User login
AGA Research Foundation Memorial and Honorary Gifts: A Special Tribute
Did you know you can honor a family member, friend, or colleague whose life has been touched by GI research through a gift to the AGA Research Foundation?
- Giving now or later. Any charitable gift can be made in honor or memory of someone.
- A gift today. An outright gift will help fund the AGA Research Awards Program. Your gift will assist in furthering basic digestive disease research which can ultimately advance research into all digestive diseases. The financial benefits include an income tax deduction and possible elimination of capital gains tax. A cash gift of $5,000 or more qualifies for membership in the AGA Supporter Circle.
- A gift through your will or living trust. You can include a bequest in your will or living trust stating that a specific asset, certain dollar amount, or more commonly a percentage of your estate will pass to the AGA Research Foundation in honor of your loved one. A gift in your will of $50,000 or more qualifies for membership in the AGA Legacy Society, which recognizes the foundation’s most generous individual donors.
- Named commentary section funds. You can support a commentary section in a specific AGA journal to honor or memorialize a loved one. This can be established with a gift of $100,000 over the course of 5 years or through an estate gift. The AGA Institute Publications Committee will work with you to provide name recognition for the commentary section in a specific AGA journal for 5 years. All content and editing will be conducted by the editorial board of the journal.
Your Next Step
An honorary gift is a wonderful way to acknowledge someone’s vision for the future. To learn more about ways to recognize your honoree, visit our website at www.foundation.gastro.org.
Did you know you can honor a family member, friend, or colleague whose life has been touched by GI research through a gift to the AGA Research Foundation?
- Giving now or later. Any charitable gift can be made in honor or memory of someone.
- A gift today. An outright gift will help fund the AGA Research Awards Program. Your gift will assist in furthering basic digestive disease research which can ultimately advance research into all digestive diseases. The financial benefits include an income tax deduction and possible elimination of capital gains tax. A cash gift of $5,000 or more qualifies for membership in the AGA Supporter Circle.
- A gift through your will or living trust. You can include a bequest in your will or living trust stating that a specific asset, certain dollar amount, or more commonly a percentage of your estate will pass to the AGA Research Foundation in honor of your loved one. A gift in your will of $50,000 or more qualifies for membership in the AGA Legacy Society, which recognizes the foundation’s most generous individual donors.
- Named commentary section funds. You can support a commentary section in a specific AGA journal to honor or memorialize a loved one. This can be established with a gift of $100,000 over the course of 5 years or through an estate gift. The AGA Institute Publications Committee will work with you to provide name recognition for the commentary section in a specific AGA journal for 5 years. All content and editing will be conducted by the editorial board of the journal.
Your Next Step
An honorary gift is a wonderful way to acknowledge someone’s vision for the future. To learn more about ways to recognize your honoree, visit our website at www.foundation.gastro.org.
Did you know you can honor a family member, friend, or colleague whose life has been touched by GI research through a gift to the AGA Research Foundation?
- Giving now or later. Any charitable gift can be made in honor or memory of someone.
- A gift today. An outright gift will help fund the AGA Research Awards Program. Your gift will assist in furthering basic digestive disease research which can ultimately advance research into all digestive diseases. The financial benefits include an income tax deduction and possible elimination of capital gains tax. A cash gift of $5,000 or more qualifies for membership in the AGA Supporter Circle.
- A gift through your will or living trust. You can include a bequest in your will or living trust stating that a specific asset, certain dollar amount, or more commonly a percentage of your estate will pass to the AGA Research Foundation in honor of your loved one. A gift in your will of $50,000 or more qualifies for membership in the AGA Legacy Society, which recognizes the foundation’s most generous individual donors.
- Named commentary section funds. You can support a commentary section in a specific AGA journal to honor or memorialize a loved one. This can be established with a gift of $100,000 over the course of 5 years or through an estate gift. The AGA Institute Publications Committee will work with you to provide name recognition for the commentary section in a specific AGA journal for 5 years. All content and editing will be conducted by the editorial board of the journal.
Your Next Step
An honorary gift is a wonderful way to acknowledge someone’s vision for the future. To learn more about ways to recognize your honoree, visit our website at www.foundation.gastro.org.
Managing GI and Liver Conditions During Pregnancy: New Guidance from AGA
according to a clinical practice update (CPU) from the American Gastroenterological Association.
Notably, procedures, medications, or other interventions intended to improve maternal health shouldn’t be withheld solely because the patient is pregnant, the authors wrote. Instead, treatments should be personalized based on a risk-benefit assessment.
“Pregnancy causes significant physiological changes that can affect the GI tract and liver function. Some common conditions — such as nausea, vomiting, gastroesophageal reflux disease (GERD), and constipation — may be exacerbated, and underlying GI or liver diseases can behave differently during pregnancy,” said lead author Shivangi Kothari, MD, associate professor of medicine and associate director of endoscopy at the University of Rochester Medical Center and Strong Memorial Hospital, both in Rochester, New York.
“These conditions can pose significant risks to both the mother and fetus, and their management requires a specialized, updated approach,” she said. “This clinical practice update stresses the need for coordinated, multidisciplinary care among obstetricians, gastroenterologists, hepatologists, and maternal-and-fetal medicine experts to ensure optimal outcomes, particularly in complex or high-risk cases.”
The update was published online in Gastroenterology.
Pregnancy-Related Concerns
The best path to optimal outcomes is to start early, the authors wrote. Before pregnancy, patients should consider preconception and contraceptive care counseling with a multidisciplinary team that can address GI and liver issues, especially among reproductive-age people who want to become pregnant.
Once pregnant, though, patients shouldn’t be deterred from receiving procedures, medications, or interventions just because they’re pregnant, the authors wrote. Instead, taking an individual approach will help clinicians decide what to do based on the risks and benefits.
At the beginning of pregnancy, early treatment of nausea and vomiting can reduce progression to hyperemesis gravidarum, the authors wrote. Stepwise treatment can include vitamin B6, doxylamine, hydration, and adequate nutrition, followed by ondansetron, metoclopramide, promethazine, and intravenous glucocorticoids in moderate to severe cases.
Constipation may also pose a problem because of hormonal, physiological, and medication-related changes. Treatment options can include dietary fiber, lactulose, and polyethylene glycol-based laxatives.
Patients with certain conditions — such as complex inflammatory bowel disease (IBD), advanced cirrhosis, or liver transplant — should work with a multidisciplinary team to coordinate birth, preferably in a tertiary care center, the authors wrote.
For patients with IBD, clinical remission helps to improve pregnancy outcomes, including before conception, during pregnancy, and throughout the postpartum period. Biologic agents should be used during pregnancy and postpartum, though methotrexate, thalidomide, and ozanimod should be stopped at least 6 months before conception.
For patients with chronic hepatitis B, serum hepatitis B virus DNA and liver biochemical levels should be tested. Patients with a serum level > 200,000 IU/mL during the third trimester should be considered for treatment with tenofovir disoproxil fumarate.
For patients on immunosuppressive therapy for chronic liver diseases or after liver transplantation, therapy should continue at the lowest effective dose. However, mycophenolate mofetil shouldn’t be administered during pregnancy.
Intrahepatic cholestasis of pregnancy may be diagnosed during the second or third trimester based on pruritus and a serum bile acid level > 10 μmol/L. Treatment should include oral ursodeoxycholic acid, with a total daily dose of 10-15 mg/kg.
Other pregnancy-related liver diseases — such as pre-eclampsia; hemolysis, elevated liver enzymes, and low platelets syndrome; and acute fatty liver of pregnancy — require careful birth planning and evaluation for possible liver transplantation. For certain high-risk patients, daily aspirin should start at week 12 of gestation.
In addition, elective endoscopic procedures should wait until after birth, and nonemergent but necessary procedures should be performed during the second trimester. Patients with cirrhosis should undergo evaluation for esophageal varices, and upper endoscopy should happen during the second trimester to guide beta-blocker therapy or endoscopic variceal litigation.
Endoscopic retrograde cholangiopancreatography can be performed for urgent indications, such as choledocholithiasis, cholangitis, and some gallstone pancreatitis cases, ideally during the second trimester.
Cholecystectomy is considered safe during pregnancy, with a laparoscopic approach as the standard of care regardless of trimester, though the second trimester is ideal.
Pregnancy-Related Updates in Practice
Ultimately, clinicians should familiarize themselves with the best practice advice to feel comfortable when counseling and managing pregnancy-related concerns, especially high-risk patients, said Eugenia Shmidt, MD, assistant professor of gastroenterology, hepatology, and nutrition, and founder of the IBD Preconception and Pregnancy Planning Clinic at the University of Minnesota, Minneapolis.
“Half of all patients with GI and liver disease are women, and oftentimes, they don’t have appropriate guidance regarding reproductive health in the context of their disease,” she said. “There exists a very large knowledge gap in this area, particularly because most clinical trials exclude pregnant people.”
Most importantly, the advice statements can guide practitioners on how to help pregnant patients make informed reproductive decisions, she added.
“This CPU makes it clear that preconception counseling and multidisciplinary care are key in optimizing reproductive health, regardless of the underlying GI or liver disease,” Shmidt said. “GI practitioners should be counseling women well in advance of pregnancy and recruiting all relevant stakeholders as early as possible, even prior to conception. This way, pregnancy care is not reactive, but instead proactive.”
The authors received no specific funding for this update. Kothari and Shmidt reported no relevant disclosures.
A version of this article appeared on Medscape.com.
according to a clinical practice update (CPU) from the American Gastroenterological Association.
Notably, procedures, medications, or other interventions intended to improve maternal health shouldn’t be withheld solely because the patient is pregnant, the authors wrote. Instead, treatments should be personalized based on a risk-benefit assessment.
“Pregnancy causes significant physiological changes that can affect the GI tract and liver function. Some common conditions — such as nausea, vomiting, gastroesophageal reflux disease (GERD), and constipation — may be exacerbated, and underlying GI or liver diseases can behave differently during pregnancy,” said lead author Shivangi Kothari, MD, associate professor of medicine and associate director of endoscopy at the University of Rochester Medical Center and Strong Memorial Hospital, both in Rochester, New York.
“These conditions can pose significant risks to both the mother and fetus, and their management requires a specialized, updated approach,” she said. “This clinical practice update stresses the need for coordinated, multidisciplinary care among obstetricians, gastroenterologists, hepatologists, and maternal-and-fetal medicine experts to ensure optimal outcomes, particularly in complex or high-risk cases.”
The update was published online in Gastroenterology.
Pregnancy-Related Concerns
The best path to optimal outcomes is to start early, the authors wrote. Before pregnancy, patients should consider preconception and contraceptive care counseling with a multidisciplinary team that can address GI and liver issues, especially among reproductive-age people who want to become pregnant.
Once pregnant, though, patients shouldn’t be deterred from receiving procedures, medications, or interventions just because they’re pregnant, the authors wrote. Instead, taking an individual approach will help clinicians decide what to do based on the risks and benefits.
At the beginning of pregnancy, early treatment of nausea and vomiting can reduce progression to hyperemesis gravidarum, the authors wrote. Stepwise treatment can include vitamin B6, doxylamine, hydration, and adequate nutrition, followed by ondansetron, metoclopramide, promethazine, and intravenous glucocorticoids in moderate to severe cases.
Constipation may also pose a problem because of hormonal, physiological, and medication-related changes. Treatment options can include dietary fiber, lactulose, and polyethylene glycol-based laxatives.
Patients with certain conditions — such as complex inflammatory bowel disease (IBD), advanced cirrhosis, or liver transplant — should work with a multidisciplinary team to coordinate birth, preferably in a tertiary care center, the authors wrote.
For patients with IBD, clinical remission helps to improve pregnancy outcomes, including before conception, during pregnancy, and throughout the postpartum period. Biologic agents should be used during pregnancy and postpartum, though methotrexate, thalidomide, and ozanimod should be stopped at least 6 months before conception.
For patients with chronic hepatitis B, serum hepatitis B virus DNA and liver biochemical levels should be tested. Patients with a serum level > 200,000 IU/mL during the third trimester should be considered for treatment with tenofovir disoproxil fumarate.
For patients on immunosuppressive therapy for chronic liver diseases or after liver transplantation, therapy should continue at the lowest effective dose. However, mycophenolate mofetil shouldn’t be administered during pregnancy.
Intrahepatic cholestasis of pregnancy may be diagnosed during the second or third trimester based on pruritus and a serum bile acid level > 10 μmol/L. Treatment should include oral ursodeoxycholic acid, with a total daily dose of 10-15 mg/kg.
Other pregnancy-related liver diseases — such as pre-eclampsia; hemolysis, elevated liver enzymes, and low platelets syndrome; and acute fatty liver of pregnancy — require careful birth planning and evaluation for possible liver transplantation. For certain high-risk patients, daily aspirin should start at week 12 of gestation.
In addition, elective endoscopic procedures should wait until after birth, and nonemergent but necessary procedures should be performed during the second trimester. Patients with cirrhosis should undergo evaluation for esophageal varices, and upper endoscopy should happen during the second trimester to guide beta-blocker therapy or endoscopic variceal litigation.
Endoscopic retrograde cholangiopancreatography can be performed for urgent indications, such as choledocholithiasis, cholangitis, and some gallstone pancreatitis cases, ideally during the second trimester.
Cholecystectomy is considered safe during pregnancy, with a laparoscopic approach as the standard of care regardless of trimester, though the second trimester is ideal.
Pregnancy-Related Updates in Practice
Ultimately, clinicians should familiarize themselves with the best practice advice to feel comfortable when counseling and managing pregnancy-related concerns, especially high-risk patients, said Eugenia Shmidt, MD, assistant professor of gastroenterology, hepatology, and nutrition, and founder of the IBD Preconception and Pregnancy Planning Clinic at the University of Minnesota, Minneapolis.
“Half of all patients with GI and liver disease are women, and oftentimes, they don’t have appropriate guidance regarding reproductive health in the context of their disease,” she said. “There exists a very large knowledge gap in this area, particularly because most clinical trials exclude pregnant people.”
Most importantly, the advice statements can guide practitioners on how to help pregnant patients make informed reproductive decisions, she added.
“This CPU makes it clear that preconception counseling and multidisciplinary care are key in optimizing reproductive health, regardless of the underlying GI or liver disease,” Shmidt said. “GI practitioners should be counseling women well in advance of pregnancy and recruiting all relevant stakeholders as early as possible, even prior to conception. This way, pregnancy care is not reactive, but instead proactive.”
The authors received no specific funding for this update. Kothari and Shmidt reported no relevant disclosures.
A version of this article appeared on Medscape.com.
according to a clinical practice update (CPU) from the American Gastroenterological Association.
Notably, procedures, medications, or other interventions intended to improve maternal health shouldn’t be withheld solely because the patient is pregnant, the authors wrote. Instead, treatments should be personalized based on a risk-benefit assessment.
“Pregnancy causes significant physiological changes that can affect the GI tract and liver function. Some common conditions — such as nausea, vomiting, gastroesophageal reflux disease (GERD), and constipation — may be exacerbated, and underlying GI or liver diseases can behave differently during pregnancy,” said lead author Shivangi Kothari, MD, associate professor of medicine and associate director of endoscopy at the University of Rochester Medical Center and Strong Memorial Hospital, both in Rochester, New York.
“These conditions can pose significant risks to both the mother and fetus, and their management requires a specialized, updated approach,” she said. “This clinical practice update stresses the need for coordinated, multidisciplinary care among obstetricians, gastroenterologists, hepatologists, and maternal-and-fetal medicine experts to ensure optimal outcomes, particularly in complex or high-risk cases.”
The update was published online in Gastroenterology.
Pregnancy-Related Concerns
The best path to optimal outcomes is to start early, the authors wrote. Before pregnancy, patients should consider preconception and contraceptive care counseling with a multidisciplinary team that can address GI and liver issues, especially among reproductive-age people who want to become pregnant.
Once pregnant, though, patients shouldn’t be deterred from receiving procedures, medications, or interventions just because they’re pregnant, the authors wrote. Instead, taking an individual approach will help clinicians decide what to do based on the risks and benefits.
At the beginning of pregnancy, early treatment of nausea and vomiting can reduce progression to hyperemesis gravidarum, the authors wrote. Stepwise treatment can include vitamin B6, doxylamine, hydration, and adequate nutrition, followed by ondansetron, metoclopramide, promethazine, and intravenous glucocorticoids in moderate to severe cases.
Constipation may also pose a problem because of hormonal, physiological, and medication-related changes. Treatment options can include dietary fiber, lactulose, and polyethylene glycol-based laxatives.
Patients with certain conditions — such as complex inflammatory bowel disease (IBD), advanced cirrhosis, or liver transplant — should work with a multidisciplinary team to coordinate birth, preferably in a tertiary care center, the authors wrote.
For patients with IBD, clinical remission helps to improve pregnancy outcomes, including before conception, during pregnancy, and throughout the postpartum period. Biologic agents should be used during pregnancy and postpartum, though methotrexate, thalidomide, and ozanimod should be stopped at least 6 months before conception.
For patients with chronic hepatitis B, serum hepatitis B virus DNA and liver biochemical levels should be tested. Patients with a serum level > 200,000 IU/mL during the third trimester should be considered for treatment with tenofovir disoproxil fumarate.
For patients on immunosuppressive therapy for chronic liver diseases or after liver transplantation, therapy should continue at the lowest effective dose. However, mycophenolate mofetil shouldn’t be administered during pregnancy.
Intrahepatic cholestasis of pregnancy may be diagnosed during the second or third trimester based on pruritus and a serum bile acid level > 10 μmol/L. Treatment should include oral ursodeoxycholic acid, with a total daily dose of 10-15 mg/kg.
Other pregnancy-related liver diseases — such as pre-eclampsia; hemolysis, elevated liver enzymes, and low platelets syndrome; and acute fatty liver of pregnancy — require careful birth planning and evaluation for possible liver transplantation. For certain high-risk patients, daily aspirin should start at week 12 of gestation.
In addition, elective endoscopic procedures should wait until after birth, and nonemergent but necessary procedures should be performed during the second trimester. Patients with cirrhosis should undergo evaluation for esophageal varices, and upper endoscopy should happen during the second trimester to guide beta-blocker therapy or endoscopic variceal litigation.
Endoscopic retrograde cholangiopancreatography can be performed for urgent indications, such as choledocholithiasis, cholangitis, and some gallstone pancreatitis cases, ideally during the second trimester.
Cholecystectomy is considered safe during pregnancy, with a laparoscopic approach as the standard of care regardless of trimester, though the second trimester is ideal.
Pregnancy-Related Updates in Practice
Ultimately, clinicians should familiarize themselves with the best practice advice to feel comfortable when counseling and managing pregnancy-related concerns, especially high-risk patients, said Eugenia Shmidt, MD, assistant professor of gastroenterology, hepatology, and nutrition, and founder of the IBD Preconception and Pregnancy Planning Clinic at the University of Minnesota, Minneapolis.
“Half of all patients with GI and liver disease are women, and oftentimes, they don’t have appropriate guidance regarding reproductive health in the context of their disease,” she said. “There exists a very large knowledge gap in this area, particularly because most clinical trials exclude pregnant people.”
Most importantly, the advice statements can guide practitioners on how to help pregnant patients make informed reproductive decisions, she added.
“This CPU makes it clear that preconception counseling and multidisciplinary care are key in optimizing reproductive health, regardless of the underlying GI or liver disease,” Shmidt said. “GI practitioners should be counseling women well in advance of pregnancy and recruiting all relevant stakeholders as early as possible, even prior to conception. This way, pregnancy care is not reactive, but instead proactive.”
The authors received no specific funding for this update. Kothari and Shmidt reported no relevant disclosures.
A version of this article appeared on Medscape.com.
FROM GASTROENTEROLOGY
Obesity Linked with Malignant Progression of Barrett’s Esophagus
A dose-response relationship exists between body mass index (BMI) and esophageal adenocarcinoma (EAC) or high-grade dysplasia (HGD), the authors found.
“Obesity has been implicated in the pathogenesis of many reflux-related esophageal disorders such as gastroesophageal reflux disease (GERD), BE, and EAC,” said senior author Leo Alexandre, MRCP, PhD, a clinical associate professor and member of the Norwich Epidemiology Centre at the University of East Anglia and gastroenterologist with the Norfolk & Norwich University Hospital NHS Foundation Trust, both in Norwich, England.
“Guidelines advocate obesity as a criterion for targeted screening for BE in patients with chronic reflux symptoms,” he said. “While obesity is a recognized risk factor for both BE and EAC, it’s been unclear whether obesity is a risk factor for malignant progression.”
The study was published in Clinical Gastroenterology and Hepatology.
Analyzing Risk
BE, which is the only recognized precursor lesion to EAC, is associated with a 30-fold increase in the incidence of the aggressive cancer. Typically, malignant progression occurs when nondysplastic BE epithelium progresses to low-grade dysplasia (LGD) and then HGD, followed by invasive adenocarcinoma.
Current guidelines suggest that patients with BE undergo endoscopic surveillance for early detection of adenocarcinoma. However, clinical risk factors could help with risk stratification and a personalized approach to long-term BE management, the authors wrote.
Alexandre and colleagues reviewed case-control or cohort studies that reported on the effect of BMI on the progression of nondysplastic BE or LGD to EAC, HGD, or esophageal cancer (EC). Then they estimated the dose-response relationship with a two-stage dose-response meta-analysis.
Overall, 20 observational studies reported data on 38,565 adult patients, including 1684 patients who were diagnosed with EAC, HGD, or EC. The studies enrolled patients between 1976 and 2019 and were published between 2005 and 2022. Most were based in Europe or the United States, and 74.4% of participants were men.
Among 12 cohort studies with 19,223 patients who had baseline nondysplastic BE or LGD, 816 progressed to EAC, HGD, or EC. The pooled annual rate of progression was .03%.
Among eight cohort studies with 6647 male patients who had baseline nondysplastic BE or LGD, 555 progressed to EAC, HGD, or EC. The pooled annual rate of progression was .02%.
In addition, among 1992 female patients with baseline nondysplastic BE or LGD, 110 progressed to EAC, HGD, or EC. The pooled annual rate of progression was .01%, which wasn’t a significant difference compared with the progression rate among male patients.
Based on meta-analyses, obesity was associated with a 4% increase in the risk for malignant progression among patients with BE (unadjusted odds ratio, 1.04; 95% CI, 1.00-1.07; P < .001).
Notably, each 5 unit increase in BMI was associated with a 6% increase in the risk of developing HGD or EAC (adjusted odds ratio, 1.06; 95% CI, 1.02-1.10; P < .001).
“Although the exact mechanisms by which obesity promotes esophageal carcinogenesis is not fully understood, several possible mechanisms may explain it,” Alexandre said. “The most obvious pathologic link is via GERD, with the mechanical effect of visceral obesity promoting the GERD directly, and the sequence of Barrett’s dysplasia to cancer indirectly. In addition, it has been demonstrated in experimental studies that gastric acid and bile acid drive malignant changes in esophageal epithelium through stimulation of proliferation, inhibition of apoptosis, and generation of free radicals.”
Considering Risk
This study highlights the importance of recognizing the association between obesity and cancer risks, said Prateek Sharma, MD, professor of medicine and director of gastrointestinal training at the University of Kansas School of Medicine, Kansas City, Kansas.
Sharma, who wasn’t involved with this study, coauthored an American Gastroenterological Association technical review on the management of BE.
“Obesity is a known risk factor for esophageal adenocarcinoma and may be a modifiable risk factor,” he said. “Showing that BMI is related to neoplastic progression in Barrett’s esophagus may impact surveillance intervals.”
Future research should look at additional obesity-related factors, such as visceral obesity and malignant progression of BE, as well as whether diet, lifestyle, and bariatric interventions can reduce the risk for progression.
“The next steps also include plugging BMI into risk scores and risk stratification models to enable targeted surveillance among high-risk groups,” Sharma said.
One of the study coauthors received funding as a National Institute for Health Research Academic clinical fellow. No other funding sources were declared. Alexandre and Sharma reported no relevant disclosures.
A version of this article appeared on Medscape.com.
A dose-response relationship exists between body mass index (BMI) and esophageal adenocarcinoma (EAC) or high-grade dysplasia (HGD), the authors found.
“Obesity has been implicated in the pathogenesis of many reflux-related esophageal disorders such as gastroesophageal reflux disease (GERD), BE, and EAC,” said senior author Leo Alexandre, MRCP, PhD, a clinical associate professor and member of the Norwich Epidemiology Centre at the University of East Anglia and gastroenterologist with the Norfolk & Norwich University Hospital NHS Foundation Trust, both in Norwich, England.
“Guidelines advocate obesity as a criterion for targeted screening for BE in patients with chronic reflux symptoms,” he said. “While obesity is a recognized risk factor for both BE and EAC, it’s been unclear whether obesity is a risk factor for malignant progression.”
The study was published in Clinical Gastroenterology and Hepatology.
Analyzing Risk
BE, which is the only recognized precursor lesion to EAC, is associated with a 30-fold increase in the incidence of the aggressive cancer. Typically, malignant progression occurs when nondysplastic BE epithelium progresses to low-grade dysplasia (LGD) and then HGD, followed by invasive adenocarcinoma.
Current guidelines suggest that patients with BE undergo endoscopic surveillance for early detection of adenocarcinoma. However, clinical risk factors could help with risk stratification and a personalized approach to long-term BE management, the authors wrote.
Alexandre and colleagues reviewed case-control or cohort studies that reported on the effect of BMI on the progression of nondysplastic BE or LGD to EAC, HGD, or esophageal cancer (EC). Then they estimated the dose-response relationship with a two-stage dose-response meta-analysis.
Overall, 20 observational studies reported data on 38,565 adult patients, including 1684 patients who were diagnosed with EAC, HGD, or EC. The studies enrolled patients between 1976 and 2019 and were published between 2005 and 2022. Most were based in Europe or the United States, and 74.4% of participants were men.
Among 12 cohort studies with 19,223 patients who had baseline nondysplastic BE or LGD, 816 progressed to EAC, HGD, or EC. The pooled annual rate of progression was .03%.
Among eight cohort studies with 6647 male patients who had baseline nondysplastic BE or LGD, 555 progressed to EAC, HGD, or EC. The pooled annual rate of progression was .02%.
In addition, among 1992 female patients with baseline nondysplastic BE or LGD, 110 progressed to EAC, HGD, or EC. The pooled annual rate of progression was .01%, which wasn’t a significant difference compared with the progression rate among male patients.
Based on meta-analyses, obesity was associated with a 4% increase in the risk for malignant progression among patients with BE (unadjusted odds ratio, 1.04; 95% CI, 1.00-1.07; P < .001).
Notably, each 5 unit increase in BMI was associated with a 6% increase in the risk of developing HGD or EAC (adjusted odds ratio, 1.06; 95% CI, 1.02-1.10; P < .001).
“Although the exact mechanisms by which obesity promotes esophageal carcinogenesis is not fully understood, several possible mechanisms may explain it,” Alexandre said. “The most obvious pathologic link is via GERD, with the mechanical effect of visceral obesity promoting the GERD directly, and the sequence of Barrett’s dysplasia to cancer indirectly. In addition, it has been demonstrated in experimental studies that gastric acid and bile acid drive malignant changes in esophageal epithelium through stimulation of proliferation, inhibition of apoptosis, and generation of free radicals.”
Considering Risk
This study highlights the importance of recognizing the association between obesity and cancer risks, said Prateek Sharma, MD, professor of medicine and director of gastrointestinal training at the University of Kansas School of Medicine, Kansas City, Kansas.
Sharma, who wasn’t involved with this study, coauthored an American Gastroenterological Association technical review on the management of BE.
“Obesity is a known risk factor for esophageal adenocarcinoma and may be a modifiable risk factor,” he said. “Showing that BMI is related to neoplastic progression in Barrett’s esophagus may impact surveillance intervals.”
Future research should look at additional obesity-related factors, such as visceral obesity and malignant progression of BE, as well as whether diet, lifestyle, and bariatric interventions can reduce the risk for progression.
“The next steps also include plugging BMI into risk scores and risk stratification models to enable targeted surveillance among high-risk groups,” Sharma said.
One of the study coauthors received funding as a National Institute for Health Research Academic clinical fellow. No other funding sources were declared. Alexandre and Sharma reported no relevant disclosures.
A version of this article appeared on Medscape.com.
A dose-response relationship exists between body mass index (BMI) and esophageal adenocarcinoma (EAC) or high-grade dysplasia (HGD), the authors found.
“Obesity has been implicated in the pathogenesis of many reflux-related esophageal disorders such as gastroesophageal reflux disease (GERD), BE, and EAC,” said senior author Leo Alexandre, MRCP, PhD, a clinical associate professor and member of the Norwich Epidemiology Centre at the University of East Anglia and gastroenterologist with the Norfolk & Norwich University Hospital NHS Foundation Trust, both in Norwich, England.
“Guidelines advocate obesity as a criterion for targeted screening for BE in patients with chronic reflux symptoms,” he said. “While obesity is a recognized risk factor for both BE and EAC, it’s been unclear whether obesity is a risk factor for malignant progression.”
The study was published in Clinical Gastroenterology and Hepatology.
Analyzing Risk
BE, which is the only recognized precursor lesion to EAC, is associated with a 30-fold increase in the incidence of the aggressive cancer. Typically, malignant progression occurs when nondysplastic BE epithelium progresses to low-grade dysplasia (LGD) and then HGD, followed by invasive adenocarcinoma.
Current guidelines suggest that patients with BE undergo endoscopic surveillance for early detection of adenocarcinoma. However, clinical risk factors could help with risk stratification and a personalized approach to long-term BE management, the authors wrote.
Alexandre and colleagues reviewed case-control or cohort studies that reported on the effect of BMI on the progression of nondysplastic BE or LGD to EAC, HGD, or esophageal cancer (EC). Then they estimated the dose-response relationship with a two-stage dose-response meta-analysis.
Overall, 20 observational studies reported data on 38,565 adult patients, including 1684 patients who were diagnosed with EAC, HGD, or EC. The studies enrolled patients between 1976 and 2019 and were published between 2005 and 2022. Most were based in Europe or the United States, and 74.4% of participants were men.
Among 12 cohort studies with 19,223 patients who had baseline nondysplastic BE or LGD, 816 progressed to EAC, HGD, or EC. The pooled annual rate of progression was .03%.
Among eight cohort studies with 6647 male patients who had baseline nondysplastic BE or LGD, 555 progressed to EAC, HGD, or EC. The pooled annual rate of progression was .02%.
In addition, among 1992 female patients with baseline nondysplastic BE or LGD, 110 progressed to EAC, HGD, or EC. The pooled annual rate of progression was .01%, which wasn’t a significant difference compared with the progression rate among male patients.
Based on meta-analyses, obesity was associated with a 4% increase in the risk for malignant progression among patients with BE (unadjusted odds ratio, 1.04; 95% CI, 1.00-1.07; P < .001).
Notably, each 5 unit increase in BMI was associated with a 6% increase in the risk of developing HGD or EAC (adjusted odds ratio, 1.06; 95% CI, 1.02-1.10; P < .001).
“Although the exact mechanisms by which obesity promotes esophageal carcinogenesis is not fully understood, several possible mechanisms may explain it,” Alexandre said. “The most obvious pathologic link is via GERD, with the mechanical effect of visceral obesity promoting the GERD directly, and the sequence of Barrett’s dysplasia to cancer indirectly. In addition, it has been demonstrated in experimental studies that gastric acid and bile acid drive malignant changes in esophageal epithelium through stimulation of proliferation, inhibition of apoptosis, and generation of free radicals.”
Considering Risk
This study highlights the importance of recognizing the association between obesity and cancer risks, said Prateek Sharma, MD, professor of medicine and director of gastrointestinal training at the University of Kansas School of Medicine, Kansas City, Kansas.
Sharma, who wasn’t involved with this study, coauthored an American Gastroenterological Association technical review on the management of BE.
“Obesity is a known risk factor for esophageal adenocarcinoma and may be a modifiable risk factor,” he said. “Showing that BMI is related to neoplastic progression in Barrett’s esophagus may impact surveillance intervals.”
Future research should look at additional obesity-related factors, such as visceral obesity and malignant progression of BE, as well as whether diet, lifestyle, and bariatric interventions can reduce the risk for progression.
“The next steps also include plugging BMI into risk scores and risk stratification models to enable targeted surveillance among high-risk groups,” Sharma said.
One of the study coauthors received funding as a National Institute for Health Research Academic clinical fellow. No other funding sources were declared. Alexandre and Sharma reported no relevant disclosures.
A version of this article appeared on Medscape.com.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Oral Microbiome Dysbiosis: Biomarker for Upper GI Disorders?
TOPLINE:
Dysbiosis of the oral microbiome is associated with various upper gastrointestinal (UGI) disorders and precancerous lesions, with specific microbial signatures varying by disease and oral site, research shows.
METHODOLOGY:
- Emerging evidence suggests that the oral microbiota may contribute to the development of gastrointestinal malignancies, leading to efforts to identify biomarkers for early detection and progress of disease.
- In this population-based cross-sectional study, researchers studied the association between the microbiome of saliva, subgingival, and buccal mucosa and UGI disorders, particularly precancerous lesions.
- Participants included 388 adults who underwent upper endoscopy with biopsies for histopathologic analysis.
- UGI symptoms were evaluated using a validated tool, and 16S ribosomal RNA sequencing was used to characterize microbial diversity and composition of 380 saliva, 200 subgingival, and 267 buccal mucosa samples.
TAKEAWAY:
- Saliva dysbiosis was associated with several UGI disorders, including gastroesophageal reflux symptoms alone, symptomatic esophagitis, combined esophagitis and Barrett’s esophagus (BE), Helicobacter pylori–positive histology, chemical reactive gastritis, atrophic H pylori gastritis, and intestinal metaplasia.
- In contrast, dysbiosis in subgingival and buccal mucosa was more specifically associated with BE and atrophic H pylori gastritis.
- Among several identified genera, Prevotella and Fusobacterium in saliva were associated with gastric atrophy and intestinal metaplasia, and in subgingival samples, there was a notable link between Fretibacterium in BE and Fusobacterium in gastric atrophy and intestinal metaplasia.
IN PRACTICE:
“Our study for the first time suggests that microbiota in the subgingival and buccal regions may serve as more specific biomarkers for detecting precancerous lesions in asymptomatic patients, particularly for Barrett’s esophagus,” the authors wrote. “Saliva might be more appropriate for monitoring any UGI disorders at the population level.”
SOURCE:
The study, with first author Fatemeh Sadeghi, PhD, with Karolinska Institutet, Stockholm, Sweden, was published online in the American Journal of Gastroenterology.
LIMITATIONS:
The study used bacterial DNA, which cannot distinguish metabolically active bacteria. Data on diet and probiotic use were not collected. The cross-sectional design precludes conclusions about causality.
DISCLOSURES:
The authors declared no conflicts of interest. The study was funded by the Swedish Cancer Society and the Swedish Research Council.
A version of this article first appeared on Medscape.com.
TOPLINE:
Dysbiosis of the oral microbiome is associated with various upper gastrointestinal (UGI) disorders and precancerous lesions, with specific microbial signatures varying by disease and oral site, research shows.
METHODOLOGY:
- Emerging evidence suggests that the oral microbiota may contribute to the development of gastrointestinal malignancies, leading to efforts to identify biomarkers for early detection and progress of disease.
- In this population-based cross-sectional study, researchers studied the association between the microbiome of saliva, subgingival, and buccal mucosa and UGI disorders, particularly precancerous lesions.
- Participants included 388 adults who underwent upper endoscopy with biopsies for histopathologic analysis.
- UGI symptoms were evaluated using a validated tool, and 16S ribosomal RNA sequencing was used to characterize microbial diversity and composition of 380 saliva, 200 subgingival, and 267 buccal mucosa samples.
TAKEAWAY:
- Saliva dysbiosis was associated with several UGI disorders, including gastroesophageal reflux symptoms alone, symptomatic esophagitis, combined esophagitis and Barrett’s esophagus (BE), Helicobacter pylori–positive histology, chemical reactive gastritis, atrophic H pylori gastritis, and intestinal metaplasia.
- In contrast, dysbiosis in subgingival and buccal mucosa was more specifically associated with BE and atrophic H pylori gastritis.
- Among several identified genera, Prevotella and Fusobacterium in saliva were associated with gastric atrophy and intestinal metaplasia, and in subgingival samples, there was a notable link between Fretibacterium in BE and Fusobacterium in gastric atrophy and intestinal metaplasia.
IN PRACTICE:
“Our study for the first time suggests that microbiota in the subgingival and buccal regions may serve as more specific biomarkers for detecting precancerous lesions in asymptomatic patients, particularly for Barrett’s esophagus,” the authors wrote. “Saliva might be more appropriate for monitoring any UGI disorders at the population level.”
SOURCE:
The study, with first author Fatemeh Sadeghi, PhD, with Karolinska Institutet, Stockholm, Sweden, was published online in the American Journal of Gastroenterology.
LIMITATIONS:
The study used bacterial DNA, which cannot distinguish metabolically active bacteria. Data on diet and probiotic use were not collected. The cross-sectional design precludes conclusions about causality.
DISCLOSURES:
The authors declared no conflicts of interest. The study was funded by the Swedish Cancer Society and the Swedish Research Council.
A version of this article first appeared on Medscape.com.
TOPLINE:
Dysbiosis of the oral microbiome is associated with various upper gastrointestinal (UGI) disorders and precancerous lesions, with specific microbial signatures varying by disease and oral site, research shows.
METHODOLOGY:
- Emerging evidence suggests that the oral microbiota may contribute to the development of gastrointestinal malignancies, leading to efforts to identify biomarkers for early detection and progress of disease.
- In this population-based cross-sectional study, researchers studied the association between the microbiome of saliva, subgingival, and buccal mucosa and UGI disorders, particularly precancerous lesions.
- Participants included 388 adults who underwent upper endoscopy with biopsies for histopathologic analysis.
- UGI symptoms were evaluated using a validated tool, and 16S ribosomal RNA sequencing was used to characterize microbial diversity and composition of 380 saliva, 200 subgingival, and 267 buccal mucosa samples.
TAKEAWAY:
- Saliva dysbiosis was associated with several UGI disorders, including gastroesophageal reflux symptoms alone, symptomatic esophagitis, combined esophagitis and Barrett’s esophagus (BE), Helicobacter pylori–positive histology, chemical reactive gastritis, atrophic H pylori gastritis, and intestinal metaplasia.
- In contrast, dysbiosis in subgingival and buccal mucosa was more specifically associated with BE and atrophic H pylori gastritis.
- Among several identified genera, Prevotella and Fusobacterium in saliva were associated with gastric atrophy and intestinal metaplasia, and in subgingival samples, there was a notable link between Fretibacterium in BE and Fusobacterium in gastric atrophy and intestinal metaplasia.
IN PRACTICE:
“Our study for the first time suggests that microbiota in the subgingival and buccal regions may serve as more specific biomarkers for detecting precancerous lesions in asymptomatic patients, particularly for Barrett’s esophagus,” the authors wrote. “Saliva might be more appropriate for monitoring any UGI disorders at the population level.”
SOURCE:
The study, with first author Fatemeh Sadeghi, PhD, with Karolinska Institutet, Stockholm, Sweden, was published online in the American Journal of Gastroenterology.
LIMITATIONS:
The study used bacterial DNA, which cannot distinguish metabolically active bacteria. Data on diet and probiotic use were not collected. The cross-sectional design precludes conclusions about causality.
DISCLOSURES:
The authors declared no conflicts of interest. The study was funded by the Swedish Cancer Society and the Swedish Research Council.
A version of this article first appeared on Medscape.com.
Myeloma: Can Lymphopenia Help Predict Patient Outcomes?
TOPLINE:
The analysis of 11,427 US Deparment of Veterans Affairs (VA) hospital patients with multiple myeloma (MM) reveals that lymphopenia affects 53% of patients at diagnosis. The median overall survival was 2.7 years in patients with severely low absolute lymphocyte count vs 4.2 years in those with normal counts.
METHODOLOGY:
- Researchers evaluated 11,427 patients diagnosed with MM between 2000 and 2019 at VA medical centers using absolute lymphocyte count obtained closest to diagnosis and up to 2.5 years thereafter.
- Patients were stratified into three absolute lymphocyte count categories: Severely low (less than 1 × 10⁹/μL), low (1 × 10⁹/μL to 1.5 × 10⁹/μL), and normal (> 1.5 × 10⁹/μL).
- Analysis excluded patients with acute and chronic leukemias, aplastic anemia, myelodysplastic syndrome, hairy cell leukemia, or myeloproliferative neoplasms before MM diagnosis.
- Follow-up duration extended from diagnosis until development of another hematologic malignancy, death, truncation date (15 years after diagnosis), or study end date.
TAKEAWAY:
- Lymphopenia was present in 53% of patients at MM diagnosis and was associated with inferior overall survival.
- Median overall survival for patients with severely low, low, and normal absolute lymphocyte count at diagnosis was 2.7 years, 3.3 years, and 4.2 years, respectively (P < .001).
- Persistent or new development of lymphopenia during treatment and follow-up was linked to inferior overall survival.
- Standard induction therapy with lenalidomide, bortezomib, and dexamethasone did not overcome inferior outcomes in patients with lymphopenia, showing median overall survival of 3.6 years, 4.6 years, and 5.7 years among patients with severely low, low, and normal baseline absolute lymphocyte count, respectively (P less than .001).
IN PRACTICE:
“Because immune dysregulation and immunosenescence in the bone marrow microenvironment are reflected in the peripheral blood lymphocyte count and peripheral blood markers may, in turn, correlate with clinical features and outcome in MM, we sought to identify clinical features correlating with peripheral blood lymphopenia and evaluate absolute lymphocyte count at diagnosis as a predictor of outcome in MM and in the context of standard induction treatment,” the authors wrote.
SOURCE:
This study was led by Grace M. Ferri and Cenk Yildirim, Boston Medical Center in Boston. It was published online in Blood Advances.
LIMITATIONS:
This study population consisted predominantly of male participants due to being conducted in the VA system. Additionally, researchers acknowledged that lymphopenia could not be exclusively attributed to MM, as other treatments common in older populations might contribute. The use of alkylating agents like cyclophosphamide and melphalan during treatment could also influence lymphopenia levels.
DISCLOSURES:
Individual-level data underlying this study are available to researchers with VA regulatory approval, consistent with VA policy.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
A version of this article first appeared on Medscape.com.
TOPLINE:
The analysis of 11,427 US Deparment of Veterans Affairs (VA) hospital patients with multiple myeloma (MM) reveals that lymphopenia affects 53% of patients at diagnosis. The median overall survival was 2.7 years in patients with severely low absolute lymphocyte count vs 4.2 years in those with normal counts.
METHODOLOGY:
- Researchers evaluated 11,427 patients diagnosed with MM between 2000 and 2019 at VA medical centers using absolute lymphocyte count obtained closest to diagnosis and up to 2.5 years thereafter.
- Patients were stratified into three absolute lymphocyte count categories: Severely low (less than 1 × 10⁹/μL), low (1 × 10⁹/μL to 1.5 × 10⁹/μL), and normal (> 1.5 × 10⁹/μL).
- Analysis excluded patients with acute and chronic leukemias, aplastic anemia, myelodysplastic syndrome, hairy cell leukemia, or myeloproliferative neoplasms before MM diagnosis.
- Follow-up duration extended from diagnosis until development of another hematologic malignancy, death, truncation date (15 years after diagnosis), or study end date.
TAKEAWAY:
- Lymphopenia was present in 53% of patients at MM diagnosis and was associated with inferior overall survival.
- Median overall survival for patients with severely low, low, and normal absolute lymphocyte count at diagnosis was 2.7 years, 3.3 years, and 4.2 years, respectively (P < .001).
- Persistent or new development of lymphopenia during treatment and follow-up was linked to inferior overall survival.
- Standard induction therapy with lenalidomide, bortezomib, and dexamethasone did not overcome inferior outcomes in patients with lymphopenia, showing median overall survival of 3.6 years, 4.6 years, and 5.7 years among patients with severely low, low, and normal baseline absolute lymphocyte count, respectively (P less than .001).
IN PRACTICE:
“Because immune dysregulation and immunosenescence in the bone marrow microenvironment are reflected in the peripheral blood lymphocyte count and peripheral blood markers may, in turn, correlate with clinical features and outcome in MM, we sought to identify clinical features correlating with peripheral blood lymphopenia and evaluate absolute lymphocyte count at diagnosis as a predictor of outcome in MM and in the context of standard induction treatment,” the authors wrote.
SOURCE:
This study was led by Grace M. Ferri and Cenk Yildirim, Boston Medical Center in Boston. It was published online in Blood Advances.
LIMITATIONS:
This study population consisted predominantly of male participants due to being conducted in the VA system. Additionally, researchers acknowledged that lymphopenia could not be exclusively attributed to MM, as other treatments common in older populations might contribute. The use of alkylating agents like cyclophosphamide and melphalan during treatment could also influence lymphopenia levels.
DISCLOSURES:
Individual-level data underlying this study are available to researchers with VA regulatory approval, consistent with VA policy.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
A version of this article first appeared on Medscape.com.
TOPLINE:
The analysis of 11,427 US Deparment of Veterans Affairs (VA) hospital patients with multiple myeloma (MM) reveals that lymphopenia affects 53% of patients at diagnosis. The median overall survival was 2.7 years in patients with severely low absolute lymphocyte count vs 4.2 years in those with normal counts.
METHODOLOGY:
- Researchers evaluated 11,427 patients diagnosed with MM between 2000 and 2019 at VA medical centers using absolute lymphocyte count obtained closest to diagnosis and up to 2.5 years thereafter.
- Patients were stratified into three absolute lymphocyte count categories: Severely low (less than 1 × 10⁹/μL), low (1 × 10⁹/μL to 1.5 × 10⁹/μL), and normal (> 1.5 × 10⁹/μL).
- Analysis excluded patients with acute and chronic leukemias, aplastic anemia, myelodysplastic syndrome, hairy cell leukemia, or myeloproliferative neoplasms before MM diagnosis.
- Follow-up duration extended from diagnosis until development of another hematologic malignancy, death, truncation date (15 years after diagnosis), or study end date.
TAKEAWAY:
- Lymphopenia was present in 53% of patients at MM diagnosis and was associated with inferior overall survival.
- Median overall survival for patients with severely low, low, and normal absolute lymphocyte count at diagnosis was 2.7 years, 3.3 years, and 4.2 years, respectively (P < .001).
- Persistent or new development of lymphopenia during treatment and follow-up was linked to inferior overall survival.
- Standard induction therapy with lenalidomide, bortezomib, and dexamethasone did not overcome inferior outcomes in patients with lymphopenia, showing median overall survival of 3.6 years, 4.6 years, and 5.7 years among patients with severely low, low, and normal baseline absolute lymphocyte count, respectively (P less than .001).
IN PRACTICE:
“Because immune dysregulation and immunosenescence in the bone marrow microenvironment are reflected in the peripheral blood lymphocyte count and peripheral blood markers may, in turn, correlate with clinical features and outcome in MM, we sought to identify clinical features correlating with peripheral blood lymphopenia and evaluate absolute lymphocyte count at diagnosis as a predictor of outcome in MM and in the context of standard induction treatment,” the authors wrote.
SOURCE:
This study was led by Grace M. Ferri and Cenk Yildirim, Boston Medical Center in Boston. It was published online in Blood Advances.
LIMITATIONS:
This study population consisted predominantly of male participants due to being conducted in the VA system. Additionally, researchers acknowledged that lymphopenia could not be exclusively attributed to MM, as other treatments common in older populations might contribute. The use of alkylating agents like cyclophosphamide and melphalan during treatment could also influence lymphopenia levels.
DISCLOSURES:
Individual-level data underlying this study are available to researchers with VA regulatory approval, consistent with VA policy.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
A version of this article first appeared on Medscape.com.
Emergency Presentations for Vets with CRC Linked to Higher Mortality
TOPLINE: More than 28% of US Department of Veterans Affairs (VA) patients with colorectal cancer were diagnosed through emergency presentations, which were associated with a higher mortality risk. Emergency presentations increased during COVID-19 from prepandemic rates.
METHODOLOGY:
- A retrospective cohort study analyzed 9096 incident colorectal cancer cancer cases diagnosed in the Veterans Health Administration from 2017 to 2021.
- Researchers applied a validated algorithm to identify emergency presentations, defined as cancer diagnoses within 30 days following emergency care episodes or unplanned hospital admissions.
- Analysis utilized multivariable logistic regression and Cox proportional hazards models to examine associations between emergency presentations and cancer stage, treatment, and mortality.
TAKEAWAY:
- Patients with emergency presentations were more likely to have advanced stage disease (odds ratio [OR], 1.70; 95% CI, 1.53-1.88) compared to those without emergency presentations.
- Emergency presentations were associated with lower likelihood of receiving cancer treatment (OR, 0.65; 95% CI, 0.56-0.75) and higher mortality risk (hazard ratio [HR], 1.70; 95% CI, 1.56-1.84).
- The proportion of emergency presentations increased from 26.4% in 2017-2019 to 31.4% during the COVID-19 pandemic years 2020-2021 (P < .0001).
IN PRACTICE: " Our findings from one of the largest studies within a US population to examine emergency presentations among patients with colorectal cancer show that emergency presentations are common and an important negative predictor of cancer outcomes…Our study findings highlight the need for continued research and implementation efforts focused on measurement and mitigation of emergency presentations among patients with colorectal cancer.”
SOURCE: The study was led by the Center for Innovations in Quality, Effectiveness and Safety at Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine in Houston. It was published online on December 11 in Digestive Diseases and Sciences.
LIMITATIONS: The study's findings are limited by the predominantly male veteran population with lower socioeconomic status, which may affect generalizability. The equal access health care model used by the VA and its and strong screening programs may result in emergency presentation rates that differ from the private sector.
TOPLINE: More than 28% of US Department of Veterans Affairs (VA) patients with colorectal cancer were diagnosed through emergency presentations, which were associated with a higher mortality risk. Emergency presentations increased during COVID-19 from prepandemic rates.
METHODOLOGY:
- A retrospective cohort study analyzed 9096 incident colorectal cancer cancer cases diagnosed in the Veterans Health Administration from 2017 to 2021.
- Researchers applied a validated algorithm to identify emergency presentations, defined as cancer diagnoses within 30 days following emergency care episodes or unplanned hospital admissions.
- Analysis utilized multivariable logistic regression and Cox proportional hazards models to examine associations between emergency presentations and cancer stage, treatment, and mortality.
TAKEAWAY:
- Patients with emergency presentations were more likely to have advanced stage disease (odds ratio [OR], 1.70; 95% CI, 1.53-1.88) compared to those without emergency presentations.
- Emergency presentations were associated with lower likelihood of receiving cancer treatment (OR, 0.65; 95% CI, 0.56-0.75) and higher mortality risk (hazard ratio [HR], 1.70; 95% CI, 1.56-1.84).
- The proportion of emergency presentations increased from 26.4% in 2017-2019 to 31.4% during the COVID-19 pandemic years 2020-2021 (P < .0001).
IN PRACTICE: " Our findings from one of the largest studies within a US population to examine emergency presentations among patients with colorectal cancer show that emergency presentations are common and an important negative predictor of cancer outcomes…Our study findings highlight the need for continued research and implementation efforts focused on measurement and mitigation of emergency presentations among patients with colorectal cancer.”
SOURCE: The study was led by the Center for Innovations in Quality, Effectiveness and Safety at Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine in Houston. It was published online on December 11 in Digestive Diseases and Sciences.
LIMITATIONS: The study's findings are limited by the predominantly male veteran population with lower socioeconomic status, which may affect generalizability. The equal access health care model used by the VA and its and strong screening programs may result in emergency presentation rates that differ from the private sector.
TOPLINE: More than 28% of US Department of Veterans Affairs (VA) patients with colorectal cancer were diagnosed through emergency presentations, which were associated with a higher mortality risk. Emergency presentations increased during COVID-19 from prepandemic rates.
METHODOLOGY:
- A retrospective cohort study analyzed 9096 incident colorectal cancer cancer cases diagnosed in the Veterans Health Administration from 2017 to 2021.
- Researchers applied a validated algorithm to identify emergency presentations, defined as cancer diagnoses within 30 days following emergency care episodes or unplanned hospital admissions.
- Analysis utilized multivariable logistic regression and Cox proportional hazards models to examine associations between emergency presentations and cancer stage, treatment, and mortality.
TAKEAWAY:
- Patients with emergency presentations were more likely to have advanced stage disease (odds ratio [OR], 1.70; 95% CI, 1.53-1.88) compared to those without emergency presentations.
- Emergency presentations were associated with lower likelihood of receiving cancer treatment (OR, 0.65; 95% CI, 0.56-0.75) and higher mortality risk (hazard ratio [HR], 1.70; 95% CI, 1.56-1.84).
- The proportion of emergency presentations increased from 26.4% in 2017-2019 to 31.4% during the COVID-19 pandemic years 2020-2021 (P < .0001).
IN PRACTICE: " Our findings from one of the largest studies within a US population to examine emergency presentations among patients with colorectal cancer show that emergency presentations are common and an important negative predictor of cancer outcomes…Our study findings highlight the need for continued research and implementation efforts focused on measurement and mitigation of emergency presentations among patients with colorectal cancer.”
SOURCE: The study was led by the Center for Innovations in Quality, Effectiveness and Safety at Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine in Houston. It was published online on December 11 in Digestive Diseases and Sciences.
LIMITATIONS: The study's findings are limited by the predominantly male veteran population with lower socioeconomic status, which may affect generalizability. The equal access health care model used by the VA and its and strong screening programs may result in emergency presentation rates that differ from the private sector.
FDA Approves Sotorasib + Panitumumab for mCRC
The US Food and Drug Administration (FDA) has approved sotorasib (Lumakras, Amgen Inc.) with panitumumab (Vectibix, Amgen Inc.) for the treatment of certain adult patients with metastatic colorectal cancer (mCRC).
Specifically, the combination therapy is indicated for those with KRAS G12C-mutated mCRC, as determined using an FDA-approved test, who have received prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, according to the FDA notice. The FDA also approved the therascreen KRAS RGQ PCR Kit (QIAGEN GmbH) as a companion diagnostic device for identifying eligible patients.
Approval of sotorasib with panitumumab was based on findings from the randomized, open-label, controlled CodeBreaK 300 trial showing improved overall response rates (ORR) and progression-free survival (PFS) with sotorasib and panitumumab vs investigator’s choice of trifluridine/tipiracil or regorafenib, which are current standard-of-care options.
Median PFS was 5.6 months in 53 patients randomized to receive 960 mg of oral sotorasib once daily plus 6 mg/kg of intravenous (IV) panitumumab every 2 weeks, and 2 months in 54 patients randomized to receive standard-of-care therapy (hazard ratio, 0.48). The ORR was 26% vs 0% in the arms, respectively, and the duration of response in the sotorasib/panitumumab arm was 4.4 months. No significant difference in PFS was observed between the standard-of-care arm and a third arm with 53 patients who received 240 mg of oral sotorasib daily plus 6 mg/kg of IV panitumumab every 2 weeks.
Overall survival (OS) did not differ significantly between the treatment arms in the final analysis, but the study was not statistically powered for OS.
Adverse reactions occurring in at least 20% of patients receiving sotorasib/panitumumab were rash, dry skin, diarrhea, stomatitis, fatigue, and musculoskeletal pain. Common grade 3-4 laboratory abnormalities, which occurred in two or more patients, included decreased magnesium, decreased potassium, decreased corrected calcium, and increased potassium.
The recommended dose of sotorasib is 960 mg given orally once daily and administered before the first panitumumab infusion. The recommended panitumumab dose is 6 mg/kg as an IV infusion every 14 days until disease progression, unacceptable toxicity, or until sotorasib is withheld or discontinued, according to the full prescribing information.
A version of this article first appeared on Medscape.com.
The US Food and Drug Administration (FDA) has approved sotorasib (Lumakras, Amgen Inc.) with panitumumab (Vectibix, Amgen Inc.) for the treatment of certain adult patients with metastatic colorectal cancer (mCRC).
Specifically, the combination therapy is indicated for those with KRAS G12C-mutated mCRC, as determined using an FDA-approved test, who have received prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, according to the FDA notice. The FDA also approved the therascreen KRAS RGQ PCR Kit (QIAGEN GmbH) as a companion diagnostic device for identifying eligible patients.
Approval of sotorasib with panitumumab was based on findings from the randomized, open-label, controlled CodeBreaK 300 trial showing improved overall response rates (ORR) and progression-free survival (PFS) with sotorasib and panitumumab vs investigator’s choice of trifluridine/tipiracil or regorafenib, which are current standard-of-care options.
Median PFS was 5.6 months in 53 patients randomized to receive 960 mg of oral sotorasib once daily plus 6 mg/kg of intravenous (IV) panitumumab every 2 weeks, and 2 months in 54 patients randomized to receive standard-of-care therapy (hazard ratio, 0.48). The ORR was 26% vs 0% in the arms, respectively, and the duration of response in the sotorasib/panitumumab arm was 4.4 months. No significant difference in PFS was observed between the standard-of-care arm and a third arm with 53 patients who received 240 mg of oral sotorasib daily plus 6 mg/kg of IV panitumumab every 2 weeks.
Overall survival (OS) did not differ significantly between the treatment arms in the final analysis, but the study was not statistically powered for OS.
Adverse reactions occurring in at least 20% of patients receiving sotorasib/panitumumab were rash, dry skin, diarrhea, stomatitis, fatigue, and musculoskeletal pain. Common grade 3-4 laboratory abnormalities, which occurred in two or more patients, included decreased magnesium, decreased potassium, decreased corrected calcium, and increased potassium.
The recommended dose of sotorasib is 960 mg given orally once daily and administered before the first panitumumab infusion. The recommended panitumumab dose is 6 mg/kg as an IV infusion every 14 days until disease progression, unacceptable toxicity, or until sotorasib is withheld or discontinued, according to the full prescribing information.
A version of this article first appeared on Medscape.com.
The US Food and Drug Administration (FDA) has approved sotorasib (Lumakras, Amgen Inc.) with panitumumab (Vectibix, Amgen Inc.) for the treatment of certain adult patients with metastatic colorectal cancer (mCRC).
Specifically, the combination therapy is indicated for those with KRAS G12C-mutated mCRC, as determined using an FDA-approved test, who have received prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, according to the FDA notice. The FDA also approved the therascreen KRAS RGQ PCR Kit (QIAGEN GmbH) as a companion diagnostic device for identifying eligible patients.
Approval of sotorasib with panitumumab was based on findings from the randomized, open-label, controlled CodeBreaK 300 trial showing improved overall response rates (ORR) and progression-free survival (PFS) with sotorasib and panitumumab vs investigator’s choice of trifluridine/tipiracil or regorafenib, which are current standard-of-care options.
Median PFS was 5.6 months in 53 patients randomized to receive 960 mg of oral sotorasib once daily plus 6 mg/kg of intravenous (IV) panitumumab every 2 weeks, and 2 months in 54 patients randomized to receive standard-of-care therapy (hazard ratio, 0.48). The ORR was 26% vs 0% in the arms, respectively, and the duration of response in the sotorasib/panitumumab arm was 4.4 months. No significant difference in PFS was observed between the standard-of-care arm and a third arm with 53 patients who received 240 mg of oral sotorasib daily plus 6 mg/kg of IV panitumumab every 2 weeks.
Overall survival (OS) did not differ significantly between the treatment arms in the final analysis, but the study was not statistically powered for OS.
Adverse reactions occurring in at least 20% of patients receiving sotorasib/panitumumab were rash, dry skin, diarrhea, stomatitis, fatigue, and musculoskeletal pain. Common grade 3-4 laboratory abnormalities, which occurred in two or more patients, included decreased magnesium, decreased potassium, decreased corrected calcium, and increased potassium.
The recommended dose of sotorasib is 960 mg given orally once daily and administered before the first panitumumab infusion. The recommended panitumumab dose is 6 mg/kg as an IV infusion every 14 days until disease progression, unacceptable toxicity, or until sotorasib is withheld or discontinued, according to the full prescribing information.
A version of this article first appeared on Medscape.com.
Physical Activity Before Cancer Diagnosis Linked to Lower Progression and Mortality Risk
TOPLINE:
Physical activity before stage I cancer diagnosis is associated with reduced risk for disease progression and mortality. Members engaging in at least 60 minutes of weekly physical activity showed a 27% lower risk for progression and 47% lower risk for mortality compared with inactive individuals.
METHODOLOGY:
- Physical activity plays a significant role in reducing cancer mortality with high levels having been associated with an 18% reduction in cancer-specific mortality compared with lower levels in patients with pre- and/or post-diagnosed cancer.
- The new analysis included 28,248 members with stage I cancers enrolled in an oncology programme in South Africa, with physical activity recorded through fitness devices, logged gym sessions, and participation in organized events.
- Participants were categorized into three groups: No physical activity (0 min/wk), low physical activity (< 60 min/wk), and moderate to high physical activity (≥ 60 min/wk) based on activity levels 12 months before diagnosis.
- Researchers measured outcomes including time to progression, time to death, and all-cause mortality, with a follow-up period ranging from 1-154 months.
- Analysis adjusted for covariates including age, sex, socioeconomic status, and patient complexity measured by Johns Hopkins Adjusted Clinical Groups Systems software.
TAKEAWAY:
- Members with low physical activity showed a hazard ratio (HR) of 0.84 (95% CI, 0.79-0.89) for progression or death compared with those with no activity, whereas those with moderate to high activity showed an HR of 0.73 (95% CI, 0.70-0.77).
- For all-cause mortality, low physical activity members demonstrated an HR of 0.67 (95% CI, 0.61-0.74), whereas moderate to high activity members showed an HR of 0.53 (95% CI, 0.50-0.58) compared with inactive members.
- At 24 months post-diagnosis, individuals with moderate to high physical activity showed 80% probability of nonprogression compared with 74% for inactive individuals.
- Survival probability at 24 months was 95% for moderate to high activity members vs 91% for those with no physical activity.
IN PRACTICE:
“Physical activity may be considered to confer substantial benefits in terms of progression and overall mortality to those diagnosed with cancer. In a world where cancer continues to be a significant public health burden, the promotion of physical activity can yield important benefits regarding the progression of cancer as well as its prevention and management,” the authors of the study wrote.
SOURCE:
This study was led by Ntokozo Mabena of Discovery Vitality in Sandton, South Africa. It was published online in British Journal of Sports Medicine.
LIMITATIONS:
According to the authors, potential biases exist from not adjusting for confounding factors such as smoking status and alcohol consumption, along with incomplete body mass index data. The study assumed members without recorded physical activity points were inactive, which may not be accurate for all individuals. The findings may not be generalizable to the broader South African population as the study cohort had access to private medical insurance.
DISCLOSURES:
Authors Mabena, Sandra Lehmann, Deepak Patel, and Mosima Mabunda are employed by Discovery. Other authors Mike Greyling and Jon S. Patricios serve as a consultant for Discovery and an editor of British Journal of Sports Medicine, respectively.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
A version of this article first appeared on Medscape.com.
TOPLINE:
Physical activity before stage I cancer diagnosis is associated with reduced risk for disease progression and mortality. Members engaging in at least 60 minutes of weekly physical activity showed a 27% lower risk for progression and 47% lower risk for mortality compared with inactive individuals.
METHODOLOGY:
- Physical activity plays a significant role in reducing cancer mortality with high levels having been associated with an 18% reduction in cancer-specific mortality compared with lower levels in patients with pre- and/or post-diagnosed cancer.
- The new analysis included 28,248 members with stage I cancers enrolled in an oncology programme in South Africa, with physical activity recorded through fitness devices, logged gym sessions, and participation in organized events.
- Participants were categorized into three groups: No physical activity (0 min/wk), low physical activity (< 60 min/wk), and moderate to high physical activity (≥ 60 min/wk) based on activity levels 12 months before diagnosis.
- Researchers measured outcomes including time to progression, time to death, and all-cause mortality, with a follow-up period ranging from 1-154 months.
- Analysis adjusted for covariates including age, sex, socioeconomic status, and patient complexity measured by Johns Hopkins Adjusted Clinical Groups Systems software.
TAKEAWAY:
- Members with low physical activity showed a hazard ratio (HR) of 0.84 (95% CI, 0.79-0.89) for progression or death compared with those with no activity, whereas those with moderate to high activity showed an HR of 0.73 (95% CI, 0.70-0.77).
- For all-cause mortality, low physical activity members demonstrated an HR of 0.67 (95% CI, 0.61-0.74), whereas moderate to high activity members showed an HR of 0.53 (95% CI, 0.50-0.58) compared with inactive members.
- At 24 months post-diagnosis, individuals with moderate to high physical activity showed 80% probability of nonprogression compared with 74% for inactive individuals.
- Survival probability at 24 months was 95% for moderate to high activity members vs 91% for those with no physical activity.
IN PRACTICE:
“Physical activity may be considered to confer substantial benefits in terms of progression and overall mortality to those diagnosed with cancer. In a world where cancer continues to be a significant public health burden, the promotion of physical activity can yield important benefits regarding the progression of cancer as well as its prevention and management,” the authors of the study wrote.
SOURCE:
This study was led by Ntokozo Mabena of Discovery Vitality in Sandton, South Africa. It was published online in British Journal of Sports Medicine.
LIMITATIONS:
According to the authors, potential biases exist from not adjusting for confounding factors such as smoking status and alcohol consumption, along with incomplete body mass index data. The study assumed members without recorded physical activity points were inactive, which may not be accurate for all individuals. The findings may not be generalizable to the broader South African population as the study cohort had access to private medical insurance.
DISCLOSURES:
Authors Mabena, Sandra Lehmann, Deepak Patel, and Mosima Mabunda are employed by Discovery. Other authors Mike Greyling and Jon S. Patricios serve as a consultant for Discovery and an editor of British Journal of Sports Medicine, respectively.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
A version of this article first appeared on Medscape.com.
TOPLINE:
Physical activity before stage I cancer diagnosis is associated with reduced risk for disease progression and mortality. Members engaging in at least 60 minutes of weekly physical activity showed a 27% lower risk for progression and 47% lower risk for mortality compared with inactive individuals.
METHODOLOGY:
- Physical activity plays a significant role in reducing cancer mortality with high levels having been associated with an 18% reduction in cancer-specific mortality compared with lower levels in patients with pre- and/or post-diagnosed cancer.
- The new analysis included 28,248 members with stage I cancers enrolled in an oncology programme in South Africa, with physical activity recorded through fitness devices, logged gym sessions, and participation in organized events.
- Participants were categorized into three groups: No physical activity (0 min/wk), low physical activity (< 60 min/wk), and moderate to high physical activity (≥ 60 min/wk) based on activity levels 12 months before diagnosis.
- Researchers measured outcomes including time to progression, time to death, and all-cause mortality, with a follow-up period ranging from 1-154 months.
- Analysis adjusted for covariates including age, sex, socioeconomic status, and patient complexity measured by Johns Hopkins Adjusted Clinical Groups Systems software.
TAKEAWAY:
- Members with low physical activity showed a hazard ratio (HR) of 0.84 (95% CI, 0.79-0.89) for progression or death compared with those with no activity, whereas those with moderate to high activity showed an HR of 0.73 (95% CI, 0.70-0.77).
- For all-cause mortality, low physical activity members demonstrated an HR of 0.67 (95% CI, 0.61-0.74), whereas moderate to high activity members showed an HR of 0.53 (95% CI, 0.50-0.58) compared with inactive members.
- At 24 months post-diagnosis, individuals with moderate to high physical activity showed 80% probability of nonprogression compared with 74% for inactive individuals.
- Survival probability at 24 months was 95% for moderate to high activity members vs 91% for those with no physical activity.
IN PRACTICE:
“Physical activity may be considered to confer substantial benefits in terms of progression and overall mortality to those diagnosed with cancer. In a world where cancer continues to be a significant public health burden, the promotion of physical activity can yield important benefits regarding the progression of cancer as well as its prevention and management,” the authors of the study wrote.
SOURCE:
This study was led by Ntokozo Mabena of Discovery Vitality in Sandton, South Africa. It was published online in British Journal of Sports Medicine.
LIMITATIONS:
According to the authors, potential biases exist from not adjusting for confounding factors such as smoking status and alcohol consumption, along with incomplete body mass index data. The study assumed members without recorded physical activity points were inactive, which may not be accurate for all individuals. The findings may not be generalizable to the broader South African population as the study cohort had access to private medical insurance.
DISCLOSURES:
Authors Mabena, Sandra Lehmann, Deepak Patel, and Mosima Mabunda are employed by Discovery. Other authors Mike Greyling and Jon S. Patricios serve as a consultant for Discovery and an editor of British Journal of Sports Medicine, respectively.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
A version of this article first appeared on Medscape.com.
Lack of Chemoradiation Impact in Endometrial Cancer: The Need for Quicker Results in the Future
This transcript has been edited for clarity.
Hello. I’m Dr. Maurie Markman from City of Hope. I wanted to briefly discuss a very important paper. This is one that probably didn’t get as much attention as I believe it should. It looks at a very important clinically relevant question, and one that might very much say, can we do more such studies but only do them faster?
This was a trial reported in the Journal of Clinical Oncology earlier this year titled, “Radiation Therapy With or Without Cisplatin for Local Recurrences of Endometrial Cancer: Results From an NRG Oncology/GOG Prospective Randomized Multicenter Clinical Study.”
Fortunately, most patients with endometrial cancer have low-grade cancers and are cured with standard surgery, plus or minus radiation. However, a small percentage of patients, even with low-grade endometrial cancer, will recur.
There are several questions that come up. What is the optimal therapy? What is the outcome for such patients? Should we perhaps give chemotherapy along with the radiation as we do, for example, standardly in cervical cancer?
This study attempted to address that question. There was a total of 165 patients randomized in this trial that went on for 12 years, looking at local radiation vs radiation plus cisplatin — which is, again, standardly given as chemoradiation in cervical cancer.
What were the results? When this paper was reported 16 years after the study was initiated, the results showed the addition of chemotherapy did not add to the benefits of the radiation and in fact increased toxicity. Very importantly, the local control and overall control of the disease was excellent. In fact, at 3 years, 73% of the patients treated with radiation alone were disease-free.
It’s very important to know this, the value of radiation, and that adding chemotherapy with radiation doesn’t make a difference.
One might ask, if this is an important clinical question, is there a way or would there be a way in the future to take a question like this and significantly expand the population of individuals and the population of oncologists that might participate in community-based studies, where you’re asking a very simple question?
You irradiate vs something else; you have a standard of care; you’re looking at progression-free survival, which is a very valid endpoint, or overall survival, and you don’t anticipate significant differences in toxicity because you might use this therapy otherwise.
Would it be possible to answer the question not in 12 years, but in half that time or maybe 20% of that time? The results are important for patients being treated today and their doctors who are advising on optimal therapy.
For those of you who are interested in the question of the management of endometrial cancer, this type of pragmatic trial, I would encourage you to read this important paper. Thank you for your attention.
Maurie Markman, Professor of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center; President, Medicine & Science, City of Hope Atlanta, Chicago, Phoenix, has disclosed the following relevant financial relationships: Received income in an amount equal to or greater than $250 from GlaxoSmithKline and AstraZeneca.
A version of this article first appeared on Medscape.com.
This transcript has been edited for clarity.
Hello. I’m Dr. Maurie Markman from City of Hope. I wanted to briefly discuss a very important paper. This is one that probably didn’t get as much attention as I believe it should. It looks at a very important clinically relevant question, and one that might very much say, can we do more such studies but only do them faster?
This was a trial reported in the Journal of Clinical Oncology earlier this year titled, “Radiation Therapy With or Without Cisplatin for Local Recurrences of Endometrial Cancer: Results From an NRG Oncology/GOG Prospective Randomized Multicenter Clinical Study.”
Fortunately, most patients with endometrial cancer have low-grade cancers and are cured with standard surgery, plus or minus radiation. However, a small percentage of patients, even with low-grade endometrial cancer, will recur.
There are several questions that come up. What is the optimal therapy? What is the outcome for such patients? Should we perhaps give chemotherapy along with the radiation as we do, for example, standardly in cervical cancer?
This study attempted to address that question. There was a total of 165 patients randomized in this trial that went on for 12 years, looking at local radiation vs radiation plus cisplatin — which is, again, standardly given as chemoradiation in cervical cancer.
What were the results? When this paper was reported 16 years after the study was initiated, the results showed the addition of chemotherapy did not add to the benefits of the radiation and in fact increased toxicity. Very importantly, the local control and overall control of the disease was excellent. In fact, at 3 years, 73% of the patients treated with radiation alone were disease-free.
It’s very important to know this, the value of radiation, and that adding chemotherapy with radiation doesn’t make a difference.
One might ask, if this is an important clinical question, is there a way or would there be a way in the future to take a question like this and significantly expand the population of individuals and the population of oncologists that might participate in community-based studies, where you’re asking a very simple question?
You irradiate vs something else; you have a standard of care; you’re looking at progression-free survival, which is a very valid endpoint, or overall survival, and you don’t anticipate significant differences in toxicity because you might use this therapy otherwise.
Would it be possible to answer the question not in 12 years, but in half that time or maybe 20% of that time? The results are important for patients being treated today and their doctors who are advising on optimal therapy.
For those of you who are interested in the question of the management of endometrial cancer, this type of pragmatic trial, I would encourage you to read this important paper. Thank you for your attention.
Maurie Markman, Professor of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center; President, Medicine & Science, City of Hope Atlanta, Chicago, Phoenix, has disclosed the following relevant financial relationships: Received income in an amount equal to or greater than $250 from GlaxoSmithKline and AstraZeneca.
A version of this article first appeared on Medscape.com.
This transcript has been edited for clarity.
Hello. I’m Dr. Maurie Markman from City of Hope. I wanted to briefly discuss a very important paper. This is one that probably didn’t get as much attention as I believe it should. It looks at a very important clinically relevant question, and one that might very much say, can we do more such studies but only do them faster?
This was a trial reported in the Journal of Clinical Oncology earlier this year titled, “Radiation Therapy With or Without Cisplatin for Local Recurrences of Endometrial Cancer: Results From an NRG Oncology/GOG Prospective Randomized Multicenter Clinical Study.”
Fortunately, most patients with endometrial cancer have low-grade cancers and are cured with standard surgery, plus or minus radiation. However, a small percentage of patients, even with low-grade endometrial cancer, will recur.
There are several questions that come up. What is the optimal therapy? What is the outcome for such patients? Should we perhaps give chemotherapy along with the radiation as we do, for example, standardly in cervical cancer?
This study attempted to address that question. There was a total of 165 patients randomized in this trial that went on for 12 years, looking at local radiation vs radiation plus cisplatin — which is, again, standardly given as chemoradiation in cervical cancer.
What were the results? When this paper was reported 16 years after the study was initiated, the results showed the addition of chemotherapy did not add to the benefits of the radiation and in fact increased toxicity. Very importantly, the local control and overall control of the disease was excellent. In fact, at 3 years, 73% of the patients treated with radiation alone were disease-free.
It’s very important to know this, the value of radiation, and that adding chemotherapy with radiation doesn’t make a difference.
One might ask, if this is an important clinical question, is there a way or would there be a way in the future to take a question like this and significantly expand the population of individuals and the population of oncologists that might participate in community-based studies, where you’re asking a very simple question?
You irradiate vs something else; you have a standard of care; you’re looking at progression-free survival, which is a very valid endpoint, or overall survival, and you don’t anticipate significant differences in toxicity because you might use this therapy otherwise.
Would it be possible to answer the question not in 12 years, but in half that time or maybe 20% of that time? The results are important for patients being treated today and their doctors who are advising on optimal therapy.
For those of you who are interested in the question of the management of endometrial cancer, this type of pragmatic trial, I would encourage you to read this important paper. Thank you for your attention.
Maurie Markman, Professor of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center; President, Medicine & Science, City of Hope Atlanta, Chicago, Phoenix, has disclosed the following relevant financial relationships: Received income in an amount equal to or greater than $250 from GlaxoSmithKline and AstraZeneca.
A version of this article first appeared on Medscape.com.
New Model Estimates Hepatocellular Carcinoma Risk in Patients With Chronic Hepatitis B
The model, called Revised REACH-B or reREACH-B, stems from cohort studies in Hong Kong, South Korea, and Taiwan, and looks at the nonlinear parabolic association between serum hepatitis B virus (HBV) DNA levels and HCC risk.
“Current clinical practice guidelines don’t advocate antiviral treatment for patients with CHB who don’t show elevated alanine aminotransferase (ALT) levels, even in those with high HBV viral loads,” said coauthor Young-Suk Lim, MD, PhD, professor of gastroenterology at the University of Ulsan College of Medicine and Asan Medical Center in Seoul, South Korea.
“This stance is rooted in the notion that patients in the immune-tolerant phase are at very low risk for developing HCC,” Lim said. “However, the immune-tolerant phase includes patients with HBV DNA levels who face the highest risk for HCC, and many patients with moderate HBV viremia fall into an undefined gray zone.”
The study was published in Annals of Internal Medicine.
Validating reREACH-B
During a course of CHB, HBV viral loads and HCC risks evolve over time because of viral replication and host immune responses, Lim explained. Most patients typically move to seroclearance and an “inactive hepatitis” phase, but about 10%-20% can progress to a “reactivation” phase, where HBV DNA levels and ALT levels increase, which can increase HCC risk as well.
In a previous cohort study in Taiwan, a prognostic model called Risk Estimation for HCC in CHB — or REACH-B — found the risk for HCC increases tenfold with increasing levels of HBV DNA up to 5 log10IU/mL in noncirrhotic patients with CHB, regardless of ALT levels. Another cohort study in South Korea found a nonlinear parabolic association between HCC risk and HBV DNA levels up to 9 log10 IU/mL, with the highest risks found for moderate HBV DNA levels around 6 log10 IU/mL.
In this study, Lim and colleagues developed a prognostic model to integrate the nonlinear relationship and validated it externally, as well as compared it with the previous REACH-B model. The Revised REACH-B model incorporates six variables: age, sex, platelet count, HBV DNA level, ALT, and hepatitis B e-antigen (HBeAg).
The study included 14,378 treatment-naive, noncirrhotic adults with CHB and serum ALT levels < two times the upper limit of normal for at least 1 year and serum hepatitis B surface antigen for at least 6 months. The internal validation cohort included 6,949 patients from Asan Medical Center, and the external validation cohort included 7,429 patients from previous studies in Hong Kong, South Korea, and Taiwan.
Among the Asan cohort, the mean age was 45 years, 29.9% were HBeAg positive, median HBV DNA levels were 3.1 log10 IU/mL, and the median ALT level was 25 U/L. In the external cohort, the mean age was 46 years, 21% were HBeAg positive, median HBV DNA levels were 3.4 log10 IU/mL, and the median ALT level was 20 U/L.
In the Asan cohort, 435 patients (6.3%) developed HCC during a median follow-up of 10 years. The annual HCC incidence rate was 0.63 per 100 person-years, and the estimated cumulative probability of developing HCC at 10 years was 6.4%.
In the external cohort, 467 patients (6.3%) developed HCC during a median follow-up of 12 years. The annual HCC incidence rate was 0.42 per 100 person-years, and the estimated cumulative probability of developing HCC at 10 years was 3.1%.
Overall, the association between HBV viral load and HCC risk was linear in the HBeAg-negative groups and inverse in the HBeAg-positive groups, with the association between HBV viral load and HCC risk showing a nonlinear parabolic pattern.
Across both cohorts, patients with HBV DNA levels between 5 and 6 log10 IU/mL had the highest risk for HCC in both the HBeAg-negative and HBeAg-positive groups, which was more than eight times higher than those HBV DNA levels ≤ 3 log10 IU/mL.
For internal validation, the Revised REACH-B model had a c-statistic of 0.844 and 5-year area under the curve of 0.864. For external validation across the three external cohorts, the reREACH-B had c-statistics of 0.804, 0.808, and 0.813, and 5-year area under the curve of 0.839, 0.860, and 0.865.
In addition, the revised model yielded a greater positive net benefit than the REACH-B model in the threshold probability range between 0% and 18%.
“These analyses indicate the reREACH-B model can be a valuable tool in clinical practice, aiding in timely management decisions,” Lim said.
Considering Prognostic Models
This study highlights the importance of recognizing that the association between HBV DNA viral load and HCC risk isn’t linear, said Norah Terrault, MD, chief of Gastroenterology and Hepatology at the Keck School of Medicine at the University of Southern California, Los Angeles.
“In contrast to most chronic liver diseases where liver cancer develops only among those with advanced fibrosis/cirrhosis, people with chronic hepatitis B are at risk prior to the development of cirrhosis,” she said. “Risk prediction scores for HCC can be a useful means of identifying those without cirrhosis who should be enrolled in HCC surveillance programs.”
For instance, patients with HBV DNA levels < 3 log10 IU/mL or > 8 log10 IU/mL don’t have an increased risk, Terrault noted. However, the highest risk group appears to be around 5-6 log10 IU/mL.
“Future risk prediction models should acknowledge that relationship in modeling HCC risk,” she said. “The re-REACH-B provides modest improvement over the REACH-B, but further validation of this score in more diverse cohorts is essential.”
The study received financial support from the Korean government and grants from the Patient-Centered Clinical Research Coordinating Center of the National Evidence-based Healthcare Collaborating Agency and the National R&D Program for Cancer Control through the National Cancer Center, which is funded by Korea’s Ministry of Health and Welfare. Lim and Terrault reported no relevant disclosures.
A version of this article first appeared on Medscape.com.
The model, called Revised REACH-B or reREACH-B, stems from cohort studies in Hong Kong, South Korea, and Taiwan, and looks at the nonlinear parabolic association between serum hepatitis B virus (HBV) DNA levels and HCC risk.
“Current clinical practice guidelines don’t advocate antiviral treatment for patients with CHB who don’t show elevated alanine aminotransferase (ALT) levels, even in those with high HBV viral loads,” said coauthor Young-Suk Lim, MD, PhD, professor of gastroenterology at the University of Ulsan College of Medicine and Asan Medical Center in Seoul, South Korea.
“This stance is rooted in the notion that patients in the immune-tolerant phase are at very low risk for developing HCC,” Lim said. “However, the immune-tolerant phase includes patients with HBV DNA levels who face the highest risk for HCC, and many patients with moderate HBV viremia fall into an undefined gray zone.”
The study was published in Annals of Internal Medicine.
Validating reREACH-B
During a course of CHB, HBV viral loads and HCC risks evolve over time because of viral replication and host immune responses, Lim explained. Most patients typically move to seroclearance and an “inactive hepatitis” phase, but about 10%-20% can progress to a “reactivation” phase, where HBV DNA levels and ALT levels increase, which can increase HCC risk as well.
In a previous cohort study in Taiwan, a prognostic model called Risk Estimation for HCC in CHB — or REACH-B — found the risk for HCC increases tenfold with increasing levels of HBV DNA up to 5 log10IU/mL in noncirrhotic patients with CHB, regardless of ALT levels. Another cohort study in South Korea found a nonlinear parabolic association between HCC risk and HBV DNA levels up to 9 log10 IU/mL, with the highest risks found for moderate HBV DNA levels around 6 log10 IU/mL.
In this study, Lim and colleagues developed a prognostic model to integrate the nonlinear relationship and validated it externally, as well as compared it with the previous REACH-B model. The Revised REACH-B model incorporates six variables: age, sex, platelet count, HBV DNA level, ALT, and hepatitis B e-antigen (HBeAg).
The study included 14,378 treatment-naive, noncirrhotic adults with CHB and serum ALT levels < two times the upper limit of normal for at least 1 year and serum hepatitis B surface antigen for at least 6 months. The internal validation cohort included 6,949 patients from Asan Medical Center, and the external validation cohort included 7,429 patients from previous studies in Hong Kong, South Korea, and Taiwan.
Among the Asan cohort, the mean age was 45 years, 29.9% were HBeAg positive, median HBV DNA levels were 3.1 log10 IU/mL, and the median ALT level was 25 U/L. In the external cohort, the mean age was 46 years, 21% were HBeAg positive, median HBV DNA levels were 3.4 log10 IU/mL, and the median ALT level was 20 U/L.
In the Asan cohort, 435 patients (6.3%) developed HCC during a median follow-up of 10 years. The annual HCC incidence rate was 0.63 per 100 person-years, and the estimated cumulative probability of developing HCC at 10 years was 6.4%.
In the external cohort, 467 patients (6.3%) developed HCC during a median follow-up of 12 years. The annual HCC incidence rate was 0.42 per 100 person-years, and the estimated cumulative probability of developing HCC at 10 years was 3.1%.
Overall, the association between HBV viral load and HCC risk was linear in the HBeAg-negative groups and inverse in the HBeAg-positive groups, with the association between HBV viral load and HCC risk showing a nonlinear parabolic pattern.
Across both cohorts, patients with HBV DNA levels between 5 and 6 log10 IU/mL had the highest risk for HCC in both the HBeAg-negative and HBeAg-positive groups, which was more than eight times higher than those HBV DNA levels ≤ 3 log10 IU/mL.
For internal validation, the Revised REACH-B model had a c-statistic of 0.844 and 5-year area under the curve of 0.864. For external validation across the three external cohorts, the reREACH-B had c-statistics of 0.804, 0.808, and 0.813, and 5-year area under the curve of 0.839, 0.860, and 0.865.
In addition, the revised model yielded a greater positive net benefit than the REACH-B model in the threshold probability range between 0% and 18%.
“These analyses indicate the reREACH-B model can be a valuable tool in clinical practice, aiding in timely management decisions,” Lim said.
Considering Prognostic Models
This study highlights the importance of recognizing that the association between HBV DNA viral load and HCC risk isn’t linear, said Norah Terrault, MD, chief of Gastroenterology and Hepatology at the Keck School of Medicine at the University of Southern California, Los Angeles.
“In contrast to most chronic liver diseases where liver cancer develops only among those with advanced fibrosis/cirrhosis, people with chronic hepatitis B are at risk prior to the development of cirrhosis,” she said. “Risk prediction scores for HCC can be a useful means of identifying those without cirrhosis who should be enrolled in HCC surveillance programs.”
For instance, patients with HBV DNA levels < 3 log10 IU/mL or > 8 log10 IU/mL don’t have an increased risk, Terrault noted. However, the highest risk group appears to be around 5-6 log10 IU/mL.
“Future risk prediction models should acknowledge that relationship in modeling HCC risk,” she said. “The re-REACH-B provides modest improvement over the REACH-B, but further validation of this score in more diverse cohorts is essential.”
The study received financial support from the Korean government and grants from the Patient-Centered Clinical Research Coordinating Center of the National Evidence-based Healthcare Collaborating Agency and the National R&D Program for Cancer Control through the National Cancer Center, which is funded by Korea’s Ministry of Health and Welfare. Lim and Terrault reported no relevant disclosures.
A version of this article first appeared on Medscape.com.
The model, called Revised REACH-B or reREACH-B, stems from cohort studies in Hong Kong, South Korea, and Taiwan, and looks at the nonlinear parabolic association between serum hepatitis B virus (HBV) DNA levels and HCC risk.
“Current clinical practice guidelines don’t advocate antiviral treatment for patients with CHB who don’t show elevated alanine aminotransferase (ALT) levels, even in those with high HBV viral loads,” said coauthor Young-Suk Lim, MD, PhD, professor of gastroenterology at the University of Ulsan College of Medicine and Asan Medical Center in Seoul, South Korea.
“This stance is rooted in the notion that patients in the immune-tolerant phase are at very low risk for developing HCC,” Lim said. “However, the immune-tolerant phase includes patients with HBV DNA levels who face the highest risk for HCC, and many patients with moderate HBV viremia fall into an undefined gray zone.”
The study was published in Annals of Internal Medicine.
Validating reREACH-B
During a course of CHB, HBV viral loads and HCC risks evolve over time because of viral replication and host immune responses, Lim explained. Most patients typically move to seroclearance and an “inactive hepatitis” phase, but about 10%-20% can progress to a “reactivation” phase, where HBV DNA levels and ALT levels increase, which can increase HCC risk as well.
In a previous cohort study in Taiwan, a prognostic model called Risk Estimation for HCC in CHB — or REACH-B — found the risk for HCC increases tenfold with increasing levels of HBV DNA up to 5 log10IU/mL in noncirrhotic patients with CHB, regardless of ALT levels. Another cohort study in South Korea found a nonlinear parabolic association between HCC risk and HBV DNA levels up to 9 log10 IU/mL, with the highest risks found for moderate HBV DNA levels around 6 log10 IU/mL.
In this study, Lim and colleagues developed a prognostic model to integrate the nonlinear relationship and validated it externally, as well as compared it with the previous REACH-B model. The Revised REACH-B model incorporates six variables: age, sex, platelet count, HBV DNA level, ALT, and hepatitis B e-antigen (HBeAg).
The study included 14,378 treatment-naive, noncirrhotic adults with CHB and serum ALT levels < two times the upper limit of normal for at least 1 year and serum hepatitis B surface antigen for at least 6 months. The internal validation cohort included 6,949 patients from Asan Medical Center, and the external validation cohort included 7,429 patients from previous studies in Hong Kong, South Korea, and Taiwan.
Among the Asan cohort, the mean age was 45 years, 29.9% were HBeAg positive, median HBV DNA levels were 3.1 log10 IU/mL, and the median ALT level was 25 U/L. In the external cohort, the mean age was 46 years, 21% were HBeAg positive, median HBV DNA levels were 3.4 log10 IU/mL, and the median ALT level was 20 U/L.
In the Asan cohort, 435 patients (6.3%) developed HCC during a median follow-up of 10 years. The annual HCC incidence rate was 0.63 per 100 person-years, and the estimated cumulative probability of developing HCC at 10 years was 6.4%.
In the external cohort, 467 patients (6.3%) developed HCC during a median follow-up of 12 years. The annual HCC incidence rate was 0.42 per 100 person-years, and the estimated cumulative probability of developing HCC at 10 years was 3.1%.
Overall, the association between HBV viral load and HCC risk was linear in the HBeAg-negative groups and inverse in the HBeAg-positive groups, with the association between HBV viral load and HCC risk showing a nonlinear parabolic pattern.
Across both cohorts, patients with HBV DNA levels between 5 and 6 log10 IU/mL had the highest risk for HCC in both the HBeAg-negative and HBeAg-positive groups, which was more than eight times higher than those HBV DNA levels ≤ 3 log10 IU/mL.
For internal validation, the Revised REACH-B model had a c-statistic of 0.844 and 5-year area under the curve of 0.864. For external validation across the three external cohorts, the reREACH-B had c-statistics of 0.804, 0.808, and 0.813, and 5-year area under the curve of 0.839, 0.860, and 0.865.
In addition, the revised model yielded a greater positive net benefit than the REACH-B model in the threshold probability range between 0% and 18%.
“These analyses indicate the reREACH-B model can be a valuable tool in clinical practice, aiding in timely management decisions,” Lim said.
Considering Prognostic Models
This study highlights the importance of recognizing that the association between HBV DNA viral load and HCC risk isn’t linear, said Norah Terrault, MD, chief of Gastroenterology and Hepatology at the Keck School of Medicine at the University of Southern California, Los Angeles.
“In contrast to most chronic liver diseases where liver cancer develops only among those with advanced fibrosis/cirrhosis, people with chronic hepatitis B are at risk prior to the development of cirrhosis,” she said. “Risk prediction scores for HCC can be a useful means of identifying those without cirrhosis who should be enrolled in HCC surveillance programs.”
For instance, patients with HBV DNA levels < 3 log10 IU/mL or > 8 log10 IU/mL don’t have an increased risk, Terrault noted. However, the highest risk group appears to be around 5-6 log10 IU/mL.
“Future risk prediction models should acknowledge that relationship in modeling HCC risk,” she said. “The re-REACH-B provides modest improvement over the REACH-B, but further validation of this score in more diverse cohorts is essential.”
The study received financial support from the Korean government and grants from the Patient-Centered Clinical Research Coordinating Center of the National Evidence-based Healthcare Collaborating Agency and the National R&D Program for Cancer Control through the National Cancer Center, which is funded by Korea’s Ministry of Health and Welfare. Lim and Terrault reported no relevant disclosures.
A version of this article first appeared on Medscape.com.
FROM ANNALS OF INTERNAL MEDICINE