AVAHO

Purpose

To compare vial utilization and spending between fixed and weight-based dosing of pembrolizumab in Veterans. Promote and assess pembrolizumab extended interval dosing.

Background

FDA approved pembrolizumab label change from weight-based to fixed dosing without evidence of fixed-dosing’s superiority. Retrospective studies demonstrate equivalent outcomes for 2 mg/kg every 3 weeks (Q3W), 200 mg Q3W, 4 mg/kg every 6 weeks (Q6W), and 400 mg Q6W.

Methods

In July 2024 VAAAHS (VA Ann Arbor Healthcare System) initiated an immunotherapy stewardship quality improvement program to deprescribe unnecessary pembrolizumab units and promote extended-interval dosing. Specific interventions included order template modification and targeted outreach to key stakeholders.

Data Analysis

All pembrolizumab doses administered at VAAAHS between July 1, 2024 (launch) and March 31, 2025 (data cutoff) were extracted from EHR. Drug utilization, spending, and healthcare contact hours averted were compared to a fixed-dosing counterfactual.

Results

Sixty-three Veterans received 286 total pembrolizumab doses, of which 107 (37.4%) were Q6W and 179 (62.6%) were Q3W. In total, 741 vials were utilized, against expectation of 786 (5.7% reduction), reflecting approximately $182,000 in savings (annualized, $243,000) and 86.5% of the theoretical maximum savings were captured. Q6W’s share of all doses rose from 27.3% in July 2024 to 53.8% in March 2025. Amongst monotherapy, Q6W’s share rose from 60.0% in July 2024 to 86.7% in March 2025. Q6W adoption saved 381 Veteran-healthcare contact hours, not including travel time.

Conclusions

Stewardship efforts reduced unnecessary pembrolizumab utilization and spending while saving Veterans and VAAAHS providers’ time. Continued provider reinforcement, preparation for Oracle/ Cerner implementation, VISN expansion, refinement of pembrolizumab dose-banding, and development of dose bands for other immunotherapies are underway.

Significance

National implementation would improve Veteran convenience and quality of life, enable reductions in drug and resource costs, and enhance clinic throughput.

Purpose

To compare vial utilization and spending between fixed and weight-based dosing of pembrolizumab in Veterans. Promote and assess pembrolizumab extended interval dosing.

Background

FDA approved pembrolizumab label change from weight-based to fixed dosing without evidence of fixed-dosing’s superiority. Retrospective studies demonstrate equivalent outcomes for 2 mg/kg every 3 weeks (Q3W), 200 mg Q3W, 4 mg/kg every 6 weeks (Q6W), and 400 mg Q6W.

Methods

In July 2024 VAAAHS (VA Ann Arbor Healthcare System) initiated an immunotherapy stewardship quality improvement program to deprescribe unnecessary pembrolizumab units and promote extended-interval dosing. Specific interventions included order template modification and targeted outreach to key stakeholders.

Data Analysis

All pembrolizumab doses administered at VAAAHS between July 1, 2024 (launch) and March 31, 2025 (data cutoff) were extracted from EHR. Drug utilization, spending, and healthcare contact hours averted were compared to a fixed-dosing counterfactual.

Results

Sixty-three Veterans received 286 total pembrolizumab doses, of which 107 (37.4%) were Q6W and 179 (62.6%) were Q3W. In total, 741 vials were utilized, against expectation of 786 (5.7% reduction), reflecting approximately $182,000 in savings (annualized, $243,000) and 86.5% of the theoretical maximum savings were captured. Q6W’s share of all doses rose from 27.3% in July 2024 to 53.8% in March 2025. Amongst monotherapy, Q6W’s share rose from 60.0% in July 2024 to 86.7% in March 2025. Q6W adoption saved 381 Veteran-healthcare contact hours, not including travel time.

Conclusions

Stewardship efforts reduced unnecessary pembrolizumab utilization and spending while saving Veterans and VAAAHS providers’ time. Continued provider reinforcement, preparation for Oracle/ Cerner implementation, VISN expansion, refinement of pembrolizumab dose-banding, and development of dose bands for other immunotherapies are underway.

Significance

National implementation would improve Veteran convenience and quality of life, enable reductions in drug and resource costs, and enhance clinic throughput.

Purpose

To compare vial utilization and spending between fixed and weight-based dosing of pembrolizumab in Veterans. Promote and assess pembrolizumab extended interval dosing.

Background

FDA approved pembrolizumab label change from weight-based to fixed dosing without evidence of fixed-dosing’s superiority. Retrospective studies demonstrate equivalent outcomes for 2 mg/kg every 3 weeks (Q3W), 200 mg Q3W, 4 mg/kg every 6 weeks (Q6W), and 400 mg Q6W.

Methods

In July 2024 VAAAHS (VA Ann Arbor Healthcare System) initiated an immunotherapy stewardship quality improvement program to deprescribe unnecessary pembrolizumab units and promote extended-interval dosing. Specific interventions included order template modification and targeted outreach to key stakeholders.

Data Analysis

All pembrolizumab doses administered at VAAAHS between July 1, 2024 (launch) and March 31, 2025 (data cutoff) were extracted from EHR. Drug utilization, spending, and healthcare contact hours averted were compared to a fixed-dosing counterfactual.

Results

Sixty-three Veterans received 286 total pembrolizumab doses, of which 107 (37.4%) were Q6W and 179 (62.6%) were Q3W. In total, 741 vials were utilized, against expectation of 786 (5.7% reduction), reflecting approximately $182,000 in savings (annualized, $243,000) and 86.5% of the theoretical maximum savings were captured. Q6W’s share of all doses rose from 27.3% in July 2024 to 53.8% in March 2025. Amongst monotherapy, Q6W’s share rose from 60.0% in July 2024 to 86.7% in March 2025. Q6W adoption saved 381 Veteran-healthcare contact hours, not including travel time.

Conclusions

Stewardship efforts reduced unnecessary pembrolizumab utilization and spending while saving Veterans and VAAAHS providers’ time. Continued provider reinforcement, preparation for Oracle/ Cerner implementation, VISN expansion, refinement of pembrolizumab dose-banding, and development of dose bands for other immunotherapies are underway.

Significance

National implementation would improve Veteran convenience and quality of life, enable reductions in drug and resource costs, and enhance clinic throughput.

Background

Addressing cancer-related distress is a critical component of comprehensive oncology care. In alignment with the National Comprehensive Cancer Network (NCCN) guidelines, which advocate for routine distress screening as a standard of care, our institution aimed to enhance a previously underutilized paper-based screening process by implementing a more efficient and accessible solution.

Objective

To improve screening rates and streamline the identification of psychosocial needs of Veterans who have cancer.

Population

This initiative was conducted in an outpatient Hematology/Oncology clinic at a Midwest Federal Healthcare Center.

Methods

The Plan-Do-Study-Act (PDSA) quality improvement model was used to guide the implementation of the electronic screener. The eScreener was integrated into routine clinical workflow and staff received training to facilitate implementation. Veterans self-identified their needs through the screener, which included a range of practical, family/social, physical, religious or emotional concerns. Clinical staff then review the responses, assessed the identified needs, and entered appropriate referrals into the electronic health record. A dedicated certified nursing assistant (CNA) was incorporated into the workflow to support implementation efforts. As part of their role, the CNA was tasked with ensuring that all Veterans completed the distress screener either electronically or on paper during their visit

Results

Between January 2025 and March 2025, a total of 180 distress screens were completed using the newly implement method. During the same period in the previous year, only 60 screens were completed, representing a 200% increase. The new process enabled timely referrals based on identified needs, resulting in 39 referrals to physicians, 32 to psychologists, 10 to social work, 7 to dieticians, 6 to nurses, and 1 to pastoral care. These outcomes reflect a significant improvement in both accessibility and patient engagement.

Conclusions

The implementation of an electronic cancer distress screener, along with a dedicated staff member resulted in a substantial increase in screening completion rates and multidisciplinary referrals. These preliminary finds suggest that digital tools can significantly enhance psychosocial assessment, improve coordination, and support the delivery of timely, patient-centered oncology care.

Background

Addressing cancer-related distress is a critical component of comprehensive oncology care. In alignment with the National Comprehensive Cancer Network (NCCN) guidelines, which advocate for routine distress screening as a standard of care, our institution aimed to enhance a previously underutilized paper-based screening process by implementing a more efficient and accessible solution.

Objective

To improve screening rates and streamline the identification of psychosocial needs of Veterans who have cancer.

Population

This initiative was conducted in an outpatient Hematology/Oncology clinic at a Midwest Federal Healthcare Center.

Methods

The Plan-Do-Study-Act (PDSA) quality improvement model was used to guide the implementation of the electronic screener. The eScreener was integrated into routine clinical workflow and staff received training to facilitate implementation. Veterans self-identified their needs through the screener, which included a range of practical, family/social, physical, religious or emotional concerns. Clinical staff then review the responses, assessed the identified needs, and entered appropriate referrals into the electronic health record. A dedicated certified nursing assistant (CNA) was incorporated into the workflow to support implementation efforts. As part of their role, the CNA was tasked with ensuring that all Veterans completed the distress screener either electronically or on paper during their visit

Results

Between January 2025 and March 2025, a total of 180 distress screens were completed using the newly implement method. During the same period in the previous year, only 60 screens were completed, representing a 200% increase. The new process enabled timely referrals based on identified needs, resulting in 39 referrals to physicians, 32 to psychologists, 10 to social work, 7 to dieticians, 6 to nurses, and 1 to pastoral care. These outcomes reflect a significant improvement in both accessibility and patient engagement.

Conclusions

The implementation of an electronic cancer distress screener, along with a dedicated staff member resulted in a substantial increase in screening completion rates and multidisciplinary referrals. These preliminary finds suggest that digital tools can significantly enhance psychosocial assessment, improve coordination, and support the delivery of timely, patient-centered oncology care.

Background

Addressing cancer-related distress is a critical component of comprehensive oncology care. In alignment with the National Comprehensive Cancer Network (NCCN) guidelines, which advocate for routine distress screening as a standard of care, our institution aimed to enhance a previously underutilized paper-based screening process by implementing a more efficient and accessible solution.

Objective

To improve screening rates and streamline the identification of psychosocial needs of Veterans who have cancer.

Population

This initiative was conducted in an outpatient Hematology/Oncology clinic at a Midwest Federal Healthcare Center.

Methods

The Plan-Do-Study-Act (PDSA) quality improvement model was used to guide the implementation of the electronic screener. The eScreener was integrated into routine clinical workflow and staff received training to facilitate implementation. Veterans self-identified their needs through the screener, which included a range of practical, family/social, physical, religious or emotional concerns. Clinical staff then review the responses, assessed the identified needs, and entered appropriate referrals into the electronic health record. A dedicated certified nursing assistant (CNA) was incorporated into the workflow to support implementation efforts. As part of their role, the CNA was tasked with ensuring that all Veterans completed the distress screener either electronically or on paper during their visit

Results

Between January 2025 and March 2025, a total of 180 distress screens were completed using the newly implement method. During the same period in the previous year, only 60 screens were completed, representing a 200% increase. The new process enabled timely referrals based on identified needs, resulting in 39 referrals to physicians, 32 to psychologists, 10 to social work, 7 to dieticians, 6 to nurses, and 1 to pastoral care. These outcomes reflect a significant improvement in both accessibility and patient engagement.

Conclusions

The implementation of an electronic cancer distress screener, along with a dedicated staff member resulted in a substantial increase in screening completion rates and multidisciplinary referrals. These preliminary finds suggest that digital tools can significantly enhance psychosocial assessment, improve coordination, and support the delivery of timely, patient-centered oncology care.

Background

Autologous stem cell transplant (ASCT) is an important part of the treatment paradigm for patients with multiple myeloma (MM) and remains the standard of care for newly diagnosed patients. Blood product transfusion support in the form of platelets and packed red blood cells (pRBCs) is part of the standard of practice as supportive measures during the severely pancytopenic period. Some MM patients, such as those of Jehovah’s Witness (JW) faith, may have religious beliefs or preferences that preclude acceptance of such blood products. Some transplant centers have developed protocols to allow safe “bloodless” ASCT that allows these patients to receive this important treatment while adhering to their beliefs or preferences.

Case Presentation

A 61-year-old veteran of JW faith with newly diagnosed IgG Kappa Multiple Myeloma was referred to the Tennessee Valley Healthcare System (TVHS) Stem Cell Transplant program for consideration of “bloodless” ASCT. With the assistance and expertise of the academic affiliate, Vanderbilt University Medical Center’s established bloodless ASCT protocol, this same protocol was established at TVHS to optimize the patient’s care pretransplant (use of erythropoiesis stimulating agents, intravenous iron, B12 supplementation) as well as post-transplant (use of antifibrinolytics, close inpatient monitoring). Both Ethics and Legal consultation was obtained, and guidance was provided to create a life sustaining treatment (LST) note in the veteran’s electronic health record that captured the veteran’s blood product preference. Once all protocols and guidance were in place, the TVHS SCT/CT program proceeded to treat the veteran with a myeloablative melphalan ASCT. The patient tolerated the procedure exceptionally well with minimal complications. He achieved full engraftment on day +14 after ASCT as expected and was discharged from the inpatient setting. He was monitored in the outpatient setting until day +30 without further complications.

Conclusions

The TVHS SCT/CT performed the first ever bloodless autologous stem cell transplant within the VA. This pioneering effort to establish such protocols to provide care to all veterans whatever their personal or religious preferences is a testament to commitment of VA to provide care for all veterans and the willingness to innovate to do so.

Background

Autologous stem cell transplant (ASCT) is an important part of the treatment paradigm for patients with multiple myeloma (MM) and remains the standard of care for newly diagnosed patients. Blood product transfusion support in the form of platelets and packed red blood cells (pRBCs) is part of the standard of practice as supportive measures during the severely pancytopenic period. Some MM patients, such as those of Jehovah’s Witness (JW) faith, may have religious beliefs or preferences that preclude acceptance of such blood products. Some transplant centers have developed protocols to allow safe “bloodless” ASCT that allows these patients to receive this important treatment while adhering to their beliefs or preferences.

Case Presentation

A 61-year-old veteran of JW faith with newly diagnosed IgG Kappa Multiple Myeloma was referred to the Tennessee Valley Healthcare System (TVHS) Stem Cell Transplant program for consideration of “bloodless” ASCT. With the assistance and expertise of the academic affiliate, Vanderbilt University Medical Center’s established bloodless ASCT protocol, this same protocol was established at TVHS to optimize the patient’s care pretransplant (use of erythropoiesis stimulating agents, intravenous iron, B12 supplementation) as well as post-transplant (use of antifibrinolytics, close inpatient monitoring). Both Ethics and Legal consultation was obtained, and guidance was provided to create a life sustaining treatment (LST) note in the veteran’s electronic health record that captured the veteran’s blood product preference. Once all protocols and guidance were in place, the TVHS SCT/CT program proceeded to treat the veteran with a myeloablative melphalan ASCT. The patient tolerated the procedure exceptionally well with minimal complications. He achieved full engraftment on day +14 after ASCT as expected and was discharged from the inpatient setting. He was monitored in the outpatient setting until day +30 without further complications.

Conclusions

The TVHS SCT/CT performed the first ever bloodless autologous stem cell transplant within the VA. This pioneering effort to establish such protocols to provide care to all veterans whatever their personal or religious preferences is a testament to commitment of VA to provide care for all veterans and the willingness to innovate to do so.

Background

Autologous stem cell transplant (ASCT) is an important part of the treatment paradigm for patients with multiple myeloma (MM) and remains the standard of care for newly diagnosed patients. Blood product transfusion support in the form of platelets and packed red blood cells (pRBCs) is part of the standard of practice as supportive measures during the severely pancytopenic period. Some MM patients, such as those of Jehovah’s Witness (JW) faith, may have religious beliefs or preferences that preclude acceptance of such blood products. Some transplant centers have developed protocols to allow safe “bloodless” ASCT that allows these patients to receive this important treatment while adhering to their beliefs or preferences.

Case Presentation

A 61-year-old veteran of JW faith with newly diagnosed IgG Kappa Multiple Myeloma was referred to the Tennessee Valley Healthcare System (TVHS) Stem Cell Transplant program for consideration of “bloodless” ASCT. With the assistance and expertise of the academic affiliate, Vanderbilt University Medical Center’s established bloodless ASCT protocol, this same protocol was established at TVHS to optimize the patient’s care pretransplant (use of erythropoiesis stimulating agents, intravenous iron, B12 supplementation) as well as post-transplant (use of antifibrinolytics, close inpatient monitoring). Both Ethics and Legal consultation was obtained, and guidance was provided to create a life sustaining treatment (LST) note in the veteran’s electronic health record that captured the veteran’s blood product preference. Once all protocols and guidance were in place, the TVHS SCT/CT program proceeded to treat the veteran with a myeloablative melphalan ASCT. The patient tolerated the procedure exceptionally well with minimal complications. He achieved full engraftment on day +14 after ASCT as expected and was discharged from the inpatient setting. He was monitored in the outpatient setting until day +30 without further complications.

Conclusions

The TVHS SCT/CT performed the first ever bloodless autologous stem cell transplant within the VA. This pioneering effort to establish such protocols to provide care to all veterans whatever their personal or religious preferences is a testament to commitment of VA to provide care for all veterans and the willingness to innovate to do so.

A bipartisan bill establishing research directives aimed at revealing cancer risks among military aviators and aircrews recently became law.

Spearheaded by Sen. Mark Kelly (D-AZ) and Sen. Tom Cotton (R-AR), as well as Rep. August Pfluger (R-TX-11) and Rep. Jimmy Panetta (D-CA-19), all of whom are veterans, the Aviator Cancer Examination Study (ACES) Act was signed into law on August 14. The ACES Act will address cancer rates among Army, Navy, Air Force, and Marine Corps aircrew members by directing the Secretary of the US Department of Veterans Affairs to study cancer incidence and mortality rates among these populations.

Military aviators and aircrews face a 15% to 24% higher rate of cancer compared with the general US population, including a 75% higher rate of melanoma, 31% higher rate of thyroid cancer, 20% higher rate of prostate cancer, and 11% higher rate of female breast cancer, with potential links to non-Hodgkin lymphoma and testicular cancer. These individuals are also diagnosed earlier in life, at the median age of 55 years compared with 67 years. However, further investigation is still needed to understand why. 

“By better understanding the correlation between aviator service and cancer, we can better assist our military and provide more adequate care for our veterans,” Kelly said.

Some reasons for the higher rates of cancer in aviators seem clear, such as the association between dioxin exposure and cancer. In a study of cancer incidence and mortality in Air Force veterans of the Vietnam War, incidence of melanoma and prostate cancer was increased among White veterans who sprayed herbicides during Operation Ranch Hand. The risk of cancer at any site, prostate cancer, and melanoma was increased in the highest dioxin exposure category among veterans who spent ≤ 2 years in Southeast Asia.

However, some links between these veterans and increased cancer rates are less clear. In a review of 28 studies (including 18 studies in military settings), slight evidence was found for associations between jet fuel exposure and various outcomes including cancer. Cosmic ionizing radiation (CIR) exposure is another possible cause. Several epidemiological studies have documented elevated incidence and mortality for several cancers in flight crews, but a link between them and CIR exposure has not been established.

Certain occupations have been associated with increased risk of testicular germ cell tumors, including aircraft maintenance, military pilots, fighter pilots, and aircrews. Those associations led to hypotheses that job-related chemical exposures (eg, per- and polyfluoroalkyl substances, solvents, paints, hydrocarbons in degreasing/lubricating agents, lubricating oils) may increase risk. A study of young active-duty Air Force servicemen found that pilots and men with aircraft maintenance jobs had elevated tenosynovial giant cell tumor risk, but indicates that further research is needed to “elucidate specific occupational exposures underlying these associations.”

“As a former Navy pilot, there are certain risks that we know and accept come with our service, but we know far less about the health risks that are affecting many aviators and aircrews years later,” Kelly said in a statement. “Veteran aviators and aircrews deserve answers about the correlation between their job and cancer risks so we can reduce those risks for future pilots. Getting this across the finish line has been a bipartisan effort from the start, and I’m proud to see this bill become law so we can deliver real answers and accountability for those who served.”   

“The ACES Act is now the law of the land,” Cotton added. “We owe it to past, present, and future aviators in the armed forces to study the prevalence of cancer among this group of veterans.”

The ACES Act complements Kelly’s bipartisan Counting Veterans’ Cancer Act, which requires Veterans Health Administration facilities to share cancer data with state cancer registries, thereby guaranteeing their inclusion in the national registries. Key provisions of the Counting Veterans’ Cancer Act were included in the first government funding package of fiscal year 2024. 

A bipartisan bill establishing research directives aimed at revealing cancer risks among military aviators and aircrews recently became law.

Spearheaded by Sen. Mark Kelly (D-AZ) and Sen. Tom Cotton (R-AR), as well as Rep. August Pfluger (R-TX-11) and Rep. Jimmy Panetta (D-CA-19), all of whom are veterans, the Aviator Cancer Examination Study (ACES) Act was signed into law on August 14. The ACES Act will address cancer rates among Army, Navy, Air Force, and Marine Corps aircrew members by directing the Secretary of the US Department of Veterans Affairs to study cancer incidence and mortality rates among these populations.

Military aviators and aircrews face a 15% to 24% higher rate of cancer compared with the general US population, including a 75% higher rate of melanoma, 31% higher rate of thyroid cancer, 20% higher rate of prostate cancer, and 11% higher rate of female breast cancer, with potential links to non-Hodgkin lymphoma and testicular cancer. These individuals are also diagnosed earlier in life, at the median age of 55 years compared with 67 years. However, further investigation is still needed to understand why. 

“By better understanding the correlation between aviator service and cancer, we can better assist our military and provide more adequate care for our veterans,” Kelly said.

Some reasons for the higher rates of cancer in aviators seem clear, such as the association between dioxin exposure and cancer. In a study of cancer incidence and mortality in Air Force veterans of the Vietnam War, incidence of melanoma and prostate cancer was increased among White veterans who sprayed herbicides during Operation Ranch Hand. The risk of cancer at any site, prostate cancer, and melanoma was increased in the highest dioxin exposure category among veterans who spent ≤ 2 years in Southeast Asia.

However, some links between these veterans and increased cancer rates are less clear. In a review of 28 studies (including 18 studies in military settings), slight evidence was found for associations between jet fuel exposure and various outcomes including cancer. Cosmic ionizing radiation (CIR) exposure is another possible cause. Several epidemiological studies have documented elevated incidence and mortality for several cancers in flight crews, but a link between them and CIR exposure has not been established.

Certain occupations have been associated with increased risk of testicular germ cell tumors, including aircraft maintenance, military pilots, fighter pilots, and aircrews. Those associations led to hypotheses that job-related chemical exposures (eg, per- and polyfluoroalkyl substances, solvents, paints, hydrocarbons in degreasing/lubricating agents, lubricating oils) may increase risk. A study of young active-duty Air Force servicemen found that pilots and men with aircraft maintenance jobs had elevated tenosynovial giant cell tumor risk, but indicates that further research is needed to “elucidate specific occupational exposures underlying these associations.”

“As a former Navy pilot, there are certain risks that we know and accept come with our service, but we know far less about the health risks that are affecting many aviators and aircrews years later,” Kelly said in a statement. “Veteran aviators and aircrews deserve answers about the correlation between their job and cancer risks so we can reduce those risks for future pilots. Getting this across the finish line has been a bipartisan effort from the start, and I’m proud to see this bill become law so we can deliver real answers and accountability for those who served.”   

“The ACES Act is now the law of the land,” Cotton added. “We owe it to past, present, and future aviators in the armed forces to study the prevalence of cancer among this group of veterans.”

The ACES Act complements Kelly’s bipartisan Counting Veterans’ Cancer Act, which requires Veterans Health Administration facilities to share cancer data with state cancer registries, thereby guaranteeing their inclusion in the national registries. Key provisions of the Counting Veterans’ Cancer Act were included in the first government funding package of fiscal year 2024. 

A bipartisan bill establishing research directives aimed at revealing cancer risks among military aviators and aircrews recently became law.

Spearheaded by Sen. Mark Kelly (D-AZ) and Sen. Tom Cotton (R-AR), as well as Rep. August Pfluger (R-TX-11) and Rep. Jimmy Panetta (D-CA-19), all of whom are veterans, the Aviator Cancer Examination Study (ACES) Act was signed into law on August 14. The ACES Act will address cancer rates among Army, Navy, Air Force, and Marine Corps aircrew members by directing the Secretary of the US Department of Veterans Affairs to study cancer incidence and mortality rates among these populations.

Military aviators and aircrews face a 15% to 24% higher rate of cancer compared with the general US population, including a 75% higher rate of melanoma, 31% higher rate of thyroid cancer, 20% higher rate of prostate cancer, and 11% higher rate of female breast cancer, with potential links to non-Hodgkin lymphoma and testicular cancer. These individuals are also diagnosed earlier in life, at the median age of 55 years compared with 67 years. However, further investigation is still needed to understand why. 

“By better understanding the correlation between aviator service and cancer, we can better assist our military and provide more adequate care for our veterans,” Kelly said.

Some reasons for the higher rates of cancer in aviators seem clear, such as the association between dioxin exposure and cancer. In a study of cancer incidence and mortality in Air Force veterans of the Vietnam War, incidence of melanoma and prostate cancer was increased among White veterans who sprayed herbicides during Operation Ranch Hand. The risk of cancer at any site, prostate cancer, and melanoma was increased in the highest dioxin exposure category among veterans who spent ≤ 2 years in Southeast Asia.

However, some links between these veterans and increased cancer rates are less clear. In a review of 28 studies (including 18 studies in military settings), slight evidence was found for associations between jet fuel exposure and various outcomes including cancer. Cosmic ionizing radiation (CIR) exposure is another possible cause. Several epidemiological studies have documented elevated incidence and mortality for several cancers in flight crews, but a link between them and CIR exposure has not been established.

Certain occupations have been associated with increased risk of testicular germ cell tumors, including aircraft maintenance, military pilots, fighter pilots, and aircrews. Those associations led to hypotheses that job-related chemical exposures (eg, per- and polyfluoroalkyl substances, solvents, paints, hydrocarbons in degreasing/lubricating agents, lubricating oils) may increase risk. A study of young active-duty Air Force servicemen found that pilots and men with aircraft maintenance jobs had elevated tenosynovial giant cell tumor risk, but indicates that further research is needed to “elucidate specific occupational exposures underlying these associations.”

“As a former Navy pilot, there are certain risks that we know and accept come with our service, but we know far less about the health risks that are affecting many aviators and aircrews years later,” Kelly said in a statement. “Veteran aviators and aircrews deserve answers about the correlation between their job and cancer risks so we can reduce those risks for future pilots. Getting this across the finish line has been a bipartisan effort from the start, and I’m proud to see this bill become law so we can deliver real answers and accountability for those who served.”   

“The ACES Act is now the law of the land,” Cotton added. “We owe it to past, present, and future aviators in the armed forces to study the prevalence of cancer among this group of veterans.”

The ACES Act complements Kelly’s bipartisan Counting Veterans’ Cancer Act, which requires Veterans Health Administration facilities to share cancer data with state cancer registries, thereby guaranteeing their inclusion in the national registries. Key provisions of the Counting Veterans’ Cancer Act were included in the first government funding package of fiscal year 2024. 

This transcript has been edited for clarity. 

Hello. It’s Mark Kris, from Memorial Sloan Kettering, talking about a birthday gift I received on June 23 when the FDA approved the indication of datopotamab deruxtecan for people with lung cancers. We have another drug, our third ADC (antibody-drug conjugate) to fight lung cancer, so that’s a gift. 

Let’s talk a little bit about that agent. It’s an interesting twist in our practice patterns. What can the drug do? It had a response rate of 45%, which is really important in patients that had EGFR mutations with progression on osimertinib. We really need drugs in that space. The duration of response was about 7 months, which is significant.

One interesting thing in the approval, [was] that the response rate of the blinded folks was greater than that in the investigator-assessed response by about 10%. It’s very interesting. Clearly, we have another drug, and we have it in a space where we need it. 

Let’s talk a bit about the toxicity. I’m going to focus more on the paper by Bardia et al that compared datopotamab deruxtecan to various chemo drugs in breast cancer, not in lung cancer. You can take this a little bit with a grain of salt. 

First, they saw a whole different array of side effects with datopotamab deruxtecan, things that we don’t normally deal with here. Nausea, stomatitis, alopecia, dry eye, and vomiting. All of those were more than 10% more common in patients that received datopotamab deruxtecan compared to the control. The only things that were more common with the control were neutropenia, leukopenia, and hand-foot syndrome in patients that had capecitabine. 

One thing, though, is while you say, “Oh, these weren’t dangerous side effects,” they surely were lifestyle altering. Nobody wants to have these side effects on a daily basis. Again, there’s an increasing awareness about these kinds of lower-grade but still lifestyle-disrupting side effects. When it goes on day after day, you really have to balance that into the benefit you’re going to receive.

I think the second important point is how, when we use this drug, we’re going to have to go to another level to deal with the adverse effects that we are going to see. The first would be nausea and emesis. It is a highly emetogenic regimen based on the NCCN (National Comprehensive Cancer Network) guidelines, so you would need either 3 or 4 antiemetic drugs. That’s number one. 

Number two, because of the potential eye problems, you need an eye exam before treatment — and the label says at least annually — with any symptoms. I think it’s very important that you give the patients eyedrops, and in general, the preservative-free eyedrops are the ones that are most effective.

Stomatitis is a very common side effect with that agent. It’s really not seen with the other drugs that even contain the same warhead. There, dexamethasone rinses are important. Now, this is a compounded medicine so you need to be very careful in making sure that you identify pharmacies that will prepare this and will have it available for the patients that need it.

Last, there is the risk of hypersensitivity reactions and there’s a recommendation for premedication for that. As you think about using datopotamab deruxtecan, you need to have all your ducks in a row to treat side effects. You need prophylaxis for hypersensitivity reactions, nausea, and emesis. 

The patient will need an eye exam. You need to prepare the patient for possible dry eye and teach them which eyedrops are the best. You also need to ensure the availability of dexamethasone rinses and mouth washes. All that needs to be in place to make sure that the patient can safely use the drug. 

I think it’s going to be a useful drug. We don’t yet have a uniformly available way to select patients for its use other than EGFR. I should note that the approval is for EGFR-mutated lung cancers. It doesn’t say which type of mutation, so that would give you some latitude in giving it for exon 20 atypicals as well as for the common sensitizing mutation.

We have another drug. It’s clearly going to be a useful one. It clearly comes with many adverse effects that we don’t normally treat on an everyday basis, we’re used to the diarrhea and skin changes that come on with the EGFR TKIs. 

This pattern of side effects is different and requires some additional attention, but with it, the drug can be useful. I’m glad that we have yet another way to fight this disease.

Mark G. Kris, MD, Professor of Medicine, Weill Cornell Medical College; Attending Physician, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York , has disclosed the following relevant financial relationships:

Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: AstraZeneca; Bristol-Myers Squibb; Merck; Daiichi Sankyo; Received research grant from: National Institute of Health; Received income in an amount equal to or greater than $250 from: AstraZeneca; Bristol-Myers Squibb; Merck; Daiichi Sankyo Others: Editorial support from Genentech

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

This transcript has been edited for clarity. 

Hello. It’s Mark Kris, from Memorial Sloan Kettering, talking about a birthday gift I received on June 23 when the FDA approved the indication of datopotamab deruxtecan for people with lung cancers. We have another drug, our third ADC (antibody-drug conjugate) to fight lung cancer, so that’s a gift. 

Let’s talk a little bit about that agent. It’s an interesting twist in our practice patterns. What can the drug do? It had a response rate of 45%, which is really important in patients that had EGFR mutations with progression on osimertinib. We really need drugs in that space. The duration of response was about 7 months, which is significant.

One interesting thing in the approval, [was] that the response rate of the blinded folks was greater than that in the investigator-assessed response by about 10%. It’s very interesting. Clearly, we have another drug, and we have it in a space where we need it. 

Let’s talk a bit about the toxicity. I’m going to focus more on the paper by Bardia et al that compared datopotamab deruxtecan to various chemo drugs in breast cancer, not in lung cancer. You can take this a little bit with a grain of salt. 

First, they saw a whole different array of side effects with datopotamab deruxtecan, things that we don’t normally deal with here. Nausea, stomatitis, alopecia, dry eye, and vomiting. All of those were more than 10% more common in patients that received datopotamab deruxtecan compared to the control. The only things that were more common with the control were neutropenia, leukopenia, and hand-foot syndrome in patients that had capecitabine. 

One thing, though, is while you say, “Oh, these weren’t dangerous side effects,” they surely were lifestyle altering. Nobody wants to have these side effects on a daily basis. Again, there’s an increasing awareness about these kinds of lower-grade but still lifestyle-disrupting side effects. When it goes on day after day, you really have to balance that into the benefit you’re going to receive.

I think the second important point is how, when we use this drug, we’re going to have to go to another level to deal with the adverse effects that we are going to see. The first would be nausea and emesis. It is a highly emetogenic regimen based on the NCCN (National Comprehensive Cancer Network) guidelines, so you would need either 3 or 4 antiemetic drugs. That’s number one. 

Number two, because of the potential eye problems, you need an eye exam before treatment — and the label says at least annually — with any symptoms. I think it’s very important that you give the patients eyedrops, and in general, the preservative-free eyedrops are the ones that are most effective.

Stomatitis is a very common side effect with that agent. It’s really not seen with the other drugs that even contain the same warhead. There, dexamethasone rinses are important. Now, this is a compounded medicine so you need to be very careful in making sure that you identify pharmacies that will prepare this and will have it available for the patients that need it.

Last, there is the risk of hypersensitivity reactions and there’s a recommendation for premedication for that. As you think about using datopotamab deruxtecan, you need to have all your ducks in a row to treat side effects. You need prophylaxis for hypersensitivity reactions, nausea, and emesis. 

The patient will need an eye exam. You need to prepare the patient for possible dry eye and teach them which eyedrops are the best. You also need to ensure the availability of dexamethasone rinses and mouth washes. All that needs to be in place to make sure that the patient can safely use the drug. 

I think it’s going to be a useful drug. We don’t yet have a uniformly available way to select patients for its use other than EGFR. I should note that the approval is for EGFR-mutated lung cancers. It doesn’t say which type of mutation, so that would give you some latitude in giving it for exon 20 atypicals as well as for the common sensitizing mutation.

We have another drug. It’s clearly going to be a useful one. It clearly comes with many adverse effects that we don’t normally treat on an everyday basis, we’re used to the diarrhea and skin changes that come on with the EGFR TKIs. 

This pattern of side effects is different and requires some additional attention, but with it, the drug can be useful. I’m glad that we have yet another way to fight this disease.

Mark G. Kris, MD, Professor of Medicine, Weill Cornell Medical College; Attending Physician, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York , has disclosed the following relevant financial relationships:

Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: AstraZeneca; Bristol-Myers Squibb; Merck; Daiichi Sankyo; Received research grant from: National Institute of Health; Received income in an amount equal to or greater than $250 from: AstraZeneca; Bristol-Myers Squibb; Merck; Daiichi Sankyo Others: Editorial support from Genentech

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

This transcript has been edited for clarity. 

Hello. It’s Mark Kris, from Memorial Sloan Kettering, talking about a birthday gift I received on June 23 when the FDA approved the indication of datopotamab deruxtecan for people with lung cancers. We have another drug, our third ADC (antibody-drug conjugate) to fight lung cancer, so that’s a gift. 

Let’s talk a little bit about that agent. It’s an interesting twist in our practice patterns. What can the drug do? It had a response rate of 45%, which is really important in patients that had EGFR mutations with progression on osimertinib. We really need drugs in that space. The duration of response was about 7 months, which is significant.

One interesting thing in the approval, [was] that the response rate of the blinded folks was greater than that in the investigator-assessed response by about 10%. It’s very interesting. Clearly, we have another drug, and we have it in a space where we need it. 

Let’s talk a bit about the toxicity. I’m going to focus more on the paper by Bardia et al that compared datopotamab deruxtecan to various chemo drugs in breast cancer, not in lung cancer. You can take this a little bit with a grain of salt. 

First, they saw a whole different array of side effects with datopotamab deruxtecan, things that we don’t normally deal with here. Nausea, stomatitis, alopecia, dry eye, and vomiting. All of those were more than 10% more common in patients that received datopotamab deruxtecan compared to the control. The only things that were more common with the control were neutropenia, leukopenia, and hand-foot syndrome in patients that had capecitabine. 

One thing, though, is while you say, “Oh, these weren’t dangerous side effects,” they surely were lifestyle altering. Nobody wants to have these side effects on a daily basis. Again, there’s an increasing awareness about these kinds of lower-grade but still lifestyle-disrupting side effects. When it goes on day after day, you really have to balance that into the benefit you’re going to receive.

I think the second important point is how, when we use this drug, we’re going to have to go to another level to deal with the adverse effects that we are going to see. The first would be nausea and emesis. It is a highly emetogenic regimen based on the NCCN (National Comprehensive Cancer Network) guidelines, so you would need either 3 or 4 antiemetic drugs. That’s number one. 

Number two, because of the potential eye problems, you need an eye exam before treatment — and the label says at least annually — with any symptoms. I think it’s very important that you give the patients eyedrops, and in general, the preservative-free eyedrops are the ones that are most effective.

Stomatitis is a very common side effect with that agent. It’s really not seen with the other drugs that even contain the same warhead. There, dexamethasone rinses are important. Now, this is a compounded medicine so you need to be very careful in making sure that you identify pharmacies that will prepare this and will have it available for the patients that need it.

Last, there is the risk of hypersensitivity reactions and there’s a recommendation for premedication for that. As you think about using datopotamab deruxtecan, you need to have all your ducks in a row to treat side effects. You need prophylaxis for hypersensitivity reactions, nausea, and emesis. 

The patient will need an eye exam. You need to prepare the patient for possible dry eye and teach them which eyedrops are the best. You also need to ensure the availability of dexamethasone rinses and mouth washes. All that needs to be in place to make sure that the patient can safely use the drug. 

I think it’s going to be a useful drug. We don’t yet have a uniformly available way to select patients for its use other than EGFR. I should note that the approval is for EGFR-mutated lung cancers. It doesn’t say which type of mutation, so that would give you some latitude in giving it for exon 20 atypicals as well as for the common sensitizing mutation.

We have another drug. It’s clearly going to be a useful one. It clearly comes with many adverse effects that we don’t normally treat on an everyday basis, we’re used to the diarrhea and skin changes that come on with the EGFR TKIs. 

This pattern of side effects is different and requires some additional attention, but with it, the drug can be useful. I’m glad that we have yet another way to fight this disease.

Mark G. Kris, MD, Professor of Medicine, Weill Cornell Medical College; Attending Physician, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York , has disclosed the following relevant financial relationships:

Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: AstraZeneca; Bristol-Myers Squibb; Merck; Daiichi Sankyo; Received research grant from: National Institute of Health; Received income in an amount equal to or greater than $250 from: AstraZeneca; Bristol-Myers Squibb; Merck; Daiichi Sankyo Others: Editorial support from Genentech

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

At some point, most Americans will experience the anxiety associated with an organizational restructure or a corporate budget cut that leads to job loss. Self-assurances may follow by telling ourselves we will be fine, and we could even start a new position that (if we're lucky) will be better than our previous one. It can be devastating, but is not a life-or-death scenario.

Unless you care for veterans with cancer.

The recent workforce reductions across the US Department of Veterans of Affairs (VA) health care system, whether through voluntary retirements or forced layoffs, is a life-threatening crisis. Every position lost has the potential to directly impact whether a veteran receives the necessary care in their battle with cancer.

Veterans deserve every opportunity, treatment plan, and resource available to ensure their comfort and survival. They are entitled to the specialized, comprehensive, and thorough care they receive through the VA—care that cannot be duplicated in community health care. Because many of the health challenges they face are a direct result of serving our country, we owe it to them to provide the best care available from the most highly-trained and competent clinicians. This level of excellence cannot be achieved in a gutted or chaotic system.

Reducing or eliminating VA health care positions is a decision that demands careful examination. Like any organization, the VA experiences some measure of waste or inefficiency that should be eliminated. But that cannot be done swiftly or in large-scale action.

Consider these examples: the reduction of force resulting in the removal of those deemed to hold unnecessary administrative positions—such as continuing education or physician oversight—has a direct impact on a clinician's ability to provide the most current and precise care. Reduced research funding limits the VA's contribution to health care innovation. The loss of contract positions that appear superfluous on paper represent the staff who schedule appointments, chemotherapy or radiation therapy, and wrap-around services for veterans. Even reducing auxiliary services like laundry may seem like a cost-saving measure—until the hospital can't admit new patients due to lack of sanitized linens.

VA employees know that veterans need specialized care for their complex and unique challenges. That individualized care has led to the VA nearly eliminating disparity gaps experienced in traditional health care. The removal of support positions and opportunities in professional development demands coordination with less-prepared community-based health care; overpopulated work environments will have a lasting impact. Limiting the workforce will make it impossible to provide coordinated and exceptional care.

The Association of VA Hematology/Oncology (AVAHO) is a leader in professional development opportunities for those who care for veterans with cancer. As a nonprofit organization, AVAHO is also a voice for those working with veterans with cancer to ensure they receive the care they deserve. AVAHO is calling on its colleagues, veterans, and those committed to supporting veterans to voice their opposition to reducing critical staff, research, and resources within the VA.

We ask veterans to share stories describing the difference VA care makes. We ask clinicians—including those within the federal system—to explain how a system that is well-staffed, supported, and with ample resources can impact patient care. Americans must stand for the care our veterans have earned.

Most importantly, we call on policymakers to carefully consider the impact each position has on the outcome of excellent, well-coordinated, and state-of-the-art care. The lives of our veterans depend on it.

AVAHO is a 501(c)3 nonprofit organization dedicated to supporting and educating health care providers who serve veterans with cancer and hematological disorders. You can find out more and support their advocacy initiatives at www.avaho.org.

At some point, most Americans will experience the anxiety associated with an organizational restructure or a corporate budget cut that leads to job loss. Self-assurances may follow by telling ourselves we will be fine, and we could even start a new position that (if we're lucky) will be better than our previous one. It can be devastating, but is not a life-or-death scenario.

Unless you care for veterans with cancer.

The recent workforce reductions across the US Department of Veterans of Affairs (VA) health care system, whether through voluntary retirements or forced layoffs, is a life-threatening crisis. Every position lost has the potential to directly impact whether a veteran receives the necessary care in their battle with cancer.

Veterans deserve every opportunity, treatment plan, and resource available to ensure their comfort and survival. They are entitled to the specialized, comprehensive, and thorough care they receive through the VA—care that cannot be duplicated in community health care. Because many of the health challenges they face are a direct result of serving our country, we owe it to them to provide the best care available from the most highly-trained and competent clinicians. This level of excellence cannot be achieved in a gutted or chaotic system.

Reducing or eliminating VA health care positions is a decision that demands careful examination. Like any organization, the VA experiences some measure of waste or inefficiency that should be eliminated. But that cannot be done swiftly or in large-scale action.

Consider these examples: the reduction of force resulting in the removal of those deemed to hold unnecessary administrative positions—such as continuing education or physician oversight—has a direct impact on a clinician's ability to provide the most current and precise care. Reduced research funding limits the VA's contribution to health care innovation. The loss of contract positions that appear superfluous on paper represent the staff who schedule appointments, chemotherapy or radiation therapy, and wrap-around services for veterans. Even reducing auxiliary services like laundry may seem like a cost-saving measure—until the hospital can't admit new patients due to lack of sanitized linens.

VA employees know that veterans need specialized care for their complex and unique challenges. That individualized care has led to the VA nearly eliminating disparity gaps experienced in traditional health care. The removal of support positions and opportunities in professional development demands coordination with less-prepared community-based health care; overpopulated work environments will have a lasting impact. Limiting the workforce will make it impossible to provide coordinated and exceptional care.

The Association of VA Hematology/Oncology (AVAHO) is a leader in professional development opportunities for those who care for veterans with cancer. As a nonprofit organization, AVAHO is also a voice for those working with veterans with cancer to ensure they receive the care they deserve. AVAHO is calling on its colleagues, veterans, and those committed to supporting veterans to voice their opposition to reducing critical staff, research, and resources within the VA.

We ask veterans to share stories describing the difference VA care makes. We ask clinicians—including those within the federal system—to explain how a system that is well-staffed, supported, and with ample resources can impact patient care. Americans must stand for the care our veterans have earned.

Most importantly, we call on policymakers to carefully consider the impact each position has on the outcome of excellent, well-coordinated, and state-of-the-art care. The lives of our veterans depend on it.

AVAHO is a 501(c)3 nonprofit organization dedicated to supporting and educating health care providers who serve veterans with cancer and hematological disorders. You can find out more and support their advocacy initiatives at www.avaho.org.

At some point, most Americans will experience the anxiety associated with an organizational restructure or a corporate budget cut that leads to job loss. Self-assurances may follow by telling ourselves we will be fine, and we could even start a new position that (if we're lucky) will be better than our previous one. It can be devastating, but is not a life-or-death scenario.

Unless you care for veterans with cancer.

The recent workforce reductions across the US Department of Veterans of Affairs (VA) health care system, whether through voluntary retirements or forced layoffs, is a life-threatening crisis. Every position lost has the potential to directly impact whether a veteran receives the necessary care in their battle with cancer.

Veterans deserve every opportunity, treatment plan, and resource available to ensure their comfort and survival. They are entitled to the specialized, comprehensive, and thorough care they receive through the VA—care that cannot be duplicated in community health care. Because many of the health challenges they face are a direct result of serving our country, we owe it to them to provide the best care available from the most highly-trained and competent clinicians. This level of excellence cannot be achieved in a gutted or chaotic system.

Reducing or eliminating VA health care positions is a decision that demands careful examination. Like any organization, the VA experiences some measure of waste or inefficiency that should be eliminated. But that cannot be done swiftly or in large-scale action.

Consider these examples: the reduction of force resulting in the removal of those deemed to hold unnecessary administrative positions—such as continuing education or physician oversight—has a direct impact on a clinician's ability to provide the most current and precise care. Reduced research funding limits the VA's contribution to health care innovation. The loss of contract positions that appear superfluous on paper represent the staff who schedule appointments, chemotherapy or radiation therapy, and wrap-around services for veterans. Even reducing auxiliary services like laundry may seem like a cost-saving measure—until the hospital can't admit new patients due to lack of sanitized linens.

VA employees know that veterans need specialized care for their complex and unique challenges. That individualized care has led to the VA nearly eliminating disparity gaps experienced in traditional health care. The removal of support positions and opportunities in professional development demands coordination with less-prepared community-based health care; overpopulated work environments will have a lasting impact. Limiting the workforce will make it impossible to provide coordinated and exceptional care.

The Association of VA Hematology/Oncology (AVAHO) is a leader in professional development opportunities for those who care for veterans with cancer. As a nonprofit organization, AVAHO is also a voice for those working with veterans with cancer to ensure they receive the care they deserve. AVAHO is calling on its colleagues, veterans, and those committed to supporting veterans to voice their opposition to reducing critical staff, research, and resources within the VA.

We ask veterans to share stories describing the difference VA care makes. We ask clinicians—including those within the federal system—to explain how a system that is well-staffed, supported, and with ample resources can impact patient care. Americans must stand for the care our veterans have earned.

Most importantly, we call on policymakers to carefully consider the impact each position has on the outcome of excellent, well-coordinated, and state-of-the-art care. The lives of our veterans depend on it.

AVAHO is a 501(c)3 nonprofit organization dedicated to supporting and educating health care providers who serve veterans with cancer and hematological disorders. You can find out more and support their advocacy initiatives at www.avaho.org.

The treatment of metastatic solid tumors has been based historically on systemic therapies, with the goal of delaying progression and extend life as long as possible, with tolerable treatment-related adverse events. Some exceptions were made for local treatment with surgery or radiotherapy (RT), often for patients with a single metastasis. A 1939 report describes a patient with renal adenocarcinoma and a solitary lung metastasis who underwent RT to the lung lesion after nephrectomy and subsequently partial lobectomy after the metastatic lesion progressed. The authors argued that if a metastasis appears solitary and accessible, it is plausible to remove it in addition to the primary growth.¹

In 1995 Hellman and Weichselbaum proposed oligometastatic disease (OMD). They reasoned that malignancy exists along a spectrum from localized disease to widely disseminated disease, with OMD existing in between with a still-restricted tumor metastatic capacity. Appropriately selected patients with OMD may be candidates for prolonged disease-free survival or cure with the addition of local therapy to systemic therapy.²

The EORTC 4004 phase 2 randomized control trial (RCT) analyzed radiofrequency ablation (RFA) for colorectal liver metastases with systemic therapy vs systemic therapy alone for patients with ≤ 9 liver lesions.³ Systemic therapyconsisted of 5-FU/leucovorin/oxaliplatin, with bevacizumab added to the regimen 3.5 years into the study, per updated standard- of-care. This trial was the first to demonstrate the benefit of aggressive local treatment vs system treatment alone for OMD with a progression-free survival (PFS) benefit (16.8 vs 9.9 months; hazard ratio [HR], 0.63; P = .03) and overall survival (OS) benefit (45.3 vs 40.5 months; HR, 0.74; P = .02) with the addition of local treatment with RFA.

Since the presentations of the SABR-COMET phase 2 RCT and another study by Gomez et al at the American Society for Radiation Oncology (ASTRO) 2018 annual meeting, the paradigm for offering local RT for OMD has rapidly evolved. Both studies found PFS and OS benefits of RT for patients with OMD.^4,5 Additional RCTs have since demonstrated that for properly selected patients with OMD, aggressive local RT improved PFS and OS.^6-9 These small studies have led to larger RCTs to better understand who benefits from local consolidative treatment, particularly RT.^10,11

There is a large degree of heterogeneity in how oncologists define and approach OMD treatment. The 2020 European Society for Radiotherapy and Oncology (ESTRO) and ASTRO consensus guidelines defined the OMD state as 1 to 5 metastatic lesions for which all metastatic sites are safely treatable.¹² The purpose of this study was to evaluate perceptions and practice patterns among radiation oncologists and medical oncologists regarding the use of local RT for OMD across the Veterans Health Administration (VHA).

Methods

A 12-question survey was developed by the VHA Palliative Radiotherapy Task Force using the ESTRO-ASTRO consensus guidelines to define OMD. The survey was emailed to the VHA radiation oncology and medical oncology listservs on August 1, 2023. These listservs consist of physicians in these specialties either directly employed by the VHA or serve in its facilities as contractors. The original response closure date was August 11, 2023, but it was extended to August 18, 2023, to increase responses. No incentives were offered to respondents. Two email reminders were sent to the medical oncology listserv and 3 to the radiation oncology listserv. Descriptive statistics and X² tests were used for data analysis. The impact of specialty and presence of an on-site department of radiation oncology were reviewed. This project was approved by the VHA National Oncology Program and National Radiation Oncology Program.

Results

The survey was sent to 125 radiation oncologists and 515 medical oncologists and 106 were completed for a 16.6% response rate. There were 59 (55.7%) radiation oncologist responses and 47 (44.3%) medical oncologist responses. Most (96.2%) respondents were board-certified, and 84 (79.2%) were affiliated with an academic center. Not every respondent answered every question (Table).

All respondents (n = 105) indicated there is a potential benefit of high-dose RT for appropriately selected cases. Ninety-four oncologists (88.7%) believed that RT for OMD contributes to cure (88.1% of radiation oncologists, 89.4% of medical oncologists; P = .84) for appropriately selected cases. Some respondents who did not believe RT for OMD contributes to cure added comments about other perceived benefits, such as local disease control for palliation, delaying systemic therapy with its associated toxicities, and prolongation of disease-free survival or OS. A higher percentage of respondents with academic affiliations believed high-dose RT contributes to cure, although this difference did not reach statistical significance (Figure 1).

Fifty-five respondents (51.9%; 55.2% radiation oncologists vs 50.0% medical oncologists; P = .60) responded that local RT for OMD treatment should not be limited by primary tumor type. Of respondents who responded that OMD treatment should be limited based on the type of primary tumor, many provided comments that argued there was a benefit for non-small cell lung cancer (NSCLC), prostate adenocarcinoma (PCa), and colorectal cancer.

The definition of how many metastatic lesions qualify as OMD varied. A total of 48.6% of respondents defined OMD as ≤ 3 lesions and 42.9% answered ≤ 5 lesions. A majority of radiation oncologists (55.2%) classified ≤ 5 lesions as OMD, whereas a majority of medical oncologists (66.0%) considered ≤ 3 lesions as OMD (P = .006) (Figure 2).

Thirty-six medical oncologists (76.6%) report having an on-site department of radiation oncology (Figure 3). This subgroup was more likely to consider local RT potentially curative compared with their medical oncology peers without on-site radiation oncology (94.4% vs 72.7%; P = .04).

Case Management

The 3 clinical cases demonstrated the heterogeneity of management approaches for OMD. The first described a man aged 65 years with PCa and 2 asymptomatic pelvic bone metastases. Ninety-three respondents (90.3%) recommended RT at the primary site and 74.8% recommended RT to both the primary site and metastatic foci. Sixty-three respondents (67.7%) recommended a STAMPEDE-compatible dose, and 30 (32.3%) recommended a definitive dose.

The second clinical case was a 60-year-old man with a cT1N2M1 NSCLC, with a solitary metastatic focus to the left iliac wing. Fifty-eight respondents (54.7%) recommended upfront systemic chemotherapy and the option of local therapy to the chest and metastatic focus after initial chemotherapy; 28 respondents (26.4%) recommended upfront chemoradiation to the chest and definitive radiation to the left iliac wing metastasis.

The third clinical case described a male aged 70 years with a history of a treated base of tongue squamous cell carcinoma, with a solitary metastatic focus within the right lung. Respondents could pick multiple treatment options and 85 (81.7%) favored upfront definitive local therapy with surgery or stereotactic body radiotherapy (SBRT), rather than upfront chemotherapy, with future consideration for local treatment. About half of respondents (51.8%) recommended SBRT and 41.2% would let the patient decide between surgery or SBRT. Additionally, 39.6% included in their patient counselling that the treatment may be for curative intent.

Discussion

The use of local treatment to increased PFS, OS, or even cure treatment for OMD has become more accepted since the 2018 ASTRO meeting.^4,5 Palma et al analyzed a controlled primary malignancy of any histology and ≤ 5 metastatic lesions, with all lesions amenable to SBRT.⁴ With a median follow-up of 51 months when comparing the standard-of-care (SOC) arm and the SBRT arm, the 5-year PFS was not reached and the 5-year OS rates were 17.7% and 42.3% (P = .006), respectively. In the SBRT arm, about 1 in 5 patients survived > 5 years without a recurrence or disease progression, vs 0 patients in the control arm. There was a 29% rate of grade 2 or higher toxicity in the SBRT arm, including 3 deaths that were likely due to treatment. Subsequent trials, such as the phase 3 SABR-COMET-3 (1-3 metastases), phase 3 SABR-COMET-10 (4-10 metastases), and phase 1 ARREST (> 10 metastases) trials, have been specifically designed to minimize treatment-related toxicities.^13-15

Gomez et al analyzed patients at 3 sites with a controlled NSCLC primary tumor and ≤ 3 metastases.⁵ At a follow-up of 38.8 months, the PFS was 4.4 months in the SOC arm vs 14.2 months in the RT and/or surgery local treatment arm (P = .02). There was also an OS benefit of 17.0 vs 41.2 months (P = .02), respectively.

Several RCTs soon followed that demonstrated improved PFS and OS with local radiotherapy for OMD; however, total metastatic ablation of the foci is necessary to attain these PFS and OS benefits.^6-9 Still, an oncologic benefit has yet to be proven. The randomized NRGBR002 study phase 2/3 trial for oligometastatic breast cancer included patients with ≤ 4 extracranial metastases and controlled primary disease to metastasis-directed therapy (SBRT and/ or surgical resection) and systemic therapy vs systemic therapy alone.¹⁰ The study did not demonstrate improved PFS or OS at 3 years. However, for most breast cancers, especially with the rapid advancements in systemic therapy that have been achieved, longer follow-up may be necessary to detect a significant difference.

The prospective single-arm phase 2 SABR-5 trial retrospectively demonstrated important lessons about the timing of SBRT and systemic therapy.¹¹ This study included patients with ≤ 5 metastases of any histology, and they received SBRT to all lesions. SABR-5 retrospectively compared patients who received upfront systemic therapy followed by SBRT vs another cohort that first received SBRT and did not receive systemic therapy until there was disease progression. Patients with oligo-progression were excluded, as it demonstrated systemic drug resistance. At a median follow-up time of 34 months, delayed systemic treatment was associated with shorter PFS (23 vs 34 months, respectively; P = .001), but not worse 3-year OS (80% vs 85%, respectively; P = .66). In addition, the delayed systemic treatment arm demonstrated a reduced risk of grade 2 or higher SBRT-related toxicity (odds ratio, 0.35; P < .001).

Similarly, the STOMP phase 2 trial analyzed the role of metastasis-directed therapy (MDT) in delaying initiation of androgen deprivation therapy (ADT) in a randomized phase 2 trial.¹⁶ This study included patients with asymptomatic PCa with a biochemical recurrence after primary treatment, 1 to 3 extracranial metastatic lesions, and serum testosterone levels > 50 ng/mL. Sixty-two patients were randomized 1:1 to either MDT (SBRT or surgery) of all lesions or surveillance. The 5-year ADT-free survival was 34% for MDT vs 8% for surveillance (P = .06).

VHA Radiation Oncology

The VHA has 138 departments of medical oncology, but only 41 departments of radiation oncology. Compared with medical oncologists without an on-site radiation oncology department, those with on-site departments were more likely to believe that local RT was potentially curative (94.4% vs 72.7%, respectively; P = .04). This finding suggests that a cancer center that includes both specialties has closer collaboration, which results in greater inclination to embrace local RT for OMD, as it has demonstrated PFS and OS benefits.

The radiation and medical oncologists surveyed had statistically significant differences in response by specialty regarding the maximal number of lesions still believed to constitute OMD. Most radiation oncologists classified ≤ 5 lesions as OMD, whereas most medical oncologists classified ≤ 3 lesions as OMD. This difference is not unexpected. There is no universally agreed-upon definition of OMD, and criteria differ across studies.

While the SABR-COMET trial did include ≤ 5 metastatic lesions, it was a phase 2 RCT, making subgroup analysis difficult. Ongoing phase 3 trials that are more specific in the number of metastases, comparing 1 to 3 vs 4 to 10 metastases (SABR-COMET-3 and SABR-COMET-10, respectively).^13,14 There is even an ongoing phase 1 trial (ARREST) studying the potential benefits of treating (“restraining”) > 10 metastases, if dosimetrically feasible.¹⁵ Within the VHA, VA STARPORT is investigating MDT for recurrent or de novo hormone-sensitive metastatic PCa.¹⁷ The ongoing HALT phase 2/3 trial focuses on patients with actionable mutations to help determine management of oligo-progression in mutation-positive NSCLC.¹⁸

There was no significant difference by specialty in who responded that offering local RT for OMD treatment should not be limited by histology (55.2% of radiation oncologists and 50.0% of medical oncologists; P = .60). Oncologists could make the argument that some histologies (eg, pancreatic adenocarcinomas) have such poor prognoses that local RT would not meaningfully affect oncologic outcomes, while potentially adding toxicity, whereas others could point to improved systemic therapy regimens and the low toxicity rates with careful hypofractionation regimens. Of note, the 41-patient phase 2 EXTEND trial for pancreatic ductal adenocarcinoma suggested an oncologic benefit to MDT, with far better PFS and no grade ≥ 3 toxicities related to MDT.¹⁹ About half of respondents for each specialty believed the primary histology should affect the decision. Further clarification may emerge from phase 3 trials.

Of note, a 2023 study of 44 radiation and medical oncologists at 2 Harvard Medical School-affiliated hospitals found that for synchronous OMD, 50.0% of medical oncologists and 5.3% (P < .01) of radiation oncologists recommended systemic treatment, suggesting a greater divergence in approach than found in this study.²⁰

Limitations

The response rate of 17.0% raised a potential for selection bias, but this rate is expected for a nonincentivized medical survey. A study by the American Board of Internal Medicine with 11 surveys and 6 weekly email contacts only generated a 23.7% response rate, while another study among physicians demonstrated a 4.5% response rate for email-based contact and 11.8% for mail-based contact.^21,22 We could have asked participants questions regarding demographics and geography to ensure the survey represented a diverse sample of the medical community, although additional questions would likely suppress the response rate. Additional data collection about respondents may elucidate the rationale for differences in their responses, especially between the specialties. In a planned subsequent survey in several years, the question on the number of lesions that qualifies as OMD may be amended to reflect the context and dosimetry for the maximal number of metastases constituting OMD; the joint ESTRO-ASTRO consensus defined OMD as 1 to 5 metastatic lesions, but in which all metastatic sites must be safely treatable.¹² Also, fewer example cases could be included to simplify the survey and boost response rates. A future survey may ask about the timing of SBRT and systemic therapy, and whether SBRT can safely delay systemic therapy.

Conclusions

Survey results demonstrated significant confidence among both radiation oncologists and medical oncologists that local RT for OMD improves outcomes, which is encouraging and a reflection of the recent evidence-based paradigm shift in viewing metastatic disease as a spectrum. However, there is a difference between radiation oncologists and medical oncologists in how they define OMD, and preferred treatment of the sample cases presented revealed nuanced differences by specialty. Close collaboration with radiation oncologists influences the belief of medical oncologists in the beneficial role of RT for OMD. As more phase 3 data for OMD local treatments emerge, additional investigation is needed on how beliefs and practice patterns evolve among radiation and medical oncologists.

The treatment of metastatic solid tumors has been based historically on systemic therapies, with the goal of delaying progression and extend life as long as possible, with tolerable treatment-related adverse events. Some exceptions were made for local treatment with surgery or radiotherapy (RT), often for patients with a single metastasis. A 1939 report describes a patient with renal adenocarcinoma and a solitary lung metastasis who underwent RT to the lung lesion after nephrectomy and subsequently partial lobectomy after the metastatic lesion progressed. The authors argued that if a metastasis appears solitary and accessible, it is plausible to remove it in addition to the primary growth.¹

In 1995 Hellman and Weichselbaum proposed oligometastatic disease (OMD). They reasoned that malignancy exists along a spectrum from localized disease to widely disseminated disease, with OMD existing in between with a still-restricted tumor metastatic capacity. Appropriately selected patients with OMD may be candidates for prolonged disease-free survival or cure with the addition of local therapy to systemic therapy.²

The EORTC 4004 phase 2 randomized control trial (RCT) analyzed radiofrequency ablation (RFA) for colorectal liver metastases with systemic therapy vs systemic therapy alone for patients with ≤ 9 liver lesions.³ Systemic therapyconsisted of 5-FU/leucovorin/oxaliplatin, with bevacizumab added to the regimen 3.5 years into the study, per updated standard- of-care. This trial was the first to demonstrate the benefit of aggressive local treatment vs system treatment alone for OMD with a progression-free survival (PFS) benefit (16.8 vs 9.9 months; hazard ratio [HR], 0.63; P = .03) and overall survival (OS) benefit (45.3 vs 40.5 months; HR, 0.74; P = .02) with the addition of local treatment with RFA.

Since the presentations of the SABR-COMET phase 2 RCT and another study by Gomez et al at the American Society for Radiation Oncology (ASTRO) 2018 annual meeting, the paradigm for offering local RT for OMD has rapidly evolved. Both studies found PFS and OS benefits of RT for patients with OMD.^4,5 Additional RCTs have since demonstrated that for properly selected patients with OMD, aggressive local RT improved PFS and OS.^6-9 These small studies have led to larger RCTs to better understand who benefits from local consolidative treatment, particularly RT.^10,11

There is a large degree of heterogeneity in how oncologists define and approach OMD treatment. The 2020 European Society for Radiotherapy and Oncology (ESTRO) and ASTRO consensus guidelines defined the OMD state as 1 to 5 metastatic lesions for which all metastatic sites are safely treatable.¹² The purpose of this study was to evaluate perceptions and practice patterns among radiation oncologists and medical oncologists regarding the use of local RT for OMD across the Veterans Health Administration (VHA).

Methods

A 12-question survey was developed by the VHA Palliative Radiotherapy Task Force using the ESTRO-ASTRO consensus guidelines to define OMD. The survey was emailed to the VHA radiation oncology and medical oncology listservs on August 1, 2023. These listservs consist of physicians in these specialties either directly employed by the VHA or serve in its facilities as contractors. The original response closure date was August 11, 2023, but it was extended to August 18, 2023, to increase responses. No incentives were offered to respondents. Two email reminders were sent to the medical oncology listserv and 3 to the radiation oncology listserv. Descriptive statistics and X² tests were used for data analysis. The impact of specialty and presence of an on-site department of radiation oncology were reviewed. This project was approved by the VHA National Oncology Program and National Radiation Oncology Program.

Results

The survey was sent to 125 radiation oncologists and 515 medical oncologists and 106 were completed for a 16.6% response rate. There were 59 (55.7%) radiation oncologist responses and 47 (44.3%) medical oncologist responses. Most (96.2%) respondents were board-certified, and 84 (79.2%) were affiliated with an academic center. Not every respondent answered every question (Table).

All respondents (n = 105) indicated there is a potential benefit of high-dose RT for appropriately selected cases. Ninety-four oncologists (88.7%) believed that RT for OMD contributes to cure (88.1% of radiation oncologists, 89.4% of medical oncologists; P = .84) for appropriately selected cases. Some respondents who did not believe RT for OMD contributes to cure added comments about other perceived benefits, such as local disease control for palliation, delaying systemic therapy with its associated toxicities, and prolongation of disease-free survival or OS. A higher percentage of respondents with academic affiliations believed high-dose RT contributes to cure, although this difference did not reach statistical significance (Figure 1).

Fifty-five respondents (51.9%; 55.2% radiation oncologists vs 50.0% medical oncologists; P = .60) responded that local RT for OMD treatment should not be limited by primary tumor type. Of respondents who responded that OMD treatment should be limited based on the type of primary tumor, many provided comments that argued there was a benefit for non-small cell lung cancer (NSCLC), prostate adenocarcinoma (PCa), and colorectal cancer.

The definition of how many metastatic lesions qualify as OMD varied. A total of 48.6% of respondents defined OMD as ≤ 3 lesions and 42.9% answered ≤ 5 lesions. A majority of radiation oncologists (55.2%) classified ≤ 5 lesions as OMD, whereas a majority of medical oncologists (66.0%) considered ≤ 3 lesions as OMD (P = .006) (Figure 2).

Thirty-six medical oncologists (76.6%) report having an on-site department of radiation oncology (Figure 3). This subgroup was more likely to consider local RT potentially curative compared with their medical oncology peers without on-site radiation oncology (94.4% vs 72.7%; P = .04).

Case Management

The 3 clinical cases demonstrated the heterogeneity of management approaches for OMD. The first described a man aged 65 years with PCa and 2 asymptomatic pelvic bone metastases. Ninety-three respondents (90.3%) recommended RT at the primary site and 74.8% recommended RT to both the primary site and metastatic foci. Sixty-three respondents (67.7%) recommended a STAMPEDE-compatible dose, and 30 (32.3%) recommended a definitive dose.

The second clinical case was a 60-year-old man with a cT1N2M1 NSCLC, with a solitary metastatic focus to the left iliac wing. Fifty-eight respondents (54.7%) recommended upfront systemic chemotherapy and the option of local therapy to the chest and metastatic focus after initial chemotherapy; 28 respondents (26.4%) recommended upfront chemoradiation to the chest and definitive radiation to the left iliac wing metastasis.

The third clinical case described a male aged 70 years with a history of a treated base of tongue squamous cell carcinoma, with a solitary metastatic focus within the right lung. Respondents could pick multiple treatment options and 85 (81.7%) favored upfront definitive local therapy with surgery or stereotactic body radiotherapy (SBRT), rather than upfront chemotherapy, with future consideration for local treatment. About half of respondents (51.8%) recommended SBRT and 41.2% would let the patient decide between surgery or SBRT. Additionally, 39.6% included in their patient counselling that the treatment may be for curative intent.

Discussion

The use of local treatment to increased PFS, OS, or even cure treatment for OMD has become more accepted since the 2018 ASTRO meeting.^4,5 Palma et al analyzed a controlled primary malignancy of any histology and ≤ 5 metastatic lesions, with all lesions amenable to SBRT.⁴ With a median follow-up of 51 months when comparing the standard-of-care (SOC) arm and the SBRT arm, the 5-year PFS was not reached and the 5-year OS rates were 17.7% and 42.3% (P = .006), respectively. In the SBRT arm, about 1 in 5 patients survived > 5 years without a recurrence or disease progression, vs 0 patients in the control arm. There was a 29% rate of grade 2 or higher toxicity in the SBRT arm, including 3 deaths that were likely due to treatment. Subsequent trials, such as the phase 3 SABR-COMET-3 (1-3 metastases), phase 3 SABR-COMET-10 (4-10 metastases), and phase 1 ARREST (> 10 metastases) trials, have been specifically designed to minimize treatment-related toxicities.^13-15

Gomez et al analyzed patients at 3 sites with a controlled NSCLC primary tumor and ≤ 3 metastases.⁵ At a follow-up of 38.8 months, the PFS was 4.4 months in the SOC arm vs 14.2 months in the RT and/or surgery local treatment arm (P = .02). There was also an OS benefit of 17.0 vs 41.2 months (P = .02), respectively.

Several RCTs soon followed that demonstrated improved PFS and OS with local radiotherapy for OMD; however, total metastatic ablation of the foci is necessary to attain these PFS and OS benefits.^6-9 Still, an oncologic benefit has yet to be proven. The randomized NRGBR002 study phase 2/3 trial for oligometastatic breast cancer included patients with ≤ 4 extracranial metastases and controlled primary disease to metastasis-directed therapy (SBRT and/ or surgical resection) and systemic therapy vs systemic therapy alone.¹⁰ The study did not demonstrate improved PFS or OS at 3 years. However, for most breast cancers, especially with the rapid advancements in systemic therapy that have been achieved, longer follow-up may be necessary to detect a significant difference.

The prospective single-arm phase 2 SABR-5 trial retrospectively demonstrated important lessons about the timing of SBRT and systemic therapy.¹¹ This study included patients with ≤ 5 metastases of any histology, and they received SBRT to all lesions. SABR-5 retrospectively compared patients who received upfront systemic therapy followed by SBRT vs another cohort that first received SBRT and did not receive systemic therapy until there was disease progression. Patients with oligo-progression were excluded, as it demonstrated systemic drug resistance. At a median follow-up time of 34 months, delayed systemic treatment was associated with shorter PFS (23 vs 34 months, respectively; P = .001), but not worse 3-year OS (80% vs 85%, respectively; P = .66). In addition, the delayed systemic treatment arm demonstrated a reduced risk of grade 2 or higher SBRT-related toxicity (odds ratio, 0.35; P < .001).

Similarly, the STOMP phase 2 trial analyzed the role of metastasis-directed therapy (MDT) in delaying initiation of androgen deprivation therapy (ADT) in a randomized phase 2 trial.¹⁶ This study included patients with asymptomatic PCa with a biochemical recurrence after primary treatment, 1 to 3 extracranial metastatic lesions, and serum testosterone levels > 50 ng/mL. Sixty-two patients were randomized 1:1 to either MDT (SBRT or surgery) of all lesions or surveillance. The 5-year ADT-free survival was 34% for MDT vs 8% for surveillance (P = .06).

VHA Radiation Oncology

The VHA has 138 departments of medical oncology, but only 41 departments of radiation oncology. Compared with medical oncologists without an on-site radiation oncology department, those with on-site departments were more likely to believe that local RT was potentially curative (94.4% vs 72.7%, respectively; P = .04). This finding suggests that a cancer center that includes both specialties has closer collaboration, which results in greater inclination to embrace local RT for OMD, as it has demonstrated PFS and OS benefits.

The radiation and medical oncologists surveyed had statistically significant differences in response by specialty regarding the maximal number of lesions still believed to constitute OMD. Most radiation oncologists classified ≤ 5 lesions as OMD, whereas most medical oncologists classified ≤ 3 lesions as OMD. This difference is not unexpected. There is no universally agreed-upon definition of OMD, and criteria differ across studies.

While the SABR-COMET trial did include ≤ 5 metastatic lesions, it was a phase 2 RCT, making subgroup analysis difficult. Ongoing phase 3 trials that are more specific in the number of metastases, comparing 1 to 3 vs 4 to 10 metastases (SABR-COMET-3 and SABR-COMET-10, respectively).^13,14 There is even an ongoing phase 1 trial (ARREST) studying the potential benefits of treating (“restraining”) > 10 metastases, if dosimetrically feasible.¹⁵ Within the VHA, VA STARPORT is investigating MDT for recurrent or de novo hormone-sensitive metastatic PCa.¹⁷ The ongoing HALT phase 2/3 trial focuses on patients with actionable mutations to help determine management of oligo-progression in mutation-positive NSCLC.¹⁸

There was no significant difference by specialty in who responded that offering local RT for OMD treatment should not be limited by histology (55.2% of radiation oncologists and 50.0% of medical oncologists; P = .60). Oncologists could make the argument that some histologies (eg, pancreatic adenocarcinomas) have such poor prognoses that local RT would not meaningfully affect oncologic outcomes, while potentially adding toxicity, whereas others could point to improved systemic therapy regimens and the low toxicity rates with careful hypofractionation regimens. Of note, the 41-patient phase 2 EXTEND trial for pancreatic ductal adenocarcinoma suggested an oncologic benefit to MDT, with far better PFS and no grade ≥ 3 toxicities related to MDT.¹⁹ About half of respondents for each specialty believed the primary histology should affect the decision. Further clarification may emerge from phase 3 trials.

Of note, a 2023 study of 44 radiation and medical oncologists at 2 Harvard Medical School-affiliated hospitals found that for synchronous OMD, 50.0% of medical oncologists and 5.3% (P < .01) of radiation oncologists recommended systemic treatment, suggesting a greater divergence in approach than found in this study.²⁰

Limitations

The response rate of 17.0% raised a potential for selection bias, but this rate is expected for a nonincentivized medical survey. A study by the American Board of Internal Medicine with 11 surveys and 6 weekly email contacts only generated a 23.7% response rate, while another study among physicians demonstrated a 4.5% response rate for email-based contact and 11.8% for mail-based contact.^21,22 We could have asked participants questions regarding demographics and geography to ensure the survey represented a diverse sample of the medical community, although additional questions would likely suppress the response rate. Additional data collection about respondents may elucidate the rationale for differences in their responses, especially between the specialties. In a planned subsequent survey in several years, the question on the number of lesions that qualifies as OMD may be amended to reflect the context and dosimetry for the maximal number of metastases constituting OMD; the joint ESTRO-ASTRO consensus defined OMD as 1 to 5 metastatic lesions, but in which all metastatic sites must be safely treatable.¹² Also, fewer example cases could be included to simplify the survey and boost response rates. A future survey may ask about the timing of SBRT and systemic therapy, and whether SBRT can safely delay systemic therapy.

Conclusions

Survey results demonstrated significant confidence among both radiation oncologists and medical oncologists that local RT for OMD improves outcomes, which is encouraging and a reflection of the recent evidence-based paradigm shift in viewing metastatic disease as a spectrum. However, there is a difference between radiation oncologists and medical oncologists in how they define OMD, and preferred treatment of the sample cases presented revealed nuanced differences by specialty. Close collaboration with radiation oncologists influences the belief of medical oncologists in the beneficial role of RT for OMD. As more phase 3 data for OMD local treatments emerge, additional investigation is needed on how beliefs and practice patterns evolve among radiation and medical oncologists.

The treatment of metastatic solid tumors has been based historically on systemic therapies, with the goal of delaying progression and extend life as long as possible, with tolerable treatment-related adverse events. Some exceptions were made for local treatment with surgery or radiotherapy (RT), often for patients with a single metastasis. A 1939 report describes a patient with renal adenocarcinoma and a solitary lung metastasis who underwent RT to the lung lesion after nephrectomy and subsequently partial lobectomy after the metastatic lesion progressed. The authors argued that if a metastasis appears solitary and accessible, it is plausible to remove it in addition to the primary growth.¹

In 1995 Hellman and Weichselbaum proposed oligometastatic disease (OMD). They reasoned that malignancy exists along a spectrum from localized disease to widely disseminated disease, with OMD existing in between with a still-restricted tumor metastatic capacity. Appropriately selected patients with OMD may be candidates for prolonged disease-free survival or cure with the addition of local therapy to systemic therapy.²

The EORTC 4004 phase 2 randomized control trial (RCT) analyzed radiofrequency ablation (RFA) for colorectal liver metastases with systemic therapy vs systemic therapy alone for patients with ≤ 9 liver lesions.³ Systemic therapyconsisted of 5-FU/leucovorin/oxaliplatin, with bevacizumab added to the regimen 3.5 years into the study, per updated standard- of-care. This trial was the first to demonstrate the benefit of aggressive local treatment vs system treatment alone for OMD with a progression-free survival (PFS) benefit (16.8 vs 9.9 months; hazard ratio [HR], 0.63; P = .03) and overall survival (OS) benefit (45.3 vs 40.5 months; HR, 0.74; P = .02) with the addition of local treatment with RFA.

Since the presentations of the SABR-COMET phase 2 RCT and another study by Gomez et al at the American Society for Radiation Oncology (ASTRO) 2018 annual meeting, the paradigm for offering local RT for OMD has rapidly evolved. Both studies found PFS and OS benefits of RT for patients with OMD.^4,5 Additional RCTs have since demonstrated that for properly selected patients with OMD, aggressive local RT improved PFS and OS.^6-9 These small studies have led to larger RCTs to better understand who benefits from local consolidative treatment, particularly RT.^10,11

There is a large degree of heterogeneity in how oncologists define and approach OMD treatment. The 2020 European Society for Radiotherapy and Oncology (ESTRO) and ASTRO consensus guidelines defined the OMD state as 1 to 5 metastatic lesions for which all metastatic sites are safely treatable.¹² The purpose of this study was to evaluate perceptions and practice patterns among radiation oncologists and medical oncologists regarding the use of local RT for OMD across the Veterans Health Administration (VHA).

Methods

A 12-question survey was developed by the VHA Palliative Radiotherapy Task Force using the ESTRO-ASTRO consensus guidelines to define OMD. The survey was emailed to the VHA radiation oncology and medical oncology listservs on August 1, 2023. These listservs consist of physicians in these specialties either directly employed by the VHA or serve in its facilities as contractors. The original response closure date was August 11, 2023, but it was extended to August 18, 2023, to increase responses. No incentives were offered to respondents. Two email reminders were sent to the medical oncology listserv and 3 to the radiation oncology listserv. Descriptive statistics and X² tests were used for data analysis. The impact of specialty and presence of an on-site department of radiation oncology were reviewed. This project was approved by the VHA National Oncology Program and National Radiation Oncology Program.

Results

The survey was sent to 125 radiation oncologists and 515 medical oncologists and 106 were completed for a 16.6% response rate. There were 59 (55.7%) radiation oncologist responses and 47 (44.3%) medical oncologist responses. Most (96.2%) respondents were board-certified, and 84 (79.2%) were affiliated with an academic center. Not every respondent answered every question (Table).

All respondents (n = 105) indicated there is a potential benefit of high-dose RT for appropriately selected cases. Ninety-four oncologists (88.7%) believed that RT for OMD contributes to cure (88.1% of radiation oncologists, 89.4% of medical oncologists; P = .84) for appropriately selected cases. Some respondents who did not believe RT for OMD contributes to cure added comments about other perceived benefits, such as local disease control for palliation, delaying systemic therapy with its associated toxicities, and prolongation of disease-free survival or OS. A higher percentage of respondents with academic affiliations believed high-dose RT contributes to cure, although this difference did not reach statistical significance (Figure 1).

Fifty-five respondents (51.9%; 55.2% radiation oncologists vs 50.0% medical oncologists; P = .60) responded that local RT for OMD treatment should not be limited by primary tumor type. Of respondents who responded that OMD treatment should be limited based on the type of primary tumor, many provided comments that argued there was a benefit for non-small cell lung cancer (NSCLC), prostate adenocarcinoma (PCa), and colorectal cancer.

The definition of how many metastatic lesions qualify as OMD varied. A total of 48.6% of respondents defined OMD as ≤ 3 lesions and 42.9% answered ≤ 5 lesions. A majority of radiation oncologists (55.2%) classified ≤ 5 lesions as OMD, whereas a majority of medical oncologists (66.0%) considered ≤ 3 lesions as OMD (P = .006) (Figure 2).

Thirty-six medical oncologists (76.6%) report having an on-site department of radiation oncology (Figure 3). This subgroup was more likely to consider local RT potentially curative compared with their medical oncology peers without on-site radiation oncology (94.4% vs 72.7%; P = .04).

Case Management

The 3 clinical cases demonstrated the heterogeneity of management approaches for OMD. The first described a man aged 65 years with PCa and 2 asymptomatic pelvic bone metastases. Ninety-three respondents (90.3%) recommended RT at the primary site and 74.8% recommended RT to both the primary site and metastatic foci. Sixty-three respondents (67.7%) recommended a STAMPEDE-compatible dose, and 30 (32.3%) recommended a definitive dose.

The second clinical case was a 60-year-old man with a cT1N2M1 NSCLC, with a solitary metastatic focus to the left iliac wing. Fifty-eight respondents (54.7%) recommended upfront systemic chemotherapy and the option of local therapy to the chest and metastatic focus after initial chemotherapy; 28 respondents (26.4%) recommended upfront chemoradiation to the chest and definitive radiation to the left iliac wing metastasis.

The third clinical case described a male aged 70 years with a history of a treated base of tongue squamous cell carcinoma, with a solitary metastatic focus within the right lung. Respondents could pick multiple treatment options and 85 (81.7%) favored upfront definitive local therapy with surgery or stereotactic body radiotherapy (SBRT), rather than upfront chemotherapy, with future consideration for local treatment. About half of respondents (51.8%) recommended SBRT and 41.2% would let the patient decide between surgery or SBRT. Additionally, 39.6% included in their patient counselling that the treatment may be for curative intent.

Discussion

The use of local treatment to increased PFS, OS, or even cure treatment for OMD has become more accepted since the 2018 ASTRO meeting.^4,5 Palma et al analyzed a controlled primary malignancy of any histology and ≤ 5 metastatic lesions, with all lesions amenable to SBRT.⁴ With a median follow-up of 51 months when comparing the standard-of-care (SOC) arm and the SBRT arm, the 5-year PFS was not reached and the 5-year OS rates were 17.7% and 42.3% (P = .006), respectively. In the SBRT arm, about 1 in 5 patients survived > 5 years without a recurrence or disease progression, vs 0 patients in the control arm. There was a 29% rate of grade 2 or higher toxicity in the SBRT arm, including 3 deaths that were likely due to treatment. Subsequent trials, such as the phase 3 SABR-COMET-3 (1-3 metastases), phase 3 SABR-COMET-10 (4-10 metastases), and phase 1 ARREST (> 10 metastases) trials, have been specifically designed to minimize treatment-related toxicities.^13-15

Gomez et al analyzed patients at 3 sites with a controlled NSCLC primary tumor and ≤ 3 metastases.⁵ At a follow-up of 38.8 months, the PFS was 4.4 months in the SOC arm vs 14.2 months in the RT and/or surgery local treatment arm (P = .02). There was also an OS benefit of 17.0 vs 41.2 months (P = .02), respectively.

Several RCTs soon followed that demonstrated improved PFS and OS with local radiotherapy for OMD; however, total metastatic ablation of the foci is necessary to attain these PFS and OS benefits.^6-9 Still, an oncologic benefit has yet to be proven. The randomized NRGBR002 study phase 2/3 trial for oligometastatic breast cancer included patients with ≤ 4 extracranial metastases and controlled primary disease to metastasis-directed therapy (SBRT and/ or surgical resection) and systemic therapy vs systemic therapy alone.¹⁰ The study did not demonstrate improved PFS or OS at 3 years. However, for most breast cancers, especially with the rapid advancements in systemic therapy that have been achieved, longer follow-up may be necessary to detect a significant difference.

The prospective single-arm phase 2 SABR-5 trial retrospectively demonstrated important lessons about the timing of SBRT and systemic therapy.¹¹ This study included patients with ≤ 5 metastases of any histology, and they received SBRT to all lesions. SABR-5 retrospectively compared patients who received upfront systemic therapy followed by SBRT vs another cohort that first received SBRT and did not receive systemic therapy until there was disease progression. Patients with oligo-progression were excluded, as it demonstrated systemic drug resistance. At a median follow-up time of 34 months, delayed systemic treatment was associated with shorter PFS (23 vs 34 months, respectively; P = .001), but not worse 3-year OS (80% vs 85%, respectively; P = .66). In addition, the delayed systemic treatment arm demonstrated a reduced risk of grade 2 or higher SBRT-related toxicity (odds ratio, 0.35; P < .001).

Similarly, the STOMP phase 2 trial analyzed the role of metastasis-directed therapy (MDT) in delaying initiation of androgen deprivation therapy (ADT) in a randomized phase 2 trial.¹⁶ This study included patients with asymptomatic PCa with a biochemical recurrence after primary treatment, 1 to 3 extracranial metastatic lesions, and serum testosterone levels > 50 ng/mL. Sixty-two patients were randomized 1:1 to either MDT (SBRT or surgery) of all lesions or surveillance. The 5-year ADT-free survival was 34% for MDT vs 8% for surveillance (P = .06).

VHA Radiation Oncology

The VHA has 138 departments of medical oncology, but only 41 departments of radiation oncology. Compared with medical oncologists without an on-site radiation oncology department, those with on-site departments were more likely to believe that local RT was potentially curative (94.4% vs 72.7%, respectively; P = .04). This finding suggests that a cancer center that includes both specialties has closer collaboration, which results in greater inclination to embrace local RT for OMD, as it has demonstrated PFS and OS benefits.

The radiation and medical oncologists surveyed had statistically significant differences in response by specialty regarding the maximal number of lesions still believed to constitute OMD. Most radiation oncologists classified ≤ 5 lesions as OMD, whereas most medical oncologists classified ≤ 3 lesions as OMD. This difference is not unexpected. There is no universally agreed-upon definition of OMD, and criteria differ across studies.

While the SABR-COMET trial did include ≤ 5 metastatic lesions, it was a phase 2 RCT, making subgroup analysis difficult. Ongoing phase 3 trials that are more specific in the number of metastases, comparing 1 to 3 vs 4 to 10 metastases (SABR-COMET-3 and SABR-COMET-10, respectively).^13,14 There is even an ongoing phase 1 trial (ARREST) studying the potential benefits of treating (“restraining”) > 10 metastases, if dosimetrically feasible.¹⁵ Within the VHA, VA STARPORT is investigating MDT for recurrent or de novo hormone-sensitive metastatic PCa.¹⁷ The ongoing HALT phase 2/3 trial focuses on patients with actionable mutations to help determine management of oligo-progression in mutation-positive NSCLC.¹⁸

There was no significant difference by specialty in who responded that offering local RT for OMD treatment should not be limited by histology (55.2% of radiation oncologists and 50.0% of medical oncologists; P = .60). Oncologists could make the argument that some histologies (eg, pancreatic adenocarcinomas) have such poor prognoses that local RT would not meaningfully affect oncologic outcomes, while potentially adding toxicity, whereas others could point to improved systemic therapy regimens and the low toxicity rates with careful hypofractionation regimens. Of note, the 41-patient phase 2 EXTEND trial for pancreatic ductal adenocarcinoma suggested an oncologic benefit to MDT, with far better PFS and no grade ≥ 3 toxicities related to MDT.¹⁹ About half of respondents for each specialty believed the primary histology should affect the decision. Further clarification may emerge from phase 3 trials.

Of note, a 2023 study of 44 radiation and medical oncologists at 2 Harvard Medical School-affiliated hospitals found that for synchronous OMD, 50.0% of medical oncologists and 5.3% (P < .01) of radiation oncologists recommended systemic treatment, suggesting a greater divergence in approach than found in this study.²⁰

Limitations

The response rate of 17.0% raised a potential for selection bias, but this rate is expected for a nonincentivized medical survey. A study by the American Board of Internal Medicine with 11 surveys and 6 weekly email contacts only generated a 23.7% response rate, while another study among physicians demonstrated a 4.5% response rate for email-based contact and 11.8% for mail-based contact.^21,22 We could have asked participants questions regarding demographics and geography to ensure the survey represented a diverse sample of the medical community, although additional questions would likely suppress the response rate. Additional data collection about respondents may elucidate the rationale for differences in their responses, especially between the specialties. In a planned subsequent survey in several years, the question on the number of lesions that qualifies as OMD may be amended to reflect the context and dosimetry for the maximal number of metastases constituting OMD; the joint ESTRO-ASTRO consensus defined OMD as 1 to 5 metastatic lesions, but in which all metastatic sites must be safely treatable.¹² Also, fewer example cases could be included to simplify the survey and boost response rates. A future survey may ask about the timing of SBRT and systemic therapy, and whether SBRT can safely delay systemic therapy.

Conclusions

Survey results demonstrated significant confidence among both radiation oncologists and medical oncologists that local RT for OMD improves outcomes, which is encouraging and a reflection of the recent evidence-based paradigm shift in viewing metastatic disease as a spectrum. However, there is a difference between radiation oncologists and medical oncologists in how they define OMD, and preferred treatment of the sample cases presented revealed nuanced differences by specialty. Close collaboration with radiation oncologists influences the belief of medical oncologists in the beneficial role of RT for OMD. As more phase 3 data for OMD local treatments emerge, additional investigation is needed on how beliefs and practice patterns evolve among radiation and medical oncologists.