The spleen stiffness (SS) to liver stiffness (LS) ratio was significantly higher in patients with hepatitis C virus infection (HCV) than in patients with alcohol-related liver disease (ALD), according to the results of a multicenter prospective study. In addition, long-term outcome and complications differed dramatically between HCV and ALD. Variceal bleeding was the most common sign of decompensation and cause of death in patients with HCV, while jaundice was the most common sign of decompensation in patients with ALD.

©pixologicstudio/thinkstockphotos.com

Omar Elshaarawy, MSc, of the University of Heidelberg (Germany) and colleagues reported on their prospective study of 411 patients with HCV (220 patients) or ALD (191 patients) that were assessed for both LS and SS using the Fibroscan device. They also discussed their retrospective analysis of LS and spleen length (SL) from a separate, retrospective cohort of 449 patients (267 with HCV, 182 with ALD) for whom long-term data on decompensation/death were available.

The researchers found that SS was significantly higher in HCV patients, compared with those with ALD (42.0 vs. 32.6 kPa; P less than .0001), as was SL (15.6 vs. 11.9 cm, P less than .0001); this was despite a lower mean LS in HCV. As a result, the SS/LS ratio and the SL/LS ratio were both significantly higher in HCV (3.8 vs. 1.72 and 1.46 vs. 0.86, P less than .0001) through all fibrosis stages.

They also found that patients with ALD had higher LS values (30.5 vs. 21.3 kPa) and predominantly presented with jaundice (65.2%), with liver failure as the major cause of death (P less than .01). In contrast, in HCV, spleens were larger (17.6 vs. 12.1 cm) while variceal bleeding was the major cause of decompensation (73.2%) and death (P less than .001).

“We have demonstrated the disease-specific differences in SS/LS and SL/LS ratio between HCV and ALD. They underscore the role of the intrahepatic histological site of inflammation/fibrosis. We suggest that the SS/LS ratio could be used to confirm the disease etiology and predict disease-specific complications,” the researchers concluded.

The study was supported by the Dietmar Hopp Foundation. The authors reported they had no conflicts.

mlesney@mdedge.com

SOURCE: Elshaarawy O et al. J Hepatol Reports. 2019 Jun 20. doi: 10.1016/j.jhepr.2019.05.003.

The spleen stiffness (SS) to liver stiffness (LS) ratio was significantly higher in patients with hepatitis C virus infection (HCV) than in patients with alcohol-related liver disease (ALD), according to the results of a multicenter prospective study. In addition, long-term outcome and complications differed dramatically between HCV and ALD. Variceal bleeding was the most common sign of decompensation and cause of death in patients with HCV, while jaundice was the most common sign of decompensation in patients with ALD.

©pixologicstudio/thinkstockphotos.com

Omar Elshaarawy, MSc, of the University of Heidelberg (Germany) and colleagues reported on their prospective study of 411 patients with HCV (220 patients) or ALD (191 patients) that were assessed for both LS and SS using the Fibroscan device. They also discussed their retrospective analysis of LS and spleen length (SL) from a separate, retrospective cohort of 449 patients (267 with HCV, 182 with ALD) for whom long-term data on decompensation/death were available.

The researchers found that SS was significantly higher in HCV patients, compared with those with ALD (42.0 vs. 32.6 kPa; P less than .0001), as was SL (15.6 vs. 11.9 cm, P less than .0001); this was despite a lower mean LS in HCV. As a result, the SS/LS ratio and the SL/LS ratio were both significantly higher in HCV (3.8 vs. 1.72 and 1.46 vs. 0.86, P less than .0001) through all fibrosis stages.

They also found that patients with ALD had higher LS values (30.5 vs. 21.3 kPa) and predominantly presented with jaundice (65.2%), with liver failure as the major cause of death (P less than .01). In contrast, in HCV, spleens were larger (17.6 vs. 12.1 cm) while variceal bleeding was the major cause of decompensation (73.2%) and death (P less than .001).

“We have demonstrated the disease-specific differences in SS/LS and SL/LS ratio between HCV and ALD. They underscore the role of the intrahepatic histological site of inflammation/fibrosis. We suggest that the SS/LS ratio could be used to confirm the disease etiology and predict disease-specific complications,” the researchers concluded.

The study was supported by the Dietmar Hopp Foundation. The authors reported they had no conflicts.

mlesney@mdedge.com

SOURCE: Elshaarawy O et al. J Hepatol Reports. 2019 Jun 20. doi: 10.1016/j.jhepr.2019.05.003.

The spleen stiffness (SS) to liver stiffness (LS) ratio was significantly higher in patients with hepatitis C virus infection (HCV) than in patients with alcohol-related liver disease (ALD), according to the results of a multicenter prospective study. In addition, long-term outcome and complications differed dramatically between HCV and ALD. Variceal bleeding was the most common sign of decompensation and cause of death in patients with HCV, while jaundice was the most common sign of decompensation in patients with ALD.

©pixologicstudio/thinkstockphotos.com

Omar Elshaarawy, MSc, of the University of Heidelberg (Germany) and colleagues reported on their prospective study of 411 patients with HCV (220 patients) or ALD (191 patients) that were assessed for both LS and SS using the Fibroscan device. They also discussed their retrospective analysis of LS and spleen length (SL) from a separate, retrospective cohort of 449 patients (267 with HCV, 182 with ALD) for whom long-term data on decompensation/death were available.

The researchers found that SS was significantly higher in HCV patients, compared with those with ALD (42.0 vs. 32.6 kPa; P less than .0001), as was SL (15.6 vs. 11.9 cm, P less than .0001); this was despite a lower mean LS in HCV. As a result, the SS/LS ratio and the SL/LS ratio were both significantly higher in HCV (3.8 vs. 1.72 and 1.46 vs. 0.86, P less than .0001) through all fibrosis stages.

They also found that patients with ALD had higher LS values (30.5 vs. 21.3 kPa) and predominantly presented with jaundice (65.2%), with liver failure as the major cause of death (P less than .01). In contrast, in HCV, spleens were larger (17.6 vs. 12.1 cm) while variceal bleeding was the major cause of decompensation (73.2%) and death (P less than .001).

“We have demonstrated the disease-specific differences in SS/LS and SL/LS ratio between HCV and ALD. They underscore the role of the intrahepatic histological site of inflammation/fibrosis. We suggest that the SS/LS ratio could be used to confirm the disease etiology and predict disease-specific complications,” the researchers concluded.

The study was supported by the Dietmar Hopp Foundation. The authors reported they had no conflicts.

mlesney@mdedge.com

SOURCE: Elshaarawy O et al. J Hepatol Reports. 2019 Jun 20. doi: 10.1016/j.jhepr.2019.05.003.

AGA member Zobair Younossi, MD, MPH, and three other expert and patient panelists called upon Congress to help educate policymakers and the public on the increasing burden of NASH and to take steps to prevent its increase, including more funding for research.

Dr. Younossi provided congressional staffers with an informative presentation on the prevalence, adverse clinical outcomes, and economic outcomes of nonalcoholic steatohepatitis (NASH). He noted that 6.65 million adults have NASH – 688,000 have advanced NASH. Treatment of these patients carries an economic burden of $222.6 billion in direct costs and $95.4 billion in lifetime direct costs of advanced NASH.

Although NASH was discovered almost 40 years ago, the prevalence has doubled in the last 15 years and challenges to optimize disease diagnosis and management remain. The briefing was sponsored by the Global Liver Institute and its founder and CEO, Donna Cryer, JD, is a NASH patient and liver transplant recipient. Dr. Younossi noted that, between 2015 and 2030, the percentage of nonalcoholic fatty liver disease (NAFLD) that is related to NASH is projected to increase from 20% to 27%.

AGA thanks Dr. Younossi, the other panelists, and the Global Liver Institute for assembling this important educational forum and encouraging Congress to take action.
 

ginews@gastro.org

AGA member Zobair Younossi, MD, MPH, and three other expert and patient panelists called upon Congress to help educate policymakers and the public on the increasing burden of NASH and to take steps to prevent its increase, including more funding for research.

Dr. Younossi provided congressional staffers with an informative presentation on the prevalence, adverse clinical outcomes, and economic outcomes of nonalcoholic steatohepatitis (NASH). He noted that 6.65 million adults have NASH – 688,000 have advanced NASH. Treatment of these patients carries an economic burden of $222.6 billion in direct costs and $95.4 billion in lifetime direct costs of advanced NASH.

Although NASH was discovered almost 40 years ago, the prevalence has doubled in the last 15 years and challenges to optimize disease diagnosis and management remain. The briefing was sponsored by the Global Liver Institute and its founder and CEO, Donna Cryer, JD, is a NASH patient and liver transplant recipient. Dr. Younossi noted that, between 2015 and 2030, the percentage of nonalcoholic fatty liver disease (NAFLD) that is related to NASH is projected to increase from 20% to 27%.

AGA thanks Dr. Younossi, the other panelists, and the Global Liver Institute for assembling this important educational forum and encouraging Congress to take action.
 

ginews@gastro.org

AGA member Zobair Younossi, MD, MPH, and three other expert and patient panelists called upon Congress to help educate policymakers and the public on the increasing burden of NASH and to take steps to prevent its increase, including more funding for research.

Dr. Younossi provided congressional staffers with an informative presentation on the prevalence, adverse clinical outcomes, and economic outcomes of nonalcoholic steatohepatitis (NASH). He noted that 6.65 million adults have NASH – 688,000 have advanced NASH. Treatment of these patients carries an economic burden of $222.6 billion in direct costs and $95.4 billion in lifetime direct costs of advanced NASH.

Although NASH was discovered almost 40 years ago, the prevalence has doubled in the last 15 years and challenges to optimize disease diagnosis and management remain. The briefing was sponsored by the Global Liver Institute and its founder and CEO, Donna Cryer, JD, is a NASH patient and liver transplant recipient. Dr. Younossi noted that, between 2015 and 2030, the percentage of nonalcoholic fatty liver disease (NAFLD) that is related to NASH is projected to increase from 20% to 27%.

AGA thanks Dr. Younossi, the other panelists, and the Global Liver Institute for assembling this important educational forum and encouraging Congress to take action.
 

ginews@gastro.org

The AGA journals – Gastroenterology, Clinical Gastroenterology and Hepatology (CGH), and Cellular and Molecular Gastroenterology and Hepatology (CMGH) – are pleased to announce their 2019-2020 editorial fellows.


Gastroenterology
Feng Su, MD
University of Washington, Seattle
@FengSu_MD

Victoria Weis, PhD
Wake Forest School of Medicine, Winston-Salem, N.C.

CGH
Austin Chiang, MD, MPH
Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia
@AustinChiangMD

Jennifer Kolb, MD
University of Colorado Anschutz Medical Campus, Aurora

CMGH
Cambrian Liu, PhD
The Saban Research Institute, Children’s Hospital Los Angeles

Tirthadipa Pradhan-Sundd, PhD
University of Pittsburgh, Pennsylvania
@Tirthadipa

The editorial fellows will be mentored on their respective journals’ editorial processes, including peer review and the publication process from manuscript submission to acceptance. They will participate in discussions and conferences with the boards of editors and work closely with the AGA editorial staff. Additionally, the fellows will participate in AGA’s new reviewer education program and will also be offered the opportunity to contribute content to their respective journals. The newly expanded program builds on the success of the previous 2 years when Gastroenterology had an editorial fellow.

The journals’ board of editors and editorial staff congratulate the fellows and are excited to work with them over the next year.
 

ginews@gastro.org

The AGA journals – Gastroenterology, Clinical Gastroenterology and Hepatology (CGH), and Cellular and Molecular Gastroenterology and Hepatology (CMGH) – are pleased to announce their 2019-2020 editorial fellows.


Gastroenterology
Feng Su, MD
University of Washington, Seattle
@FengSu_MD

Victoria Weis, PhD
Wake Forest School of Medicine, Winston-Salem, N.C.

CGH
Austin Chiang, MD, MPH
Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia
@AustinChiangMD

Jennifer Kolb, MD
University of Colorado Anschutz Medical Campus, Aurora

CMGH
Cambrian Liu, PhD
The Saban Research Institute, Children’s Hospital Los Angeles

Tirthadipa Pradhan-Sundd, PhD
University of Pittsburgh, Pennsylvania
@Tirthadipa

The editorial fellows will be mentored on their respective journals’ editorial processes, including peer review and the publication process from manuscript submission to acceptance. They will participate in discussions and conferences with the boards of editors and work closely with the AGA editorial staff. Additionally, the fellows will participate in AGA’s new reviewer education program and will also be offered the opportunity to contribute content to their respective journals. The newly expanded program builds on the success of the previous 2 years when Gastroenterology had an editorial fellow.

The journals’ board of editors and editorial staff congratulate the fellows and are excited to work with them over the next year.
 

ginews@gastro.org

The AGA journals – Gastroenterology, Clinical Gastroenterology and Hepatology (CGH), and Cellular and Molecular Gastroenterology and Hepatology (CMGH) – are pleased to announce their 2019-2020 editorial fellows.


Gastroenterology
Feng Su, MD
University of Washington, Seattle
@FengSu_MD

Victoria Weis, PhD
Wake Forest School of Medicine, Winston-Salem, N.C.

CGH
Austin Chiang, MD, MPH
Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia
@AustinChiangMD

Jennifer Kolb, MD
University of Colorado Anschutz Medical Campus, Aurora

CMGH
Cambrian Liu, PhD
The Saban Research Institute, Children’s Hospital Los Angeles

Tirthadipa Pradhan-Sundd, PhD
University of Pittsburgh, Pennsylvania
@Tirthadipa

The editorial fellows will be mentored on their respective journals’ editorial processes, including peer review and the publication process from manuscript submission to acceptance. They will participate in discussions and conferences with the boards of editors and work closely with the AGA editorial staff. Additionally, the fellows will participate in AGA’s new reviewer education program and will also be offered the opportunity to contribute content to their respective journals. The newly expanded program builds on the success of the previous 2 years when Gastroenterology had an editorial fellow.

The journals’ board of editors and editorial staff congratulate the fellows and are excited to work with them over the next year.
 

ginews@gastro.org

AGA’s microbiome leaders recently met with representatives from FDA’s Center for Biologics Evaluation and Research (CBER) to share clinician and researcher perspectives on fecal microbiota transplantation (FMT) and understand CBER’s current thinking on the regulation of FMT for the treatment of Clostridioides difficile (C. difficile) infection. Here are the key takeaways from AGA’s discussion with CBER.

AGA made clear to FDA the needs and concerns of the clinical and research communities regarding FMT. AGA communicated clinician concerns about patient access to whole-stool FMT being restricted or perhaps eliminated once drugs containing live microbials are FDA approved. AGA’s representatives also shared concerns about the narrow inclusion criteria for current clinical trials and whether the new drugs will be as effective as whole-stool FMT for vulnerable populations such as the elderly or immunocompromised, who make up the majority of patients with C. difficile infection but are often excluded from current trials. Finally, AGA emphasized the need to encourage innovation in product development and the importance of performing controlled safety and efficacy studies on products that can be manufactured predictably and reproducibly.

All stakeholders agreed that the AGA FMT National Registry is an important effort to collect short- and long-term data on the safety and efficacy of FMT. AGA will maintain dialogue with CBER regarding data from the registry and lessons learned. Clinicians practicing FMT are strongly encouraged to participate in the FMT National Registry, which will follow short- and long-term outcomes of patients receiving FMT for up to 10 years. The registry is funded by a grant from the National Institute of Allergy and Infectious Diseases at the National Institutes of Health (award number R24 AI118629) and is a partnership of AGA, the Crohn’s &nd Colitis Foundation, the Infectious Diseases Society of America and North American Society for Pediatric Gastroenterology, Hepatology and Nutrition.

CBER is currently working on an update to the enforcement discretion policy on the use of FMT for C. difficile infection not responsive to standard therapies.Agency representatives noted that all comments will be considered as the agency finalizes the guidance. The current enforcement discretion policy has been in place since July 2013 and was most recently updated by CBER in a draft guidance in March 2016. The policy enables clinicians to use FMT for the treatment of C. difficile infection not responsive to standard therapies without having an investigational new drug (IND) application in place.

Human stool will continue to be regulated as a drug and biological product. The agency stated that human stool does not meet the definition of a tissue and FDA does not intend to change how it is currently classified.

CBER is interested in hearing ideas for novel trial designs that may help address the challenges of patient recruitment for clinical trials in C. difficile infection and other indications for FMT. AGA encourages members to share their thoughts on this topic through the AGA Community.

Following AGA’s meeting with CBER, FDA issued a safety alert because of the death of a patient who died from an FMT containing a multi-drug resistant organism. The agency has since issued additional requirements for IND holders on stool donor screening. AGA will continue to engage with FDA on this issue and share updates as they become available with all members.

Meeting participants from AGA membership included:

• Gail A. Hecht, MD, MS, AGAF, immediate past chair, AGA Center for Gut Microbiome Research and Education Scientific Advisory Board

• Colleen R. Kelly, MD, co-chair, AGA FMT National Registry Steering Committee

• Alexander Khoruts, MD, member, AGA Center for Gut Microbiome Research and Education Scientific Advisory Board

• Gary D. Wu, MD, AGAF, basic research councilor, AGA Institute Governing Board, and member, AGA FMT National Registry Steering Committee


Meeting participants from FDA/CBER included:

• Peter Marks, MD, PhD, Director, CBER

• Celia Witten, PhD, MD, Deputy Director, CBER

• Diane Maloney, JD, Associate Director for Policy, CBER

• Julie Tierney, JD, Senior Policy Advisor for Strategic Planning & Legislation, CBER

• Marion Gruber, PhD, Director, Office of Vaccines Research and Review (OVRR), CBER

• Theresa Finn, PhD, Associate Director for Policy, OVRR, CBER

• Doran Fink, MD, PhD, Deputy Director, Clinical, Division of Vaccines and Related Products Applications, OVRR, CBER

• Paul Carlson, PhD, Senior Staff Fellow, OVRR

• Lorrie McNeill, Director, Office of Communication, Outreach and Development, CBER


This meeting took place on May 6, 2019, at the FDA headquarters in Silver Spring, Md.
 

ginews@gastro.org

AGA’s microbiome leaders recently met with representatives from FDA’s Center for Biologics Evaluation and Research (CBER) to share clinician and researcher perspectives on fecal microbiota transplantation (FMT) and understand CBER’s current thinking on the regulation of FMT for the treatment of Clostridioides difficile (C. difficile) infection. Here are the key takeaways from AGA’s discussion with CBER.

AGA made clear to FDA the needs and concerns of the clinical and research communities regarding FMT. AGA communicated clinician concerns about patient access to whole-stool FMT being restricted or perhaps eliminated once drugs containing live microbials are FDA approved. AGA’s representatives also shared concerns about the narrow inclusion criteria for current clinical trials and whether the new drugs will be as effective as whole-stool FMT for vulnerable populations such as the elderly or immunocompromised, who make up the majority of patients with C. difficile infection but are often excluded from current trials. Finally, AGA emphasized the need to encourage innovation in product development and the importance of performing controlled safety and efficacy studies on products that can be manufactured predictably and reproducibly.

All stakeholders agreed that the AGA FMT National Registry is an important effort to collect short- and long-term data on the safety and efficacy of FMT. AGA will maintain dialogue with CBER regarding data from the registry and lessons learned. Clinicians practicing FMT are strongly encouraged to participate in the FMT National Registry, which will follow short- and long-term outcomes of patients receiving FMT for up to 10 years. The registry is funded by a grant from the National Institute of Allergy and Infectious Diseases at the National Institutes of Health (award number R24 AI118629) and is a partnership of AGA, the Crohn’s &nd Colitis Foundation, the Infectious Diseases Society of America and North American Society for Pediatric Gastroenterology, Hepatology and Nutrition.

CBER is currently working on an update to the enforcement discretion policy on the use of FMT for C. difficile infection not responsive to standard therapies.Agency representatives noted that all comments will be considered as the agency finalizes the guidance. The current enforcement discretion policy has been in place since July 2013 and was most recently updated by CBER in a draft guidance in March 2016. The policy enables clinicians to use FMT for the treatment of C. difficile infection not responsive to standard therapies without having an investigational new drug (IND) application in place.

Human stool will continue to be regulated as a drug and biological product. The agency stated that human stool does not meet the definition of a tissue and FDA does not intend to change how it is currently classified.

CBER is interested in hearing ideas for novel trial designs that may help address the challenges of patient recruitment for clinical trials in C. difficile infection and other indications for FMT. AGA encourages members to share their thoughts on this topic through the AGA Community.

Following AGA’s meeting with CBER, FDA issued a safety alert because of the death of a patient who died from an FMT containing a multi-drug resistant organism. The agency has since issued additional requirements for IND holders on stool donor screening. AGA will continue to engage with FDA on this issue and share updates as they become available with all members.

Meeting participants from AGA membership included:

• Gail A. Hecht, MD, MS, AGAF, immediate past chair, AGA Center for Gut Microbiome Research and Education Scientific Advisory Board

• Colleen R. Kelly, MD, co-chair, AGA FMT National Registry Steering Committee

• Alexander Khoruts, MD, member, AGA Center for Gut Microbiome Research and Education Scientific Advisory Board

• Gary D. Wu, MD, AGAF, basic research councilor, AGA Institute Governing Board, and member, AGA FMT National Registry Steering Committee


Meeting participants from FDA/CBER included:

• Peter Marks, MD, PhD, Director, CBER

• Celia Witten, PhD, MD, Deputy Director, CBER

• Diane Maloney, JD, Associate Director for Policy, CBER

• Julie Tierney, JD, Senior Policy Advisor for Strategic Planning & Legislation, CBER

• Marion Gruber, PhD, Director, Office of Vaccines Research and Review (OVRR), CBER

• Theresa Finn, PhD, Associate Director for Policy, OVRR, CBER

• Doran Fink, MD, PhD, Deputy Director, Clinical, Division of Vaccines and Related Products Applications, OVRR, CBER

• Paul Carlson, PhD, Senior Staff Fellow, OVRR

• Lorrie McNeill, Director, Office of Communication, Outreach and Development, CBER


This meeting took place on May 6, 2019, at the FDA headquarters in Silver Spring, Md.
 

ginews@gastro.org

AGA’s microbiome leaders recently met with representatives from FDA’s Center for Biologics Evaluation and Research (CBER) to share clinician and researcher perspectives on fecal microbiota transplantation (FMT) and understand CBER’s current thinking on the regulation of FMT for the treatment of Clostridioides difficile (C. difficile) infection. Here are the key takeaways from AGA’s discussion with CBER.

AGA made clear to FDA the needs and concerns of the clinical and research communities regarding FMT. AGA communicated clinician concerns about patient access to whole-stool FMT being restricted or perhaps eliminated once drugs containing live microbials are FDA approved. AGA’s representatives also shared concerns about the narrow inclusion criteria for current clinical trials and whether the new drugs will be as effective as whole-stool FMT for vulnerable populations such as the elderly or immunocompromised, who make up the majority of patients with C. difficile infection but are often excluded from current trials. Finally, AGA emphasized the need to encourage innovation in product development and the importance of performing controlled safety and efficacy studies on products that can be manufactured predictably and reproducibly.

All stakeholders agreed that the AGA FMT National Registry is an important effort to collect short- and long-term data on the safety and efficacy of FMT. AGA will maintain dialogue with CBER regarding data from the registry and lessons learned. Clinicians practicing FMT are strongly encouraged to participate in the FMT National Registry, which will follow short- and long-term outcomes of patients receiving FMT for up to 10 years. The registry is funded by a grant from the National Institute of Allergy and Infectious Diseases at the National Institutes of Health (award number R24 AI118629) and is a partnership of AGA, the Crohn’s &nd Colitis Foundation, the Infectious Diseases Society of America and North American Society for Pediatric Gastroenterology, Hepatology and Nutrition.

CBER is currently working on an update to the enforcement discretion policy on the use of FMT for C. difficile infection not responsive to standard therapies.Agency representatives noted that all comments will be considered as the agency finalizes the guidance. The current enforcement discretion policy has been in place since July 2013 and was most recently updated by CBER in a draft guidance in March 2016. The policy enables clinicians to use FMT for the treatment of C. difficile infection not responsive to standard therapies without having an investigational new drug (IND) application in place.

Human stool will continue to be regulated as a drug and biological product. The agency stated that human stool does not meet the definition of a tissue and FDA does not intend to change how it is currently classified.

CBER is interested in hearing ideas for novel trial designs that may help address the challenges of patient recruitment for clinical trials in C. difficile infection and other indications for FMT. AGA encourages members to share their thoughts on this topic through the AGA Community.

Following AGA’s meeting with CBER, FDA issued a safety alert because of the death of a patient who died from an FMT containing a multi-drug resistant organism. The agency has since issued additional requirements for IND holders on stool donor screening. AGA will continue to engage with FDA on this issue and share updates as they become available with all members.

Meeting participants from AGA membership included:

• Gail A. Hecht, MD, MS, AGAF, immediate past chair, AGA Center for Gut Microbiome Research and Education Scientific Advisory Board

• Colleen R. Kelly, MD, co-chair, AGA FMT National Registry Steering Committee

• Alexander Khoruts, MD, member, AGA Center for Gut Microbiome Research and Education Scientific Advisory Board

• Gary D. Wu, MD, AGAF, basic research councilor, AGA Institute Governing Board, and member, AGA FMT National Registry Steering Committee


Meeting participants from FDA/CBER included:

• Peter Marks, MD, PhD, Director, CBER

• Celia Witten, PhD, MD, Deputy Director, CBER

• Diane Maloney, JD, Associate Director for Policy, CBER

• Julie Tierney, JD, Senior Policy Advisor for Strategic Planning & Legislation, CBER

• Marion Gruber, PhD, Director, Office of Vaccines Research and Review (OVRR), CBER

• Theresa Finn, PhD, Associate Director for Policy, OVRR, CBER

• Doran Fink, MD, PhD, Deputy Director, Clinical, Division of Vaccines and Related Products Applications, OVRR, CBER

• Paul Carlson, PhD, Senior Staff Fellow, OVRR

• Lorrie McNeill, Director, Office of Communication, Outreach and Development, CBER


This meeting took place on May 6, 2019, at the FDA headquarters in Silver Spring, Md.
 

ginews@gastro.org

Oncologists who specialize in treating hematologic malignancies or breast cancer will have more options for fulfilling their maintenance of certification exam requirements beginning next year.

The American Board of Internal Medicine (ABIM), in partnership with the American Society of Clinical Oncology (ASCO), will begin offering a more frequent, more specialized, and lower-stakes exam as an alternative to the current 10-year examination.

The new pathway was announced by ABIM and ASCO in May 2018 after 2 years of gathering feedback from physicians about the need for an exam that tests them in their area of practice – rather than all areas of oncology.

Now the groups are rolling out the first three assessments created under this model – general oncology, hematologic malignancies, and breast cancer. This will be followed in 2022 by exams in gastrointestinal malignancies and lung cancer/thoracic malignancies. Additional new exams will roll out in even-numbered years based on the level of physician interest.

Registration will begin on Dec. 1, 2019, for the 2020 exam, which will be offered in March and September.

Here’s how it works: Oncologists who choose the new ABIM/ASCO Medical Oncology Learning & Assessment pathway will forgo the 10-year exam in favor of shorter exams every 2 years. The new exam – which is about one-third the size of the traditional exam – is given online and can be taken at home, at the office, or at a test center.

The 2-year exam is pass/fail and physicians are allowed one retake. If they fail twice, they must take the 10-year exam.

The cost over 10 years will be the same, regardless of whether one takes the traditional exam or follows the newer path, according to ABIM.

ABIM and ASCO also have designed education around the exam. After registration, test-takers will be supplied with study materials and after the test they’ll receive additional, tailored education on questions that they got wrong.

Giving physicians feedback on how they can improve is a major change, said Richard G. Battaglia, MD, chief medical officer for ABIM. He said that one of the main messages they heard from physicians was that the exam needed to have educational value.

The other message they heard over and over, Dr. Battaglia said, is that practice tends to focus over time and that physicians want to be assessed on what they see every day.

For that reason, the big shift is in the tailored nature of the exam. All of the 2-year exams offered will contain a core module with questions that every oncologist should know, related to symptom management, disease assessment, and principles of genetics and genomics. That core module will make up 25% of the test.

The remaining 75% of the exam will be disease focused, with questions on diagnosis, testing, treatment, prognosis, and common case examples, said Jamie Von Roenn, MD, vice president of education, science, and professional development at ASCO.

While test takers will have access to resources, such as UpToDate, during the exam, Dr. Von Roenn said don’t expect to be tested on obscure knowledge or asked about rare conditions. “All of the questions are clinical vignettes,” she said. “These are common questions that oncologists face in practice.”

The 2-year general oncology exam will follow the same overall blueprint as the traditional maintenance of certification exam, but will be “very clinically based,” Dr. Von Roenn said. “We’re not asking for things that you can look up,” she said. The exam will instead be focused on how to apply knowledge to common clinical examples.

For that reason, Dr. Von Roenn and Dr. Battaglia said physicians won’t need to spend time and money on intensive exam preparation.

“I actually suspect that people who are busy clinicians wouldn’t need to study, period,” Dr. Von Roenn said.

Richard Larson, MD, reviewed some of the materials for the hematologic malignancies exam and said the test is focused on practical scenarios.

“It’s certainly reasonable to take the test without taking a lot of time to prepare for it,” if physicians are attending annual meetings and grand rounds, and staying current on the medical literature, said Dr. Larson, professor of medicine in the department of hematology-oncology at the University of Chicago, “We’re not aiming at the zebras.”

Thomas LeBlanc, MD, who was not involved with the development of the exam, called this a welcome and overdue change.

mschneider@mdedge.com

Oncologists who specialize in treating hematologic malignancies or breast cancer will have more options for fulfilling their maintenance of certification exam requirements beginning next year.

The American Board of Internal Medicine (ABIM), in partnership with the American Society of Clinical Oncology (ASCO), will begin offering a more frequent, more specialized, and lower-stakes exam as an alternative to the current 10-year examination.

The new pathway was announced by ABIM and ASCO in May 2018 after 2 years of gathering feedback from physicians about the need for an exam that tests them in their area of practice – rather than all areas of oncology.

Now the groups are rolling out the first three assessments created under this model – general oncology, hematologic malignancies, and breast cancer. This will be followed in 2022 by exams in gastrointestinal malignancies and lung cancer/thoracic malignancies. Additional new exams will roll out in even-numbered years based on the level of physician interest.

Registration will begin on Dec. 1, 2019, for the 2020 exam, which will be offered in March and September.

Here’s how it works: Oncologists who choose the new ABIM/ASCO Medical Oncology Learning & Assessment pathway will forgo the 10-year exam in favor of shorter exams every 2 years. The new exam – which is about one-third the size of the traditional exam – is given online and can be taken at home, at the office, or at a test center.

The 2-year exam is pass/fail and physicians are allowed one retake. If they fail twice, they must take the 10-year exam.

The cost over 10 years will be the same, regardless of whether one takes the traditional exam or follows the newer path, according to ABIM.

ABIM and ASCO also have designed education around the exam. After registration, test-takers will be supplied with study materials and after the test they’ll receive additional, tailored education on questions that they got wrong.

Giving physicians feedback on how they can improve is a major change, said Richard G. Battaglia, MD, chief medical officer for ABIM. He said that one of the main messages they heard from physicians was that the exam needed to have educational value.

The other message they heard over and over, Dr. Battaglia said, is that practice tends to focus over time and that physicians want to be assessed on what they see every day.

For that reason, the big shift is in the tailored nature of the exam. All of the 2-year exams offered will contain a core module with questions that every oncologist should know, related to symptom management, disease assessment, and principles of genetics and genomics. That core module will make up 25% of the test.

The remaining 75% of the exam will be disease focused, with questions on diagnosis, testing, treatment, prognosis, and common case examples, said Jamie Von Roenn, MD, vice president of education, science, and professional development at ASCO.

While test takers will have access to resources, such as UpToDate, during the exam, Dr. Von Roenn said don’t expect to be tested on obscure knowledge or asked about rare conditions. “All of the questions are clinical vignettes,” she said. “These are common questions that oncologists face in practice.”

The 2-year general oncology exam will follow the same overall blueprint as the traditional maintenance of certification exam, but will be “very clinically based,” Dr. Von Roenn said. “We’re not asking for things that you can look up,” she said. The exam will instead be focused on how to apply knowledge to common clinical examples.

For that reason, Dr. Von Roenn and Dr. Battaglia said physicians won’t need to spend time and money on intensive exam preparation.

“I actually suspect that people who are busy clinicians wouldn’t need to study, period,” Dr. Von Roenn said.

Richard Larson, MD, reviewed some of the materials for the hematologic malignancies exam and said the test is focused on practical scenarios.

“It’s certainly reasonable to take the test without taking a lot of time to prepare for it,” if physicians are attending annual meetings and grand rounds, and staying current on the medical literature, said Dr. Larson, professor of medicine in the department of hematology-oncology at the University of Chicago, “We’re not aiming at the zebras.”

Thomas LeBlanc, MD, who was not involved with the development of the exam, called this a welcome and overdue change.

mschneider@mdedge.com

Oncologists who specialize in treating hematologic malignancies or breast cancer will have more options for fulfilling their maintenance of certification exam requirements beginning next year.

The American Board of Internal Medicine (ABIM), in partnership with the American Society of Clinical Oncology (ASCO), will begin offering a more frequent, more specialized, and lower-stakes exam as an alternative to the current 10-year examination.

The new pathway was announced by ABIM and ASCO in May 2018 after 2 years of gathering feedback from physicians about the need for an exam that tests them in their area of practice – rather than all areas of oncology.

Now the groups are rolling out the first three assessments created under this model – general oncology, hematologic malignancies, and breast cancer. This will be followed in 2022 by exams in gastrointestinal malignancies and lung cancer/thoracic malignancies. Additional new exams will roll out in even-numbered years based on the level of physician interest.

Registration will begin on Dec. 1, 2019, for the 2020 exam, which will be offered in March and September.

Here’s how it works: Oncologists who choose the new ABIM/ASCO Medical Oncology Learning & Assessment pathway will forgo the 10-year exam in favor of shorter exams every 2 years. The new exam – which is about one-third the size of the traditional exam – is given online and can be taken at home, at the office, or at a test center.

The 2-year exam is pass/fail and physicians are allowed one retake. If they fail twice, they must take the 10-year exam.

The cost over 10 years will be the same, regardless of whether one takes the traditional exam or follows the newer path, according to ABIM.

ABIM and ASCO also have designed education around the exam. After registration, test-takers will be supplied with study materials and after the test they’ll receive additional, tailored education on questions that they got wrong.

Giving physicians feedback on how they can improve is a major change, said Richard G. Battaglia, MD, chief medical officer for ABIM. He said that one of the main messages they heard from physicians was that the exam needed to have educational value.

The other message they heard over and over, Dr. Battaglia said, is that practice tends to focus over time and that physicians want to be assessed on what they see every day.

For that reason, the big shift is in the tailored nature of the exam. All of the 2-year exams offered will contain a core module with questions that every oncologist should know, related to symptom management, disease assessment, and principles of genetics and genomics. That core module will make up 25% of the test.

The remaining 75% of the exam will be disease focused, with questions on diagnosis, testing, treatment, prognosis, and common case examples, said Jamie Von Roenn, MD, vice president of education, science, and professional development at ASCO.

While test takers will have access to resources, such as UpToDate, during the exam, Dr. Von Roenn said don’t expect to be tested on obscure knowledge or asked about rare conditions. “All of the questions are clinical vignettes,” she said. “These are common questions that oncologists face in practice.”

The 2-year general oncology exam will follow the same overall blueprint as the traditional maintenance of certification exam, but will be “very clinically based,” Dr. Von Roenn said. “We’re not asking for things that you can look up,” she said. The exam will instead be focused on how to apply knowledge to common clinical examples.

For that reason, Dr. Von Roenn and Dr. Battaglia said physicians won’t need to spend time and money on intensive exam preparation.

“I actually suspect that people who are busy clinicians wouldn’t need to study, period,” Dr. Von Roenn said.

Richard Larson, MD, reviewed some of the materials for the hematologic malignancies exam and said the test is focused on practical scenarios.

“It’s certainly reasonable to take the test without taking a lot of time to prepare for it,” if physicians are attending annual meetings and grand rounds, and staying current on the medical literature, said Dr. Larson, professor of medicine in the department of hematology-oncology at the University of Chicago, “We’re not aiming at the zebras.”

Thomas LeBlanc, MD, who was not involved with the development of the exam, called this a welcome and overdue change.

mschneider@mdedge.com

Exposure to air pollution may contribute to significant reductions in life expectancy in the United States, particularly among lower-income populations, research suggests.

copyright Sergiy Serdyuk/istockphoto.com

A study published in PLOS Medicine used vital registration and population data from across the United States for 1999-2015 to estimate the number of deaths and loss of life expectancy associated with four different models of concentrations of fine particulate matter pollution, and examine how that has changed over time.

While the current national ambient air quality standard for particle pollution is 12 mcg/m³ in almost all counties, the study found that in 1999, 59% of the 1,339 county units had concentrations above this level. At that time, the population-weighted average fine particulate matter pollution concentration for the entire country was 13.6mcg/m³. The highest level was seen in Fresno county in California, which had a fine particulate pollution concentration of 22.1 mcg/m³.

By 2015, national concentrations had declined to 8.0 mcg/m³, and the lowest observed concentration was 2.8 mcg/m³.

The investigators wrote, “Each model was applied to county-level cardiorespiratory death rates separately by sex and age group (5-year age groups from birth to 85 years and 85 years and older) because death rates vary by age group and sex, as might their associations with air pollution. From each model we estimated age-specific proportional increases in death rates (i.e. rate ratios) for each 1 mcg/m³ of PM_2.5 [fine particulate matter].” The analysis revealed that fine particulate matter pollution above the lowest observed concentration of 2.8 mcg/m³ was associated with higher death rates from cardiorespiratory diseases.

Overall, researchers estimated that these higher levels contributed to 15,612 deaths from cardiorespiratory diseases in women and 14,757 deaths in men, representing 2.8% and 2.7% of all cardiorespiratory deaths, respectively. This amounted to 0.15 years of life expectancy lost in women and 0.13 years lost in men.

There was significant variation in the cost to life expectancy around the country. In the midwestern and Rocky Mountain counties in states such as New Mexico, Colorado, and Arizona, which had lower levels of air pollution, life expectancy loss was less than 0.05 years. But in southern states where the air pollution levels were highest, such as Arkansas, Oklahoma, Alabama, and around Los Angeles, the life expectancy loss was greater than 0.3 years.

“While current PM_2.5 pollution is responsible for a significant mortality burden and loss of longevity, reductions in pollution since the late 1990s have benefited virtually the entire country, with the exception of 14 counties where PM_2.5 increased slightly over this period,” wrote James E. Bennett, PhD, of the School of Public Health at Imperial College London and coauthors.

The primary limitation of the study is that this association between air pollution and cardiorespiratory health or life expectancy cannot be shown to be causal. Other pollutants and other environmental and behavioral factors that impact cardiorespiratory health may be significant. For example, including ozone and nitrogen dioxide levels in the models could result in different results in terms of the impact of PM2.5 on cardiorespiratory health.

The data highlighted that life expectancy loss associated with air pollution was larger in lower-income counties, those where a higher proportion of the population had a family income below the poverty line, and those where a higher proportion of the population were black or African American.

“This inequality in mortality burden occurs because lower-income counties, those with more poverty, with a greater proportion who are of black or African American race, or with a lower proportion who have graduated high school tend to have higher baseline death rates at any pollution level because of conditions associated with these covariates and hence experience a larger absolute number of deaths as a result of air pollution,” the authors wrote.

The study was funded by the U.S. Environmental Protection Agency and the Wellcome Trust. One author declared grants and personal fees from private industry, outside the submitted work.
 

SOURCE: Bennett JE et al. PLoS Med. 2019 Jul 23. doi: 10.1371/journal.pmed.1002856.

Exposure to air pollution may contribute to significant reductions in life expectancy in the United States, particularly among lower-income populations, research suggests.

copyright Sergiy Serdyuk/istockphoto.com

A study published in PLOS Medicine used vital registration and population data from across the United States for 1999-2015 to estimate the number of deaths and loss of life expectancy associated with four different models of concentrations of fine particulate matter pollution, and examine how that has changed over time.

While the current national ambient air quality standard for particle pollution is 12 mcg/m³ in almost all counties, the study found that in 1999, 59% of the 1,339 county units had concentrations above this level. At that time, the population-weighted average fine particulate matter pollution concentration for the entire country was 13.6mcg/m³. The highest level was seen in Fresno county in California, which had a fine particulate pollution concentration of 22.1 mcg/m³.

By 2015, national concentrations had declined to 8.0 mcg/m³, and the lowest observed concentration was 2.8 mcg/m³.

The investigators wrote, “Each model was applied to county-level cardiorespiratory death rates separately by sex and age group (5-year age groups from birth to 85 years and 85 years and older) because death rates vary by age group and sex, as might their associations with air pollution. From each model we estimated age-specific proportional increases in death rates (i.e. rate ratios) for each 1 mcg/m³ of PM_2.5 [fine particulate matter].” The analysis revealed that fine particulate matter pollution above the lowest observed concentration of 2.8 mcg/m³ was associated with higher death rates from cardiorespiratory diseases.

Overall, researchers estimated that these higher levels contributed to 15,612 deaths from cardiorespiratory diseases in women and 14,757 deaths in men, representing 2.8% and 2.7% of all cardiorespiratory deaths, respectively. This amounted to 0.15 years of life expectancy lost in women and 0.13 years lost in men.

There was significant variation in the cost to life expectancy around the country. In the midwestern and Rocky Mountain counties in states such as New Mexico, Colorado, and Arizona, which had lower levels of air pollution, life expectancy loss was less than 0.05 years. But in southern states where the air pollution levels were highest, such as Arkansas, Oklahoma, Alabama, and around Los Angeles, the life expectancy loss was greater than 0.3 years.

“While current PM_2.5 pollution is responsible for a significant mortality burden and loss of longevity, reductions in pollution since the late 1990s have benefited virtually the entire country, with the exception of 14 counties where PM_2.5 increased slightly over this period,” wrote James E. Bennett, PhD, of the School of Public Health at Imperial College London and coauthors.

The primary limitation of the study is that this association between air pollution and cardiorespiratory health or life expectancy cannot be shown to be causal. Other pollutants and other environmental and behavioral factors that impact cardiorespiratory health may be significant. For example, including ozone and nitrogen dioxide levels in the models could result in different results in terms of the impact of PM2.5 on cardiorespiratory health.

The data highlighted that life expectancy loss associated with air pollution was larger in lower-income counties, those where a higher proportion of the population had a family income below the poverty line, and those where a higher proportion of the population were black or African American.

“This inequality in mortality burden occurs because lower-income counties, those with more poverty, with a greater proportion who are of black or African American race, or with a lower proportion who have graduated high school tend to have higher baseline death rates at any pollution level because of conditions associated with these covariates and hence experience a larger absolute number of deaths as a result of air pollution,” the authors wrote.

The study was funded by the U.S. Environmental Protection Agency and the Wellcome Trust. One author declared grants and personal fees from private industry, outside the submitted work.
 

SOURCE: Bennett JE et al. PLoS Med. 2019 Jul 23. doi: 10.1371/journal.pmed.1002856.

Exposure to air pollution may contribute to significant reductions in life expectancy in the United States, particularly among lower-income populations, research suggests.

copyright Sergiy Serdyuk/istockphoto.com

A study published in PLOS Medicine used vital registration and population data from across the United States for 1999-2015 to estimate the number of deaths and loss of life expectancy associated with four different models of concentrations of fine particulate matter pollution, and examine how that has changed over time.

While the current national ambient air quality standard for particle pollution is 12 mcg/m³ in almost all counties, the study found that in 1999, 59% of the 1,339 county units had concentrations above this level. At that time, the population-weighted average fine particulate matter pollution concentration for the entire country was 13.6mcg/m³. The highest level was seen in Fresno county in California, which had a fine particulate pollution concentration of 22.1 mcg/m³.

By 2015, national concentrations had declined to 8.0 mcg/m³, and the lowest observed concentration was 2.8 mcg/m³.

The investigators wrote, “Each model was applied to county-level cardiorespiratory death rates separately by sex and age group (5-year age groups from birth to 85 years and 85 years and older) because death rates vary by age group and sex, as might their associations with air pollution. From each model we estimated age-specific proportional increases in death rates (i.e. rate ratios) for each 1 mcg/m³ of PM_2.5 [fine particulate matter].” The analysis revealed that fine particulate matter pollution above the lowest observed concentration of 2.8 mcg/m³ was associated with higher death rates from cardiorespiratory diseases.

Overall, researchers estimated that these higher levels contributed to 15,612 deaths from cardiorespiratory diseases in women and 14,757 deaths in men, representing 2.8% and 2.7% of all cardiorespiratory deaths, respectively. This amounted to 0.15 years of life expectancy lost in women and 0.13 years lost in men.

There was significant variation in the cost to life expectancy around the country. In the midwestern and Rocky Mountain counties in states such as New Mexico, Colorado, and Arizona, which had lower levels of air pollution, life expectancy loss was less than 0.05 years. But in southern states where the air pollution levels were highest, such as Arkansas, Oklahoma, Alabama, and around Los Angeles, the life expectancy loss was greater than 0.3 years.

“While current PM_2.5 pollution is responsible for a significant mortality burden and loss of longevity, reductions in pollution since the late 1990s have benefited virtually the entire country, with the exception of 14 counties where PM_2.5 increased slightly over this period,” wrote James E. Bennett, PhD, of the School of Public Health at Imperial College London and coauthors.

The primary limitation of the study is that this association between air pollution and cardiorespiratory health or life expectancy cannot be shown to be causal. Other pollutants and other environmental and behavioral factors that impact cardiorespiratory health may be significant. For example, including ozone and nitrogen dioxide levels in the models could result in different results in terms of the impact of PM2.5 on cardiorespiratory health.

The data highlighted that life expectancy loss associated with air pollution was larger in lower-income counties, those where a higher proportion of the population had a family income below the poverty line, and those where a higher proportion of the population were black or African American.

“This inequality in mortality burden occurs because lower-income counties, those with more poverty, with a greater proportion who are of black or African American race, or with a lower proportion who have graduated high school tend to have higher baseline death rates at any pollution level because of conditions associated with these covariates and hence experience a larger absolute number of deaths as a result of air pollution,” the authors wrote.

The study was funded by the U.S. Environmental Protection Agency and the Wellcome Trust. One author declared grants and personal fees from private industry, outside the submitted work.
 

SOURCE: Bennett JE et al. PLoS Med. 2019 Jul 23. doi: 10.1371/journal.pmed.1002856.

A landmark study of advanced endometrial cancer, GOG 258, was published in the New England Journal of Medicine this summer.¹ This clinical trial compared the use of carboplatin and paclitaxel chemotherapy with a combination of chemotherapy with external beam radiation, exploring the notion of “more is better.” The results of the trial revealed that the “more” (chemotherapy with external beam radiation) was no better than chemotherapy alone with respect to overall survival. These results have challenged a creeping dogma in gynecologic oncology, which has seen many providers embrace combination therapy, particularly for patients with stage III (node-positive) endometrial cancer, a group of patients who made up approximately three-quarters of GOG 258’s study population. Many have been left searching for justification of their early adoption of combination therapy before the results of a trial such as this were available. For me it also raised a slightly different question: In the light of these results, what IS the role of para-aortic lymphadenectomy in the staging of endometrial cancers? If radiation to the nodal basins is no longer part of adjuvant therapy, then is pelvic lymphadenectomy or pelvic-only sentinel lymph node (SLN) biopsy enough in determining which patients need chemotherapy?

It was in the 1980s that the removal of clinically normal para-aortic lymph nodes (those residing between the renal and proximal common iliac vessels) became a part of surgical staging. This practice was endorsed by the International Federation of Gynecology and Obstetrics (FIGO) and the Gynecologic Oncology Group (GOG) surgical committee in response to findings that 11% of women with clinical stage I endometrial cancer had microscopic lymph node metastases which were discovered only with routine pathologic evaluation of these tissues. Among those with pelvic lymph node metastases (stage IIIC disease), approximately one-third also harbored disease in para-aortic nodal regions.² Among all patients with endometrial cancer, including those with low-grade disease, only a small fraction (approximately 2%) have isolated para-aortic lymph nodes (positive para-aortic nodes, but negative pelvic nodes). However, among patients with deeply invasive higher-grade tumors, the likelihood of discovering isolated para-aortic metastases is higher at approximately 16%.³ Therefore, the dominant pattern of lymph node metastases and lymphatic dissemination of endometrial cancer appears to be via the parametrial channels laterally towards the pelvic basins, and then sequentially to the para-aortic regions. The direct lymphatic pathway to the para-aortic basins from the uterine fundus through the adnexal lymphatics misses the pelvic regions altogether and may seen logical, but actually is observed fairly infrequently.⁴

Over the subsequent decades, there have been debates and schools of thought regarding what is the optimal degree of lymphatic dissection for endometrial cancer staging. Some advocated for full pelvic and infrarenal para-aortic nodal dissections in all patients, including even those in the lowest risk for metastases. Others advocated for a more limited, inframesenteric para-aortic nodal dissection, although the origins of such a distinction appear to be largely arbitrary. The inferior mesenteric artery is not a physiologic landmark for lymphatic pathways, and approximately half of para-aortic metastases are located above the level of the inferior mesenteric artery. This limited sampling may have been preferred because of relative ease of dissection rather than diagnostic or therapeutic efficacy.

As the population became more obese, making para-aortic nodal dissections less feasible, and laparoscopic staging became accepted as the standard of care in endometrial cancer staging, there was a further push towards limiting the scope of lymphadenectomy. Selective algorithms, such as the so-called “Mayo clinic criteria,” were widely adopted. In this approach, gynecologic oncologists perform full pelvic and infrarenal para-aortic lymphadenectomies but only in the presence of a high-risk uterine feature such as tumor size greater than 2 cm, deep myometrial invasion, or grade 3 histology.³ While this reduced the number of para-aortic dissections being performed, it did not eliminate them, as approximately 40% of patients with endometrial cancer meet at least one of those criteria.

At this same time, we learned something else critical about the benefits, or lack thereof, of lymphadenectomy. Two landmark surgical-staging trials were published in 2009 which randomly assigned women to hysterectomy with lymphadenectomy or hysterectomy alone, and found no survival benefit for lymphadenectomy.^5,6 While these trial results initially were met with noisy backlash, particularly from those who had legitimate concerns regarding study design and conclusions that reach beyond the scope of this column, ultimately their findings (that there is no therapeutic benefit to surgically removing clinically normal lymph nodes) has become largely accepted. The subsequent findings of the Laparoscopic Approach to Cancer of the Endometrium (LACE) trial further support this, as there was no difference in survival found between patients who were randomly assigned to laparoscopic versus open staging for endometrial cancer, even despite a significantly lower rate of lymphadenectomy among the laparoscopic arm.⁷

SLN biopsy, in which the specific nodes which drain the uterus are selectively removed, represents the most recent development in lymph node assessment for endometrial cancer. On average, only three lymph nodes are removed per patient, and para-aortic nodes infrequently are removed, because it is rare that lymphatic pathways drain directly into the aortic basins after cervical injection. Yet despite this more limited dissection of lymph nodes, especially para-aortic, with SLN biopsy, surgeons still observe similar rates of IIIC disease, compared with full lymphadenectomy, suggesting that the presence or absence of lymphatic metastases still is able to be adequately determined. SLN biopsy misses only 3% of lymphatic disease.⁸ What is of particular interest to practitioners of the SLN approach is that “atypical” pathways are discovered approximately 20% of the time, and nodes are harvested from locations such as the presacral space or medial to the internal iliac vessels. These nodes are in locations previously overlooked by even the most comprehensive pelvic and para-aortic lymphadenectomy. Therefore, while the para-aortic nodes may not be systematically removed with SLN biopsy, new and arguably more relevant regions are interrogated, which might explain its equivalent diagnostic virtue.

With this evolution in surgical-staging practice, what we have come to recognize is that the role of lymph node assessment is predominantly, if not exclusively, diagnostic. It can help us determine which patients are at risk for distant relapse and therefore candidates for systemic therapy (chemotherapy), versus those whose risk is predominantly of local relapse and can be adequately treated with local therapies alone, such as vaginal radiation. This brings us to the results of GOG 258. If defining the specific and complete extent of lymph node metastases (as if that was ever truly what surgeons were doing) is no longer necessary to guide the prescription and extent of external beam radiation, then lymph node dissection need only inform us of whether or not there are nodal metastases, not specifically the location of those nodal metastases. The prescription of chemotherapy is the same whether the disease is limited to the pelvic nodes or also includes the para-aortic nodes. While GOG 258 discovered more para-aortic failures among the chemotherapy-alone group, suggesting there may be some therapeutic role of radiation in preventing this, it should be noted that these para-aortic relapses did not negatively impact relapse-free survival, and these patients still can presumably be salvaged with external beam radiation to the site of para-aortic relapse.

It would seem logical that the results of GOG 258 further limit the potential role of para-aortic lymphadenectomy in women with clinical stage I disease. Perhaps para-aortic dissection can be limited to women who are at highest risk for isolated para-aortic disease, such as those with deeply invasive high-grade tumors not successfully mapped with the highly targeted sentinel node biopsy technique? Most clinicians look forward to an era in which we no longer rely on crude dissections of disease-free tissue just to prove they are disease free, but instead can utilize more sophisticated diagnostic methods to recognize disseminated disease.
 

Dr. Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill. Email her at obnews@mdedge.com.

References

1. N Engl J Med. 2019 Jun 13;380(24):2317-26.

2. Cancer. 1987 Oct 15;60(8 Suppl):2035-41.

3. Gynecol Oncol. 2008;109(1):11-8.

4. Int J Gynecol Cancer. 2019 Mar;29(3):613-21.

5. J Natl Cancer Inst. 2008 Dec 3;100(23):1707-16.

6. Lancet. 2009 Jan 10;373(9658):125-36.

7. JAMA. 2017 Mar 28;317(12):1224-33.

8. Lancet Oncol. 2017 Mar;18(3):384-92.

A landmark study of advanced endometrial cancer, GOG 258, was published in the New England Journal of Medicine this summer.¹ This clinical trial compared the use of carboplatin and paclitaxel chemotherapy with a combination of chemotherapy with external beam radiation, exploring the notion of “more is better.” The results of the trial revealed that the “more” (chemotherapy with external beam radiation) was no better than chemotherapy alone with respect to overall survival. These results have challenged a creeping dogma in gynecologic oncology, which has seen many providers embrace combination therapy, particularly for patients with stage III (node-positive) endometrial cancer, a group of patients who made up approximately three-quarters of GOG 258’s study population. Many have been left searching for justification of their early adoption of combination therapy before the results of a trial such as this were available. For me it also raised a slightly different question: In the light of these results, what IS the role of para-aortic lymphadenectomy in the staging of endometrial cancers? If radiation to the nodal basins is no longer part of adjuvant therapy, then is pelvic lymphadenectomy or pelvic-only sentinel lymph node (SLN) biopsy enough in determining which patients need chemotherapy?

It was in the 1980s that the removal of clinically normal para-aortic lymph nodes (those residing between the renal and proximal common iliac vessels) became a part of surgical staging. This practice was endorsed by the International Federation of Gynecology and Obstetrics (FIGO) and the Gynecologic Oncology Group (GOG) surgical committee in response to findings that 11% of women with clinical stage I endometrial cancer had microscopic lymph node metastases which were discovered only with routine pathologic evaluation of these tissues. Among those with pelvic lymph node metastases (stage IIIC disease), approximately one-third also harbored disease in para-aortic nodal regions.² Among all patients with endometrial cancer, including those with low-grade disease, only a small fraction (approximately 2%) have isolated para-aortic lymph nodes (positive para-aortic nodes, but negative pelvic nodes). However, among patients with deeply invasive higher-grade tumors, the likelihood of discovering isolated para-aortic metastases is higher at approximately 16%.³ Therefore, the dominant pattern of lymph node metastases and lymphatic dissemination of endometrial cancer appears to be via the parametrial channels laterally towards the pelvic basins, and then sequentially to the para-aortic regions. The direct lymphatic pathway to the para-aortic basins from the uterine fundus through the adnexal lymphatics misses the pelvic regions altogether and may seen logical, but actually is observed fairly infrequently.⁴

Over the subsequent decades, there have been debates and schools of thought regarding what is the optimal degree of lymphatic dissection for endometrial cancer staging. Some advocated for full pelvic and infrarenal para-aortic nodal dissections in all patients, including even those in the lowest risk for metastases. Others advocated for a more limited, inframesenteric para-aortic nodal dissection, although the origins of such a distinction appear to be largely arbitrary. The inferior mesenteric artery is not a physiologic landmark for lymphatic pathways, and approximately half of para-aortic metastases are located above the level of the inferior mesenteric artery. This limited sampling may have been preferred because of relative ease of dissection rather than diagnostic or therapeutic efficacy.

As the population became more obese, making para-aortic nodal dissections less feasible, and laparoscopic staging became accepted as the standard of care in endometrial cancer staging, there was a further push towards limiting the scope of lymphadenectomy. Selective algorithms, such as the so-called “Mayo clinic criteria,” were widely adopted. In this approach, gynecologic oncologists perform full pelvic and infrarenal para-aortic lymphadenectomies but only in the presence of a high-risk uterine feature such as tumor size greater than 2 cm, deep myometrial invasion, or grade 3 histology.³ While this reduced the number of para-aortic dissections being performed, it did not eliminate them, as approximately 40% of patients with endometrial cancer meet at least one of those criteria.

At this same time, we learned something else critical about the benefits, or lack thereof, of lymphadenectomy. Two landmark surgical-staging trials were published in 2009 which randomly assigned women to hysterectomy with lymphadenectomy or hysterectomy alone, and found no survival benefit for lymphadenectomy.^5,6 While these trial results initially were met with noisy backlash, particularly from those who had legitimate concerns regarding study design and conclusions that reach beyond the scope of this column, ultimately their findings (that there is no therapeutic benefit to surgically removing clinically normal lymph nodes) has become largely accepted. The subsequent findings of the Laparoscopic Approach to Cancer of the Endometrium (LACE) trial further support this, as there was no difference in survival found between patients who were randomly assigned to laparoscopic versus open staging for endometrial cancer, even despite a significantly lower rate of lymphadenectomy among the laparoscopic arm.⁷

SLN biopsy, in which the specific nodes which drain the uterus are selectively removed, represents the most recent development in lymph node assessment for endometrial cancer. On average, only three lymph nodes are removed per patient, and para-aortic nodes infrequently are removed, because it is rare that lymphatic pathways drain directly into the aortic basins after cervical injection. Yet despite this more limited dissection of lymph nodes, especially para-aortic, with SLN biopsy, surgeons still observe similar rates of IIIC disease, compared with full lymphadenectomy, suggesting that the presence or absence of lymphatic metastases still is able to be adequately determined. SLN biopsy misses only 3% of lymphatic disease.⁸ What is of particular interest to practitioners of the SLN approach is that “atypical” pathways are discovered approximately 20% of the time, and nodes are harvested from locations such as the presacral space or medial to the internal iliac vessels. These nodes are in locations previously overlooked by even the most comprehensive pelvic and para-aortic lymphadenectomy. Therefore, while the para-aortic nodes may not be systematically removed with SLN biopsy, new and arguably more relevant regions are interrogated, which might explain its equivalent diagnostic virtue.

With this evolution in surgical-staging practice, what we have come to recognize is that the role of lymph node assessment is predominantly, if not exclusively, diagnostic. It can help us determine which patients are at risk for distant relapse and therefore candidates for systemic therapy (chemotherapy), versus those whose risk is predominantly of local relapse and can be adequately treated with local therapies alone, such as vaginal radiation. This brings us to the results of GOG 258. If defining the specific and complete extent of lymph node metastases (as if that was ever truly what surgeons were doing) is no longer necessary to guide the prescription and extent of external beam radiation, then lymph node dissection need only inform us of whether or not there are nodal metastases, not specifically the location of those nodal metastases. The prescription of chemotherapy is the same whether the disease is limited to the pelvic nodes or also includes the para-aortic nodes. While GOG 258 discovered more para-aortic failures among the chemotherapy-alone group, suggesting there may be some therapeutic role of radiation in preventing this, it should be noted that these para-aortic relapses did not negatively impact relapse-free survival, and these patients still can presumably be salvaged with external beam radiation to the site of para-aortic relapse.

It would seem logical that the results of GOG 258 further limit the potential role of para-aortic lymphadenectomy in women with clinical stage I disease. Perhaps para-aortic dissection can be limited to women who are at highest risk for isolated para-aortic disease, such as those with deeply invasive high-grade tumors not successfully mapped with the highly targeted sentinel node biopsy technique? Most clinicians look forward to an era in which we no longer rely on crude dissections of disease-free tissue just to prove they are disease free, but instead can utilize more sophisticated diagnostic methods to recognize disseminated disease.
 

Dr. Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill. Email her at obnews@mdedge.com.

References

1. N Engl J Med. 2019 Jun 13;380(24):2317-26.

2. Cancer. 1987 Oct 15;60(8 Suppl):2035-41.

3. Gynecol Oncol. 2008;109(1):11-8.

4. Int J Gynecol Cancer. 2019 Mar;29(3):613-21.

5. J Natl Cancer Inst. 2008 Dec 3;100(23):1707-16.

6. Lancet. 2009 Jan 10;373(9658):125-36.

7. JAMA. 2017 Mar 28;317(12):1224-33.

8. Lancet Oncol. 2017 Mar;18(3):384-92.

A landmark study of advanced endometrial cancer, GOG 258, was published in the New England Journal of Medicine this summer.¹ This clinical trial compared the use of carboplatin and paclitaxel chemotherapy with a combination of chemotherapy with external beam radiation, exploring the notion of “more is better.” The results of the trial revealed that the “more” (chemotherapy with external beam radiation) was no better than chemotherapy alone with respect to overall survival. These results have challenged a creeping dogma in gynecologic oncology, which has seen many providers embrace combination therapy, particularly for patients with stage III (node-positive) endometrial cancer, a group of patients who made up approximately three-quarters of GOG 258’s study population. Many have been left searching for justification of their early adoption of combination therapy before the results of a trial such as this were available. For me it also raised a slightly different question: In the light of these results, what IS the role of para-aortic lymphadenectomy in the staging of endometrial cancers? If radiation to the nodal basins is no longer part of adjuvant therapy, then is pelvic lymphadenectomy or pelvic-only sentinel lymph node (SLN) biopsy enough in determining which patients need chemotherapy?

It was in the 1980s that the removal of clinically normal para-aortic lymph nodes (those residing between the renal and proximal common iliac vessels) became a part of surgical staging. This practice was endorsed by the International Federation of Gynecology and Obstetrics (FIGO) and the Gynecologic Oncology Group (GOG) surgical committee in response to findings that 11% of women with clinical stage I endometrial cancer had microscopic lymph node metastases which were discovered only with routine pathologic evaluation of these tissues. Among those with pelvic lymph node metastases (stage IIIC disease), approximately one-third also harbored disease in para-aortic nodal regions.² Among all patients with endometrial cancer, including those with low-grade disease, only a small fraction (approximately 2%) have isolated para-aortic lymph nodes (positive para-aortic nodes, but negative pelvic nodes). However, among patients with deeply invasive higher-grade tumors, the likelihood of discovering isolated para-aortic metastases is higher at approximately 16%.³ Therefore, the dominant pattern of lymph node metastases and lymphatic dissemination of endometrial cancer appears to be via the parametrial channels laterally towards the pelvic basins, and then sequentially to the para-aortic regions. The direct lymphatic pathway to the para-aortic basins from the uterine fundus through the adnexal lymphatics misses the pelvic regions altogether and may seen logical, but actually is observed fairly infrequently.⁴

Over the subsequent decades, there have been debates and schools of thought regarding what is the optimal degree of lymphatic dissection for endometrial cancer staging. Some advocated for full pelvic and infrarenal para-aortic nodal dissections in all patients, including even those in the lowest risk for metastases. Others advocated for a more limited, inframesenteric para-aortic nodal dissection, although the origins of such a distinction appear to be largely arbitrary. The inferior mesenteric artery is not a physiologic landmark for lymphatic pathways, and approximately half of para-aortic metastases are located above the level of the inferior mesenteric artery. This limited sampling may have been preferred because of relative ease of dissection rather than diagnostic or therapeutic efficacy.

As the population became more obese, making para-aortic nodal dissections less feasible, and laparoscopic staging became accepted as the standard of care in endometrial cancer staging, there was a further push towards limiting the scope of lymphadenectomy. Selective algorithms, such as the so-called “Mayo clinic criteria,” were widely adopted. In this approach, gynecologic oncologists perform full pelvic and infrarenal para-aortic lymphadenectomies but only in the presence of a high-risk uterine feature such as tumor size greater than 2 cm, deep myometrial invasion, or grade 3 histology.³ While this reduced the number of para-aortic dissections being performed, it did not eliminate them, as approximately 40% of patients with endometrial cancer meet at least one of those criteria.

At this same time, we learned something else critical about the benefits, or lack thereof, of lymphadenectomy. Two landmark surgical-staging trials were published in 2009 which randomly assigned women to hysterectomy with lymphadenectomy or hysterectomy alone, and found no survival benefit for lymphadenectomy.^5,6 While these trial results initially were met with noisy backlash, particularly from those who had legitimate concerns regarding study design and conclusions that reach beyond the scope of this column, ultimately their findings (that there is no therapeutic benefit to surgically removing clinically normal lymph nodes) has become largely accepted. The subsequent findings of the Laparoscopic Approach to Cancer of the Endometrium (LACE) trial further support this, as there was no difference in survival found between patients who were randomly assigned to laparoscopic versus open staging for endometrial cancer, even despite a significantly lower rate of lymphadenectomy among the laparoscopic arm.⁷

SLN biopsy, in which the specific nodes which drain the uterus are selectively removed, represents the most recent development in lymph node assessment for endometrial cancer. On average, only three lymph nodes are removed per patient, and para-aortic nodes infrequently are removed, because it is rare that lymphatic pathways drain directly into the aortic basins after cervical injection. Yet despite this more limited dissection of lymph nodes, especially para-aortic, with SLN biopsy, surgeons still observe similar rates of IIIC disease, compared with full lymphadenectomy, suggesting that the presence or absence of lymphatic metastases still is able to be adequately determined. SLN biopsy misses only 3% of lymphatic disease.⁸ What is of particular interest to practitioners of the SLN approach is that “atypical” pathways are discovered approximately 20% of the time, and nodes are harvested from locations such as the presacral space or medial to the internal iliac vessels. These nodes are in locations previously overlooked by even the most comprehensive pelvic and para-aortic lymphadenectomy. Therefore, while the para-aortic nodes may not be systematically removed with SLN biopsy, new and arguably more relevant regions are interrogated, which might explain its equivalent diagnostic virtue.

With this evolution in surgical-staging practice, what we have come to recognize is that the role of lymph node assessment is predominantly, if not exclusively, diagnostic. It can help us determine which patients are at risk for distant relapse and therefore candidates for systemic therapy (chemotherapy), versus those whose risk is predominantly of local relapse and can be adequately treated with local therapies alone, such as vaginal radiation. This brings us to the results of GOG 258. If defining the specific and complete extent of lymph node metastases (as if that was ever truly what surgeons were doing) is no longer necessary to guide the prescription and extent of external beam radiation, then lymph node dissection need only inform us of whether or not there are nodal metastases, not specifically the location of those nodal metastases. The prescription of chemotherapy is the same whether the disease is limited to the pelvic nodes or also includes the para-aortic nodes. While GOG 258 discovered more para-aortic failures among the chemotherapy-alone group, suggesting there may be some therapeutic role of radiation in preventing this, it should be noted that these para-aortic relapses did not negatively impact relapse-free survival, and these patients still can presumably be salvaged with external beam radiation to the site of para-aortic relapse.

It would seem logical that the results of GOG 258 further limit the potential role of para-aortic lymphadenectomy in women with clinical stage I disease. Perhaps para-aortic dissection can be limited to women who are at highest risk for isolated para-aortic disease, such as those with deeply invasive high-grade tumors not successfully mapped with the highly targeted sentinel node biopsy technique? Most clinicians look forward to an era in which we no longer rely on crude dissections of disease-free tissue just to prove they are disease free, but instead can utilize more sophisticated diagnostic methods to recognize disseminated disease.
 

Dr. Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill. Email her at obnews@mdedge.com.

References

1. N Engl J Med. 2019 Jun 13;380(24):2317-26.

2. Cancer. 1987 Oct 15;60(8 Suppl):2035-41.

3. Gynecol Oncol. 2008;109(1):11-8.

4. Int J Gynecol Cancer. 2019 Mar;29(3):613-21.

5. J Natl Cancer Inst. 2008 Dec 3;100(23):1707-16.

6. Lancet. 2009 Jan 10;373(9658):125-36.

7. JAMA. 2017 Mar 28;317(12):1224-33.

8. Lancet Oncol. 2017 Mar;18(3):384-92.

The use of administrative data may improve the accuracy and reduce costs of oncology clinical trial economic analyses, according to a retrospective study.

“We investigated whether administrative data could improve the performance of cancer trial economic analysis,” Timothy P. Hanna, MD, MSc, PhD, of Queen’s University in Kingston, Ont., and colleagues wrote in the Journal of Oncology Practice.

The researchers linked clinical trial and health administrative data to evaluate the utility of administrative data in a group of 572 patients with previously treated metastatic colorectal cancer.

The phase 3 trial assessed cetuximab plus best supportive care versus best supportive care alone in these patients. The trial data set was used to obtain information related to resource utilization, such as hospitalization or treatment costs, in addition to clinical reports, such as vital status.

Several measures were estimated by the team, including the incremental cost-effectiveness ratio (ICER) and total costs.

After analysis, the researchers found that ICER measures were comparable with the use of administrative data versus trial data alone ($164,378 vs. $211,128 per QALY added up to last contact).

“Up to trial date of last contact, vital status was in agreement for more than 96% of patients,” Dr. Hanna and colleagues reported.

These findings highlight the potential utility of administrative data in reducing the costs of collecting applicable data from clinical trials alone.

“A harmonized approach has the potential to provide more complete information on clinical trial participants at reduced cost,” they concluded.

The study was funded by the Institute for Clinical Evaluative Sciences and Queen’s University. The authors reported financial affiliations with Amgen, Janssen, Novartis, and UpToDate.

SOURCE: Hanna TP et al. J Oncol Pract. 2019 Jul 15. doi: 10.1200/JOP.18.00691.

The use of administrative data may improve the accuracy and reduce costs of oncology clinical trial economic analyses, according to a retrospective study.

“We investigated whether administrative data could improve the performance of cancer trial economic analysis,” Timothy P. Hanna, MD, MSc, PhD, of Queen’s University in Kingston, Ont., and colleagues wrote in the Journal of Oncology Practice.

The researchers linked clinical trial and health administrative data to evaluate the utility of administrative data in a group of 572 patients with previously treated metastatic colorectal cancer.

The phase 3 trial assessed cetuximab plus best supportive care versus best supportive care alone in these patients. The trial data set was used to obtain information related to resource utilization, such as hospitalization or treatment costs, in addition to clinical reports, such as vital status.

Several measures were estimated by the team, including the incremental cost-effectiveness ratio (ICER) and total costs.

After analysis, the researchers found that ICER measures were comparable with the use of administrative data versus trial data alone ($164,378 vs. $211,128 per QALY added up to last contact).

“Up to trial date of last contact, vital status was in agreement for more than 96% of patients,” Dr. Hanna and colleagues reported.

These findings highlight the potential utility of administrative data in reducing the costs of collecting applicable data from clinical trials alone.

“A harmonized approach has the potential to provide more complete information on clinical trial participants at reduced cost,” they concluded.

The study was funded by the Institute for Clinical Evaluative Sciences and Queen’s University. The authors reported financial affiliations with Amgen, Janssen, Novartis, and UpToDate.

SOURCE: Hanna TP et al. J Oncol Pract. 2019 Jul 15. doi: 10.1200/JOP.18.00691.

The use of administrative data may improve the accuracy and reduce costs of oncology clinical trial economic analyses, according to a retrospective study.

“We investigated whether administrative data could improve the performance of cancer trial economic analysis,” Timothy P. Hanna, MD, MSc, PhD, of Queen’s University in Kingston, Ont., and colleagues wrote in the Journal of Oncology Practice.

The researchers linked clinical trial and health administrative data to evaluate the utility of administrative data in a group of 572 patients with previously treated metastatic colorectal cancer.

The phase 3 trial assessed cetuximab plus best supportive care versus best supportive care alone in these patients. The trial data set was used to obtain information related to resource utilization, such as hospitalization or treatment costs, in addition to clinical reports, such as vital status.

Several measures were estimated by the team, including the incremental cost-effectiveness ratio (ICER) and total costs.

After analysis, the researchers found that ICER measures were comparable with the use of administrative data versus trial data alone ($164,378 vs. $211,128 per QALY added up to last contact).

“Up to trial date of last contact, vital status was in agreement for more than 96% of patients,” Dr. Hanna and colleagues reported.

These findings highlight the potential utility of administrative data in reducing the costs of collecting applicable data from clinical trials alone.

“A harmonized approach has the potential to provide more complete information on clinical trial participants at reduced cost,” they concluded.

The study was funded by the Institute for Clinical Evaluative Sciences and Queen’s University. The authors reported financial affiliations with Amgen, Janssen, Novartis, and UpToDate.

SOURCE: Hanna TP et al. J Oncol Pract. 2019 Jul 15. doi: 10.1200/JOP.18.00691.

The Food and Drug Administration has expanded the indication for apremilast (Otezla) to include the treatment of oral ulcers associated with Behçet’s disease in adults, according to an announcement from the manufacturer, Celgene.

FDA approval was based on results of the randomized, placebo-controlled, double-blind, phase 3 RELIEF trial, in which 207 patients with Behçet’s disease with active ulcers underwent treatment for 12 weeks with 30 mg apremilast or placebo. When measured on a visual analog scale, the reduction in pain from oral ulcers after 12 weeks in patients receiving apremilast was 42.7 points, compared with 18.7 points in the placebo group. Just over 50% of apremilast patients achieved complete response by week 12, compared with 22.3% in the placebo group.

The most common adverse events associated with apremilast during RELIEF were diarrhea, nausea, headache, and upper respiratory infection. This was consistent with apremilast’s known safety profile.


Apremilast is also indicated for treatment of patients with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy, and for patients with active psoriatic arthritis.

“Oral ulcers are a recurring and debilitating manifestation that affects nearly everyone living with Behçet’s disease and have an important negative impact on the quality of life for these patients. In the clinical trial, Otezla demonstrated improvements in measures of oral ulcers at week 12. Otezla has the potential to be a needed treatment option for U.S. patients and their physicians, who previously had limited options available,” Yusuf Yazici, MD, clinical associate professor in the department of medicine at New York University, said in the announcement.

lfranki@mdedge.com

The Food and Drug Administration has expanded the indication for apremilast (Otezla) to include the treatment of oral ulcers associated with Behçet’s disease in adults, according to an announcement from the manufacturer, Celgene.

FDA approval was based on results of the randomized, placebo-controlled, double-blind, phase 3 RELIEF trial, in which 207 patients with Behçet’s disease with active ulcers underwent treatment for 12 weeks with 30 mg apremilast or placebo. When measured on a visual analog scale, the reduction in pain from oral ulcers after 12 weeks in patients receiving apremilast was 42.7 points, compared with 18.7 points in the placebo group. Just over 50% of apremilast patients achieved complete response by week 12, compared with 22.3% in the placebo group.

The most common adverse events associated with apremilast during RELIEF were diarrhea, nausea, headache, and upper respiratory infection. This was consistent with apremilast’s known safety profile.


Apremilast is also indicated for treatment of patients with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy, and for patients with active psoriatic arthritis.

“Oral ulcers are a recurring and debilitating manifestation that affects nearly everyone living with Behçet’s disease and have an important negative impact on the quality of life for these patients. In the clinical trial, Otezla demonstrated improvements in measures of oral ulcers at week 12. Otezla has the potential to be a needed treatment option for U.S. patients and their physicians, who previously had limited options available,” Yusuf Yazici, MD, clinical associate professor in the department of medicine at New York University, said in the announcement.

lfranki@mdedge.com

The Food and Drug Administration has expanded the indication for apremilast (Otezla) to include the treatment of oral ulcers associated with Behçet’s disease in adults, according to an announcement from the manufacturer, Celgene.

FDA approval was based on results of the randomized, placebo-controlled, double-blind, phase 3 RELIEF trial, in which 207 patients with Behçet’s disease with active ulcers underwent treatment for 12 weeks with 30 mg apremilast or placebo. When measured on a visual analog scale, the reduction in pain from oral ulcers after 12 weeks in patients receiving apremilast was 42.7 points, compared with 18.7 points in the placebo group. Just over 50% of apremilast patients achieved complete response by week 12, compared with 22.3% in the placebo group.

The most common adverse events associated with apremilast during RELIEF were diarrhea, nausea, headache, and upper respiratory infection. This was consistent with apremilast’s known safety profile.


Apremilast is also indicated for treatment of patients with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy, and for patients with active psoriatic arthritis.

“Oral ulcers are a recurring and debilitating manifestation that affects nearly everyone living with Behçet’s disease and have an important negative impact on the quality of life for these patients. In the clinical trial, Otezla demonstrated improvements in measures of oral ulcers at week 12. Otezla has the potential to be a needed treatment option for U.S. patients and their physicians, who previously had limited options available,” Yusuf Yazici, MD, clinical associate professor in the department of medicine at New York University, said in the announcement.

lfranki@mdedge.com

Having a first-degree relative with amyotrophic lateral sclerosis (ALS) increases the lifetime risk of developing the condition, even in the absence of a known ALS-associated genetic mutation, according to a recent Irish population–based study.

designer491/Thinkstock

Among first-degree relatives of individuals with ALS whose genetic status was unknown, the lifetime risk of developing ALS was 1.4%, compared with 0.3% in the general population (P less than .001).

Overall, lifetime heritability for the 1,117 patients in the heritability study cohort was 52.3% (95% confidence interval, 42.9%-61.7%). The highest heritability was seen in mother-daughter dyads; here, the concordance rate for ALS was 2.6% and the heritability estimate was 66.2% (95% CI, 58.5%-73.9%), “pointing to a previously unrecognized sex-mediated association with disease heritability,” Marie Ryan, MD, and coauthors at Trinity College Dublin wrote in JAMA Neurology.

For the purposes of this study, heritability was defined as “the proportion of variance in liability that is attributable to additive genetic factors,” explained the investigators. Their model was applied to 1,123 Irish patients with incident ALS over a 10-year study period, drawing on a national database. Complete medical histories were available for both parents of every individual in the cohort, and the investigators identified 32 parent-offspring dyads with ALS.

In their assessment of “liability” for ALS, Dr. Ryan and colleagues accounted for age-specific and sex-specific ALS incidence rates, using a well-delineated United States reference population. They also took into account competing mortality risks that might intervene before an individual developed ALS.

Although mother-daughter dyads yielded the highest heritability estimates, heritability was also elevated among father-son dyads, at 50.1% (95% CI, 42.0%-59.4%). Opposite-sex dyads (mother-son and father-daughter) yielded similar, and lower, heritability estimates of 34%-38%. Dr. Ryan and coinvestigators acknowledged that female sex hormones might play a role in mediating risk for ALS, but the contribution and mechanism are currently unknown.

The investigators identified 674 patients in the cohort who had been tested for C9orf72; large repeat expansions in the GGGGCC segment of this gene are known to cause ALS. In all, 69 patients were C9orf72 positive, and 14 of these individuals (20.3%) reported that one parent had ALS. Among the entire cohort, 23 of the 32 patients with parents who also had ALS had C9orf72 testing, and 14 of 23 (60.9%) were positive. This discrepancy, wrote Dr. Ryan and coauthors, suggests that “genetic anticipation or pleiotropic effects may have masked the clinical phenotype in their parents.”


Parents were a mean 69.6 years old at the time of diagnosis, and offspring were a mean 52.0 years old; 56% of patients in the study cohort were male.

“[I]n our study, ALS heritability was assessed for the first time in a population in whom genetic mutations have been excluded,” wrote Dr. Ryan and coinvestigators. “We have found that, in the absence of known ALS-associated genetic mutations in the proband, first-degree relatives of individuals with ALS remain at increased risk of developing ALS compared with the general population.”

Dr. Ryan and one coauthor reported receiving funding from Science Foundation Ireland, and one coauthor reported receiving book royalties from Taylor & Francis, and fees from Cytokinetics and Wave Pharmaceuticals. The study was funded by Science Foundation Ireland and the Motor Neurone Disease Association.

koakes@mdedge.com

SOURCE: Ryan M et al. JAMA Neurol. 2019 Jul 22. doi: 10.1001/jamaneurol.2019.2044.

Having a first-degree relative with amyotrophic lateral sclerosis (ALS) increases the lifetime risk of developing the condition, even in the absence of a known ALS-associated genetic mutation, according to a recent Irish population–based study.

designer491/Thinkstock

Among first-degree relatives of individuals with ALS whose genetic status was unknown, the lifetime risk of developing ALS was 1.4%, compared with 0.3% in the general population (P less than .001).

Overall, lifetime heritability for the 1,117 patients in the heritability study cohort was 52.3% (95% confidence interval, 42.9%-61.7%). The highest heritability was seen in mother-daughter dyads; here, the concordance rate for ALS was 2.6% and the heritability estimate was 66.2% (95% CI, 58.5%-73.9%), “pointing to a previously unrecognized sex-mediated association with disease heritability,” Marie Ryan, MD, and coauthors at Trinity College Dublin wrote in JAMA Neurology.

For the purposes of this study, heritability was defined as “the proportion of variance in liability that is attributable to additive genetic factors,” explained the investigators. Their model was applied to 1,123 Irish patients with incident ALS over a 10-year study period, drawing on a national database. Complete medical histories were available for both parents of every individual in the cohort, and the investigators identified 32 parent-offspring dyads with ALS.

In their assessment of “liability” for ALS, Dr. Ryan and colleagues accounted for age-specific and sex-specific ALS incidence rates, using a well-delineated United States reference population. They also took into account competing mortality risks that might intervene before an individual developed ALS.

Although mother-daughter dyads yielded the highest heritability estimates, heritability was also elevated among father-son dyads, at 50.1% (95% CI, 42.0%-59.4%). Opposite-sex dyads (mother-son and father-daughter) yielded similar, and lower, heritability estimates of 34%-38%. Dr. Ryan and coinvestigators acknowledged that female sex hormones might play a role in mediating risk for ALS, but the contribution and mechanism are currently unknown.

The investigators identified 674 patients in the cohort who had been tested for C9orf72; large repeat expansions in the GGGGCC segment of this gene are known to cause ALS. In all, 69 patients were C9orf72 positive, and 14 of these individuals (20.3%) reported that one parent had ALS. Among the entire cohort, 23 of the 32 patients with parents who also had ALS had C9orf72 testing, and 14 of 23 (60.9%) were positive. This discrepancy, wrote Dr. Ryan and coauthors, suggests that “genetic anticipation or pleiotropic effects may have masked the clinical phenotype in their parents.”


Parents were a mean 69.6 years old at the time of diagnosis, and offspring were a mean 52.0 years old; 56% of patients in the study cohort were male.

“[I]n our study, ALS heritability was assessed for the first time in a population in whom genetic mutations have been excluded,” wrote Dr. Ryan and coinvestigators. “We have found that, in the absence of known ALS-associated genetic mutations in the proband, first-degree relatives of individuals with ALS remain at increased risk of developing ALS compared with the general population.”

Dr. Ryan and one coauthor reported receiving funding from Science Foundation Ireland, and one coauthor reported receiving book royalties from Taylor & Francis, and fees from Cytokinetics and Wave Pharmaceuticals. The study was funded by Science Foundation Ireland and the Motor Neurone Disease Association.

koakes@mdedge.com

SOURCE: Ryan M et al. JAMA Neurol. 2019 Jul 22. doi: 10.1001/jamaneurol.2019.2044.

Having a first-degree relative with amyotrophic lateral sclerosis (ALS) increases the lifetime risk of developing the condition, even in the absence of a known ALS-associated genetic mutation, according to a recent Irish population–based study.

designer491/Thinkstock

Among first-degree relatives of individuals with ALS whose genetic status was unknown, the lifetime risk of developing ALS was 1.4%, compared with 0.3% in the general population (P less than .001).

Overall, lifetime heritability for the 1,117 patients in the heritability study cohort was 52.3% (95% confidence interval, 42.9%-61.7%). The highest heritability was seen in mother-daughter dyads; here, the concordance rate for ALS was 2.6% and the heritability estimate was 66.2% (95% CI, 58.5%-73.9%), “pointing to a previously unrecognized sex-mediated association with disease heritability,” Marie Ryan, MD, and coauthors at Trinity College Dublin wrote in JAMA Neurology.

For the purposes of this study, heritability was defined as “the proportion of variance in liability that is attributable to additive genetic factors,” explained the investigators. Their model was applied to 1,123 Irish patients with incident ALS over a 10-year study period, drawing on a national database. Complete medical histories were available for both parents of every individual in the cohort, and the investigators identified 32 parent-offspring dyads with ALS.

In their assessment of “liability” for ALS, Dr. Ryan and colleagues accounted for age-specific and sex-specific ALS incidence rates, using a well-delineated United States reference population. They also took into account competing mortality risks that might intervene before an individual developed ALS.

Although mother-daughter dyads yielded the highest heritability estimates, heritability was also elevated among father-son dyads, at 50.1% (95% CI, 42.0%-59.4%). Opposite-sex dyads (mother-son and father-daughter) yielded similar, and lower, heritability estimates of 34%-38%. Dr. Ryan and coinvestigators acknowledged that female sex hormones might play a role in mediating risk for ALS, but the contribution and mechanism are currently unknown.

The investigators identified 674 patients in the cohort who had been tested for C9orf72; large repeat expansions in the GGGGCC segment of this gene are known to cause ALS. In all, 69 patients were C9orf72 positive, and 14 of these individuals (20.3%) reported that one parent had ALS. Among the entire cohort, 23 of the 32 patients with parents who also had ALS had C9orf72 testing, and 14 of 23 (60.9%) were positive. This discrepancy, wrote Dr. Ryan and coauthors, suggests that “genetic anticipation or pleiotropic effects may have masked the clinical phenotype in their parents.”


Parents were a mean 69.6 years old at the time of diagnosis, and offspring were a mean 52.0 years old; 56% of patients in the study cohort were male.

“[I]n our study, ALS heritability was assessed for the first time in a population in whom genetic mutations have been excluded,” wrote Dr. Ryan and coinvestigators. “We have found that, in the absence of known ALS-associated genetic mutations in the proband, first-degree relatives of individuals with ALS remain at increased risk of developing ALS compared with the general population.”

Dr. Ryan and one coauthor reported receiving funding from Science Foundation Ireland, and one coauthor reported receiving book royalties from Taylor & Francis, and fees from Cytokinetics and Wave Pharmaceuticals. The study was funded by Science Foundation Ireland and the Motor Neurone Disease Association.

koakes@mdedge.com

SOURCE: Ryan M et al. JAMA Neurol. 2019 Jul 22. doi: 10.1001/jamaneurol.2019.2044.