better Understanding of Pathogenesis
“While EoE is considered a relatively new disease, there has been a concerted effort by researchers and clinicians to work together, in partnership with patients, to better understand the basic disease pathogenesis and develop the best treatment approaches,” said Marc Rothenberg, MD, PhD, director of allergy and immunology at Cincinnati Children’s Hospital Medical Center, Ohio. Rothenberg wasn’t involved with the update.
“A lot of progress has been made since the initial thought that esophageal eosinophilia was a ramification of acid reflux disease,” said Rothenberg, the founding director and a principal investigator of the Consortium of Eosinophilic Gastrointestinal Disease Researchers.
“We now understand that the esophagus is an immune-responsive organ and that food allergies can be manifested as EoE. Investment in science is paying off as the basic disease pathoetiology has been uncovered, and this has led to successful strategies for disease intervention, including precision therapy.”
When treating EoE, the goals include improving patient symptoms and quality of life, improving endoscopic and histologic findings, normalizing growth and development in children, maintaining nutrition, and preventing complications such as food impaction or perforation.
This means addressing both the inflammatory and fibrostenotic aspects of the disease, the authors wrote. Pharmacologic or dietary therapies can treat the inflammatory component and may lead to esophageal improvements, whereas esophageal dilation can treat strictures and luminal narrowing. Notably, treatment choices should be individualized based on disease characteristics and patient preferences.
In general, PPIs are suggested as treatment, even beyond reflux symptoms. In EoE, PPIs can decrease eotaxin-3 cytokines that recruit eosinophils to the esophagus, improve esophageal barrier function, and maintain esophageal epithelial transcriptional homeostasis. Although potassium-competitive acid blocker medications have been studied in EoE, data remains limited. H2 receptor blockers don’t appear to be effective for EoE.
Swallowed topical corticosteroids have shown histologic efficacy, the authors reported, particularly in recent phase 3 trials of budesonide oral suspension (BOS) and budesonide orodispersible tablet (BOT). BOS was approved for EoE by the Food and Drug Administration (FDA) in 2024, and BOT was approved for EoE by the European Medicines Agency in 2018.
In terms of dietary elimination, a range of options appear to be effective for patients, including the six-food elimination diet, which has been studied most. However, less restrictive or step-up approaches (such as four-food elimination or one-food elimination of milk) may be better for patients, the authors wrote. Ultimately, the “optimal” choice is one that patients and families can adhere to and have the resources to complete.
In addition, they noted that allergy test-directed elimination diets aren’t currently recommended because EoE has delayed hypersensitivity, so skin prick, patch, or serum Ig allergy tests tend to have limited success in predicting EoE food triggers.
In terms of biologic treatments, dupilumab is recommended for ages 12 years or older who don’t respond to PPI therapy, as well as suggested for ages 1-11 years based on previous clinical trial data. The FDA approved the use of dupilumab for ages 1-11 years in February 2024.
In this update, the authors declined to make recommendations about other biologics such as cendakimab, benralizumab, lirentelimab, mepolizumab, or reslizumab. They also advised against using omaluzumab as a treatment for EoE.
“This new 2025 guideline summarizes and synthesizes key studies in support of proton pump inhibitors, topical steroids, dietary therapy, and biologics for EoE. Additionally, the guidelines are clinically relevant in providing practical suggestions (such as medication dosing) and expert opinions on key concepts in managing EoE,” said Joy Weiling Chang, MD, assistant professor of gastroenterology at the University of Michigan, Ann Arbor, who specializes in patient-physician preferences and decision-making in EoE care.
“It’s an exciting time to take care of patients with EoE with many new therapies, but the rapidly evolving options can be overwhelming,” said Chang, who wasn’t involved with the update. “Since there are no clinical effectiveness studies between the various treatments, and therapies can differ so much (with delivery and daily use, monitoring, cost), electing EoE treatment is an ideal opportunity for shared decision-making. Equipped with these clinical guidelines, clinicians can be empowered to elicit and consider patient preferences and values in the management of this chronic disease.”
The authors received no specific funding for this update. Dellon and Rothenberg reported receiving research funding and consultant roles with numerous pharmaceutical companies and organizations. Chang reported no relevant disclosures.
A version of this article appeared on Medscape.com.
according to a new clinical guideline from the American College of Gastroenterology (ACG).
As an update to the 2013 version, the guideline covers paradigm-shifting changes in EoE knowledge about risk factors, pathogenesis, validated outcome metrics, new nomenclature, and pediatric-specific considerations.
“There have been multiple advances across diagnosis, treatment, monitoring, and other aspects of EoE management in the decade since the last ACG guidelines and in the 5 years since the last AGA [American Gastroenterological Association] guidelines, including new drug approvals globally for EoE,” said lead author Evan Dellon, MD, AGAF, professor of gastroenterology and hepatology and director of the Center for Esophageal Diseases and Swallowing at the University of North Carolina School of Medicine, Chapel Hill.
“The guidelines aimed to provide practical and evidence-based recommendations that could be implemented in daily practice, as well as to provide advice on a number of aspects of diagnosis and management of EoE where there might not be a definitive evidence base, but where clinical questions commonly arise,” he said.
The update was published online in The American Journal of Gastroenterology.
EoE Diagnosis
EoE is a chronic allergen-induced, type 2 immune-mediated disease of the esophagus, which is characterized by symptoms of esophageal dysfunction (such as dysphagia and food impaction) and an eosinophilic predominant infiltrate in the esophagus, the authors wrote.
A diagnosis should be based on the presence of esophageal dysfunction symptoms and at least 15 eosinophils per high-power field on esophageal biopsy, particularly after ruling out non-EoE disorders. A critical change from the 2013 guideline eliminates the requirement of a PPI trial for diagnosis.
Endoscopic evaluation is critical for diagnosis, assessing treatment response, and long-term monitoring, the authors wrote. The guideline advises using the EoE endoscopic reference score (EREFS) to characterize endoscopic findings, a recommendation that was also endorsed in 2022 guidelines by the American Society for Gastrointestinal Endoscopy. EREFS classifies five key EoE features, including edema, rings, exudates, furrows, and strictures, by severity.
To assess for histologic features of EoE, at least six esophageal biopsies should be taken from at least two esophageal levels (such as proximal/mid and distal halves), specifically targeted in areas of furrows or exudates.
In addition, peak eosinophil counts should be quantified on esophageal biopsies from every endoscopy performed for EoE, which will help with subsequent management and monitoring.
As new research expands on the role of mast cells, T cells, basophils, NK cells, and fibroblasts in EoE, the authors postulate that using the EoE histologic scoring system may become more relevant in the future, particularly around findings such as persistent basal zone hyperplasia or lamina propria fibrosis as drivers of ongoing symptoms when eosinophil counts decline.
A Better Understanding of Pathogenesis
“While EoE is considered a relatively new disease, there has been a concerted effort by researchers and clinicians to work together, in partnership with patients, to better understand the basic disease pathogenesis and develop the best treatment approaches,” said Marc Rothenberg, MD, PhD, director of allergy and immunology at Cincinnati Children’s Hospital Medical Center, Ohio. Rothenberg wasn’t involved with the update.
“A lot of progress has been made since the initial thought that esophageal eosinophilia was a ramification of acid reflux disease,” said Rothenberg, the founding director and a principal investigator of the Consortium of Eosinophilic Gastrointestinal Disease Researchers.
“We now understand that the esophagus is an immune-responsive organ and that food allergies can be manifested as EoE. Investment in science is paying off as the basic disease pathoetiology has been uncovered, and this has led to successful strategies for disease intervention, including precision therapy.”
When treating EoE, the goals include improving patient symptoms and quality of life, improving endoscopic and histologic findings, normalizing growth and development in children, maintaining nutrition, and preventing complications such as food impaction or perforation.
This means addressing both the inflammatory and fibrostenotic aspects of the disease, the authors wrote. Pharmacologic or dietary therapies can treat the inflammatory component and may lead to esophageal improvements, whereas esophageal dilation can treat strictures and luminal narrowing. Notably, treatment choices should be individualized based on disease characteristics and patient preferences.
In general, PPIs are suggested as treatment, even beyond reflux symptoms. In EoE, PPIs can decrease eotaxin-3 cytokines that recruit eosinophils to the esophagus, improve esophageal barrier function, and maintain esophageal epithelial transcriptional homeostasis. Although potassium-competitive acid blocker medications have been studied in EoE, data remains limited. H2 receptor blockers don’t appear to be effective for EoE.
Swallowed topical corticosteroids have shown histologic efficacy, the authors reported, particularly in recent phase 3 trials of budesonide oral suspension (BOS) and budesonide orodispersible tablet (BOT). BOS was approved for EoE by the Food and Drug Administration (FDA) in 2024, and BOT was approved for EoE by the European Medicines Agency in 2018.
In terms of dietary elimination, a range of options appear to be effective for patients, including the six-food elimination diet, which has been studied most. However, less restrictive or step-up approaches (such as four-food elimination or one-food elimination of milk) may be better for patients, the authors wrote. Ultimately, the “optimal” choice is one that patients and families can adhere to and have the resources to complete.
In addition, they noted that allergy test-directed elimination diets aren’t currently recommended because EoE has delayed hypersensitivity, so skin prick, patch, or serum Ig allergy tests tend to have limited success in predicting EoE food triggers.
In terms of biologic treatments, dupilumab is recommended for ages 12 years or older who don’t respond to PPI therapy, as well as suggested for ages 1-11 years based on previous clinical trial data. The FDA approved the use of dupilumab for ages 1-11 years in February 2024.
In this update, the authors declined to make recommendations about other biologics such as cendakimab, benralizumab, lirentelimab, mepolizumab, or reslizumab. They also advised against using omaluzumab as a treatment for EoE.
“This new 2025 guideline summarizes and synthesizes key studies in support of proton pump inhibitors, topical steroids, dietary therapy, and biologics for EoE. Additionally, the guidelines are clinically relevant in providing practical suggestions (such as medication dosing) and expert opinions on key concepts in managing EoE,” said Joy Weiling Chang, MD, assistant professor of gastroenterology at the University of Michigan, Ann Arbor, who specializes in patient-physician preferences and decision-making in EoE care.
“It’s an exciting time to take care of patients with EoE with many new therapies, but the rapidly evolving options can be overwhelming,” said Chang, who wasn’t involved with the update. “Since there are no clinical effectiveness studies between the various treatments, and therapies can differ so much (with delivery and daily use, monitoring, cost), electing EoE treatment is an ideal opportunity for shared decision-making. Equipped with these clinical guidelines, clinicians can be empowered to elicit and consider patient preferences and values in the management of this chronic disease.”
The authors received no specific funding for this update. Dellon and Rothenberg reported receiving research funding and consultant roles with numerous pharmaceutical companies and organizations. Chang reported no relevant disclosures.
A version of this article appeared on Medscape.com.
FROM THE AMERICAN JOURNAL OF GASTROENTEROLOGY
High-Intensity Focused Ultrasound Ablation Shows Promise in Veterans
TOPLINE: A small study of veterans found that high-intensity focused ultrasound (HIFU) demonstrated similar oncologic outcomes when compared to standard treatments for localized prostate cancer, while maintaining erectile and urinary function.
METHODOLOGY:
- A retrospective analysis at the Michael E. DeBakey Veterans Affairs Medical Center in Houston between 2018 and 2022, with data acquired from electronic health record.
- A total of 43 veterans were included in the analysis; 31 patients (72%) receiving primary treatment and 12 patients (28%) receiving salvage therapy.
- Patient risk stratification was performed using prostate specific antigen (PSA), Gleason Score, and clinical stage based on National Comprehensive Cancer Network and D'Amico criteria.
- Follow-up assessments included serial PSA measurements at 3, 6, 12, 18, and 24 months, with functional outcomes evaluated through Sexual Health Inventory for Men and American Urological Association Symptom Score questionnaires.
TAKEAWAY:
- The 31 patients in the primary treatment group had a median PSA nadir of 0.16, while the 12 patients in the salvage therapy group had a median PSA nadir of 0.12, with median follow-up periods of 23 and 25 months, respectively.
- Local recurrence rates were comparable between groups, occurring in 5 patients (16%) in the primary group and 2 (17%) in the salvage group.
- Sexual Health Inventory for Men scores and American Urological Association Symptom Score showed no statistically significant differences before and after HIFU therapy in both groups (P = .35). > .05).
- Short- and intermediate-term results demonstrated HIFU's effectiveness in maintaining potency and urinary function while providing adequate oncological control for both primary and salvage therapies.
- Two patients (7%) from the primary treatment group experienced 30-day complications, including one case of epididymo-orchitis and 1 case of urethral stricture.
- Three patients (25%) from the salvage treatment group experienced 30-day complications, including one bladder neck contracture.
IN PRACTICE: "The application of HIFU in a veteran population is of particular interest due to the unique medical challenges this group faces. Veterans often present with complex medical conditions and a higher comorbidity burden compared to the general population, as indicated by a median Charleson Comorbidity Index of 7 in our primary HIFU group," wrote the authors of the study.
SOURCE: The study was led by Sagar Patel and Ali Antar, Operative Care Line, Urology Section, Michael E. DeBakey Veteran Affairs Medical Center in Houston. It was published online in Life.
LIMITATIONS: The study's relatively short median follow-up period of 23-25 months limits the assessment of long-term oncological outcomes in prostate cancer. The sample size, while substantial for an initial series, remains modest, particularly for the salvage therapy group. According to the authors, larger multi-center studies with longer follow-up periods will be necessary to confirm and extend these findings, especially for establishing the durability of oncological control and functional preservation.
DISCLOSURES: The study received no external funding. The research was conducted in accordance with the Declaration of Helsinki and received approval from the Institutional Review Board in February 2024. Support was obtained from the Prostate Cancer Foundation-VALOR Challenge Program. The authors declared no conflicts of interest.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication
TOPLINE: A small study of veterans found that high-intensity focused ultrasound (HIFU) demonstrated similar oncologic outcomes when compared to standard treatments for localized prostate cancer, while maintaining erectile and urinary function.
METHODOLOGY:
- A retrospective analysis at the Michael E. DeBakey Veterans Affairs Medical Center in Houston between 2018 and 2022, with data acquired from electronic health record.
- A total of 43 veterans were included in the analysis; 31 patients (72%) receiving primary treatment and 12 patients (28%) receiving salvage therapy.
- Patient risk stratification was performed using prostate specific antigen (PSA), Gleason Score, and clinical stage based on National Comprehensive Cancer Network and D'Amico criteria.
- Follow-up assessments included serial PSA measurements at 3, 6, 12, 18, and 24 months, with functional outcomes evaluated through Sexual Health Inventory for Men and American Urological Association Symptom Score questionnaires.
TAKEAWAY:
- The 31 patients in the primary treatment group had a median PSA nadir of 0.16, while the 12 patients in the salvage therapy group had a median PSA nadir of 0.12, with median follow-up periods of 23 and 25 months, respectively.
- Local recurrence rates were comparable between groups, occurring in 5 patients (16%) in the primary group and 2 (17%) in the salvage group.
- Sexual Health Inventory for Men scores and American Urological Association Symptom Score showed no statistically significant differences before and after HIFU therapy in both groups (P = .35). > .05).
- Short- and intermediate-term results demonstrated HIFU's effectiveness in maintaining potency and urinary function while providing adequate oncological control for both primary and salvage therapies.
- Two patients (7%) from the primary treatment group experienced 30-day complications, including one case of epididymo-orchitis and 1 case of urethral stricture.
- Three patients (25%) from the salvage treatment group experienced 30-day complications, including one bladder neck contracture.
IN PRACTICE: "The application of HIFU in a veteran population is of particular interest due to the unique medical challenges this group faces. Veterans often present with complex medical conditions and a higher comorbidity burden compared to the general population, as indicated by a median Charleson Comorbidity Index of 7 in our primary HIFU group," wrote the authors of the study.
SOURCE: The study was led by Sagar Patel and Ali Antar, Operative Care Line, Urology Section, Michael E. DeBakey Veteran Affairs Medical Center in Houston. It was published online in Life.
LIMITATIONS: The study's relatively short median follow-up period of 23-25 months limits the assessment of long-term oncological outcomes in prostate cancer. The sample size, while substantial for an initial series, remains modest, particularly for the salvage therapy group. According to the authors, larger multi-center studies with longer follow-up periods will be necessary to confirm and extend these findings, especially for establishing the durability of oncological control and functional preservation.
DISCLOSURES: The study received no external funding. The research was conducted in accordance with the Declaration of Helsinki and received approval from the Institutional Review Board in February 2024. Support was obtained from the Prostate Cancer Foundation-VALOR Challenge Program. The authors declared no conflicts of interest.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication
TOPLINE: A small study of veterans found that high-intensity focused ultrasound (HIFU) demonstrated similar oncologic outcomes when compared to standard treatments for localized prostate cancer, while maintaining erectile and urinary function.
METHODOLOGY:
- A retrospective analysis at the Michael E. DeBakey Veterans Affairs Medical Center in Houston between 2018 and 2022, with data acquired from electronic health record.
- A total of 43 veterans were included in the analysis; 31 patients (72%) receiving primary treatment and 12 patients (28%) receiving salvage therapy.
- Patient risk stratification was performed using prostate specific antigen (PSA), Gleason Score, and clinical stage based on National Comprehensive Cancer Network and D'Amico criteria.
- Follow-up assessments included serial PSA measurements at 3, 6, 12, 18, and 24 months, with functional outcomes evaluated through Sexual Health Inventory for Men and American Urological Association Symptom Score questionnaires.
TAKEAWAY:
- The 31 patients in the primary treatment group had a median PSA nadir of 0.16, while the 12 patients in the salvage therapy group had a median PSA nadir of 0.12, with median follow-up periods of 23 and 25 months, respectively.
- Local recurrence rates were comparable between groups, occurring in 5 patients (16%) in the primary group and 2 (17%) in the salvage group.
- Sexual Health Inventory for Men scores and American Urological Association Symptom Score showed no statistically significant differences before and after HIFU therapy in both groups (P = .35). > .05).
- Short- and intermediate-term results demonstrated HIFU's effectiveness in maintaining potency and urinary function while providing adequate oncological control for both primary and salvage therapies.
- Two patients (7%) from the primary treatment group experienced 30-day complications, including one case of epididymo-orchitis and 1 case of urethral stricture.
- Three patients (25%) from the salvage treatment group experienced 30-day complications, including one bladder neck contracture.
IN PRACTICE: "The application of HIFU in a veteran population is of particular interest due to the unique medical challenges this group faces. Veterans often present with complex medical conditions and a higher comorbidity burden compared to the general population, as indicated by a median Charleson Comorbidity Index of 7 in our primary HIFU group," wrote the authors of the study.
SOURCE: The study was led by Sagar Patel and Ali Antar, Operative Care Line, Urology Section, Michael E. DeBakey Veteran Affairs Medical Center in Houston. It was published online in Life.
LIMITATIONS: The study's relatively short median follow-up period of 23-25 months limits the assessment of long-term oncological outcomes in prostate cancer. The sample size, while substantial for an initial series, remains modest, particularly for the salvage therapy group. According to the authors, larger multi-center studies with longer follow-up periods will be necessary to confirm and extend these findings, especially for establishing the durability of oncological control and functional preservation.
DISCLOSURES: The study received no external funding. The research was conducted in accordance with the Declaration of Helsinki and received approval from the Institutional Review Board in February 2024. Support was obtained from the Prostate Cancer Foundation-VALOR Challenge Program. The authors declared no conflicts of interest.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication
VA Study Asks: Has Active Surveillance Solved the Problem of Overtreatment?
Overtreatment of men with prostate cancer and limited life expectancy (LE) has persisted in the era of active surveillance and worsened in some instances, according to a new study of nearly 250,000 veterans.
“Overtreatment of men with limited longevity for intermediate- and high-risk tumors has not only failed to improve but has actually worsened over the last 20 years,” Timothy Daskivich, MD, MSHPM, with Cedars-Sinai Medical Center, Los Angeles, said in an interview.
“Many doctors assume that the increase in uptake of active surveillance for low-risk prostate cancers has solved the problem of overtreatment, but this trend has not affected overtreatment of men with low likelihood of living long enough to benefit from treatment who have higher-risk tumors,” Daskivich said.
The study was published online on November 11 in JAMA Internal Medicine.
‘Concerning’ Real-World Data
For men with low- and intermediate-risk prostate cancer expected to live fewer than 10 years, prostate cancer screening and aggressive treatment are not recommended.
Daskivich and colleagues analyzed data on 243,928 men (mean age, 66 years) in the Veterans Affairs (VA) Health System with clinically localized prostate cancer diagnosed between 2000 and 2019.
About 21% had LE < 10 years, and about 4% had LE < 5 years, according to the validated age-adjusted Prostate Cancer Comorbidity Index.
Overtreatment was defined as aggressive treatment (surgery or radiation) in those with LE < 10 years and low- to intermediate-risk disease and in those with LE < 5 years and high-risk disease, in line with current guidelines.
Among men with LE < 10 years, the proportion of men overtreated with surgery or radiotherapy for low-risk disease decreased 22% but increased 22% for intermediate-risk disease during the study period.
Among men with LE < 5 years, the proportion of men treated with definitive treatment for high-risk disease increased 29%.
“While lower-risk tumors are treated less aggressively across the board, including in men with limited longevity, it seems that we are more indiscriminately treating men with higher-risk disease without considering their expected longevity,” Daskivich said, in an interview.
Is This Happening in the General US Population?
Daskivich noted that the sample included a large sample of men diagnosed with localized prostate cancer in the VA Health System.
“Rates of overtreatment are likely to be lower in the VA [Health System], so the problem may be worse in the community setting. The VA [Health System] has been exemplary in its uptake of active surveillance for low-risk cancers, leading the effort to reduce overtreatment of men with low-risk cancers. However, the problem of overtreatment of men with limited longevity persists in the VA [Health System], underscoring the pervasiveness of this problem,” he explained.
“We don’t have a perfect head-to-head comparison of overtreatment in the VA setting vs in the community. [However, one study shows] that this is not a VA-specific phenomenon and that there is an increase in overtreatment of men with limited longevity in a Medicare population as well,” Daskivich noted.
Is Overtreatment All Bad?
Overtreatment of prostate cancer, especially in cases where the cancer is unlikely to progress or cause symptoms, can lead to significant physical, psychological, and financial harms, Christopher Anderson, MD, urologist with Columbia University Irving Medical Center in New York City, who wasn’t involved in the study, noted in an interview.
In the study by Daskivich and colleagues, over three quarters of the overtreatment was radiation therapy, which carries the risk for urinary, bowel, and sexual issues.
“Overscreening, which can lead to overtreatment, is a core issue,” Anderson said. It’s easy to order a “simple” prostate-specific antigen blood test, but in an older man with limited LE, that can lead to a host of further testing, he commented.
Stopping the pipeline of overscreening that then feeds into the cascade of overtreatment is the first step in addressing the problem of prostate cancer overtreatment, Nancy Li Schoenborn, MD, MHS, with Johns Hopkins University School of Medicine, Baltimore, and Louise C. Walter, MD, with University of California San Francisco, wrote in an editorial in JAMA Internal Medicine.
Considering LE during screening decision-making is “fundamental to reducing harms of prostate cancer overdiagnosis and overtreatment” because limited LE increases the likelihood of experiencing “harms all along the diagnostic and treatment cascade following screening,” the editorial writers said.
The time spent diagnosing, monitoring, and treating asymptomatic prostate cancer in men with limited LE distracts from monitoring and treating chronic symptomatic life-limiting illnesses, they noted.
Tough to Talk About?
Anderson noted that, in general, doctors are not great at estimating and counseling patients on LE. “It’s sometimes difficult to have that conversation,” he said.
Daskivich said physicians may fail to include average LE when advising patients on treatments because they believe that the patients do not want to discuss this topic. “Yet, in interviews with patients, we found that prostate cancer patients reported they wanted this information,” he continued, in an interview.
Solving the problem of overscreening and overtreatment will require a “multifaceted approach, including improving access to life expectancy data at the point of care for providers, educating providers on how to communicate this information, and improving data sources to predict longevity,” Daskivich said.
He said it’s equally important to note that some men with prostate cancer may choose treatment even if they have a limited longevity.
“Not all patients will choose conservative management, even if it is recommended by guidelines. However, they need to be given the opportunity to make a good decision for themselves with the best possible data,” Daskivich said.
This work was supported in part by a US Department of VA Merit Review. Daskivich reported receiving personal fees from the Medical Education Speakers Network, EDAP, and RAND; research support from Lantheus and Janssen; and a patent pending for a system for healthcare visit quality assessment outside the submitted work. Schoenborn, Walter, and Anderson had no relevant disclosures.
A version of this article first appeared on Medscape.com.
Overtreatment of men with prostate cancer and limited life expectancy (LE) has persisted in the era of active surveillance and worsened in some instances, according to a new study of nearly 250,000 veterans.
“Overtreatment of men with limited longevity for intermediate- and high-risk tumors has not only failed to improve but has actually worsened over the last 20 years,” Timothy Daskivich, MD, MSHPM, with Cedars-Sinai Medical Center, Los Angeles, said in an interview.
“Many doctors assume that the increase in uptake of active surveillance for low-risk prostate cancers has solved the problem of overtreatment, but this trend has not affected overtreatment of men with low likelihood of living long enough to benefit from treatment who have higher-risk tumors,” Daskivich said.
The study was published online on November 11 in JAMA Internal Medicine.
‘Concerning’ Real-World Data
For men with low- and intermediate-risk prostate cancer expected to live fewer than 10 years, prostate cancer screening and aggressive treatment are not recommended.
Daskivich and colleagues analyzed data on 243,928 men (mean age, 66 years) in the Veterans Affairs (VA) Health System with clinically localized prostate cancer diagnosed between 2000 and 2019.
About 21% had LE < 10 years, and about 4% had LE < 5 years, according to the validated age-adjusted Prostate Cancer Comorbidity Index.
Overtreatment was defined as aggressive treatment (surgery or radiation) in those with LE < 10 years and low- to intermediate-risk disease and in those with LE < 5 years and high-risk disease, in line with current guidelines.
Among men with LE < 10 years, the proportion of men overtreated with surgery or radiotherapy for low-risk disease decreased 22% but increased 22% for intermediate-risk disease during the study period.
Among men with LE < 5 years, the proportion of men treated with definitive treatment for high-risk disease increased 29%.
“While lower-risk tumors are treated less aggressively across the board, including in men with limited longevity, it seems that we are more indiscriminately treating men with higher-risk disease without considering their expected longevity,” Daskivich said, in an interview.
Is This Happening in the General US Population?
Daskivich noted that the sample included a large sample of men diagnosed with localized prostate cancer in the VA Health System.
“Rates of overtreatment are likely to be lower in the VA [Health System], so the problem may be worse in the community setting. The VA [Health System] has been exemplary in its uptake of active surveillance for low-risk cancers, leading the effort to reduce overtreatment of men with low-risk cancers. However, the problem of overtreatment of men with limited longevity persists in the VA [Health System], underscoring the pervasiveness of this problem,” he explained.
“We don’t have a perfect head-to-head comparison of overtreatment in the VA setting vs in the community. [However, one study shows] that this is not a VA-specific phenomenon and that there is an increase in overtreatment of men with limited longevity in a Medicare population as well,” Daskivich noted.
Is Overtreatment All Bad?
Overtreatment of prostate cancer, especially in cases where the cancer is unlikely to progress or cause symptoms, can lead to significant physical, psychological, and financial harms, Christopher Anderson, MD, urologist with Columbia University Irving Medical Center in New York City, who wasn’t involved in the study, noted in an interview.
In the study by Daskivich and colleagues, over three quarters of the overtreatment was radiation therapy, which carries the risk for urinary, bowel, and sexual issues.
“Overscreening, which can lead to overtreatment, is a core issue,” Anderson said. It’s easy to order a “simple” prostate-specific antigen blood test, but in an older man with limited LE, that can lead to a host of further testing, he commented.
Stopping the pipeline of overscreening that then feeds into the cascade of overtreatment is the first step in addressing the problem of prostate cancer overtreatment, Nancy Li Schoenborn, MD, MHS, with Johns Hopkins University School of Medicine, Baltimore, and Louise C. Walter, MD, with University of California San Francisco, wrote in an editorial in JAMA Internal Medicine.
Considering LE during screening decision-making is “fundamental to reducing harms of prostate cancer overdiagnosis and overtreatment” because limited LE increases the likelihood of experiencing “harms all along the diagnostic and treatment cascade following screening,” the editorial writers said.
The time spent diagnosing, monitoring, and treating asymptomatic prostate cancer in men with limited LE distracts from monitoring and treating chronic symptomatic life-limiting illnesses, they noted.
Tough to Talk About?
Anderson noted that, in general, doctors are not great at estimating and counseling patients on LE. “It’s sometimes difficult to have that conversation,” he said.
Daskivich said physicians may fail to include average LE when advising patients on treatments because they believe that the patients do not want to discuss this topic. “Yet, in interviews with patients, we found that prostate cancer patients reported they wanted this information,” he continued, in an interview.
Solving the problem of overscreening and overtreatment will require a “multifaceted approach, including improving access to life expectancy data at the point of care for providers, educating providers on how to communicate this information, and improving data sources to predict longevity,” Daskivich said.
He said it’s equally important to note that some men with prostate cancer may choose treatment even if they have a limited longevity.
“Not all patients will choose conservative management, even if it is recommended by guidelines. However, they need to be given the opportunity to make a good decision for themselves with the best possible data,” Daskivich said.
This work was supported in part by a US Department of VA Merit Review. Daskivich reported receiving personal fees from the Medical Education Speakers Network, EDAP, and RAND; research support from Lantheus and Janssen; and a patent pending for a system for healthcare visit quality assessment outside the submitted work. Schoenborn, Walter, and Anderson had no relevant disclosures.
A version of this article first appeared on Medscape.com.
Overtreatment of men with prostate cancer and limited life expectancy (LE) has persisted in the era of active surveillance and worsened in some instances, according to a new study of nearly 250,000 veterans.
“Overtreatment of men with limited longevity for intermediate- and high-risk tumors has not only failed to improve but has actually worsened over the last 20 years,” Timothy Daskivich, MD, MSHPM, with Cedars-Sinai Medical Center, Los Angeles, said in an interview.
“Many doctors assume that the increase in uptake of active surveillance for low-risk prostate cancers has solved the problem of overtreatment, but this trend has not affected overtreatment of men with low likelihood of living long enough to benefit from treatment who have higher-risk tumors,” Daskivich said.
The study was published online on November 11 in JAMA Internal Medicine.
‘Concerning’ Real-World Data
For men with low- and intermediate-risk prostate cancer expected to live fewer than 10 years, prostate cancer screening and aggressive treatment are not recommended.
Daskivich and colleagues analyzed data on 243,928 men (mean age, 66 years) in the Veterans Affairs (VA) Health System with clinically localized prostate cancer diagnosed between 2000 and 2019.
About 21% had LE < 10 years, and about 4% had LE < 5 years, according to the validated age-adjusted Prostate Cancer Comorbidity Index.
Overtreatment was defined as aggressive treatment (surgery or radiation) in those with LE < 10 years and low- to intermediate-risk disease and in those with LE < 5 years and high-risk disease, in line with current guidelines.
Among men with LE < 10 years, the proportion of men overtreated with surgery or radiotherapy for low-risk disease decreased 22% but increased 22% for intermediate-risk disease during the study period.
Among men with LE < 5 years, the proportion of men treated with definitive treatment for high-risk disease increased 29%.
“While lower-risk tumors are treated less aggressively across the board, including in men with limited longevity, it seems that we are more indiscriminately treating men with higher-risk disease without considering their expected longevity,” Daskivich said, in an interview.
Is This Happening in the General US Population?
Daskivich noted that the sample included a large sample of men diagnosed with localized prostate cancer in the VA Health System.
“Rates of overtreatment are likely to be lower in the VA [Health System], so the problem may be worse in the community setting. The VA [Health System] has been exemplary in its uptake of active surveillance for low-risk cancers, leading the effort to reduce overtreatment of men with low-risk cancers. However, the problem of overtreatment of men with limited longevity persists in the VA [Health System], underscoring the pervasiveness of this problem,” he explained.
“We don’t have a perfect head-to-head comparison of overtreatment in the VA setting vs in the community. [However, one study shows] that this is not a VA-specific phenomenon and that there is an increase in overtreatment of men with limited longevity in a Medicare population as well,” Daskivich noted.
Is Overtreatment All Bad?
Overtreatment of prostate cancer, especially in cases where the cancer is unlikely to progress or cause symptoms, can lead to significant physical, psychological, and financial harms, Christopher Anderson, MD, urologist with Columbia University Irving Medical Center in New York City, who wasn’t involved in the study, noted in an interview.
In the study by Daskivich and colleagues, over three quarters of the overtreatment was radiation therapy, which carries the risk for urinary, bowel, and sexual issues.
“Overscreening, which can lead to overtreatment, is a core issue,” Anderson said. It’s easy to order a “simple” prostate-specific antigen blood test, but in an older man with limited LE, that can lead to a host of further testing, he commented.
Stopping the pipeline of overscreening that then feeds into the cascade of overtreatment is the first step in addressing the problem of prostate cancer overtreatment, Nancy Li Schoenborn, MD, MHS, with Johns Hopkins University School of Medicine, Baltimore, and Louise C. Walter, MD, with University of California San Francisco, wrote in an editorial in JAMA Internal Medicine.
Considering LE during screening decision-making is “fundamental to reducing harms of prostate cancer overdiagnosis and overtreatment” because limited LE increases the likelihood of experiencing “harms all along the diagnostic and treatment cascade following screening,” the editorial writers said.
The time spent diagnosing, monitoring, and treating asymptomatic prostate cancer in men with limited LE distracts from monitoring and treating chronic symptomatic life-limiting illnesses, they noted.
Tough to Talk About?
Anderson noted that, in general, doctors are not great at estimating and counseling patients on LE. “It’s sometimes difficult to have that conversation,” he said.
Daskivich said physicians may fail to include average LE when advising patients on treatments because they believe that the patients do not want to discuss this topic. “Yet, in interviews with patients, we found that prostate cancer patients reported they wanted this information,” he continued, in an interview.
Solving the problem of overscreening and overtreatment will require a “multifaceted approach, including improving access to life expectancy data at the point of care for providers, educating providers on how to communicate this information, and improving data sources to predict longevity,” Daskivich said.
He said it’s equally important to note that some men with prostate cancer may choose treatment even if they have a limited longevity.
“Not all patients will choose conservative management, even if it is recommended by guidelines. However, they need to be given the opportunity to make a good decision for themselves with the best possible data,” Daskivich said.
This work was supported in part by a US Department of VA Merit Review. Daskivich reported receiving personal fees from the Medical Education Speakers Network, EDAP, and RAND; research support from Lantheus and Janssen; and a patent pending for a system for healthcare visit quality assessment outside the submitted work. Schoenborn, Walter, and Anderson had no relevant disclosures.
A version of this article first appeared on Medscape.com.
PharmDs, Not MDs, RNs in VA Hiring Freeze Exemption List
The US Department of Veterans Affairs (VA) has outlined > 300,000 exemptions to the federal hiring freeze to fill essential benefits and health positions. The exempted positions are primarily medical support staff. While the exemptions include pharmacists, physicians and nurses were not included. The day after taking office for the second time, President Trump signed an Executive Order implementing a “freeze on the hiring of Federal civilian employees, to be applied throughout the executive branch” but left many of the details to individual agencies.
Set to last 90 days, the hiring freeze forced Federal agencies to develop plans to reduce the size of their workforces through efficiencies and attrition, Trump said. These agencies would also not be able to hire contractors.
Three days later, however, the VA responded “Following successful implementation of President Trump’s federal hiring freeze, the Department of Veterans Affairs announced several exemptions to the policy. These exemptions clarify the department’s ability to continue filling essential positions that provide health care and other vital services to Veterans and VA beneficiaries.”
This allowed > 304,000 jobs to be exempt from the freeze. Almost 92% of the VA’s 450,000 employees work in health care and health administration and support services. Most of the exemptions involve support staff. No physicians, mental health professionals or nursing positions are on the list. However, it does include 12,622 pharmacists and 5,975 pharmacy technicians.
The VA worked in accordance with the White House and Office of Personnel Management to develop the updated guidance, Acting Veterans Affairs Secretary Todd Hunter said. In a Jan. 21 memo, Hunter wrote: "Positions critical to delivering care to veterans in the Veteran[s] Health Administration ... are exempted under the category of public safety.”
According to Hunter's memo, no other vacancies that existed as of midday Monday will be filled. Candidates who received job offers before noon on Jan. 20 and have a start date on or before Feb. 8 will be onboarded, while those with a start date after Feb. 8—or one that is undetermined—will have their offers rescinded.
The first Trump Administration began the same way in 2017, initiating a freeze on Federal hiring and receiving a similar response from the VA. In 2017, the hiring of doctors and nurses continued while that freeze was in effect, but onboarding of new support and administrative staff was not. Then-Secretary of Veterans Affairs Dr. David J. Shulkin said, “VA is committed to serving veterans, but at the same time improving efficiency and reducing bureaucracy.”
The current Executive Order states it “shall not adversely impact veterans’ benefits and does not apply to positions related to public safety” (or military personnel, immigration enforcement, and national security). It also says it does not adversely impact the provision of Social Security, Medicare, or Veterans’ benefits.
“Under President Trump’s leadership, VA will always do what is necessary to provide America’s Veterans with the benefits and services they have earned. The targeted hiring-freeze exemptions announced today underscore that fact,” said VA Director of Media Affairs Morgan Ackley.
Some in Congress feel the VA should be doing more, though, and are pushing for an exemption of all VA employees. On Friday, Senate Veterans’ Affairs Committee Ranking Member Richard Blumenthal (D-CT) released a statement on the exemptions. “The latest Administration hiring freeze announcement still falls short. While I’m encouraged the President responded to our concerns by exempting certain VA personnel, only a clear, unequivocal statement to exempt all VA employees from the hiring freeze will reassure me—and veterans—they will receive the care and benefits they need and deserve. The exemptions listed yesterday provide more questions than answers and fail to include key personnel, including Veterans Benefits Administration employees. The Trump Administration is going to try to confuse the issue with a lot of vague assurances. We need a clear commitment every VA employee is exempt—effective immediately. Moreover, the Trump Administration must address the offers it has already rescinded that are now exempt.”
Blumenthal and 24 Democratic Senators also signed a letter to that effect, stressing concerns about the negative impact the hiring freeze will have on the delivery of veterans’ health care and benefits nationwide “if not quickly reversed.” Blumenthal also pressed Doug Collins (R-GA), Trump’s nominee for VA Secretary, to push back against a hiring freeze at VA, if his nomination is confirmed: “This is going to be a first test of your leadership.”
“We’ll take a look at the current levels of employees that we have and where they’re properly located,” Collins said, adding that he was “still examining” the freeze’s impact on the VA. “We will work under the Executive Order [Trump] has given us.”
Blumenthal argued that the new exemptions exclude a number of critical positions at VA. Among them include all positions at the Veterans Benefits Administration and National Cemetery Administration, which provide veterans’ claims processing, survivor benefits, GI Bill education benefits, and burial scheduling and operations; many nonclinical positions critical to VA hospital functioning, including patient advocates, food service workers, and chaplains; and positions relating to construction project management for new hospitals and clinics, new nursing homes, new cemetery construction, leases, and repairs to existing VA facilities.
The US Department of Veterans Affairs (VA) has outlined > 300,000 exemptions to the federal hiring freeze to fill essential benefits and health positions. The exempted positions are primarily medical support staff. While the exemptions include pharmacists, physicians and nurses were not included. The day after taking office for the second time, President Trump signed an Executive Order implementing a “freeze on the hiring of Federal civilian employees, to be applied throughout the executive branch” but left many of the details to individual agencies.
Set to last 90 days, the hiring freeze forced Federal agencies to develop plans to reduce the size of their workforces through efficiencies and attrition, Trump said. These agencies would also not be able to hire contractors.
Three days later, however, the VA responded “Following successful implementation of President Trump’s federal hiring freeze, the Department of Veterans Affairs announced several exemptions to the policy. These exemptions clarify the department’s ability to continue filling essential positions that provide health care and other vital services to Veterans and VA beneficiaries.”
This allowed > 304,000 jobs to be exempt from the freeze. Almost 92% of the VA’s 450,000 employees work in health care and health administration and support services. Most of the exemptions involve support staff. No physicians, mental health professionals or nursing positions are on the list. However, it does include 12,622 pharmacists and 5,975 pharmacy technicians.
The VA worked in accordance with the White House and Office of Personnel Management to develop the updated guidance, Acting Veterans Affairs Secretary Todd Hunter said. In a Jan. 21 memo, Hunter wrote: "Positions critical to delivering care to veterans in the Veteran[s] Health Administration ... are exempted under the category of public safety.”
According to Hunter's memo, no other vacancies that existed as of midday Monday will be filled. Candidates who received job offers before noon on Jan. 20 and have a start date on or before Feb. 8 will be onboarded, while those with a start date after Feb. 8—or one that is undetermined—will have their offers rescinded.
The first Trump Administration began the same way in 2017, initiating a freeze on Federal hiring and receiving a similar response from the VA. In 2017, the hiring of doctors and nurses continued while that freeze was in effect, but onboarding of new support and administrative staff was not. Then-Secretary of Veterans Affairs Dr. David J. Shulkin said, “VA is committed to serving veterans, but at the same time improving efficiency and reducing bureaucracy.”
The current Executive Order states it “shall not adversely impact veterans’ benefits and does not apply to positions related to public safety” (or military personnel, immigration enforcement, and national security). It also says it does not adversely impact the provision of Social Security, Medicare, or Veterans’ benefits.
“Under President Trump’s leadership, VA will always do what is necessary to provide America’s Veterans with the benefits and services they have earned. The targeted hiring-freeze exemptions announced today underscore that fact,” said VA Director of Media Affairs Morgan Ackley.
Some in Congress feel the VA should be doing more, though, and are pushing for an exemption of all VA employees. On Friday, Senate Veterans’ Affairs Committee Ranking Member Richard Blumenthal (D-CT) released a statement on the exemptions. “The latest Administration hiring freeze announcement still falls short. While I’m encouraged the President responded to our concerns by exempting certain VA personnel, only a clear, unequivocal statement to exempt all VA employees from the hiring freeze will reassure me—and veterans—they will receive the care and benefits they need and deserve. The exemptions listed yesterday provide more questions than answers and fail to include key personnel, including Veterans Benefits Administration employees. The Trump Administration is going to try to confuse the issue with a lot of vague assurances. We need a clear commitment every VA employee is exempt—effective immediately. Moreover, the Trump Administration must address the offers it has already rescinded that are now exempt.”
Blumenthal and 24 Democratic Senators also signed a letter to that effect, stressing concerns about the negative impact the hiring freeze will have on the delivery of veterans’ health care and benefits nationwide “if not quickly reversed.” Blumenthal also pressed Doug Collins (R-GA), Trump’s nominee for VA Secretary, to push back against a hiring freeze at VA, if his nomination is confirmed: “This is going to be a first test of your leadership.”
“We’ll take a look at the current levels of employees that we have and where they’re properly located,” Collins said, adding that he was “still examining” the freeze’s impact on the VA. “We will work under the Executive Order [Trump] has given us.”
Blumenthal argued that the new exemptions exclude a number of critical positions at VA. Among them include all positions at the Veterans Benefits Administration and National Cemetery Administration, which provide veterans’ claims processing, survivor benefits, GI Bill education benefits, and burial scheduling and operations; many nonclinical positions critical to VA hospital functioning, including patient advocates, food service workers, and chaplains; and positions relating to construction project management for new hospitals and clinics, new nursing homes, new cemetery construction, leases, and repairs to existing VA facilities.
The US Department of Veterans Affairs (VA) has outlined > 300,000 exemptions to the federal hiring freeze to fill essential benefits and health positions. The exempted positions are primarily medical support staff. While the exemptions include pharmacists, physicians and nurses were not included. The day after taking office for the second time, President Trump signed an Executive Order implementing a “freeze on the hiring of Federal civilian employees, to be applied throughout the executive branch” but left many of the details to individual agencies.
Set to last 90 days, the hiring freeze forced Federal agencies to develop plans to reduce the size of their workforces through efficiencies and attrition, Trump said. These agencies would also not be able to hire contractors.
Three days later, however, the VA responded “Following successful implementation of President Trump’s federal hiring freeze, the Department of Veterans Affairs announced several exemptions to the policy. These exemptions clarify the department’s ability to continue filling essential positions that provide health care and other vital services to Veterans and VA beneficiaries.”
This allowed > 304,000 jobs to be exempt from the freeze. Almost 92% of the VA’s 450,000 employees work in health care and health administration and support services. Most of the exemptions involve support staff. No physicians, mental health professionals or nursing positions are on the list. However, it does include 12,622 pharmacists and 5,975 pharmacy technicians.
The VA worked in accordance with the White House and Office of Personnel Management to develop the updated guidance, Acting Veterans Affairs Secretary Todd Hunter said. In a Jan. 21 memo, Hunter wrote: "Positions critical to delivering care to veterans in the Veteran[s] Health Administration ... are exempted under the category of public safety.”
According to Hunter's memo, no other vacancies that existed as of midday Monday will be filled. Candidates who received job offers before noon on Jan. 20 and have a start date on or before Feb. 8 will be onboarded, while those with a start date after Feb. 8—or one that is undetermined—will have their offers rescinded.
The first Trump Administration began the same way in 2017, initiating a freeze on Federal hiring and receiving a similar response from the VA. In 2017, the hiring of doctors and nurses continued while that freeze was in effect, but onboarding of new support and administrative staff was not. Then-Secretary of Veterans Affairs Dr. David J. Shulkin said, “VA is committed to serving veterans, but at the same time improving efficiency and reducing bureaucracy.”
The current Executive Order states it “shall not adversely impact veterans’ benefits and does not apply to positions related to public safety” (or military personnel, immigration enforcement, and national security). It also says it does not adversely impact the provision of Social Security, Medicare, or Veterans’ benefits.
“Under President Trump’s leadership, VA will always do what is necessary to provide America’s Veterans with the benefits and services they have earned. The targeted hiring-freeze exemptions announced today underscore that fact,” said VA Director of Media Affairs Morgan Ackley.
Some in Congress feel the VA should be doing more, though, and are pushing for an exemption of all VA employees. On Friday, Senate Veterans’ Affairs Committee Ranking Member Richard Blumenthal (D-CT) released a statement on the exemptions. “The latest Administration hiring freeze announcement still falls short. While I’m encouraged the President responded to our concerns by exempting certain VA personnel, only a clear, unequivocal statement to exempt all VA employees from the hiring freeze will reassure me—and veterans—they will receive the care and benefits they need and deserve. The exemptions listed yesterday provide more questions than answers and fail to include key personnel, including Veterans Benefits Administration employees. The Trump Administration is going to try to confuse the issue with a lot of vague assurances. We need a clear commitment every VA employee is exempt—effective immediately. Moreover, the Trump Administration must address the offers it has already rescinded that are now exempt.”
Blumenthal and 24 Democratic Senators also signed a letter to that effect, stressing concerns about the negative impact the hiring freeze will have on the delivery of veterans’ health care and benefits nationwide “if not quickly reversed.” Blumenthal also pressed Doug Collins (R-GA), Trump’s nominee for VA Secretary, to push back against a hiring freeze at VA, if his nomination is confirmed: “This is going to be a first test of your leadership.”
“We’ll take a look at the current levels of employees that we have and where they’re properly located,” Collins said, adding that he was “still examining” the freeze’s impact on the VA. “We will work under the Executive Order [Trump] has given us.”
Blumenthal argued that the new exemptions exclude a number of critical positions at VA. Among them include all positions at the Veterans Benefits Administration and National Cemetery Administration, which provide veterans’ claims processing, survivor benefits, GI Bill education benefits, and burial scheduling and operations; many nonclinical positions critical to VA hospital functioning, including patient advocates, food service workers, and chaplains; and positions relating to construction project management for new hospitals and clinics, new nursing homes, new cemetery construction, leases, and repairs to existing VA facilities.
Why Overall Survival Should Be The Oncology Trial Endpoint
The use of surrogate endpoints to predict overall survival in oncology trials has been vigorously debated in the oncology community.
In multiple studies, we have shown that the correlation of surrogate endpoints with overall survival has been weak and, in most cases, inadequate. However, others have made arguments against using overall survival as the gold standard endpoint for cancer drug trials. These arguments include claims that overall survival is not a feasible endpoint for pivotal cancer drug trials and that negative overall survival results may be unreliable.
In this column, we counter some of these arguments from the perspective of an oncologist who treats cancer and is engaged in oncology research and a patient advocate with lived experience of cancer.
Argument: Overall survival is not the only meaningful clinical endpoint. Response rates and progression-free survival also are important clinical endpoints because patients feel good when their tumor shrinks or they have more time without disease progression. Both situations can improve patients’ quality of life.
Response: On the face of it, this argument sounds reasonable, but it treats response rates and progression-free survival as clinical endpoints rather than surrogate endpoints that need to be validated. A patient would surely welcome news that treatment has reduced the size of their tumor and would feel dismayed if the tumor is growing. However, these reactions rest on the belief that these changes signal recovery in the case of a shrinking tumor, or worsening symptoms in the case of a growing tumor, neither of which may be true.
“Disease progression” and “progression-free survival” were developed as technical terms to signify whether a therapy in a phase 2 clinical trial was sufficiently promising to advance to phase 3. The terms were not intended to inform clinical practice or establish whether a new therapy provides clinically meaningful benefits for patients. In clinical trials, a progression event is defined as an increase in the sum of tumor diameters by more than 20%, or the appearance of a new lesion. These are both arbitrary benchmarks that in no way imply that a patient’s subjective experience of symptoms or their survival time would differ widely between a tumor growth of 19% vs 21%, or if a new, tiny lesion develops.
Of course, disease progression sometimes does affect a patient’s quality of life, but trials treat all progression events equally. An event in the brain that affects the patient’s ability to walk and an asymptomatic tumor growth in the lung from 1 cm to 1.3 cm are both considered disease progression in trials.
Patients care about progression-free survival because they mistakenly believe that an improvement will probably lead to improved overall survival or quality of life. But overall survival and quality of life can actually be affected detrimentally, despite progression-free survival gains, because the patient may experience treatment-related physical and financial toxicity without clinical benefit. Conversely, it is possible to have better overall survival and quality of life without any improvement in progression-free survival.
With response rates, the relationships to overall survival and quality of life are even weaker. Because progression-free survival and response rates do not represent clinical benefit, they cannot be considered clinical endpoints. They are surrogate endpoints that need to be validated.
A patient will reasonably welcome a treatment-related change that improves the prospect of living a longer life or enduring less suffering but should not be misled when these outcomes have not been demonstrated as being clinically beneficial.
Argument: It is not ethical to wait for overall survival when there is an unmet need.
Response: The phrase “unmet need” is used to represent the lack of effective treatment options for a particular condition. Regulators may expedite approval of a new drug that is intended to fulfil the need because waiting for overall survival may not seem ethical in these settings.
In reality, however, the term is used inconsistently, both when the need is either questionable (the indication is indolent) or the need is real but one or more treatment options already exist.
When the need for a drug with clinical benefit is genuinely unmet, presenting patients with just any drug is unethical; their need will continue to exist despite drug approvals if survival is not improved. In fact, approving ineffective drugs can impede the development of drugs that work.
Argument: Overall survival is not a practical endpoint for drug trials for rare cancers.
Response: This argument has some practical validity because the low prevalence of a rare cancer may limit study recruitment opportunities. From an equity perspective, however, patients with rare cancers are no less deserving of treatments based on meaningful evidence of safety and efficacy than are patients with common cancers. Like any other patient with cancer, they should know those treatments have shown the potential for an overall survival or quality of life benefit before undergoing potentially toxic treatments.
Several trials, such as FIRM-ACT, VIT-0910, AEWS0031, and rEECur, have shown that international collaboration makes randomized clinical trials with an endpoint of overall survival possible for most rare cancers. We support offering early access via accelerated approval when scientific evidence suggests a drug has potential benefit for patients, but the trial should be followed to confirm an overall survival benefit and the drug should be withdrawn if an overall survival benefit is lacking.
Argument: The point of measuring overall survival is to ensure that the treatment does not worsen overall survival.
Response: This argument is frequently made, even by regulators. However, unless a drug is tested in a justified noninferiority design trial where the aim is to determine whether it provides compensatory benefits — easier administration, lower cost, or fewer side effects than the alternative — the goal of new cancer drugs is to improve survival. Merely “not worsening survival” is incongruent with medicine’s fundamental goal of benevolence. All drugs have toxicities, some of which can be fatal. Recommending a treatment with toxicities because it did not worsen survival would harm patients and go against the Hippocratic Oath.
Argument: Overall survival in this trial was negative, but this was probably a false-negative finding. We expect future trials will be positive.
Response: When a drug fails to improve overall survival, some experts will argue that it was a false-negative result and a future trial will be positive. For instance, to explain the negative overall survival findings in a 2020 confirmatory trial, the researchers cited a subgroup analysis in which the drug received accelerated approval based on early exploratory results. However, the subgroup analysis violated the statistical plan and raised the likelihood that the early trial’s favorable outcome was false-positive.
A second trend that increases the likelihood of false-positives is when the same anticancer medications are studied across multiple trials. If we run dozens of trials of the same drug, some of them will eventually be positive by chance alone.
Dismissing a negative overall survival finding as a statistical artifact puts patients at risk because oncologists may continue to use the drug, despite it providing no discernable clinical benefit to patients.
Argument: The overall survival was negative because of crossover so that patients in the control arm received the therapy at progression.
Response: Highly effective drugs will continue to show overall survival gains despite crossover — that is, when patients in the control arm receive the experimental drug at the time of progression.
For example, a trial evaluating the addition of pertuzumab in first-line HER2-positive metastatic breast cancer allowed crossover and still showed a significant overall survival benefit. Another trial evaluating sunitinib vs placebo in advanced gastrointestinal stromal tumors showed a significant overall survival improvement despite 80% of patients in the placebo arm crossing over to sunitinib at progression.
However, in the SONIA trial, receiving cyclin-dependent kinase 4/6 inhibitors as first-line treatment of metastatic hormone receptor–positive breast cancer did not improve survival and added toxicities compared with receipt of the same agents as second-line treatment.
If crossover negates an overall survival benefit, this implies that patients in the experimental arm who received the drug upfront and patients in control arm who get the drug only at progression have no difference in survival times. If the survival outcomes in the groups are similar, that is evidence that the new drug should be given only to those who need treatment at the time of progression and not to everyone upfront.
Giving patients the drug at the time of progression would spare patients toxicities, preserve efficacy, and save health systems costs.
Argument: Although overall survival is negative in the confirmatory trial, the clinical practice guidelines recommend using the drug, and the guidelines should be followed.
Response: We cannot ignore results of a confirmatory trial just because the drug is already in the guidelines. Guidelines should be updated on the basis of the latest evidence, rather than clinical practice being dictated by outdated guidelines. When a drug given accelerated approval appears in the guidelines, the confidence level of the evidence should be rated low until confirmatory results are available. If a confirmatory trial shows that overall survival does not improve, the guidelines should be quickly updated. However, even if they are not, physicians should not just blindly follow the guidelines.
Furthermore, practitioners should be aware that members of oncology guidelines committees often have financial conflicts of interest with pharmaceutical companies, which the literature shows can bias guideline recommendations.
The Bottom Line
We believe that despite arguments put forward against relying on or measuring overall survival, it continues to be the most patient-centric marker of clinical benefit. Patients deserve to know that the cancer drugs their oncologists recommend will contribute to a longer or better life.
Bishal Gyawali, Associate Professor, Department of Oncology and Department of Public Health Sciences; Scientist, Division of Cancer Care and Epidemiology, Queen’s University, Kingston, Ontario, Canada; Affiliated Faculty at the Program on Regulation, Therapeutics, and Law, Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts, has disclosed the financial relationship by receiving consulting fees from Vivio Health. Sharon Batt, Cancer survivor and patient advocate; Adjunct professor, Department of Bioethics and Department of Political Science, Dalhousie University, Halifax, Nova Scotia, Canada, has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The use of surrogate endpoints to predict overall survival in oncology trials has been vigorously debated in the oncology community.
In multiple studies, we have shown that the correlation of surrogate endpoints with overall survival has been weak and, in most cases, inadequate. However, others have made arguments against using overall survival as the gold standard endpoint for cancer drug trials. These arguments include claims that overall survival is not a feasible endpoint for pivotal cancer drug trials and that negative overall survival results may be unreliable.
In this column, we counter some of these arguments from the perspective of an oncologist who treats cancer and is engaged in oncology research and a patient advocate with lived experience of cancer.
Argument: Overall survival is not the only meaningful clinical endpoint. Response rates and progression-free survival also are important clinical endpoints because patients feel good when their tumor shrinks or they have more time without disease progression. Both situations can improve patients’ quality of life.
Response: On the face of it, this argument sounds reasonable, but it treats response rates and progression-free survival as clinical endpoints rather than surrogate endpoints that need to be validated. A patient would surely welcome news that treatment has reduced the size of their tumor and would feel dismayed if the tumor is growing. However, these reactions rest on the belief that these changes signal recovery in the case of a shrinking tumor, or worsening symptoms in the case of a growing tumor, neither of which may be true.
“Disease progression” and “progression-free survival” were developed as technical terms to signify whether a therapy in a phase 2 clinical trial was sufficiently promising to advance to phase 3. The terms were not intended to inform clinical practice or establish whether a new therapy provides clinically meaningful benefits for patients. In clinical trials, a progression event is defined as an increase in the sum of tumor diameters by more than 20%, or the appearance of a new lesion. These are both arbitrary benchmarks that in no way imply that a patient’s subjective experience of symptoms or their survival time would differ widely between a tumor growth of 19% vs 21%, or if a new, tiny lesion develops.
Of course, disease progression sometimes does affect a patient’s quality of life, but trials treat all progression events equally. An event in the brain that affects the patient’s ability to walk and an asymptomatic tumor growth in the lung from 1 cm to 1.3 cm are both considered disease progression in trials.
Patients care about progression-free survival because they mistakenly believe that an improvement will probably lead to improved overall survival or quality of life. But overall survival and quality of life can actually be affected detrimentally, despite progression-free survival gains, because the patient may experience treatment-related physical and financial toxicity without clinical benefit. Conversely, it is possible to have better overall survival and quality of life without any improvement in progression-free survival.
With response rates, the relationships to overall survival and quality of life are even weaker. Because progression-free survival and response rates do not represent clinical benefit, they cannot be considered clinical endpoints. They are surrogate endpoints that need to be validated.
A patient will reasonably welcome a treatment-related change that improves the prospect of living a longer life or enduring less suffering but should not be misled when these outcomes have not been demonstrated as being clinically beneficial.
Argument: It is not ethical to wait for overall survival when there is an unmet need.
Response: The phrase “unmet need” is used to represent the lack of effective treatment options for a particular condition. Regulators may expedite approval of a new drug that is intended to fulfil the need because waiting for overall survival may not seem ethical in these settings.
In reality, however, the term is used inconsistently, both when the need is either questionable (the indication is indolent) or the need is real but one or more treatment options already exist.
When the need for a drug with clinical benefit is genuinely unmet, presenting patients with just any drug is unethical; their need will continue to exist despite drug approvals if survival is not improved. In fact, approving ineffective drugs can impede the development of drugs that work.
Argument: Overall survival is not a practical endpoint for drug trials for rare cancers.
Response: This argument has some practical validity because the low prevalence of a rare cancer may limit study recruitment opportunities. From an equity perspective, however, patients with rare cancers are no less deserving of treatments based on meaningful evidence of safety and efficacy than are patients with common cancers. Like any other patient with cancer, they should know those treatments have shown the potential for an overall survival or quality of life benefit before undergoing potentially toxic treatments.
Several trials, such as FIRM-ACT, VIT-0910, AEWS0031, and rEECur, have shown that international collaboration makes randomized clinical trials with an endpoint of overall survival possible for most rare cancers. We support offering early access via accelerated approval when scientific evidence suggests a drug has potential benefit for patients, but the trial should be followed to confirm an overall survival benefit and the drug should be withdrawn if an overall survival benefit is lacking.
Argument: The point of measuring overall survival is to ensure that the treatment does not worsen overall survival.
Response: This argument is frequently made, even by regulators. However, unless a drug is tested in a justified noninferiority design trial where the aim is to determine whether it provides compensatory benefits — easier administration, lower cost, or fewer side effects than the alternative — the goal of new cancer drugs is to improve survival. Merely “not worsening survival” is incongruent with medicine’s fundamental goal of benevolence. All drugs have toxicities, some of which can be fatal. Recommending a treatment with toxicities because it did not worsen survival would harm patients and go against the Hippocratic Oath.
Argument: Overall survival in this trial was negative, but this was probably a false-negative finding. We expect future trials will be positive.
Response: When a drug fails to improve overall survival, some experts will argue that it was a false-negative result and a future trial will be positive. For instance, to explain the negative overall survival findings in a 2020 confirmatory trial, the researchers cited a subgroup analysis in which the drug received accelerated approval based on early exploratory results. However, the subgroup analysis violated the statistical plan and raised the likelihood that the early trial’s favorable outcome was false-positive.
A second trend that increases the likelihood of false-positives is when the same anticancer medications are studied across multiple trials. If we run dozens of trials of the same drug, some of them will eventually be positive by chance alone.
Dismissing a negative overall survival finding as a statistical artifact puts patients at risk because oncologists may continue to use the drug, despite it providing no discernable clinical benefit to patients.
Argument: The overall survival was negative because of crossover so that patients in the control arm received the therapy at progression.
Response: Highly effective drugs will continue to show overall survival gains despite crossover — that is, when patients in the control arm receive the experimental drug at the time of progression.
For example, a trial evaluating the addition of pertuzumab in first-line HER2-positive metastatic breast cancer allowed crossover and still showed a significant overall survival benefit. Another trial evaluating sunitinib vs placebo in advanced gastrointestinal stromal tumors showed a significant overall survival improvement despite 80% of patients in the placebo arm crossing over to sunitinib at progression.
However, in the SONIA trial, receiving cyclin-dependent kinase 4/6 inhibitors as first-line treatment of metastatic hormone receptor–positive breast cancer did not improve survival and added toxicities compared with receipt of the same agents as second-line treatment.
If crossover negates an overall survival benefit, this implies that patients in the experimental arm who received the drug upfront and patients in control arm who get the drug only at progression have no difference in survival times. If the survival outcomes in the groups are similar, that is evidence that the new drug should be given only to those who need treatment at the time of progression and not to everyone upfront.
Giving patients the drug at the time of progression would spare patients toxicities, preserve efficacy, and save health systems costs.
Argument: Although overall survival is negative in the confirmatory trial, the clinical practice guidelines recommend using the drug, and the guidelines should be followed.
Response: We cannot ignore results of a confirmatory trial just because the drug is already in the guidelines. Guidelines should be updated on the basis of the latest evidence, rather than clinical practice being dictated by outdated guidelines. When a drug given accelerated approval appears in the guidelines, the confidence level of the evidence should be rated low until confirmatory results are available. If a confirmatory trial shows that overall survival does not improve, the guidelines should be quickly updated. However, even if they are not, physicians should not just blindly follow the guidelines.
Furthermore, practitioners should be aware that members of oncology guidelines committees often have financial conflicts of interest with pharmaceutical companies, which the literature shows can bias guideline recommendations.
The Bottom Line
We believe that despite arguments put forward against relying on or measuring overall survival, it continues to be the most patient-centric marker of clinical benefit. Patients deserve to know that the cancer drugs their oncologists recommend will contribute to a longer or better life.
Bishal Gyawali, Associate Professor, Department of Oncology and Department of Public Health Sciences; Scientist, Division of Cancer Care and Epidemiology, Queen’s University, Kingston, Ontario, Canada; Affiliated Faculty at the Program on Regulation, Therapeutics, and Law, Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts, has disclosed the financial relationship by receiving consulting fees from Vivio Health. Sharon Batt, Cancer survivor and patient advocate; Adjunct professor, Department of Bioethics and Department of Political Science, Dalhousie University, Halifax, Nova Scotia, Canada, has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The use of surrogate endpoints to predict overall survival in oncology trials has been vigorously debated in the oncology community.
In multiple studies, we have shown that the correlation of surrogate endpoints with overall survival has been weak and, in most cases, inadequate. However, others have made arguments against using overall survival as the gold standard endpoint for cancer drug trials. These arguments include claims that overall survival is not a feasible endpoint for pivotal cancer drug trials and that negative overall survival results may be unreliable.
In this column, we counter some of these arguments from the perspective of an oncologist who treats cancer and is engaged in oncology research and a patient advocate with lived experience of cancer.
Argument: Overall survival is not the only meaningful clinical endpoint. Response rates and progression-free survival also are important clinical endpoints because patients feel good when their tumor shrinks or they have more time without disease progression. Both situations can improve patients’ quality of life.
Response: On the face of it, this argument sounds reasonable, but it treats response rates and progression-free survival as clinical endpoints rather than surrogate endpoints that need to be validated. A patient would surely welcome news that treatment has reduced the size of their tumor and would feel dismayed if the tumor is growing. However, these reactions rest on the belief that these changes signal recovery in the case of a shrinking tumor, or worsening symptoms in the case of a growing tumor, neither of which may be true.
“Disease progression” and “progression-free survival” were developed as technical terms to signify whether a therapy in a phase 2 clinical trial was sufficiently promising to advance to phase 3. The terms were not intended to inform clinical practice or establish whether a new therapy provides clinically meaningful benefits for patients. In clinical trials, a progression event is defined as an increase in the sum of tumor diameters by more than 20%, or the appearance of a new lesion. These are both arbitrary benchmarks that in no way imply that a patient’s subjective experience of symptoms or their survival time would differ widely between a tumor growth of 19% vs 21%, or if a new, tiny lesion develops.
Of course, disease progression sometimes does affect a patient’s quality of life, but trials treat all progression events equally. An event in the brain that affects the patient’s ability to walk and an asymptomatic tumor growth in the lung from 1 cm to 1.3 cm are both considered disease progression in trials.
Patients care about progression-free survival because they mistakenly believe that an improvement will probably lead to improved overall survival or quality of life. But overall survival and quality of life can actually be affected detrimentally, despite progression-free survival gains, because the patient may experience treatment-related physical and financial toxicity without clinical benefit. Conversely, it is possible to have better overall survival and quality of life without any improvement in progression-free survival.
With response rates, the relationships to overall survival and quality of life are even weaker. Because progression-free survival and response rates do not represent clinical benefit, they cannot be considered clinical endpoints. They are surrogate endpoints that need to be validated.
A patient will reasonably welcome a treatment-related change that improves the prospect of living a longer life or enduring less suffering but should not be misled when these outcomes have not been demonstrated as being clinically beneficial.
Argument: It is not ethical to wait for overall survival when there is an unmet need.
Response: The phrase “unmet need” is used to represent the lack of effective treatment options for a particular condition. Regulators may expedite approval of a new drug that is intended to fulfil the need because waiting for overall survival may not seem ethical in these settings.
In reality, however, the term is used inconsistently, both when the need is either questionable (the indication is indolent) or the need is real but one or more treatment options already exist.
When the need for a drug with clinical benefit is genuinely unmet, presenting patients with just any drug is unethical; their need will continue to exist despite drug approvals if survival is not improved. In fact, approving ineffective drugs can impede the development of drugs that work.
Argument: Overall survival is not a practical endpoint for drug trials for rare cancers.
Response: This argument has some practical validity because the low prevalence of a rare cancer may limit study recruitment opportunities. From an equity perspective, however, patients with rare cancers are no less deserving of treatments based on meaningful evidence of safety and efficacy than are patients with common cancers. Like any other patient with cancer, they should know those treatments have shown the potential for an overall survival or quality of life benefit before undergoing potentially toxic treatments.
Several trials, such as FIRM-ACT, VIT-0910, AEWS0031, and rEECur, have shown that international collaboration makes randomized clinical trials with an endpoint of overall survival possible for most rare cancers. We support offering early access via accelerated approval when scientific evidence suggests a drug has potential benefit for patients, but the trial should be followed to confirm an overall survival benefit and the drug should be withdrawn if an overall survival benefit is lacking.
Argument: The point of measuring overall survival is to ensure that the treatment does not worsen overall survival.
Response: This argument is frequently made, even by regulators. However, unless a drug is tested in a justified noninferiority design trial where the aim is to determine whether it provides compensatory benefits — easier administration, lower cost, or fewer side effects than the alternative — the goal of new cancer drugs is to improve survival. Merely “not worsening survival” is incongruent with medicine’s fundamental goal of benevolence. All drugs have toxicities, some of which can be fatal. Recommending a treatment with toxicities because it did not worsen survival would harm patients and go against the Hippocratic Oath.
Argument: Overall survival in this trial was negative, but this was probably a false-negative finding. We expect future trials will be positive.
Response: When a drug fails to improve overall survival, some experts will argue that it was a false-negative result and a future trial will be positive. For instance, to explain the negative overall survival findings in a 2020 confirmatory trial, the researchers cited a subgroup analysis in which the drug received accelerated approval based on early exploratory results. However, the subgroup analysis violated the statistical plan and raised the likelihood that the early trial’s favorable outcome was false-positive.
A second trend that increases the likelihood of false-positives is when the same anticancer medications are studied across multiple trials. If we run dozens of trials of the same drug, some of them will eventually be positive by chance alone.
Dismissing a negative overall survival finding as a statistical artifact puts patients at risk because oncologists may continue to use the drug, despite it providing no discernable clinical benefit to patients.
Argument: The overall survival was negative because of crossover so that patients in the control arm received the therapy at progression.
Response: Highly effective drugs will continue to show overall survival gains despite crossover — that is, when patients in the control arm receive the experimental drug at the time of progression.
For example, a trial evaluating the addition of pertuzumab in first-line HER2-positive metastatic breast cancer allowed crossover and still showed a significant overall survival benefit. Another trial evaluating sunitinib vs placebo in advanced gastrointestinal stromal tumors showed a significant overall survival improvement despite 80% of patients in the placebo arm crossing over to sunitinib at progression.
However, in the SONIA trial, receiving cyclin-dependent kinase 4/6 inhibitors as first-line treatment of metastatic hormone receptor–positive breast cancer did not improve survival and added toxicities compared with receipt of the same agents as second-line treatment.
If crossover negates an overall survival benefit, this implies that patients in the experimental arm who received the drug upfront and patients in control arm who get the drug only at progression have no difference in survival times. If the survival outcomes in the groups are similar, that is evidence that the new drug should be given only to those who need treatment at the time of progression and not to everyone upfront.
Giving patients the drug at the time of progression would spare patients toxicities, preserve efficacy, and save health systems costs.
Argument: Although overall survival is negative in the confirmatory trial, the clinical practice guidelines recommend using the drug, and the guidelines should be followed.
Response: We cannot ignore results of a confirmatory trial just because the drug is already in the guidelines. Guidelines should be updated on the basis of the latest evidence, rather than clinical practice being dictated by outdated guidelines. When a drug given accelerated approval appears in the guidelines, the confidence level of the evidence should be rated low until confirmatory results are available. If a confirmatory trial shows that overall survival does not improve, the guidelines should be quickly updated. However, even if they are not, physicians should not just blindly follow the guidelines.
Furthermore, practitioners should be aware that members of oncology guidelines committees often have financial conflicts of interest with pharmaceutical companies, which the literature shows can bias guideline recommendations.
The Bottom Line
We believe that despite arguments put forward against relying on or measuring overall survival, it continues to be the most patient-centric marker of clinical benefit. Patients deserve to know that the cancer drugs their oncologists recommend will contribute to a longer or better life.
Bishal Gyawali, Associate Professor, Department of Oncology and Department of Public Health Sciences; Scientist, Division of Cancer Care and Epidemiology, Queen’s University, Kingston, Ontario, Canada; Affiliated Faculty at the Program on Regulation, Therapeutics, and Law, Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts, has disclosed the financial relationship by receiving consulting fees from Vivio Health. Sharon Batt, Cancer survivor and patient advocate; Adjunct professor, Department of Bioethics and Department of Political Science, Dalhousie University, Halifax, Nova Scotia, Canada, has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Quality, Not Type, of Diet Linked to Microbiome Health
new research suggested.
For example, red meat was a strong driver of omnivore microbiomes, with corresponding signature microbes that are negatively correlated with host cardiometabolic health.
In contrast, the signature microbes found in vegans’ gut microbiomes were correlated with favorable cardiometabolic markers and were enriched in omnivores who ate more plant-based foods.
“From the viewpoint of the impact of diet on the gut microbiome, what seems to be more important is the diversity of healthy plant-based foods that are consumed,” principal author Nicola Segata, PhD, University of Trento in Italy, said in an interview. “Whether this comes within a vegan or an omnivore diet is less crucial, as long as there is no specific overconsumption of unhealthy food categories, such as red meat.”
Excluding broad categories of foods also can have consequences, he added. “For example, we saw that the exclusion of dairy fermented foods is associated with decreased presence of potentially probiotic microbes that are constitutive of such foods. Avoiding meat or dairy products does not necessarily have a positive effect if it does not come with a variety of quality plant-based products.”
The study was published online in Nature Microbiology.
Diet Tied to Microbial Signature
The researchers analyzed biological samples from 21,561 individuals across five multi-national cohorts to map how differences in diet patterns (omnivore, vegetarian, and vegan) are reflected in gut microbiomes.
They found that the three diet patterns are highly distinguishable by their microbial profiles and that each diet has corresponding unique signature microbes, including those tied to digestion of specific types of food and sometimes those derived from food itself.
The microbiomes of omnivores had an increased presence of bacteria associated with meat digestion, such as Alistipes putredinis, which is involved in protein fermentation. Omnivores also had more bacteria associated with both inflammatory bowel disease and increased colon cancer risk, such as Ruminococcus torques and Bilophila wadsworthia.
The microbiomes of vegans had an abundance of bacteria involved in fiber fermentation, such as several species of Bacteroides and Firmicutes phyla, which help produce short-chain fatty acids. These compounds have beneficial effects on gut health by reducing inflammation and helping to maintain a better homeostatic balance between an individual’s metabolism and immune system.
The main difference between vegetarians and vegans was the presence in vegetarians’ microbiomes of Streptococcus thermophilus, a bacterium found mainly in dairy products and used in the production of yogurt.
Dietary factors within each diet pattern, such as the amount of plant-based food, shape the microbiome more than the type of diet and are important for gut health, according to the authors. For example, by eating more plant-based foods, people with an omnivorous diet can bring the proportion of beneficial signature microbes in their microbiomes more in line with the levels in people who are vegan or vegetarian.
“Since our data showed that omnivores on average ingest significantly fewer healthy plant-based foods than vegetarians or vegans, optimizing the quality of omnivore diets by increasing dietary plant diversity could lead to better gut health,” they wrote.
The ultimate goal, Segata said, is “a precision nutrition approach that recommends foods based on the configuration of the microbiome of patients and of the aspects of the microbiome one wants to enhance. We are not there yet, but it is nonetheless important to know which foods are usually boosting which types of members of the gut microbiome.”
His team is currently analyzing changes in the gut microbiome induced by diet changes among thousands of participants in various cohorts.
“This is one of the next steps toward unraveling causality along the diet-microbiome-health axis, together with the cultivation of specific microbiome members of interest for potential prebiotic and probiotic strategies,” he said.
Conventional Dietary Advice for Now
The findings are consistent with those of previous studies, Jack Gilbert, MD, director of the Microbiome and Metagenomics Center at the University of California, San Diego, and president of Applied Microbiology International, Cambridge, England, said in an interview.
“Future research needs to focus on whether the gut microbial signature can predict those that develop cardiovascular disease in each cohort — ie, the n-of-1 studies, whereby a vegan develops cardiovascular disease, or a carnivore does not,” said Gilbert, who was not involved in the study.
With more data, he said, “we can also start examining these trends over time to understand what might be going on with these ‘oddballs.’ ”
“There is not much you can do with the ‘eat a healthy balanced diet’ routine,” he noted. “If I got a microbiome signature, I could potentially tell you what to eat to optimize your blood glucose trends and your lipid panels but not to handle long-term disease risk, yet. So sticking with the guideline-recommended dietary advice seems best, until we can provide more nuanced advice for the patient.
“Importantly, I would also like to see time-resolved data,” he added. “Signatures can fluctuate over time, even over days, and so collecting a few weeks of stool samples would help us to better align the microbiome signatures to clinical endpoints.”
Segata is a consultant to and receives options from ZOE. Gilbert is a member of the scientific advisory boards of Holobiome, BiomeSense, EcoBiomics Canadian Research Program, MASTER EU, Sun Genomics, and Oath; the editorial advisory board for The Scientist; and the external advisory board for the Binational Early Asthma & Microbiome Study. He is also an adviser for Bened Life.
A version of this article appeared on Medscape.com.
new research suggested.
For example, red meat was a strong driver of omnivore microbiomes, with corresponding signature microbes that are negatively correlated with host cardiometabolic health.
In contrast, the signature microbes found in vegans’ gut microbiomes were correlated with favorable cardiometabolic markers and were enriched in omnivores who ate more plant-based foods.
“From the viewpoint of the impact of diet on the gut microbiome, what seems to be more important is the diversity of healthy plant-based foods that are consumed,” principal author Nicola Segata, PhD, University of Trento in Italy, said in an interview. “Whether this comes within a vegan or an omnivore diet is less crucial, as long as there is no specific overconsumption of unhealthy food categories, such as red meat.”
Excluding broad categories of foods also can have consequences, he added. “For example, we saw that the exclusion of dairy fermented foods is associated with decreased presence of potentially probiotic microbes that are constitutive of such foods. Avoiding meat or dairy products does not necessarily have a positive effect if it does not come with a variety of quality plant-based products.”
The study was published online in Nature Microbiology.
Diet Tied to Microbial Signature
The researchers analyzed biological samples from 21,561 individuals across five multi-national cohorts to map how differences in diet patterns (omnivore, vegetarian, and vegan) are reflected in gut microbiomes.
They found that the three diet patterns are highly distinguishable by their microbial profiles and that each diet has corresponding unique signature microbes, including those tied to digestion of specific types of food and sometimes those derived from food itself.
The microbiomes of omnivores had an increased presence of bacteria associated with meat digestion, such as Alistipes putredinis, which is involved in protein fermentation. Omnivores also had more bacteria associated with both inflammatory bowel disease and increased colon cancer risk, such as Ruminococcus torques and Bilophila wadsworthia.
The microbiomes of vegans had an abundance of bacteria involved in fiber fermentation, such as several species of Bacteroides and Firmicutes phyla, which help produce short-chain fatty acids. These compounds have beneficial effects on gut health by reducing inflammation and helping to maintain a better homeostatic balance between an individual’s metabolism and immune system.
The main difference between vegetarians and vegans was the presence in vegetarians’ microbiomes of Streptococcus thermophilus, a bacterium found mainly in dairy products and used in the production of yogurt.
Dietary factors within each diet pattern, such as the amount of plant-based food, shape the microbiome more than the type of diet and are important for gut health, according to the authors. For example, by eating more plant-based foods, people with an omnivorous diet can bring the proportion of beneficial signature microbes in their microbiomes more in line with the levels in people who are vegan or vegetarian.
“Since our data showed that omnivores on average ingest significantly fewer healthy plant-based foods than vegetarians or vegans, optimizing the quality of omnivore diets by increasing dietary plant diversity could lead to better gut health,” they wrote.
The ultimate goal, Segata said, is “a precision nutrition approach that recommends foods based on the configuration of the microbiome of patients and of the aspects of the microbiome one wants to enhance. We are not there yet, but it is nonetheless important to know which foods are usually boosting which types of members of the gut microbiome.”
His team is currently analyzing changes in the gut microbiome induced by diet changes among thousands of participants in various cohorts.
“This is one of the next steps toward unraveling causality along the diet-microbiome-health axis, together with the cultivation of specific microbiome members of interest for potential prebiotic and probiotic strategies,” he said.
Conventional Dietary Advice for Now
The findings are consistent with those of previous studies, Jack Gilbert, MD, director of the Microbiome and Metagenomics Center at the University of California, San Diego, and president of Applied Microbiology International, Cambridge, England, said in an interview.
“Future research needs to focus on whether the gut microbial signature can predict those that develop cardiovascular disease in each cohort — ie, the n-of-1 studies, whereby a vegan develops cardiovascular disease, or a carnivore does not,” said Gilbert, who was not involved in the study.
With more data, he said, “we can also start examining these trends over time to understand what might be going on with these ‘oddballs.’ ”
“There is not much you can do with the ‘eat a healthy balanced diet’ routine,” he noted. “If I got a microbiome signature, I could potentially tell you what to eat to optimize your blood glucose trends and your lipid panels but not to handle long-term disease risk, yet. So sticking with the guideline-recommended dietary advice seems best, until we can provide more nuanced advice for the patient.
“Importantly, I would also like to see time-resolved data,” he added. “Signatures can fluctuate over time, even over days, and so collecting a few weeks of stool samples would help us to better align the microbiome signatures to clinical endpoints.”
Segata is a consultant to and receives options from ZOE. Gilbert is a member of the scientific advisory boards of Holobiome, BiomeSense, EcoBiomics Canadian Research Program, MASTER EU, Sun Genomics, and Oath; the editorial advisory board for The Scientist; and the external advisory board for the Binational Early Asthma & Microbiome Study. He is also an adviser for Bened Life.
A version of this article appeared on Medscape.com.
new research suggested.
For example, red meat was a strong driver of omnivore microbiomes, with corresponding signature microbes that are negatively correlated with host cardiometabolic health.
In contrast, the signature microbes found in vegans’ gut microbiomes were correlated with favorable cardiometabolic markers and were enriched in omnivores who ate more plant-based foods.
“From the viewpoint of the impact of diet on the gut microbiome, what seems to be more important is the diversity of healthy plant-based foods that are consumed,” principal author Nicola Segata, PhD, University of Trento in Italy, said in an interview. “Whether this comes within a vegan or an omnivore diet is less crucial, as long as there is no specific overconsumption of unhealthy food categories, such as red meat.”
Excluding broad categories of foods also can have consequences, he added. “For example, we saw that the exclusion of dairy fermented foods is associated with decreased presence of potentially probiotic microbes that are constitutive of such foods. Avoiding meat or dairy products does not necessarily have a positive effect if it does not come with a variety of quality plant-based products.”
The study was published online in Nature Microbiology.
Diet Tied to Microbial Signature
The researchers analyzed biological samples from 21,561 individuals across five multi-national cohorts to map how differences in diet patterns (omnivore, vegetarian, and vegan) are reflected in gut microbiomes.
They found that the three diet patterns are highly distinguishable by their microbial profiles and that each diet has corresponding unique signature microbes, including those tied to digestion of specific types of food and sometimes those derived from food itself.
The microbiomes of omnivores had an increased presence of bacteria associated with meat digestion, such as Alistipes putredinis, which is involved in protein fermentation. Omnivores also had more bacteria associated with both inflammatory bowel disease and increased colon cancer risk, such as Ruminococcus torques and Bilophila wadsworthia.
The microbiomes of vegans had an abundance of bacteria involved in fiber fermentation, such as several species of Bacteroides and Firmicutes phyla, which help produce short-chain fatty acids. These compounds have beneficial effects on gut health by reducing inflammation and helping to maintain a better homeostatic balance between an individual’s metabolism and immune system.
The main difference between vegetarians and vegans was the presence in vegetarians’ microbiomes of Streptococcus thermophilus, a bacterium found mainly in dairy products and used in the production of yogurt.
Dietary factors within each diet pattern, such as the amount of plant-based food, shape the microbiome more than the type of diet and are important for gut health, according to the authors. For example, by eating more plant-based foods, people with an omnivorous diet can bring the proportion of beneficial signature microbes in their microbiomes more in line with the levels in people who are vegan or vegetarian.
“Since our data showed that omnivores on average ingest significantly fewer healthy plant-based foods than vegetarians or vegans, optimizing the quality of omnivore diets by increasing dietary plant diversity could lead to better gut health,” they wrote.
The ultimate goal, Segata said, is “a precision nutrition approach that recommends foods based on the configuration of the microbiome of patients and of the aspects of the microbiome one wants to enhance. We are not there yet, but it is nonetheless important to know which foods are usually boosting which types of members of the gut microbiome.”
His team is currently analyzing changes in the gut microbiome induced by diet changes among thousands of participants in various cohorts.
“This is one of the next steps toward unraveling causality along the diet-microbiome-health axis, together with the cultivation of specific microbiome members of interest for potential prebiotic and probiotic strategies,” he said.
Conventional Dietary Advice for Now
The findings are consistent with those of previous studies, Jack Gilbert, MD, director of the Microbiome and Metagenomics Center at the University of California, San Diego, and president of Applied Microbiology International, Cambridge, England, said in an interview.
“Future research needs to focus on whether the gut microbial signature can predict those that develop cardiovascular disease in each cohort — ie, the n-of-1 studies, whereby a vegan develops cardiovascular disease, or a carnivore does not,” said Gilbert, who was not involved in the study.
With more data, he said, “we can also start examining these trends over time to understand what might be going on with these ‘oddballs.’ ”
“There is not much you can do with the ‘eat a healthy balanced diet’ routine,” he noted. “If I got a microbiome signature, I could potentially tell you what to eat to optimize your blood glucose trends and your lipid panels but not to handle long-term disease risk, yet. So sticking with the guideline-recommended dietary advice seems best, until we can provide more nuanced advice for the patient.
“Importantly, I would also like to see time-resolved data,” he added. “Signatures can fluctuate over time, even over days, and so collecting a few weeks of stool samples would help us to better align the microbiome signatures to clinical endpoints.”
Segata is a consultant to and receives options from ZOE. Gilbert is a member of the scientific advisory boards of Holobiome, BiomeSense, EcoBiomics Canadian Research Program, MASTER EU, Sun Genomics, and Oath; the editorial advisory board for The Scientist; and the external advisory board for the Binational Early Asthma & Microbiome Study. He is also an adviser for Bened Life.
A version of this article appeared on Medscape.com.
FROM NATURE MICROBIOLOGY