Will Pass

The number of people with hemophilia worldwide is higher than previously estimated, and patients still face a shortened life expectancy, according to an international meta-analysis of registry data.

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Approximately 1.125 million people have hemophilia worldwide, compared with the previous estimate of 400,000, reported lead author Alfonso Iorio, MD, PhD, of McMaster University, Hamilton, Ont., and colleagues.

The previous estimate, from the early 2000s, was based on prevalence in the United States and the global population at the time, the investigators explained. Their report is in Annals of Internal Medicine.

They noted a lack of clarity in prior estimates concerning type and severity of hemophilia, and aimed to correct this knowledge gap with the present meta-analysis.

Prevalence was estimated using data from registries in Australia, Canada, Italy, France, the United Kingdom, and New Zealand, which are all high-income countries. Prevalence at birth was estimated using the Canadian, French, and British registries, as these are the most established databases, according to the investigators. The World Federation of Hemophilia Annual Global survey was used to estimate the total global number of patients with hemophilia, while national statistics databases were used to determine the number of males and live male births.

Of the 1.125 million cases of hemophilia worldwide, the investigators estimated that 418,000 are likely severe. Proportionally, 17.1 out of 100,000 males have hemophilia A, with 6.0 out of 100,000 males exhibiting severe hemophilia A. Hemophilia B is less common, occurring in 3.8 out of 100,000 males, with a 1.1 out of 100,000 classified as severe.

Turning to prevalence at birth, the investigators estimated that there are 24.6 cases of hemophilia A per 100,000 male births and 5.0 cases of hemophilia B per 100,000 male births.

The associated life expectancy disadvantage in high-income countries is highest for severe hemophilia A (37%), followed by all severities of hemophilia A (30%), severe hemophilia B (27%), and all severities of hemophilia B (24%).

“Having 1,125,000 persons with hemophilia worldwide, of whom about 418,000 have severe and mostly undiagnosed disease, constitutes a formidable challenge and burden for researchers and health care systems, especially because only 196,706 patients have been identified and reported globally,” the investigators wrote. “More efficient diagnostic approaches are needed in less wealthy countries to take advantage of current and future treatment modalities, including gene therapy. Increased demand for care should drive new policy planning and spur renewed effort toward the development and manufacture of new drugs.”

The updated prevalence figures will serve as a valuable roadmap for the future, according to J. Michael Soucie, PhD, of the Centers for Disease Control and Prevention, Atlanta.

“Although the magnitude of the global gaps in care for persons with hemophilia is daunting, country specific data generated by application of the prevalence estimates reported by Iorio and colleagues are an important step toward prioritizing efforts to address these gaps,” Dr. Soucie wrote in an accompanying editorial. “Having more accurate prevalence data might also allow identification of ways in which regional efforts to improve care access could generate considerable benefits for patients and cost savings for countries. Armed with these data for action, we can hope to make substantial progress toward the goal of improving the lives of persons with hemophilia wherever they live.”

The study received no financial support. The investigators reported relationships with Pfizer, Roche, Novo Nordisk, and others. Dr. Soucie reported having no conflicts of interest.

SOURCE: Iorio A et al. Ann Intern Med. 2019 Sept 10. doi: 10.7326/M19-1208.

The number of people with hemophilia worldwide is higher than previously estimated, and patients still face a shortened life expectancy, according to an international meta-analysis of registry data.

©designer491/Thinkstock

Approximately 1.125 million people have hemophilia worldwide, compared with the previous estimate of 400,000, reported lead author Alfonso Iorio, MD, PhD, of McMaster University, Hamilton, Ont., and colleagues.

The previous estimate, from the early 2000s, was based on prevalence in the United States and the global population at the time, the investigators explained. Their report is in Annals of Internal Medicine.

They noted a lack of clarity in prior estimates concerning type and severity of hemophilia, and aimed to correct this knowledge gap with the present meta-analysis.

Prevalence was estimated using data from registries in Australia, Canada, Italy, France, the United Kingdom, and New Zealand, which are all high-income countries. Prevalence at birth was estimated using the Canadian, French, and British registries, as these are the most established databases, according to the investigators. The World Federation of Hemophilia Annual Global survey was used to estimate the total global number of patients with hemophilia, while national statistics databases were used to determine the number of males and live male births.

Of the 1.125 million cases of hemophilia worldwide, the investigators estimated that 418,000 are likely severe. Proportionally, 17.1 out of 100,000 males have hemophilia A, with 6.0 out of 100,000 males exhibiting severe hemophilia A. Hemophilia B is less common, occurring in 3.8 out of 100,000 males, with a 1.1 out of 100,000 classified as severe.

Turning to prevalence at birth, the investigators estimated that there are 24.6 cases of hemophilia A per 100,000 male births and 5.0 cases of hemophilia B per 100,000 male births.

The associated life expectancy disadvantage in high-income countries is highest for severe hemophilia A (37%), followed by all severities of hemophilia A (30%), severe hemophilia B (27%), and all severities of hemophilia B (24%).

“Having 1,125,000 persons with hemophilia worldwide, of whom about 418,000 have severe and mostly undiagnosed disease, constitutes a formidable challenge and burden for researchers and health care systems, especially because only 196,706 patients have been identified and reported globally,” the investigators wrote. “More efficient diagnostic approaches are needed in less wealthy countries to take advantage of current and future treatment modalities, including gene therapy. Increased demand for care should drive new policy planning and spur renewed effort toward the development and manufacture of new drugs.”

The updated prevalence figures will serve as a valuable roadmap for the future, according to J. Michael Soucie, PhD, of the Centers for Disease Control and Prevention, Atlanta.

“Although the magnitude of the global gaps in care for persons with hemophilia is daunting, country specific data generated by application of the prevalence estimates reported by Iorio and colleagues are an important step toward prioritizing efforts to address these gaps,” Dr. Soucie wrote in an accompanying editorial. “Having more accurate prevalence data might also allow identification of ways in which regional efforts to improve care access could generate considerable benefits for patients and cost savings for countries. Armed with these data for action, we can hope to make substantial progress toward the goal of improving the lives of persons with hemophilia wherever they live.”

The study received no financial support. The investigators reported relationships with Pfizer, Roche, Novo Nordisk, and others. Dr. Soucie reported having no conflicts of interest.

SOURCE: Iorio A et al. Ann Intern Med. 2019 Sept 10. doi: 10.7326/M19-1208.

The number of people with hemophilia worldwide is higher than previously estimated, and patients still face a shortened life expectancy, according to an international meta-analysis of registry data.

©designer491/Thinkstock

Approximately 1.125 million people have hemophilia worldwide, compared with the previous estimate of 400,000, reported lead author Alfonso Iorio, MD, PhD, of McMaster University, Hamilton, Ont., and colleagues.

The previous estimate, from the early 2000s, was based on prevalence in the United States and the global population at the time, the investigators explained. Their report is in Annals of Internal Medicine.

They noted a lack of clarity in prior estimates concerning type and severity of hemophilia, and aimed to correct this knowledge gap with the present meta-analysis.

Prevalence was estimated using data from registries in Australia, Canada, Italy, France, the United Kingdom, and New Zealand, which are all high-income countries. Prevalence at birth was estimated using the Canadian, French, and British registries, as these are the most established databases, according to the investigators. The World Federation of Hemophilia Annual Global survey was used to estimate the total global number of patients with hemophilia, while national statistics databases were used to determine the number of males and live male births.

Of the 1.125 million cases of hemophilia worldwide, the investigators estimated that 418,000 are likely severe. Proportionally, 17.1 out of 100,000 males have hemophilia A, with 6.0 out of 100,000 males exhibiting severe hemophilia A. Hemophilia B is less common, occurring in 3.8 out of 100,000 males, with a 1.1 out of 100,000 classified as severe.

Turning to prevalence at birth, the investigators estimated that there are 24.6 cases of hemophilia A per 100,000 male births and 5.0 cases of hemophilia B per 100,000 male births.

The associated life expectancy disadvantage in high-income countries is highest for severe hemophilia A (37%), followed by all severities of hemophilia A (30%), severe hemophilia B (27%), and all severities of hemophilia B (24%).

“Having 1,125,000 persons with hemophilia worldwide, of whom about 418,000 have severe and mostly undiagnosed disease, constitutes a formidable challenge and burden for researchers and health care systems, especially because only 196,706 patients have been identified and reported globally,” the investigators wrote. “More efficient diagnostic approaches are needed in less wealthy countries to take advantage of current and future treatment modalities, including gene therapy. Increased demand for care should drive new policy planning and spur renewed effort toward the development and manufacture of new drugs.”

The updated prevalence figures will serve as a valuable roadmap for the future, according to J. Michael Soucie, PhD, of the Centers for Disease Control and Prevention, Atlanta.

“Although the magnitude of the global gaps in care for persons with hemophilia is daunting, country specific data generated by application of the prevalence estimates reported by Iorio and colleagues are an important step toward prioritizing efforts to address these gaps,” Dr. Soucie wrote in an accompanying editorial. “Having more accurate prevalence data might also allow identification of ways in which regional efforts to improve care access could generate considerable benefits for patients and cost savings for countries. Armed with these data for action, we can hope to make substantial progress toward the goal of improving the lives of persons with hemophilia wherever they live.”

The study received no financial support. The investigators reported relationships with Pfizer, Roche, Novo Nordisk, and others. Dr. Soucie reported having no conflicts of interest.

SOURCE: Iorio A et al. Ann Intern Med. 2019 Sept 10. doi: 10.7326/M19-1208.

Continuous use of NSAIDs could increase the risk of incident hypertension among patients with ankylosing spondylitis (AS), according to findings from a recent prospective study.

dolgachov/Thinkstock

Against expectations, data also suggested that tumor necrosis factor inhibitor (TNFi) therapy could increase blood pressure, although this finding was not significant across all methods of analysis, reported lead author Jean W. Liew, MD, of the University of Washington, Seattle, and colleagues.

The investigators noted that patients with AS already have a greater risk of cardiovascular disease than that of the general population, making any added risks that much more concerning.

“[T]he evidence for increased cardiovascular disease burden and cardiovascular risk in patients with inflammatory rheumatic diseases is well recognized,” the investigators wrote in Arthritis Care & Research. “Multiple population-based studies have demonstrated increased cardiovascular events and cardiovascular-related mortality in AS. There is a high prevalence of cardiovascular risk factors among individuals with AS, particularly hypertension.”

Exacerbation of this risk by NSAIDs has been previously studied with mixed results, according to the investigators. Meta-analyses have suggested that NSAIDs increase blood pressure in normotensive and hypertensive individuals, but some data point to a cardioprotective effect among those with AS, possibly as a consequence of dampened inflammation, and/or improved physical activity, which could lead to a secondary CV benefit. Still, the relationship between NSAIDs and CV risk was unclear, prompting the current study.

The investigators enrolled 1,282 patients with AS at five centers in the United States and Australia. Using a combination of clinical evaluations and self-reporting, enrollees were monitored at regular intervals. Disease activity was tracked with the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), while the Bath Ankylosing Spondylitis Functional Index (BASFI) was used for functional impairments. Patients were also checked for a variety of comorbidities such as hypertension, coronary artery disease, mental health conditions, and renal disorders. Medication data included type, dosage, frequency, duration, and number of missed doses.

Including only baseline normotensive patients with at least 1 year of follow-up, 628 participants were eligible for analysis, of whom 200 used NSAIDs continuously. After a median of 7 years follow-up, 129 out of 628 patients developed hypertension. This translated to a hazard ratio (HR) for incident hypertension of 1.12 (95% confidence interval, 1.04-1.20), compared with nonusers or those who took NSAIDs intermittently. This relationship did not differ across subgroups defined by age, disease activity, body mass index, or TNFi use. Multiple sensitivity analyses added support to the association between continuous NSAID use and hypertension.

“The association of NSAIDs and incident hypertension remains particularly concerning, as the early development of hypertension may portend a higher risk of premature CV events due to cumulative exposure,” the investigators wrote.

In contrast with NSAIDs, TNFi therapy was not associated with hypertension across all models; however, against expectations, two models of analysis pointed to an 8% increased risk.

“Although TNFi use did not reach statistical significance in the main model, the direction of association was opposite that hypothesized based on prior data, specifically that TNFi use reduces CV risk by suppressing chronic inflammation,” the investigators wrote.

Considering the present findings, and previous studies, which have reported conflicting associations between TNFi use and hypertension, the investigators suggested that more research is needed, and offered specific methods to approach the topic.

“The association of TNFi use and incident hypertension requires further clarification in future studies,” they wrote, “which may be done by applying a marginal structural modeling (MSM) framework and inverse probability of treatment weighting (IPTW) statistical analyses to account for the relationships between TNFi use, disease activity, and NSAID use.”

In their concluding remarks, the investigators further emphasized the current knowledge gap in this area.

“There is an unmet need to clarify how treatment choices, particularly the use of NSAIDs and TNFi, impact CV risk factors and CV events in AS,” they wrote. “Further studies are needed to focus on precision medicine and predicting risk and benefit for patients in whom continuous NSAIDs are being considered. These further studies can inform the revision of guidelines to address the management of CV risk factors and CV disease in AS and axial spondyloarthritis more broadly.”

The investigators reported funding from the National Institutes of Health, the Assessment of Spondyloarthritis International Society, the Spondylitis Association of America, and the Russel Engleman Rheumatology Research Center at the University of California, San Francisco. Some authors reported ties with Eli Lilly, Novartis, and other pharmaceutical companies..

SOURCE: Liew et al. Arthritis Care Res. 2019 Sep 17. doi: 10.1002/acr.24070.

Continuous use of NSAIDs could increase the risk of incident hypertension among patients with ankylosing spondylitis (AS), according to findings from a recent prospective study.

dolgachov/Thinkstock

Against expectations, data also suggested that tumor necrosis factor inhibitor (TNFi) therapy could increase blood pressure, although this finding was not significant across all methods of analysis, reported lead author Jean W. Liew, MD, of the University of Washington, Seattle, and colleagues.

The investigators noted that patients with AS already have a greater risk of cardiovascular disease than that of the general population, making any added risks that much more concerning.

“[T]he evidence for increased cardiovascular disease burden and cardiovascular risk in patients with inflammatory rheumatic diseases is well recognized,” the investigators wrote in Arthritis Care & Research. “Multiple population-based studies have demonstrated increased cardiovascular events and cardiovascular-related mortality in AS. There is a high prevalence of cardiovascular risk factors among individuals with AS, particularly hypertension.”

Exacerbation of this risk by NSAIDs has been previously studied with mixed results, according to the investigators. Meta-analyses have suggested that NSAIDs increase blood pressure in normotensive and hypertensive individuals, but some data point to a cardioprotective effect among those with AS, possibly as a consequence of dampened inflammation, and/or improved physical activity, which could lead to a secondary CV benefit. Still, the relationship between NSAIDs and CV risk was unclear, prompting the current study.

The investigators enrolled 1,282 patients with AS at five centers in the United States and Australia. Using a combination of clinical evaluations and self-reporting, enrollees were monitored at regular intervals. Disease activity was tracked with the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), while the Bath Ankylosing Spondylitis Functional Index (BASFI) was used for functional impairments. Patients were also checked for a variety of comorbidities such as hypertension, coronary artery disease, mental health conditions, and renal disorders. Medication data included type, dosage, frequency, duration, and number of missed doses.

Including only baseline normotensive patients with at least 1 year of follow-up, 628 participants were eligible for analysis, of whom 200 used NSAIDs continuously. After a median of 7 years follow-up, 129 out of 628 patients developed hypertension. This translated to a hazard ratio (HR) for incident hypertension of 1.12 (95% confidence interval, 1.04-1.20), compared with nonusers or those who took NSAIDs intermittently. This relationship did not differ across subgroups defined by age, disease activity, body mass index, or TNFi use. Multiple sensitivity analyses added support to the association between continuous NSAID use and hypertension.

“The association of NSAIDs and incident hypertension remains particularly concerning, as the early development of hypertension may portend a higher risk of premature CV events due to cumulative exposure,” the investigators wrote.

In contrast with NSAIDs, TNFi therapy was not associated with hypertension across all models; however, against expectations, two models of analysis pointed to an 8% increased risk.

“Although TNFi use did not reach statistical significance in the main model, the direction of association was opposite that hypothesized based on prior data, specifically that TNFi use reduces CV risk by suppressing chronic inflammation,” the investigators wrote.

Considering the present findings, and previous studies, which have reported conflicting associations between TNFi use and hypertension, the investigators suggested that more research is needed, and offered specific methods to approach the topic.

“The association of TNFi use and incident hypertension requires further clarification in future studies,” they wrote, “which may be done by applying a marginal structural modeling (MSM) framework and inverse probability of treatment weighting (IPTW) statistical analyses to account for the relationships between TNFi use, disease activity, and NSAID use.”

In their concluding remarks, the investigators further emphasized the current knowledge gap in this area.

“There is an unmet need to clarify how treatment choices, particularly the use of NSAIDs and TNFi, impact CV risk factors and CV events in AS,” they wrote. “Further studies are needed to focus on precision medicine and predicting risk and benefit for patients in whom continuous NSAIDs are being considered. These further studies can inform the revision of guidelines to address the management of CV risk factors and CV disease in AS and axial spondyloarthritis more broadly.”

The investigators reported funding from the National Institutes of Health, the Assessment of Spondyloarthritis International Society, the Spondylitis Association of America, and the Russel Engleman Rheumatology Research Center at the University of California, San Francisco. Some authors reported ties with Eli Lilly, Novartis, and other pharmaceutical companies..

SOURCE: Liew et al. Arthritis Care Res. 2019 Sep 17. doi: 10.1002/acr.24070.

Continuous use of NSAIDs could increase the risk of incident hypertension among patients with ankylosing spondylitis (AS), according to findings from a recent prospective study.

dolgachov/Thinkstock

Against expectations, data also suggested that tumor necrosis factor inhibitor (TNFi) therapy could increase blood pressure, although this finding was not significant across all methods of analysis, reported lead author Jean W. Liew, MD, of the University of Washington, Seattle, and colleagues.

The investigators noted that patients with AS already have a greater risk of cardiovascular disease than that of the general population, making any added risks that much more concerning.

“[T]he evidence for increased cardiovascular disease burden and cardiovascular risk in patients with inflammatory rheumatic diseases is well recognized,” the investigators wrote in Arthritis Care & Research. “Multiple population-based studies have demonstrated increased cardiovascular events and cardiovascular-related mortality in AS. There is a high prevalence of cardiovascular risk factors among individuals with AS, particularly hypertension.”

Exacerbation of this risk by NSAIDs has been previously studied with mixed results, according to the investigators. Meta-analyses have suggested that NSAIDs increase blood pressure in normotensive and hypertensive individuals, but some data point to a cardioprotective effect among those with AS, possibly as a consequence of dampened inflammation, and/or improved physical activity, which could lead to a secondary CV benefit. Still, the relationship between NSAIDs and CV risk was unclear, prompting the current study.

The investigators enrolled 1,282 patients with AS at five centers in the United States and Australia. Using a combination of clinical evaluations and self-reporting, enrollees were monitored at regular intervals. Disease activity was tracked with the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), while the Bath Ankylosing Spondylitis Functional Index (BASFI) was used for functional impairments. Patients were also checked for a variety of comorbidities such as hypertension, coronary artery disease, mental health conditions, and renal disorders. Medication data included type, dosage, frequency, duration, and number of missed doses.

Including only baseline normotensive patients with at least 1 year of follow-up, 628 participants were eligible for analysis, of whom 200 used NSAIDs continuously. After a median of 7 years follow-up, 129 out of 628 patients developed hypertension. This translated to a hazard ratio (HR) for incident hypertension of 1.12 (95% confidence interval, 1.04-1.20), compared with nonusers or those who took NSAIDs intermittently. This relationship did not differ across subgroups defined by age, disease activity, body mass index, or TNFi use. Multiple sensitivity analyses added support to the association between continuous NSAID use and hypertension.

“The association of NSAIDs and incident hypertension remains particularly concerning, as the early development of hypertension may portend a higher risk of premature CV events due to cumulative exposure,” the investigators wrote.

In contrast with NSAIDs, TNFi therapy was not associated with hypertension across all models; however, against expectations, two models of analysis pointed to an 8% increased risk.

“Although TNFi use did not reach statistical significance in the main model, the direction of association was opposite that hypothesized based on prior data, specifically that TNFi use reduces CV risk by suppressing chronic inflammation,” the investigators wrote.

Considering the present findings, and previous studies, which have reported conflicting associations between TNFi use and hypertension, the investigators suggested that more research is needed, and offered specific methods to approach the topic.

“The association of TNFi use and incident hypertension requires further clarification in future studies,” they wrote, “which may be done by applying a marginal structural modeling (MSM) framework and inverse probability of treatment weighting (IPTW) statistical analyses to account for the relationships between TNFi use, disease activity, and NSAID use.”

In their concluding remarks, the investigators further emphasized the current knowledge gap in this area.

“There is an unmet need to clarify how treatment choices, particularly the use of NSAIDs and TNFi, impact CV risk factors and CV events in AS,” they wrote. “Further studies are needed to focus on precision medicine and predicting risk and benefit for patients in whom continuous NSAIDs are being considered. These further studies can inform the revision of guidelines to address the management of CV risk factors and CV disease in AS and axial spondyloarthritis more broadly.”

The investigators reported funding from the National Institutes of Health, the Assessment of Spondyloarthritis International Society, the Spondylitis Association of America, and the Russel Engleman Rheumatology Research Center at the University of California, San Francisco. Some authors reported ties with Eli Lilly, Novartis, and other pharmaceutical companies..

SOURCE: Liew et al. Arthritis Care Res. 2019 Sep 17. doi: 10.1002/acr.24070.

High-risk multigene testing for all patients with breast cancer may be a cost-effective way to reduce rates of breast cancer and ovarian cancer, according to investigators.

A microsimulation modeling study suggested that moving from standard BRCA testing based on clinical criteria or family history to widespread adoption of multigene testing could potentially save more than 2,400 lives per year in the United States, reported lead author Li Sun, MSc, of the London School of Hygiene & Tropical Medicine, and colleagues.

“Moving toward unselected BC testing may give an impetus for prevention in unaffected family members along with clinical implications for the patient with BC. Pathogenic variant carriers with newly diagnosed BC can opt for bilateral mastectomy rather than breast conservation at initial BC surgery,” the investigators wrote in JAMA Oncology. They noted that, presently, only 20%-30% of eligible patients are actually tested. “Testing all patients with breast cancer at diagnosis can increase testing access and uptake and identify many more pathogenic variant carriers for screening and prevention.”

To see if such a broad roll-out would be economically and medically feasible and beneficial, the investigators performed a modeling study involving 11,836 women with breast cancer, with data drawn from four large databases in the United Kingdom, the United States, and Australia.

The model compared annual costs, number of detected cases of breast cancer and ovarian cancer, and related rates of mortality between standard BRCA testing based on clinical criteria or family history versus high-risk multigene testing (BRCA1/BRCA2/PALB2) for all patients with breast cancer.

Resultant incremental cost-effectiveness ratios (ICERs) showed that in both the United Kingdom and the United States, multigene testing would cost, on average, significantly less than minimum willingness-to-pay thresholds of £30,000 per quality-adjusted life-year (QALY) and $100,000/QALY, respectively. In the United Kingdom, the estimated cost of multigene testing was £10,464/QALY from a payer’s perspective and £7,216/QALY from a societal perspective, the latter of which incorporates economic costs beyond the health care system. In the United States, these values rose to $65,661/QALY (payer perspective) and $61,618/QALY (societal perspective). Probabilistic sensitivity analysis suggested that multigene testing would be cost-effective for almost all health system simulations in the United Kingdom (98%-99%) and approximately two-thirds of those in the United States (64%-68%).

Epidemiologically, in the United Kingdom, multigene testing could potentially prevent 2,101 cases of breast cancer and ovarian cancer and 633 deaths per year, while in the United States, 9,733 cases might be prevented, with 2,406 lives saved.

“Our analysis suggests that an unselected testing strategy is extremely cost-effective for U.K. and U.S. health systems and provides a basis for change in current guidelines and policy to implement this strategy,” the investigators said.

The study was funded by the National Cancer Institute, the State of Washington, the Fred Hutchinson Cancer Research Center, and others. The investigators reported additional relationships with AstraZeneca, the Manchester National Institute for Health Research Biomedical Research Centre, Cancer Research UK, an others.

SOURCE: Sun et al. JAMA Oncol. 2019 Oct 3. doi: 10.1001/jamaoncol.2019.3323.

High-risk multigene testing for all patients with breast cancer may be a cost-effective way to reduce rates of breast cancer and ovarian cancer, according to investigators.

A microsimulation modeling study suggested that moving from standard BRCA testing based on clinical criteria or family history to widespread adoption of multigene testing could potentially save more than 2,400 lives per year in the United States, reported lead author Li Sun, MSc, of the London School of Hygiene & Tropical Medicine, and colleagues.

“Moving toward unselected BC testing may give an impetus for prevention in unaffected family members along with clinical implications for the patient with BC. Pathogenic variant carriers with newly diagnosed BC can opt for bilateral mastectomy rather than breast conservation at initial BC surgery,” the investigators wrote in JAMA Oncology. They noted that, presently, only 20%-30% of eligible patients are actually tested. “Testing all patients with breast cancer at diagnosis can increase testing access and uptake and identify many more pathogenic variant carriers for screening and prevention.”

To see if such a broad roll-out would be economically and medically feasible and beneficial, the investigators performed a modeling study involving 11,836 women with breast cancer, with data drawn from four large databases in the United Kingdom, the United States, and Australia.

The model compared annual costs, number of detected cases of breast cancer and ovarian cancer, and related rates of mortality between standard BRCA testing based on clinical criteria or family history versus high-risk multigene testing (BRCA1/BRCA2/PALB2) for all patients with breast cancer.

Resultant incremental cost-effectiveness ratios (ICERs) showed that in both the United Kingdom and the United States, multigene testing would cost, on average, significantly less than minimum willingness-to-pay thresholds of £30,000 per quality-adjusted life-year (QALY) and $100,000/QALY, respectively. In the United Kingdom, the estimated cost of multigene testing was £10,464/QALY from a payer’s perspective and £7,216/QALY from a societal perspective, the latter of which incorporates economic costs beyond the health care system. In the United States, these values rose to $65,661/QALY (payer perspective) and $61,618/QALY (societal perspective). Probabilistic sensitivity analysis suggested that multigene testing would be cost-effective for almost all health system simulations in the United Kingdom (98%-99%) and approximately two-thirds of those in the United States (64%-68%).

Epidemiologically, in the United Kingdom, multigene testing could potentially prevent 2,101 cases of breast cancer and ovarian cancer and 633 deaths per year, while in the United States, 9,733 cases might be prevented, with 2,406 lives saved.

“Our analysis suggests that an unselected testing strategy is extremely cost-effective for U.K. and U.S. health systems and provides a basis for change in current guidelines and policy to implement this strategy,” the investigators said.

The study was funded by the National Cancer Institute, the State of Washington, the Fred Hutchinson Cancer Research Center, and others. The investigators reported additional relationships with AstraZeneca, the Manchester National Institute for Health Research Biomedical Research Centre, Cancer Research UK, an others.

SOURCE: Sun et al. JAMA Oncol. 2019 Oct 3. doi: 10.1001/jamaoncol.2019.3323.

High-risk multigene testing for all patients with breast cancer may be a cost-effective way to reduce rates of breast cancer and ovarian cancer, according to investigators.

A microsimulation modeling study suggested that moving from standard BRCA testing based on clinical criteria or family history to widespread adoption of multigene testing could potentially save more than 2,400 lives per year in the United States, reported lead author Li Sun, MSc, of the London School of Hygiene & Tropical Medicine, and colleagues.

“Moving toward unselected BC testing may give an impetus for prevention in unaffected family members along with clinical implications for the patient with BC. Pathogenic variant carriers with newly diagnosed BC can opt for bilateral mastectomy rather than breast conservation at initial BC surgery,” the investigators wrote in JAMA Oncology. They noted that, presently, only 20%-30% of eligible patients are actually tested. “Testing all patients with breast cancer at diagnosis can increase testing access and uptake and identify many more pathogenic variant carriers for screening and prevention.”

To see if such a broad roll-out would be economically and medically feasible and beneficial, the investigators performed a modeling study involving 11,836 women with breast cancer, with data drawn from four large databases in the United Kingdom, the United States, and Australia.

The model compared annual costs, number of detected cases of breast cancer and ovarian cancer, and related rates of mortality between standard BRCA testing based on clinical criteria or family history versus high-risk multigene testing (BRCA1/BRCA2/PALB2) for all patients with breast cancer.

Resultant incremental cost-effectiveness ratios (ICERs) showed that in both the United Kingdom and the United States, multigene testing would cost, on average, significantly less than minimum willingness-to-pay thresholds of £30,000 per quality-adjusted life-year (QALY) and $100,000/QALY, respectively. In the United Kingdom, the estimated cost of multigene testing was £10,464/QALY from a payer’s perspective and £7,216/QALY from a societal perspective, the latter of which incorporates economic costs beyond the health care system. In the United States, these values rose to $65,661/QALY (payer perspective) and $61,618/QALY (societal perspective). Probabilistic sensitivity analysis suggested that multigene testing would be cost-effective for almost all health system simulations in the United Kingdom (98%-99%) and approximately two-thirds of those in the United States (64%-68%).

Epidemiologically, in the United Kingdom, multigene testing could potentially prevent 2,101 cases of breast cancer and ovarian cancer and 633 deaths per year, while in the United States, 9,733 cases might be prevented, with 2,406 lives saved.

“Our analysis suggests that an unselected testing strategy is extremely cost-effective for U.K. and U.S. health systems and provides a basis for change in current guidelines and policy to implement this strategy,” the investigators said.

The study was funded by the National Cancer Institute, the State of Washington, the Fred Hutchinson Cancer Research Center, and others. The investigators reported additional relationships with AstraZeneca, the Manchester National Institute for Health Research Biomedical Research Centre, Cancer Research UK, an others.

SOURCE: Sun et al. JAMA Oncol. 2019 Oct 3. doi: 10.1001/jamaoncol.2019.3323.

Molecular pathways linked with CD44 variant 9 (CD44v9), a cell surface glycoprotein tied to aggressive gastric cancer after Helicobacter pylori infection, may open doors to stop cancer before it starts, according to two recent studies.

Findings from the first study suggest that persistent inflammation after eradication therapy may continue to drive cancer risk after infection, while the second study revealed a potential therapeutic target related to preneoplastic changes.

The first study, conducted by lead author Hitoshi Tsugawa, PhD, of Keio University, Tokyo, and colleagues, aimed to determine the origin of CD44v9-positive cancer stem-like cells.

“These cells strongly contribute to the development and recurrence of gastric cancer,” the investigators wrote. Their report is in Cellular and Molecular Gastroenterology and Hepatology. “However, the origin of CD44v9-positive cells is uncertain.”

The association between H. pylori infection and gastric cancer has been documented, along with a high risk of cancer when gastric epithelial cells overexpress capping actin protein of muscle Z-line alpha subunit 1 (CAPZA1), the researchers noted. Although it has also been shown that CAPZA1 overexpression leads to intracellular accumulations of the H. pylori–derived oncoprotein cytotoxin-associated gene A (CagA), just how these phenomena were connected remained unknown.

Through in vitro analyses of human cells, and in vitro and in vivo experiments involving Mongolian gerbils, the investigators uncovered a chain of events between H. pylori infection and CD44v9 expression. First, the investigators showed that expression levels of CD44v9 and CAPZA1 were directly correlated in five human cases of gastric cancer. Next, several experiments revealed that H. pylori–related oxidative stress drives overexpression of CAPZA1, which, in combination with high levels of beta-catenin, ESRP1, and CagA, promotes expression of CD44v9.

Most directly relevant to future therapies, the investigators compared levels of CAPZA1 between five active cases of H. pylori infection versus five cases successfully treated with eradication therapy. After eradication therapy, CAPZA1 overexpression decreased, but not to a significant degree.

“Our findings suggest that CAPZA1-overexpressing cells remaining in the gastric mucosa after eradication therapy increase the risk of metachronous gastric cancer and that reduction of CAPZA1 expression by amelioration of chronic inflammation after eradication therapy is important to prevent the development of gastric cancer,” the investigators concluded.

The second study, by lead author Anne R. Meyer, a graduate student at Vanderbilt University, Nashville, Tenn., and colleagues, evaluated how zymogenic chief cells are reprogrammed into spasmolytic polypeptide-expressing metaplasia (SPEM), a precursor to dysplasia and gastric cancer.

It had been previously shown that reprogramming to SPEM is promoted and maintained by epithelial cell damage, such as that caused by H. pylori infection, but underlying processes remained unclear, until recent studies suggested a link between SPEM transition and upregulation of CD44v9. Knowing that CD44v9 stabilizes the cystine/glutamate antiporter xCT, the investigators homed in on xCT for a closer look, questioning what role it had in chief cell reprogramming. Again, oxidative stress was identified as the inciting pathophysiologic driver.

“The oxidative stress response, including upregulation of nutrient transporters, plays an important role in many biological processes and the pathogenesis of a variety of diseases,” the investigators wrote in their report, published in Cellular and Molecular Gastroenterology and Hepatology. “Perturbations to the CD44v9-xCT system often result in redox imbalance.”

Using a combination of mouse and human cell lines, and a mouse model, the investigators demonstrated that xCT was upregulated during the initial stages of chief cell programming. Blocking xCT with sulfasalazine after acute gastric injury limited SPEM transition by more than 80%, an effect that was further supported by xCT siRNA knockdown and observations in xCT knockout mice. Reduction in chief cell reprogramming was not observed in the presence of sulfasalazine metabolites, suggesting that the anti-inflammatory properties of sulfasalazine were not responsible for downregulation of reprogramming.

“Targeting xCT may prove an effective tool for arresting metaplasia development in the stomach as well as mucous metaplasia in other epithelial tissues for the analysis of cellular plasticity and oxidative stress response,” the investigators concluded.

The study by Tsugawa and colleagues was funded by Grants-in-Aid for Scientific Research; the Yakult Bio-Science Foundation; the Ministry of Education, Culture, Sports, Science and Technology (MEXT)-supported program for the Strategic Research Foundation at Private Universities; and Keio Gijuku Academic Development Funds. Dr. Suzuki disclosed relationships with Daiichi-Sankyo Co, EA Pharma Co, Otsuka Pharmaceutical Co Ltd, and others. The study by Meyer and colleagues was funded by the National Institutes of Health, the American Association of Cancer Research, the Department of Defense, and others, with no relevant conflicts of interest.

SOURCES: Meyer et al. CMGH. 2019 May 6. doi: 10.1016/j.jcmgh.2019.04.015; Tsugawa et al. CMGH. 2019 May 27. doi: 10.1016/j.jcmgh.2019.05.008.

Molecular pathways linked with CD44 variant 9 (CD44v9), a cell surface glycoprotein tied to aggressive gastric cancer after Helicobacter pylori infection, may open doors to stop cancer before it starts, according to two recent studies.

Findings from the first study suggest that persistent inflammation after eradication therapy may continue to drive cancer risk after infection, while the second study revealed a potential therapeutic target related to preneoplastic changes.

The first study, conducted by lead author Hitoshi Tsugawa, PhD, of Keio University, Tokyo, and colleagues, aimed to determine the origin of CD44v9-positive cancer stem-like cells.

“These cells strongly contribute to the development and recurrence of gastric cancer,” the investigators wrote. Their report is in Cellular and Molecular Gastroenterology and Hepatology. “However, the origin of CD44v9-positive cells is uncertain.”

The association between H. pylori infection and gastric cancer has been documented, along with a high risk of cancer when gastric epithelial cells overexpress capping actin protein of muscle Z-line alpha subunit 1 (CAPZA1), the researchers noted. Although it has also been shown that CAPZA1 overexpression leads to intracellular accumulations of the H. pylori–derived oncoprotein cytotoxin-associated gene A (CagA), just how these phenomena were connected remained unknown.

Through in vitro analyses of human cells, and in vitro and in vivo experiments involving Mongolian gerbils, the investigators uncovered a chain of events between H. pylori infection and CD44v9 expression. First, the investigators showed that expression levels of CD44v9 and CAPZA1 were directly correlated in five human cases of gastric cancer. Next, several experiments revealed that H. pylori–related oxidative stress drives overexpression of CAPZA1, which, in combination with high levels of beta-catenin, ESRP1, and CagA, promotes expression of CD44v9.

Most directly relevant to future therapies, the investigators compared levels of CAPZA1 between five active cases of H. pylori infection versus five cases successfully treated with eradication therapy. After eradication therapy, CAPZA1 overexpression decreased, but not to a significant degree.

“Our findings suggest that CAPZA1-overexpressing cells remaining in the gastric mucosa after eradication therapy increase the risk of metachronous gastric cancer and that reduction of CAPZA1 expression by amelioration of chronic inflammation after eradication therapy is important to prevent the development of gastric cancer,” the investigators concluded.

The second study, by lead author Anne R. Meyer, a graduate student at Vanderbilt University, Nashville, Tenn., and colleagues, evaluated how zymogenic chief cells are reprogrammed into spasmolytic polypeptide-expressing metaplasia (SPEM), a precursor to dysplasia and gastric cancer.

It had been previously shown that reprogramming to SPEM is promoted and maintained by epithelial cell damage, such as that caused by H. pylori infection, but underlying processes remained unclear, until recent studies suggested a link between SPEM transition and upregulation of CD44v9. Knowing that CD44v9 stabilizes the cystine/glutamate antiporter xCT, the investigators homed in on xCT for a closer look, questioning what role it had in chief cell reprogramming. Again, oxidative stress was identified as the inciting pathophysiologic driver.

“The oxidative stress response, including upregulation of nutrient transporters, plays an important role in many biological processes and the pathogenesis of a variety of diseases,” the investigators wrote in their report, published in Cellular and Molecular Gastroenterology and Hepatology. “Perturbations to the CD44v9-xCT system often result in redox imbalance.”

Using a combination of mouse and human cell lines, and a mouse model, the investigators demonstrated that xCT was upregulated during the initial stages of chief cell programming. Blocking xCT with sulfasalazine after acute gastric injury limited SPEM transition by more than 80%, an effect that was further supported by xCT siRNA knockdown and observations in xCT knockout mice. Reduction in chief cell reprogramming was not observed in the presence of sulfasalazine metabolites, suggesting that the anti-inflammatory properties of sulfasalazine were not responsible for downregulation of reprogramming.

“Targeting xCT may prove an effective tool for arresting metaplasia development in the stomach as well as mucous metaplasia in other epithelial tissues for the analysis of cellular plasticity and oxidative stress response,” the investigators concluded.

The study by Tsugawa and colleagues was funded by Grants-in-Aid for Scientific Research; the Yakult Bio-Science Foundation; the Ministry of Education, Culture, Sports, Science and Technology (MEXT)-supported program for the Strategic Research Foundation at Private Universities; and Keio Gijuku Academic Development Funds. Dr. Suzuki disclosed relationships with Daiichi-Sankyo Co, EA Pharma Co, Otsuka Pharmaceutical Co Ltd, and others. The study by Meyer and colleagues was funded by the National Institutes of Health, the American Association of Cancer Research, the Department of Defense, and others, with no relevant conflicts of interest.

SOURCES: Meyer et al. CMGH. 2019 May 6. doi: 10.1016/j.jcmgh.2019.04.015; Tsugawa et al. CMGH. 2019 May 27. doi: 10.1016/j.jcmgh.2019.05.008.

Molecular pathways linked with CD44 variant 9 (CD44v9), a cell surface glycoprotein tied to aggressive gastric cancer after Helicobacter pylori infection, may open doors to stop cancer before it starts, according to two recent studies.

Findings from the first study suggest that persistent inflammation after eradication therapy may continue to drive cancer risk after infection, while the second study revealed a potential therapeutic target related to preneoplastic changes.

The first study, conducted by lead author Hitoshi Tsugawa, PhD, of Keio University, Tokyo, and colleagues, aimed to determine the origin of CD44v9-positive cancer stem-like cells.

“These cells strongly contribute to the development and recurrence of gastric cancer,” the investigators wrote. Their report is in Cellular and Molecular Gastroenterology and Hepatology. “However, the origin of CD44v9-positive cells is uncertain.”

The association between H. pylori infection and gastric cancer has been documented, along with a high risk of cancer when gastric epithelial cells overexpress capping actin protein of muscle Z-line alpha subunit 1 (CAPZA1), the researchers noted. Although it has also been shown that CAPZA1 overexpression leads to intracellular accumulations of the H. pylori–derived oncoprotein cytotoxin-associated gene A (CagA), just how these phenomena were connected remained unknown.

Through in vitro analyses of human cells, and in vitro and in vivo experiments involving Mongolian gerbils, the investigators uncovered a chain of events between H. pylori infection and CD44v9 expression. First, the investigators showed that expression levels of CD44v9 and CAPZA1 were directly correlated in five human cases of gastric cancer. Next, several experiments revealed that H. pylori–related oxidative stress drives overexpression of CAPZA1, which, in combination with high levels of beta-catenin, ESRP1, and CagA, promotes expression of CD44v9.

Most directly relevant to future therapies, the investigators compared levels of CAPZA1 between five active cases of H. pylori infection versus five cases successfully treated with eradication therapy. After eradication therapy, CAPZA1 overexpression decreased, but not to a significant degree.

“Our findings suggest that CAPZA1-overexpressing cells remaining in the gastric mucosa after eradication therapy increase the risk of metachronous gastric cancer and that reduction of CAPZA1 expression by amelioration of chronic inflammation after eradication therapy is important to prevent the development of gastric cancer,” the investigators concluded.

The second study, by lead author Anne R. Meyer, a graduate student at Vanderbilt University, Nashville, Tenn., and colleagues, evaluated how zymogenic chief cells are reprogrammed into spasmolytic polypeptide-expressing metaplasia (SPEM), a precursor to dysplasia and gastric cancer.

It had been previously shown that reprogramming to SPEM is promoted and maintained by epithelial cell damage, such as that caused by H. pylori infection, but underlying processes remained unclear, until recent studies suggested a link between SPEM transition and upregulation of CD44v9. Knowing that CD44v9 stabilizes the cystine/glutamate antiporter xCT, the investigators homed in on xCT for a closer look, questioning what role it had in chief cell reprogramming. Again, oxidative stress was identified as the inciting pathophysiologic driver.

“The oxidative stress response, including upregulation of nutrient transporters, plays an important role in many biological processes and the pathogenesis of a variety of diseases,” the investigators wrote in their report, published in Cellular and Molecular Gastroenterology and Hepatology. “Perturbations to the CD44v9-xCT system often result in redox imbalance.”

Using a combination of mouse and human cell lines, and a mouse model, the investigators demonstrated that xCT was upregulated during the initial stages of chief cell programming. Blocking xCT with sulfasalazine after acute gastric injury limited SPEM transition by more than 80%, an effect that was further supported by xCT siRNA knockdown and observations in xCT knockout mice. Reduction in chief cell reprogramming was not observed in the presence of sulfasalazine metabolites, suggesting that the anti-inflammatory properties of sulfasalazine were not responsible for downregulation of reprogramming.

“Targeting xCT may prove an effective tool for arresting metaplasia development in the stomach as well as mucous metaplasia in other epithelial tissues for the analysis of cellular plasticity and oxidative stress response,” the investigators concluded.

The study by Tsugawa and colleagues was funded by Grants-in-Aid for Scientific Research; the Yakult Bio-Science Foundation; the Ministry of Education, Culture, Sports, Science and Technology (MEXT)-supported program for the Strategic Research Foundation at Private Universities; and Keio Gijuku Academic Development Funds. Dr. Suzuki disclosed relationships with Daiichi-Sankyo Co, EA Pharma Co, Otsuka Pharmaceutical Co Ltd, and others. The study by Meyer and colleagues was funded by the National Institutes of Health, the American Association of Cancer Research, the Department of Defense, and others, with no relevant conflicts of interest.

SOURCES: Meyer et al. CMGH. 2019 May 6. doi: 10.1016/j.jcmgh.2019.04.015; Tsugawa et al. CMGH. 2019 May 27. doi: 10.1016/j.jcmgh.2019.05.008.

Endoscopic submucosal dissection (ESD) is a viable treatment option for patients with submucosal (T1b) esophageal cancer who have a low risk of lymph node metastasis, according to an expert review.

Among patients with T1b esophageal cancer, ideal candidates for ESD have small (less than 2 cm), well-differentiated tumors that do not invade beyond the superficial submucosa (SM1) and lack lymphovascular invasion, reported lead author Mohamed O. Othman, MD, of Baylor College of Medicine in Houston, and colleagues. The literature review was recently commissioned by the American Gastroenterological Association (AGA), because of high clinical relevance.

“[ESD] has been gaining momentum as an alternative to surgery in treating early gastrointestinal neoplasms,” the investigators wrote in Clinical Gastroenterology and Hepatology.

Most patients who undergo surgical resection develop gastroesophageal reflux, the investigators noted, and many others develop serious complications or do not survive the procedure.

“Even a high-volume center such as Mayo Clinic reported a surgical mortality of 4% for T1a esophageal cancer,” the investigators wrote. “Moreover, 34% of patients developed postoperative complications such as anastomotic leaks, anastomotic strictures, cardiopulmonary complications, and feeding jejunostomy leaks. ... Therefore, a less-invasive alternative to esophagectomy would be extremely valuable in the management of early stage [esophageal cancer] if proven effective.”

The investigators reviewed studies evaluating safety and efficacy of surgical and endoscopic techniques, as well as available data for chemoradiation and radiofrequency ablation combinations, which could potentially optimize outcomes of endoscopic resection.

They concluded that most patients with esophageal cancer that does not extend beyond the mucosa (T1a) can be cured with endoscopic resection, based on 5-year survival rates from several Japanese trials. For patients with T1b disease, however, ESD is best suited for those with a low risk of lymph node metastasis. Unfortunately, identifying these candidates can be challenging, according to the investigators.

“The risk of lymph node metastasis depends on the depth of invasion, histologic type, and molecular characterization of the tumor,” the investigators explained, noting that depth of invasion is the trickiest to discern. Although endoscopic ultrasound (EUS) is still recommended for submucosal imaging, the review showed that EUS may overstage cancer in Barrett’s esophagus. The investigators suggested that volume laser endoscopy with infrared light could be a more accurate alternative, but it is not yet a clinical reality.

The review also showed potential for combining ESD with other modalities. For example, a study by Hamada and colleagues involving 66 patients with submucosal (T1b) esophageal squamous cell carcinoma found that a combination of ESD with chemoradiation led to similar 3- and 5-year survival rates as radical esophagectomy. The investigators highlighted the importance of lymph node metastasis in this study, as none of the 30 patients lacking lymph node involvement had metastatic recurrence, compared with 6 of the 36 patients who exhibited lymph node metastasis. According to the investigators, promising data are also anticipated for this combination among those with adenocarcinoma. And for patients with intestinal metaplasia and/or dysplasia, adding radiofrequency ablation after ESD appears to be an effective option; one recent study by Sharmila Subramaniam, BMBS, and colleagues found that this strategy led to clearance rates of 85% and 96% for metaplasia and dysplasia, respectively.

“Additional treatment should be determined by factors such as tumor grade, status of lymphovascular invasion, and depth of tumor, which have a direct influence on metastatic potential,” the investigators wrote.

The investigators suggested that, in the future, better diagnostics will be needed to characterize T1b disease, as this could streamline patient selection. “Future research should focus on novel biological and immunohistochemistry markers that can aid in the prediction of tumor behavior and [lymph node metastasis] in T1b esophageal cancer,” they concluded.

The study was commissioned by the American Gastroenterological Association. The investigators disclosed additional relationships with Boston Scientific, Olympus, Lumendi, and others.

SOURCE: Othman MO et al. CGH. 2019 Jun 4. doi: 10.1016/j.cgh.2019.05.045.

Endoscopic submucosal dissection (ESD) is a viable treatment option for patients with submucosal (T1b) esophageal cancer who have a low risk of lymph node metastasis, according to an expert review.

Among patients with T1b esophageal cancer, ideal candidates for ESD have small (less than 2 cm), well-differentiated tumors that do not invade beyond the superficial submucosa (SM1) and lack lymphovascular invasion, reported lead author Mohamed O. Othman, MD, of Baylor College of Medicine in Houston, and colleagues. The literature review was recently commissioned by the American Gastroenterological Association (AGA), because of high clinical relevance.

“[ESD] has been gaining momentum as an alternative to surgery in treating early gastrointestinal neoplasms,” the investigators wrote in Clinical Gastroenterology and Hepatology.

Most patients who undergo surgical resection develop gastroesophageal reflux, the investigators noted, and many others develop serious complications or do not survive the procedure.

“Even a high-volume center such as Mayo Clinic reported a surgical mortality of 4% for T1a esophageal cancer,” the investigators wrote. “Moreover, 34% of patients developed postoperative complications such as anastomotic leaks, anastomotic strictures, cardiopulmonary complications, and feeding jejunostomy leaks. ... Therefore, a less-invasive alternative to esophagectomy would be extremely valuable in the management of early stage [esophageal cancer] if proven effective.”

The investigators reviewed studies evaluating safety and efficacy of surgical and endoscopic techniques, as well as available data for chemoradiation and radiofrequency ablation combinations, which could potentially optimize outcomes of endoscopic resection.

They concluded that most patients with esophageal cancer that does not extend beyond the mucosa (T1a) can be cured with endoscopic resection, based on 5-year survival rates from several Japanese trials. For patients with T1b disease, however, ESD is best suited for those with a low risk of lymph node metastasis. Unfortunately, identifying these candidates can be challenging, according to the investigators.

“The risk of lymph node metastasis depends on the depth of invasion, histologic type, and molecular characterization of the tumor,” the investigators explained, noting that depth of invasion is the trickiest to discern. Although endoscopic ultrasound (EUS) is still recommended for submucosal imaging, the review showed that EUS may overstage cancer in Barrett’s esophagus. The investigators suggested that volume laser endoscopy with infrared light could be a more accurate alternative, but it is not yet a clinical reality.

The review also showed potential for combining ESD with other modalities. For example, a study by Hamada and colleagues involving 66 patients with submucosal (T1b) esophageal squamous cell carcinoma found that a combination of ESD with chemoradiation led to similar 3- and 5-year survival rates as radical esophagectomy. The investigators highlighted the importance of lymph node metastasis in this study, as none of the 30 patients lacking lymph node involvement had metastatic recurrence, compared with 6 of the 36 patients who exhibited lymph node metastasis. According to the investigators, promising data are also anticipated for this combination among those with adenocarcinoma. And for patients with intestinal metaplasia and/or dysplasia, adding radiofrequency ablation after ESD appears to be an effective option; one recent study by Sharmila Subramaniam, BMBS, and colleagues found that this strategy led to clearance rates of 85% and 96% for metaplasia and dysplasia, respectively.

“Additional treatment should be determined by factors such as tumor grade, status of lymphovascular invasion, and depth of tumor, which have a direct influence on metastatic potential,” the investigators wrote.

The investigators suggested that, in the future, better diagnostics will be needed to characterize T1b disease, as this could streamline patient selection. “Future research should focus on novel biological and immunohistochemistry markers that can aid in the prediction of tumor behavior and [lymph node metastasis] in T1b esophageal cancer,” they concluded.

The study was commissioned by the American Gastroenterological Association. The investigators disclosed additional relationships with Boston Scientific, Olympus, Lumendi, and others.

SOURCE: Othman MO et al. CGH. 2019 Jun 4. doi: 10.1016/j.cgh.2019.05.045.

Endoscopic submucosal dissection (ESD) is a viable treatment option for patients with submucosal (T1b) esophageal cancer who have a low risk of lymph node metastasis, according to an expert review.

Among patients with T1b esophageal cancer, ideal candidates for ESD have small (less than 2 cm), well-differentiated tumors that do not invade beyond the superficial submucosa (SM1) and lack lymphovascular invasion, reported lead author Mohamed O. Othman, MD, of Baylor College of Medicine in Houston, and colleagues. The literature review was recently commissioned by the American Gastroenterological Association (AGA), because of high clinical relevance.

“[ESD] has been gaining momentum as an alternative to surgery in treating early gastrointestinal neoplasms,” the investigators wrote in Clinical Gastroenterology and Hepatology.

Most patients who undergo surgical resection develop gastroesophageal reflux, the investigators noted, and many others develop serious complications or do not survive the procedure.

“Even a high-volume center such as Mayo Clinic reported a surgical mortality of 4% for T1a esophageal cancer,” the investigators wrote. “Moreover, 34% of patients developed postoperative complications such as anastomotic leaks, anastomotic strictures, cardiopulmonary complications, and feeding jejunostomy leaks. ... Therefore, a less-invasive alternative to esophagectomy would be extremely valuable in the management of early stage [esophageal cancer] if proven effective.”

The investigators reviewed studies evaluating safety and efficacy of surgical and endoscopic techniques, as well as available data for chemoradiation and radiofrequency ablation combinations, which could potentially optimize outcomes of endoscopic resection.

They concluded that most patients with esophageal cancer that does not extend beyond the mucosa (T1a) can be cured with endoscopic resection, based on 5-year survival rates from several Japanese trials. For patients with T1b disease, however, ESD is best suited for those with a low risk of lymph node metastasis. Unfortunately, identifying these candidates can be challenging, according to the investigators.

“The risk of lymph node metastasis depends on the depth of invasion, histologic type, and molecular characterization of the tumor,” the investigators explained, noting that depth of invasion is the trickiest to discern. Although endoscopic ultrasound (EUS) is still recommended for submucosal imaging, the review showed that EUS may overstage cancer in Barrett’s esophagus. The investigators suggested that volume laser endoscopy with infrared light could be a more accurate alternative, but it is not yet a clinical reality.

The review also showed potential for combining ESD with other modalities. For example, a study by Hamada and colleagues involving 66 patients with submucosal (T1b) esophageal squamous cell carcinoma found that a combination of ESD with chemoradiation led to similar 3- and 5-year survival rates as radical esophagectomy. The investigators highlighted the importance of lymph node metastasis in this study, as none of the 30 patients lacking lymph node involvement had metastatic recurrence, compared with 6 of the 36 patients who exhibited lymph node metastasis. According to the investigators, promising data are also anticipated for this combination among those with adenocarcinoma. And for patients with intestinal metaplasia and/or dysplasia, adding radiofrequency ablation after ESD appears to be an effective option; one recent study by Sharmila Subramaniam, BMBS, and colleagues found that this strategy led to clearance rates of 85% and 96% for metaplasia and dysplasia, respectively.

“Additional treatment should be determined by factors such as tumor grade, status of lymphovascular invasion, and depth of tumor, which have a direct influence on metastatic potential,” the investigators wrote.

The investigators suggested that, in the future, better diagnostics will be needed to characterize T1b disease, as this could streamline patient selection. “Future research should focus on novel biological and immunohistochemistry markers that can aid in the prediction of tumor behavior and [lymph node metastasis] in T1b esophageal cancer,” they concluded.

The study was commissioned by the American Gastroenterological Association. The investigators disclosed additional relationships with Boston Scientific, Olympus, Lumendi, and others.

SOURCE: Othman MO et al. CGH. 2019 Jun 4. doi: 10.1016/j.cgh.2019.05.045.

For men with prostate cancer who have a low prostate-specific antigen (PSA) level prior to salvage radiation therapy (SRT), adding an antiandrogen may increase the risk of other-cause mortality by twofold or more, according to investigators.

This finding was drawn from a secondary analysis of the NRG Oncology/RTOG 9601 phase 3 trial, a practice-changing study that showed that 2 years of antiandrogen therapy with bicalutamide improved overall survival when added to SRT, compared with that of SRT alone.

Results from the present analysis paint a more complex picture, revealing that patients with low PSA levels who received hormone therapy had a higher rate of other-cause mortality, primarily because of high-grade cardiac and neurologic events, reported lead author Daniel Spratt, MD, of the University of Michigan Rogel Cancer Center, Ann Arbor, who presented findings at the annual meeting of the American Society for Radiation Oncology.

Dr. Spratt described how treatment paradigms have changed since RTOG 9601 began in 1998, which prompted a revisitation of the trial. “Almost half of the men [in the trial] had a persistently elevated PSA after they underwent their initial surgery,” Dr. Spratt said. “This is uncommonly seen today. Additionally, about 60% of patients received what we call late salvage radiation therapy, where PSA was monitored and continued to rise beyond 0.5 [ng/mL]; again, this is not what is recommended to be used today.”

In the present analysis, the investigators stratified patients by PSA level. Of the 760 men involved, 85% had a PSA of 0.2-1.5 ng/mL. Patients were further subgrouped by those with a PSA of 0.2-0.6 ng/mL and those with a very low PSA, of 0.2-0.3 ng/mL. Multiple endpoints were assessed, including overall survival, other-cause mortality, distant metastasis, and rates of grade 3-5 cardiac or neurologic events.

The analysis showed that men with a PSA greater than 1.5 ng/mL had improved survival (hazard ratio, 0.45; 95% confidence interval, 0.25-0.81) when treated with bicalutamide, but those with PSA of 1.5 ng/mL or less did not (HR, 0.87; 95% CI, 0.66-1.16). Looking more closely at patients with a PSA of 1.5 ng/mL or less, those with a PSA of 0.2-0.6 ng/mL had a twofold increased rate of other-cause mortality (subdistribution HR, 1.94; P = .009). The picture became even more concerning for patients with a PSA of 0.2-0.3 ng/mL who were treated with bicalutamide: They had a fourfold increased risk of other cause mortality (sHR, 4.14). Among the cases with elevated other-cause mortality, grade 3-4 cardiac and neurologic events were likely to be blamed.

“What is likely driving this, and of concern, is that for [patients with a] PSA of less than 1.5 [ng/mL] … there was a three- to four-and-a-half-fold increased risk of high grade cardiac events,” Dr. Spratt said.

“The current guidelines recommend that all men be offered hormone therapy when receiving salvage radiation therapy, but our data demonstrate that men with lower PSA’s are probably more harmed than helped by long-term hormone therapy,” Dr. Spratt concluded. “We now have three randomized trials with over 2,400 men in total, [none of which showed that] short- or long-term hormone therapy improves overall survival in men [with a low PSA level who receive] early salvage radiotherapy. Thus, PSA prior to salvage radiation actually is not only prognostic, it predicts who will benefit most from hormone therapy, and guidelines should now be updated to reflect this finding.”

The session moderator, Anthony Zietman, MD, of Massachusetts General Hospital, Boston, helped put the findings in perspective: “This really suggests that we’ve got to hold back a little,” Dr. Zietman said. “There are some people who really benefit [from hormone therapy], some who don’t benefit, and some who just might be harmed, so I think we can be much more thoughtful and cautious in the future. … Thirty thousand men a year are in this situation who could be receiving this treatment. You could fill Fenway Park with that many people. So there are some big downstream implications. From here on out, I’m going to be a lot more cautious with my patients.”

The study was primarily funded by AstraZeneca with additional support from the Korea Institute of Radiological and Medical Sciences. The investigators disclosed relationships with Novartis, Roche, Amgen, and others.

SOURCE: Spratt et al. ASTRO 2019, Abstract LBA1.

For men with prostate cancer who have a low prostate-specific antigen (PSA) level prior to salvage radiation therapy (SRT), adding an antiandrogen may increase the risk of other-cause mortality by twofold or more, according to investigators.

This finding was drawn from a secondary analysis of the NRG Oncology/RTOG 9601 phase 3 trial, a practice-changing study that showed that 2 years of antiandrogen therapy with bicalutamide improved overall survival when added to SRT, compared with that of SRT alone.

Results from the present analysis paint a more complex picture, revealing that patients with low PSA levels who received hormone therapy had a higher rate of other-cause mortality, primarily because of high-grade cardiac and neurologic events, reported lead author Daniel Spratt, MD, of the University of Michigan Rogel Cancer Center, Ann Arbor, who presented findings at the annual meeting of the American Society for Radiation Oncology.

Dr. Spratt described how treatment paradigms have changed since RTOG 9601 began in 1998, which prompted a revisitation of the trial. “Almost half of the men [in the trial] had a persistently elevated PSA after they underwent their initial surgery,” Dr. Spratt said. “This is uncommonly seen today. Additionally, about 60% of patients received what we call late salvage radiation therapy, where PSA was monitored and continued to rise beyond 0.5 [ng/mL]; again, this is not what is recommended to be used today.”

In the present analysis, the investigators stratified patients by PSA level. Of the 760 men involved, 85% had a PSA of 0.2-1.5 ng/mL. Patients were further subgrouped by those with a PSA of 0.2-0.6 ng/mL and those with a very low PSA, of 0.2-0.3 ng/mL. Multiple endpoints were assessed, including overall survival, other-cause mortality, distant metastasis, and rates of grade 3-5 cardiac or neurologic events.

The analysis showed that men with a PSA greater than 1.5 ng/mL had improved survival (hazard ratio, 0.45; 95% confidence interval, 0.25-0.81) when treated with bicalutamide, but those with PSA of 1.5 ng/mL or less did not (HR, 0.87; 95% CI, 0.66-1.16). Looking more closely at patients with a PSA of 1.5 ng/mL or less, those with a PSA of 0.2-0.6 ng/mL had a twofold increased rate of other-cause mortality (subdistribution HR, 1.94; P = .009). The picture became even more concerning for patients with a PSA of 0.2-0.3 ng/mL who were treated with bicalutamide: They had a fourfold increased risk of other cause mortality (sHR, 4.14). Among the cases with elevated other-cause mortality, grade 3-4 cardiac and neurologic events were likely to be blamed.

“What is likely driving this, and of concern, is that for [patients with a] PSA of less than 1.5 [ng/mL] … there was a three- to four-and-a-half-fold increased risk of high grade cardiac events,” Dr. Spratt said.

“The current guidelines recommend that all men be offered hormone therapy when receiving salvage radiation therapy, but our data demonstrate that men with lower PSA’s are probably more harmed than helped by long-term hormone therapy,” Dr. Spratt concluded. “We now have three randomized trials with over 2,400 men in total, [none of which showed that] short- or long-term hormone therapy improves overall survival in men [with a low PSA level who receive] early salvage radiotherapy. Thus, PSA prior to salvage radiation actually is not only prognostic, it predicts who will benefit most from hormone therapy, and guidelines should now be updated to reflect this finding.”

The session moderator, Anthony Zietman, MD, of Massachusetts General Hospital, Boston, helped put the findings in perspective: “This really suggests that we’ve got to hold back a little,” Dr. Zietman said. “There are some people who really benefit [from hormone therapy], some who don’t benefit, and some who just might be harmed, so I think we can be much more thoughtful and cautious in the future. … Thirty thousand men a year are in this situation who could be receiving this treatment. You could fill Fenway Park with that many people. So there are some big downstream implications. From here on out, I’m going to be a lot more cautious with my patients.”

The study was primarily funded by AstraZeneca with additional support from the Korea Institute of Radiological and Medical Sciences. The investigators disclosed relationships with Novartis, Roche, Amgen, and others.

SOURCE: Spratt et al. ASTRO 2019, Abstract LBA1.

For men with prostate cancer who have a low prostate-specific antigen (PSA) level prior to salvage radiation therapy (SRT), adding an antiandrogen may increase the risk of other-cause mortality by twofold or more, according to investigators.

This finding was drawn from a secondary analysis of the NRG Oncology/RTOG 9601 phase 3 trial, a practice-changing study that showed that 2 years of antiandrogen therapy with bicalutamide improved overall survival when added to SRT, compared with that of SRT alone.

Results from the present analysis paint a more complex picture, revealing that patients with low PSA levels who received hormone therapy had a higher rate of other-cause mortality, primarily because of high-grade cardiac and neurologic events, reported lead author Daniel Spratt, MD, of the University of Michigan Rogel Cancer Center, Ann Arbor, who presented findings at the annual meeting of the American Society for Radiation Oncology.

Dr. Spratt described how treatment paradigms have changed since RTOG 9601 began in 1998, which prompted a revisitation of the trial. “Almost half of the men [in the trial] had a persistently elevated PSA after they underwent their initial surgery,” Dr. Spratt said. “This is uncommonly seen today. Additionally, about 60% of patients received what we call late salvage radiation therapy, where PSA was monitored and continued to rise beyond 0.5 [ng/mL]; again, this is not what is recommended to be used today.”

In the present analysis, the investigators stratified patients by PSA level. Of the 760 men involved, 85% had a PSA of 0.2-1.5 ng/mL. Patients were further subgrouped by those with a PSA of 0.2-0.6 ng/mL and those with a very low PSA, of 0.2-0.3 ng/mL. Multiple endpoints were assessed, including overall survival, other-cause mortality, distant metastasis, and rates of grade 3-5 cardiac or neurologic events.

The analysis showed that men with a PSA greater than 1.5 ng/mL had improved survival (hazard ratio, 0.45; 95% confidence interval, 0.25-0.81) when treated with bicalutamide, but those with PSA of 1.5 ng/mL or less did not (HR, 0.87; 95% CI, 0.66-1.16). Looking more closely at patients with a PSA of 1.5 ng/mL or less, those with a PSA of 0.2-0.6 ng/mL had a twofold increased rate of other-cause mortality (subdistribution HR, 1.94; P = .009). The picture became even more concerning for patients with a PSA of 0.2-0.3 ng/mL who were treated with bicalutamide: They had a fourfold increased risk of other cause mortality (sHR, 4.14). Among the cases with elevated other-cause mortality, grade 3-4 cardiac and neurologic events were likely to be blamed.

“What is likely driving this, and of concern, is that for [patients with a] PSA of less than 1.5 [ng/mL] … there was a three- to four-and-a-half-fold increased risk of high grade cardiac events,” Dr. Spratt said.

“The current guidelines recommend that all men be offered hormone therapy when receiving salvage radiation therapy, but our data demonstrate that men with lower PSA’s are probably more harmed than helped by long-term hormone therapy,” Dr. Spratt concluded. “We now have three randomized trials with over 2,400 men in total, [none of which showed that] short- or long-term hormone therapy improves overall survival in men [with a low PSA level who receive] early salvage radiotherapy. Thus, PSA prior to salvage radiation actually is not only prognostic, it predicts who will benefit most from hormone therapy, and guidelines should now be updated to reflect this finding.”

The session moderator, Anthony Zietman, MD, of Massachusetts General Hospital, Boston, helped put the findings in perspective: “This really suggests that we’ve got to hold back a little,” Dr. Zietman said. “There are some people who really benefit [from hormone therapy], some who don’t benefit, and some who just might be harmed, so I think we can be much more thoughtful and cautious in the future. … Thirty thousand men a year are in this situation who could be receiving this treatment. You could fill Fenway Park with that many people. So there are some big downstream implications. From here on out, I’m going to be a lot more cautious with my patients.”

The study was primarily funded by AstraZeneca with additional support from the Korea Institute of Radiological and Medical Sciences. The investigators disclosed relationships with Novartis, Roche, Amgen, and others.

SOURCE: Spratt et al. ASTRO 2019, Abstract LBA1.

Most patients with stage III non–small cell lung cancer (NSCLC) who have distant progression on standard therapy typically have one or two new lesions, often in the same organ, which suggests a role for local ablative therapy, according to investigators.

This conclusion was drawn from an exploratory analysis of the phase 3 PACIFIC trial, which previously showed that durvalumab prolonged survival among patients with NSCLC who did not progress after chemoradiotherapy, which turned the trial protocol into a new standard of care.

At the annual meeting of the American Society for Radiation Oncology, coauthor Andreas Rimner, MD, of the Memorial Sloan Kettering Cancer Center in New York presented findings.

“There were always questions regarding detailed patterns of failure and disease progression in [the PACIFIC] trial,” Dr. Rimner said. “This study ... focuses on these patterns of failure, including the type of first progression in the patients on the PACIFIC trial.”

During the trial, 713 patients with NSCLC were randomized in a 2:1 ratio to receive either durvalumab or placebo. After a median follow-up of 25.2 months, the superiority of durvalumab was clear, with a lower rate of progression (45.4% vs. 64.6%).

But the present analysis dug deeper into this finding by dividing patients into three groups based on site or sites of first progression: local (intrathoracic) progression only, distant (extrathoracic) progression only, or simultaneously local and distant progression. Scans were reviewed by an independent radiologist who was not involved in the original PACIFIC trial. In addition to spatial data, the investigators reported times until progression.

Regardless of site, durvalumab was associated with a longer time until progression or death. Although comparative values were not reached for distant or simultaneous spread, median time until local progression or death was reportable, at 25.2 months in the durvalumab group versus with 9.2 months in the placebo group.

These values were available, in part, because local spread was the most common type of progression: It occurred in 80.6% of patients who progressed on durvalumab and 74.5% of progressors in the placebo group.

Durvalumab reduced the rate of progression across the three spatial categories, compared with placebo, including local only (36.6% vs. 48.1%, respectively), distant only (6.9% vs. 13.1%), and simultaneously local and distant (1.9% vs. 3.4%). This means that, at first progression, new distant lesions were found in 8.8% of patients treated with durvalumab, compared with 16.5% of those treated with placebo. Of note, approximately two-thirds of patients with distant progression had only one or two distant lesions, often confined to one organ, most commonly the brain. This pattern of progression was observed in both treatment arms.

According to Dr. Rimner, this finding is clinically relevant because it suggests a potential role for local ablative therapy.

Expert perspective on the analysis was provided by Benjamin Movsas, MD, chair of radiation oncology at the Henry Ford Cancer Institute in Detroit.

“The PACIFIC trial has really transformed the standard of care for patients with locally advanced, inoperable non–small cell lung cancer by adding immunotherapy to the prior standard of care combining chemotherapy and radiation, and this has shown a dramatic improvement in survival,” Dr. Movsas said.

“By adding the immunotherapy durvalumab, you can reduce risk of local failure, you can reduce the risk of distant failure, and interestingly enough, when patients do fail distantly, and this is true in both arms, they tended to fail in only one or two spots, which is encouraging because that suggests maybe a window of opportunity to treat those one or two spots, and we have newer technologies that allow us to consider that. So we really have a new paradigm.”

The study was funded by AstraZeneca. The investigators disclosed additional relationships with Merck, Nanobiotix, Boehringer Ingelheim, and others.

SOURCE: Rimner A et al. ASTRO 2019, Abstract LBA6.

Most patients with stage III non–small cell lung cancer (NSCLC) who have distant progression on standard therapy typically have one or two new lesions, often in the same organ, which suggests a role for local ablative therapy, according to investigators.

This conclusion was drawn from an exploratory analysis of the phase 3 PACIFIC trial, which previously showed that durvalumab prolonged survival among patients with NSCLC who did not progress after chemoradiotherapy, which turned the trial protocol into a new standard of care.

At the annual meeting of the American Society for Radiation Oncology, coauthor Andreas Rimner, MD, of the Memorial Sloan Kettering Cancer Center in New York presented findings.

“There were always questions regarding detailed patterns of failure and disease progression in [the PACIFIC] trial,” Dr. Rimner said. “This study ... focuses on these patterns of failure, including the type of first progression in the patients on the PACIFIC trial.”

During the trial, 713 patients with NSCLC were randomized in a 2:1 ratio to receive either durvalumab or placebo. After a median follow-up of 25.2 months, the superiority of durvalumab was clear, with a lower rate of progression (45.4% vs. 64.6%).

But the present analysis dug deeper into this finding by dividing patients into three groups based on site or sites of first progression: local (intrathoracic) progression only, distant (extrathoracic) progression only, or simultaneously local and distant progression. Scans were reviewed by an independent radiologist who was not involved in the original PACIFIC trial. In addition to spatial data, the investigators reported times until progression.

Regardless of site, durvalumab was associated with a longer time until progression or death. Although comparative values were not reached for distant or simultaneous spread, median time until local progression or death was reportable, at 25.2 months in the durvalumab group versus with 9.2 months in the placebo group.

These values were available, in part, because local spread was the most common type of progression: It occurred in 80.6% of patients who progressed on durvalumab and 74.5% of progressors in the placebo group.

Durvalumab reduced the rate of progression across the three spatial categories, compared with placebo, including local only (36.6% vs. 48.1%, respectively), distant only (6.9% vs. 13.1%), and simultaneously local and distant (1.9% vs. 3.4%). This means that, at first progression, new distant lesions were found in 8.8% of patients treated with durvalumab, compared with 16.5% of those treated with placebo. Of note, approximately two-thirds of patients with distant progression had only one or two distant lesions, often confined to one organ, most commonly the brain. This pattern of progression was observed in both treatment arms.

According to Dr. Rimner, this finding is clinically relevant because it suggests a potential role for local ablative therapy.

Expert perspective on the analysis was provided by Benjamin Movsas, MD, chair of radiation oncology at the Henry Ford Cancer Institute in Detroit.

“The PACIFIC trial has really transformed the standard of care for patients with locally advanced, inoperable non–small cell lung cancer by adding immunotherapy to the prior standard of care combining chemotherapy and radiation, and this has shown a dramatic improvement in survival,” Dr. Movsas said.

“By adding the immunotherapy durvalumab, you can reduce risk of local failure, you can reduce the risk of distant failure, and interestingly enough, when patients do fail distantly, and this is true in both arms, they tended to fail in only one or two spots, which is encouraging because that suggests maybe a window of opportunity to treat those one or two spots, and we have newer technologies that allow us to consider that. So we really have a new paradigm.”

The study was funded by AstraZeneca. The investigators disclosed additional relationships with Merck, Nanobiotix, Boehringer Ingelheim, and others.

SOURCE: Rimner A et al. ASTRO 2019, Abstract LBA6.

Most patients with stage III non–small cell lung cancer (NSCLC) who have distant progression on standard therapy typically have one or two new lesions, often in the same organ, which suggests a role for local ablative therapy, according to investigators.

This conclusion was drawn from an exploratory analysis of the phase 3 PACIFIC trial, which previously showed that durvalumab prolonged survival among patients with NSCLC who did not progress after chemoradiotherapy, which turned the trial protocol into a new standard of care.

At the annual meeting of the American Society for Radiation Oncology, coauthor Andreas Rimner, MD, of the Memorial Sloan Kettering Cancer Center in New York presented findings.

“There were always questions regarding detailed patterns of failure and disease progression in [the PACIFIC] trial,” Dr. Rimner said. “This study ... focuses on these patterns of failure, including the type of first progression in the patients on the PACIFIC trial.”

During the trial, 713 patients with NSCLC were randomized in a 2:1 ratio to receive either durvalumab or placebo. After a median follow-up of 25.2 months, the superiority of durvalumab was clear, with a lower rate of progression (45.4% vs. 64.6%).

But the present analysis dug deeper into this finding by dividing patients into three groups based on site or sites of first progression: local (intrathoracic) progression only, distant (extrathoracic) progression only, or simultaneously local and distant progression. Scans were reviewed by an independent radiologist who was not involved in the original PACIFIC trial. In addition to spatial data, the investigators reported times until progression.

Regardless of site, durvalumab was associated with a longer time until progression or death. Although comparative values were not reached for distant or simultaneous spread, median time until local progression or death was reportable, at 25.2 months in the durvalumab group versus with 9.2 months in the placebo group.

These values were available, in part, because local spread was the most common type of progression: It occurred in 80.6% of patients who progressed on durvalumab and 74.5% of progressors in the placebo group.

Durvalumab reduced the rate of progression across the three spatial categories, compared with placebo, including local only (36.6% vs. 48.1%, respectively), distant only (6.9% vs. 13.1%), and simultaneously local and distant (1.9% vs. 3.4%). This means that, at first progression, new distant lesions were found in 8.8% of patients treated with durvalumab, compared with 16.5% of those treated with placebo. Of note, approximately two-thirds of patients with distant progression had only one or two distant lesions, often confined to one organ, most commonly the brain. This pattern of progression was observed in both treatment arms.

According to Dr. Rimner, this finding is clinically relevant because it suggests a potential role for local ablative therapy.

Expert perspective on the analysis was provided by Benjamin Movsas, MD, chair of radiation oncology at the Henry Ford Cancer Institute in Detroit.

“The PACIFIC trial has really transformed the standard of care for patients with locally advanced, inoperable non–small cell lung cancer by adding immunotherapy to the prior standard of care combining chemotherapy and radiation, and this has shown a dramatic improvement in survival,” Dr. Movsas said.

“By adding the immunotherapy durvalumab, you can reduce risk of local failure, you can reduce the risk of distant failure, and interestingly enough, when patients do fail distantly, and this is true in both arms, they tended to fail in only one or two spots, which is encouraging because that suggests maybe a window of opportunity to treat those one or two spots, and we have newer technologies that allow us to consider that. So we really have a new paradigm.”

The study was funded by AstraZeneca. The investigators disclosed additional relationships with Merck, Nanobiotix, Boehringer Ingelheim, and others.

SOURCE: Rimner A et al. ASTRO 2019, Abstract LBA6.

Stereotactic ablative radiation therapy (SABR) may be able to extend progression-free survival (PFS) among patients with oligometastatic prostate cancer, based on results from the phase 2 ORIOLE trial.

Will Pass/MDedge News

SABR appeared to control disease, in part, by triggering a systemic immune response, reported lead author Ryan Phillips, MD, PhD, chief resident of radiation oncology at Johns Hopkins Sidney Kimmel Cancer Center in Baltimore, at the annual meeting of the American Society for Radiation Oncology. This is a particularly noteworthy finding, since prostate cancer is generally considered to be immunologically cold, Dr. Phillips explained.

The ORIOLE trial also demonstrated how prostate-specific membrane antigen (PSMA)–based PET/CT scans can be used to more accurately predict metastasis by detecting lesions that would otherwise be missed by standard imaging.

“There’s a hypothesis that these first few sites of spread pave the way for additional widespread metastasis down the road,” Dr. Phillips said, “and that if we can treat all detectable disease early enough, we may be able to provide long-term control or in the best-case scenario, be able to cure these patients of early metastatic disease.”

The trial involved 54 men with recurrent, hormone-sensitive prostate cancer who had been previously treated with radiation therapy or surgery. Additional eligibility requirements included one to three lesions that were 5 cm or smaller, detectable by MRI, CT, or bone scan; a prostate-specific antigen (PSA) doubling time of less than 15 months; and an Eastern Cooperative Oncology Group performance status of 2 or less.

Patients were randomized in a 2:1 ratio to receive either SABR or observation, with follow-up every 3 months including physical exam and PSA measurement, and at 6 months, CT and bone scan. The primary endpoint was disease progression at 6 months.

In addition to this protocol, biomarker correlative analyses were performed, including PSMA-based PET/CT, T-cell clonality testing, and circulating tumor DNA (ctDNA) assessment.

Results showed that significantly fewer men treated with SABR had disease progression at 6 months (19% vs. 61%; P = .005). This benefit extended beyond the primary endpoint, as median PFS among patients treated with SABR was not yet reached after more than a year of follow-up, while those in the observation group had a median PFS of 5.8 months (P = .0023).

“Clinically, this is promising,” Dr. Phillips said, “but we also were really interested in learning more about oligometastatic prostate cancer, and something that sets ORIOLE apart are the correlative studies.”

The first of these studies involved PSMA-based PET/CT, which can identify lesions that may be missed or underappreciated with conventional imaging. Within the SABR group, 35 of 36 men had PSMA-based PET/CT performed at baseline and 6 months later. Of these, 19 had all PSMA-based PET/CT–detectable lesions treated with SABR (total consolidation), while 16 had subtotal consolidation. This difference was predictive of outcome, as only 16% of patients with total consolidation developed new lesions 6 months later, compared with 63% of those who had subtotal consolidation (P = .006).

“Not only are we treating the disease we’re detecting, but it seems to be preventing the development of new metastases outside the areas that we treated,” Dr. Phillips said. “This also held when we looked at points beyond 6 months,” he added.

Further testing showed that SABR triggered a systemic adaptive immune response involving expansion of T-cell clones. “There’s a lot more activity and changes within the immune system that were only seen within the SABR arm,” Dr. Phillips said, noting that these changes were “similar in scope to what we see after a vaccination.”

Finally, the investigators assessed ctDNA, which showed that men with at least one high-risk mutation had similar outcomes regardless of treatment group; in contrast, those without any high-risk mutations had significantly better PFS when treated with SABR.

“These are low sample size, hypothesis-generating experiments,” Dr. Phillips said, “but it is promising that there may be measurable baseline factors that will help us decide which patients are likely to benefit from this approach, and which would really be better served with an alternate treatment strategy.”

Will Pass/MDedge News

Session moderator Anthony Zietman, MD, of Massachusetts General Hospital, Boston, suggested that the ORIOLE trial could have a big future. “This is a small study, but it’s a prospective study, and the findings are really provocative,” Dr. Zietman said. “Just imagine, if there was a patient with just two or three metastatic lesions, and by irradiating those, you could liberate proteins from the destroyed metastases, generate an immune response, and suppress the development of new metastases, that will be something extraordinary. So this trial will be followed very closely as it seems to be hinting at something that’s a bit of a Holy Grail in oncology.”

The investigators disclosed relationships with RefleXion Medical, Pfizer, Genentech, and others.

SOURCE: Phillips R et al. ASTRO 2019. Abstract LBA3.

Stereotactic ablative radiation therapy (SABR) may be able to extend progression-free survival (PFS) among patients with oligometastatic prostate cancer, based on results from the phase 2 ORIOLE trial.

Will Pass/MDedge News

SABR appeared to control disease, in part, by triggering a systemic immune response, reported lead author Ryan Phillips, MD, PhD, chief resident of radiation oncology at Johns Hopkins Sidney Kimmel Cancer Center in Baltimore, at the annual meeting of the American Society for Radiation Oncology. This is a particularly noteworthy finding, since prostate cancer is generally considered to be immunologically cold, Dr. Phillips explained.

The ORIOLE trial also demonstrated how prostate-specific membrane antigen (PSMA)–based PET/CT scans can be used to more accurately predict metastasis by detecting lesions that would otherwise be missed by standard imaging.

“There’s a hypothesis that these first few sites of spread pave the way for additional widespread metastasis down the road,” Dr. Phillips said, “and that if we can treat all detectable disease early enough, we may be able to provide long-term control or in the best-case scenario, be able to cure these patients of early metastatic disease.”

The trial involved 54 men with recurrent, hormone-sensitive prostate cancer who had been previously treated with radiation therapy or surgery. Additional eligibility requirements included one to three lesions that were 5 cm or smaller, detectable by MRI, CT, or bone scan; a prostate-specific antigen (PSA) doubling time of less than 15 months; and an Eastern Cooperative Oncology Group performance status of 2 or less.

Patients were randomized in a 2:1 ratio to receive either SABR or observation, with follow-up every 3 months including physical exam and PSA measurement, and at 6 months, CT and bone scan. The primary endpoint was disease progression at 6 months.

In addition to this protocol, biomarker correlative analyses were performed, including PSMA-based PET/CT, T-cell clonality testing, and circulating tumor DNA (ctDNA) assessment.

Results showed that significantly fewer men treated with SABR had disease progression at 6 months (19% vs. 61%; P = .005). This benefit extended beyond the primary endpoint, as median PFS among patients treated with SABR was not yet reached after more than a year of follow-up, while those in the observation group had a median PFS of 5.8 months (P = .0023).

“Clinically, this is promising,” Dr. Phillips said, “but we also were really interested in learning more about oligometastatic prostate cancer, and something that sets ORIOLE apart are the correlative studies.”

The first of these studies involved PSMA-based PET/CT, which can identify lesions that may be missed or underappreciated with conventional imaging. Within the SABR group, 35 of 36 men had PSMA-based PET/CT performed at baseline and 6 months later. Of these, 19 had all PSMA-based PET/CT–detectable lesions treated with SABR (total consolidation), while 16 had subtotal consolidation. This difference was predictive of outcome, as only 16% of patients with total consolidation developed new lesions 6 months later, compared with 63% of those who had subtotal consolidation (P = .006).

“Not only are we treating the disease we’re detecting, but it seems to be preventing the development of new metastases outside the areas that we treated,” Dr. Phillips said. “This also held when we looked at points beyond 6 months,” he added.

Further testing showed that SABR triggered a systemic adaptive immune response involving expansion of T-cell clones. “There’s a lot more activity and changes within the immune system that were only seen within the SABR arm,” Dr. Phillips said, noting that these changes were “similar in scope to what we see after a vaccination.”

Finally, the investigators assessed ctDNA, which showed that men with at least one high-risk mutation had similar outcomes regardless of treatment group; in contrast, those without any high-risk mutations had significantly better PFS when treated with SABR.

“These are low sample size, hypothesis-generating experiments,” Dr. Phillips said, “but it is promising that there may be measurable baseline factors that will help us decide which patients are likely to benefit from this approach, and which would really be better served with an alternate treatment strategy.”

Will Pass/MDedge News

Session moderator Anthony Zietman, MD, of Massachusetts General Hospital, Boston, suggested that the ORIOLE trial could have a big future. “This is a small study, but it’s a prospective study, and the findings are really provocative,” Dr. Zietman said. “Just imagine, if there was a patient with just two or three metastatic lesions, and by irradiating those, you could liberate proteins from the destroyed metastases, generate an immune response, and suppress the development of new metastases, that will be something extraordinary. So this trial will be followed very closely as it seems to be hinting at something that’s a bit of a Holy Grail in oncology.”

The investigators disclosed relationships with RefleXion Medical, Pfizer, Genentech, and others.

SOURCE: Phillips R et al. ASTRO 2019. Abstract LBA3.

Stereotactic ablative radiation therapy (SABR) may be able to extend progression-free survival (PFS) among patients with oligometastatic prostate cancer, based on results from the phase 2 ORIOLE trial.

Will Pass/MDedge News

SABR appeared to control disease, in part, by triggering a systemic immune response, reported lead author Ryan Phillips, MD, PhD, chief resident of radiation oncology at Johns Hopkins Sidney Kimmel Cancer Center in Baltimore, at the annual meeting of the American Society for Radiation Oncology. This is a particularly noteworthy finding, since prostate cancer is generally considered to be immunologically cold, Dr. Phillips explained.

The ORIOLE trial also demonstrated how prostate-specific membrane antigen (PSMA)–based PET/CT scans can be used to more accurately predict metastasis by detecting lesions that would otherwise be missed by standard imaging.

“There’s a hypothesis that these first few sites of spread pave the way for additional widespread metastasis down the road,” Dr. Phillips said, “and that if we can treat all detectable disease early enough, we may be able to provide long-term control or in the best-case scenario, be able to cure these patients of early metastatic disease.”

The trial involved 54 men with recurrent, hormone-sensitive prostate cancer who had been previously treated with radiation therapy or surgery. Additional eligibility requirements included one to three lesions that were 5 cm or smaller, detectable by MRI, CT, or bone scan; a prostate-specific antigen (PSA) doubling time of less than 15 months; and an Eastern Cooperative Oncology Group performance status of 2 or less.

Patients were randomized in a 2:1 ratio to receive either SABR or observation, with follow-up every 3 months including physical exam and PSA measurement, and at 6 months, CT and bone scan. The primary endpoint was disease progression at 6 months.

In addition to this protocol, biomarker correlative analyses were performed, including PSMA-based PET/CT, T-cell clonality testing, and circulating tumor DNA (ctDNA) assessment.

Results showed that significantly fewer men treated with SABR had disease progression at 6 months (19% vs. 61%; P = .005). This benefit extended beyond the primary endpoint, as median PFS among patients treated with SABR was not yet reached after more than a year of follow-up, while those in the observation group had a median PFS of 5.8 months (P = .0023).

“Clinically, this is promising,” Dr. Phillips said, “but we also were really interested in learning more about oligometastatic prostate cancer, and something that sets ORIOLE apart are the correlative studies.”

The first of these studies involved PSMA-based PET/CT, which can identify lesions that may be missed or underappreciated with conventional imaging. Within the SABR group, 35 of 36 men had PSMA-based PET/CT performed at baseline and 6 months later. Of these, 19 had all PSMA-based PET/CT–detectable lesions treated with SABR (total consolidation), while 16 had subtotal consolidation. This difference was predictive of outcome, as only 16% of patients with total consolidation developed new lesions 6 months later, compared with 63% of those who had subtotal consolidation (P = .006).

“Not only are we treating the disease we’re detecting, but it seems to be preventing the development of new metastases outside the areas that we treated,” Dr. Phillips said. “This also held when we looked at points beyond 6 months,” he added.

Further testing showed that SABR triggered a systemic adaptive immune response involving expansion of T-cell clones. “There’s a lot more activity and changes within the immune system that were only seen within the SABR arm,” Dr. Phillips said, noting that these changes were “similar in scope to what we see after a vaccination.”

Finally, the investigators assessed ctDNA, which showed that men with at least one high-risk mutation had similar outcomes regardless of treatment group; in contrast, those without any high-risk mutations had significantly better PFS when treated with SABR.

“These are low sample size, hypothesis-generating experiments,” Dr. Phillips said, “but it is promising that there may be measurable baseline factors that will help us decide which patients are likely to benefit from this approach, and which would really be better served with an alternate treatment strategy.”

Will Pass/MDedge News

Session moderator Anthony Zietman, MD, of Massachusetts General Hospital, Boston, suggested that the ORIOLE trial could have a big future. “This is a small study, but it’s a prospective study, and the findings are really provocative,” Dr. Zietman said. “Just imagine, if there was a patient with just two or three metastatic lesions, and by irradiating those, you could liberate proteins from the destroyed metastases, generate an immune response, and suppress the development of new metastases, that will be something extraordinary. So this trial will be followed very closely as it seems to be hinting at something that’s a bit of a Holy Grail in oncology.”

The investigators disclosed relationships with RefleXion Medical, Pfizer, Genentech, and others.

SOURCE: Phillips R et al. ASTRO 2019. Abstract LBA3.

For patients with metastatic non–small cell lung cancer (NSCLC) who have disease progression on immunotherapy, adding stereotactic body radiotherapy (SBRT) could improve progression-free survival (PFS), according to investigators.

Will Pass/MDedge News

Patients with more CD8+ T cells in circulation, and those with higher tumor infiltrating lymphocyte (TIL) scores derived the most benefit from SBRT, lead author Allison Campbell, MD, PhD, of Yale Cancer Center in New Haven, Conn., and colleagues, reported at the annual meeting of the American Society for Radiation Oncology.

“In rare cases, adding radiation to immunotherapy has been shown to result in therapeutic synergy,” Dr. Campbell said. “When we give high-dose radiation to patients on immunotherapy, some tumors that were not targeted by the radiation can shrink, and this is called ‘the abscopal effect.’ ”

The investigators designed the phase 2 trial to determine if the abscopal effect would occur if high-dose radiation was delivered to a single site in patients who had progressed on checkpoint inhibitor therapy. Fifty-six patients were enrolled, all with at least two sites of metastatic NSCLC. Of these patients, 6 had already progressed on immunotherapy, while 50 were naive to immunotherapy and began pembrolizumab during the trial, with 16 eventually progressing; collectively, these 22 patients with disease progression were identified as candidates for SBRT. Almost all candidates (21 out of 22) completed SBRT, which was delivered in three or five high-dose fractions. Only one site was treated, while other sites were tracked over time with computed tomography (CT) to assess for the abscopal effect. In addition, blood was analyzed for circulating immune cell composition.

After a median follow-up of 15.2 months, the disease control rate was 57%, with some abscopal responses detected. Two patients (10%) achieved a partial response lasting more than 1 year, and 10 patients (48%) maintained stable disease after SBRT. Although programmed death-ligand 1 (PD-L1) positivity was associated with a trend toward increased PFS, this was not statistically significant. In contrast, TIL score was significantly correlated with PFS; patients with TIL scores of 2-3 had a median PFS of 6.7 months, compared with 2.2 months among those with TIL scores of 1 or less. Similarly, immune-related adverse events predicted outcome, with patients who experienced such events achieving longer median PFS than those who did not (6.5 vs 2.2 months). Furthermore, blood testing revealed that the best responders had more CD8+ killer T cells and fewer CD4+ regulatory T cells in peripheral blood compared with patients who responded poorly.

After Dr. Campbell’s presentation, Benjamin Movsas, MD, chair of radiation oncology at the Henry Ford Cancer Institute in Detroit, offered some expert insight. “[The findings from this study] suggest perhaps that radiation may be able to reinvigorate the immune system,” Dr. Movsas said. “Maybe we can get more mileage out of the immunotherapy with this approach. Could radiation kind of be like an immune vaccine of sorts? There’s a lot of exciting possibilities.”

Will Pass/MDedge News

Dr. Movsas also noted how biomarker findings may be able to guide treatment decisions, highlighting how T cell populations predicted outcomes. “This era of precision medicine is really helping us improve benefits,” he said. “The immune profile really matters.”

The investigators disclosed relationships with Genentech, AstraZeneca, Merck, and others.

SOURCE: Campbell et al. ASTRO 2019. Abstract 74.

For patients with metastatic non–small cell lung cancer (NSCLC) who have disease progression on immunotherapy, adding stereotactic body radiotherapy (SBRT) could improve progression-free survival (PFS), according to investigators.

Will Pass/MDedge News

Patients with more CD8+ T cells in circulation, and those with higher tumor infiltrating lymphocyte (TIL) scores derived the most benefit from SBRT, lead author Allison Campbell, MD, PhD, of Yale Cancer Center in New Haven, Conn., and colleagues, reported at the annual meeting of the American Society for Radiation Oncology.

“In rare cases, adding radiation to immunotherapy has been shown to result in therapeutic synergy,” Dr. Campbell said. “When we give high-dose radiation to patients on immunotherapy, some tumors that were not targeted by the radiation can shrink, and this is called ‘the abscopal effect.’ ”

The investigators designed the phase 2 trial to determine if the abscopal effect would occur if high-dose radiation was delivered to a single site in patients who had progressed on checkpoint inhibitor therapy. Fifty-six patients were enrolled, all with at least two sites of metastatic NSCLC. Of these patients, 6 had already progressed on immunotherapy, while 50 were naive to immunotherapy and began pembrolizumab during the trial, with 16 eventually progressing; collectively, these 22 patients with disease progression were identified as candidates for SBRT. Almost all candidates (21 out of 22) completed SBRT, which was delivered in three or five high-dose fractions. Only one site was treated, while other sites were tracked over time with computed tomography (CT) to assess for the abscopal effect. In addition, blood was analyzed for circulating immune cell composition.

After a median follow-up of 15.2 months, the disease control rate was 57%, with some abscopal responses detected. Two patients (10%) achieved a partial response lasting more than 1 year, and 10 patients (48%) maintained stable disease after SBRT. Although programmed death-ligand 1 (PD-L1) positivity was associated with a trend toward increased PFS, this was not statistically significant. In contrast, TIL score was significantly correlated with PFS; patients with TIL scores of 2-3 had a median PFS of 6.7 months, compared with 2.2 months among those with TIL scores of 1 or less. Similarly, immune-related adverse events predicted outcome, with patients who experienced such events achieving longer median PFS than those who did not (6.5 vs 2.2 months). Furthermore, blood testing revealed that the best responders had more CD8+ killer T cells and fewer CD4+ regulatory T cells in peripheral blood compared with patients who responded poorly.

After Dr. Campbell’s presentation, Benjamin Movsas, MD, chair of radiation oncology at the Henry Ford Cancer Institute in Detroit, offered some expert insight. “[The findings from this study] suggest perhaps that radiation may be able to reinvigorate the immune system,” Dr. Movsas said. “Maybe we can get more mileage out of the immunotherapy with this approach. Could radiation kind of be like an immune vaccine of sorts? There’s a lot of exciting possibilities.”

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Dr. Movsas also noted how biomarker findings may be able to guide treatment decisions, highlighting how T cell populations predicted outcomes. “This era of precision medicine is really helping us improve benefits,” he said. “The immune profile really matters.”

The investigators disclosed relationships with Genentech, AstraZeneca, Merck, and others.

SOURCE: Campbell et al. ASTRO 2019. Abstract 74.

For patients with metastatic non–small cell lung cancer (NSCLC) who have disease progression on immunotherapy, adding stereotactic body radiotherapy (SBRT) could improve progression-free survival (PFS), according to investigators.

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Patients with more CD8+ T cells in circulation, and those with higher tumor infiltrating lymphocyte (TIL) scores derived the most benefit from SBRT, lead author Allison Campbell, MD, PhD, of Yale Cancer Center in New Haven, Conn., and colleagues, reported at the annual meeting of the American Society for Radiation Oncology.

“In rare cases, adding radiation to immunotherapy has been shown to result in therapeutic synergy,” Dr. Campbell said. “When we give high-dose radiation to patients on immunotherapy, some tumors that were not targeted by the radiation can shrink, and this is called ‘the abscopal effect.’ ”

The investigators designed the phase 2 trial to determine if the abscopal effect would occur if high-dose radiation was delivered to a single site in patients who had progressed on checkpoint inhibitor therapy. Fifty-six patients were enrolled, all with at least two sites of metastatic NSCLC. Of these patients, 6 had already progressed on immunotherapy, while 50 were naive to immunotherapy and began pembrolizumab during the trial, with 16 eventually progressing; collectively, these 22 patients with disease progression were identified as candidates for SBRT. Almost all candidates (21 out of 22) completed SBRT, which was delivered in three or five high-dose fractions. Only one site was treated, while other sites were tracked over time with computed tomography (CT) to assess for the abscopal effect. In addition, blood was analyzed for circulating immune cell composition.

After a median follow-up of 15.2 months, the disease control rate was 57%, with some abscopal responses detected. Two patients (10%) achieved a partial response lasting more than 1 year, and 10 patients (48%) maintained stable disease after SBRT. Although programmed death-ligand 1 (PD-L1) positivity was associated with a trend toward increased PFS, this was not statistically significant. In contrast, TIL score was significantly correlated with PFS; patients with TIL scores of 2-3 had a median PFS of 6.7 months, compared with 2.2 months among those with TIL scores of 1 or less. Similarly, immune-related adverse events predicted outcome, with patients who experienced such events achieving longer median PFS than those who did not (6.5 vs 2.2 months). Furthermore, blood testing revealed that the best responders had more CD8+ killer T cells and fewer CD4+ regulatory T cells in peripheral blood compared with patients who responded poorly.

After Dr. Campbell’s presentation, Benjamin Movsas, MD, chair of radiation oncology at the Henry Ford Cancer Institute in Detroit, offered some expert insight. “[The findings from this study] suggest perhaps that radiation may be able to reinvigorate the immune system,” Dr. Movsas said. “Maybe we can get more mileage out of the immunotherapy with this approach. Could radiation kind of be like an immune vaccine of sorts? There’s a lot of exciting possibilities.”

Will Pass/MDedge News

Dr. Movsas also noted how biomarker findings may be able to guide treatment decisions, highlighting how T cell populations predicted outcomes. “This era of precision medicine is really helping us improve benefits,” he said. “The immune profile really matters.”

The investigators disclosed relationships with Genentech, AstraZeneca, Merck, and others.

SOURCE: Campbell et al. ASTRO 2019. Abstract 74.

The closure of women’s clinics appears to negatively impact outcomes among patients with cervical cancer, based on an epidemiological study involving more than 200,000 cases.

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States with a decreased number of women’s clinics per capita between 2010 and 2013 were found to have less screening for cervical cancer, more advanced stage of cervical cancer at presentation, and higher mortality from cervical cancer than states with no decrease in clinics, reported lead author Amar J. Srivastava, MD, of Washington University in St. Louis, who also noted that these changes occurred within a relatively short time frame.

“We know that women are generally diagnosed through the utilization of Pap smears,” Dr. Srivastava said during a presentation at the annual meeting of the American Society for Radiation Oncology. “These are low-cost tests that are available at multiple low-cost women’s health clinics. Unfortunately ... over the course of the past decade, we’ve seen a significant reduction of these clinics throughout the United States.”

“Between 2010 and 2013, which is the period of interest in this study, we know that about 100 of these women’s health clinics closed,” Dr. Srivastava said. “This was due to a combination of several factors; some of it was due to funding, some of it was due to restructuring of the clinics, and there were also laws passed throughout many states that ultimately led to the closure of many clinics.”

To determine the impact of these closures, the investigators first divided states into those that had women’s clinic closures between 2010 and 2013 and those that did not. Comparisons between these two cohorts involved the use of two databases. The first was the Behavioral Risk Factors Surveillance Study (BRFSS), which provided data from 197,143 cases, enabling assessment of differences between screening availability. The second database was the Surveillance, Epidemiology, and End Results (SEER) registry, which provided data from 10,652 patients, facilitating comparisons of stage at time of diagnosis and mortality rate.

Results were described in terms of relative differences between the two cohorts. For instance, screening rate among women with cervical cancer in states that had a decreased number of clinics was 1.63% lower than in states that did not lose clinics. This disparity was more pronounced in specific demographic subgroups, including Hispanic women (–5.82%), women aged between 21 and 34 years (–5.19%), unmarried women (–4.10%), and uninsured women (–6.88%).

“Historically, these are marginalized, underserved groups, and unfortunately, it comes as no surprise that these were the groups of women who were most dramatically hit by these changes,” Dr. Srivastava said.

Early-stage diagnosis was also significantly less common in states that had a decreased number of clinics, by a margin of 13.2%. Finally, the overall mortality rate among women with cervical cancer was 36% higher in states with clinic closures, a difference that climbed to 40% when comparing only metro residents.

Connecting the dots, Dr. Srivastava suggested that the decreased availability of screening may have led to fewer diagnoses at an early stage, which is more curable than late-stage disease, ultimately translating to a higher mortality rate. After noting that this chain of causality cannot be confirmed, owing to the retrospective nature of the study, Dr. Srivastava finished his presentation with a call to action.

“These findings should really give us some pause,” he said, “as physicians, as people who care about other people, to spend some time, try to figure out what’s going on, and try to address this disparity.”

Will Pass/MDedge News

After the presentation, Geraldine M. Jacobsen, MD, chair of radiation oncology at West Virginia University Cancer Institute, in Morgantown, W.V., echoed Dr. Srivastava’s concern.

“This study really raises broader questions,” Dr. Jacobsen said. “In the United States we’re always engaged in an ongoing dialogue about health care, health care policy, [and] health care costs. But a study like this brings to us the human face of what these dialogues mean. Policy affects people, and if we make changes in health care policy or health care legislation, we’re impacting people’s health and people’s lives.”

The investigators disclosed relationships with Phelps County Regional Medical Center, the Elsa U. Pardee Foundation, the American Society of Clinical Oncology, and ASTRO.

SOURCE: Srivastava AJ et al. ASTRO 2019, Abstract 202.

The closure of women’s clinics appears to negatively impact outcomes among patients with cervical cancer, based on an epidemiological study involving more than 200,000 cases.

Will Pass/MDedge News

States with a decreased number of women’s clinics per capita between 2010 and 2013 were found to have less screening for cervical cancer, more advanced stage of cervical cancer at presentation, and higher mortality from cervical cancer than states with no decrease in clinics, reported lead author Amar J. Srivastava, MD, of Washington University in St. Louis, who also noted that these changes occurred within a relatively short time frame.

“We know that women are generally diagnosed through the utilization of Pap smears,” Dr. Srivastava said during a presentation at the annual meeting of the American Society for Radiation Oncology. “These are low-cost tests that are available at multiple low-cost women’s health clinics. Unfortunately ... over the course of the past decade, we’ve seen a significant reduction of these clinics throughout the United States.”

“Between 2010 and 2013, which is the period of interest in this study, we know that about 100 of these women’s health clinics closed,” Dr. Srivastava said. “This was due to a combination of several factors; some of it was due to funding, some of it was due to restructuring of the clinics, and there were also laws passed throughout many states that ultimately led to the closure of many clinics.”

To determine the impact of these closures, the investigators first divided states into those that had women’s clinic closures between 2010 and 2013 and those that did not. Comparisons between these two cohorts involved the use of two databases. The first was the Behavioral Risk Factors Surveillance Study (BRFSS), which provided data from 197,143 cases, enabling assessment of differences between screening availability. The second database was the Surveillance, Epidemiology, and End Results (SEER) registry, which provided data from 10,652 patients, facilitating comparisons of stage at time of diagnosis and mortality rate.

Results were described in terms of relative differences between the two cohorts. For instance, screening rate among women with cervical cancer in states that had a decreased number of clinics was 1.63% lower than in states that did not lose clinics. This disparity was more pronounced in specific demographic subgroups, including Hispanic women (–5.82%), women aged between 21 and 34 years (–5.19%), unmarried women (–4.10%), and uninsured women (–6.88%).

“Historically, these are marginalized, underserved groups, and unfortunately, it comes as no surprise that these were the groups of women who were most dramatically hit by these changes,” Dr. Srivastava said.

Early-stage diagnosis was also significantly less common in states that had a decreased number of clinics, by a margin of 13.2%. Finally, the overall mortality rate among women with cervical cancer was 36% higher in states with clinic closures, a difference that climbed to 40% when comparing only metro residents.

Connecting the dots, Dr. Srivastava suggested that the decreased availability of screening may have led to fewer diagnoses at an early stage, which is more curable than late-stage disease, ultimately translating to a higher mortality rate. After noting that this chain of causality cannot be confirmed, owing to the retrospective nature of the study, Dr. Srivastava finished his presentation with a call to action.

“These findings should really give us some pause,” he said, “as physicians, as people who care about other people, to spend some time, try to figure out what’s going on, and try to address this disparity.”

Will Pass/MDedge News

After the presentation, Geraldine M. Jacobsen, MD, chair of radiation oncology at West Virginia University Cancer Institute, in Morgantown, W.V., echoed Dr. Srivastava’s concern.

“This study really raises broader questions,” Dr. Jacobsen said. “In the United States we’re always engaged in an ongoing dialogue about health care, health care policy, [and] health care costs. But a study like this brings to us the human face of what these dialogues mean. Policy affects people, and if we make changes in health care policy or health care legislation, we’re impacting people’s health and people’s lives.”

The investigators disclosed relationships with Phelps County Regional Medical Center, the Elsa U. Pardee Foundation, the American Society of Clinical Oncology, and ASTRO.

SOURCE: Srivastava AJ et al. ASTRO 2019, Abstract 202.

The closure of women’s clinics appears to negatively impact outcomes among patients with cervical cancer, based on an epidemiological study involving more than 200,000 cases.

Will Pass/MDedge News

States with a decreased number of women’s clinics per capita between 2010 and 2013 were found to have less screening for cervical cancer, more advanced stage of cervical cancer at presentation, and higher mortality from cervical cancer than states with no decrease in clinics, reported lead author Amar J. Srivastava, MD, of Washington University in St. Louis, who also noted that these changes occurred within a relatively short time frame.

“We know that women are generally diagnosed through the utilization of Pap smears,” Dr. Srivastava said during a presentation at the annual meeting of the American Society for Radiation Oncology. “These are low-cost tests that are available at multiple low-cost women’s health clinics. Unfortunately ... over the course of the past decade, we’ve seen a significant reduction of these clinics throughout the United States.”

“Between 2010 and 2013, which is the period of interest in this study, we know that about 100 of these women’s health clinics closed,” Dr. Srivastava said. “This was due to a combination of several factors; some of it was due to funding, some of it was due to restructuring of the clinics, and there were also laws passed throughout many states that ultimately led to the closure of many clinics.”

To determine the impact of these closures, the investigators first divided states into those that had women’s clinic closures between 2010 and 2013 and those that did not. Comparisons between these two cohorts involved the use of two databases. The first was the Behavioral Risk Factors Surveillance Study (BRFSS), which provided data from 197,143 cases, enabling assessment of differences between screening availability. The second database was the Surveillance, Epidemiology, and End Results (SEER) registry, which provided data from 10,652 patients, facilitating comparisons of stage at time of diagnosis and mortality rate.

Results were described in terms of relative differences between the two cohorts. For instance, screening rate among women with cervical cancer in states that had a decreased number of clinics was 1.63% lower than in states that did not lose clinics. This disparity was more pronounced in specific demographic subgroups, including Hispanic women (–5.82%), women aged between 21 and 34 years (–5.19%), unmarried women (–4.10%), and uninsured women (–6.88%).

“Historically, these are marginalized, underserved groups, and unfortunately, it comes as no surprise that these were the groups of women who were most dramatically hit by these changes,” Dr. Srivastava said.

Early-stage diagnosis was also significantly less common in states that had a decreased number of clinics, by a margin of 13.2%. Finally, the overall mortality rate among women with cervical cancer was 36% higher in states with clinic closures, a difference that climbed to 40% when comparing only metro residents.

Connecting the dots, Dr. Srivastava suggested that the decreased availability of screening may have led to fewer diagnoses at an early stage, which is more curable than late-stage disease, ultimately translating to a higher mortality rate. After noting that this chain of causality cannot be confirmed, owing to the retrospective nature of the study, Dr. Srivastava finished his presentation with a call to action.

“These findings should really give us some pause,” he said, “as physicians, as people who care about other people, to spend some time, try to figure out what’s going on, and try to address this disparity.”

Will Pass/MDedge News

After the presentation, Geraldine M. Jacobsen, MD, chair of radiation oncology at West Virginia University Cancer Institute, in Morgantown, W.V., echoed Dr. Srivastava’s concern.

“This study really raises broader questions,” Dr. Jacobsen said. “In the United States we’re always engaged in an ongoing dialogue about health care, health care policy, [and] health care costs. But a study like this brings to us the human face of what these dialogues mean. Policy affects people, and if we make changes in health care policy or health care legislation, we’re impacting people’s health and people’s lives.”

The investigators disclosed relationships with Phelps County Regional Medical Center, the Elsa U. Pardee Foundation, the American Society of Clinical Oncology, and ASTRO.

SOURCE: Srivastava AJ et al. ASTRO 2019, Abstract 202.