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Skin patch testing pinpoints dietary triggers of IBS
SAN DIEGO – About 90% of patients reported improvement in symptoms of irritable bowel syndrome after avoiding type 4 food allergens identified by skin patch testing, according to an uncontrolled study.
Furthermore, 69% of patients reported at least moderate improvement after eliminating foods to which they reacted, said Dr. Michael Stierstorfer, a dermatologist at East Penn Dermatology in North Wales, Pa., who partnered with gastroenterologists at Temple University to conduct the study. “This raises questions about a possible overlap between IBS and allergic contact enteritis,” the researchers stated in a poster presented at the annual Digestive Disease Week.
Irritable bowel syndrome is often treatment refractory and tends to elude conventional diagnostics. That was the case for Dr. Stierstorfer, who several years ago developed symptoms of IBS with constipation (IBS-C) that eventually affected him about half the time, he said in an interview. A hydrogen breath test, upper endoscopy, colonoscopy, abdominal/pelvic CT, and tests for gluten-sensitive enteropathy and parasites revealed no abnormalities except decreased small intestinal motility, he said.
But after “flaring badly” twice when he ate Indian food, he began to suspect a cause. “I stopped eating garlic and within a day, I was absolutely fine,” Dr. Stierstorfer said. “The symptoms recurred only if I accidentally ate garlic again.”
Studies had refuted links between IBS and type 1 hypersensitivity but had not explored the role of type 4 (delayed) hypersensitivity in the disorder, Dr. Stierstorfer discovered. “Dermatologists do patch testing all the time for patients with refractory eczema to search for type 4 allergic contact factors that might be causing their rash,” he said. “I performed a patch test of garlic on myself to look for a type 4 allergy, and it was strongly positive. I thought I probably wasn’t the only person walking around with symptoms that mimicked IBS but were really from a type 4 food allergy.”
He tested that idea by skin patch testing 50 patients with IBS symptoms whom he recruited through his dermatology practice. In all, 30 (60%) patients reacted to at least one food allergen, of whom 14 (46%) reported symptomatic improvement after eliminating the suspected triggers from their diets. The findings appeared in the March 2013 Journal of the American Academy of Dermatology (68:377-84).
Next, Dr. Stierstorfer partnered with Dr. Grace Shin, a 3rd-year gastroenterology fellow at Temple University, Philadelphia, and her colleagues. Together, they tested 57 patients with physician-diagnosed IBS with diarrhea (about 43% of patients), IBS with constipation (16%), mixed IBS (30%), or unsubtyped IBS (11%). Patients averaged 41 years of age (standard deviation, 15 years) and 77% were female. Each patient had between 118 and 122 individual allergen patches placed on his or her back. Two days later, the patches were removed and the skin evaluated for macular erythema consistent with a type 4 hypersensitivity reaction. The patients were checked again a day or 2 later to catch any highly delayed reactions.
In all, 56 patients (98%) showed evidence of at least one hypersensitivity, and most reacted to between two and three allergens, Dr. Stierstorfer said. The most commonly identified triggers were cinnamon bark (35 patients; 61%) and sodium bisulfite (26 patients; 46%). At baseline, patients rated their abdominal pain or discomfort at an average of 6.7 on a 10-point severity scale (SD, 2.3 points). After 2-4 weeks of avoiding allergens to which they developed macular edema, they reported a mean 4.4-point improvement in their abdominal symptoms (SD, 2.7 points; P less than .001).
The patients also reported an average 5.8-point improvement on a 10-point scale of global IBS symptom severity (SD, 3.2 points; P less than .001). Overall, 91% of patients reported at least partial relief of abdominal symptoms, while 89% of patients reported at least partial relief of global symptoms, the investigators reported.
Based on these results, “food-related type 4 hypersensitivity reactions may contribute to the pathogenesis of IBS and IBS-like symptoms,” Dr. Shin said in an interview. “The idea of allergic contact enteritis intrigued me, because it made me think that some patients diagnosed with IBS, especially IBS with diarrhea, might benefit from allergy testing when the standard approaches don’t work.”
Another dietary intervention for IBS, the low-FODMAP diet, can help relieve symptoms, “but it’s a hard diet to follow,” Dr. Shin added. “Being able to focus on eliminating one or two things would be easier than eliminating multiple classes of foods that are so common to an American diet.”
Next, the team is planning a controlled trial of the skin patch test. “There is still more validation work to do,” said Dr. Stierstorfer. “But I think this shows that looking at something from a unique perspective – in this case, a dermatologic perspective for a GI problem – can result in a new approach, and potentially an advance in medicine.”
Dr. Shin had no disclosures. Dr. Stierstorfer disclosed financial ties to IBS Centers for Advanced Food Allergy Testing.
SAN DIEGO – About 90% of patients reported improvement in symptoms of irritable bowel syndrome after avoiding type 4 food allergens identified by skin patch testing, according to an uncontrolled study.
Furthermore, 69% of patients reported at least moderate improvement after eliminating foods to which they reacted, said Dr. Michael Stierstorfer, a dermatologist at East Penn Dermatology in North Wales, Pa., who partnered with gastroenterologists at Temple University to conduct the study. “This raises questions about a possible overlap between IBS and allergic contact enteritis,” the researchers stated in a poster presented at the annual Digestive Disease Week.
Irritable bowel syndrome is often treatment refractory and tends to elude conventional diagnostics. That was the case for Dr. Stierstorfer, who several years ago developed symptoms of IBS with constipation (IBS-C) that eventually affected him about half the time, he said in an interview. A hydrogen breath test, upper endoscopy, colonoscopy, abdominal/pelvic CT, and tests for gluten-sensitive enteropathy and parasites revealed no abnormalities except decreased small intestinal motility, he said.
But after “flaring badly” twice when he ate Indian food, he began to suspect a cause. “I stopped eating garlic and within a day, I was absolutely fine,” Dr. Stierstorfer said. “The symptoms recurred only if I accidentally ate garlic again.”
Studies had refuted links between IBS and type 1 hypersensitivity but had not explored the role of type 4 (delayed) hypersensitivity in the disorder, Dr. Stierstorfer discovered. “Dermatologists do patch testing all the time for patients with refractory eczema to search for type 4 allergic contact factors that might be causing their rash,” he said. “I performed a patch test of garlic on myself to look for a type 4 allergy, and it was strongly positive. I thought I probably wasn’t the only person walking around with symptoms that mimicked IBS but were really from a type 4 food allergy.”
He tested that idea by skin patch testing 50 patients with IBS symptoms whom he recruited through his dermatology practice. In all, 30 (60%) patients reacted to at least one food allergen, of whom 14 (46%) reported symptomatic improvement after eliminating the suspected triggers from their diets. The findings appeared in the March 2013 Journal of the American Academy of Dermatology (68:377-84).
Next, Dr. Stierstorfer partnered with Dr. Grace Shin, a 3rd-year gastroenterology fellow at Temple University, Philadelphia, and her colleagues. Together, they tested 57 patients with physician-diagnosed IBS with diarrhea (about 43% of patients), IBS with constipation (16%), mixed IBS (30%), or unsubtyped IBS (11%). Patients averaged 41 years of age (standard deviation, 15 years) and 77% were female. Each patient had between 118 and 122 individual allergen patches placed on his or her back. Two days later, the patches were removed and the skin evaluated for macular erythema consistent with a type 4 hypersensitivity reaction. The patients were checked again a day or 2 later to catch any highly delayed reactions.
In all, 56 patients (98%) showed evidence of at least one hypersensitivity, and most reacted to between two and three allergens, Dr. Stierstorfer said. The most commonly identified triggers were cinnamon bark (35 patients; 61%) and sodium bisulfite (26 patients; 46%). At baseline, patients rated their abdominal pain or discomfort at an average of 6.7 on a 10-point severity scale (SD, 2.3 points). After 2-4 weeks of avoiding allergens to which they developed macular edema, they reported a mean 4.4-point improvement in their abdominal symptoms (SD, 2.7 points; P less than .001).
The patients also reported an average 5.8-point improvement on a 10-point scale of global IBS symptom severity (SD, 3.2 points; P less than .001). Overall, 91% of patients reported at least partial relief of abdominal symptoms, while 89% of patients reported at least partial relief of global symptoms, the investigators reported.
Based on these results, “food-related type 4 hypersensitivity reactions may contribute to the pathogenesis of IBS and IBS-like symptoms,” Dr. Shin said in an interview. “The idea of allergic contact enteritis intrigued me, because it made me think that some patients diagnosed with IBS, especially IBS with diarrhea, might benefit from allergy testing when the standard approaches don’t work.”
Another dietary intervention for IBS, the low-FODMAP diet, can help relieve symptoms, “but it’s a hard diet to follow,” Dr. Shin added. “Being able to focus on eliminating one or two things would be easier than eliminating multiple classes of foods that are so common to an American diet.”
Next, the team is planning a controlled trial of the skin patch test. “There is still more validation work to do,” said Dr. Stierstorfer. “But I think this shows that looking at something from a unique perspective – in this case, a dermatologic perspective for a GI problem – can result in a new approach, and potentially an advance in medicine.”
Dr. Shin had no disclosures. Dr. Stierstorfer disclosed financial ties to IBS Centers for Advanced Food Allergy Testing.
SAN DIEGO – About 90% of patients reported improvement in symptoms of irritable bowel syndrome after avoiding type 4 food allergens identified by skin patch testing, according to an uncontrolled study.
Furthermore, 69% of patients reported at least moderate improvement after eliminating foods to which they reacted, said Dr. Michael Stierstorfer, a dermatologist at East Penn Dermatology in North Wales, Pa., who partnered with gastroenterologists at Temple University to conduct the study. “This raises questions about a possible overlap between IBS and allergic contact enteritis,” the researchers stated in a poster presented at the annual Digestive Disease Week.
Irritable bowel syndrome is often treatment refractory and tends to elude conventional diagnostics. That was the case for Dr. Stierstorfer, who several years ago developed symptoms of IBS with constipation (IBS-C) that eventually affected him about half the time, he said in an interview. A hydrogen breath test, upper endoscopy, colonoscopy, abdominal/pelvic CT, and tests for gluten-sensitive enteropathy and parasites revealed no abnormalities except decreased small intestinal motility, he said.
But after “flaring badly” twice when he ate Indian food, he began to suspect a cause. “I stopped eating garlic and within a day, I was absolutely fine,” Dr. Stierstorfer said. “The symptoms recurred only if I accidentally ate garlic again.”
Studies had refuted links between IBS and type 1 hypersensitivity but had not explored the role of type 4 (delayed) hypersensitivity in the disorder, Dr. Stierstorfer discovered. “Dermatologists do patch testing all the time for patients with refractory eczema to search for type 4 allergic contact factors that might be causing their rash,” he said. “I performed a patch test of garlic on myself to look for a type 4 allergy, and it was strongly positive. I thought I probably wasn’t the only person walking around with symptoms that mimicked IBS but were really from a type 4 food allergy.”
He tested that idea by skin patch testing 50 patients with IBS symptoms whom he recruited through his dermatology practice. In all, 30 (60%) patients reacted to at least one food allergen, of whom 14 (46%) reported symptomatic improvement after eliminating the suspected triggers from their diets. The findings appeared in the March 2013 Journal of the American Academy of Dermatology (68:377-84).
Next, Dr. Stierstorfer partnered with Dr. Grace Shin, a 3rd-year gastroenterology fellow at Temple University, Philadelphia, and her colleagues. Together, they tested 57 patients with physician-diagnosed IBS with diarrhea (about 43% of patients), IBS with constipation (16%), mixed IBS (30%), or unsubtyped IBS (11%). Patients averaged 41 years of age (standard deviation, 15 years) and 77% were female. Each patient had between 118 and 122 individual allergen patches placed on his or her back. Two days later, the patches were removed and the skin evaluated for macular erythema consistent with a type 4 hypersensitivity reaction. The patients were checked again a day or 2 later to catch any highly delayed reactions.
In all, 56 patients (98%) showed evidence of at least one hypersensitivity, and most reacted to between two and three allergens, Dr. Stierstorfer said. The most commonly identified triggers were cinnamon bark (35 patients; 61%) and sodium bisulfite (26 patients; 46%). At baseline, patients rated their abdominal pain or discomfort at an average of 6.7 on a 10-point severity scale (SD, 2.3 points). After 2-4 weeks of avoiding allergens to which they developed macular edema, they reported a mean 4.4-point improvement in their abdominal symptoms (SD, 2.7 points; P less than .001).
The patients also reported an average 5.8-point improvement on a 10-point scale of global IBS symptom severity (SD, 3.2 points; P less than .001). Overall, 91% of patients reported at least partial relief of abdominal symptoms, while 89% of patients reported at least partial relief of global symptoms, the investigators reported.
Based on these results, “food-related type 4 hypersensitivity reactions may contribute to the pathogenesis of IBS and IBS-like symptoms,” Dr. Shin said in an interview. “The idea of allergic contact enteritis intrigued me, because it made me think that some patients diagnosed with IBS, especially IBS with diarrhea, might benefit from allergy testing when the standard approaches don’t work.”
Another dietary intervention for IBS, the low-FODMAP diet, can help relieve symptoms, “but it’s a hard diet to follow,” Dr. Shin added. “Being able to focus on eliminating one or two things would be easier than eliminating multiple classes of foods that are so common to an American diet.”
Next, the team is planning a controlled trial of the skin patch test. “There is still more validation work to do,” said Dr. Stierstorfer. “But I think this shows that looking at something from a unique perspective – in this case, a dermatologic perspective for a GI problem – can result in a new approach, and potentially an advance in medicine.”
Dr. Shin had no disclosures. Dr. Stierstorfer disclosed financial ties to IBS Centers for Advanced Food Allergy Testing.
AT DDW® 2016
Key clinical point: Avoiding food allergens identified by skin patch testing significantly improved self-reported symptoms of irritable bowel syndrome.
Major finding: In all, 69% of patients reported at least moderate improvement after eliminating foods to which they reacted.
Data source: A single-arm proof-of-concept study of 57 patients with physician-diagnosed IBS.
Disclosures: Dr. Shin had no disclosures. Dr. Stierstorfer disclosed financial ties to IBS Centers for Advanced Food Allergy Testing.
IASLC lung cancer staging project proposes changes for new TNM classification
The International Association for the Study of Lung Cancer (IASLC) Staging and Prognostic Factors Committee has developed proposals for revision of the T, N, and M categories of the 8th edition of the TNM Classification for lung cancer due to be published in late 2016. The new classification will be enacted in January 2017.
The changes proposed were based on the results of an analysis of a new database of 94,708 cases donated from 35 sources in 16 countries around the world.
The methods used and the proposals made were published in the Journal of Thoracic Oncology (2016;11:39-51).
Candidate proposals for the TNM stage groups were developed in conjunction with proposed changes to the T and M categories, which were previously published (J Thorac Oncol 2015;10:990-1003, and 2015;10:1515-22). There were no proposed changes to the N.
Changes to some T and M descriptors will result in these cases being assigned to a different stage than that to which they would have been assigned in the 7th edition. In addition, some TNM subsets have been moved to a new stage grouping, according to Dr. Peter Goldstraw of Imperial College, London, and his colleagues on behalf of the IASLC Staging and Prognostic Factors Committee.
Major new proposals
T1 changes: Size cut points have further proliferated in the proposals for the 8th edition, and outgrowth of the emphasis on tumor size in the 7th edition, such that size will now be a descriptor in all T categories, according to the authors. New stage groupings proposed divide stage T1 into T1a, T1b, and T1c, based on the new size cut points of 1 cm and 2 cm. This results in these cases (when associated with the categories N0 and M0) being assigned to stages 1A1, 1A2, and 1A3, respectively, which reflects the statistically different prognosis of these cases.
T3, T4 changes: A new group has been created for the most advanced local disease categories, T3 and T4 associated with N3 disease, but category M0. Such cases will now be classified as stage IIIC, reflecting their worse outcomes than seen in cases involving tumors that remain in stage IIIB. The prognosis for stage IIIC cases is similar to that of stage IVA cases, however the researchers justified the separation, based upon the different treatment approaches used for such cases.
M changes: Although cases with intrathoracic metastatic disease to the contralateral lung or with pleural/pericardial dissemination remain classified as M1a disease, the category M1b will now be assigned to cases with a single metastatic deposit (in one organ) and M1a and M1b cases will be moored to a new stage grouping called IVA. The more common situation of multiple metastatic deposits, usually in more than one organ, will be classified as M1c and staged as IVB. Separation of the M1a and M1b categories was maintained both for further data analysis and because some patients with oligometastatic disease are now receiving more aggressive local therapy in addition to systemic treatment, according to the authors.
Other proposals
A variety of more minor changes to stage groupings has also been proposed, some of which will result in a T descriptor being allocated to a higher stage. In some cases, tumors may be allocated to a different T category entirely, leading to a reclassification of stage. Among the examples given were tumors associated with diaphragmatic invasion to TV, which, when associated with N0 disease, will move from stage IIB to IIA.
Impact on treatment
The relationship of the proposed classification changes to treatment decisions is not direct, the authors stated in their discussion. “Although such changes might raise the issue of whether consequent changes to treatment algorithms are needed, it is important to remind ourselves that stage does not dictate treatment. Stage is one, and perhaps the most important, of several prognostic factors that guide the appropriate treatment option[s] to offer the patient. Any change to established treatment algorithms should be based on clinical judgment informed by prospective trials,” they emphasized.
New stage groupings should be used in any trials of novel therapies, they added.
“We hope that the thoracic oncology community finds the proposals of value and that, when accepted, will have a positive impact on the effectiveness of treatment for lung cancer, which will benefit patients around the globe,” the researchers concluded.
The research to develop the new proposals was funded by the IASLC, including funds obtained through unrestricted grants obtained from the pharmaceutical industry. The authors reported no other disclosures.
The 8th edition of the TNM staging is upon us. It is the summary of analysis of 90,000 cases and data collected over 11 years. It behooves every thoracic surgeon taking care of patients with lung cancer to familiarize themselves with the new version. The staging proposal is available as an open access article on the Journal of Thoracic Oncology website.
From a statistical viewpoint, this edition fits the data better than previous editions did. However, from a practical application, it is more cumbersome to use routinely in a busy clinic. One hopes that we can soon say, “There’s an app for that!” Such interfacing will enhance the application of this edition significantly.
 |
Dr. Sai Yendamuri |
The new edition of the staging system is particularly important for surgeons for two reasons. The first is the formal recognition that patients with oligometastatic disease have a better prognosis than other stage IV disease and may be amenable to multimodality therapies with curative intent, as is currently performed by select clinical teams. The second is the further refinement of stage I disease with respect to tumor size. Combined with the new histologic classification of adenocarcinoma and its proposed integration with the TNM classification, the debate of sublobar vs. lobar resection for stage I NSCLC will become more nuanced. These implications for the practicing thoracic surgeon make the manuscript mandatory reading.
Dr. Sai Yendamuri is chair, department of thoracic surgery, and director, thoracic surgery research laboratory, and a professor of oncology at Roswell Park Cancer Institute, Buffalo, N.Y. He is also the general thoracic editor for Thoracic Surgery News.
The 8th edition of the TNM staging is upon us. It is the summary of analysis of 90,000 cases and data collected over 11 years. It behooves every thoracic surgeon taking care of patients with lung cancer to familiarize themselves with the new version. The staging proposal is available as an open access article on the Journal of Thoracic Oncology website.
From a statistical viewpoint, this edition fits the data better than previous editions did. However, from a practical application, it is more cumbersome to use routinely in a busy clinic. One hopes that we can soon say, “There’s an app for that!” Such interfacing will enhance the application of this edition significantly.
|
Dr. Sai Yendamuri |
The new edition of the staging system is particularly important for surgeons for two reasons. The first is the formal recognition that patients with oligometastatic disease have a better prognosis than other stage IV disease and may be amenable to multimodality therapies with curative intent, as is currently performed by select clinical teams. The second is the further refinement of stage I disease with respect to tumor size. Combined with the new histologic classification of adenocarcinoma and its proposed integration with the TNM classification, the debate of sublobar vs. lobar resection for stage I NSCLC will become more nuanced. These implications for the practicing thoracic surgeon make the manuscript mandatory reading.
Dr. Sai Yendamuri is chair, department of thoracic surgery, and director, thoracic surgery research laboratory, and a professor of oncology at Roswell Park Cancer Institute, Buffalo, N.Y. He is also the general thoracic editor for Thoracic Surgery News.
The 8th edition of the TNM staging is upon us. It is the summary of analysis of 90,000 cases and data collected over 11 years. It behooves every thoracic surgeon taking care of patients with lung cancer to familiarize themselves with the new version. The staging proposal is available as an open access article on the Journal of Thoracic Oncology website.
From a statistical viewpoint, this edition fits the data better than previous editions did. However, from a practical application, it is more cumbersome to use routinely in a busy clinic. One hopes that we can soon say, “There’s an app for that!” Such interfacing will enhance the application of this edition significantly.
|
Dr. Sai Yendamuri |
The new edition of the staging system is particularly important for surgeons for two reasons. The first is the formal recognition that patients with oligometastatic disease have a better prognosis than other stage IV disease and may be amenable to multimodality therapies with curative intent, as is currently performed by select clinical teams. The second is the further refinement of stage I disease with respect to tumor size. Combined with the new histologic classification of adenocarcinoma and its proposed integration with the TNM classification, the debate of sublobar vs. lobar resection for stage I NSCLC will become more nuanced. These implications for the practicing thoracic surgeon make the manuscript mandatory reading.
Dr. Sai Yendamuri is chair, department of thoracic surgery, and director, thoracic surgery research laboratory, and a professor of oncology at Roswell Park Cancer Institute, Buffalo, N.Y. He is also the general thoracic editor for Thoracic Surgery News.
The International Association for the Study of Lung Cancer (IASLC) Staging and Prognostic Factors Committee has developed proposals for revision of the T, N, and M categories of the 8th edition of the TNM Classification for lung cancer due to be published in late 2016. The new classification will be enacted in January 2017.
The changes proposed were based on the results of an analysis of a new database of 94,708 cases donated from 35 sources in 16 countries around the world.
The methods used and the proposals made were published in the Journal of Thoracic Oncology (2016;11:39-51).
Candidate proposals for the TNM stage groups were developed in conjunction with proposed changes to the T and M categories, which were previously published (J Thorac Oncol 2015;10:990-1003, and 2015;10:1515-22). There were no proposed changes to the N.
Changes to some T and M descriptors will result in these cases being assigned to a different stage than that to which they would have been assigned in the 7th edition. In addition, some TNM subsets have been moved to a new stage grouping, according to Dr. Peter Goldstraw of Imperial College, London, and his colleagues on behalf of the IASLC Staging and Prognostic Factors Committee.
Major new proposals
T1 changes: Size cut points have further proliferated in the proposals for the 8th edition, and outgrowth of the emphasis on tumor size in the 7th edition, such that size will now be a descriptor in all T categories, according to the authors. New stage groupings proposed divide stage T1 into T1a, T1b, and T1c, based on the new size cut points of 1 cm and 2 cm. This results in these cases (when associated with the categories N0 and M0) being assigned to stages 1A1, 1A2, and 1A3, respectively, which reflects the statistically different prognosis of these cases.
T3, T4 changes: A new group has been created for the most advanced local disease categories, T3 and T4 associated with N3 disease, but category M0. Such cases will now be classified as stage IIIC, reflecting their worse outcomes than seen in cases involving tumors that remain in stage IIIB. The prognosis for stage IIIC cases is similar to that of stage IVA cases, however the researchers justified the separation, based upon the different treatment approaches used for such cases.
M changes: Although cases with intrathoracic metastatic disease to the contralateral lung or with pleural/pericardial dissemination remain classified as M1a disease, the category M1b will now be assigned to cases with a single metastatic deposit (in one organ) and M1a and M1b cases will be moored to a new stage grouping called IVA. The more common situation of multiple metastatic deposits, usually in more than one organ, will be classified as M1c and staged as IVB. Separation of the M1a and M1b categories was maintained both for further data analysis and because some patients with oligometastatic disease are now receiving more aggressive local therapy in addition to systemic treatment, according to the authors.
Other proposals
A variety of more minor changes to stage groupings has also been proposed, some of which will result in a T descriptor being allocated to a higher stage. In some cases, tumors may be allocated to a different T category entirely, leading to a reclassification of stage. Among the examples given were tumors associated with diaphragmatic invasion to TV, which, when associated with N0 disease, will move from stage IIB to IIA.
Impact on treatment
The relationship of the proposed classification changes to treatment decisions is not direct, the authors stated in their discussion. “Although such changes might raise the issue of whether consequent changes to treatment algorithms are needed, it is important to remind ourselves that stage does not dictate treatment. Stage is one, and perhaps the most important, of several prognostic factors that guide the appropriate treatment option[s] to offer the patient. Any change to established treatment algorithms should be based on clinical judgment informed by prospective trials,” they emphasized.
New stage groupings should be used in any trials of novel therapies, they added.
“We hope that the thoracic oncology community finds the proposals of value and that, when accepted, will have a positive impact on the effectiveness of treatment for lung cancer, which will benefit patients around the globe,” the researchers concluded.
The research to develop the new proposals was funded by the IASLC, including funds obtained through unrestricted grants obtained from the pharmaceutical industry. The authors reported no other disclosures.
The International Association for the Study of Lung Cancer (IASLC) Staging and Prognostic Factors Committee has developed proposals for revision of the T, N, and M categories of the 8th edition of the TNM Classification for lung cancer due to be published in late 2016. The new classification will be enacted in January 2017.
The changes proposed were based on the results of an analysis of a new database of 94,708 cases donated from 35 sources in 16 countries around the world.
The methods used and the proposals made were published in the Journal of Thoracic Oncology (2016;11:39-51).
Candidate proposals for the TNM stage groups were developed in conjunction with proposed changes to the T and M categories, which were previously published (J Thorac Oncol 2015;10:990-1003, and 2015;10:1515-22). There were no proposed changes to the N.
Changes to some T and M descriptors will result in these cases being assigned to a different stage than that to which they would have been assigned in the 7th edition. In addition, some TNM subsets have been moved to a new stage grouping, according to Dr. Peter Goldstraw of Imperial College, London, and his colleagues on behalf of the IASLC Staging and Prognostic Factors Committee.
Major new proposals
T1 changes: Size cut points have further proliferated in the proposals for the 8th edition, and outgrowth of the emphasis on tumor size in the 7th edition, such that size will now be a descriptor in all T categories, according to the authors. New stage groupings proposed divide stage T1 into T1a, T1b, and T1c, based on the new size cut points of 1 cm and 2 cm. This results in these cases (when associated with the categories N0 and M0) being assigned to stages 1A1, 1A2, and 1A3, respectively, which reflects the statistically different prognosis of these cases.
T3, T4 changes: A new group has been created for the most advanced local disease categories, T3 and T4 associated with N3 disease, but category M0. Such cases will now be classified as stage IIIC, reflecting their worse outcomes than seen in cases involving tumors that remain in stage IIIB. The prognosis for stage IIIC cases is similar to that of stage IVA cases, however the researchers justified the separation, based upon the different treatment approaches used for such cases.
M changes: Although cases with intrathoracic metastatic disease to the contralateral lung or with pleural/pericardial dissemination remain classified as M1a disease, the category M1b will now be assigned to cases with a single metastatic deposit (in one organ) and M1a and M1b cases will be moored to a new stage grouping called IVA. The more common situation of multiple metastatic deposits, usually in more than one organ, will be classified as M1c and staged as IVB. Separation of the M1a and M1b categories was maintained both for further data analysis and because some patients with oligometastatic disease are now receiving more aggressive local therapy in addition to systemic treatment, according to the authors.
Other proposals
A variety of more minor changes to stage groupings has also been proposed, some of which will result in a T descriptor being allocated to a higher stage. In some cases, tumors may be allocated to a different T category entirely, leading to a reclassification of stage. Among the examples given were tumors associated with diaphragmatic invasion to TV, which, when associated with N0 disease, will move from stage IIB to IIA.
Impact on treatment
The relationship of the proposed classification changes to treatment decisions is not direct, the authors stated in their discussion. “Although such changes might raise the issue of whether consequent changes to treatment algorithms are needed, it is important to remind ourselves that stage does not dictate treatment. Stage is one, and perhaps the most important, of several prognostic factors that guide the appropriate treatment option[s] to offer the patient. Any change to established treatment algorithms should be based on clinical judgment informed by prospective trials,” they emphasized.
New stage groupings should be used in any trials of novel therapies, they added.
“We hope that the thoracic oncology community finds the proposals of value and that, when accepted, will have a positive impact on the effectiveness of treatment for lung cancer, which will benefit patients around the globe,” the researchers concluded.
The research to develop the new proposals was funded by the IASLC, including funds obtained through unrestricted grants obtained from the pharmaceutical industry. The authors reported no other disclosures.
FROM THE JOURNAL OF THORACIC ONCOLOGY
Key clinical point: New lung cancer classification to become effective January 2017.
Major finding: Size will now be a descriptor in all T categories, according to the authors. New stage groupings proposed dividing stage T1 into T1a, T1b, and T1c, based on the new size cut points of 1 cm and 2 cm.
Data source: The International Association for the Study of Lung Cancer (IASLC) Staging and Prognostic Factors Committee has developed proposals for revision of the T, N, and M categories of the 8th edition of the TNM Classification for lung cancer.
Disclosures: The research to develop the new proposals was funded by the IASLC, including funds obtained through unrestricted grants obtained from the pharmaceutical industry. The authors reported no other disclosures.
Recognizing Contributions Physician Personalities Make to the Greater Good
My family and I recently took a spring break trip out west to see a few national parks. During the trip, we stayed on a family ranch in Utah. It had a wide variety of livestock, including a large number of mules and horses.
During our stay at this family-owned ranch, two things really stood out and made me think:
- The guesthouse we stayed in had an inordinate volume of collections dedicated to the science and art of raising horses and mules. Everywhere one looked you could find a wall-mounted picture, poem, or coffee table book about these species. My favorite, written by the owner of the ranch, John Hauer, was The Natural Superiority of Mules.1
- The second thing I noticed was that every member of the ranch-owning family had fairly strong opinions about which was better—horse or mule. Just to recap the biology, a horse is the product of two horses, whereas a mule is the progeny of a male donkey and a female horse. It turns out that their physical structure and demeanors are very different.
One of the oldest members of the ranch family (who I believe was a “distant uncle”) had a very strong opinion about the superiority of the mule. His opinion was based on selected facts, including that mules are “steadier on their feet” in unstable ground, require less volume and less frequent food and water, and very rarely became ill or need costly veterinary care.
Another mule-favoring family member told us how mules get a “bad rap” for being stubborn when they actually are much smarter and better decision makers than horses. She recalled a famous folklore of a farmer who took his mule out to gather materials from across a field. When the farmer and the mule approached a wooden bridge, the mule absolutely refused to cross the bridge. After much back and forth between the farmer and the mule (involving both coaxing and cussing), the farmer gave up and returned to the farm with the mule. He then took his horse on the same errand. When they came to the same bridge, the horse also hesitated but required little bargaining from the farmer to coax it to cross the bridge. When barely halfway across, a rotten board in the bridge gave way, almost sending both the horse and the farmer to their deaths in the ravine below.
The moral of the folklore is that mules cannot be coaxed (or cussed) into performing behaviors that will put themselves or those around them at risk of injury or death. Mules will stop when exhausted or profoundly dehydrated, for example, whereas a horse will continue on if ordered by their farmer, even to the point of running themselves to their eventual demise.
One of the younger members of the family-owned ranch, however, had very strong opinions on the superiority of the horse. Horses are loyal and unwavering in their dedication to please those that they serve. They will put the needs of others before themselves in most situations and therefore almost always “outperform” a mule in all respects. They are willing and (usually) able to perform in uncertain conditions, even despite some reservations. They are loyal and loving, and they have unique and inquisitive personalities, which makes them fun to raise and to ride any day.
Test Drives
Our family of four went on a ride with some of these animals and randomly got two horses and two mules. Interestingly, during our ride, we all did indeed notice the differences between the horses and the mules.
The horses were seemingly easygoing and quick to please, easily following cues to change direction or course. The mules were more hesitant and seemed to need to understand why they were being asked to do something before they acquiesced to the demand.
And when we approached a narrow rocky downslope, the mules were slow, steady, and confident, whereas the horses were seemingly uncomfortable and less agile. And, indeed in researching mules, they seem to have gotten a very bad rap over time (as evidenced by the term “stubborn as a mule”).
Charles Darwin actually categorized mules as an example of “hybrid vigor,” which is a rare example of when an offspring is actually better in most ways than either of its parents. Compared to its parental species, mules have more intelligence, endurance, longevity, health, speed, height, and agility. Also to their advantage, they have harder skin and hooves, allowing them to weather and endure more treacherous conditions.
With all of this newfound knowledge of the mule, it struck me what remarkable similarity some physicians have with mules and the role that these mules are likely serving within our organizations. These physicians are probably labeled as stubborn, obstinate, resistant, or impatient. But maybe they are actually intelligent, agile, and appropriately cautious. Maybe the resistance they express in the organization is serving to warn others about the rotten wooden bridges.
HM Takeaway
Similar to a ranch, most hospitals probably function best with a healthy combination of horses and mules. So if you get an opportunity, next time you encounter physicians at your hospital acting like mules, you should congratulate them and appreciate their mule-like characteristics. Recognize the contribution these types of physicians are making, in their own way, to the greater good of the organization.
After all, we can’t—and shouldn’t—all be horses. TH
Reference
1. Hauer J. The Natural Superiority of Mules: A Celebration of One of the Most Intelligent, Sure-footed, and Misunderstood Animals in the World. New York, NY: Skyhorse Publishing; 2006.
My family and I recently took a spring break trip out west to see a few national parks. During the trip, we stayed on a family ranch in Utah. It had a wide variety of livestock, including a large number of mules and horses.
During our stay at this family-owned ranch, two things really stood out and made me think:
- The guesthouse we stayed in had an inordinate volume of collections dedicated to the science and art of raising horses and mules. Everywhere one looked you could find a wall-mounted picture, poem, or coffee table book about these species. My favorite, written by the owner of the ranch, John Hauer, was The Natural Superiority of Mules.1
- The second thing I noticed was that every member of the ranch-owning family had fairly strong opinions about which was better—horse or mule. Just to recap the biology, a horse is the product of two horses, whereas a mule is the progeny of a male donkey and a female horse. It turns out that their physical structure and demeanors are very different.
One of the oldest members of the ranch family (who I believe was a “distant uncle”) had a very strong opinion about the superiority of the mule. His opinion was based on selected facts, including that mules are “steadier on their feet” in unstable ground, require less volume and less frequent food and water, and very rarely became ill or need costly veterinary care.
Another mule-favoring family member told us how mules get a “bad rap” for being stubborn when they actually are much smarter and better decision makers than horses. She recalled a famous folklore of a farmer who took his mule out to gather materials from across a field. When the farmer and the mule approached a wooden bridge, the mule absolutely refused to cross the bridge. After much back and forth between the farmer and the mule (involving both coaxing and cussing), the farmer gave up and returned to the farm with the mule. He then took his horse on the same errand. When they came to the same bridge, the horse also hesitated but required little bargaining from the farmer to coax it to cross the bridge. When barely halfway across, a rotten board in the bridge gave way, almost sending both the horse and the farmer to their deaths in the ravine below.
The moral of the folklore is that mules cannot be coaxed (or cussed) into performing behaviors that will put themselves or those around them at risk of injury or death. Mules will stop when exhausted or profoundly dehydrated, for example, whereas a horse will continue on if ordered by their farmer, even to the point of running themselves to their eventual demise.
One of the younger members of the family-owned ranch, however, had very strong opinions on the superiority of the horse. Horses are loyal and unwavering in their dedication to please those that they serve. They will put the needs of others before themselves in most situations and therefore almost always “outperform” a mule in all respects. They are willing and (usually) able to perform in uncertain conditions, even despite some reservations. They are loyal and loving, and they have unique and inquisitive personalities, which makes them fun to raise and to ride any day.
Test Drives
Our family of four went on a ride with some of these animals and randomly got two horses and two mules. Interestingly, during our ride, we all did indeed notice the differences between the horses and the mules.
The horses were seemingly easygoing and quick to please, easily following cues to change direction or course. The mules were more hesitant and seemed to need to understand why they were being asked to do something before they acquiesced to the demand.
And when we approached a narrow rocky downslope, the mules were slow, steady, and confident, whereas the horses were seemingly uncomfortable and less agile. And, indeed in researching mules, they seem to have gotten a very bad rap over time (as evidenced by the term “stubborn as a mule”).
Charles Darwin actually categorized mules as an example of “hybrid vigor,” which is a rare example of when an offspring is actually better in most ways than either of its parents. Compared to its parental species, mules have more intelligence, endurance, longevity, health, speed, height, and agility. Also to their advantage, they have harder skin and hooves, allowing them to weather and endure more treacherous conditions.
With all of this newfound knowledge of the mule, it struck me what remarkable similarity some physicians have with mules and the role that these mules are likely serving within our organizations. These physicians are probably labeled as stubborn, obstinate, resistant, or impatient. But maybe they are actually intelligent, agile, and appropriately cautious. Maybe the resistance they express in the organization is serving to warn others about the rotten wooden bridges.
HM Takeaway
Similar to a ranch, most hospitals probably function best with a healthy combination of horses and mules. So if you get an opportunity, next time you encounter physicians at your hospital acting like mules, you should congratulate them and appreciate their mule-like characteristics. Recognize the contribution these types of physicians are making, in their own way, to the greater good of the organization.
After all, we can’t—and shouldn’t—all be horses. TH
Reference
1. Hauer J. The Natural Superiority of Mules: A Celebration of One of the Most Intelligent, Sure-footed, and Misunderstood Animals in the World. New York, NY: Skyhorse Publishing; 2006.
My family and I recently took a spring break trip out west to see a few national parks. During the trip, we stayed on a family ranch in Utah. It had a wide variety of livestock, including a large number of mules and horses.
During our stay at this family-owned ranch, two things really stood out and made me think:
- The guesthouse we stayed in had an inordinate volume of collections dedicated to the science and art of raising horses and mules. Everywhere one looked you could find a wall-mounted picture, poem, or coffee table book about these species. My favorite, written by the owner of the ranch, John Hauer, was The Natural Superiority of Mules.1
- The second thing I noticed was that every member of the ranch-owning family had fairly strong opinions about which was better—horse or mule. Just to recap the biology, a horse is the product of two horses, whereas a mule is the progeny of a male donkey and a female horse. It turns out that their physical structure and demeanors are very different.
One of the oldest members of the ranch family (who I believe was a “distant uncle”) had a very strong opinion about the superiority of the mule. His opinion was based on selected facts, including that mules are “steadier on their feet” in unstable ground, require less volume and less frequent food and water, and very rarely became ill or need costly veterinary care.
Another mule-favoring family member told us how mules get a “bad rap” for being stubborn when they actually are much smarter and better decision makers than horses. She recalled a famous folklore of a farmer who took his mule out to gather materials from across a field. When the farmer and the mule approached a wooden bridge, the mule absolutely refused to cross the bridge. After much back and forth between the farmer and the mule (involving both coaxing and cussing), the farmer gave up and returned to the farm with the mule. He then took his horse on the same errand. When they came to the same bridge, the horse also hesitated but required little bargaining from the farmer to coax it to cross the bridge. When barely halfway across, a rotten board in the bridge gave way, almost sending both the horse and the farmer to their deaths in the ravine below.
The moral of the folklore is that mules cannot be coaxed (or cussed) into performing behaviors that will put themselves or those around them at risk of injury or death. Mules will stop when exhausted or profoundly dehydrated, for example, whereas a horse will continue on if ordered by their farmer, even to the point of running themselves to their eventual demise.
One of the younger members of the family-owned ranch, however, had very strong opinions on the superiority of the horse. Horses are loyal and unwavering in their dedication to please those that they serve. They will put the needs of others before themselves in most situations and therefore almost always “outperform” a mule in all respects. They are willing and (usually) able to perform in uncertain conditions, even despite some reservations. They are loyal and loving, and they have unique and inquisitive personalities, which makes them fun to raise and to ride any day.
Test Drives
Our family of four went on a ride with some of these animals and randomly got two horses and two mules. Interestingly, during our ride, we all did indeed notice the differences between the horses and the mules.
The horses were seemingly easygoing and quick to please, easily following cues to change direction or course. The mules were more hesitant and seemed to need to understand why they were being asked to do something before they acquiesced to the demand.
And when we approached a narrow rocky downslope, the mules were slow, steady, and confident, whereas the horses were seemingly uncomfortable and less agile. And, indeed in researching mules, they seem to have gotten a very bad rap over time (as evidenced by the term “stubborn as a mule”).
Charles Darwin actually categorized mules as an example of “hybrid vigor,” which is a rare example of when an offspring is actually better in most ways than either of its parents. Compared to its parental species, mules have more intelligence, endurance, longevity, health, speed, height, and agility. Also to their advantage, they have harder skin and hooves, allowing them to weather and endure more treacherous conditions.
With all of this newfound knowledge of the mule, it struck me what remarkable similarity some physicians have with mules and the role that these mules are likely serving within our organizations. These physicians are probably labeled as stubborn, obstinate, resistant, or impatient. But maybe they are actually intelligent, agile, and appropriately cautious. Maybe the resistance they express in the organization is serving to warn others about the rotten wooden bridges.
HM Takeaway
Similar to a ranch, most hospitals probably function best with a healthy combination of horses and mules. So if you get an opportunity, next time you encounter physicians at your hospital acting like mules, you should congratulate them and appreciate their mule-like characteristics. Recognize the contribution these types of physicians are making, in their own way, to the greater good of the organization.
After all, we can’t—and shouldn’t—all be horses. TH
Reference
1. Hauer J. The Natural Superiority of Mules: A Celebration of One of the Most Intelligent, Sure-footed, and Misunderstood Animals in the World. New York, NY: Skyhorse Publishing; 2006.
Drug can address unmet need in cHL, doc says
COPENHAGEN—The PD-1 checkpoint inhibitor nivolumab can address an unmet need in patients with classical Hodgkin lymphoma (cHL) who have progressive or relapsed disease, according to a speaker at the 21st Congress of the European Hematology Association.
In the phase 2 Checkmate-205 trial, nivolumab produced an objective response rate of 66% in cHL patients who had relapsed or progressed after autologous hematopoietic stem cell transplant (HSCT) and subsequent brentuximab vedotin.
The median duration of response was 7.8 months, and most patients had a response that was ongoing at the time of analysis.
Although the safety profile of nivolumab was considered “acceptable” by researchers, the drug has been linked to serious complications, including death, among patients who proceeded to allogeneic HSCT after receiving nivolumab.
Still, nivolumab is “an important new therapy to meet the unmet need” in cHL, according to Anas Younes, MD, of Memorial Sloan Kettering Cancer Center in New York, New York.
Dr Younes presented results with nivolumab from cohort B of the Checkmate-205 trial as abstract S793. Checkmate-205 was sponsored by Bristol-Myers Squibb.
Cohort B included 80 cHL patients who had relapsed or progressed after autologous HSCT and post-transplant brentuximab vedotin. (Cohort A included patients who had not previously received brentuximab vedotin.)
The patients’ median age was 37 (range, 18-72), and 64% were male. The median number of prior lines of therapy was 4 (range, 3-15), and 49% of patients had received at least 5 previous lines of therapy.
Seventy-four percent of patients had previously received radiation, 93% had received 1 prior autologous HSCT, and 8% had received 2. All patients had received brentuximab vedotin after transplant, and 54% had not responded to that treatment.
Study treatment
Patients received nivolumab at 3 mg/kg intravenously every 2 weeks until disease progression or unacceptable toxicity.
At a median follow-up of 8.9 months (range, 1.9-11.7), 36% of patients had come off treatment—16% due to disease progression, 5% due to toxicity, 8% because they had gone on to allogeneic HSCT, and 8% for other reasons (the patient’s request, the investigator’s decision, the patient was lost to follow-up, or the reason was not reported).
Dr Younes noted that all patients who stopped nivolumab to undergo HSCT were still alive at the data cut-off.
Efficacy
The objective response rate, per an independent radiologic review committee, was 66%. Nine percent of patients achieved a complete response, 58% had a partial response, 23% had stable disease, and 8% had progressive disease. The committee was unable to determine the status of 4% of patients.
The median time to response was 2.1 months, and the estimated median duration of response was 7.8 months.
“Keep in mind that the majority of patients are still on therapy, so this is expected to improve with time,” Dr Younes said.
The majority of responses (62%) were ongoing at the time of analysis. In an exploratory analysis, the researchers observed that 72% of patients who did not respond to their most recent prior brentuximab vedotin treatment did respond to nivolumab.
At 6 months, the progression-free survival rate was 77%, and the overall survival rate was 99%. The median progression-free survival was 10 months, and the median overall survival has not been reached.
Dr Younes said that, although the follow-up is short, the survival data are “still impressive.”
Safety
Adverse events (AEs) occurred in 99% of patients, grade 3/4 AEs occurred in 40% of patients, and there was 1 grade 5 AE (multi-organ failure due to Epstein-Barr-virus-positive T-cell lymphoma).
Treatment-related AEs occurred in 90% of patients. The most common of these were fatigue (25%), infusion-related reactions (20%), rash (16%), arthralgia (14%), pyrexia (14%), nausea (13%), diarrhea (10%), and pruritus (10%).
Treatment-related serious AEs occurred in 6% of patients and included pyrexia, tumor progression, arrhythmia, infusion reactions, septic meningitis, and pneumonia.
Extended safety follow-up of cHL patients treated in the nivolumab clinical trial program who were subsequently treated with allogeneic HSCT (n=17) revealed complications, including fatal events.
A warning about such complications has been added to the US prescribing information for nivolumab, which was recently granted accelerated approval from the US Food and Drug Administration (FDA) to treat patients with relapsed or refractory cHL who have received an autologous HSCT and post-transplant brentuximab vedotin.
Because of these transplant-related deaths, the FDA has advised that healthcare professionals follow patients closely for early evidence of transplant-related complications, such as hyperacute graft-versus-host disease, severe acute graft-versus-host disease, steroid-requiring febrile syndrome, hepatic veno-occlusive disease, and other immune-mediated adverse reactions.
The FDA has also required that Bristol-Myers Squibb further study the safety of allogeneic HSCT after nivolumab. 
COPENHAGEN—The PD-1 checkpoint inhibitor nivolumab can address an unmet need in patients with classical Hodgkin lymphoma (cHL) who have progressive or relapsed disease, according to a speaker at the 21st Congress of the European Hematology Association.
In the phase 2 Checkmate-205 trial, nivolumab produced an objective response rate of 66% in cHL patients who had relapsed or progressed after autologous hematopoietic stem cell transplant (HSCT) and subsequent brentuximab vedotin.
The median duration of response was 7.8 months, and most patients had a response that was ongoing at the time of analysis.
Although the safety profile of nivolumab was considered “acceptable” by researchers, the drug has been linked to serious complications, including death, among patients who proceeded to allogeneic HSCT after receiving nivolumab.
Still, nivolumab is “an important new therapy to meet the unmet need” in cHL, according to Anas Younes, MD, of Memorial Sloan Kettering Cancer Center in New York, New York.
Dr Younes presented results with nivolumab from cohort B of the Checkmate-205 trial as abstract S793. Checkmate-205 was sponsored by Bristol-Myers Squibb.
Cohort B included 80 cHL patients who had relapsed or progressed after autologous HSCT and post-transplant brentuximab vedotin. (Cohort A included patients who had not previously received brentuximab vedotin.)
The patients’ median age was 37 (range, 18-72), and 64% were male. The median number of prior lines of therapy was 4 (range, 3-15), and 49% of patients had received at least 5 previous lines of therapy.
Seventy-four percent of patients had previously received radiation, 93% had received 1 prior autologous HSCT, and 8% had received 2. All patients had received brentuximab vedotin after transplant, and 54% had not responded to that treatment.
Study treatment
Patients received nivolumab at 3 mg/kg intravenously every 2 weeks until disease progression or unacceptable toxicity.
At a median follow-up of 8.9 months (range, 1.9-11.7), 36% of patients had come off treatment—16% due to disease progression, 5% due to toxicity, 8% because they had gone on to allogeneic HSCT, and 8% for other reasons (the patient’s request, the investigator’s decision, the patient was lost to follow-up, or the reason was not reported).
Dr Younes noted that all patients who stopped nivolumab to undergo HSCT were still alive at the data cut-off.
Efficacy
The objective response rate, per an independent radiologic review committee, was 66%. Nine percent of patients achieved a complete response, 58% had a partial response, 23% had stable disease, and 8% had progressive disease. The committee was unable to determine the status of 4% of patients.
The median time to response was 2.1 months, and the estimated median duration of response was 7.8 months.
“Keep in mind that the majority of patients are still on therapy, so this is expected to improve with time,” Dr Younes said.
The majority of responses (62%) were ongoing at the time of analysis. In an exploratory analysis, the researchers observed that 72% of patients who did not respond to their most recent prior brentuximab vedotin treatment did respond to nivolumab.
At 6 months, the progression-free survival rate was 77%, and the overall survival rate was 99%. The median progression-free survival was 10 months, and the median overall survival has not been reached.
Dr Younes said that, although the follow-up is short, the survival data are “still impressive.”
Safety
Adverse events (AEs) occurred in 99% of patients, grade 3/4 AEs occurred in 40% of patients, and there was 1 grade 5 AE (multi-organ failure due to Epstein-Barr-virus-positive T-cell lymphoma).
Treatment-related AEs occurred in 90% of patients. The most common of these were fatigue (25%), infusion-related reactions (20%), rash (16%), arthralgia (14%), pyrexia (14%), nausea (13%), diarrhea (10%), and pruritus (10%).
Treatment-related serious AEs occurred in 6% of patients and included pyrexia, tumor progression, arrhythmia, infusion reactions, septic meningitis, and pneumonia.
Extended safety follow-up of cHL patients treated in the nivolumab clinical trial program who were subsequently treated with allogeneic HSCT (n=17) revealed complications, including fatal events.
A warning about such complications has been added to the US prescribing information for nivolumab, which was recently granted accelerated approval from the US Food and Drug Administration (FDA) to treat patients with relapsed or refractory cHL who have received an autologous HSCT and post-transplant brentuximab vedotin.
Because of these transplant-related deaths, the FDA has advised that healthcare professionals follow patients closely for early evidence of transplant-related complications, such as hyperacute graft-versus-host disease, severe acute graft-versus-host disease, steroid-requiring febrile syndrome, hepatic veno-occlusive disease, and other immune-mediated adverse reactions.
The FDA has also required that Bristol-Myers Squibb further study the safety of allogeneic HSCT after nivolumab.
COPENHAGEN—The PD-1 checkpoint inhibitor nivolumab can address an unmet need in patients with classical Hodgkin lymphoma (cHL) who have progressive or relapsed disease, according to a speaker at the 21st Congress of the European Hematology Association.
In the phase 2 Checkmate-205 trial, nivolumab produced an objective response rate of 66% in cHL patients who had relapsed or progressed after autologous hematopoietic stem cell transplant (HSCT) and subsequent brentuximab vedotin.
The median duration of response was 7.8 months, and most patients had a response that was ongoing at the time of analysis.
Although the safety profile of nivolumab was considered “acceptable” by researchers, the drug has been linked to serious complications, including death, among patients who proceeded to allogeneic HSCT after receiving nivolumab.
Still, nivolumab is “an important new therapy to meet the unmet need” in cHL, according to Anas Younes, MD, of Memorial Sloan Kettering Cancer Center in New York, New York.
Dr Younes presented results with nivolumab from cohort B of the Checkmate-205 trial as abstract S793. Checkmate-205 was sponsored by Bristol-Myers Squibb.
Cohort B included 80 cHL patients who had relapsed or progressed after autologous HSCT and post-transplant brentuximab vedotin. (Cohort A included patients who had not previously received brentuximab vedotin.)
The patients’ median age was 37 (range, 18-72), and 64% were male. The median number of prior lines of therapy was 4 (range, 3-15), and 49% of patients had received at least 5 previous lines of therapy.
Seventy-four percent of patients had previously received radiation, 93% had received 1 prior autologous HSCT, and 8% had received 2. All patients had received brentuximab vedotin after transplant, and 54% had not responded to that treatment.
Study treatment
Patients received nivolumab at 3 mg/kg intravenously every 2 weeks until disease progression or unacceptable toxicity.
At a median follow-up of 8.9 months (range, 1.9-11.7), 36% of patients had come off treatment—16% due to disease progression, 5% due to toxicity, 8% because they had gone on to allogeneic HSCT, and 8% for other reasons (the patient’s request, the investigator’s decision, the patient was lost to follow-up, or the reason was not reported).
Dr Younes noted that all patients who stopped nivolumab to undergo HSCT were still alive at the data cut-off.
Efficacy
The objective response rate, per an independent radiologic review committee, was 66%. Nine percent of patients achieved a complete response, 58% had a partial response, 23% had stable disease, and 8% had progressive disease. The committee was unable to determine the status of 4% of patients.
The median time to response was 2.1 months, and the estimated median duration of response was 7.8 months.
“Keep in mind that the majority of patients are still on therapy, so this is expected to improve with time,” Dr Younes said.
The majority of responses (62%) were ongoing at the time of analysis. In an exploratory analysis, the researchers observed that 72% of patients who did not respond to their most recent prior brentuximab vedotin treatment did respond to nivolumab.
At 6 months, the progression-free survival rate was 77%, and the overall survival rate was 99%. The median progression-free survival was 10 months, and the median overall survival has not been reached.
Dr Younes said that, although the follow-up is short, the survival data are “still impressive.”
Safety
Adverse events (AEs) occurred in 99% of patients, grade 3/4 AEs occurred in 40% of patients, and there was 1 grade 5 AE (multi-organ failure due to Epstein-Barr-virus-positive T-cell lymphoma).
Treatment-related AEs occurred in 90% of patients. The most common of these were fatigue (25%), infusion-related reactions (20%), rash (16%), arthralgia (14%), pyrexia (14%), nausea (13%), diarrhea (10%), and pruritus (10%).
Treatment-related serious AEs occurred in 6% of patients and included pyrexia, tumor progression, arrhythmia, infusion reactions, septic meningitis, and pneumonia.
Extended safety follow-up of cHL patients treated in the nivolumab clinical trial program who were subsequently treated with allogeneic HSCT (n=17) revealed complications, including fatal events.
A warning about such complications has been added to the US prescribing information for nivolumab, which was recently granted accelerated approval from the US Food and Drug Administration (FDA) to treat patients with relapsed or refractory cHL who have received an autologous HSCT and post-transplant brentuximab vedotin.
Because of these transplant-related deaths, the FDA has advised that healthcare professionals follow patients closely for early evidence of transplant-related complications, such as hyperacute graft-versus-host disease, severe acute graft-versus-host disease, steroid-requiring febrile syndrome, hepatic veno-occlusive disease, and other immune-mediated adverse reactions.
The FDA has also required that Bristol-Myers Squibb further study the safety of allogeneic HSCT after nivolumab.
AGA Research Foundation announces 2016 class of Research Award winners
At Digestive Disease Week® 2016, the AGA Research Foundation honored its 2016 class of Research Award winners. The AGA Research Awards Program serves to support talented investigators who are pursuing careers in digestive disease research. A research grant from the AGA Research Foundation ensures that a major proportion of the recipient’s time is protected for research.
“The AGA Research Foundation received a record number of applications in 2016 from young investigators working to advance our understanding of digestive and liver diseases,” said Robert S. Sandler, MD, MPH, AGAF, incoming chair of the AGA Research Foundation. “AGA is proud to invest in these 66 talented scientists and looks forward to seeing how each of their research projects will ultimately lead to better care for patients suffering from digestive disorders.”
The AGA Research Awards Program is made possible thanks to the foundation’s generous donors. To show your support for GI research, visit www.gastro.org/donateonline.
The 2016 AGA Research Foundation award recipients can be found here. To learn about upcoming research funding opportunities, visit www.gastro.org/awards.
At Digestive Disease Week® 2016, the AGA Research Foundation honored its 2016 class of Research Award winners. The AGA Research Awards Program serves to support talented investigators who are pursuing careers in digestive disease research. A research grant from the AGA Research Foundation ensures that a major proportion of the recipient’s time is protected for research.
“The AGA Research Foundation received a record number of applications in 2016 from young investigators working to advance our understanding of digestive and liver diseases,” said Robert S. Sandler, MD, MPH, AGAF, incoming chair of the AGA Research Foundation. “AGA is proud to invest in these 66 talented scientists and looks forward to seeing how each of their research projects will ultimately lead to better care for patients suffering from digestive disorders.”
The AGA Research Awards Program is made possible thanks to the foundation’s generous donors. To show your support for GI research, visit www.gastro.org/donateonline.
The 2016 AGA Research Foundation award recipients can be found here. To learn about upcoming research funding opportunities, visit www.gastro.org/awards.
At Digestive Disease Week® 2016, the AGA Research Foundation honored its 2016 class of Research Award winners. The AGA Research Awards Program serves to support talented investigators who are pursuing careers in digestive disease research. A research grant from the AGA Research Foundation ensures that a major proportion of the recipient’s time is protected for research.
“The AGA Research Foundation received a record number of applications in 2016 from young investigators working to advance our understanding of digestive and liver diseases,” said Robert S. Sandler, MD, MPH, AGAF, incoming chair of the AGA Research Foundation. “AGA is proud to invest in these 66 talented scientists and looks forward to seeing how each of their research projects will ultimately lead to better care for patients suffering from digestive disorders.”
The AGA Research Awards Program is made possible thanks to the foundation’s generous donors. To show your support for GI research, visit www.gastro.org/donateonline.
The 2016 AGA Research Foundation award recipients can be found here. To learn about upcoming research funding opportunities, visit www.gastro.org/awards.
Finding Alternatives to Open Surgical Resection for Patients With Epilepsy
Although open surgical resection is considered the gold standard for patients with epilepsy who do not respond to medical therapy, there are several viable alternatives, according to Englot and associates writing in Neurosurgical Review. Among the minimally invasive procedures to consider: stereotactic laser ablation and stereotactic radiosurgery, which the researchers say can offer relatively favorable seizure outcomes, especially in patients with mesial temporary lobe epilepsy. Other options include multiple subpial transections and corpus callosotomy in select patients. Among the palliative procedures to consider are vagus nerve stimulation, deep brain stimulation, and responsive neurostimulation, which the authors say may significantly decrease seizure frequency and improve quality of life.
Englot DJ, Birk H, Chang EF. Seizure outcomes in nonresective epilepsy surgery: an update. Neurosurg Rev. 2016; May 21 [Epub ahead of print]
Although open surgical resection is considered the gold standard for patients with epilepsy who do not respond to medical therapy, there are several viable alternatives, according to Englot and associates writing in Neurosurgical Review. Among the minimally invasive procedures to consider: stereotactic laser ablation and stereotactic radiosurgery, which the researchers say can offer relatively favorable seizure outcomes, especially in patients with mesial temporary lobe epilepsy. Other options include multiple subpial transections and corpus callosotomy in select patients. Among the palliative procedures to consider are vagus nerve stimulation, deep brain stimulation, and responsive neurostimulation, which the authors say may significantly decrease seizure frequency and improve quality of life.
Englot DJ, Birk H, Chang EF. Seizure outcomes in nonresective epilepsy surgery: an update. Neurosurg Rev. 2016; May 21 [Epub ahead of print]
Although open surgical resection is considered the gold standard for patients with epilepsy who do not respond to medical therapy, there are several viable alternatives, according to Englot and associates writing in Neurosurgical Review. Among the minimally invasive procedures to consider: stereotactic laser ablation and stereotactic radiosurgery, which the researchers say can offer relatively favorable seizure outcomes, especially in patients with mesial temporary lobe epilepsy. Other options include multiple subpial transections and corpus callosotomy in select patients. Among the palliative procedures to consider are vagus nerve stimulation, deep brain stimulation, and responsive neurostimulation, which the authors say may significantly decrease seizure frequency and improve quality of life.
Englot DJ, Birk H, Chang EF. Seizure outcomes in nonresective epilepsy surgery: an update. Neurosurg Rev. 2016; May 21 [Epub ahead of print]
Patients with Epilepsy with Chromosome 15 Duplications Face Increased Risk of Sudden Death
In order to determine how common sudden unexpected death from epilepsy (SUDEP) is in people with an extra isodicentric 15 chromosome (idic15), researchers studied approximately 709 families registered with the Dup15Q Alliance. Their case-control study found 19 deaths among patients with idic15, 17 of whom had epilepsy. Nine of these deaths were caused by probable or definite SUDEP; 2 others had what investigators considered possible SUDEP. Researchers concluded that SUDEP is common among children and young adults with duplications of the idic15 chromosome and that the risk of death is most likely to occur in patients with the most severe neurologic dysfunction.
Friedman D, Thaler A, Thaler J et al. Mortality in isodicentric chromosome 15 syndrome: the role of SUDEP. Epilepsy Behav. 2016;61:1-5.
In order to determine how common sudden unexpected death from epilepsy (SUDEP) is in people with an extra isodicentric 15 chromosome (idic15), researchers studied approximately 709 families registered with the Dup15Q Alliance. Their case-control study found 19 deaths among patients with idic15, 17 of whom had epilepsy. Nine of these deaths were caused by probable or definite SUDEP; 2 others had what investigators considered possible SUDEP. Researchers concluded that SUDEP is common among children and young adults with duplications of the idic15 chromosome and that the risk of death is most likely to occur in patients with the most severe neurologic dysfunction.
Friedman D, Thaler A, Thaler J et al. Mortality in isodicentric chromosome 15 syndrome: the role of SUDEP. Epilepsy Behav. 2016;61:1-5.
In order to determine how common sudden unexpected death from epilepsy (SUDEP) is in people with an extra isodicentric 15 chromosome (idic15), researchers studied approximately 709 families registered with the Dup15Q Alliance. Their case-control study found 19 deaths among patients with idic15, 17 of whom had epilepsy. Nine of these deaths were caused by probable or definite SUDEP; 2 others had what investigators considered possible SUDEP. Researchers concluded that SUDEP is common among children and young adults with duplications of the idic15 chromosome and that the risk of death is most likely to occur in patients with the most severe neurologic dysfunction.
Friedman D, Thaler A, Thaler J et al. Mortality in isodicentric chromosome 15 syndrome: the role of SUDEP. Epilepsy Behav. 2016;61:1-5.
Adult Epilepsy Surgeries Have “Flatlined”
Contrary to conventional wisdom, the epilepsy surgery rate among adults in North America has remained stagnant according to a recent analysis of data from the Centers for Medicare and Medicaid Services Part B National Summary Data File and the American College of Surgeons National Surgical Quality Improvement Program. A review of 6200 surgeries performed from 2000 to 2013 revealed that temporal lobectomy, the most common operation, was done in 59% of patients, but surgical rates for temporal and extra-temporal surgery did not change significantly during the study period. The researchers concluded that the findings in this study contrasted with previously published reports that suggested a dramatic decline in temporal lobectomy rates at high volume epilepsy centers in recent years. However, investigators did find that surgical adverse effects were higher when statistics from low and high volume centers were combined.
Rolston JD, Englot DJ, Knowlton RC, Chang EF. Rate and complications of adult epilepsy surgery in North America: Analysis of multiple databases. Epilepsy Res. 2016;124:55-62.
Contrary to conventional wisdom, the epilepsy surgery rate among adults in North America has remained stagnant according to a recent analysis of data from the Centers for Medicare and Medicaid Services Part B National Summary Data File and the American College of Surgeons National Surgical Quality Improvement Program. A review of 6200 surgeries performed from 2000 to 2013 revealed that temporal lobectomy, the most common operation, was done in 59% of patients, but surgical rates for temporal and extra-temporal surgery did not change significantly during the study period. The researchers concluded that the findings in this study contrasted with previously published reports that suggested a dramatic decline in temporal lobectomy rates at high volume epilepsy centers in recent years. However, investigators did find that surgical adverse effects were higher when statistics from low and high volume centers were combined.
Rolston JD, Englot DJ, Knowlton RC, Chang EF. Rate and complications of adult epilepsy surgery in North America: Analysis of multiple databases. Epilepsy Res. 2016;124:55-62.
Contrary to conventional wisdom, the epilepsy surgery rate among adults in North America has remained stagnant according to a recent analysis of data from the Centers for Medicare and Medicaid Services Part B National Summary Data File and the American College of Surgeons National Surgical Quality Improvement Program. A review of 6200 surgeries performed from 2000 to 2013 revealed that temporal lobectomy, the most common operation, was done in 59% of patients, but surgical rates for temporal and extra-temporal surgery did not change significantly during the study period. The researchers concluded that the findings in this study contrasted with previously published reports that suggested a dramatic decline in temporal lobectomy rates at high volume epilepsy centers in recent years. However, investigators did find that surgical adverse effects were higher when statistics from low and high volume centers were combined.
Rolston JD, Englot DJ, Knowlton RC, Chang EF. Rate and complications of adult epilepsy surgery in North America: Analysis of multiple databases. Epilepsy Res. 2016;124:55-62.
AGA Governing Board welcomes new members at DDW® 2016
The new AGA Institute Governing Board began its term immediately following Digestive Disease Week® (DDW) 2016. In addition to Timothy Wang, MD, AGAF, of Columbia University, who began his term as the 111th president of AGA Institute, the other 2016-2017 board members include:
• Sheila E. Crowe, MD, AGAF, President-Elect
• David A. Lieberman, MD, AGAF, Vice President
• Francis M. Giardiello, MD, AGAF, Secretary/Treasurer
• Michael Camilleri, MD, AGAF, Past President
Additionally, the Councillors of the 2016-2017 board include:
• Marcia R. Cruz-Correa, MD, PhD, AGAF, At-Large Councillor
• Gregory J. Gores, MD, AGAF, Basic Research Councillor
• John M. Inadomi, MD, AGAF, Clinical Research Councillor
• Rajeev Jain, MD, AGAF, Practice Councillor
• Lawrence R. Kosinski, MD, MBA, AGAF, Practice Councillor
• Deborah D. Proctor, MD, AGAF, Education & Training Councillor
• Robert S. Sandler, MD, MPH, AGAF, AGA Research Foundation Chair
AGA also thanks the outgoing board members for their service, including John Allen, MD, MBA; Martin Brotman, MD; Byron Cryer, MD; and Suzanne Rose, MD, MSed. AGA congratulates both the incoming and outgoing board members, and thanks them for their commitment to advancing the science and practice of gastroenterology.
The new AGA Institute Governing Board began its term immediately following Digestive Disease Week® (DDW) 2016. In addition to Timothy Wang, MD, AGAF, of Columbia University, who began his term as the 111th president of AGA Institute, the other 2016-2017 board members include:
• Sheila E. Crowe, MD, AGAF, President-Elect
• David A. Lieberman, MD, AGAF, Vice President
• Francis M. Giardiello, MD, AGAF, Secretary/Treasurer
• Michael Camilleri, MD, AGAF, Past President
Additionally, the Councillors of the 2016-2017 board include:
• Marcia R. Cruz-Correa, MD, PhD, AGAF, At-Large Councillor
• Gregory J. Gores, MD, AGAF, Basic Research Councillor
• John M. Inadomi, MD, AGAF, Clinical Research Councillor
• Rajeev Jain, MD, AGAF, Practice Councillor
• Lawrence R. Kosinski, MD, MBA, AGAF, Practice Councillor
• Deborah D. Proctor, MD, AGAF, Education & Training Councillor
• Robert S. Sandler, MD, MPH, AGAF, AGA Research Foundation Chair
AGA also thanks the outgoing board members for their service, including John Allen, MD, MBA; Martin Brotman, MD; Byron Cryer, MD; and Suzanne Rose, MD, MSed. AGA congratulates both the incoming and outgoing board members, and thanks them for their commitment to advancing the science and practice of gastroenterology.
The new AGA Institute Governing Board began its term immediately following Digestive Disease Week® (DDW) 2016. In addition to Timothy Wang, MD, AGAF, of Columbia University, who began his term as the 111th president of AGA Institute, the other 2016-2017 board members include:
• Sheila E. Crowe, MD, AGAF, President-Elect
• David A. Lieberman, MD, AGAF, Vice President
• Francis M. Giardiello, MD, AGAF, Secretary/Treasurer
• Michael Camilleri, MD, AGAF, Past President
Additionally, the Councillors of the 2016-2017 board include:
• Marcia R. Cruz-Correa, MD, PhD, AGAF, At-Large Councillor
• Gregory J. Gores, MD, AGAF, Basic Research Councillor
• John M. Inadomi, MD, AGAF, Clinical Research Councillor
• Rajeev Jain, MD, AGAF, Practice Councillor
• Lawrence R. Kosinski, MD, MBA, AGAF, Practice Councillor
• Deborah D. Proctor, MD, AGAF, Education & Training Councillor
• Robert S. Sandler, MD, MPH, AGAF, AGA Research Foundation Chair
AGA also thanks the outgoing board members for their service, including John Allen, MD, MBA; Martin Brotman, MD; Byron Cryer, MD; and Suzanne Rose, MD, MSed. AGA congratulates both the incoming and outgoing board members, and thanks them for their commitment to advancing the science and practice of gastroenterology.
AGA joins campaign for sustainable Rx pricing
This June AGA announced it has joined the Campaign for Sustainable Rx Pricing (CSRxP), a broad-based campaign that works to curb rising drug costs.
“Gastroenterologists have a unique view of rising drug prices because the patients they treat are subjected to some of the most expensive medications on the market,” said CSRxP Executive Director John Rother, noting pricey hepatitis C medications, injectables, and other specialty drugs that often force patients to delay or forgo treatment because of cost. “AGA’s voice is a welcome addition to our diverse campaign as we call on policy makers to increase transparency, competition, and value in the prescription drug market.”
“Given that some of the most expensive drugs on the market are drugs that treat GI and hepatology diseases, I believe it is important that AGA be part of the dialogue addressing drug costs. These treatments have been revolutionary and lifesaving, but we need to ensure that all patients have access to the right treatments and are not prevented from receiving the proper therapy because of cost. AGA looks forward to working with the coalition and policy makers on finding common-sense solutions to address the growing problem of drug prices,” said Dr. Timothy C. Wang, AGAF, AGA Institute president.
Prices for specialty drugs, which require special handling, administration, or monitoring, are one of the largest drivers of increased health care costs, even for those who do not use medication. Today, prescription drug expenditures are nearly 20% of health care costs and prescription spending is growing faster than any other part of the health care dollar, according to data from IMS and Medicare Payment Advisory Commission. Additionally, IMS found that spending on specialty medicines has increased by $54 billion over the past 5 years, accounting for 73% of all medicine spending growth.
This June AGA announced it has joined the Campaign for Sustainable Rx Pricing (CSRxP), a broad-based campaign that works to curb rising drug costs.
“Gastroenterologists have a unique view of rising drug prices because the patients they treat are subjected to some of the most expensive medications on the market,” said CSRxP Executive Director John Rother, noting pricey hepatitis C medications, injectables, and other specialty drugs that often force patients to delay or forgo treatment because of cost. “AGA’s voice is a welcome addition to our diverse campaign as we call on policy makers to increase transparency, competition, and value in the prescription drug market.”
“Given that some of the most expensive drugs on the market are drugs that treat GI and hepatology diseases, I believe it is important that AGA be part of the dialogue addressing drug costs. These treatments have been revolutionary and lifesaving, but we need to ensure that all patients have access to the right treatments and are not prevented from receiving the proper therapy because of cost. AGA looks forward to working with the coalition and policy makers on finding common-sense solutions to address the growing problem of drug prices,” said Dr. Timothy C. Wang, AGAF, AGA Institute president.
Prices for specialty drugs, which require special handling, administration, or monitoring, are one of the largest drivers of increased health care costs, even for those who do not use medication. Today, prescription drug expenditures are nearly 20% of health care costs and prescription spending is growing faster than any other part of the health care dollar, according to data from IMS and Medicare Payment Advisory Commission. Additionally, IMS found that spending on specialty medicines has increased by $54 billion over the past 5 years, accounting for 73% of all medicine spending growth.
This June AGA announced it has joined the Campaign for Sustainable Rx Pricing (CSRxP), a broad-based campaign that works to curb rising drug costs.
“Gastroenterologists have a unique view of rising drug prices because the patients they treat are subjected to some of the most expensive medications on the market,” said CSRxP Executive Director John Rother, noting pricey hepatitis C medications, injectables, and other specialty drugs that often force patients to delay or forgo treatment because of cost. “AGA’s voice is a welcome addition to our diverse campaign as we call on policy makers to increase transparency, competition, and value in the prescription drug market.”
“Given that some of the most expensive drugs on the market are drugs that treat GI and hepatology diseases, I believe it is important that AGA be part of the dialogue addressing drug costs. These treatments have been revolutionary and lifesaving, but we need to ensure that all patients have access to the right treatments and are not prevented from receiving the proper therapy because of cost. AGA looks forward to working with the coalition and policy makers on finding common-sense solutions to address the growing problem of drug prices,” said Dr. Timothy C. Wang, AGAF, AGA Institute president.
Prices for specialty drugs, which require special handling, administration, or monitoring, are one of the largest drivers of increased health care costs, even for those who do not use medication. Today, prescription drug expenditures are nearly 20% of health care costs and prescription spending is growing faster than any other part of the health care dollar, according to data from IMS and Medicare Payment Advisory Commission. Additionally, IMS found that spending on specialty medicines has increased by $54 billion over the past 5 years, accounting for 73% of all medicine spending growth.
