As hospitalists, many of us see things in our daily practice that help inform our efforts to improve quality of care, organizational efficiency, and medical education, and to reduce physician burnout. But many of those efforts, while well intended, lack rigorous empirical evaluation.

Indeed, it is the complexity of hospital care that leads scholars across many disciplines—including economics, epidemiology, and sociology—to look to hospital medicine as a place where “natural experimentation” can inform us about what works and doesn’t work in medical care. As a hospitalist and economist, I find that the very best of my ideas come from what I see in the hospital. And for many hospital-based clinicians and physician leaders, translating everyday insights into rigorous scientific explorations is not only feasible but is a natural extension of the curiosity that drives good clinical work. It is also a way to drive quality improvement.

Consider, for example, a question that hospitalists face every day: when to discharge a patient from the hospital. Hospital leaders and frontline clinicians are increasingly under pressure to discharge patients earlier and earlier, with some concerned that earlier discharge poses safety risks. Short of randomizing patients to earlier discharge and studying the effects on outcomes, how can a data-driven hospital leader identify which patients can be safely discharged earlier and how much earlier?

A simple observation of a practicing hospitalist could be a clue to elegantly and rigorously answering this question. It turns out that some patients happen to be hospitalized days before their birthday and it wouldn’t be absurd to think that a physician treating such a patient might be more likely to discharge that patient home on or before their birthday so they can celebrate it at home. The same might be true for patients who are in the hospital before an impending storm. Patient-level data could be used to assess whether length of stay is shorter for patients who are admitted to the hospital a few days before their birthday (or just before a storm), compared with otherwise similar patients admitted to the hospital several weeks earlier, and whether outcomes are any different, on average, or in specific subpopulations. For hospital leaders, this could not only be convincing “quasi-experimental” evidence that length of stay can be safely reduced, but it could also contribute to the scholarly literature.

How can hospitalists generate ideas like these, rigorously evaluate them, and translate them into practice? It turns out that examples such as these abound for the practicing hospitalist, yet few draw the link between these everyday phenomena and the larger question of how length of stay affects patient outcomes. To start, a systematic approach to generating ideas is important: “idea rounds”—a dedicated group discussion in which physicians and other providers brainstorm ideas for quality improvement—can leverage the wisdom of frontline clinicians. But, clever insights aren’t enough. Data and statistical expertise are needed, but with the growing use of electronic health record data and administrative data from large insurers, lack of data is less of a challenge. The larger challenge is data expertise. Data-driven hospital leaders should invest in personnel with statistical expertise to not only complement the scholarly endeavors of hospital medicine faculty, but also to conduct larger, more rigorous quality improvement studies. Particularly as hospitals are increasingly being measured and reimbursed on the basis of data-oriented quality-of-care metrics, it makes sense for hospital leaders to analogously invest in data infrastructure and the analytic capability to analyze that data. The innovation of this approach lies in the simple insight that the everyday activities of hospitalists can be used to answer interesting questions about what works, what doesn’t, and potentially why in healthcare.

Disclosures

Dr. Jena reports receiving consulting fees unrelated to this work from Pfizer, Hill Rom Services, Bristol Myers Squibb, Novartis, Amgen, Eli Lilly, Vertex Pharmaceuticals, AstraZeneca, Celgene, Tesaro, Sanofi Aventis, Biogen, Precision Health Economics, and Analysis Group.

Funding

Support was provided by the Office of the Director, National Institutes of Health (1DP5OD017897, Dr. Jena).

As hospitalists, many of us see things in our daily practice that help inform our efforts to improve quality of care, organizational efficiency, and medical education, and to reduce physician burnout. But many of those efforts, while well intended, lack rigorous empirical evaluation.

Indeed, it is the complexity of hospital care that leads scholars across many disciplines—including economics, epidemiology, and sociology—to look to hospital medicine as a place where “natural experimentation” can inform us about what works and doesn’t work in medical care. As a hospitalist and economist, I find that the very best of my ideas come from what I see in the hospital. And for many hospital-based clinicians and physician leaders, translating everyday insights into rigorous scientific explorations is not only feasible but is a natural extension of the curiosity that drives good clinical work. It is also a way to drive quality improvement.

Consider, for example, a question that hospitalists face every day: when to discharge a patient from the hospital. Hospital leaders and frontline clinicians are increasingly under pressure to discharge patients earlier and earlier, with some concerned that earlier discharge poses safety risks. Short of randomizing patients to earlier discharge and studying the effects on outcomes, how can a data-driven hospital leader identify which patients can be safely discharged earlier and how much earlier?

A simple observation of a practicing hospitalist could be a clue to elegantly and rigorously answering this question. It turns out that some patients happen to be hospitalized days before their birthday and it wouldn’t be absurd to think that a physician treating such a patient might be more likely to discharge that patient home on or before their birthday so they can celebrate it at home. The same might be true for patients who are in the hospital before an impending storm. Patient-level data could be used to assess whether length of stay is shorter for patients who are admitted to the hospital a few days before their birthday (or just before a storm), compared with otherwise similar patients admitted to the hospital several weeks earlier, and whether outcomes are any different, on average, or in specific subpopulations. For hospital leaders, this could not only be convincing “quasi-experimental” evidence that length of stay can be safely reduced, but it could also contribute to the scholarly literature.

How can hospitalists generate ideas like these, rigorously evaluate them, and translate them into practice? It turns out that examples such as these abound for the practicing hospitalist, yet few draw the link between these everyday phenomena and the larger question of how length of stay affects patient outcomes. To start, a systematic approach to generating ideas is important: “idea rounds”—a dedicated group discussion in which physicians and other providers brainstorm ideas for quality improvement—can leverage the wisdom of frontline clinicians. But, clever insights aren’t enough. Data and statistical expertise are needed, but with the growing use of electronic health record data and administrative data from large insurers, lack of data is less of a challenge. The larger challenge is data expertise. Data-driven hospital leaders should invest in personnel with statistical expertise to not only complement the scholarly endeavors of hospital medicine faculty, but also to conduct larger, more rigorous quality improvement studies. Particularly as hospitals are increasingly being measured and reimbursed on the basis of data-oriented quality-of-care metrics, it makes sense for hospital leaders to analogously invest in data infrastructure and the analytic capability to analyze that data. The innovation of this approach lies in the simple insight that the everyday activities of hospitalists can be used to answer interesting questions about what works, what doesn’t, and potentially why in healthcare.

Disclosures

Dr. Jena reports receiving consulting fees unrelated to this work from Pfizer, Hill Rom Services, Bristol Myers Squibb, Novartis, Amgen, Eli Lilly, Vertex Pharmaceuticals, AstraZeneca, Celgene, Tesaro, Sanofi Aventis, Biogen, Precision Health Economics, and Analysis Group.

Funding

Support was provided by the Office of the Director, National Institutes of Health (1DP5OD017897, Dr. Jena).

As hospitalists, many of us see things in our daily practice that help inform our efforts to improve quality of care, organizational efficiency, and medical education, and to reduce physician burnout. But many of those efforts, while well intended, lack rigorous empirical evaluation.

Indeed, it is the complexity of hospital care that leads scholars across many disciplines—including economics, epidemiology, and sociology—to look to hospital medicine as a place where “natural experimentation” can inform us about what works and doesn’t work in medical care. As a hospitalist and economist, I find that the very best of my ideas come from what I see in the hospital. And for many hospital-based clinicians and physician leaders, translating everyday insights into rigorous scientific explorations is not only feasible but is a natural extension of the curiosity that drives good clinical work. It is also a way to drive quality improvement.

Consider, for example, a question that hospitalists face every day: when to discharge a patient from the hospital. Hospital leaders and frontline clinicians are increasingly under pressure to discharge patients earlier and earlier, with some concerned that earlier discharge poses safety risks. Short of randomizing patients to earlier discharge and studying the effects on outcomes, how can a data-driven hospital leader identify which patients can be safely discharged earlier and how much earlier?

A simple observation of a practicing hospitalist could be a clue to elegantly and rigorously answering this question. It turns out that some patients happen to be hospitalized days before their birthday and it wouldn’t be absurd to think that a physician treating such a patient might be more likely to discharge that patient home on or before their birthday so they can celebrate it at home. The same might be true for patients who are in the hospital before an impending storm. Patient-level data could be used to assess whether length of stay is shorter for patients who are admitted to the hospital a few days before their birthday (or just before a storm), compared with otherwise similar patients admitted to the hospital several weeks earlier, and whether outcomes are any different, on average, or in specific subpopulations. For hospital leaders, this could not only be convincing “quasi-experimental” evidence that length of stay can be safely reduced, but it could also contribute to the scholarly literature.

How can hospitalists generate ideas like these, rigorously evaluate them, and translate them into practice? It turns out that examples such as these abound for the practicing hospitalist, yet few draw the link between these everyday phenomena and the larger question of how length of stay affects patient outcomes. To start, a systematic approach to generating ideas is important: “idea rounds”—a dedicated group discussion in which physicians and other providers brainstorm ideas for quality improvement—can leverage the wisdom of frontline clinicians. But, clever insights aren’t enough. Data and statistical expertise are needed, but with the growing use of electronic health record data and administrative data from large insurers, lack of data is less of a challenge. The larger challenge is data expertise. Data-driven hospital leaders should invest in personnel with statistical expertise to not only complement the scholarly endeavors of hospital medicine faculty, but also to conduct larger, more rigorous quality improvement studies. Particularly as hospitals are increasingly being measured and reimbursed on the basis of data-oriented quality-of-care metrics, it makes sense for hospital leaders to analogously invest in data infrastructure and the analytic capability to analyze that data. The innovation of this approach lies in the simple insight that the everyday activities of hospitalists can be used to answer interesting questions about what works, what doesn’t, and potentially why in healthcare.

Disclosures

Dr. Jena reports receiving consulting fees unrelated to this work from Pfizer, Hill Rom Services, Bristol Myers Squibb, Novartis, Amgen, Eli Lilly, Vertex Pharmaceuticals, AstraZeneca, Celgene, Tesaro, Sanofi Aventis, Biogen, Precision Health Economics, and Analysis Group.

Funding

Support was provided by the Office of the Director, National Institutes of Health (1DP5OD017897, Dr. Jena).

The American College of Rheumatology, Spondylitis Association of America, and Spondyloarthritis Research and Treatment Network have updated their guidelines on management of ankylosing spondylitis and nonradiographic axial spondyloarthritis.

These guidelines serve as an update to the previous guidelines that were first published in 2015 (Arthritis Care Res. 2016;68:151–66). While the new guidelines did not review all recommendations from the 2015 guidelines, 20 questions on pharmacologic treatment were re-reviewed in addition to 26 new questions and recommendations.

Michael M. Ward, MD, chief of the Clinical Trials and Outcomes Branch at the National Institute of Arthritis and Musculoskeletal and Skin Diseases, said in an interview that the availability of new medications to treat axial spondyloarthritis (axSpA) prompted the updated guidelines.

“We took the opportunity to revisit some previous recommendations for which substantial new evidence was available, and also included new recommendations on some other topics, such as imaging,” said Dr. Ward, who is also first author of the new guidelines.

The panel that developed the questions focused on scenarios that a clinician would likely encounter in clinical practice, or situations in which how to manage a case is not clear. “Given this perspective, there were many questions that had limited evidence, but recommendations were made for all questions. For those questions that had less evidence in the literature, we relied more on the expertise of the panel,” Dr. Ward said.

The questions and recommendations for ankylosing spondylitis (AS) and nonradiographic axSpA centered around use of interleukin-17 (IL-17) inhibitors, tofacitinib (Xeljanz), and biosimilars of tumor necrosis factor-alpha inhibitors (TNFi), as well as when to taper and discontinue these medications.

Strong recommendations for patients with AS included using NSAIDs (low level of evidence), using TNFi when active disease remains despite NSAID treatment (high level of evidence), and using secukinumab (Cosentyx) or ixekizumab (Taltz) when active disease remains despite NSAID treatment over no treatment (high level of evidence). The guidelines also strongly recommend the use of physical therapy for adults with stable AS over no physical therapy (low level of evidence), as well as total hip arthroplasty in cases of advanced hip arthritis. The writing panel also strongly advised that adults with AS-related comorbidities should receive treatment by an ophthalmologist in cases of acute iritis. Strong recommendations were made against switching to a biosimilar of a TNFi after receiving treatment with an originator TNFi (regardless of whether it is for active or stable AS), use of systemic glucocorticoids in adults with active AS, treatment with spinal manipulation in patients with spinal fusion or advanced spinal osteoporosis, and screening for cardiac conduction defects and valvular heart disease with electrocardiograms.

Strong recommendations for nonradiographic axSpA were similar to those made for patients with AS, and the panel made strong recommendations for use of NSAIDs in patients with active disease; for TNFi treatment when NSAIDs fail; against switching to a biosimilar of a TNFi after starting the originator TNFi; against using systemic glucocorticoids; and in favor of using physical therapy rather than not.

The panel also made a number of conditional recommendations for AS and nonradiographic axSpA patients with regard to biologic preference and imaging. TNFis were conditionally recommended over secukinumab or ixekizumab in patients with active disease despite NSAIDs treatment, and in cases where a patient is not responding to a first TNFi treatment, the panel conditionally recommended secukinumab or ixekizumab over a second TNFi (very low evidence for all). Secukinumab or ixekizumab were also conditionally recommended over tofacitinib (very low evidence). Sulfasalazine, methotrexate, and tofacitinib were conditionally recommended in cases where patients had prominent peripheral arthritis or when TNFis are not available (very low to moderate evidence). The panel recommended against adding sulfasalazine or methotrexate to existing TNFi treatment (very low evidence), and they also advised against tapering as a standard treatment approach or discontinuing the biologic (very low evidence). MRI of the spine or pelvis was conditionally recommended to examine disease activity in unclear cases, but the panel recommended against ordering MRI scans to monitor disease inactivity (very low evidence).

“Most of the recommendations are conditional, primarily because of the relatively low level of evidence in the literature that addressed many of the questions,” while stronger recommendations came from larger clinical trials, Dr. Ward said. “The need for this update demonstrates the rapid progress in treatment that is occurring in axial spondyloarthritis, but the low level of evidence for many questions indicates that much more research is needed.”

Nine authors reported personal and institutional relationships in the form of consultancies, educational advisory board memberships, and site investigator appointments for AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, GlaxoSmithKline, Galapagos, Janssen, Novartis, Pfizer, and UCB. The other authors reported no relevant conflicts of interest.

SOURCE: Ward MM et al. Arthritis Care Res. 2019 Aug 21. doi: 10.1002/acr.24025.

The American College of Rheumatology, Spondylitis Association of America, and Spondyloarthritis Research and Treatment Network have updated their guidelines on management of ankylosing spondylitis and nonradiographic axial spondyloarthritis.

These guidelines serve as an update to the previous guidelines that were first published in 2015 (Arthritis Care Res. 2016;68:151–66). While the new guidelines did not review all recommendations from the 2015 guidelines, 20 questions on pharmacologic treatment were re-reviewed in addition to 26 new questions and recommendations.

Michael M. Ward, MD, chief of the Clinical Trials and Outcomes Branch at the National Institute of Arthritis and Musculoskeletal and Skin Diseases, said in an interview that the availability of new medications to treat axial spondyloarthritis (axSpA) prompted the updated guidelines.

“We took the opportunity to revisit some previous recommendations for which substantial new evidence was available, and also included new recommendations on some other topics, such as imaging,” said Dr. Ward, who is also first author of the new guidelines.

The panel that developed the questions focused on scenarios that a clinician would likely encounter in clinical practice, or situations in which how to manage a case is not clear. “Given this perspective, there were many questions that had limited evidence, but recommendations were made for all questions. For those questions that had less evidence in the literature, we relied more on the expertise of the panel,” Dr. Ward said.

The questions and recommendations for ankylosing spondylitis (AS) and nonradiographic axSpA centered around use of interleukin-17 (IL-17) inhibitors, tofacitinib (Xeljanz), and biosimilars of tumor necrosis factor-alpha inhibitors (TNFi), as well as when to taper and discontinue these medications.

Strong recommendations for patients with AS included using NSAIDs (low level of evidence), using TNFi when active disease remains despite NSAID treatment (high level of evidence), and using secukinumab (Cosentyx) or ixekizumab (Taltz) when active disease remains despite NSAID treatment over no treatment (high level of evidence). The guidelines also strongly recommend the use of physical therapy for adults with stable AS over no physical therapy (low level of evidence), as well as total hip arthroplasty in cases of advanced hip arthritis. The writing panel also strongly advised that adults with AS-related comorbidities should receive treatment by an ophthalmologist in cases of acute iritis. Strong recommendations were made against switching to a biosimilar of a TNFi after receiving treatment with an originator TNFi (regardless of whether it is for active or stable AS), use of systemic glucocorticoids in adults with active AS, treatment with spinal manipulation in patients with spinal fusion or advanced spinal osteoporosis, and screening for cardiac conduction defects and valvular heart disease with electrocardiograms.

Strong recommendations for nonradiographic axSpA were similar to those made for patients with AS, and the panel made strong recommendations for use of NSAIDs in patients with active disease; for TNFi treatment when NSAIDs fail; against switching to a biosimilar of a TNFi after starting the originator TNFi; against using systemic glucocorticoids; and in favor of using physical therapy rather than not.

The panel also made a number of conditional recommendations for AS and nonradiographic axSpA patients with regard to biologic preference and imaging. TNFis were conditionally recommended over secukinumab or ixekizumab in patients with active disease despite NSAIDs treatment, and in cases where a patient is not responding to a first TNFi treatment, the panel conditionally recommended secukinumab or ixekizumab over a second TNFi (very low evidence for all). Secukinumab or ixekizumab were also conditionally recommended over tofacitinib (very low evidence). Sulfasalazine, methotrexate, and tofacitinib were conditionally recommended in cases where patients had prominent peripheral arthritis or when TNFis are not available (very low to moderate evidence). The panel recommended against adding sulfasalazine or methotrexate to existing TNFi treatment (very low evidence), and they also advised against tapering as a standard treatment approach or discontinuing the biologic (very low evidence). MRI of the spine or pelvis was conditionally recommended to examine disease activity in unclear cases, but the panel recommended against ordering MRI scans to monitor disease inactivity (very low evidence).

“Most of the recommendations are conditional, primarily because of the relatively low level of evidence in the literature that addressed many of the questions,” while stronger recommendations came from larger clinical trials, Dr. Ward said. “The need for this update demonstrates the rapid progress in treatment that is occurring in axial spondyloarthritis, but the low level of evidence for many questions indicates that much more research is needed.”

Nine authors reported personal and institutional relationships in the form of consultancies, educational advisory board memberships, and site investigator appointments for AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, GlaxoSmithKline, Galapagos, Janssen, Novartis, Pfizer, and UCB. The other authors reported no relevant conflicts of interest.

SOURCE: Ward MM et al. Arthritis Care Res. 2019 Aug 21. doi: 10.1002/acr.24025.

The American College of Rheumatology, Spondylitis Association of America, and Spondyloarthritis Research and Treatment Network have updated their guidelines on management of ankylosing spondylitis and nonradiographic axial spondyloarthritis.

These guidelines serve as an update to the previous guidelines that were first published in 2015 (Arthritis Care Res. 2016;68:151–66). While the new guidelines did not review all recommendations from the 2015 guidelines, 20 questions on pharmacologic treatment were re-reviewed in addition to 26 new questions and recommendations.

Michael M. Ward, MD, chief of the Clinical Trials and Outcomes Branch at the National Institute of Arthritis and Musculoskeletal and Skin Diseases, said in an interview that the availability of new medications to treat axial spondyloarthritis (axSpA) prompted the updated guidelines.

“We took the opportunity to revisit some previous recommendations for which substantial new evidence was available, and also included new recommendations on some other topics, such as imaging,” said Dr. Ward, who is also first author of the new guidelines.

The panel that developed the questions focused on scenarios that a clinician would likely encounter in clinical practice, or situations in which how to manage a case is not clear. “Given this perspective, there were many questions that had limited evidence, but recommendations were made for all questions. For those questions that had less evidence in the literature, we relied more on the expertise of the panel,” Dr. Ward said.

The questions and recommendations for ankylosing spondylitis (AS) and nonradiographic axSpA centered around use of interleukin-17 (IL-17) inhibitors, tofacitinib (Xeljanz), and biosimilars of tumor necrosis factor-alpha inhibitors (TNFi), as well as when to taper and discontinue these medications.

Strong recommendations for patients with AS included using NSAIDs (low level of evidence), using TNFi when active disease remains despite NSAID treatment (high level of evidence), and using secukinumab (Cosentyx) or ixekizumab (Taltz) when active disease remains despite NSAID treatment over no treatment (high level of evidence). The guidelines also strongly recommend the use of physical therapy for adults with stable AS over no physical therapy (low level of evidence), as well as total hip arthroplasty in cases of advanced hip arthritis. The writing panel also strongly advised that adults with AS-related comorbidities should receive treatment by an ophthalmologist in cases of acute iritis. Strong recommendations were made against switching to a biosimilar of a TNFi after receiving treatment with an originator TNFi (regardless of whether it is for active or stable AS), use of systemic glucocorticoids in adults with active AS, treatment with spinal manipulation in patients with spinal fusion or advanced spinal osteoporosis, and screening for cardiac conduction defects and valvular heart disease with electrocardiograms.

Strong recommendations for nonradiographic axSpA were similar to those made for patients with AS, and the panel made strong recommendations for use of NSAIDs in patients with active disease; for TNFi treatment when NSAIDs fail; against switching to a biosimilar of a TNFi after starting the originator TNFi; against using systemic glucocorticoids; and in favor of using physical therapy rather than not.

The panel also made a number of conditional recommendations for AS and nonradiographic axSpA patients with regard to biologic preference and imaging. TNFis were conditionally recommended over secukinumab or ixekizumab in patients with active disease despite NSAIDs treatment, and in cases where a patient is not responding to a first TNFi treatment, the panel conditionally recommended secukinumab or ixekizumab over a second TNFi (very low evidence for all). Secukinumab or ixekizumab were also conditionally recommended over tofacitinib (very low evidence). Sulfasalazine, methotrexate, and tofacitinib were conditionally recommended in cases where patients had prominent peripheral arthritis or when TNFis are not available (very low to moderate evidence). The panel recommended against adding sulfasalazine or methotrexate to existing TNFi treatment (very low evidence), and they also advised against tapering as a standard treatment approach or discontinuing the biologic (very low evidence). MRI of the spine or pelvis was conditionally recommended to examine disease activity in unclear cases, but the panel recommended against ordering MRI scans to monitor disease inactivity (very low evidence).

“Most of the recommendations are conditional, primarily because of the relatively low level of evidence in the literature that addressed many of the questions,” while stronger recommendations came from larger clinical trials, Dr. Ward said. “The need for this update demonstrates the rapid progress in treatment that is occurring in axial spondyloarthritis, but the low level of evidence for many questions indicates that much more research is needed.”

Nine authors reported personal and institutional relationships in the form of consultancies, educational advisory board memberships, and site investigator appointments for AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, GlaxoSmithKline, Galapagos, Janssen, Novartis, Pfizer, and UCB. The other authors reported no relevant conflicts of interest.

SOURCE: Ward MM et al. Arthritis Care Res. 2019 Aug 21. doi: 10.1002/acr.24025.

The National Rosacea Society has released a booklet for patients called “Recognizing Redness” to help them assess their complexion before and after a rosacea flare or treatment, as well as better understand their disease, according to a release from the society. The booklet contains a redness register that lets patients compare their skin’s natural redness with that of areas affected by their rosacea; it also contains information about the disease, its diagnosis, and common triggers. The booklet is freely available on the society’s website www.rosacea.org/patients/recognizing-redness-patient-guide-rosacea. It can also be provided in bulk to health care providers and acquired directly by writing the National Rosacea Society, 196 James Street, Barrington, IL 60010, calling the society toll-free at 1-888-NO-BLUSH, or via e-mail at [email protected]. The new booklet was made possible by support from Aclaris.

The National Rosacea Society has released a booklet for patients called “Recognizing Redness” to help them assess their complexion before and after a rosacea flare or treatment, as well as better understand their disease, according to a release from the society. The booklet contains a redness register that lets patients compare their skin’s natural redness with that of areas affected by their rosacea; it also contains information about the disease, its diagnosis, and common triggers. The booklet is freely available on the society’s website www.rosacea.org/patients/recognizing-redness-patient-guide-rosacea. It can also be provided in bulk to health care providers and acquired directly by writing the National Rosacea Society, 196 James Street, Barrington, IL 60010, calling the society toll-free at 1-888-NO-BLUSH, or via e-mail at [email protected]. The new booklet was made possible by support from Aclaris.

The National Rosacea Society has released a booklet for patients called “Recognizing Redness” to help them assess their complexion before and after a rosacea flare or treatment, as well as better understand their disease, according to a release from the society. The booklet contains a redness register that lets patients compare their skin’s natural redness with that of areas affected by their rosacea; it also contains information about the disease, its diagnosis, and common triggers. The booklet is freely available on the society’s website www.rosacea.org/patients/recognizing-redness-patient-guide-rosacea. It can also be provided in bulk to health care providers and acquired directly by writing the National Rosacea Society, 196 James Street, Barrington, IL 60010, calling the society toll-free at 1-888-NO-BLUSH, or via e-mail at [email protected]. The new booklet was made possible by support from Aclaris.

AUSTIN, TEX. – For children and adolescents with severe, refractory atopic dermatitis, Peter A. Lio, MD, often turns to cyclosporine as his systemic treatment of choice.

Doug Brunk/MDedge News

Cyclosporine “works quickly, and it’s very reliable,” Dr. Lio said at the annual meeting of the Society for Pediatric Dermatology. “In my experience, more than 90% of patients will see significant improvement, but there are real risks, including hypertension, kidney damage, monthly blood work, tremor, hypertrichosis, gum hypertrophy, and cancer/infection risk.”

To mitigate those risks, Dr. Lio, of the departments of dermatology and pediatrics at Northwestern University, Chicago, prescribes cyclosporine for 3-6 months at a dose of 5 mg/kg per day with a cap of 300 mg per day to “to cool things down.” He then transitions patients to phototherapy or mycophenolate right away. “Those are my two favorites,” he said. “Methotrexate can also be used, but I rarely use azathioprine.

“If you do this, you avoid most of the major risks and you can put people in a remission. More than half of the time, maybe two-thirds of the time, I get them into at least a relative remission,” Dr. Lio said.

While patients are on cyclosporine, blood pressure should be monitored each week for 4 weeks, and then monthly, he said. Draws for complete blood count, liver function tests, comprehensive metabolic panel, uric acid, and lipids should be performed monthly for 3 months, then every 8 weeks, he advised. Dr. Lio typically maintains the cyclosporine for 3 months, then tapers patients off the drug.

Patients who continue to struggle for relief might try taking cyclosporine on weekends only, a concept reported by Spanish investigators in 2015 (Pediatr Dermatol 2015 32[4]:551-2). “This involves twice-daily full dosing just on Saturdays and Sundays,” Dr. Lio said. “I now have quite a few patients doing well with this approach.”

Dr. Lio disclosed having financial ties to numerous pharmaceutical companies but none related to cyclosporine.

[email protected]

AUSTIN, TEX. – For children and adolescents with severe, refractory atopic dermatitis, Peter A. Lio, MD, often turns to cyclosporine as his systemic treatment of choice.

Doug Brunk/MDedge News

Cyclosporine “works quickly, and it’s very reliable,” Dr. Lio said at the annual meeting of the Society for Pediatric Dermatology. “In my experience, more than 90% of patients will see significant improvement, but there are real risks, including hypertension, kidney damage, monthly blood work, tremor, hypertrichosis, gum hypertrophy, and cancer/infection risk.”

To mitigate those risks, Dr. Lio, of the departments of dermatology and pediatrics at Northwestern University, Chicago, prescribes cyclosporine for 3-6 months at a dose of 5 mg/kg per day with a cap of 300 mg per day to “to cool things down.” He then transitions patients to phototherapy or mycophenolate right away. “Those are my two favorites,” he said. “Methotrexate can also be used, but I rarely use azathioprine.

“If you do this, you avoid most of the major risks and you can put people in a remission. More than half of the time, maybe two-thirds of the time, I get them into at least a relative remission,” Dr. Lio said.

While patients are on cyclosporine, blood pressure should be monitored each week for 4 weeks, and then monthly, he said. Draws for complete blood count, liver function tests, comprehensive metabolic panel, uric acid, and lipids should be performed monthly for 3 months, then every 8 weeks, he advised. Dr. Lio typically maintains the cyclosporine for 3 months, then tapers patients off the drug.

Patients who continue to struggle for relief might try taking cyclosporine on weekends only, a concept reported by Spanish investigators in 2015 (Pediatr Dermatol 2015 32[4]:551-2). “This involves twice-daily full dosing just on Saturdays and Sundays,” Dr. Lio said. “I now have quite a few patients doing well with this approach.”

Dr. Lio disclosed having financial ties to numerous pharmaceutical companies but none related to cyclosporine.

[email protected]

AUSTIN, TEX. – For children and adolescents with severe, refractory atopic dermatitis, Peter A. Lio, MD, often turns to cyclosporine as his systemic treatment of choice.

Doug Brunk/MDedge News

Cyclosporine “works quickly, and it’s very reliable,” Dr. Lio said at the annual meeting of the Society for Pediatric Dermatology. “In my experience, more than 90% of patients will see significant improvement, but there are real risks, including hypertension, kidney damage, monthly blood work, tremor, hypertrichosis, gum hypertrophy, and cancer/infection risk.”

To mitigate those risks, Dr. Lio, of the departments of dermatology and pediatrics at Northwestern University, Chicago, prescribes cyclosporine for 3-6 months at a dose of 5 mg/kg per day with a cap of 300 mg per day to “to cool things down.” He then transitions patients to phototherapy or mycophenolate right away. “Those are my two favorites,” he said. “Methotrexate can also be used, but I rarely use azathioprine.

“If you do this, you avoid most of the major risks and you can put people in a remission. More than half of the time, maybe two-thirds of the time, I get them into at least a relative remission,” Dr. Lio said.

While patients are on cyclosporine, blood pressure should be monitored each week for 4 weeks, and then monthly, he said. Draws for complete blood count, liver function tests, comprehensive metabolic panel, uric acid, and lipids should be performed monthly for 3 months, then every 8 weeks, he advised. Dr. Lio typically maintains the cyclosporine for 3 months, then tapers patients off the drug.

Patients who continue to struggle for relief might try taking cyclosporine on weekends only, a concept reported by Spanish investigators in 2015 (Pediatr Dermatol 2015 32[4]:551-2). “This involves twice-daily full dosing just on Saturdays and Sundays,” Dr. Lio said. “I now have quite a few patients doing well with this approach.”

Dr. Lio disclosed having financial ties to numerous pharmaceutical companies but none related to cyclosporine.

[email protected]

The role of minimally invasive surgery for early-stage cervical cancer has been the subject of heated debate since the presentation of the results of the Laparoscopic Approach to Cervical Cancer (LACC) Trial at the Society of Gynecologic Oncology Annual Meeting on Women’s Cancer in 2018. This was an international, randomized, phase 3 trial comparing minimally invasive radical hysterectomy (MH) to open radical hysterectomy (OH) in the treatment of early-stage cervical cancer. The trial was closed early by the study’s Data and Safety Monitoring Committee due to an imbalance of deaths between the groups, with a higher rate in the minimally invasive arm. The final results, which were largely unexpected by the medical community, showed that the disease-free survival (DFS) at 4.5 years was 86.0% in the MH arm and 96.5% in the OH arm, which was a larger difference than their noninferiority cutoff of -7.2 percentage points.¹ Results of an epidemiologic study, which used data from the Surveillance, Epidemiology, and End Results (SEER) program and the National Cancer Database, also were presented at this meeting, and they reinforced the findings of the LACC trial.²

The combined results have caused significant concern and confusion from the medical community regarding the clinical implication that minimally invasive surgery may be an unacceptable approach for radical hysterectomy in cervical cancer. Prior to this study, retrospective data supported similar outcomes between the two approaches.³ Additionally, robotic surgery has made radical hysterectomy an option for those with a higher body mass index, as an open radical hysterectomy can be technically challenging in larger patients and result in a higher rate of adverse outcomes.

LACC trial questioned by US surgeons

Many in the United States have questioned the design and conclusions of the LACC trial. This trial was conducted primarily outside of North America and utilized conventional laparoscopic surgery 85% of the time as opposed to robotic surgery. Additionally, the found difference in DFS between MH and OH may have been driven more by the superior performance of the OH group (compared with historical data) than the poorly performing MH group.⁴ Other criticisms have touched on the low number of overall survival events, the low bar for surgeon volume or skill assessment, and the inability to make conclusions regarding “low-risk” lesions (<2 cm, no lymphovascular space invasion, <1 cm depth of invasion).

Were requirements for surgical skill adequate? Regarding surgeon skill, the LACC trial required documentation of the perioperative outcomes from 10 laparoscopic or robotic radical hysterectomies, as well as 2 unedited videos of each surgeon participating in the study to verify their technique, which some have considered inadequate to sufficiently vet a surgeon’s ability. Additionally, 14 of the 33 centers enrolled in the study accrued 71% of the patients, and concerns about the surgeon volume of the remaining 19 centers have been raised. Finally, there has been discussion about whether the variance in surgical approach can even be adequately assessed in a trial of this nature, as surgical skill is not a binary variable that is easily amenable to randomization. Unlike other trials, which have clear exposure and control arms, no 2 surgeries are exactly alike, and surgical technique is highly variable between surgeons, institutions, and countries.

Continue to: New data evaluate for surgeon volume

New data evaluate for surgeon volume

In an effort to address the concerns regarding surgical approach and expertise, the recently published study by Cusimano and colleagues uses population-based data from Ontario for all women undergoing radical hysterectomy for cervical cancer over a 10-year period from 2006 through 2016.⁵ The primary outcome was all-cause death, but the study also sought to address whether surgeon volume has an impact on recurrence rates for patients undergoing MH versus OH. To measure this impact the authors stratified surgeon characteristics by technique-specific volume and cervical cancer volume, splitting these volumes at the 50% percentile for low- and high-volume surgeons. They defined technique-specific volume as the number of simple and radical hysterectomies performed in the prior year using the selected approach (MH or OH). Cervical cancer volume was calculated as the number of hysterectomies of any type for cervical cancer in the previous 2 years. The technique-specific volume variable was subsequently re-categorized into tertiles, examined as a continuous variable, and analyzed at the 50th percentile for each year of the study.

Death and recurrence rates better in the OH group. The final cohort included 958 women that were relatively evenly split between MH and OH procedures. Results from their analysis show no difference in terms of all-cause death, cervical cancer–specific death, or recurrence. However, all 3 of these parameters were significantly different in favor of the OH group in women with Stage IB disease, which comprised over half of the overall cohort. Importantly, neither technique-specific volume nor cervical cancer volume had an effect on death or recurrence in Stage IB patients in any of the investigators’ analyses.

Important limitations. There are several limitations to this study that have to be taken into account before drawing any conclusions. Pathologic data were obtained from the database and did not include some important details about the tumor specimens (including specifying subgroups of Stage IA and IB disease, tumor size, presence of lymphovascular space invasion, and depth of stromal invasion). All of these details have been shown to be important prognostic variables in early-stage cervical cancer. Additionally, the MH group included a predominantly laparoscopic approach with only 10% of cases performed robotically, which again brings into question the generalizability of the data.

However, despite some of these shortcomings, the study authors do make a compelling argument that surgeon volume alone does not seem to play a significant role in cancer outcomes after MH.

With surgical approaches hard to compare, turn to careful patient counseling

Definitive assessment of the impact of surgical skill and experience on cervical cancer outcomes is probably an impossible task, as even a perfectly designed trial cannot entirely account for the intricacies of a complex surgical procedure. Variations in tumor characteristics and patient anatomy that affect operative decision making are not likely to be reflected when a patient’s outcome is plugged into a database. As a result, some surgeons and departments have turned to reporting personal or institutional recurrence rates for MH, which they believe may be a better representation of a patient’s risk in their hands. Meanwhile, many surgeons and groups have stopped performing MH altogether, largely due to the results of the LACC trial. Irrespective of final surgical route, it is important that the risks and benefits of both minimally invasive and open approaches be adequately discussed with patients so that they can make informed decisions regarding their own medical care.

The role of minimally invasive surgery for early-stage cervical cancer has been the subject of heated debate since the presentation of the results of the Laparoscopic Approach to Cervical Cancer (LACC) Trial at the Society of Gynecologic Oncology Annual Meeting on Women’s Cancer in 2018. This was an international, randomized, phase 3 trial comparing minimally invasive radical hysterectomy (MH) to open radical hysterectomy (OH) in the treatment of early-stage cervical cancer. The trial was closed early by the study’s Data and Safety Monitoring Committee due to an imbalance of deaths between the groups, with a higher rate in the minimally invasive arm. The final results, which were largely unexpected by the medical community, showed that the disease-free survival (DFS) at 4.5 years was 86.0% in the MH arm and 96.5% in the OH arm, which was a larger difference than their noninferiority cutoff of -7.2 percentage points.¹ Results of an epidemiologic study, which used data from the Surveillance, Epidemiology, and End Results (SEER) program and the National Cancer Database, also were presented at this meeting, and they reinforced the findings of the LACC trial.²

The combined results have caused significant concern and confusion from the medical community regarding the clinical implication that minimally invasive surgery may be an unacceptable approach for radical hysterectomy in cervical cancer. Prior to this study, retrospective data supported similar outcomes between the two approaches.³ Additionally, robotic surgery has made radical hysterectomy an option for those with a higher body mass index, as an open radical hysterectomy can be technically challenging in larger patients and result in a higher rate of adverse outcomes.

LACC trial questioned by US surgeons

Many in the United States have questioned the design and conclusions of the LACC trial. This trial was conducted primarily outside of North America and utilized conventional laparoscopic surgery 85% of the time as opposed to robotic surgery. Additionally, the found difference in DFS between MH and OH may have been driven more by the superior performance of the OH group (compared with historical data) than the poorly performing MH group.⁴ Other criticisms have touched on the low number of overall survival events, the low bar for surgeon volume or skill assessment, and the inability to make conclusions regarding “low-risk” lesions (<2 cm, no lymphovascular space invasion, <1 cm depth of invasion).

Were requirements for surgical skill adequate? Regarding surgeon skill, the LACC trial required documentation of the perioperative outcomes from 10 laparoscopic or robotic radical hysterectomies, as well as 2 unedited videos of each surgeon participating in the study to verify their technique, which some have considered inadequate to sufficiently vet a surgeon’s ability. Additionally, 14 of the 33 centers enrolled in the study accrued 71% of the patients, and concerns about the surgeon volume of the remaining 19 centers have been raised. Finally, there has been discussion about whether the variance in surgical approach can even be adequately assessed in a trial of this nature, as surgical skill is not a binary variable that is easily amenable to randomization. Unlike other trials, which have clear exposure and control arms, no 2 surgeries are exactly alike, and surgical technique is highly variable between surgeons, institutions, and countries.

Continue to: New data evaluate for surgeon volume

New data evaluate for surgeon volume

In an effort to address the concerns regarding surgical approach and expertise, the recently published study by Cusimano and colleagues uses population-based data from Ontario for all women undergoing radical hysterectomy for cervical cancer over a 10-year period from 2006 through 2016.⁵ The primary outcome was all-cause death, but the study also sought to address whether surgeon volume has an impact on recurrence rates for patients undergoing MH versus OH. To measure this impact the authors stratified surgeon characteristics by technique-specific volume and cervical cancer volume, splitting these volumes at the 50% percentile for low- and high-volume surgeons. They defined technique-specific volume as the number of simple and radical hysterectomies performed in the prior year using the selected approach (MH or OH). Cervical cancer volume was calculated as the number of hysterectomies of any type for cervical cancer in the previous 2 years. The technique-specific volume variable was subsequently re-categorized into tertiles, examined as a continuous variable, and analyzed at the 50th percentile for each year of the study.

Death and recurrence rates better in the OH group. The final cohort included 958 women that were relatively evenly split between MH and OH procedures. Results from their analysis show no difference in terms of all-cause death, cervical cancer–specific death, or recurrence. However, all 3 of these parameters were significantly different in favor of the OH group in women with Stage IB disease, which comprised over half of the overall cohort. Importantly, neither technique-specific volume nor cervical cancer volume had an effect on death or recurrence in Stage IB patients in any of the investigators’ analyses.

Important limitations. There are several limitations to this study that have to be taken into account before drawing any conclusions. Pathologic data were obtained from the database and did not include some important details about the tumor specimens (including specifying subgroups of Stage IA and IB disease, tumor size, presence of lymphovascular space invasion, and depth of stromal invasion). All of these details have been shown to be important prognostic variables in early-stage cervical cancer. Additionally, the MH group included a predominantly laparoscopic approach with only 10% of cases performed robotically, which again brings into question the generalizability of the data.

However, despite some of these shortcomings, the study authors do make a compelling argument that surgeon volume alone does not seem to play a significant role in cancer outcomes after MH.

With surgical approaches hard to compare, turn to careful patient counseling

Definitive assessment of the impact of surgical skill and experience on cervical cancer outcomes is probably an impossible task, as even a perfectly designed trial cannot entirely account for the intricacies of a complex surgical procedure. Variations in tumor characteristics and patient anatomy that affect operative decision making are not likely to be reflected when a patient’s outcome is plugged into a database. As a result, some surgeons and departments have turned to reporting personal or institutional recurrence rates for MH, which they believe may be a better representation of a patient’s risk in their hands. Meanwhile, many surgeons and groups have stopped performing MH altogether, largely due to the results of the LACC trial. Irrespective of final surgical route, it is important that the risks and benefits of both minimally invasive and open approaches be adequately discussed with patients so that they can make informed decisions regarding their own medical care.

The role of minimally invasive surgery for early-stage cervical cancer has been the subject of heated debate since the presentation of the results of the Laparoscopic Approach to Cervical Cancer (LACC) Trial at the Society of Gynecologic Oncology Annual Meeting on Women’s Cancer in 2018. This was an international, randomized, phase 3 trial comparing minimally invasive radical hysterectomy (MH) to open radical hysterectomy (OH) in the treatment of early-stage cervical cancer. The trial was closed early by the study’s Data and Safety Monitoring Committee due to an imbalance of deaths between the groups, with a higher rate in the minimally invasive arm. The final results, which were largely unexpected by the medical community, showed that the disease-free survival (DFS) at 4.5 years was 86.0% in the MH arm and 96.5% in the OH arm, which was a larger difference than their noninferiority cutoff of -7.2 percentage points.¹ Results of an epidemiologic study, which used data from the Surveillance, Epidemiology, and End Results (SEER) program and the National Cancer Database, also were presented at this meeting, and they reinforced the findings of the LACC trial.²

The combined results have caused significant concern and confusion from the medical community regarding the clinical implication that minimally invasive surgery may be an unacceptable approach for radical hysterectomy in cervical cancer. Prior to this study, retrospective data supported similar outcomes between the two approaches.³ Additionally, robotic surgery has made radical hysterectomy an option for those with a higher body mass index, as an open radical hysterectomy can be technically challenging in larger patients and result in a higher rate of adverse outcomes.

LACC trial questioned by US surgeons

Many in the United States have questioned the design and conclusions of the LACC trial. This trial was conducted primarily outside of North America and utilized conventional laparoscopic surgery 85% of the time as opposed to robotic surgery. Additionally, the found difference in DFS between MH and OH may have been driven more by the superior performance of the OH group (compared with historical data) than the poorly performing MH group.⁴ Other criticisms have touched on the low number of overall survival events, the low bar for surgeon volume or skill assessment, and the inability to make conclusions regarding “low-risk” lesions (<2 cm, no lymphovascular space invasion, <1 cm depth of invasion).

Were requirements for surgical skill adequate? Regarding surgeon skill, the LACC trial required documentation of the perioperative outcomes from 10 laparoscopic or robotic radical hysterectomies, as well as 2 unedited videos of each surgeon participating in the study to verify their technique, which some have considered inadequate to sufficiently vet a surgeon’s ability. Additionally, 14 of the 33 centers enrolled in the study accrued 71% of the patients, and concerns about the surgeon volume of the remaining 19 centers have been raised. Finally, there has been discussion about whether the variance in surgical approach can even be adequately assessed in a trial of this nature, as surgical skill is not a binary variable that is easily amenable to randomization. Unlike other trials, which have clear exposure and control arms, no 2 surgeries are exactly alike, and surgical technique is highly variable between surgeons, institutions, and countries.

Continue to: New data evaluate for surgeon volume

New data evaluate for surgeon volume

In an effort to address the concerns regarding surgical approach and expertise, the recently published study by Cusimano and colleagues uses population-based data from Ontario for all women undergoing radical hysterectomy for cervical cancer over a 10-year period from 2006 through 2016.⁵ The primary outcome was all-cause death, but the study also sought to address whether surgeon volume has an impact on recurrence rates for patients undergoing MH versus OH. To measure this impact the authors stratified surgeon characteristics by technique-specific volume and cervical cancer volume, splitting these volumes at the 50% percentile for low- and high-volume surgeons. They defined technique-specific volume as the number of simple and radical hysterectomies performed in the prior year using the selected approach (MH or OH). Cervical cancer volume was calculated as the number of hysterectomies of any type for cervical cancer in the previous 2 years. The technique-specific volume variable was subsequently re-categorized into tertiles, examined as a continuous variable, and analyzed at the 50th percentile for each year of the study.

Death and recurrence rates better in the OH group. The final cohort included 958 women that were relatively evenly split between MH and OH procedures. Results from their analysis show no difference in terms of all-cause death, cervical cancer–specific death, or recurrence. However, all 3 of these parameters were significantly different in favor of the OH group in women with Stage IB disease, which comprised over half of the overall cohort. Importantly, neither technique-specific volume nor cervical cancer volume had an effect on death or recurrence in Stage IB patients in any of the investigators’ analyses.

Important limitations. There are several limitations to this study that have to be taken into account before drawing any conclusions. Pathologic data were obtained from the database and did not include some important details about the tumor specimens (including specifying subgroups of Stage IA and IB disease, tumor size, presence of lymphovascular space invasion, and depth of stromal invasion). All of these details have been shown to be important prognostic variables in early-stage cervical cancer. Additionally, the MH group included a predominantly laparoscopic approach with only 10% of cases performed robotically, which again brings into question the generalizability of the data.

However, despite some of these shortcomings, the study authors do make a compelling argument that surgeon volume alone does not seem to play a significant role in cancer outcomes after MH.

With surgical approaches hard to compare, turn to careful patient counseling

Definitive assessment of the impact of surgical skill and experience on cervical cancer outcomes is probably an impossible task, as even a perfectly designed trial cannot entirely account for the intricacies of a complex surgical procedure. Variations in tumor characteristics and patient anatomy that affect operative decision making are not likely to be reflected when a patient’s outcome is plugged into a database. As a result, some surgeons and departments have turned to reporting personal or institutional recurrence rates for MH, which they believe may be a better representation of a patient’s risk in their hands. Meanwhile, many surgeons and groups have stopped performing MH altogether, largely due to the results of the LACC trial. Irrespective of final surgical route, it is important that the risks and benefits of both minimally invasive and open approaches be adequately discussed with patients so that they can make informed decisions regarding their own medical care.

In women with nonmetastatic breast cancer, postoperative regional node irradiation with proton-beam radiation was associated with low rates of toxicity and with disease control rates similar to those reported with conventional photon-based radiation therapy (RT), investigators in a small prospective clinical study reported.

Among 62 survivors of a cohort of 69 women with nonmetastatic breast cancer who required postoperative radiation to the internal mammary nodes (IMN) and for whom conventional radiation was thought to pose excess risks of toxicity, there were no cases of the primary endpoint of grade 3 or greater radiation pneumonitis and no grade 4 toxicities within 3 months of therapy, reported Rachel B. Jimenez, MD, of the Massachusetts General Hospital Cancer Center in Boston and colleagues.

“In our prospective trial of women with locally advanced breast cancer who required treatment of the IMNs, proton beam RT was safe and effective. Future research will provide needed information about the potential long-term normal tissue–sparing benefits of this complex treatment modality compared with conventional radiation,” they wrote in the Journal of Clinical Oncology.

Protons offer the theoretic advantage over photons of minimizing radiation dose to the heart and lungs when treating the breast, chest wall, or regional lymph nodes. Protons, unlike photons, deliver their maximum ionizing energy to tissues immediately before they come to rest, allowing for a more precise dose of radiation to local tissues.

“Multiple dosimetric planning studies that compared proton RT with photon RT have demonstrated superior delivery to targeted areas while sparing more of the heart and lungs. However, prospective clinical data are lacking to support the safety and efficacy of proton RT for breast cancer,” the investigators wrote.

To rectify this, they enrolled adult patients with nonmetastatic breast cancer who required postoperative radiation therapy inclusive of the IMNs and for whom the treating physician determined that either breast reconstruction would prevent adequate target coverage or conventional radiation would deliver 20 Gy or more to 5% or more of the heart and/or the left anterior descending artery (LAD).

A total of 69 patients (median age 45 years) were evaluable for the primary endpoint. In all, 63 of the 70 enrolled patients had left-sided breast cancer, 5 had right-sided breast cancer, and 2 had bilateral breast cancer. The majority of patients (65) had stage II-III disease. All but 2 patients underwent systemic chemotherapy, and 50 underwent immediate reconstruction.

The median of the mean proton radiation dose to the chest wall/breast was 49.7 Gy (relative biological effectiveness) and to the IMN was 48.8 Gy (relative biological effectiveness), indicating comprehensive coverage. The mean heart dose was a median of 0.50 Gy, and the mean dose to the LAD was a median of 1.16 Gy.

After a median follow-up of 55 months, the 5-year rate for locoregional failure among 62 surviving patients was 1.5%

As noted before, there were no cases of grade 3 radiation pneumonitis and no grade 4 toxicities of any type within 3 months of radiation therapy. One patient developed grade 2 radiation pneumonitis 4 months after therapy and was successfully treated with oral corticosteroids, and one developed a severe infection of the bilateral chest wall 4 months after radiation to the left-side chest wall. She was treated with intravenous antibiotics.

There were no significant changes in either echocardiography or cardiac biomarkers after radiotherapy.

The authors noted that the toxicity and disease control rates compared favorably with those of historical data on conventional radiation therapy from two studies published in 2015 (N Engl J Med. 2015;373:307-16; N Engl J Med. 2015;373:317-27).

The study was supported by a grant from the National Institutes of Health. Dr. Jimenez disclosed research funding from Focal Therapeutics.

SOURCE: Jimenez RB et al. J Clin Oncol 2019 Aug 26. doi: 10.1200/JCO.18.02366.

In women with nonmetastatic breast cancer, postoperative regional node irradiation with proton-beam radiation was associated with low rates of toxicity and with disease control rates similar to those reported with conventional photon-based radiation therapy (RT), investigators in a small prospective clinical study reported.

Among 62 survivors of a cohort of 69 women with nonmetastatic breast cancer who required postoperative radiation to the internal mammary nodes (IMN) and for whom conventional radiation was thought to pose excess risks of toxicity, there were no cases of the primary endpoint of grade 3 or greater radiation pneumonitis and no grade 4 toxicities within 3 months of therapy, reported Rachel B. Jimenez, MD, of the Massachusetts General Hospital Cancer Center in Boston and colleagues.

“In our prospective trial of women with locally advanced breast cancer who required treatment of the IMNs, proton beam RT was safe and effective. Future research will provide needed information about the potential long-term normal tissue–sparing benefits of this complex treatment modality compared with conventional radiation,” they wrote in the Journal of Clinical Oncology.

Protons offer the theoretic advantage over photons of minimizing radiation dose to the heart and lungs when treating the breast, chest wall, or regional lymph nodes. Protons, unlike photons, deliver their maximum ionizing energy to tissues immediately before they come to rest, allowing for a more precise dose of radiation to local tissues.

“Multiple dosimetric planning studies that compared proton RT with photon RT have demonstrated superior delivery to targeted areas while sparing more of the heart and lungs. However, prospective clinical data are lacking to support the safety and efficacy of proton RT for breast cancer,” the investigators wrote.

To rectify this, they enrolled adult patients with nonmetastatic breast cancer who required postoperative radiation therapy inclusive of the IMNs and for whom the treating physician determined that either breast reconstruction would prevent adequate target coverage or conventional radiation would deliver 20 Gy or more to 5% or more of the heart and/or the left anterior descending artery (LAD).

A total of 69 patients (median age 45 years) were evaluable for the primary endpoint. In all, 63 of the 70 enrolled patients had left-sided breast cancer, 5 had right-sided breast cancer, and 2 had bilateral breast cancer. The majority of patients (65) had stage II-III disease. All but 2 patients underwent systemic chemotherapy, and 50 underwent immediate reconstruction.

The median of the mean proton radiation dose to the chest wall/breast was 49.7 Gy (relative biological effectiveness) and to the IMN was 48.8 Gy (relative biological effectiveness), indicating comprehensive coverage. The mean heart dose was a median of 0.50 Gy, and the mean dose to the LAD was a median of 1.16 Gy.

After a median follow-up of 55 months, the 5-year rate for locoregional failure among 62 surviving patients was 1.5%

As noted before, there were no cases of grade 3 radiation pneumonitis and no grade 4 toxicities of any type within 3 months of radiation therapy. One patient developed grade 2 radiation pneumonitis 4 months after therapy and was successfully treated with oral corticosteroids, and one developed a severe infection of the bilateral chest wall 4 months after radiation to the left-side chest wall. She was treated with intravenous antibiotics.

There were no significant changes in either echocardiography or cardiac biomarkers after radiotherapy.

The authors noted that the toxicity and disease control rates compared favorably with those of historical data on conventional radiation therapy from two studies published in 2015 (N Engl J Med. 2015;373:307-16; N Engl J Med. 2015;373:317-27).

The study was supported by a grant from the National Institutes of Health. Dr. Jimenez disclosed research funding from Focal Therapeutics.

SOURCE: Jimenez RB et al. J Clin Oncol 2019 Aug 26. doi: 10.1200/JCO.18.02366.

In women with nonmetastatic breast cancer, postoperative regional node irradiation with proton-beam radiation was associated with low rates of toxicity and with disease control rates similar to those reported with conventional photon-based radiation therapy (RT), investigators in a small prospective clinical study reported.

Among 62 survivors of a cohort of 69 women with nonmetastatic breast cancer who required postoperative radiation to the internal mammary nodes (IMN) and for whom conventional radiation was thought to pose excess risks of toxicity, there were no cases of the primary endpoint of grade 3 or greater radiation pneumonitis and no grade 4 toxicities within 3 months of therapy, reported Rachel B. Jimenez, MD, of the Massachusetts General Hospital Cancer Center in Boston and colleagues.

“In our prospective trial of women with locally advanced breast cancer who required treatment of the IMNs, proton beam RT was safe and effective. Future research will provide needed information about the potential long-term normal tissue–sparing benefits of this complex treatment modality compared with conventional radiation,” they wrote in the Journal of Clinical Oncology.

Protons offer the theoretic advantage over photons of minimizing radiation dose to the heart and lungs when treating the breast, chest wall, or regional lymph nodes. Protons, unlike photons, deliver their maximum ionizing energy to tissues immediately before they come to rest, allowing for a more precise dose of radiation to local tissues.

“Multiple dosimetric planning studies that compared proton RT with photon RT have demonstrated superior delivery to targeted areas while sparing more of the heart and lungs. However, prospective clinical data are lacking to support the safety and efficacy of proton RT for breast cancer,” the investigators wrote.

To rectify this, they enrolled adult patients with nonmetastatic breast cancer who required postoperative radiation therapy inclusive of the IMNs and for whom the treating physician determined that either breast reconstruction would prevent adequate target coverage or conventional radiation would deliver 20 Gy or more to 5% or more of the heart and/or the left anterior descending artery (LAD).

A total of 69 patients (median age 45 years) were evaluable for the primary endpoint. In all, 63 of the 70 enrolled patients had left-sided breast cancer, 5 had right-sided breast cancer, and 2 had bilateral breast cancer. The majority of patients (65) had stage II-III disease. All but 2 patients underwent systemic chemotherapy, and 50 underwent immediate reconstruction.

The median of the mean proton radiation dose to the chest wall/breast was 49.7 Gy (relative biological effectiveness) and to the IMN was 48.8 Gy (relative biological effectiveness), indicating comprehensive coverage. The mean heart dose was a median of 0.50 Gy, and the mean dose to the LAD was a median of 1.16 Gy.

After a median follow-up of 55 months, the 5-year rate for locoregional failure among 62 surviving patients was 1.5%

As noted before, there were no cases of grade 3 radiation pneumonitis and no grade 4 toxicities of any type within 3 months of radiation therapy. One patient developed grade 2 radiation pneumonitis 4 months after therapy and was successfully treated with oral corticosteroids, and one developed a severe infection of the bilateral chest wall 4 months after radiation to the left-side chest wall. She was treated with intravenous antibiotics.

There were no significant changes in either echocardiography or cardiac biomarkers after radiotherapy.

The authors noted that the toxicity and disease control rates compared favorably with those of historical data on conventional radiation therapy from two studies published in 2015 (N Engl J Med. 2015;373:307-16; N Engl J Med. 2015;373:317-27).

The study was supported by a grant from the National Institutes of Health. Dr. Jimenez disclosed research funding from Focal Therapeutics.

SOURCE: Jimenez RB et al. J Clin Oncol 2019 Aug 26. doi: 10.1200/JCO.18.02366.

Background: Although new payment models have been implemented by the Centers for Medicare & Medicaid Services (CMS) for hospital reimbursement, little is known about the effects of reimbursement models on the culture of providing value-based care among individual hospitalists. The concern is that productivity-based models increase pressure on hospitalists to maximize volume and billing, as opposed to focusing on value.

A total of 255 hospitalists completed the survey. The mean HVCCS score was 50.2 on a 0-100 scale. Hospitalists who reported reimbursement with salary plus productivity adjustments had a lower mean HVCCS score (beta = –6.2; 95% confidence interval, –9.9 to –2.5) when compared with hospitalists paid with salary alone. An association was not found between HVCCS score and reimbursement with salary plus value-based adjustments when compared with salary alone, though this finding may have been limited by sample size.

Bottom line: A hospitalist reimbursement model of salary plus productivity was associated with lower measures of value-based care culture.

Citation: Gupta R et al. Association between hospitalist productivity payments and high-value care culture. J Hosp Med. 2019;14(1):16-21.

Dr. Huang is a physician adviser and associate clinical professor in the division of hospital medicine at the University of California, San Diego.

Background: Although new payment models have been implemented by the Centers for Medicare & Medicaid Services (CMS) for hospital reimbursement, little is known about the effects of reimbursement models on the culture of providing value-based care among individual hospitalists. The concern is that productivity-based models increase pressure on hospitalists to maximize volume and billing, as opposed to focusing on value.

A total of 255 hospitalists completed the survey. The mean HVCCS score was 50.2 on a 0-100 scale. Hospitalists who reported reimbursement with salary plus productivity adjustments had a lower mean HVCCS score (beta = –6.2; 95% confidence interval, –9.9 to –2.5) when compared with hospitalists paid with salary alone. An association was not found between HVCCS score and reimbursement with salary plus value-based adjustments when compared with salary alone, though this finding may have been limited by sample size.

Bottom line: A hospitalist reimbursement model of salary plus productivity was associated with lower measures of value-based care culture.

Citation: Gupta R et al. Association between hospitalist productivity payments and high-value care culture. J Hosp Med. 2019;14(1):16-21.

Dr. Huang is a physician adviser and associate clinical professor in the division of hospital medicine at the University of California, San Diego.

Background: Although new payment models have been implemented by the Centers for Medicare & Medicaid Services (CMS) for hospital reimbursement, little is known about the effects of reimbursement models on the culture of providing value-based care among individual hospitalists. The concern is that productivity-based models increase pressure on hospitalists to maximize volume and billing, as opposed to focusing on value.

A total of 255 hospitalists completed the survey. The mean HVCCS score was 50.2 on a 0-100 scale. Hospitalists who reported reimbursement with salary plus productivity adjustments had a lower mean HVCCS score (beta = –6.2; 95% confidence interval, –9.9 to –2.5) when compared with hospitalists paid with salary alone. An association was not found between HVCCS score and reimbursement with salary plus value-based adjustments when compared with salary alone, though this finding may have been limited by sample size.

Bottom line: A hospitalist reimbursement model of salary plus productivity was associated with lower measures of value-based care culture.

Citation: Gupta R et al. Association between hospitalist productivity payments and high-value care culture. J Hosp Med. 2019;14(1):16-21.

Dr. Huang is a physician adviser and associate clinical professor in the division of hospital medicine at the University of California, San Diego.

A study of patients with Barrett’s esophagus found that, although intestinal metaplasia and dysplasia in the cardia were common before treatment, they were more frequently present at higher levels and successful endoscopic eradication therapy lessened the risk.

©Nephron/Wikimedia Commons/CC BY-SA 3.0/No changes

“The results of this study provide evidence to suggest that, in Barrett’s esophagus patients who have achieved CEIM [complete eradication of intestinal metaplasia], it is sufficient to perform a close examination of the cardia and, in the absence of visible abnormalities, to randomly biopsy only at the level of TGF [top of gastric folds], rather than deeper into the cardia, during surveillance exams,” wrote Swathi Eluri, MD, of the University of North Carolina in Chapel Hill and coauthors. The study was published in Clinical Gastroenterology and Hepatology.

To determine the prevalence of intestinal metaplasia or dysplasia in the cardia of patients with Barrett’s esophagus who successfully underwent endoscopic eradication therapy (EET), along with the incidence of cardia intestinal metaplasia or dysplasia in patients undergoing EET, this single-center study examined two groups: a cross-sectional group of 116 patients who had achieved CEIM, and a longitudinal group of 42 treatment-naive patients who were receiving EET and subsequently achieved CEIM.

Along with clinical biopsies, the cross-sectional group underwent standardized biopsies from four quadrants in four locations: the distal esophagus, 1 cm proximal to top of gastric folds (TGF–1); at TGF; 1 cm into the gastric cardia (TGF+1); and 2 cm into the cardia (TGF+2). The longitudinal group also underwent 16 biopsies in the same areas; after CEIM was achieved, they underwent standard research biopsies of the distal esophagus and cardia at 6- and 18-month follow-ups.

Within the cross-sectional group, 15% of patients (n = 17) had intestinal metaplasia or dysplasia in the cardia after CEIM. Of those 17 patients, 12 had intestinal metaplasia, 2 were indefinite for dysplasia, and 3 had low-grade dysplasia. Of the 12 patients with cardia intestinal metaplasia, 83% had it at the level of TGF; 50% at TGF+1; and 25% at TGF+2.

Within the longitudinal group, 28% of patients (n = 12) had intestinal metaplasia or dysplasia in the cardia before ablation. Of those 12 patients, 9 had dysplastic intestinal metaplasia. Cases of pretreatment dysplasia were all found at the level of TGF, with one case extended to TGF+1. All patients achieved CEIM; at 18 months post CEIM, two patients had intestinal metaplasia and none had dysplasia.

The authors shared their study’s limitations, which included the lack of generalizability of a single-center study and a notable number of dropouts in the longitudinal group. They also acknowledged using multiple ablation modalities, although they added that most patients in both groups underwent radiofrequency ablation, the most commonly used treatment method and one that made “the results of the study more applicable to real-world practice.”

In turn, the authors noted their study’s strengths, which included the collection of data in a standardized manner and the availability of complete ablation history for all patients. Theirs was also the first study to systematically sample the cardia at multiple levels, which allows for “a more granular understanding of the location of initial and incident cardia lesions, which can guide depth of ablation during EET.”

The study was funded by an American Gastroenterological Association Research Scholar Award and CSA Medical. The authors reported no conflicts of interest.

SOURCE: Eluri S et al. Clin Gastroenterol Hepatol. 2019 May 8. doi: 10.1016/j.cgh.2019.04.065.

A study of patients with Barrett’s esophagus found that, although intestinal metaplasia and dysplasia in the cardia were common before treatment, they were more frequently present at higher levels and successful endoscopic eradication therapy lessened the risk.

©Nephron/Wikimedia Commons/CC BY-SA 3.0/No changes

“The results of this study provide evidence to suggest that, in Barrett’s esophagus patients who have achieved CEIM [complete eradication of intestinal metaplasia], it is sufficient to perform a close examination of the cardia and, in the absence of visible abnormalities, to randomly biopsy only at the level of TGF [top of gastric folds], rather than deeper into the cardia, during surveillance exams,” wrote Swathi Eluri, MD, of the University of North Carolina in Chapel Hill and coauthors. The study was published in Clinical Gastroenterology and Hepatology.

To determine the prevalence of intestinal metaplasia or dysplasia in the cardia of patients with Barrett’s esophagus who successfully underwent endoscopic eradication therapy (EET), along with the incidence of cardia intestinal metaplasia or dysplasia in patients undergoing EET, this single-center study examined two groups: a cross-sectional group of 116 patients who had achieved CEIM, and a longitudinal group of 42 treatment-naive patients who were receiving EET and subsequently achieved CEIM.

Along with clinical biopsies, the cross-sectional group underwent standardized biopsies from four quadrants in four locations: the distal esophagus, 1 cm proximal to top of gastric folds (TGF–1); at TGF; 1 cm into the gastric cardia (TGF+1); and 2 cm into the cardia (TGF+2). The longitudinal group also underwent 16 biopsies in the same areas; after CEIM was achieved, they underwent standard research biopsies of the distal esophagus and cardia at 6- and 18-month follow-ups.

Within the cross-sectional group, 15% of patients (n = 17) had intestinal metaplasia or dysplasia in the cardia after CEIM. Of those 17 patients, 12 had intestinal metaplasia, 2 were indefinite for dysplasia, and 3 had low-grade dysplasia. Of the 12 patients with cardia intestinal metaplasia, 83% had it at the level of TGF; 50% at TGF+1; and 25% at TGF+2.

Within the longitudinal group, 28% of patients (n = 12) had intestinal metaplasia or dysplasia in the cardia before ablation. Of those 12 patients, 9 had dysplastic intestinal metaplasia. Cases of pretreatment dysplasia were all found at the level of TGF, with one case extended to TGF+1. All patients achieved CEIM; at 18 months post CEIM, two patients had intestinal metaplasia and none had dysplasia.

The authors shared their study’s limitations, which included the lack of generalizability of a single-center study and a notable number of dropouts in the longitudinal group. They also acknowledged using multiple ablation modalities, although they added that most patients in both groups underwent radiofrequency ablation, the most commonly used treatment method and one that made “the results of the study more applicable to real-world practice.”

In turn, the authors noted their study’s strengths, which included the collection of data in a standardized manner and the availability of complete ablation history for all patients. Theirs was also the first study to systematically sample the cardia at multiple levels, which allows for “a more granular understanding of the location of initial and incident cardia lesions, which can guide depth of ablation during EET.”

The study was funded by an American Gastroenterological Association Research Scholar Award and CSA Medical. The authors reported no conflicts of interest.

SOURCE: Eluri S et al. Clin Gastroenterol Hepatol. 2019 May 8. doi: 10.1016/j.cgh.2019.04.065.

A study of patients with Barrett’s esophagus found that, although intestinal metaplasia and dysplasia in the cardia were common before treatment, they were more frequently present at higher levels and successful endoscopic eradication therapy lessened the risk.

©Nephron/Wikimedia Commons/CC BY-SA 3.0/No changes

“The results of this study provide evidence to suggest that, in Barrett’s esophagus patients who have achieved CEIM [complete eradication of intestinal metaplasia], it is sufficient to perform a close examination of the cardia and, in the absence of visible abnormalities, to randomly biopsy only at the level of TGF [top of gastric folds], rather than deeper into the cardia, during surveillance exams,” wrote Swathi Eluri, MD, of the University of North Carolina in Chapel Hill and coauthors. The study was published in Clinical Gastroenterology and Hepatology.

To determine the prevalence of intestinal metaplasia or dysplasia in the cardia of patients with Barrett’s esophagus who successfully underwent endoscopic eradication therapy (EET), along with the incidence of cardia intestinal metaplasia or dysplasia in patients undergoing EET, this single-center study examined two groups: a cross-sectional group of 116 patients who had achieved CEIM, and a longitudinal group of 42 treatment-naive patients who were receiving EET and subsequently achieved CEIM.

Along with clinical biopsies, the cross-sectional group underwent standardized biopsies from four quadrants in four locations: the distal esophagus, 1 cm proximal to top of gastric folds (TGF–1); at TGF; 1 cm into the gastric cardia (TGF+1); and 2 cm into the cardia (TGF+2). The longitudinal group also underwent 16 biopsies in the same areas; after CEIM was achieved, they underwent standard research biopsies of the distal esophagus and cardia at 6- and 18-month follow-ups.

Within the cross-sectional group, 15% of patients (n = 17) had intestinal metaplasia or dysplasia in the cardia after CEIM. Of those 17 patients, 12 had intestinal metaplasia, 2 were indefinite for dysplasia, and 3 had low-grade dysplasia. Of the 12 patients with cardia intestinal metaplasia, 83% had it at the level of TGF; 50% at TGF+1; and 25% at TGF+2.

Within the longitudinal group, 28% of patients (n = 12) had intestinal metaplasia or dysplasia in the cardia before ablation. Of those 12 patients, 9 had dysplastic intestinal metaplasia. Cases of pretreatment dysplasia were all found at the level of TGF, with one case extended to TGF+1. All patients achieved CEIM; at 18 months post CEIM, two patients had intestinal metaplasia and none had dysplasia.

The authors shared their study’s limitations, which included the lack of generalizability of a single-center study and a notable number of dropouts in the longitudinal group. They also acknowledged using multiple ablation modalities, although they added that most patients in both groups underwent radiofrequency ablation, the most commonly used treatment method and one that made “the results of the study more applicable to real-world practice.”

In turn, the authors noted their study’s strengths, which included the collection of data in a standardized manner and the availability of complete ablation history for all patients. Theirs was also the first study to systematically sample the cardia at multiple levels, which allows for “a more granular understanding of the location of initial and incident cardia lesions, which can guide depth of ablation during EET.”

The study was funded by an American Gastroenterological Association Research Scholar Award and CSA Medical. The authors reported no conflicts of interest.

SOURCE: Eluri S et al. Clin Gastroenterol Hepatol. 2019 May 8. doi: 10.1016/j.cgh.2019.04.065.

In this edition of “How I will treat my next patient,” I examine two recently published efforts to enlighten our sensitivity to the seriousness of immune-related adverse events (IrAEs) in patients on immune checkpoint inhibitors (ICIs) and the effect of delays in initiating systemic adjuvant therapy on the long-term outcomes of patients with resected pancreatic cancer.

IrAEs requiring hospitalization

Investigators led by Aanika Balaji of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, reviewed a 6-month audit of inpatient oncology admissions of solid-tumor patients who had ever received ICIs and ascertained the prevalence of hospitalization for management of IrAEs (J Oncol Pract. 2019 Aug 6. doi: 10.1200/JOP.18.00703). To determine that an IrAE had occurred they required: consensus among two oncologists, clinical improvement with immune-directed therapy, exclusion of alternative diagnoses or pathologic confirmation of an IrAE, or chronic management of an IrAE for more than 6 months.

The bottom line: They found a cumulative incidence of a confirmed IrAEs among hospitalized ICI-treated solid tumor patients of 23%. As expected, the majority (65%) were grade 3-4 in severity. In total, 91% required multidisciplinary management, and 65% improved or resolved. But 87% of patients never received an ICI again.

Patients with preexisting autoimmune disease (25% of patients, although they included hypothyroidism in that group) were not more vulnerable to an IrAE with ICI therapy (odds ratio, 1.0; 95% confidence interval, 0.3-4.0). Not unsurprisingly, the median age was higher for ICI-treated patients who were admitted for IrAEs than for those not admitted (68 years vs. 59 years; OR, 5.4; 95% CI, 1.6-17.8), and more admitted patients had received combination ICIs than single agents (OR, 6.8; 95% CI, 2.0-23.2).

The median time from beginning ICIs to an IrAE-related hospitalization was 64 days, and the median number of ICI doses was one, with a wide range for both days and doses. The authors were quick to comment that this is a small, academic, single-institution survey over a brief period of time and that the generalizability of the results is uncertain.

What this means in practice

This publication changes very little for most practicing oncologists, but it does reinforce that ICI therapy can cause unpredictable, severe IrAEs. Clinical markers for selecting patients at highest risk are imperfect. As with chemotherapy, the patients we worry about the most – older individuals and patients treated with drug combinations – are, in fact, the ones we should be worrying about the most.

In view of the potential severity and impact of IrAEs, research efforts should place equal priority on identifying biomarkers of toxicity, such as tumor mutation burden, and biomarkers of efficacy (JAMA Oncol. 2019 Aug 22. doi: 10.1001/jamaoncol.2019.3221). The potential financial and societal effects, as well as lost opportunity costs in the form of alternative therapies and early referral to hospice, demand no less, particularly in an era of value-based health care reimbursement.
 

Timing of adjuvant treatment

Sung Jun Ma, MD, department of radiation medicine at Roswell Park Comprehensive Cancer Center, Buffalo, N.Y., and colleagues analyzed data from the more than 7,500 stage I-II resected pancreatic cancer patients in the National Cancer Database, of whom more than 5,400 ultimately received adjuvant therapy (chemotherapy with or without radiation). The patients were treated during 2004-2015. Appropriately, the investigators focused on correlating survival duration with the interval between surgery and initiation of adjuvant therapy. Other endpoints would be hard to accurately measure and verify without detailed clinical information (JAMA Network Open. 2019 Aug 14. doi: 10.1001/jamanetworkopen.2019.9126).

They found that the best overall survival was associated with starting adjuvant treatment 28-59 days after surgery – not earlier (17% higher mortality) and not later (9% higher). Patients who did not start adjuvant treatment until more than 90 days post operatively still had an overall survival benefit (hazard ratio, 0.75; 95% confidence interval, 0.66-0.85; P less than .001), a more impressive hazard ratio than that seen for any particular interval between surgery and adjuvant treatment. Overall survival at 2 years was 47.2% versus 38% for the adjuvant therapy and surgery alone cohorts, respectively, with no overlap in the 95% confidence intervals.

As expected, longer delays to receive adjuvant treatment were associated with longer inpatient surgical stays, advanced age, black race, lower income, and a readmission for a postoperative complication within 30 days.

What this means in practice

This is another study that verifies that the patients we worry about most – older patients, those with a complicated recovery from surgery, and those with fewer supportive resources – are exactly the patients we should worry about most. It changes very little for most practicing oncologists. The analysis validates the importance of adjuvant therapy for patients who are able to receive it – whenever that is.

The data collection in this publication precedes recent improvements in adjuvant chemotherapy for resected pancreatic cancer, such as FOLFIRINOX or gemcitabine plus capecitabine. In an era of improved treatment, delays in initiating therapy may be less important since better treatment overcomes many prognostic variables that are significant for less effective therapy.

In my opinion, this large-data analysis is not really hypothesis-generating or practice-changing, but it does compel us to continue research efforts to improve surgical morbidity, identify better adjuvant and advanced disease regimens, and consider neoadjuvant treatment so that more than 72% of patients can receive all components of the multimodality treatment they need.
 

Dr. Lyss has been a community-based medical oncologist and clinical researcher for more than 35 years, practicing in St. Louis. His clinical and research interests are in the prevention, diagnosis, and treatment of breast and lung cancers and in expanding access to clinical trials to medically underserved populations.

In this edition of “How I will treat my next patient,” I examine two recently published efforts to enlighten our sensitivity to the seriousness of immune-related adverse events (IrAEs) in patients on immune checkpoint inhibitors (ICIs) and the effect of delays in initiating systemic adjuvant therapy on the long-term outcomes of patients with resected pancreatic cancer.

IrAEs requiring hospitalization

Investigators led by Aanika Balaji of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, reviewed a 6-month audit of inpatient oncology admissions of solid-tumor patients who had ever received ICIs and ascertained the prevalence of hospitalization for management of IrAEs (J Oncol Pract. 2019 Aug 6. doi: 10.1200/JOP.18.00703). To determine that an IrAE had occurred they required: consensus among two oncologists, clinical improvement with immune-directed therapy, exclusion of alternative diagnoses or pathologic confirmation of an IrAE, or chronic management of an IrAE for more than 6 months.

The bottom line: They found a cumulative incidence of a confirmed IrAEs among hospitalized ICI-treated solid tumor patients of 23%. As expected, the majority (65%) were grade 3-4 in severity. In total, 91% required multidisciplinary management, and 65% improved or resolved. But 87% of patients never received an ICI again.

Patients with preexisting autoimmune disease (25% of patients, although they included hypothyroidism in that group) were not more vulnerable to an IrAE with ICI therapy (odds ratio, 1.0; 95% confidence interval, 0.3-4.0). Not unsurprisingly, the median age was higher for ICI-treated patients who were admitted for IrAEs than for those not admitted (68 years vs. 59 years; OR, 5.4; 95% CI, 1.6-17.8), and more admitted patients had received combination ICIs than single agents (OR, 6.8; 95% CI, 2.0-23.2).

The median time from beginning ICIs to an IrAE-related hospitalization was 64 days, and the median number of ICI doses was one, with a wide range for both days and doses. The authors were quick to comment that this is a small, academic, single-institution survey over a brief period of time and that the generalizability of the results is uncertain.

What this means in practice

This publication changes very little for most practicing oncologists, but it does reinforce that ICI therapy can cause unpredictable, severe IrAEs. Clinical markers for selecting patients at highest risk are imperfect. As with chemotherapy, the patients we worry about the most – older individuals and patients treated with drug combinations – are, in fact, the ones we should be worrying about the most.

In view of the potential severity and impact of IrAEs, research efforts should place equal priority on identifying biomarkers of toxicity, such as tumor mutation burden, and biomarkers of efficacy (JAMA Oncol. 2019 Aug 22. doi: 10.1001/jamaoncol.2019.3221). The potential financial and societal effects, as well as lost opportunity costs in the form of alternative therapies and early referral to hospice, demand no less, particularly in an era of value-based health care reimbursement.
 

Timing of adjuvant treatment

Sung Jun Ma, MD, department of radiation medicine at Roswell Park Comprehensive Cancer Center, Buffalo, N.Y., and colleagues analyzed data from the more than 7,500 stage I-II resected pancreatic cancer patients in the National Cancer Database, of whom more than 5,400 ultimately received adjuvant therapy (chemotherapy with or without radiation). The patients were treated during 2004-2015. Appropriately, the investigators focused on correlating survival duration with the interval between surgery and initiation of adjuvant therapy. Other endpoints would be hard to accurately measure and verify without detailed clinical information (JAMA Network Open. 2019 Aug 14. doi: 10.1001/jamanetworkopen.2019.9126).

They found that the best overall survival was associated with starting adjuvant treatment 28-59 days after surgery – not earlier (17% higher mortality) and not later (9% higher). Patients who did not start adjuvant treatment until more than 90 days post operatively still had an overall survival benefit (hazard ratio, 0.75; 95% confidence interval, 0.66-0.85; P less than .001), a more impressive hazard ratio than that seen for any particular interval between surgery and adjuvant treatment. Overall survival at 2 years was 47.2% versus 38% for the adjuvant therapy and surgery alone cohorts, respectively, with no overlap in the 95% confidence intervals.

As expected, longer delays to receive adjuvant treatment were associated with longer inpatient surgical stays, advanced age, black race, lower income, and a readmission for a postoperative complication within 30 days.

What this means in practice

This is another study that verifies that the patients we worry about most – older patients, those with a complicated recovery from surgery, and those with fewer supportive resources – are exactly the patients we should worry about most. It changes very little for most practicing oncologists. The analysis validates the importance of adjuvant therapy for patients who are able to receive it – whenever that is.

The data collection in this publication precedes recent improvements in adjuvant chemotherapy for resected pancreatic cancer, such as FOLFIRINOX or gemcitabine plus capecitabine. In an era of improved treatment, delays in initiating therapy may be less important since better treatment overcomes many prognostic variables that are significant for less effective therapy.

In my opinion, this large-data analysis is not really hypothesis-generating or practice-changing, but it does compel us to continue research efforts to improve surgical morbidity, identify better adjuvant and advanced disease regimens, and consider neoadjuvant treatment so that more than 72% of patients can receive all components of the multimodality treatment they need.
 

Dr. Lyss has been a community-based medical oncologist and clinical researcher for more than 35 years, practicing in St. Louis. His clinical and research interests are in the prevention, diagnosis, and treatment of breast and lung cancers and in expanding access to clinical trials to medically underserved populations.

In this edition of “How I will treat my next patient,” I examine two recently published efforts to enlighten our sensitivity to the seriousness of immune-related adverse events (IrAEs) in patients on immune checkpoint inhibitors (ICIs) and the effect of delays in initiating systemic adjuvant therapy on the long-term outcomes of patients with resected pancreatic cancer.

IrAEs requiring hospitalization

Investigators led by Aanika Balaji of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, reviewed a 6-month audit of inpatient oncology admissions of solid-tumor patients who had ever received ICIs and ascertained the prevalence of hospitalization for management of IrAEs (J Oncol Pract. 2019 Aug 6. doi: 10.1200/JOP.18.00703). To determine that an IrAE had occurred they required: consensus among two oncologists, clinical improvement with immune-directed therapy, exclusion of alternative diagnoses or pathologic confirmation of an IrAE, or chronic management of an IrAE for more than 6 months.

The bottom line: They found a cumulative incidence of a confirmed IrAEs among hospitalized ICI-treated solid tumor patients of 23%. As expected, the majority (65%) were grade 3-4 in severity. In total, 91% required multidisciplinary management, and 65% improved or resolved. But 87% of patients never received an ICI again.

Patients with preexisting autoimmune disease (25% of patients, although they included hypothyroidism in that group) were not more vulnerable to an IrAE with ICI therapy (odds ratio, 1.0; 95% confidence interval, 0.3-4.0). Not unsurprisingly, the median age was higher for ICI-treated patients who were admitted for IrAEs than for those not admitted (68 years vs. 59 years; OR, 5.4; 95% CI, 1.6-17.8), and more admitted patients had received combination ICIs than single agents (OR, 6.8; 95% CI, 2.0-23.2).

The median time from beginning ICIs to an IrAE-related hospitalization was 64 days, and the median number of ICI doses was one, with a wide range for both days and doses. The authors were quick to comment that this is a small, academic, single-institution survey over a brief period of time and that the generalizability of the results is uncertain.

What this means in practice

This publication changes very little for most practicing oncologists, but it does reinforce that ICI therapy can cause unpredictable, severe IrAEs. Clinical markers for selecting patients at highest risk are imperfect. As with chemotherapy, the patients we worry about the most – older individuals and patients treated with drug combinations – are, in fact, the ones we should be worrying about the most.

In view of the potential severity and impact of IrAEs, research efforts should place equal priority on identifying biomarkers of toxicity, such as tumor mutation burden, and biomarkers of efficacy (JAMA Oncol. 2019 Aug 22. doi: 10.1001/jamaoncol.2019.3221). The potential financial and societal effects, as well as lost opportunity costs in the form of alternative therapies and early referral to hospice, demand no less, particularly in an era of value-based health care reimbursement.
 

Timing of adjuvant treatment

Sung Jun Ma, MD, department of radiation medicine at Roswell Park Comprehensive Cancer Center, Buffalo, N.Y., and colleagues analyzed data from the more than 7,500 stage I-II resected pancreatic cancer patients in the National Cancer Database, of whom more than 5,400 ultimately received adjuvant therapy (chemotherapy with or without radiation). The patients were treated during 2004-2015. Appropriately, the investigators focused on correlating survival duration with the interval between surgery and initiation of adjuvant therapy. Other endpoints would be hard to accurately measure and verify without detailed clinical information (JAMA Network Open. 2019 Aug 14. doi: 10.1001/jamanetworkopen.2019.9126).

They found that the best overall survival was associated with starting adjuvant treatment 28-59 days after surgery – not earlier (17% higher mortality) and not later (9% higher). Patients who did not start adjuvant treatment until more than 90 days post operatively still had an overall survival benefit (hazard ratio, 0.75; 95% confidence interval, 0.66-0.85; P less than .001), a more impressive hazard ratio than that seen for any particular interval between surgery and adjuvant treatment. Overall survival at 2 years was 47.2% versus 38% for the adjuvant therapy and surgery alone cohorts, respectively, with no overlap in the 95% confidence intervals.

As expected, longer delays to receive adjuvant treatment were associated with longer inpatient surgical stays, advanced age, black race, lower income, and a readmission for a postoperative complication within 30 days.

What this means in practice

This is another study that verifies that the patients we worry about most – older patients, those with a complicated recovery from surgery, and those with fewer supportive resources – are exactly the patients we should worry about most. It changes very little for most practicing oncologists. The analysis validates the importance of adjuvant therapy for patients who are able to receive it – whenever that is.

The data collection in this publication precedes recent improvements in adjuvant chemotherapy for resected pancreatic cancer, such as FOLFIRINOX or gemcitabine plus capecitabine. In an era of improved treatment, delays in initiating therapy may be less important since better treatment overcomes many prognostic variables that are significant for less effective therapy.

In my opinion, this large-data analysis is not really hypothesis-generating or practice-changing, but it does compel us to continue research efforts to improve surgical morbidity, identify better adjuvant and advanced disease regimens, and consider neoadjuvant treatment so that more than 72% of patients can receive all components of the multimodality treatment they need.
 

Dr. Lyss has been a community-based medical oncologist and clinical researcher for more than 35 years, practicing in St. Louis. His clinical and research interests are in the prevention, diagnosis, and treatment of breast and lung cancers and in expanding access to clinical trials to medically underserved populations.

A history of using multiple conventional synthetic disease-modifying antirheumatic drugs (DMARDs) is a key predictor for poorer response to adalimumab therapy in rheumatoid arthritis patients, according to data from a pair of studies with a total of 274 patients.

Although patients with RA who have failed methotrexate or tumor necrosis factor inhibitor therapy respond less than methotrexate-naive patients, “it remains unknown if response to the first biologic DMARD, in particular a [tumor necrosis factor inhibitor], depends on disease duration or prior numbers of failed [conventional synthetic] DMARDs,” wrote Daniel Aletaha, MD, of the Medical University of Vienna and colleagues.

In a study published in Annals of the Rheumatic Diseases, the researchers reviewed data from two randomized, controlled trials of patients with RA. In the larger trial of 207 adults (known as DE019), past use of two or more conventional synthetic DMARDs was associated with less improvement in 28-joint Disease Activity Score using C-reactive protein (DAS28-CRP) after 24 weeks of adalimumab (Humira), compared with use of one or no DMARDs (–1.8 vs. –2.2, respectively). Similarly, disease activity and disability scores improved significantly less in patients who had used two or more DMARDs, compared with those who used one or no DMARDs, according to the Simplified Disease Activity Index (SDAI; –22.1 vs. –26.9) and the Health Assessment Questionnaire Disability Index (HAQ-DI; –0.43 vs. –0.64).

The researchers also examined the role of disease duration on treatment response. Overall, patients with disease duration greater than 10 years showed more improvement at 24 weeks than did those with disease duration less than 1 year, based on HAQ-DI scores (1.1 vs. 0.7), but final scores on the SDAI and DAS28-CRP were not significantly different between those with disease duration greater than 10 years and those with duration of less than 1 year. These results suggest that the impact of DMARDs holds true regardless of disease duration, the researchers noted.

The findings were similar with regard to number of prior conventional synthetic DMARDs and the effects of disease duration in the second trial of 67 patients, known as the ARMADA study.

The study findings were limited by several factors, including the post hoc analysis design, use of only adalimumab data, and the small number of patients in several subgroups, the researchers noted. However, the results support the need for more standardized treatment guidelines and suggest that RA patients who fail to respond to methotrexate soon after RA diagnosis may benefit most from adding adalimumab, they said.

“Furthermore, these findings should be considered in future trials when defining inclusion criteria not only by duration of disease but also by number of prior DMARDs,” they concluded.

The study was sponsored by AbbVie, which markets adalimumab. Dr. Aletaha disclosed grants and consulting fees from AbbVie, as well as other pharmaceutical companies. Four of the authors were current or former employees of AbbVie, and some other authors also reported financial relationships with the company.

SOURCE: Aletaha D et al. Ann Rheum Dis. 2019 Aug 21. doi: 10.1136/annrheumdis-2018-214918.

A history of using multiple conventional synthetic disease-modifying antirheumatic drugs (DMARDs) is a key predictor for poorer response to adalimumab therapy in rheumatoid arthritis patients, according to data from a pair of studies with a total of 274 patients.

Although patients with RA who have failed methotrexate or tumor necrosis factor inhibitor therapy respond less than methotrexate-naive patients, “it remains unknown if response to the first biologic DMARD, in particular a [tumor necrosis factor inhibitor], depends on disease duration or prior numbers of failed [conventional synthetic] DMARDs,” wrote Daniel Aletaha, MD, of the Medical University of Vienna and colleagues.

In a study published in Annals of the Rheumatic Diseases, the researchers reviewed data from two randomized, controlled trials of patients with RA. In the larger trial of 207 adults (known as DE019), past use of two or more conventional synthetic DMARDs was associated with less improvement in 28-joint Disease Activity Score using C-reactive protein (DAS28-CRP) after 24 weeks of adalimumab (Humira), compared with use of one or no DMARDs (–1.8 vs. –2.2, respectively). Similarly, disease activity and disability scores improved significantly less in patients who had used two or more DMARDs, compared with those who used one or no DMARDs, according to the Simplified Disease Activity Index (SDAI; –22.1 vs. –26.9) and the Health Assessment Questionnaire Disability Index (HAQ-DI; –0.43 vs. –0.64).

The researchers also examined the role of disease duration on treatment response. Overall, patients with disease duration greater than 10 years showed more improvement at 24 weeks than did those with disease duration less than 1 year, based on HAQ-DI scores (1.1 vs. 0.7), but final scores on the SDAI and DAS28-CRP were not significantly different between those with disease duration greater than 10 years and those with duration of less than 1 year. These results suggest that the impact of DMARDs holds true regardless of disease duration, the researchers noted.

The findings were similar with regard to number of prior conventional synthetic DMARDs and the effects of disease duration in the second trial of 67 patients, known as the ARMADA study.

The study findings were limited by several factors, including the post hoc analysis design, use of only adalimumab data, and the small number of patients in several subgroups, the researchers noted. However, the results support the need for more standardized treatment guidelines and suggest that RA patients who fail to respond to methotrexate soon after RA diagnosis may benefit most from adding adalimumab, they said.

“Furthermore, these findings should be considered in future trials when defining inclusion criteria not only by duration of disease but also by number of prior DMARDs,” they concluded.

The study was sponsored by AbbVie, which markets adalimumab. Dr. Aletaha disclosed grants and consulting fees from AbbVie, as well as other pharmaceutical companies. Four of the authors were current or former employees of AbbVie, and some other authors also reported financial relationships with the company.

SOURCE: Aletaha D et al. Ann Rheum Dis. 2019 Aug 21. doi: 10.1136/annrheumdis-2018-214918.

A history of using multiple conventional synthetic disease-modifying antirheumatic drugs (DMARDs) is a key predictor for poorer response to adalimumab therapy in rheumatoid arthritis patients, according to data from a pair of studies with a total of 274 patients.

Although patients with RA who have failed methotrexate or tumor necrosis factor inhibitor therapy respond less than methotrexate-naive patients, “it remains unknown if response to the first biologic DMARD, in particular a [tumor necrosis factor inhibitor], depends on disease duration or prior numbers of failed [conventional synthetic] DMARDs,” wrote Daniel Aletaha, MD, of the Medical University of Vienna and colleagues.

In a study published in Annals of the Rheumatic Diseases, the researchers reviewed data from two randomized, controlled trials of patients with RA. In the larger trial of 207 adults (known as DE019), past use of two or more conventional synthetic DMARDs was associated with less improvement in 28-joint Disease Activity Score using C-reactive protein (DAS28-CRP) after 24 weeks of adalimumab (Humira), compared with use of one or no DMARDs (–1.8 vs. –2.2, respectively). Similarly, disease activity and disability scores improved significantly less in patients who had used two or more DMARDs, compared with those who used one or no DMARDs, according to the Simplified Disease Activity Index (SDAI; –22.1 vs. –26.9) and the Health Assessment Questionnaire Disability Index (HAQ-DI; –0.43 vs. –0.64).

The researchers also examined the role of disease duration on treatment response. Overall, patients with disease duration greater than 10 years showed more improvement at 24 weeks than did those with disease duration less than 1 year, based on HAQ-DI scores (1.1 vs. 0.7), but final scores on the SDAI and DAS28-CRP were not significantly different between those with disease duration greater than 10 years and those with duration of less than 1 year. These results suggest that the impact of DMARDs holds true regardless of disease duration, the researchers noted.

The findings were similar with regard to number of prior conventional synthetic DMARDs and the effects of disease duration in the second trial of 67 patients, known as the ARMADA study.

The study findings were limited by several factors, including the post hoc analysis design, use of only adalimumab data, and the small number of patients in several subgroups, the researchers noted. However, the results support the need for more standardized treatment guidelines and suggest that RA patients who fail to respond to methotrexate soon after RA diagnosis may benefit most from adding adalimumab, they said.

“Furthermore, these findings should be considered in future trials when defining inclusion criteria not only by duration of disease but also by number of prior DMARDs,” they concluded.

The study was sponsored by AbbVie, which markets adalimumab. Dr. Aletaha disclosed grants and consulting fees from AbbVie, as well as other pharmaceutical companies. Four of the authors were current or former employees of AbbVie, and some other authors also reported financial relationships with the company.

SOURCE: Aletaha D et al. Ann Rheum Dis. 2019 Aug 21. doi: 10.1136/annrheumdis-2018-214918.