Feature

Preconception and prenatal care are more complicated in women with chronic health conditions but attention to disease management and promoting the adoption of a healthier lifestyle can improve outcomes for mothers and infants, according to a growing body of research.

The latest version of the International Federation of Gynecology and Obstetrics Preconception Checklist, published in the International Journal of Gynecology & Obstetrics, highlights preexisting chronic medical conditions such as diabetes, lupus, and obesity as key factors to address in preconception care through disease management. A growing number of studies support the impact of these strategies on short- and long-term outcomes for mothers and babies, according to the authors.
 

Meet Glycemic Control Goals Prior to Pregnancy

“Women with diabetes can have healthy pregnancies but need to prepare for pregnancy in advance,” Ellen W. Seely, MD, professor of medicine at Harvard Medical School and director of clinical research in the endocrinology, diabetes, and hypertension division of Brigham and Women’s Hospital, Boston, said in an interview.

“If glucose levels are running high in the first trimester, this is associated with an increased risk of birth defects, some of which are very serious,” said Dr. Seely. Getting glucose levels under control reduces the risk of birth defects in women with diabetes close to that of the general population, she said.

The American Diabetes Association has set a goal for women to attain an HbA1c of less than 6.5% before conception, Dr. Seely said. “In addition, some women with diabetes may be on medications that should be changed to another class prior to pregnancy,” she noted. Women with type 1 or type 2 diabetes often have hypertension as well, but ACE inhibitors are associated with an increased risk of fetal renal damage that can result in neonatal death; therefore, these medications should be stopped prior to pregnancy, Dr. Seely emphasized.

“If a woman with type 2 diabetes is on medications other than insulin, recommendations from the ADA are to change to insulin prior to pregnancy, since we have the most data on the safety profile of insulin use in pregnancy,” she said.

To help women with diabetes improve glycemic control prior to pregnancy, Dr. Seely recommends home glucose monitoring, with checks of glucose four times a day, fasting, and 2 hours after each meal, and adjustment of insulin accordingly.

A healthy diet and physical activity remain important components of glycemic control as well. A barrier to proper preconception and prenatal care for women with diabetes is not knowing that a pregnancy should be planned, Dr. Seely said. Discussions about pregnancy should start at puberty for women with diabetes, according to the ADA, and the topic should be raised yearly so women can optimize their health and adjust medications prior to conception.

Although studies of drugs have been done to inform preconception care for women with diabetes, research is lacking in several areas, notably the safety of GLP-1 agonists in pregnancy, said Dr. Seely. “This class of drug is commonly used in type 2 diabetes and the current recommendation is to stop these agents 2 months prior to conception,” she said.
 

Conceive in Times of Lupus Remission

Advance planning also is important for a healthy pregnancy in women with systemic lupus erythematosus (SLE), Sayna Norouzi, MD, director of the glomerular disease clinic and polycystic kidney disease clinic of Loma Linda University Medical Center, California, said in an interview.

“Lupus mostly affects women of childbearing age and can create many challenges during pregnancy,” said Dr. Norouzi, the corresponding author of a recent review on managing lupus nephritis during pregnancy.

“Women with lupus face an increased risk of pregnancy complications such as preeclampsia, problems with fetal growth, stillbirth, and premature birth, and these risks increase based on factors such as disease activity, certain antibodies in the body, and other baseline existing conditions such as high blood pressure,” she said.

“It can be difficult to distinguish between a lupus flare and pregnancy-related issues, so proper management is important,” she noted. The Predictors of Pregnancy Outcome: Biomarkers in Antiphospholipid Syndrome and Systemic Lupus Erythematosus (PROMISSE) study findings indicated a lupus nephritis relapse rate of 7.8% of patients in complete remission and 21% of those in partial remission during pregnancy, said Dr. Norouzi. “Current evidence has shown that SLE patients without lupus nephritis flare in the preconception period have a small risk of relapse during pregnancy,” she said.

Before and during pregnancy, women with lupus should work with their treating physicians to adjust medications for safety, watch for signs of flare, and aim to conceive during a period of lupus remission.

Preconception care for women with lupus nephritis involves a careful review of the medications used to control the disease and protect the kidneys and other organs, said Dr. Norouzi.

“Adjustments,” she said, “should be personalized, taking into account the mother’s health and the safety of the baby. Managing the disease actively during pregnancy may require changes to the treatment plan while minimizing risks,” she noted. However, changing medications can cause challenges for patients, as medications that are safer for pregnancy may lead to new symptoms and side effects, and patients will need to work closely with their healthcare providers to overcome new issues that arise, she added.

Preconception lifestyle changes such as increasing exercise and adopting a healthier diet can help with blood pressure control for kidney disease patients, said Dr. Norouzi.

In the review article, Dr. Norouzi and colleagues noted that preconception counseling for patients with lupus should address common comorbidities such as hypertension, diabetes, obesity, and dyslipidemia, and the risk for immediate and long-term cardiovascular complications.
 

Benefits of Preconception Obesity Care Extend to Infants

Current guidelines from the American College of Obstetricians and Gynecologists and the Institute of Medicine advise lifestyle interventions to reduce excessive weight gain during pregnancy and reduce the risk of inflammation, oxidative stress, insulin resistance, and lipotoxicity that can promote complications in the mother and fetus during pregnancy.

In addition, a growing number of studies suggest that women with obesity who make healthy lifestyle changes prior to conception can reduce obesity-associated risks to their infants.

Adults born to women with obesity are at increased risk of cardiovascular disease and early signs of heart remodeling are identifiable in newborns, Samuel J. Burden, PhD, a research associate in the department of women and children’s health, Kings’ College, London, said in an interview. “It is therefore important to investigate whether intervening either before or during pregnancy by promoting a healthy lifestyle can reduce this adverse impact on the heart and blood vessels,” he said.

In a recent study published in the International Journal of Obesity, Dr. Burden and colleagues examined data from eight studies based on data from five randomized, controlled trials including children of mothers with obesity who engaged in healthy lifestyle interventions of improved diet and increased physical activity prior to and during pregnancy. The study population included children ranging in age from less than 2 months to 3-7 years.

Lifestyle interventions for mothers both before conception and during pregnancy were associated with significant changes in cardiac remodeling in the children, notably reduced interventricular septal wall thickness. Additionally, five studies of cardiac systolic function and three studies of diastolic function showed improvement in blood pressure in children of mothers who took part in the interventions.

Dr. Burden acknowledged that lifestyle changes in women with obesity before conception and during pregnancy can be challenging, but should be encouraged. “During pregnancy, it may also seem unnatural to increase daily physical activity or change the way you are eating.” He emphasized that patients should consult their physicians and follow an established program. More randomized, controlled trials are needed from the preconception period to examine whether the health benefits are greater if the intervention begins prior to pregnancy, said Dr. Burden. However, “the current findings indeed indicate that women with obesity who lead a healthy lifestyle before and during their pregnancy can reduce the degree of unhealthy heart remodeling in their children,” he said.

Dr. Seely, Dr. Norouzi, and Dr. Burden had no financial conflicts to disclose.

Preconception and prenatal care are more complicated in women with chronic health conditions but attention to disease management and promoting the adoption of a healthier lifestyle can improve outcomes for mothers and infants, according to a growing body of research.

The latest version of the International Federation of Gynecology and Obstetrics Preconception Checklist, published in the International Journal of Gynecology & Obstetrics, highlights preexisting chronic medical conditions such as diabetes, lupus, and obesity as key factors to address in preconception care through disease management. A growing number of studies support the impact of these strategies on short- and long-term outcomes for mothers and babies, according to the authors.
 

Meet Glycemic Control Goals Prior to Pregnancy

“Women with diabetes can have healthy pregnancies but need to prepare for pregnancy in advance,” Ellen W. Seely, MD, professor of medicine at Harvard Medical School and director of clinical research in the endocrinology, diabetes, and hypertension division of Brigham and Women’s Hospital, Boston, said in an interview.

“If glucose levels are running high in the first trimester, this is associated with an increased risk of birth defects, some of which are very serious,” said Dr. Seely. Getting glucose levels under control reduces the risk of birth defects in women with diabetes close to that of the general population, she said.

The American Diabetes Association has set a goal for women to attain an HbA1c of less than 6.5% before conception, Dr. Seely said. “In addition, some women with diabetes may be on medications that should be changed to another class prior to pregnancy,” she noted. Women with type 1 or type 2 diabetes often have hypertension as well, but ACE inhibitors are associated with an increased risk of fetal renal damage that can result in neonatal death; therefore, these medications should be stopped prior to pregnancy, Dr. Seely emphasized.

“If a woman with type 2 diabetes is on medications other than insulin, recommendations from the ADA are to change to insulin prior to pregnancy, since we have the most data on the safety profile of insulin use in pregnancy,” she said.

To help women with diabetes improve glycemic control prior to pregnancy, Dr. Seely recommends home glucose monitoring, with checks of glucose four times a day, fasting, and 2 hours after each meal, and adjustment of insulin accordingly.

A healthy diet and physical activity remain important components of glycemic control as well. A barrier to proper preconception and prenatal care for women with diabetes is not knowing that a pregnancy should be planned, Dr. Seely said. Discussions about pregnancy should start at puberty for women with diabetes, according to the ADA, and the topic should be raised yearly so women can optimize their health and adjust medications prior to conception.

Although studies of drugs have been done to inform preconception care for women with diabetes, research is lacking in several areas, notably the safety of GLP-1 agonists in pregnancy, said Dr. Seely. “This class of drug is commonly used in type 2 diabetes and the current recommendation is to stop these agents 2 months prior to conception,” she said.
 

Conceive in Times of Lupus Remission

Advance planning also is important for a healthy pregnancy in women with systemic lupus erythematosus (SLE), Sayna Norouzi, MD, director of the glomerular disease clinic and polycystic kidney disease clinic of Loma Linda University Medical Center, California, said in an interview.

“Lupus mostly affects women of childbearing age and can create many challenges during pregnancy,” said Dr. Norouzi, the corresponding author of a recent review on managing lupus nephritis during pregnancy.

“Women with lupus face an increased risk of pregnancy complications such as preeclampsia, problems with fetal growth, stillbirth, and premature birth, and these risks increase based on factors such as disease activity, certain antibodies in the body, and other baseline existing conditions such as high blood pressure,” she said.

“It can be difficult to distinguish between a lupus flare and pregnancy-related issues, so proper management is important,” she noted. The Predictors of Pregnancy Outcome: Biomarkers in Antiphospholipid Syndrome and Systemic Lupus Erythematosus (PROMISSE) study findings indicated a lupus nephritis relapse rate of 7.8% of patients in complete remission and 21% of those in partial remission during pregnancy, said Dr. Norouzi. “Current evidence has shown that SLE patients without lupus nephritis flare in the preconception period have a small risk of relapse during pregnancy,” she said.

Before and during pregnancy, women with lupus should work with their treating physicians to adjust medications for safety, watch for signs of flare, and aim to conceive during a period of lupus remission.

Preconception care for women with lupus nephritis involves a careful review of the medications used to control the disease and protect the kidneys and other organs, said Dr. Norouzi.

“Adjustments,” she said, “should be personalized, taking into account the mother’s health and the safety of the baby. Managing the disease actively during pregnancy may require changes to the treatment plan while minimizing risks,” she noted. However, changing medications can cause challenges for patients, as medications that are safer for pregnancy may lead to new symptoms and side effects, and patients will need to work closely with their healthcare providers to overcome new issues that arise, she added.

Preconception lifestyle changes such as increasing exercise and adopting a healthier diet can help with blood pressure control for kidney disease patients, said Dr. Norouzi.

In the review article, Dr. Norouzi and colleagues noted that preconception counseling for patients with lupus should address common comorbidities such as hypertension, diabetes, obesity, and dyslipidemia, and the risk for immediate and long-term cardiovascular complications.
 

Benefits of Preconception Obesity Care Extend to Infants

Current guidelines from the American College of Obstetricians and Gynecologists and the Institute of Medicine advise lifestyle interventions to reduce excessive weight gain during pregnancy and reduce the risk of inflammation, oxidative stress, insulin resistance, and lipotoxicity that can promote complications in the mother and fetus during pregnancy.

In addition, a growing number of studies suggest that women with obesity who make healthy lifestyle changes prior to conception can reduce obesity-associated risks to their infants.

Adults born to women with obesity are at increased risk of cardiovascular disease and early signs of heart remodeling are identifiable in newborns, Samuel J. Burden, PhD, a research associate in the department of women and children’s health, Kings’ College, London, said in an interview. “It is therefore important to investigate whether intervening either before or during pregnancy by promoting a healthy lifestyle can reduce this adverse impact on the heart and blood vessels,” he said.

In a recent study published in the International Journal of Obesity, Dr. Burden and colleagues examined data from eight studies based on data from five randomized, controlled trials including children of mothers with obesity who engaged in healthy lifestyle interventions of improved diet and increased physical activity prior to and during pregnancy. The study population included children ranging in age from less than 2 months to 3-7 years.

Lifestyle interventions for mothers both before conception and during pregnancy were associated with significant changes in cardiac remodeling in the children, notably reduced interventricular septal wall thickness. Additionally, five studies of cardiac systolic function and three studies of diastolic function showed improvement in blood pressure in children of mothers who took part in the interventions.

Dr. Burden acknowledged that lifestyle changes in women with obesity before conception and during pregnancy can be challenging, but should be encouraged. “During pregnancy, it may also seem unnatural to increase daily physical activity or change the way you are eating.” He emphasized that patients should consult their physicians and follow an established program. More randomized, controlled trials are needed from the preconception period to examine whether the health benefits are greater if the intervention begins prior to pregnancy, said Dr. Burden. However, “the current findings indeed indicate that women with obesity who lead a healthy lifestyle before and during their pregnancy can reduce the degree of unhealthy heart remodeling in their children,” he said.

Dr. Seely, Dr. Norouzi, and Dr. Burden had no financial conflicts to disclose.

Preconception and prenatal care are more complicated in women with chronic health conditions but attention to disease management and promoting the adoption of a healthier lifestyle can improve outcomes for mothers and infants, according to a growing body of research.

The latest version of the International Federation of Gynecology and Obstetrics Preconception Checklist, published in the International Journal of Gynecology & Obstetrics, highlights preexisting chronic medical conditions such as diabetes, lupus, and obesity as key factors to address in preconception care through disease management. A growing number of studies support the impact of these strategies on short- and long-term outcomes for mothers and babies, according to the authors.
 

Meet Glycemic Control Goals Prior to Pregnancy

“Women with diabetes can have healthy pregnancies but need to prepare for pregnancy in advance,” Ellen W. Seely, MD, professor of medicine at Harvard Medical School and director of clinical research in the endocrinology, diabetes, and hypertension division of Brigham and Women’s Hospital, Boston, said in an interview.

“If glucose levels are running high in the first trimester, this is associated with an increased risk of birth defects, some of which are very serious,” said Dr. Seely. Getting glucose levels under control reduces the risk of birth defects in women with diabetes close to that of the general population, she said.

The American Diabetes Association has set a goal for women to attain an HbA1c of less than 6.5% before conception, Dr. Seely said. “In addition, some women with diabetes may be on medications that should be changed to another class prior to pregnancy,” she noted. Women with type 1 or type 2 diabetes often have hypertension as well, but ACE inhibitors are associated with an increased risk of fetal renal damage that can result in neonatal death; therefore, these medications should be stopped prior to pregnancy, Dr. Seely emphasized.

“If a woman with type 2 diabetes is on medications other than insulin, recommendations from the ADA are to change to insulin prior to pregnancy, since we have the most data on the safety profile of insulin use in pregnancy,” she said.

To help women with diabetes improve glycemic control prior to pregnancy, Dr. Seely recommends home glucose monitoring, with checks of glucose four times a day, fasting, and 2 hours after each meal, and adjustment of insulin accordingly.

A healthy diet and physical activity remain important components of glycemic control as well. A barrier to proper preconception and prenatal care for women with diabetes is not knowing that a pregnancy should be planned, Dr. Seely said. Discussions about pregnancy should start at puberty for women with diabetes, according to the ADA, and the topic should be raised yearly so women can optimize their health and adjust medications prior to conception.

Although studies of drugs have been done to inform preconception care for women with diabetes, research is lacking in several areas, notably the safety of GLP-1 agonists in pregnancy, said Dr. Seely. “This class of drug is commonly used in type 2 diabetes and the current recommendation is to stop these agents 2 months prior to conception,” she said.
 

Conceive in Times of Lupus Remission

Advance planning also is important for a healthy pregnancy in women with systemic lupus erythematosus (SLE), Sayna Norouzi, MD, director of the glomerular disease clinic and polycystic kidney disease clinic of Loma Linda University Medical Center, California, said in an interview.

“Lupus mostly affects women of childbearing age and can create many challenges during pregnancy,” said Dr. Norouzi, the corresponding author of a recent review on managing lupus nephritis during pregnancy.

“Women with lupus face an increased risk of pregnancy complications such as preeclampsia, problems with fetal growth, stillbirth, and premature birth, and these risks increase based on factors such as disease activity, certain antibodies in the body, and other baseline existing conditions such as high blood pressure,” she said.

“It can be difficult to distinguish between a lupus flare and pregnancy-related issues, so proper management is important,” she noted. The Predictors of Pregnancy Outcome: Biomarkers in Antiphospholipid Syndrome and Systemic Lupus Erythematosus (PROMISSE) study findings indicated a lupus nephritis relapse rate of 7.8% of patients in complete remission and 21% of those in partial remission during pregnancy, said Dr. Norouzi. “Current evidence has shown that SLE patients without lupus nephritis flare in the preconception period have a small risk of relapse during pregnancy,” she said.

Before and during pregnancy, women with lupus should work with their treating physicians to adjust medications for safety, watch for signs of flare, and aim to conceive during a period of lupus remission.

Preconception care for women with lupus nephritis involves a careful review of the medications used to control the disease and protect the kidneys and other organs, said Dr. Norouzi.

“Adjustments,” she said, “should be personalized, taking into account the mother’s health and the safety of the baby. Managing the disease actively during pregnancy may require changes to the treatment plan while minimizing risks,” she noted. However, changing medications can cause challenges for patients, as medications that are safer for pregnancy may lead to new symptoms and side effects, and patients will need to work closely with their healthcare providers to overcome new issues that arise, she added.

Preconception lifestyle changes such as increasing exercise and adopting a healthier diet can help with blood pressure control for kidney disease patients, said Dr. Norouzi.

In the review article, Dr. Norouzi and colleagues noted that preconception counseling for patients with lupus should address common comorbidities such as hypertension, diabetes, obesity, and dyslipidemia, and the risk for immediate and long-term cardiovascular complications.
 

Benefits of Preconception Obesity Care Extend to Infants

Current guidelines from the American College of Obstetricians and Gynecologists and the Institute of Medicine advise lifestyle interventions to reduce excessive weight gain during pregnancy and reduce the risk of inflammation, oxidative stress, insulin resistance, and lipotoxicity that can promote complications in the mother and fetus during pregnancy.

In addition, a growing number of studies suggest that women with obesity who make healthy lifestyle changes prior to conception can reduce obesity-associated risks to their infants.

Adults born to women with obesity are at increased risk of cardiovascular disease and early signs of heart remodeling are identifiable in newborns, Samuel J. Burden, PhD, a research associate in the department of women and children’s health, Kings’ College, London, said in an interview. “It is therefore important to investigate whether intervening either before or during pregnancy by promoting a healthy lifestyle can reduce this adverse impact on the heart and blood vessels,” he said.

In a recent study published in the International Journal of Obesity, Dr. Burden and colleagues examined data from eight studies based on data from five randomized, controlled trials including children of mothers with obesity who engaged in healthy lifestyle interventions of improved diet and increased physical activity prior to and during pregnancy. The study population included children ranging in age from less than 2 months to 3-7 years.

Lifestyle interventions for mothers both before conception and during pregnancy were associated with significant changes in cardiac remodeling in the children, notably reduced interventricular septal wall thickness. Additionally, five studies of cardiac systolic function and three studies of diastolic function showed improvement in blood pressure in children of mothers who took part in the interventions.

Dr. Burden acknowledged that lifestyle changes in women with obesity before conception and during pregnancy can be challenging, but should be encouraged. “During pregnancy, it may also seem unnatural to increase daily physical activity or change the way you are eating.” He emphasized that patients should consult their physicians and follow an established program. More randomized, controlled trials are needed from the preconception period to examine whether the health benefits are greater if the intervention begins prior to pregnancy, said Dr. Burden. However, “the current findings indeed indicate that women with obesity who lead a healthy lifestyle before and during their pregnancy can reduce the degree of unhealthy heart remodeling in their children,” he said.

Dr. Seely, Dr. Norouzi, and Dr. Burden had no financial conflicts to disclose.

Some degree of pain is inevitable in older individuals, and as people pass 80 years of age, the harms of medications used to control chronic pain increase. Pain-reducing medication use in this age group may cause inflammation, gastric bleeding, kidney damage, or constipation.

These risks may lead some clinicians to avoid aggressive pain treatment in their eldest patients, resulting in unnecessary suffering.

“Pain causes harm beyond just the physical suffering associated with it,” said Diane Meier, MD, a geriatrician and palliative care specialist at Mount Sinai Medicine in New York City who treats many people in their 80s and 90s.

Downstream effects of untreated pain could include a loss of mobility and isolation, Dr. Meier said. And, as these harms are mounting, some clinicians may avoid using an analgesic that could bring great relief: buprenorphine.

“People think about buprenorphine like they think about methadone,” Dr. Meier said, as something prescribed to treat substance use disorder. In reality, it is an effective analgesic in other situations.

Buprenorphine is better at treating chronic pain than other opioids that carry a higher addiction risk and often cause constipation in elderly patients. Buprenorphine is easier on the kidneys and has a lower addiction risk than opioids like oxycodone.

The transdermal patch form of buprenorphine (Butrans, PurduePharma) is changed weekly and starts at low doses.

“There’s an adage in geriatrics: start low and go slow,” said Jessica Merlin, MD, PhD, a palliative care and addiction medicine physician at the University of Pittsburgh Medical Center in Pittsburgh, Pennsylvania.

Dr. Merlin recommends beginning elderly patients with chronic pain on a 10-microgram/hour dose of Butrans, among the lowest doses available. Physicians could monitor side effects, which will generally be mild, with the aim of never increasing the dose if pain is managed.
 

Nonpharmacologic Remedies, Drug Considerations

“Nonpharmacologic therapy is very underutilized,” Dr. Merlin said, even though multiple alternatives to medications can improve chronic pain symptoms at any age.

Cognitive-behavioral therapy or acceptance and commitment therapy can both help people reduce the impact of pain, Dr. Merlin said. And for people who can do so, physical therapy programs, yoga, or tai chi are all ways to strengthen the body’s defenses against pain, Dr. Merlin added.

Sometimes medication is necessary, however.

“You can’t get an older person to participate in rehab if they are in severe pain,” Dr. Meier said, adding that judicious use of medications should go hand in hand with nonpharmacologic treatment.

When medications are unavoidable, internist Douglas S. Paauw, MD, starts with topical injections at the site of the pain — a troublesome joint, for example — rather than systemic medications that affect multiple organs and the brain.

“We try not to flood their body with meds” for localized problems, Dr. Paauw said, whose goal when treating elderly patients with pain is to improve their daily functioning and quality of life.

Dr. Paauw works at the University of Washington in Seattle and treats people who are approaching 100 years old. As some of his patients have grown older, Dr. Paauw’s interest in effective pain management has grown; he thinks that all internists and family medicine physician need to know how to manage chronic pain in their eldest patients.

“Were you able to play with your grandkid? Were you able to go grocery shopping? Were you able to take a walk outside?” These are the kinds of improvements Dr. Paauw hopes to see in older patients, recognizing that the wear and tear of life — orthopedic stresses or healed fractures that cause lingering pain — make it impossible for many older people to be pain free.

Pain is often spread throughout the body rather than focusing at one point, which requires systemic medications if physical therapy and similar approaches have not reduced pain. Per American Geriatrics Society (AGS) guidelines, in this situation Dr. Paauw starts with acetaminophen (Tylenol) as the lowest-risk systemic pain treatment.

Dr. Pauuw often counsels older patients to begin with 2 grams/day of acetaminophen and then progress to 3 grams if the lower dose has manageable side effects, rather than the standard dose of 4 grams that he feels is geared toward younger patients.

When acetaminophen doesn’t reduce pain sufficiently, or aggravates inflammation, Dr. Paauw may use the nerve pain medication pregabalin, or the antidepressant duloxetine — especially if the pain appears to be neuropathic.

Tricyclic antidepressants used to be recommended for neuropathic pain in older adults, but are now on the AGS’s Beers Criteria of drugs to avoid in elderly patients due to risk of causing dizziness or cardiac stress. Dr. Paauw might still use a tricyclic, but only after a careful risk-benefit analysis.

Nonsteroidal anti-inflammatory drugs (NSAIDs) like ibuprofen (Motrin) or naproxen (Aleve) could work in short bursts, Dr. Paauw said, although they may cause stomach bleeding or kidney damage in older patients.

This is why NSAIDs are not recommended by the AGS for chronic pain management. And opioids like oxycodone don’t work long at low doses, often leading to dose escalation and addiction.

“The American Geriatrics Society really puts opioids down at the bottom of the list,” Dr. Paauw said, to be used “judiciously and rarely.”

Opioids may interact with other drugs to increase risk of a fall, Dr. Meier added, making them inadvisable for older patients who live alone.

“That’s why knowing something about buprenorphine is so important,” Dr. Meier said.

Dr. Meier and Dr. Paauw are on the editorial board for Internal Medicine News. Dr. Merlin is a trainer for the Center to Advance Palliative Care, which Dr. Meier founded.
 

Some degree of pain is inevitable in older individuals, and as people pass 80 years of age, the harms of medications used to control chronic pain increase. Pain-reducing medication use in this age group may cause inflammation, gastric bleeding, kidney damage, or constipation.

These risks may lead some clinicians to avoid aggressive pain treatment in their eldest patients, resulting in unnecessary suffering.

“Pain causes harm beyond just the physical suffering associated with it,” said Diane Meier, MD, a geriatrician and palliative care specialist at Mount Sinai Medicine in New York City who treats many people in their 80s and 90s.

Downstream effects of untreated pain could include a loss of mobility and isolation, Dr. Meier said. And, as these harms are mounting, some clinicians may avoid using an analgesic that could bring great relief: buprenorphine.

“People think about buprenorphine like they think about methadone,” Dr. Meier said, as something prescribed to treat substance use disorder. In reality, it is an effective analgesic in other situations.

Buprenorphine is better at treating chronic pain than other opioids that carry a higher addiction risk and often cause constipation in elderly patients. Buprenorphine is easier on the kidneys and has a lower addiction risk than opioids like oxycodone.

The transdermal patch form of buprenorphine (Butrans, PurduePharma) is changed weekly and starts at low doses.

“There’s an adage in geriatrics: start low and go slow,” said Jessica Merlin, MD, PhD, a palliative care and addiction medicine physician at the University of Pittsburgh Medical Center in Pittsburgh, Pennsylvania.

Dr. Merlin recommends beginning elderly patients with chronic pain on a 10-microgram/hour dose of Butrans, among the lowest doses available. Physicians could monitor side effects, which will generally be mild, with the aim of never increasing the dose if pain is managed.
 

Nonpharmacologic Remedies, Drug Considerations

“Nonpharmacologic therapy is very underutilized,” Dr. Merlin said, even though multiple alternatives to medications can improve chronic pain symptoms at any age.

Cognitive-behavioral therapy or acceptance and commitment therapy can both help people reduce the impact of pain, Dr. Merlin said. And for people who can do so, physical therapy programs, yoga, or tai chi are all ways to strengthen the body’s defenses against pain, Dr. Merlin added.

Sometimes medication is necessary, however.

“You can’t get an older person to participate in rehab if they are in severe pain,” Dr. Meier said, adding that judicious use of medications should go hand in hand with nonpharmacologic treatment.

When medications are unavoidable, internist Douglas S. Paauw, MD, starts with topical injections at the site of the pain — a troublesome joint, for example — rather than systemic medications that affect multiple organs and the brain.

“We try not to flood their body with meds” for localized problems, Dr. Paauw said, whose goal when treating elderly patients with pain is to improve their daily functioning and quality of life.

Dr. Paauw works at the University of Washington in Seattle and treats people who are approaching 100 years old. As some of his patients have grown older, Dr. Paauw’s interest in effective pain management has grown; he thinks that all internists and family medicine physician need to know how to manage chronic pain in their eldest patients.

“Were you able to play with your grandkid? Were you able to go grocery shopping? Were you able to take a walk outside?” These are the kinds of improvements Dr. Paauw hopes to see in older patients, recognizing that the wear and tear of life — orthopedic stresses or healed fractures that cause lingering pain — make it impossible for many older people to be pain free.

Pain is often spread throughout the body rather than focusing at one point, which requires systemic medications if physical therapy and similar approaches have not reduced pain. Per American Geriatrics Society (AGS) guidelines, in this situation Dr. Paauw starts with acetaminophen (Tylenol) as the lowest-risk systemic pain treatment.

Dr. Pauuw often counsels older patients to begin with 2 grams/day of acetaminophen and then progress to 3 grams if the lower dose has manageable side effects, rather than the standard dose of 4 grams that he feels is geared toward younger patients.

When acetaminophen doesn’t reduce pain sufficiently, or aggravates inflammation, Dr. Paauw may use the nerve pain medication pregabalin, or the antidepressant duloxetine — especially if the pain appears to be neuropathic.

Tricyclic antidepressants used to be recommended for neuropathic pain in older adults, but are now on the AGS’s Beers Criteria of drugs to avoid in elderly patients due to risk of causing dizziness or cardiac stress. Dr. Paauw might still use a tricyclic, but only after a careful risk-benefit analysis.

Nonsteroidal anti-inflammatory drugs (NSAIDs) like ibuprofen (Motrin) or naproxen (Aleve) could work in short bursts, Dr. Paauw said, although they may cause stomach bleeding or kidney damage in older patients.

This is why NSAIDs are not recommended by the AGS for chronic pain management. And opioids like oxycodone don’t work long at low doses, often leading to dose escalation and addiction.

“The American Geriatrics Society really puts opioids down at the bottom of the list,” Dr. Paauw said, to be used “judiciously and rarely.”

Opioids may interact with other drugs to increase risk of a fall, Dr. Meier added, making them inadvisable for older patients who live alone.

“That’s why knowing something about buprenorphine is so important,” Dr. Meier said.

Dr. Meier and Dr. Paauw are on the editorial board for Internal Medicine News. Dr. Merlin is a trainer for the Center to Advance Palliative Care, which Dr. Meier founded.
 

Some degree of pain is inevitable in older individuals, and as people pass 80 years of age, the harms of medications used to control chronic pain increase. Pain-reducing medication use in this age group may cause inflammation, gastric bleeding, kidney damage, or constipation.

These risks may lead some clinicians to avoid aggressive pain treatment in their eldest patients, resulting in unnecessary suffering.

“Pain causes harm beyond just the physical suffering associated with it,” said Diane Meier, MD, a geriatrician and palliative care specialist at Mount Sinai Medicine in New York City who treats many people in their 80s and 90s.

Downstream effects of untreated pain could include a loss of mobility and isolation, Dr. Meier said. And, as these harms are mounting, some clinicians may avoid using an analgesic that could bring great relief: buprenorphine.

“People think about buprenorphine like they think about methadone,” Dr. Meier said, as something prescribed to treat substance use disorder. In reality, it is an effective analgesic in other situations.

Buprenorphine is better at treating chronic pain than other opioids that carry a higher addiction risk and often cause constipation in elderly patients. Buprenorphine is easier on the kidneys and has a lower addiction risk than opioids like oxycodone.

The transdermal patch form of buprenorphine (Butrans, PurduePharma) is changed weekly and starts at low doses.

“There’s an adage in geriatrics: start low and go slow,” said Jessica Merlin, MD, PhD, a palliative care and addiction medicine physician at the University of Pittsburgh Medical Center in Pittsburgh, Pennsylvania.

Dr. Merlin recommends beginning elderly patients with chronic pain on a 10-microgram/hour dose of Butrans, among the lowest doses available. Physicians could monitor side effects, which will generally be mild, with the aim of never increasing the dose if pain is managed.
 

Nonpharmacologic Remedies, Drug Considerations

“Nonpharmacologic therapy is very underutilized,” Dr. Merlin said, even though multiple alternatives to medications can improve chronic pain symptoms at any age.

Cognitive-behavioral therapy or acceptance and commitment therapy can both help people reduce the impact of pain, Dr. Merlin said. And for people who can do so, physical therapy programs, yoga, or tai chi are all ways to strengthen the body’s defenses against pain, Dr. Merlin added.

Sometimes medication is necessary, however.

“You can’t get an older person to participate in rehab if they are in severe pain,” Dr. Meier said, adding that judicious use of medications should go hand in hand with nonpharmacologic treatment.

When medications are unavoidable, internist Douglas S. Paauw, MD, starts with topical injections at the site of the pain — a troublesome joint, for example — rather than systemic medications that affect multiple organs and the brain.

“We try not to flood their body with meds” for localized problems, Dr. Paauw said, whose goal when treating elderly patients with pain is to improve their daily functioning and quality of life.

Dr. Paauw works at the University of Washington in Seattle and treats people who are approaching 100 years old. As some of his patients have grown older, Dr. Paauw’s interest in effective pain management has grown; he thinks that all internists and family medicine physician need to know how to manage chronic pain in their eldest patients.

“Were you able to play with your grandkid? Were you able to go grocery shopping? Were you able to take a walk outside?” These are the kinds of improvements Dr. Paauw hopes to see in older patients, recognizing that the wear and tear of life — orthopedic stresses or healed fractures that cause lingering pain — make it impossible for many older people to be pain free.

Pain is often spread throughout the body rather than focusing at one point, which requires systemic medications if physical therapy and similar approaches have not reduced pain. Per American Geriatrics Society (AGS) guidelines, in this situation Dr. Paauw starts with acetaminophen (Tylenol) as the lowest-risk systemic pain treatment.

Dr. Pauuw often counsels older patients to begin with 2 grams/day of acetaminophen and then progress to 3 grams if the lower dose has manageable side effects, rather than the standard dose of 4 grams that he feels is geared toward younger patients.

When acetaminophen doesn’t reduce pain sufficiently, or aggravates inflammation, Dr. Paauw may use the nerve pain medication pregabalin, or the antidepressant duloxetine — especially if the pain appears to be neuropathic.

Tricyclic antidepressants used to be recommended for neuropathic pain in older adults, but are now on the AGS’s Beers Criteria of drugs to avoid in elderly patients due to risk of causing dizziness or cardiac stress. Dr. Paauw might still use a tricyclic, but only after a careful risk-benefit analysis.

Nonsteroidal anti-inflammatory drugs (NSAIDs) like ibuprofen (Motrin) or naproxen (Aleve) could work in short bursts, Dr. Paauw said, although they may cause stomach bleeding or kidney damage in older patients.

This is why NSAIDs are not recommended by the AGS for chronic pain management. And opioids like oxycodone don’t work long at low doses, often leading to dose escalation and addiction.

“The American Geriatrics Society really puts opioids down at the bottom of the list,” Dr. Paauw said, to be used “judiciously and rarely.”

Opioids may interact with other drugs to increase risk of a fall, Dr. Meier added, making them inadvisable for older patients who live alone.

“That’s why knowing something about buprenorphine is so important,” Dr. Meier said.

Dr. Meier and Dr. Paauw are on the editorial board for Internal Medicine News. Dr. Merlin is a trainer for the Center to Advance Palliative Care, which Dr. Meier founded.
 

By now, it is widely accepted that artificial intelligence (AI) will reshape contemporary medicine. The question is simply when this hypothetical will become an everyday reality. For gastroenterologists involved in the management of inflammatory bowel disease (IBD), the waiting period may be ending.

AI “is the next step in clinical care,” Jacob Kurowski, MD, medical director of pediatric inflammatory bowel diseases at Cleveland Clinic Children’s in Cleveland, Ohio, said in an interview.

“In terms of technological breakthroughs, this is like going from some of the more rigid endoscopies to high-definition and white-light endoscopy or the upgrade from paper charts to the electronic medical record (EMR), but instead of making your life more difficult, it will actually make it a lot easier,” said Dr. Kurowski, who has researched and lectured on AI applications in IBD.

Simply put, “AI is when algorithms use data to simulate human intelligence,” said Seth A. Gross, MD, clinical chief in the Division of Gastroenterology and Hepatology at NYU Langone Health and a professor at NYU Grossman School of Medicine, New York City, who has studied the use of AI for polyp detection.

IBD is ideally served by AI because to diagnose and manage the disease, gastroenterologists must gather, analyze, and weave together a particularly heterogeneous mix of information — from blood tests and imaging to patient-reported symptoms and family history — often stored in different places or formats. And to ensure patient participation in their care plans, gastroenterologists also need to help them understand this complex disease.

Because of their potential to aid gastroenterologists with these tasks, three core AI technologies — some of which already have commercial applications — are likely to become foundational in clinical practice in the coming years: Image analysis and processing, natural language processing (NLP), and generative AI, according to experts familiar with AI research in IBD.
 

Image Analysis and Processing

One of AI’s most promising applications for IBD care is in medical image and video processing and analysis. Emerging AI tools convert the essential elements of medical images into mathematical features, which they then use to train and refine themselves. The ultimate goal is to provide fast, accurate, and granular results without inter- and intraobserver variation and human potential for bias.

Today’s techniques don’t quantify IBD very well because they’re qualitative and subjective, Ryan Stidham, MD, associate professor of gastroenterology and computational medicine and bioinformatics at the University of Michigan, Ann Arbor, and a leading researcher in AI applications in IBD, said in an interview.

“Even standardized scoring systems used by the US Food and Drug Administration and the European Medicines Agency to assess disease severity and measure therapeutic response are still pretty crude systems — not because of the gastroenterologists interpreting them, who are smart — but because it’s a very difficult task to quantify these features on imaging,” he said.

Another appeal of the technology in IBD care is that it has capabilities, including complex pattern recognition, beyond those of physicians.

“What we can’t do is things such as tediously measure every single ulcer, count how many different disease features are seen throughout the entire colon, where they are and how they’re spatially correlated, or what are their color patterns,” Dr. Stidham said. “We don’t have the time, feasibility, or, frankly, the energy and cognitive attention span to be able to do that for one patient, let alone every patient.”

AI-based disease activity assessments have yielded promising results across multiple imaging systems. The technology has advanced rapidly in the last decade and is beginning to demonstrate the ability to replicate near perfectly the endoscopic interpretation of human experts.

In separate studies, AI models had high levels of agreement with experienced reviewers on Mayo endoscopic scores and ulcerative colitis endoscopic index of severity scores, and they reduced the review time of pan-enteric capsule endoscopy among patients with suspected Crohn’s disease from a range of 26-39 minutes to 3.2 minutes per patient.

A report from the PiCaSSO study showed that an AI-guided system could distinguish remission/inflammation using histologic assessments of ulcerative colitis biopsies with an accuracy rate close to that of human reviewers.

In Crohn’s disease, research indicates that cross-sectional enterography imaging could potentially be made more precise with AI, providing hope that radiologists will be freed from this time-consuming task.

“As of today, several commercial companies are producing tools that can take an endoscopic image or a full-motion video and more or less give you a standardized score that would be akin to what an expert would give you on review of a colonoscopy,” Dr. Stidham said.

This is not to say there isn’t room for improvement.

“There’s probably still a bit of work to do when looking for the difference between inflammation and adenoma,” said Dr. Kurowski. “But it’s coming sooner rather than later.”
 

NLP

NLP — a subset of applied machine learning that essentially teaches computers to read — enables automated systems to go through existing digital information, including text like clinical notes, and extract, interpret, and quantify it in a fraction of the time required by clinicians.

One area this type of AI can help in IBD care is by automating EMR chart reviews. Currently, clinicians often must conduct time-consuming reviews to gather and read all the information they need to manage the care of patients with the disease.

Evidence suggests that this task takes a considerable toll. In a 2023 report, gastroenterologists cited hassles with EMRs and too much time spent at work among the main contributors to burnout.

NLP used on entire EMR systems could be used to improve overall IBD care.

“We have 30-40 years of EMRs available at our fingertips. These reams of clinical data are just sitting out there and provide a longitudinal narrative of what’s happened to every patient and the changes in their treatment course,” Dr. Stidham said.

Results from several studies involving NLP are promising. Automated chart review models enhanced with NLP have been shown to be better at identifying patients with Crohn’s disease or ulcerative colitis and at detecting and inferring the activity status of extraintestinal manifestations of IBD than models using only medical codes.

Additional examples of NLP applications that could save physicians’ time and energy in everyday practice include automatically generating clinical notes, summarizing patient interactions, and flagging important information for follow-up.

For time-strapped, overburdened clinicians, NLP may even restore the core aspects of care that first attracted them to the profession, Dr. Kurowski noted.

“It might actually be the next best step to get physicians away from the computer and back to being face to face with the patient, which I think is one of the biggest complaints of everybody in the modern EMR world in that we live in,” he said.
 

Generative AI

Patient education likely will be reshaped by emerging AI applications that can generate digital materials in a conversational tone. These generative AI tools, including advanced chatbots, are powered by large-language models, a type of machine learning that is trained on vast amounts of text data to understand and generate natural language.

This technology will be familiar to anyone who has interacted with OpenAI’s ChatGPT, which after getting a “prompt” — a question or request — from a user provides a conversational-sounding reply.

“Chatbots have been around for a while, but what’s new is that they now can understand and generate language that’s far more realistic,” Dr. Stidham said. “Plus, they can be trained on clinical scenarios so that it can put individual patients into context when having that digital, AI-powered conversation.”

In IBD, chatbots are being used to educate patients, for example, by answering their questions before they undergo colonoscopy. In a recent analysis, the best performer of three chatbots answered 91.4% of common precolonoscopy questions accurately. Other research determined that chatbot responses to colonoscopy questions were comparable with those provided by gastroenterologists.

Dr. Stidham and colleagues have seen the technology’s potential firsthand at the University of Michigan, where they’ve successfully deployed commercial chatbots to interact with patients prior to colonoscopy.

“It’s a force multiplier, in that these chatbots are essentially allowing us to expand our staff without bringing in more humans,” he said.

Despite fears that AI will threaten healthcare jobs, that isn’t an issue in today’s environment where “we can’t hire enough help,” Dr. Stidham said.

However, this technology isn’t fully ready for large-scale implementation, he added.

“ChatGPT may be ready for general medicine, but it’s not taking care of my gastroenterology patients (yet),” Dr. Stidham and coauthors wrote in a recent article. Among their concerns was the inability of ChatGPT versions 3 and 4 to pass the American College of Gastroenterology’s self-assessment test.
 

Preparing for the Future of AI

AI technology is advancing rapidly, and gastroenterologists need to be prepared for its integration into clinical practice. One proactive step is engaging with professional societies and initiatives aimed at guiding AI implementation.

One such initiative is the American Society for Gastrointestinal Endoscopy’s AI Task Force, which is led by Dr. Gross.

“The AI Task Force, which has recently evolved into an AI institute, believes in responsible AI,” Dr. Gross said. “The group highlights the importance of transparency and partnership with all key stakeholders to ensure that AI development and integration deliver improved care to GI patients.”

Dr. Kurowski, for one, believes that as AI gets even better at quantifying patient data, it will usher in the long-sought era of personalized care.

“I think it actually moves us into the realm of talking about a cure for certain people with IBD, for certain subtypes of the disease,” he said. “AI is going to be much more your friend and less of your foe than anything else you’ve seen in the modern era of medicine.”

A version of this article first appeared on Medscape.com.

By now, it is widely accepted that artificial intelligence (AI) will reshape contemporary medicine. The question is simply when this hypothetical will become an everyday reality. For gastroenterologists involved in the management of inflammatory bowel disease (IBD), the waiting period may be ending.

AI “is the next step in clinical care,” Jacob Kurowski, MD, medical director of pediatric inflammatory bowel diseases at Cleveland Clinic Children’s in Cleveland, Ohio, said in an interview.

“In terms of technological breakthroughs, this is like going from some of the more rigid endoscopies to high-definition and white-light endoscopy or the upgrade from paper charts to the electronic medical record (EMR), but instead of making your life more difficult, it will actually make it a lot easier,” said Dr. Kurowski, who has researched and lectured on AI applications in IBD.

Simply put, “AI is when algorithms use data to simulate human intelligence,” said Seth A. Gross, MD, clinical chief in the Division of Gastroenterology and Hepatology at NYU Langone Health and a professor at NYU Grossman School of Medicine, New York City, who has studied the use of AI for polyp detection.

IBD is ideally served by AI because to diagnose and manage the disease, gastroenterologists must gather, analyze, and weave together a particularly heterogeneous mix of information — from blood tests and imaging to patient-reported symptoms and family history — often stored in different places or formats. And to ensure patient participation in their care plans, gastroenterologists also need to help them understand this complex disease.

Because of their potential to aid gastroenterologists with these tasks, three core AI technologies — some of which already have commercial applications — are likely to become foundational in clinical practice in the coming years: Image analysis and processing, natural language processing (NLP), and generative AI, according to experts familiar with AI research in IBD.
 

Image Analysis and Processing

One of AI’s most promising applications for IBD care is in medical image and video processing and analysis. Emerging AI tools convert the essential elements of medical images into mathematical features, which they then use to train and refine themselves. The ultimate goal is to provide fast, accurate, and granular results without inter- and intraobserver variation and human potential for bias.

Today’s techniques don’t quantify IBD very well because they’re qualitative and subjective, Ryan Stidham, MD, associate professor of gastroenterology and computational medicine and bioinformatics at the University of Michigan, Ann Arbor, and a leading researcher in AI applications in IBD, said in an interview.

“Even standardized scoring systems used by the US Food and Drug Administration and the European Medicines Agency to assess disease severity and measure therapeutic response are still pretty crude systems — not because of the gastroenterologists interpreting them, who are smart — but because it’s a very difficult task to quantify these features on imaging,” he said.

Another appeal of the technology in IBD care is that it has capabilities, including complex pattern recognition, beyond those of physicians.

“What we can’t do is things such as tediously measure every single ulcer, count how many different disease features are seen throughout the entire colon, where they are and how they’re spatially correlated, or what are their color patterns,” Dr. Stidham said. “We don’t have the time, feasibility, or, frankly, the energy and cognitive attention span to be able to do that for one patient, let alone every patient.”

AI-based disease activity assessments have yielded promising results across multiple imaging systems. The technology has advanced rapidly in the last decade and is beginning to demonstrate the ability to replicate near perfectly the endoscopic interpretation of human experts.

In separate studies, AI models had high levels of agreement with experienced reviewers on Mayo endoscopic scores and ulcerative colitis endoscopic index of severity scores, and they reduced the review time of pan-enteric capsule endoscopy among patients with suspected Crohn’s disease from a range of 26-39 minutes to 3.2 minutes per patient.

A report from the PiCaSSO study showed that an AI-guided system could distinguish remission/inflammation using histologic assessments of ulcerative colitis biopsies with an accuracy rate close to that of human reviewers.

In Crohn’s disease, research indicates that cross-sectional enterography imaging could potentially be made more precise with AI, providing hope that radiologists will be freed from this time-consuming task.

“As of today, several commercial companies are producing tools that can take an endoscopic image or a full-motion video and more or less give you a standardized score that would be akin to what an expert would give you on review of a colonoscopy,” Dr. Stidham said.

This is not to say there isn’t room for improvement.

“There’s probably still a bit of work to do when looking for the difference between inflammation and adenoma,” said Dr. Kurowski. “But it’s coming sooner rather than later.”
 

NLP

NLP — a subset of applied machine learning that essentially teaches computers to read — enables automated systems to go through existing digital information, including text like clinical notes, and extract, interpret, and quantify it in a fraction of the time required by clinicians.

One area this type of AI can help in IBD care is by automating EMR chart reviews. Currently, clinicians often must conduct time-consuming reviews to gather and read all the information they need to manage the care of patients with the disease.

Evidence suggests that this task takes a considerable toll. In a 2023 report, gastroenterologists cited hassles with EMRs and too much time spent at work among the main contributors to burnout.

NLP used on entire EMR systems could be used to improve overall IBD care.

“We have 30-40 years of EMRs available at our fingertips. These reams of clinical data are just sitting out there and provide a longitudinal narrative of what’s happened to every patient and the changes in their treatment course,” Dr. Stidham said.

Results from several studies involving NLP are promising. Automated chart review models enhanced with NLP have been shown to be better at identifying patients with Crohn’s disease or ulcerative colitis and at detecting and inferring the activity status of extraintestinal manifestations of IBD than models using only medical codes.

Additional examples of NLP applications that could save physicians’ time and energy in everyday practice include automatically generating clinical notes, summarizing patient interactions, and flagging important information for follow-up.

For time-strapped, overburdened clinicians, NLP may even restore the core aspects of care that first attracted them to the profession, Dr. Kurowski noted.

“It might actually be the next best step to get physicians away from the computer and back to being face to face with the patient, which I think is one of the biggest complaints of everybody in the modern EMR world in that we live in,” he said.
 

Generative AI

Patient education likely will be reshaped by emerging AI applications that can generate digital materials in a conversational tone. These generative AI tools, including advanced chatbots, are powered by large-language models, a type of machine learning that is trained on vast amounts of text data to understand and generate natural language.

This technology will be familiar to anyone who has interacted with OpenAI’s ChatGPT, which after getting a “prompt” — a question or request — from a user provides a conversational-sounding reply.

“Chatbots have been around for a while, but what’s new is that they now can understand and generate language that’s far more realistic,” Dr. Stidham said. “Plus, they can be trained on clinical scenarios so that it can put individual patients into context when having that digital, AI-powered conversation.”

In IBD, chatbots are being used to educate patients, for example, by answering their questions before they undergo colonoscopy. In a recent analysis, the best performer of three chatbots answered 91.4% of common precolonoscopy questions accurately. Other research determined that chatbot responses to colonoscopy questions were comparable with those provided by gastroenterologists.

Dr. Stidham and colleagues have seen the technology’s potential firsthand at the University of Michigan, where they’ve successfully deployed commercial chatbots to interact with patients prior to colonoscopy.

“It’s a force multiplier, in that these chatbots are essentially allowing us to expand our staff without bringing in more humans,” he said.

Despite fears that AI will threaten healthcare jobs, that isn’t an issue in today’s environment where “we can’t hire enough help,” Dr. Stidham said.

However, this technology isn’t fully ready for large-scale implementation, he added.

“ChatGPT may be ready for general medicine, but it’s not taking care of my gastroenterology patients (yet),” Dr. Stidham and coauthors wrote in a recent article. Among their concerns was the inability of ChatGPT versions 3 and 4 to pass the American College of Gastroenterology’s self-assessment test.
 

Preparing for the Future of AI

AI technology is advancing rapidly, and gastroenterologists need to be prepared for its integration into clinical practice. One proactive step is engaging with professional societies and initiatives aimed at guiding AI implementation.

One such initiative is the American Society for Gastrointestinal Endoscopy’s AI Task Force, which is led by Dr. Gross.

“The AI Task Force, which has recently evolved into an AI institute, believes in responsible AI,” Dr. Gross said. “The group highlights the importance of transparency and partnership with all key stakeholders to ensure that AI development and integration deliver improved care to GI patients.”

Dr. Kurowski, for one, believes that as AI gets even better at quantifying patient data, it will usher in the long-sought era of personalized care.

“I think it actually moves us into the realm of talking about a cure for certain people with IBD, for certain subtypes of the disease,” he said. “AI is going to be much more your friend and less of your foe than anything else you’ve seen in the modern era of medicine.”

A version of this article first appeared on Medscape.com.

By now, it is widely accepted that artificial intelligence (AI) will reshape contemporary medicine. The question is simply when this hypothetical will become an everyday reality. For gastroenterologists involved in the management of inflammatory bowel disease (IBD), the waiting period may be ending.

AI “is the next step in clinical care,” Jacob Kurowski, MD, medical director of pediatric inflammatory bowel diseases at Cleveland Clinic Children’s in Cleveland, Ohio, said in an interview.

“In terms of technological breakthroughs, this is like going from some of the more rigid endoscopies to high-definition and white-light endoscopy or the upgrade from paper charts to the electronic medical record (EMR), but instead of making your life more difficult, it will actually make it a lot easier,” said Dr. Kurowski, who has researched and lectured on AI applications in IBD.

Simply put, “AI is when algorithms use data to simulate human intelligence,” said Seth A. Gross, MD, clinical chief in the Division of Gastroenterology and Hepatology at NYU Langone Health and a professor at NYU Grossman School of Medicine, New York City, who has studied the use of AI for polyp detection.

IBD is ideally served by AI because to diagnose and manage the disease, gastroenterologists must gather, analyze, and weave together a particularly heterogeneous mix of information — from blood tests and imaging to patient-reported symptoms and family history — often stored in different places or formats. And to ensure patient participation in their care plans, gastroenterologists also need to help them understand this complex disease.

Because of their potential to aid gastroenterologists with these tasks, three core AI technologies — some of which already have commercial applications — are likely to become foundational in clinical practice in the coming years: Image analysis and processing, natural language processing (NLP), and generative AI, according to experts familiar with AI research in IBD.
 

Image Analysis and Processing

One of AI’s most promising applications for IBD care is in medical image and video processing and analysis. Emerging AI tools convert the essential elements of medical images into mathematical features, which they then use to train and refine themselves. The ultimate goal is to provide fast, accurate, and granular results without inter- and intraobserver variation and human potential for bias.

Today’s techniques don’t quantify IBD very well because they’re qualitative and subjective, Ryan Stidham, MD, associate professor of gastroenterology and computational medicine and bioinformatics at the University of Michigan, Ann Arbor, and a leading researcher in AI applications in IBD, said in an interview.

“Even standardized scoring systems used by the US Food and Drug Administration and the European Medicines Agency to assess disease severity and measure therapeutic response are still pretty crude systems — not because of the gastroenterologists interpreting them, who are smart — but because it’s a very difficult task to quantify these features on imaging,” he said.

Another appeal of the technology in IBD care is that it has capabilities, including complex pattern recognition, beyond those of physicians.

“What we can’t do is things such as tediously measure every single ulcer, count how many different disease features are seen throughout the entire colon, where they are and how they’re spatially correlated, or what are their color patterns,” Dr. Stidham said. “We don’t have the time, feasibility, or, frankly, the energy and cognitive attention span to be able to do that for one patient, let alone every patient.”

AI-based disease activity assessments have yielded promising results across multiple imaging systems. The technology has advanced rapidly in the last decade and is beginning to demonstrate the ability to replicate near perfectly the endoscopic interpretation of human experts.

In separate studies, AI models had high levels of agreement with experienced reviewers on Mayo endoscopic scores and ulcerative colitis endoscopic index of severity scores, and they reduced the review time of pan-enteric capsule endoscopy among patients with suspected Crohn’s disease from a range of 26-39 minutes to 3.2 minutes per patient.

A report from the PiCaSSO study showed that an AI-guided system could distinguish remission/inflammation using histologic assessments of ulcerative colitis biopsies with an accuracy rate close to that of human reviewers.

In Crohn’s disease, research indicates that cross-sectional enterography imaging could potentially be made more precise with AI, providing hope that radiologists will be freed from this time-consuming task.

“As of today, several commercial companies are producing tools that can take an endoscopic image or a full-motion video and more or less give you a standardized score that would be akin to what an expert would give you on review of a colonoscopy,” Dr. Stidham said.

This is not to say there isn’t room for improvement.

“There’s probably still a bit of work to do when looking for the difference between inflammation and adenoma,” said Dr. Kurowski. “But it’s coming sooner rather than later.”
 

NLP

NLP — a subset of applied machine learning that essentially teaches computers to read — enables automated systems to go through existing digital information, including text like clinical notes, and extract, interpret, and quantify it in a fraction of the time required by clinicians.

One area this type of AI can help in IBD care is by automating EMR chart reviews. Currently, clinicians often must conduct time-consuming reviews to gather and read all the information they need to manage the care of patients with the disease.

Evidence suggests that this task takes a considerable toll. In a 2023 report, gastroenterologists cited hassles with EMRs and too much time spent at work among the main contributors to burnout.

NLP used on entire EMR systems could be used to improve overall IBD care.

“We have 30-40 years of EMRs available at our fingertips. These reams of clinical data are just sitting out there and provide a longitudinal narrative of what’s happened to every patient and the changes in their treatment course,” Dr. Stidham said.

Results from several studies involving NLP are promising. Automated chart review models enhanced with NLP have been shown to be better at identifying patients with Crohn’s disease or ulcerative colitis and at detecting and inferring the activity status of extraintestinal manifestations of IBD than models using only medical codes.

Additional examples of NLP applications that could save physicians’ time and energy in everyday practice include automatically generating clinical notes, summarizing patient interactions, and flagging important information for follow-up.

For time-strapped, overburdened clinicians, NLP may even restore the core aspects of care that first attracted them to the profession, Dr. Kurowski noted.

“It might actually be the next best step to get physicians away from the computer and back to being face to face with the patient, which I think is one of the biggest complaints of everybody in the modern EMR world in that we live in,” he said.
 

Generative AI

Patient education likely will be reshaped by emerging AI applications that can generate digital materials in a conversational tone. These generative AI tools, including advanced chatbots, are powered by large-language models, a type of machine learning that is trained on vast amounts of text data to understand and generate natural language.

This technology will be familiar to anyone who has interacted with OpenAI’s ChatGPT, which after getting a “prompt” — a question or request — from a user provides a conversational-sounding reply.

“Chatbots have been around for a while, but what’s new is that they now can understand and generate language that’s far more realistic,” Dr. Stidham said. “Plus, they can be trained on clinical scenarios so that it can put individual patients into context when having that digital, AI-powered conversation.”

In IBD, chatbots are being used to educate patients, for example, by answering their questions before they undergo colonoscopy. In a recent analysis, the best performer of three chatbots answered 91.4% of common precolonoscopy questions accurately. Other research determined that chatbot responses to colonoscopy questions were comparable with those provided by gastroenterologists.

Dr. Stidham and colleagues have seen the technology’s potential firsthand at the University of Michigan, where they’ve successfully deployed commercial chatbots to interact with patients prior to colonoscopy.

“It’s a force multiplier, in that these chatbots are essentially allowing us to expand our staff without bringing in more humans,” he said.

Despite fears that AI will threaten healthcare jobs, that isn’t an issue in today’s environment where “we can’t hire enough help,” Dr. Stidham said.

However, this technology isn’t fully ready for large-scale implementation, he added.

“ChatGPT may be ready for general medicine, but it’s not taking care of my gastroenterology patients (yet),” Dr. Stidham and coauthors wrote in a recent article. Among their concerns was the inability of ChatGPT versions 3 and 4 to pass the American College of Gastroenterology’s self-assessment test.
 

Preparing for the Future of AI

AI technology is advancing rapidly, and gastroenterologists need to be prepared for its integration into clinical practice. One proactive step is engaging with professional societies and initiatives aimed at guiding AI implementation.

One such initiative is the American Society for Gastrointestinal Endoscopy’s AI Task Force, which is led by Dr. Gross.

“The AI Task Force, which has recently evolved into an AI institute, believes in responsible AI,” Dr. Gross said. “The group highlights the importance of transparency and partnership with all key stakeholders to ensure that AI development and integration deliver improved care to GI patients.”

Dr. Kurowski, for one, believes that as AI gets even better at quantifying patient data, it will usher in the long-sought era of personalized care.

“I think it actually moves us into the realm of talking about a cure for certain people with IBD, for certain subtypes of the disease,” he said. “AI is going to be much more your friend and less of your foe than anything else you’ve seen in the modern era of medicine.”

A version of this article first appeared on Medscape.com.

A growing body of evidence has shown that people who regularly take aspirin have a lower risk for colorectal cancer (CRC) and are less likely to die if they do develop the disease.

A 2020 meta-analysis, for instance, found that 325 mg of daily aspirin — the typical dose in a single tablet — conferred a 35% reduced risk of developing CRC, and a highly cited The Lancet study from 2010 found that a low dose of daily aspirin reduced the incidence of colon cancer by 24% and colon cancer deaths by 35% over 20 years.

The evidence surrounding aspirin and CRC is so intriguing that more than 70,000 people are currently participating in more than two dozen clinical studies worldwide, putting aspirin through its paces as an intervention in CRC.

But what, exactly, is aspirin doing?

We know that aspirin inhibits cyclooxygenase (COX) enzymes — COX-1 and COX-2, specifically — and that the COX-2 pathway is implicated in the development and progression of CRC, explained Marco Scarpa, MD, PhD, staff surgeon at the University of Padova in Padova, Italy.

“However, the new thing we’ve found is that aspirin may have a direct role in enhancing immunosurveillance,” Dr. Scarpa said in an interview.

In April, Dr. Scarpa’s team published a paper in Cancer describing a mechanism that provides deeper insight into the aspirin-CRC connection.

Dr. Scarpa heads up the IMMUNOREACT study group, a collaboration of dozens of researchers across Italy running studies on immunosurveillance in rectal cancer. In the baseline study, IMMUNOREACT 1, the team created and analyzed a database of records from 238 patients who underwent surgery for CRC at the Azienda Ospedale Università di Padova, Padova, Italy, from 2015 to 2019.

Using the same database, the latest findings from IMMUNOREACT 7 focused on the fate of the 31 patients (13%) who used aspirin regularly.

The researchers found that regular aspirin use did not appear to affect colorectal tumor stage at diagnosis, but tumor grading was significantly lower overall, especially in patients with BRAF mutations. Regular aspirin users were also less likely to have nodal metastases and metastatic lymph nodes, and this effect was more pronounced in patients with proximal (right-sided) colon cancer vs distal (left-sided).

Most notably, IMMUNOREACT 7 revealed that aspirin has beneficial effects on the CRC immune microenvironment.

The team found that aspirin directly boosts the presence of antigens on gastrointestinal epithelial tumor cells, which can direct the body’s immune response to combat the cancer.

At a macro level, the aspirin users in the study were more likely to have high levels of tumor-infiltrating lymphocytes (TILs). Dr. Scarpa’s team had previously shown that high levels of CD8+ and CD3+ TILs were predictive of successful neoadjuvant therapy in rectal cancer.

Cytotoxic CD8+ T cells are central to the anticancer immune response, and in the latest study, a high ratio of CD8+/CD3+ T cells was more common in aspirin users, suggesting a stronger presence of cancer-killing CD8+ cells. Expression of CD8 beta+, an activation marker of CD8+ cells, was also enhanced in aspirin users.

The most significant discovery, according to Dr. Scarpa, was that aspirin users were more likely to show high expression of CD80 on the surface of their rectal epithelial cells.

CD80 is a molecule that allows T cells to identify the tumor cell as foreign and kill it. Although cancer cells can downregulate their CD80 to avoid detection by T cells, the study suggests that aspirin appears to help foil this strategy by boosting the production of CD80 on the surface of the tumor cells.

The researchers confirmed the clinical findings by showing that aspirin increased CD80 gene expression in lab-cultivated CRC cells.

“We didn’t expect the activation through CD80,” said Dr. Scarpa. “This means that aspirin can act on this very first interaction between the epithelial cell and the CD8+ lymphocyte.”

Overall, these new data suggest that aspirin helps activate the immune system, which helps explain its potential chemopreventive effect in CRC.

However, one puzzling result was that aspirin boosted expression of PD-L1 genes in the CRC cells, said Joanna Davies, DPhil, an immunologist who heads up the San Diego Biomedical Research Institute, San Diego, California, and was not involved in the study.

PD-L1 serves as an “off” switch for patrolling T cells, which protects the tumor cell from being recognized.

“If aspirin is inducing PD-L1 on cancer cells, that is a potential problem,” said Dr. Davies. “An ideal therapy might be the combination of aspirin to enhance the CD8 T cells in the tumor and immune checkpoint blockade to block PD-L1.”

David Kerr, CBE, MD, DSc, agreed that high-dose aspirin plus immunotherapy might be “a wee bit more effective.” However, the combination would be blocked by the economics of drug development: “Will anybody ever do a trial of 10,000 patients to prove that? Not on your nelly,” said Dr. Kerr, professor of cancer medicine at the University of Oxford, Oxford, England.

Despite the small patient numbers in the study, Dr. Kerr felt encouraged by the IMMUNOREACT analysis. “It’s a plausible piece of science and some quite promising work on the tumor immune microenvironment and the effects of aspirin on it,” Dr. Kerr said in a recent commentary for this news organization.

Dr. Scarpa and Dr. Davies had no conflicts of interest to declare.

A version of this article appeared on Medscape.com .

A growing body of evidence has shown that people who regularly take aspirin have a lower risk for colorectal cancer (CRC) and are less likely to die if they do develop the disease.

A 2020 meta-analysis, for instance, found that 325 mg of daily aspirin — the typical dose in a single tablet — conferred a 35% reduced risk of developing CRC, and a highly cited The Lancet study from 2010 found that a low dose of daily aspirin reduced the incidence of colon cancer by 24% and colon cancer deaths by 35% over 20 years.

The evidence surrounding aspirin and CRC is so intriguing that more than 70,000 people are currently participating in more than two dozen clinical studies worldwide, putting aspirin through its paces as an intervention in CRC.

But what, exactly, is aspirin doing?

We know that aspirin inhibits cyclooxygenase (COX) enzymes — COX-1 and COX-2, specifically — and that the COX-2 pathway is implicated in the development and progression of CRC, explained Marco Scarpa, MD, PhD, staff surgeon at the University of Padova in Padova, Italy.

“However, the new thing we’ve found is that aspirin may have a direct role in enhancing immunosurveillance,” Dr. Scarpa said in an interview.

In April, Dr. Scarpa’s team published a paper in Cancer describing a mechanism that provides deeper insight into the aspirin-CRC connection.

Dr. Scarpa heads up the IMMUNOREACT study group, a collaboration of dozens of researchers across Italy running studies on immunosurveillance in rectal cancer. In the baseline study, IMMUNOREACT 1, the team created and analyzed a database of records from 238 patients who underwent surgery for CRC at the Azienda Ospedale Università di Padova, Padova, Italy, from 2015 to 2019.

Using the same database, the latest findings from IMMUNOREACT 7 focused on the fate of the 31 patients (13%) who used aspirin regularly.

The researchers found that regular aspirin use did not appear to affect colorectal tumor stage at diagnosis, but tumor grading was significantly lower overall, especially in patients with BRAF mutations. Regular aspirin users were also less likely to have nodal metastases and metastatic lymph nodes, and this effect was more pronounced in patients with proximal (right-sided) colon cancer vs distal (left-sided).

Most notably, IMMUNOREACT 7 revealed that aspirin has beneficial effects on the CRC immune microenvironment.

The team found that aspirin directly boosts the presence of antigens on gastrointestinal epithelial tumor cells, which can direct the body’s immune response to combat the cancer.

At a macro level, the aspirin users in the study were more likely to have high levels of tumor-infiltrating lymphocytes (TILs). Dr. Scarpa’s team had previously shown that high levels of CD8+ and CD3+ TILs were predictive of successful neoadjuvant therapy in rectal cancer.

Cytotoxic CD8+ T cells are central to the anticancer immune response, and in the latest study, a high ratio of CD8+/CD3+ T cells was more common in aspirin users, suggesting a stronger presence of cancer-killing CD8+ cells. Expression of CD8 beta+, an activation marker of CD8+ cells, was also enhanced in aspirin users.

The most significant discovery, according to Dr. Scarpa, was that aspirin users were more likely to show high expression of CD80 on the surface of their rectal epithelial cells.

CD80 is a molecule that allows T cells to identify the tumor cell as foreign and kill it. Although cancer cells can downregulate their CD80 to avoid detection by T cells, the study suggests that aspirin appears to help foil this strategy by boosting the production of CD80 on the surface of the tumor cells.

The researchers confirmed the clinical findings by showing that aspirin increased CD80 gene expression in lab-cultivated CRC cells.

“We didn’t expect the activation through CD80,” said Dr. Scarpa. “This means that aspirin can act on this very first interaction between the epithelial cell and the CD8+ lymphocyte.”

Overall, these new data suggest that aspirin helps activate the immune system, which helps explain its potential chemopreventive effect in CRC.

However, one puzzling result was that aspirin boosted expression of PD-L1 genes in the CRC cells, said Joanna Davies, DPhil, an immunologist who heads up the San Diego Biomedical Research Institute, San Diego, California, and was not involved in the study.

PD-L1 serves as an “off” switch for patrolling T cells, which protects the tumor cell from being recognized.

“If aspirin is inducing PD-L1 on cancer cells, that is a potential problem,” said Dr. Davies. “An ideal therapy might be the combination of aspirin to enhance the CD8 T cells in the tumor and immune checkpoint blockade to block PD-L1.”

David Kerr, CBE, MD, DSc, agreed that high-dose aspirin plus immunotherapy might be “a wee bit more effective.” However, the combination would be blocked by the economics of drug development: “Will anybody ever do a trial of 10,000 patients to prove that? Not on your nelly,” said Dr. Kerr, professor of cancer medicine at the University of Oxford, Oxford, England.

Despite the small patient numbers in the study, Dr. Kerr felt encouraged by the IMMUNOREACT analysis. “It’s a plausible piece of science and some quite promising work on the tumor immune microenvironment and the effects of aspirin on it,” Dr. Kerr said in a recent commentary for this news organization.

Dr. Scarpa and Dr. Davies had no conflicts of interest to declare.

A version of this article appeared on Medscape.com .

A growing body of evidence has shown that people who regularly take aspirin have a lower risk for colorectal cancer (CRC) and are less likely to die if they do develop the disease.

A 2020 meta-analysis, for instance, found that 325 mg of daily aspirin — the typical dose in a single tablet — conferred a 35% reduced risk of developing CRC, and a highly cited The Lancet study from 2010 found that a low dose of daily aspirin reduced the incidence of colon cancer by 24% and colon cancer deaths by 35% over 20 years.

The evidence surrounding aspirin and CRC is so intriguing that more than 70,000 people are currently participating in more than two dozen clinical studies worldwide, putting aspirin through its paces as an intervention in CRC.

But what, exactly, is aspirin doing?

We know that aspirin inhibits cyclooxygenase (COX) enzymes — COX-1 and COX-2, specifically — and that the COX-2 pathway is implicated in the development and progression of CRC, explained Marco Scarpa, MD, PhD, staff surgeon at the University of Padova in Padova, Italy.

“However, the new thing we’ve found is that aspirin may have a direct role in enhancing immunosurveillance,” Dr. Scarpa said in an interview.

In April, Dr. Scarpa’s team published a paper in Cancer describing a mechanism that provides deeper insight into the aspirin-CRC connection.

Dr. Scarpa heads up the IMMUNOREACT study group, a collaboration of dozens of researchers across Italy running studies on immunosurveillance in rectal cancer. In the baseline study, IMMUNOREACT 1, the team created and analyzed a database of records from 238 patients who underwent surgery for CRC at the Azienda Ospedale Università di Padova, Padova, Italy, from 2015 to 2019.

Using the same database, the latest findings from IMMUNOREACT 7 focused on the fate of the 31 patients (13%) who used aspirin regularly.

The researchers found that regular aspirin use did not appear to affect colorectal tumor stage at diagnosis, but tumor grading was significantly lower overall, especially in patients with BRAF mutations. Regular aspirin users were also less likely to have nodal metastases and metastatic lymph nodes, and this effect was more pronounced in patients with proximal (right-sided) colon cancer vs distal (left-sided).

Most notably, IMMUNOREACT 7 revealed that aspirin has beneficial effects on the CRC immune microenvironment.

The team found that aspirin directly boosts the presence of antigens on gastrointestinal epithelial tumor cells, which can direct the body’s immune response to combat the cancer.

At a macro level, the aspirin users in the study were more likely to have high levels of tumor-infiltrating lymphocytes (TILs). Dr. Scarpa’s team had previously shown that high levels of CD8+ and CD3+ TILs were predictive of successful neoadjuvant therapy in rectal cancer.

Cytotoxic CD8+ T cells are central to the anticancer immune response, and in the latest study, a high ratio of CD8+/CD3+ T cells was more common in aspirin users, suggesting a stronger presence of cancer-killing CD8+ cells. Expression of CD8 beta+, an activation marker of CD8+ cells, was also enhanced in aspirin users.

The most significant discovery, according to Dr. Scarpa, was that aspirin users were more likely to show high expression of CD80 on the surface of their rectal epithelial cells.

CD80 is a molecule that allows T cells to identify the tumor cell as foreign and kill it. Although cancer cells can downregulate their CD80 to avoid detection by T cells, the study suggests that aspirin appears to help foil this strategy by boosting the production of CD80 on the surface of the tumor cells.

The researchers confirmed the clinical findings by showing that aspirin increased CD80 gene expression in lab-cultivated CRC cells.

“We didn’t expect the activation through CD80,” said Dr. Scarpa. “This means that aspirin can act on this very first interaction between the epithelial cell and the CD8+ lymphocyte.”

Overall, these new data suggest that aspirin helps activate the immune system, which helps explain its potential chemopreventive effect in CRC.

However, one puzzling result was that aspirin boosted expression of PD-L1 genes in the CRC cells, said Joanna Davies, DPhil, an immunologist who heads up the San Diego Biomedical Research Institute, San Diego, California, and was not involved in the study.

PD-L1 serves as an “off” switch for patrolling T cells, which protects the tumor cell from being recognized.

“If aspirin is inducing PD-L1 on cancer cells, that is a potential problem,” said Dr. Davies. “An ideal therapy might be the combination of aspirin to enhance the CD8 T cells in the tumor and immune checkpoint blockade to block PD-L1.”

David Kerr, CBE, MD, DSc, agreed that high-dose aspirin plus immunotherapy might be “a wee bit more effective.” However, the combination would be blocked by the economics of drug development: “Will anybody ever do a trial of 10,000 patients to prove that? Not on your nelly,” said Dr. Kerr, professor of cancer medicine at the University of Oxford, Oxford, England.

Despite the small patient numbers in the study, Dr. Kerr felt encouraged by the IMMUNOREACT analysis. “It’s a plausible piece of science and some quite promising work on the tumor immune microenvironment and the effects of aspirin on it,” Dr. Kerr said in a recent commentary for this news organization.

Dr. Scarpa and Dr. Davies had no conflicts of interest to declare.

A version of this article appeared on Medscape.com .

Potential harms and benefits should be weighed carefully before women and their physicians decide on breast cancer screening, according to updated guidelines from the Canadian Task Force on Preventive Health Care.

The draft guidelines stem from a review of more than 165 recent randomized controlled trials, observational studies, mathematical models, and other data.

The guideline working group included four breast cancer experts (a medical oncologist, a radiation oncologist, a surgical oncologist, and a radiologist), three patient partners, six family physicians, a nurse practitioner, evidence review teams, and other experts.

To avoid potential conflicts of interest, the oncologists provided input but did not vote on the final recommendations, Guylène Thériault, MD, a family physician and chair of the task force and Breast Cancer Working Group, said in an interview. 

The guideline recommends that, after the potential benefits and harms of screening have been considered, mammography should be accessible every 2-3 years to women (ie, people assigned female at birth) between ages 40 and 74 years who are at average or moderately increased risk.

Women with a personal or extensive family history of breast cancer or genetic mutations that would increase breast cancer risk; those who have symptoms, such as a lump; those who feel they may be at high risk; and those who are transgender women should consult a healthcare provider about appropriate options, according to the updated guidelines, which do not apply to these patients.

The draft guidelines were published online on May 30 and are open for public comment until August 30.
 

‘Three Big Questions’

To develop the guidelines, the work group asked “three big questions,” said Dr. Thériault. The first was the effectiveness of breast cancer screening for women aged 40 years and over. For this question, this systematic review, unlike the 2018 guideline update, included not only randomized trials but also observational data to ensure that the work group considered all available data.

“The second question was about comparative effectiveness,” which is something the United States considered for the latest US Preventive Services Task Force (USPSTF) update, said Dr. Thériault. The USPSTF asked questions such as “What happens if we start screening patients at age 40 years? Or at age 50 years? What happens if we stop at age 74 years? Or if we use different tests such as 3D versus digital mammography?”

The Canadian Task Force relied on the evidence that the USPSTF found after grading it with its own criteria, she said. The results were similar, and so are the recommendations in this area. “For example, we don’t recommend supplementary screening for women with dense breasts because there are no studies to inform patient-oriented benefits.”

The third question was about the values and preferences of women regarding breast cancer screening, which is something the United States didn’t examine. “We had looked at that issue in 2018, and this time around, even though we expanded the type of studies, we got the same message: That there are differences between women in their 40s and those who are age 50 years and over.”

“The majority of women in their 40s think that the harms outweigh the benefits and are not interested in screening,” said Dr. Thériault. “But when I say the majority, that’s not every woman. So, we had to recognize that there is variability. And the majority, but not all, of women ages 50-74 years thinks the benefits are higher than the harms. That’s why we say in our recommendation that from ages 40 to 74, it’s a personal choice.”
 

Responding to Objections

Not surprisingly, the task force has heard objections to its draft guidelines. The first is that women aged 40-49 years are being denied mammograms, said Michelle Nadler, MD, a medical oncologist at Princess Margaret Cancer Centre in Toronto, Canada. “This [objection] has attained a lot of media coverage, which is unfortunate, because people who have not read the guidelines may believe this is true. The guidelines clearly state that an eligible, informed woman of this age group who wants a screening mammogram should receive one.”

The second commonly heard objection is that the task force is overestimating the harms of screening, such as anxiety and overdiagnosis, she said. But an outcome of “anxiety” was not factored into the guideline. Overdiagnosis was calculated on the basis of the literature, and estimates were converted to a common denominator so that they could be compared, said Dr. Nadler. The same was true of benefits.

Another objection was that screening could mean less need for chemotherapy or full axillary dissection, Dr. Nadler said. However, the task force did not find any primary studies that evaluated these outcomes.

Critics also said that the recommendations do not account for racial or ethnic variations. Although more research is likely needed in this area, “the task force states that individuals should be informed of all of their breast cancer risk factors, including race/ethnicity, and that this should be factored into decisions about screening,” said Dr. Nadler.

“I was very surprised that the task force was accused by some parties of paternalism,” added René Wittmer, MD, adjunct clinical professor of family medicine at the University of Montreal and chair of Choosing Wisely Quebec, Montreal, Canada. “In my opinion, the importance they place on shared decision-making is contrary to medical paternalism and aims to empower women to make a decision that fits with their values and preferences.”

Nevertheless, the inclusion of modeling studies and observational trials “may cause the potential benefits to be amplified, compared with what is seen in randomized controlled trials,” he said in an interview.
 

Decision Aids Help

Once the guidelines are finalized, decision aids will be available to patients and providers to help guide screening discussions, said Dr. Nadler. “Primary care providers need to be aware of an individual’s personal risk factors for breast cancer to know if they are at average, above average, or high lifetime risk of breast cancer. These guidelines do not apply to those with > 20% lifetime risk of breast cancer.”

“The standards for risk communication are in absolute numbers over a common denominator,” she noted. “This is how primary care providers discuss other important primary care topics like smoking cessation, cardiovascular disease (and decisions about statin medications), and osteoporosis risk. These same standards should apply for breast cancer screening.”

Furthermore, she said, providers “should be aware that individuals from marginalized communities may benefit from more than one conversation until they are able to make a decision about screening that is right for them.”

“There is good evidence showing that most advances we’ve seen in breast cancer outcomes (ie, reduction in breast cancer mortality) are likely due to improvements in treatment, not screening,” said Dr. Wittmer. “In fact, mortality reductions are seen even in age groups or countries where there is no routine screening. This means that women benefit from advances in treatments, whether they choose to get screened or not.”
 

‘Mammography Saves Lives’

Commenting on the updated guidelines, Janie Lee, MD, professor of radiology at the University of Washington School of Medicine and director of breast imaging at the Fred Hutchinson Cancer Center, both in Seattle, said: “For the USPSTF, benefits of life years gained were also considered, in addition to breast cancer deaths averted. To save more lives from breast cancer, guidelines may focus on screening women at older ages, when annual rates of breast cancer are higher.” By contrast, when thinking in terms of years of life saved, focusing on screening younger women, who have more years of life left, increases benefits. “Both are important outcomes that we want to improve with effective screening.”

That said, “we should follow the guidelines of our specific national organizations,” she continued. “Overall populations and healthcare systems are different between the US and Canada.”

For example, “the USPSTF specifically highlighted the potential for reducing breast cancer mortality in Black women, who are more likely to develop biologically aggressive tumors that are diagnosed at more advanced stages, when making updated recommendations earlier this year,” she said. “The Canadian guidelines did not make specific recommendations by race or ethnicity group, instead highlighting the need for more research on the impact of screening in these groups.”

In addition, “screening every year versus every other year is more routine in the US compared with Canada,” she noted. And nonmedical factors that influence health and that may influence access to medical care and timely diagnosis of breast cancer “may be different between our two countries.”

“The most important take-home message is that the scientific evidence is strong that screening mammography saves lives,” said Dr. Lee. “These new recommendations will hopefully result in more early diagnoses of breast cancer and save more lives. Screening works best when it’s used regularly, regardless of how frequently you return. Once you start screening, please urge your patients to plan to return.”

Dr. Nadler disclosed speaker honoraria and consulting fees from Novartis and Exact Sciences outside the scope of this interview and innovation funding from the NSH/UHN AMO Innovation Fund Competition for Developing and Implementing a Consensus Recommendation for Breast Cancer Screening Best Practices. Dr. Thériault is chair of the task force and chair of the working group for the draft guidelines. Dr. Wittmer is chair of Choosing Wisely Quebec. Dr. Lee reported no relevant financial relationships related to her interview.

A version of this article appeared on Medscape.com.

Potential harms and benefits should be weighed carefully before women and their physicians decide on breast cancer screening, according to updated guidelines from the Canadian Task Force on Preventive Health Care.

The draft guidelines stem from a review of more than 165 recent randomized controlled trials, observational studies, mathematical models, and other data.

The guideline working group included four breast cancer experts (a medical oncologist, a radiation oncologist, a surgical oncologist, and a radiologist), three patient partners, six family physicians, a nurse practitioner, evidence review teams, and other experts.

To avoid potential conflicts of interest, the oncologists provided input but did not vote on the final recommendations, Guylène Thériault, MD, a family physician and chair of the task force and Breast Cancer Working Group, said in an interview. 

The guideline recommends that, after the potential benefits and harms of screening have been considered, mammography should be accessible every 2-3 years to women (ie, people assigned female at birth) between ages 40 and 74 years who are at average or moderately increased risk.

Women with a personal or extensive family history of breast cancer or genetic mutations that would increase breast cancer risk; those who have symptoms, such as a lump; those who feel they may be at high risk; and those who are transgender women should consult a healthcare provider about appropriate options, according to the updated guidelines, which do not apply to these patients.

The draft guidelines were published online on May 30 and are open for public comment until August 30.
 

‘Three Big Questions’

To develop the guidelines, the work group asked “three big questions,” said Dr. Thériault. The first was the effectiveness of breast cancer screening for women aged 40 years and over. For this question, this systematic review, unlike the 2018 guideline update, included not only randomized trials but also observational data to ensure that the work group considered all available data.

“The second question was about comparative effectiveness,” which is something the United States considered for the latest US Preventive Services Task Force (USPSTF) update, said Dr. Thériault. The USPSTF asked questions such as “What happens if we start screening patients at age 40 years? Or at age 50 years? What happens if we stop at age 74 years? Or if we use different tests such as 3D versus digital mammography?”

The Canadian Task Force relied on the evidence that the USPSTF found after grading it with its own criteria, she said. The results were similar, and so are the recommendations in this area. “For example, we don’t recommend supplementary screening for women with dense breasts because there are no studies to inform patient-oriented benefits.”

The third question was about the values and preferences of women regarding breast cancer screening, which is something the United States didn’t examine. “We had looked at that issue in 2018, and this time around, even though we expanded the type of studies, we got the same message: That there are differences between women in their 40s and those who are age 50 years and over.”

“The majority of women in their 40s think that the harms outweigh the benefits and are not interested in screening,” said Dr. Thériault. “But when I say the majority, that’s not every woman. So, we had to recognize that there is variability. And the majority, but not all, of women ages 50-74 years thinks the benefits are higher than the harms. That’s why we say in our recommendation that from ages 40 to 74, it’s a personal choice.”
 

Responding to Objections

Not surprisingly, the task force has heard objections to its draft guidelines. The first is that women aged 40-49 years are being denied mammograms, said Michelle Nadler, MD, a medical oncologist at Princess Margaret Cancer Centre in Toronto, Canada. “This [objection] has attained a lot of media coverage, which is unfortunate, because people who have not read the guidelines may believe this is true. The guidelines clearly state that an eligible, informed woman of this age group who wants a screening mammogram should receive one.”

The second commonly heard objection is that the task force is overestimating the harms of screening, such as anxiety and overdiagnosis, she said. But an outcome of “anxiety” was not factored into the guideline. Overdiagnosis was calculated on the basis of the literature, and estimates were converted to a common denominator so that they could be compared, said Dr. Nadler. The same was true of benefits.

Another objection was that screening could mean less need for chemotherapy or full axillary dissection, Dr. Nadler said. However, the task force did not find any primary studies that evaluated these outcomes.

Critics also said that the recommendations do not account for racial or ethnic variations. Although more research is likely needed in this area, “the task force states that individuals should be informed of all of their breast cancer risk factors, including race/ethnicity, and that this should be factored into decisions about screening,” said Dr. Nadler.

“I was very surprised that the task force was accused by some parties of paternalism,” added René Wittmer, MD, adjunct clinical professor of family medicine at the University of Montreal and chair of Choosing Wisely Quebec, Montreal, Canada. “In my opinion, the importance they place on shared decision-making is contrary to medical paternalism and aims to empower women to make a decision that fits with their values and preferences.”

Nevertheless, the inclusion of modeling studies and observational trials “may cause the potential benefits to be amplified, compared with what is seen in randomized controlled trials,” he said in an interview.
 

Decision Aids Help

Once the guidelines are finalized, decision aids will be available to patients and providers to help guide screening discussions, said Dr. Nadler. “Primary care providers need to be aware of an individual’s personal risk factors for breast cancer to know if they are at average, above average, or high lifetime risk of breast cancer. These guidelines do not apply to those with > 20% lifetime risk of breast cancer.”

“The standards for risk communication are in absolute numbers over a common denominator,” she noted. “This is how primary care providers discuss other important primary care topics like smoking cessation, cardiovascular disease (and decisions about statin medications), and osteoporosis risk. These same standards should apply for breast cancer screening.”

Furthermore, she said, providers “should be aware that individuals from marginalized communities may benefit from more than one conversation until they are able to make a decision about screening that is right for them.”

“There is good evidence showing that most advances we’ve seen in breast cancer outcomes (ie, reduction in breast cancer mortality) are likely due to improvements in treatment, not screening,” said Dr. Wittmer. “In fact, mortality reductions are seen even in age groups or countries where there is no routine screening. This means that women benefit from advances in treatments, whether they choose to get screened or not.”
 

‘Mammography Saves Lives’

Commenting on the updated guidelines, Janie Lee, MD, professor of radiology at the University of Washington School of Medicine and director of breast imaging at the Fred Hutchinson Cancer Center, both in Seattle, said: “For the USPSTF, benefits of life years gained were also considered, in addition to breast cancer deaths averted. To save more lives from breast cancer, guidelines may focus on screening women at older ages, when annual rates of breast cancer are higher.” By contrast, when thinking in terms of years of life saved, focusing on screening younger women, who have more years of life left, increases benefits. “Both are important outcomes that we want to improve with effective screening.”

That said, “we should follow the guidelines of our specific national organizations,” she continued. “Overall populations and healthcare systems are different between the US and Canada.”

For example, “the USPSTF specifically highlighted the potential for reducing breast cancer mortality in Black women, who are more likely to develop biologically aggressive tumors that are diagnosed at more advanced stages, when making updated recommendations earlier this year,” she said. “The Canadian guidelines did not make specific recommendations by race or ethnicity group, instead highlighting the need for more research on the impact of screening in these groups.”

In addition, “screening every year versus every other year is more routine in the US compared with Canada,” she noted. And nonmedical factors that influence health and that may influence access to medical care and timely diagnosis of breast cancer “may be different between our two countries.”

“The most important take-home message is that the scientific evidence is strong that screening mammography saves lives,” said Dr. Lee. “These new recommendations will hopefully result in more early diagnoses of breast cancer and save more lives. Screening works best when it’s used regularly, regardless of how frequently you return. Once you start screening, please urge your patients to plan to return.”

Dr. Nadler disclosed speaker honoraria and consulting fees from Novartis and Exact Sciences outside the scope of this interview and innovation funding from the NSH/UHN AMO Innovation Fund Competition for Developing and Implementing a Consensus Recommendation for Breast Cancer Screening Best Practices. Dr. Thériault is chair of the task force and chair of the working group for the draft guidelines. Dr. Wittmer is chair of Choosing Wisely Quebec. Dr. Lee reported no relevant financial relationships related to her interview.

A version of this article appeared on Medscape.com.

Potential harms and benefits should be weighed carefully before women and their physicians decide on breast cancer screening, according to updated guidelines from the Canadian Task Force on Preventive Health Care.

The draft guidelines stem from a review of more than 165 recent randomized controlled trials, observational studies, mathematical models, and other data.

The guideline working group included four breast cancer experts (a medical oncologist, a radiation oncologist, a surgical oncologist, and a radiologist), three patient partners, six family physicians, a nurse practitioner, evidence review teams, and other experts.

To avoid potential conflicts of interest, the oncologists provided input but did not vote on the final recommendations, Guylène Thériault, MD, a family physician and chair of the task force and Breast Cancer Working Group, said in an interview. 

The guideline recommends that, after the potential benefits and harms of screening have been considered, mammography should be accessible every 2-3 years to women (ie, people assigned female at birth) between ages 40 and 74 years who are at average or moderately increased risk.

Women with a personal or extensive family history of breast cancer or genetic mutations that would increase breast cancer risk; those who have symptoms, such as a lump; those who feel they may be at high risk; and those who are transgender women should consult a healthcare provider about appropriate options, according to the updated guidelines, which do not apply to these patients.

The draft guidelines were published online on May 30 and are open for public comment until August 30.
 

‘Three Big Questions’

To develop the guidelines, the work group asked “three big questions,” said Dr. Thériault. The first was the effectiveness of breast cancer screening for women aged 40 years and over. For this question, this systematic review, unlike the 2018 guideline update, included not only randomized trials but also observational data to ensure that the work group considered all available data.

“The second question was about comparative effectiveness,” which is something the United States considered for the latest US Preventive Services Task Force (USPSTF) update, said Dr. Thériault. The USPSTF asked questions such as “What happens if we start screening patients at age 40 years? Or at age 50 years? What happens if we stop at age 74 years? Or if we use different tests such as 3D versus digital mammography?”

The Canadian Task Force relied on the evidence that the USPSTF found after grading it with its own criteria, she said. The results were similar, and so are the recommendations in this area. “For example, we don’t recommend supplementary screening for women with dense breasts because there are no studies to inform patient-oriented benefits.”

The third question was about the values and preferences of women regarding breast cancer screening, which is something the United States didn’t examine. “We had looked at that issue in 2018, and this time around, even though we expanded the type of studies, we got the same message: That there are differences between women in their 40s and those who are age 50 years and over.”

“The majority of women in their 40s think that the harms outweigh the benefits and are not interested in screening,” said Dr. Thériault. “But when I say the majority, that’s not every woman. So, we had to recognize that there is variability. And the majority, but not all, of women ages 50-74 years thinks the benefits are higher than the harms. That’s why we say in our recommendation that from ages 40 to 74, it’s a personal choice.”
 

Responding to Objections

Not surprisingly, the task force has heard objections to its draft guidelines. The first is that women aged 40-49 years are being denied mammograms, said Michelle Nadler, MD, a medical oncologist at Princess Margaret Cancer Centre in Toronto, Canada. “This [objection] has attained a lot of media coverage, which is unfortunate, because people who have not read the guidelines may believe this is true. The guidelines clearly state that an eligible, informed woman of this age group who wants a screening mammogram should receive one.”

The second commonly heard objection is that the task force is overestimating the harms of screening, such as anxiety and overdiagnosis, she said. But an outcome of “anxiety” was not factored into the guideline. Overdiagnosis was calculated on the basis of the literature, and estimates were converted to a common denominator so that they could be compared, said Dr. Nadler. The same was true of benefits.

Another objection was that screening could mean less need for chemotherapy or full axillary dissection, Dr. Nadler said. However, the task force did not find any primary studies that evaluated these outcomes.

Critics also said that the recommendations do not account for racial or ethnic variations. Although more research is likely needed in this area, “the task force states that individuals should be informed of all of their breast cancer risk factors, including race/ethnicity, and that this should be factored into decisions about screening,” said Dr. Nadler.

“I was very surprised that the task force was accused by some parties of paternalism,” added René Wittmer, MD, adjunct clinical professor of family medicine at the University of Montreal and chair of Choosing Wisely Quebec, Montreal, Canada. “In my opinion, the importance they place on shared decision-making is contrary to medical paternalism and aims to empower women to make a decision that fits with their values and preferences.”

Nevertheless, the inclusion of modeling studies and observational trials “may cause the potential benefits to be amplified, compared with what is seen in randomized controlled trials,” he said in an interview.
 

Decision Aids Help

Once the guidelines are finalized, decision aids will be available to patients and providers to help guide screening discussions, said Dr. Nadler. “Primary care providers need to be aware of an individual’s personal risk factors for breast cancer to know if they are at average, above average, or high lifetime risk of breast cancer. These guidelines do not apply to those with > 20% lifetime risk of breast cancer.”

“The standards for risk communication are in absolute numbers over a common denominator,” she noted. “This is how primary care providers discuss other important primary care topics like smoking cessation, cardiovascular disease (and decisions about statin medications), and osteoporosis risk. These same standards should apply for breast cancer screening.”

Furthermore, she said, providers “should be aware that individuals from marginalized communities may benefit from more than one conversation until they are able to make a decision about screening that is right for them.”

“There is good evidence showing that most advances we’ve seen in breast cancer outcomes (ie, reduction in breast cancer mortality) are likely due to improvements in treatment, not screening,” said Dr. Wittmer. “In fact, mortality reductions are seen even in age groups or countries where there is no routine screening. This means that women benefit from advances in treatments, whether they choose to get screened or not.”
 

‘Mammography Saves Lives’

Commenting on the updated guidelines, Janie Lee, MD, professor of radiology at the University of Washington School of Medicine and director of breast imaging at the Fred Hutchinson Cancer Center, both in Seattle, said: “For the USPSTF, benefits of life years gained were also considered, in addition to breast cancer deaths averted. To save more lives from breast cancer, guidelines may focus on screening women at older ages, when annual rates of breast cancer are higher.” By contrast, when thinking in terms of years of life saved, focusing on screening younger women, who have more years of life left, increases benefits. “Both are important outcomes that we want to improve with effective screening.”

That said, “we should follow the guidelines of our specific national organizations,” she continued. “Overall populations and healthcare systems are different between the US and Canada.”

For example, “the USPSTF specifically highlighted the potential for reducing breast cancer mortality in Black women, who are more likely to develop biologically aggressive tumors that are diagnosed at more advanced stages, when making updated recommendations earlier this year,” she said. “The Canadian guidelines did not make specific recommendations by race or ethnicity group, instead highlighting the need for more research on the impact of screening in these groups.”

In addition, “screening every year versus every other year is more routine in the US compared with Canada,” she noted. And nonmedical factors that influence health and that may influence access to medical care and timely diagnosis of breast cancer “may be different between our two countries.”

“The most important take-home message is that the scientific evidence is strong that screening mammography saves lives,” said Dr. Lee. “These new recommendations will hopefully result in more early diagnoses of breast cancer and save more lives. Screening works best when it’s used regularly, regardless of how frequently you return. Once you start screening, please urge your patients to plan to return.”

Dr. Nadler disclosed speaker honoraria and consulting fees from Novartis and Exact Sciences outside the scope of this interview and innovation funding from the NSH/UHN AMO Innovation Fund Competition for Developing and Implementing a Consensus Recommendation for Breast Cancer Screening Best Practices. Dr. Thériault is chair of the task force and chair of the working group for the draft guidelines. Dr. Wittmer is chair of Choosing Wisely Quebec. Dr. Lee reported no relevant financial relationships related to her interview.

A version of this article appeared on Medscape.com.

Moving for any new opportunity in medicine can feel like starting a new life, not just a new job. This is especially true for residency or fellowships, as taking a step forward in your career is exciting. But in the process, you may be leaving family and friends for an unknown city or region where you will need to find a community. And the changes could be long-term. According to the Association of American Medical Colleges’ 2023 Report on Residents, 57.1% of the individuals who completed residency training between 2013 and 2022 are still practicing in the state where they completed their residency.

The process of planning out the right timeline; securing a comfortable, convenient, and affordable place to live; and meeting people while working long hours in an unfamiliar location can be overwhelming. And in the case of many residency programs and healthcare settings, financial assistance, relocation information, and other resources are scarce.

This news organization spoke to recent residents and medical school faculty members about how to navigate a medical move and set yourself up for success.
 

1. Find Relocation Resources

First things first. Find out what your program or hospital has to offer.

Some institutions help incoming residents by providing housing options or information. The Icahn School of Medicine at Mount Sinai’s Real Estate Division, for example, provides off-campus housing resources that guide new residents and faculty toward safe, convenient places to live in New York City. It also guarantees on-campus or block-leased housing offers to all incoming residents who apply.

Michael Leitman, MD, FACS, professor of surgery and medical education and dean for Graduate Medical Education at the Icahn School of Medicine at Mount Sinai in New York City, recommends connecting with colleagues at your program for guidance on navigating a new city and a new healthcare setting. He encourages incoming residents to use the contact information they receive during the interview and orientation processes to reach out to co-residents and faculty members.

Other residency programs offer partial reimbursement or need-based financial aid to help with the expense of relocation. But this is unlikely to cover all or even most of the cost of a cross-country move.

When Morgen Owens, MD, moved from Alabama to New York City for a physical medicine and rehabilitation residency at Mount Sinai in 2021, her program offered subsidized housing options. But there was little reimbursement for relocation. She paid around $3000 for a one-way rental truck, gas, one night in a hotel, and movers to unload her belongings. She says driving herself kept the price down because full-service movers would have cost her between $4000 and $6000.

If this will strain your finances, several banks offer loans specifically for medical school graduates to cover residency and internship expenses. But be aware that these loans tend to have higher interest rates than federal student loans because they are based on credit score rather than fixed.
 

2. Reach Out and Buddy Up

Reaching out to more senior residents is essential, and some programs facilitate a buddy system for relocation advice.

Family physician Mursal Sekandari, MD, known as “Dr. Mursi,” attended a residency program at St. Luke’s University Hospital–Bethlehem Campus, in Bethlehem, Pennsylvania. The program’s official buddy system paired her with a senior resident who advised her on the area and gave tips for her apartment search.

On the other hand, when America Revere, MD, moved from Texas to Georgia for a surgery residency, she found that her program offered little relocation assistance, financial or otherwise. She leaned on her co-residents, and especially senior ones, for support while she settled in.

Dr. Revere also discovered the importance of accepting invitations to events hosted by both her fellow residents and her program itself, especially in the early stages of residency. “Accepting social invitations is really the only way to get to know people,” she said. “Sure, you’ll meet people at work and get to know their ‘work’ personalities.” But Dr. Revere’s attendings also threw parties, which she says were a great way to connect with a wider group and build a community.

To meet people both within and beyond her own residency program, Dr. Owens joined a group chat for physical medicine and rehab residents in the New York City area. She suggests looking into GroupMe or WhatsApp groups specific to your specialty.
 

3. Play the ‘Doctor Card’

Finding a place to live in an unfamiliar and competitive housing market can be one of the biggest challenges of any move. Dr. Owens’ options were limited by owning a dog, which wouldn’t be allowed in her hospital’s subsidized housing. Instead, she opted to find her own apartment in New York City. Her strategy: Playing the “doctor card.”

“I explained my situation: ‘I’m a doctor moving from out of state,’ ” Owens said. “Own that! These companies and brokers will look at you as a student and think, ‘Oh, she has no money, she has no savings, she’s got all of these loans, how is she going to pay for this apartment?’ But you have to say, ‘I’m a doctor. I’m an incoming resident who has X amount of years of job security. I’m not going to lose my job while living here.’ ”
 

4. Move Early

Dr. Revere found it important to move into her new home 2 weeks before the start of her residency program. Moving in early allowed her to settle in, get to know her area, neighbors, and co-residents, and generally prepare for her first day. It also gave her time to put furniture together — her new vanity alone took 12 hours.

Having a larger window of time before residency can also benefit those who hire movers or have their furniture shipped. When it comes to a cross-country move, it can take a few days to a few weeks for the truck to arrive — which could translate to a few nights or a few weeks without a bed.

“When residency comes, it comes fast,” Dr. Revere said. “It’s very confusing, and the last thing you need is to have half of your stuff unpacked or have no idea where you are or know nobody around you.”
 

5. Make Your New Home Your Sanctuary

During the stress of residency, your home can be a source of peace, and finding that might require trade-offs.

Dr. Sekandari’s parents urged her to live with roommates to save money on rent, but she insisted that spending more for solitude would be worth it. For her first year of residency, she barely saw her apartment. But when she did, she felt grateful to be in such a tranquil place to ease some of the stress of studying. “If you feel uncomfortable while you’re dealing with something stressful, the stress just exponentially increases,” she said. Creating an environment where you can really relax “makes a difference in how you respond to everything else around you.”

Dr. Revere agrees, urging medical professionals — and particularly residents — to invest in the most comfortable mattresses and bedding they can. Whether you are working nights, she also recommends blackout curtains to help facilitate daytime naps or better sleep in general, especially among the bright lights of bigger cities.

“You’re going to need somewhere to decompress,” she said. “That will look different for everyone. But I would definitely invest in your apartment to make it a sanctuary away from work.”
 

6. Consider a ‘Live’ Stress Reliever

When it comes to crucial stress relief during residency, “I like mine live,” Dr. Revere said in a YouTube vlog while petting her cat, Calyx.

Taking on the added responsibility of a pet during residency or any medical role may seem counterintuitive. But Revere has zero regrets about bringing Calyx along on her journey. “Cats are very easy,” she said. “I have nothing but wonderful things to say about having a cat during my difficult surgical residency.”

Dr. Owens admits that moving to New York City with her dog was difficult during her first years of residency. She worked an average of 80 hours each week and had little time for walks. She made room in her budget for dog walkers. Thankfully, her hours have eased up as she has progressed through her program, and she can now take her dog on longer walks every day. “He definitely has a better life now that I work fewer hours,” she said.

Once you’ve prepared, made the move, and found your village, it’s time for the real work to begin. “The first couple of months are certainly a challenge of adjusting to a new hospital, a new electronic medical record, a new culture, and a new geographic location,” said Dr. Leitman, who has relocated several times. “But at the end of the day ... it’s you and the patient.” By minimizing stress and getting the support you need, it can even be “a fun process,” Dr. Mursi added, “so make it an exciting chapter in your life.”

A version of this article first appeared on Medscape.com.

Moving for any new opportunity in medicine can feel like starting a new life, not just a new job. This is especially true for residency or fellowships, as taking a step forward in your career is exciting. But in the process, you may be leaving family and friends for an unknown city or region where you will need to find a community. And the changes could be long-term. According to the Association of American Medical Colleges’ 2023 Report on Residents, 57.1% of the individuals who completed residency training between 2013 and 2022 are still practicing in the state where they completed their residency.

The process of planning out the right timeline; securing a comfortable, convenient, and affordable place to live; and meeting people while working long hours in an unfamiliar location can be overwhelming. And in the case of many residency programs and healthcare settings, financial assistance, relocation information, and other resources are scarce.

This news organization spoke to recent residents and medical school faculty members about how to navigate a medical move and set yourself up for success.
 

1. Find Relocation Resources

First things first. Find out what your program or hospital has to offer.

Some institutions help incoming residents by providing housing options or information. The Icahn School of Medicine at Mount Sinai’s Real Estate Division, for example, provides off-campus housing resources that guide new residents and faculty toward safe, convenient places to live in New York City. It also guarantees on-campus or block-leased housing offers to all incoming residents who apply.

Michael Leitman, MD, FACS, professor of surgery and medical education and dean for Graduate Medical Education at the Icahn School of Medicine at Mount Sinai in New York City, recommends connecting with colleagues at your program for guidance on navigating a new city and a new healthcare setting. He encourages incoming residents to use the contact information they receive during the interview and orientation processes to reach out to co-residents and faculty members.

Other residency programs offer partial reimbursement or need-based financial aid to help with the expense of relocation. But this is unlikely to cover all or even most of the cost of a cross-country move.

When Morgen Owens, MD, moved from Alabama to New York City for a physical medicine and rehabilitation residency at Mount Sinai in 2021, her program offered subsidized housing options. But there was little reimbursement for relocation. She paid around $3000 for a one-way rental truck, gas, one night in a hotel, and movers to unload her belongings. She says driving herself kept the price down because full-service movers would have cost her between $4000 and $6000.

If this will strain your finances, several banks offer loans specifically for medical school graduates to cover residency and internship expenses. But be aware that these loans tend to have higher interest rates than federal student loans because they are based on credit score rather than fixed.
 

2. Reach Out and Buddy Up

Reaching out to more senior residents is essential, and some programs facilitate a buddy system for relocation advice.

Family physician Mursal Sekandari, MD, known as “Dr. Mursi,” attended a residency program at St. Luke’s University Hospital–Bethlehem Campus, in Bethlehem, Pennsylvania. The program’s official buddy system paired her with a senior resident who advised her on the area and gave tips for her apartment search.

On the other hand, when America Revere, MD, moved from Texas to Georgia for a surgery residency, she found that her program offered little relocation assistance, financial or otherwise. She leaned on her co-residents, and especially senior ones, for support while she settled in.

Dr. Revere also discovered the importance of accepting invitations to events hosted by both her fellow residents and her program itself, especially in the early stages of residency. “Accepting social invitations is really the only way to get to know people,” she said. “Sure, you’ll meet people at work and get to know their ‘work’ personalities.” But Dr. Revere’s attendings also threw parties, which she says were a great way to connect with a wider group and build a community.

To meet people both within and beyond her own residency program, Dr. Owens joined a group chat for physical medicine and rehab residents in the New York City area. She suggests looking into GroupMe or WhatsApp groups specific to your specialty.
 

3. Play the ‘Doctor Card’

Finding a place to live in an unfamiliar and competitive housing market can be one of the biggest challenges of any move. Dr. Owens’ options were limited by owning a dog, which wouldn’t be allowed in her hospital’s subsidized housing. Instead, she opted to find her own apartment in New York City. Her strategy: Playing the “doctor card.”

“I explained my situation: ‘I’m a doctor moving from out of state,’ ” Owens said. “Own that! These companies and brokers will look at you as a student and think, ‘Oh, she has no money, she has no savings, she’s got all of these loans, how is she going to pay for this apartment?’ But you have to say, ‘I’m a doctor. I’m an incoming resident who has X amount of years of job security. I’m not going to lose my job while living here.’ ”
 

4. Move Early

Dr. Revere found it important to move into her new home 2 weeks before the start of her residency program. Moving in early allowed her to settle in, get to know her area, neighbors, and co-residents, and generally prepare for her first day. It also gave her time to put furniture together — her new vanity alone took 12 hours.

Having a larger window of time before residency can also benefit those who hire movers or have their furniture shipped. When it comes to a cross-country move, it can take a few days to a few weeks for the truck to arrive — which could translate to a few nights or a few weeks without a bed.

“When residency comes, it comes fast,” Dr. Revere said. “It’s very confusing, and the last thing you need is to have half of your stuff unpacked or have no idea where you are or know nobody around you.”
 

5. Make Your New Home Your Sanctuary

During the stress of residency, your home can be a source of peace, and finding that might require trade-offs.

Dr. Sekandari’s parents urged her to live with roommates to save money on rent, but she insisted that spending more for solitude would be worth it. For her first year of residency, she barely saw her apartment. But when she did, she felt grateful to be in such a tranquil place to ease some of the stress of studying. “If you feel uncomfortable while you’re dealing with something stressful, the stress just exponentially increases,” she said. Creating an environment where you can really relax “makes a difference in how you respond to everything else around you.”

Dr. Revere agrees, urging medical professionals — and particularly residents — to invest in the most comfortable mattresses and bedding they can. Whether you are working nights, she also recommends blackout curtains to help facilitate daytime naps or better sleep in general, especially among the bright lights of bigger cities.

“You’re going to need somewhere to decompress,” she said. “That will look different for everyone. But I would definitely invest in your apartment to make it a sanctuary away from work.”
 

6. Consider a ‘Live’ Stress Reliever

When it comes to crucial stress relief during residency, “I like mine live,” Dr. Revere said in a YouTube vlog while petting her cat, Calyx.

Taking on the added responsibility of a pet during residency or any medical role may seem counterintuitive. But Revere has zero regrets about bringing Calyx along on her journey. “Cats are very easy,” she said. “I have nothing but wonderful things to say about having a cat during my difficult surgical residency.”

Dr. Owens admits that moving to New York City with her dog was difficult during her first years of residency. She worked an average of 80 hours each week and had little time for walks. She made room in her budget for dog walkers. Thankfully, her hours have eased up as she has progressed through her program, and she can now take her dog on longer walks every day. “He definitely has a better life now that I work fewer hours,” she said.

Once you’ve prepared, made the move, and found your village, it’s time for the real work to begin. “The first couple of months are certainly a challenge of adjusting to a new hospital, a new electronic medical record, a new culture, and a new geographic location,” said Dr. Leitman, who has relocated several times. “But at the end of the day ... it’s you and the patient.” By minimizing stress and getting the support you need, it can even be “a fun process,” Dr. Mursi added, “so make it an exciting chapter in your life.”

A version of this article first appeared on Medscape.com.

Moving for any new opportunity in medicine can feel like starting a new life, not just a new job. This is especially true for residency or fellowships, as taking a step forward in your career is exciting. But in the process, you may be leaving family and friends for an unknown city or region where you will need to find a community. And the changes could be long-term. According to the Association of American Medical Colleges’ 2023 Report on Residents, 57.1% of the individuals who completed residency training between 2013 and 2022 are still practicing in the state where they completed their residency.

The process of planning out the right timeline; securing a comfortable, convenient, and affordable place to live; and meeting people while working long hours in an unfamiliar location can be overwhelming. And in the case of many residency programs and healthcare settings, financial assistance, relocation information, and other resources are scarce.

This news organization spoke to recent residents and medical school faculty members about how to navigate a medical move and set yourself up for success.
 

1. Find Relocation Resources

First things first. Find out what your program or hospital has to offer.

Some institutions help incoming residents by providing housing options or information. The Icahn School of Medicine at Mount Sinai’s Real Estate Division, for example, provides off-campus housing resources that guide new residents and faculty toward safe, convenient places to live in New York City. It also guarantees on-campus or block-leased housing offers to all incoming residents who apply.

Michael Leitman, MD, FACS, professor of surgery and medical education and dean for Graduate Medical Education at the Icahn School of Medicine at Mount Sinai in New York City, recommends connecting with colleagues at your program for guidance on navigating a new city and a new healthcare setting. He encourages incoming residents to use the contact information they receive during the interview and orientation processes to reach out to co-residents and faculty members.

Other residency programs offer partial reimbursement or need-based financial aid to help with the expense of relocation. But this is unlikely to cover all or even most of the cost of a cross-country move.

When Morgen Owens, MD, moved from Alabama to New York City for a physical medicine and rehabilitation residency at Mount Sinai in 2021, her program offered subsidized housing options. But there was little reimbursement for relocation. She paid around $3000 for a one-way rental truck, gas, one night in a hotel, and movers to unload her belongings. She says driving herself kept the price down because full-service movers would have cost her between $4000 and $6000.

If this will strain your finances, several banks offer loans specifically for medical school graduates to cover residency and internship expenses. But be aware that these loans tend to have higher interest rates than federal student loans because they are based on credit score rather than fixed.
 

2. Reach Out and Buddy Up

Reaching out to more senior residents is essential, and some programs facilitate a buddy system for relocation advice.

Family physician Mursal Sekandari, MD, known as “Dr. Mursi,” attended a residency program at St. Luke’s University Hospital–Bethlehem Campus, in Bethlehem, Pennsylvania. The program’s official buddy system paired her with a senior resident who advised her on the area and gave tips for her apartment search.

On the other hand, when America Revere, MD, moved from Texas to Georgia for a surgery residency, she found that her program offered little relocation assistance, financial or otherwise. She leaned on her co-residents, and especially senior ones, for support while she settled in.

Dr. Revere also discovered the importance of accepting invitations to events hosted by both her fellow residents and her program itself, especially in the early stages of residency. “Accepting social invitations is really the only way to get to know people,” she said. “Sure, you’ll meet people at work and get to know their ‘work’ personalities.” But Dr. Revere’s attendings also threw parties, which she says were a great way to connect with a wider group and build a community.

To meet people both within and beyond her own residency program, Dr. Owens joined a group chat for physical medicine and rehab residents in the New York City area. She suggests looking into GroupMe or WhatsApp groups specific to your specialty.
 

3. Play the ‘Doctor Card’

Finding a place to live in an unfamiliar and competitive housing market can be one of the biggest challenges of any move. Dr. Owens’ options were limited by owning a dog, which wouldn’t be allowed in her hospital’s subsidized housing. Instead, she opted to find her own apartment in New York City. Her strategy: Playing the “doctor card.”

“I explained my situation: ‘I’m a doctor moving from out of state,’ ” Owens said. “Own that! These companies and brokers will look at you as a student and think, ‘Oh, she has no money, she has no savings, she’s got all of these loans, how is she going to pay for this apartment?’ But you have to say, ‘I’m a doctor. I’m an incoming resident who has X amount of years of job security. I’m not going to lose my job while living here.’ ”
 

4. Move Early

Dr. Revere found it important to move into her new home 2 weeks before the start of her residency program. Moving in early allowed her to settle in, get to know her area, neighbors, and co-residents, and generally prepare for her first day. It also gave her time to put furniture together — her new vanity alone took 12 hours.

Having a larger window of time before residency can also benefit those who hire movers or have their furniture shipped. When it comes to a cross-country move, it can take a few days to a few weeks for the truck to arrive — which could translate to a few nights or a few weeks without a bed.

“When residency comes, it comes fast,” Dr. Revere said. “It’s very confusing, and the last thing you need is to have half of your stuff unpacked or have no idea where you are or know nobody around you.”
 

5. Make Your New Home Your Sanctuary

During the stress of residency, your home can be a source of peace, and finding that might require trade-offs.

Dr. Sekandari’s parents urged her to live with roommates to save money on rent, but she insisted that spending more for solitude would be worth it. For her first year of residency, she barely saw her apartment. But when she did, she felt grateful to be in such a tranquil place to ease some of the stress of studying. “If you feel uncomfortable while you’re dealing with something stressful, the stress just exponentially increases,” she said. Creating an environment where you can really relax “makes a difference in how you respond to everything else around you.”

Dr. Revere agrees, urging medical professionals — and particularly residents — to invest in the most comfortable mattresses and bedding they can. Whether you are working nights, she also recommends blackout curtains to help facilitate daytime naps or better sleep in general, especially among the bright lights of bigger cities.

“You’re going to need somewhere to decompress,” she said. “That will look different for everyone. But I would definitely invest in your apartment to make it a sanctuary away from work.”
 

6. Consider a ‘Live’ Stress Reliever

When it comes to crucial stress relief during residency, “I like mine live,” Dr. Revere said in a YouTube vlog while petting her cat, Calyx.

Taking on the added responsibility of a pet during residency or any medical role may seem counterintuitive. But Revere has zero regrets about bringing Calyx along on her journey. “Cats are very easy,” she said. “I have nothing but wonderful things to say about having a cat during my difficult surgical residency.”

Dr. Owens admits that moving to New York City with her dog was difficult during her first years of residency. She worked an average of 80 hours each week and had little time for walks. She made room in her budget for dog walkers. Thankfully, her hours have eased up as she has progressed through her program, and she can now take her dog on longer walks every day. “He definitely has a better life now that I work fewer hours,” she said.

Once you’ve prepared, made the move, and found your village, it’s time for the real work to begin. “The first couple of months are certainly a challenge of adjusting to a new hospital, a new electronic medical record, a new culture, and a new geographic location,” said Dr. Leitman, who has relocated several times. “But at the end of the day ... it’s you and the patient.” By minimizing stress and getting the support you need, it can even be “a fun process,” Dr. Mursi added, “so make it an exciting chapter in your life.”

A version of this article first appeared on Medscape.com.

CHICAGO — The landscape of antibody-drug conjugates, or ADCs, continues to grow more crowded in metastatic breast cancer. Indications are expanding, new agents are emerging, combinations with other drug classes are being tested, and many patients with this disease are now receiving more than one ADC.

ADCs use antibodies to bind to the surface proteins of cancer cells to deliver a potent payload of cytotoxic chemotherapy. Three are approved for use in pretreated patients with metastatic breast cancer: sacituzumab govitecan, or SG, for patients with triple-negative disease; trastuzumab deruxtecan, or T-DXd, for patients with HER2-positive and HER2-low disease; and trastuzumab emtansine, or T-DM1, for patients with HER2-positive disease. A fourth agent, datopotamab deruxtecan, or Dato-DXd, is being assessed by the US Food and Drug Administration (FDA) for use in pretreated HR-positive, HER2-negative patients, and others, including sacituzumab tirumotecan, are being tested in clinical trials.At the annual meeting of the American Society of Clinical Oncology, T-DXd (Enhertu, AstraZeneca) showed better progression free survival than chemotherapy in people with HR-positive, HER 2-low metastatic breast cancers. These findings, from the DESTINY Breast-06 trial, were among the most talked-about at ASCO, and are likely to change clinical practice (J Clin Oncol. 2024;42[suppl 17; abstr LBA1000]).

But other ADC results presented at ASCO showed that there is still much to be worked out about the timing and sequencing of these agents, as well as their synergy with other drug classes, in metastatic breast cancer.
 

An ADC gets its first test, and falls short

Antonio Giordano, MD, PhD, of the Dana-Farber Cancer Institute in Boston, presented findings from an open-label phase 2 study of the ADC enfortumab vedotin (EV), an agent currently approved for use in advanced or metastatic urothelial cancer, at ASCO. This study included two cohorts of previously treated metastatic breast cancer patients: one with triple-negative disease (n = 42) and the other with HR-positive HER2-negative (n = 45).

Dr. Giordano and his colleagues’ study is the first to look at this ADC in breast cancer. EV’s antibody targets the cell adhesion molecule Nectin-4.

The researchers found that though EV demonstrated anti-tumor activity in both cohorts — with 19% of the triple-negative patients and 15.6% of the HR-positive/HER2-negative patients responding — the results did not meet the prespecified response thresholds for either cohort. (J Clin Oncol. 2024;42[suppl 16; abstr 1005]).

In an interview, Dr. Giordano said that studies in urothelial cancer had shown better response to EV associated with more expression of Nectin-4, but this study did not see such clear associations between expression and response. While there is no question that Nectin-4 is highly expressed in breast cancer and therefore a viable target, he said, “it may need to be looked at a little more deeply.”

It could also be the case, Dr. Giordano said, that the effect of EV’s payload may have been less robust in participants who had been previously treated with taxane chemotherapy, as nearly all patients in the two cohorts were.

“Taxanes are microtubule disruptors. And with this drug we had a payload with pretty much the same mechanism of action,” Dr. Giordano said. Ideally, he said, he would like to test the agent in a first-line setting, possibly in combination with an immunotherapy agent.

The timing of ADCs is as important as their targets and their payloads — and something that investigators are still struggling to figure out, he said.

A third of the patients in the triple-negative cohort of his study had been previously treated with SG, and a handful of individuals with T-Dxd, he noted.

“We’re in the middle of an ADC revolution,” he said. “It’s really key to figure out the best sequencing for a patient and if it’s actually worth it to do it. Very often we see patients respond best to the first ADC. But sometimes we see patients that do not respond to the first ADC and then they respond to the second one. It’s not very frequent, but it happens.”
 

Hint of Benefit from Adding Immunotherapy to SG

In a separate presentation at ASCO, Ana C. Garrido-Castro, MD, also of the Dana-Farber Cancer Institute, presented results from the SACI-IO HR+ trial, a randomized phase 2 study of SG (Trodelvy, Gilead) with and without pembrolizumab (Keytruda, Merck) in 104 patients with metastatic HR-positive/HER2-negative breast cancer who received prior endocrine therapy and up to one chemotherapy regimen for advanced disease. SACI-IO HR+ is the first randomized trial to report the efficacy of a topoisomerase I-inhibitor ADC with an immune checkpoint inhibitor for the treatment of breast cancer.

The addition of the immune checkpoint inhibitor did not result in a significant improvement in median progression-free survival in the overall population, Dr. Garrido-Castro reported. Median PFS was 8.1 vs 6.2 months with the combination of SG plus pembrolizumab or sacituzumab govitecan alone, respectively. At a median follow-up of 12.5 months, there was also no significant difference seen in median overall survival (OS): 18.5 vs 18.0 months.

About 40% of participants were found to have PD-L1-positive tumors and, among this subgroup, there was a 4.4-month increase in median PFS and 6.0-month increase in median OS with the addition of pembrolizumab to SG, although this did not reach statistical significance. (J Clin Oncol. 2024;42[suppl 17; abstr LBA1004]).

“While the study did not demonstrate a statistically significant benefit with the addition of the immune checkpoint inhibitor to the ADC, there is an interesting signal for potential synergistic activity between the two agents, particularly in those patients with PD-L1 positive tumors,” Dr. Garrido-Castro said in an interview. She noted that the sample sizes for the PD-L1 subgroup were relatively small, and overall survival data are not yet mature.

A separate phase 3 study is looking at the experimental ADC called sacituzumab tirumotecan with and without pembrolizumab compared with chemotherapy in patients with metastatic HR-positive, HER2-negative breast cancer who have received prior endocrine therapy and no prior chemotherapy for metastatic disease, she said.

Similar to SG, sacituzumab tirumotecan is a TROP2-directed ADC with a topoisomerase I-inhibitor payload. With an estimated enrollment of 1,200 patients, this trial may help shed light on whether adding the immune checkpoint inhibitor to the topoisomerase I-inhibitor TROP2-directed ADC improves outcomes in the subgroup of patients with PD-L1 positive tumors, Dr. Garrido-Castro said.
 

Unlocking the Order and Timing of ADCs

Dr. Garrido-Castro is also leading a study that will evaluate the sequential use of ADCs in metastatic breast cancer. That trial, to be called TRADE-DXd, will enroll patients with HER2-low metastatic breast cancer who have received up to one prior line of chemotherapy and no previous topoisomerase I-inhibitors. Participants will receive either T-DXd or Dato-DXd as the first ADC, and then switch to the other ADC (Dato-DXd or T-DXd, respectively) at the time of progression, thus switching the target of the ADC from HER2 to TROP2 or vice versa.

“In real-world practice now, there are patients who receive sequential ADCs, because they are candidates for both,” Dr. Garrido-Castro explained. However, more robust data are needed to refine the selection of the initial antibody drug conjugate and to determine who is more likely to benefit from a second — or maybe even third — ADC.

“One potential mechanism of resistance to antibody drug conjugates is the downregulation of the target of the antibody drug conjugate,” Dr. Garrido-Castro said. “Thus, an important question is, if you modify the target of the ADC, is it possible to overcome that mechanism of resistance?” Another possible mechanism of resistance is to the chemotherapy payload of the ADCs, she said.

Dr. Garrido-Castro’s study will collect tumor samples and blood samples for the purposes of planned correlative analyses to try to better understand the mechanisms that drive response and resistance to these agents.

Dr. Giordano commented that Dr. Garrido-Castro’s study was likely to result in a much better understanding of ADCs and how to use them strategically.

At Dana-Farber, “we collect a lot of samples of patients receiving ADCs. And we are trying to do all kinds of work on circulating tumor DNA, immunohistochemistry expression, and protein expression,” he said. “We are trying to figure out how ADCs really work, and why they stop working.”

Dr. Giordano and colleagues’ study was funded by Astellas Pharma and by Seagen, which was bought by Pfizer in 2023. Dr. Giordano disclosed receiving consulting fees from Pfizer, and several of his coauthors reported relationships with this and other companies. Two were Astellas employees.

Dr. Garrido-Castro and colleagues’ study was funded by Merck and Gilead Sciences. Dr. Garrido-Castro disclosed receiving research support from Gilead Sciences, AstraZeneca, Daiichi Sankyo, Merck, Zenith Epigenetics, Bristol-Myers Squibb, Novartis, Biovica, Foundation Medicine, 4D Path, Precede Biosciences; scientific advisory board/consulting fees from AstraZeneca, Novartis, Daiichi Sankyo; speaker honoraria from AstraZeneca, Daiichi Sankyo; and other support from Roche/Genentech, Gilead Sciences, AstraZeneca, Daiichi Sankyo, Novartis, and Merck, while her coauthors reported similar relationships.

CHICAGO — The landscape of antibody-drug conjugates, or ADCs, continues to grow more crowded in metastatic breast cancer. Indications are expanding, new agents are emerging, combinations with other drug classes are being tested, and many patients with this disease are now receiving more than one ADC.

ADCs use antibodies to bind to the surface proteins of cancer cells to deliver a potent payload of cytotoxic chemotherapy. Three are approved for use in pretreated patients with metastatic breast cancer: sacituzumab govitecan, or SG, for patients with triple-negative disease; trastuzumab deruxtecan, or T-DXd, for patients with HER2-positive and HER2-low disease; and trastuzumab emtansine, or T-DM1, for patients with HER2-positive disease. A fourth agent, datopotamab deruxtecan, or Dato-DXd, is being assessed by the US Food and Drug Administration (FDA) for use in pretreated HR-positive, HER2-negative patients, and others, including sacituzumab tirumotecan, are being tested in clinical trials.At the annual meeting of the American Society of Clinical Oncology, T-DXd (Enhertu, AstraZeneca) showed better progression free survival than chemotherapy in people with HR-positive, HER 2-low metastatic breast cancers. These findings, from the DESTINY Breast-06 trial, were among the most talked-about at ASCO, and are likely to change clinical practice (J Clin Oncol. 2024;42[suppl 17; abstr LBA1000]).

But other ADC results presented at ASCO showed that there is still much to be worked out about the timing and sequencing of these agents, as well as their synergy with other drug classes, in metastatic breast cancer.
 

An ADC gets its first test, and falls short

Antonio Giordano, MD, PhD, of the Dana-Farber Cancer Institute in Boston, presented findings from an open-label phase 2 study of the ADC enfortumab vedotin (EV), an agent currently approved for use in advanced or metastatic urothelial cancer, at ASCO. This study included two cohorts of previously treated metastatic breast cancer patients: one with triple-negative disease (n = 42) and the other with HR-positive HER2-negative (n = 45).

Dr. Giordano and his colleagues’ study is the first to look at this ADC in breast cancer. EV’s antibody targets the cell adhesion molecule Nectin-4.

The researchers found that though EV demonstrated anti-tumor activity in both cohorts — with 19% of the triple-negative patients and 15.6% of the HR-positive/HER2-negative patients responding — the results did not meet the prespecified response thresholds for either cohort. (J Clin Oncol. 2024;42[suppl 16; abstr 1005]).

In an interview, Dr. Giordano said that studies in urothelial cancer had shown better response to EV associated with more expression of Nectin-4, but this study did not see such clear associations between expression and response. While there is no question that Nectin-4 is highly expressed in breast cancer and therefore a viable target, he said, “it may need to be looked at a little more deeply.”

It could also be the case, Dr. Giordano said, that the effect of EV’s payload may have been less robust in participants who had been previously treated with taxane chemotherapy, as nearly all patients in the two cohorts were.

“Taxanes are microtubule disruptors. And with this drug we had a payload with pretty much the same mechanism of action,” Dr. Giordano said. Ideally, he said, he would like to test the agent in a first-line setting, possibly in combination with an immunotherapy agent.

The timing of ADCs is as important as their targets and their payloads — and something that investigators are still struggling to figure out, he said.

A third of the patients in the triple-negative cohort of his study had been previously treated with SG, and a handful of individuals with T-Dxd, he noted.

“We’re in the middle of an ADC revolution,” he said. “It’s really key to figure out the best sequencing for a patient and if it’s actually worth it to do it. Very often we see patients respond best to the first ADC. But sometimes we see patients that do not respond to the first ADC and then they respond to the second one. It’s not very frequent, but it happens.”
 

Hint of Benefit from Adding Immunotherapy to SG

In a separate presentation at ASCO, Ana C. Garrido-Castro, MD, also of the Dana-Farber Cancer Institute, presented results from the SACI-IO HR+ trial, a randomized phase 2 study of SG (Trodelvy, Gilead) with and without pembrolizumab (Keytruda, Merck) in 104 patients with metastatic HR-positive/HER2-negative breast cancer who received prior endocrine therapy and up to one chemotherapy regimen for advanced disease. SACI-IO HR+ is the first randomized trial to report the efficacy of a topoisomerase I-inhibitor ADC with an immune checkpoint inhibitor for the treatment of breast cancer.

The addition of the immune checkpoint inhibitor did not result in a significant improvement in median progression-free survival in the overall population, Dr. Garrido-Castro reported. Median PFS was 8.1 vs 6.2 months with the combination of SG plus pembrolizumab or sacituzumab govitecan alone, respectively. At a median follow-up of 12.5 months, there was also no significant difference seen in median overall survival (OS): 18.5 vs 18.0 months.

About 40% of participants were found to have PD-L1-positive tumors and, among this subgroup, there was a 4.4-month increase in median PFS and 6.0-month increase in median OS with the addition of pembrolizumab to SG, although this did not reach statistical significance. (J Clin Oncol. 2024;42[suppl 17; abstr LBA1004]).

“While the study did not demonstrate a statistically significant benefit with the addition of the immune checkpoint inhibitor to the ADC, there is an interesting signal for potential synergistic activity between the two agents, particularly in those patients with PD-L1 positive tumors,” Dr. Garrido-Castro said in an interview. She noted that the sample sizes for the PD-L1 subgroup were relatively small, and overall survival data are not yet mature.

A separate phase 3 study is looking at the experimental ADC called sacituzumab tirumotecan with and without pembrolizumab compared with chemotherapy in patients with metastatic HR-positive, HER2-negative breast cancer who have received prior endocrine therapy and no prior chemotherapy for metastatic disease, she said.

Similar to SG, sacituzumab tirumotecan is a TROP2-directed ADC with a topoisomerase I-inhibitor payload. With an estimated enrollment of 1,200 patients, this trial may help shed light on whether adding the immune checkpoint inhibitor to the topoisomerase I-inhibitor TROP2-directed ADC improves outcomes in the subgroup of patients with PD-L1 positive tumors, Dr. Garrido-Castro said.
 

Unlocking the Order and Timing of ADCs

Dr. Garrido-Castro is also leading a study that will evaluate the sequential use of ADCs in metastatic breast cancer. That trial, to be called TRADE-DXd, will enroll patients with HER2-low metastatic breast cancer who have received up to one prior line of chemotherapy and no previous topoisomerase I-inhibitors. Participants will receive either T-DXd or Dato-DXd as the first ADC, and then switch to the other ADC (Dato-DXd or T-DXd, respectively) at the time of progression, thus switching the target of the ADC from HER2 to TROP2 or vice versa.

“In real-world practice now, there are patients who receive sequential ADCs, because they are candidates for both,” Dr. Garrido-Castro explained. However, more robust data are needed to refine the selection of the initial antibody drug conjugate and to determine who is more likely to benefit from a second — or maybe even third — ADC.

“One potential mechanism of resistance to antibody drug conjugates is the downregulation of the target of the antibody drug conjugate,” Dr. Garrido-Castro said. “Thus, an important question is, if you modify the target of the ADC, is it possible to overcome that mechanism of resistance?” Another possible mechanism of resistance is to the chemotherapy payload of the ADCs, she said.

Dr. Garrido-Castro’s study will collect tumor samples and blood samples for the purposes of planned correlative analyses to try to better understand the mechanisms that drive response and resistance to these agents.

Dr. Giordano commented that Dr. Garrido-Castro’s study was likely to result in a much better understanding of ADCs and how to use them strategically.

At Dana-Farber, “we collect a lot of samples of patients receiving ADCs. And we are trying to do all kinds of work on circulating tumor DNA, immunohistochemistry expression, and protein expression,” he said. “We are trying to figure out how ADCs really work, and why they stop working.”

Dr. Giordano and colleagues’ study was funded by Astellas Pharma and by Seagen, which was bought by Pfizer in 2023. Dr. Giordano disclosed receiving consulting fees from Pfizer, and several of his coauthors reported relationships with this and other companies. Two were Astellas employees.

Dr. Garrido-Castro and colleagues’ study was funded by Merck and Gilead Sciences. Dr. Garrido-Castro disclosed receiving research support from Gilead Sciences, AstraZeneca, Daiichi Sankyo, Merck, Zenith Epigenetics, Bristol-Myers Squibb, Novartis, Biovica, Foundation Medicine, 4D Path, Precede Biosciences; scientific advisory board/consulting fees from AstraZeneca, Novartis, Daiichi Sankyo; speaker honoraria from AstraZeneca, Daiichi Sankyo; and other support from Roche/Genentech, Gilead Sciences, AstraZeneca, Daiichi Sankyo, Novartis, and Merck, while her coauthors reported similar relationships.

CHICAGO — The landscape of antibody-drug conjugates, or ADCs, continues to grow more crowded in metastatic breast cancer. Indications are expanding, new agents are emerging, combinations with other drug classes are being tested, and many patients with this disease are now receiving more than one ADC.

ADCs use antibodies to bind to the surface proteins of cancer cells to deliver a potent payload of cytotoxic chemotherapy. Three are approved for use in pretreated patients with metastatic breast cancer: sacituzumab govitecan, or SG, for patients with triple-negative disease; trastuzumab deruxtecan, or T-DXd, for patients with HER2-positive and HER2-low disease; and trastuzumab emtansine, or T-DM1, for patients with HER2-positive disease. A fourth agent, datopotamab deruxtecan, or Dato-DXd, is being assessed by the US Food and Drug Administration (FDA) for use in pretreated HR-positive, HER2-negative patients, and others, including sacituzumab tirumotecan, are being tested in clinical trials.At the annual meeting of the American Society of Clinical Oncology, T-DXd (Enhertu, AstraZeneca) showed better progression free survival than chemotherapy in people with HR-positive, HER 2-low metastatic breast cancers. These findings, from the DESTINY Breast-06 trial, were among the most talked-about at ASCO, and are likely to change clinical practice (J Clin Oncol. 2024;42[suppl 17; abstr LBA1000]).

But other ADC results presented at ASCO showed that there is still much to be worked out about the timing and sequencing of these agents, as well as their synergy with other drug classes, in metastatic breast cancer.
 

An ADC gets its first test, and falls short

Antonio Giordano, MD, PhD, of the Dana-Farber Cancer Institute in Boston, presented findings from an open-label phase 2 study of the ADC enfortumab vedotin (EV), an agent currently approved for use in advanced or metastatic urothelial cancer, at ASCO. This study included two cohorts of previously treated metastatic breast cancer patients: one with triple-negative disease (n = 42) and the other with HR-positive HER2-negative (n = 45).

Dr. Giordano and his colleagues’ study is the first to look at this ADC in breast cancer. EV’s antibody targets the cell adhesion molecule Nectin-4.

The researchers found that though EV demonstrated anti-tumor activity in both cohorts — with 19% of the triple-negative patients and 15.6% of the HR-positive/HER2-negative patients responding — the results did not meet the prespecified response thresholds for either cohort. (J Clin Oncol. 2024;42[suppl 16; abstr 1005]).

In an interview, Dr. Giordano said that studies in urothelial cancer had shown better response to EV associated with more expression of Nectin-4, but this study did not see such clear associations between expression and response. While there is no question that Nectin-4 is highly expressed in breast cancer and therefore a viable target, he said, “it may need to be looked at a little more deeply.”

It could also be the case, Dr. Giordano said, that the effect of EV’s payload may have been less robust in participants who had been previously treated with taxane chemotherapy, as nearly all patients in the two cohorts were.

“Taxanes are microtubule disruptors. And with this drug we had a payload with pretty much the same mechanism of action,” Dr. Giordano said. Ideally, he said, he would like to test the agent in a first-line setting, possibly in combination with an immunotherapy agent.

The timing of ADCs is as important as their targets and their payloads — and something that investigators are still struggling to figure out, he said.

A third of the patients in the triple-negative cohort of his study had been previously treated with SG, and a handful of individuals with T-Dxd, he noted.

“We’re in the middle of an ADC revolution,” he said. “It’s really key to figure out the best sequencing for a patient and if it’s actually worth it to do it. Very often we see patients respond best to the first ADC. But sometimes we see patients that do not respond to the first ADC and then they respond to the second one. It’s not very frequent, but it happens.”
 

Hint of Benefit from Adding Immunotherapy to SG

In a separate presentation at ASCO, Ana C. Garrido-Castro, MD, also of the Dana-Farber Cancer Institute, presented results from the SACI-IO HR+ trial, a randomized phase 2 study of SG (Trodelvy, Gilead) with and without pembrolizumab (Keytruda, Merck) in 104 patients with metastatic HR-positive/HER2-negative breast cancer who received prior endocrine therapy and up to one chemotherapy regimen for advanced disease. SACI-IO HR+ is the first randomized trial to report the efficacy of a topoisomerase I-inhibitor ADC with an immune checkpoint inhibitor for the treatment of breast cancer.

The addition of the immune checkpoint inhibitor did not result in a significant improvement in median progression-free survival in the overall population, Dr. Garrido-Castro reported. Median PFS was 8.1 vs 6.2 months with the combination of SG plus pembrolizumab or sacituzumab govitecan alone, respectively. At a median follow-up of 12.5 months, there was also no significant difference seen in median overall survival (OS): 18.5 vs 18.0 months.

About 40% of participants were found to have PD-L1-positive tumors and, among this subgroup, there was a 4.4-month increase in median PFS and 6.0-month increase in median OS with the addition of pembrolizumab to SG, although this did not reach statistical significance. (J Clin Oncol. 2024;42[suppl 17; abstr LBA1004]).

“While the study did not demonstrate a statistically significant benefit with the addition of the immune checkpoint inhibitor to the ADC, there is an interesting signal for potential synergistic activity between the two agents, particularly in those patients with PD-L1 positive tumors,” Dr. Garrido-Castro said in an interview. She noted that the sample sizes for the PD-L1 subgroup were relatively small, and overall survival data are not yet mature.

A separate phase 3 study is looking at the experimental ADC called sacituzumab tirumotecan with and without pembrolizumab compared with chemotherapy in patients with metastatic HR-positive, HER2-negative breast cancer who have received prior endocrine therapy and no prior chemotherapy for metastatic disease, she said.

Similar to SG, sacituzumab tirumotecan is a TROP2-directed ADC with a topoisomerase I-inhibitor payload. With an estimated enrollment of 1,200 patients, this trial may help shed light on whether adding the immune checkpoint inhibitor to the topoisomerase I-inhibitor TROP2-directed ADC improves outcomes in the subgroup of patients with PD-L1 positive tumors, Dr. Garrido-Castro said.
 

Unlocking the Order and Timing of ADCs

Dr. Garrido-Castro is also leading a study that will evaluate the sequential use of ADCs in metastatic breast cancer. That trial, to be called TRADE-DXd, will enroll patients with HER2-low metastatic breast cancer who have received up to one prior line of chemotherapy and no previous topoisomerase I-inhibitors. Participants will receive either T-DXd or Dato-DXd as the first ADC, and then switch to the other ADC (Dato-DXd or T-DXd, respectively) at the time of progression, thus switching the target of the ADC from HER2 to TROP2 or vice versa.

“In real-world practice now, there are patients who receive sequential ADCs, because they are candidates for both,” Dr. Garrido-Castro explained. However, more robust data are needed to refine the selection of the initial antibody drug conjugate and to determine who is more likely to benefit from a second — or maybe even third — ADC.

“One potential mechanism of resistance to antibody drug conjugates is the downregulation of the target of the antibody drug conjugate,” Dr. Garrido-Castro said. “Thus, an important question is, if you modify the target of the ADC, is it possible to overcome that mechanism of resistance?” Another possible mechanism of resistance is to the chemotherapy payload of the ADCs, she said.

Dr. Garrido-Castro’s study will collect tumor samples and blood samples for the purposes of planned correlative analyses to try to better understand the mechanisms that drive response and resistance to these agents.

Dr. Giordano commented that Dr. Garrido-Castro’s study was likely to result in a much better understanding of ADCs and how to use them strategically.

At Dana-Farber, “we collect a lot of samples of patients receiving ADCs. And we are trying to do all kinds of work on circulating tumor DNA, immunohistochemistry expression, and protein expression,” he said. “We are trying to figure out how ADCs really work, and why they stop working.”

Dr. Giordano and colleagues’ study was funded by Astellas Pharma and by Seagen, which was bought by Pfizer in 2023. Dr. Giordano disclosed receiving consulting fees from Pfizer, and several of his coauthors reported relationships with this and other companies. Two were Astellas employees.

Dr. Garrido-Castro and colleagues’ study was funded by Merck and Gilead Sciences. Dr. Garrido-Castro disclosed receiving research support from Gilead Sciences, AstraZeneca, Daiichi Sankyo, Merck, Zenith Epigenetics, Bristol-Myers Squibb, Novartis, Biovica, Foundation Medicine, 4D Path, Precede Biosciences; scientific advisory board/consulting fees from AstraZeneca, Novartis, Daiichi Sankyo; speaker honoraria from AstraZeneca, Daiichi Sankyo; and other support from Roche/Genentech, Gilead Sciences, AstraZeneca, Daiichi Sankyo, Novartis, and Merck, while her coauthors reported similar relationships.

Nonphysician operators (NPOs) using laser and energy-based devices are accounting for an increasing share of malpractice lawsuits in dermatology, and when they use these devices in a dermatologic practice or a dermatologist-owned medical spa, the dermatologist can be on the hook for liability. Dermatologists can protect themselves by understanding malpractice trends and taking preventive steps, such as making sure NPOs have appropriate training and using a rigorous informed consent process, according to a dermatology resident and a dermatologist who have researched recent trends in dermatology lawsuits.

“It’s really important that physicians recognize their responsibility when delegating procedures to nonphysician operators and the physician’s role in supervision of these procedures,” Scott Stratman, MD, MPH, a dermatology resident at the Icahn School of Medicine at Mount Sinai, New York City, told this news organization. He led a  study recently published in the Journal of the American Academy of Dermatology, which found that the majority (52%) of malpractice cases for cutaneous energy-based device procedures in the LexisNexis database from 1985 to September 2023 involved NPOs. The study did not break the data down between different types of NPOs.

Dr. Stratman

Trends in Dermatology Malpractice

This follows a similar trend reported in a 2014 study led by Mathew M. Avram, MD, JD, director of the MGH Dermatology Laser and Cosmetic Center at Massachusetts General Hospital, Boston. The study analyzed liability claims related to cutaneous laser surgery performed by nonphysicians from January 1999 to December 2012.

“With nonphysician litigation data, we saw trend lines beginning in 2008 where the proportion of cases began to increase,” Dr. Avram said at the American Society for Laser Medicine and Surgery (ASLMS) meeting on April 12, 2024. “Over a period of 2008-2012, it went from 36% of cases to about 78%,” he said.

About a quarter (23.4%) of those were in medical offices; 76.6% were in nontraditional settings such as medical spas, he added. The proportion of NPOs was similar in a 2022 study that looked at causes of litigation in cutaneous laser surgery from 2012 to 2020, Dr. Avram said. Again, neither study broke down cases involving NPOs by specific type, but the 2014 study reported that 64% of cases by NPOs occurred outside of a traditional medical setting.

“So it seems that the location and potentially the supervision are issues that are important to patient safety,” Dr. Avram said at the meeting. While state laws regarding laser delegation vary widely, “depending on where you practice, it’s incumbent upon you to know that.”

Dr. Avram and colleagues were also the authors of a study published in June in Dermatologic Surgery that looked at the reasons behind ligations involving dermatologists in a retrospective analysis of 48 state and federal cases between 2011 and 2022. The majority of cases — 54.2% — were for unexpected harm, followed by wrong or delayed diagnoses, which accounted for a third of litigations.

Dr. Stratman’s study found that laser hair removal was the most common procedure for malpractice claims in dermatology among cutaneous energy-based device procedures. Complications from energy-based devices included burns, scarring, and pigmentation changes.

The growth of malpractice suits involving NPOs could be because NPOs are performing a greater proportion of dermatologic procedures, “particularly those practicing without direct supervision, such as in the context of a medical spa,” Dr. Stratman said in the interview. “Again, this highlights a physician’s responsibility in delegating these kinds of procedures to NPOs.”
 

Training Is a Must — But Not Standardized

Comprehensive training for physicians, staff, NPOs, and physicians “is all necessary and paramount in order to diminish adverse outcomes and legal risk, and then, of course, all these practitioners, be it staff or [NPOs], and, of course, physicians, are all held to the same standard of care,” Dr. Stratman said.

However, he added, “There is really no standardized training to operate these devices. That being said, it’s really important to know that both providers and facility owners have a significant obligation to their patients to make sure that their staff in their centers are appropriately trained.”

Training not only involves protocols and procedures but also how to handle patient interactions, Dr. Stratman said.

The legal concept of respondeat superior applies when nonphysicians participate in a patient’s care, Dr. Avram said at the ASLMS meeting. The physician is held liable for a nonphysician’s “negligence provided he or she is an employee receiving a salary [and] benefits and is performing within the scope of his or her duty,” regardless of whether the physician saw the patient or not at that visit, he said. Again, supervision of nonphysician laser procedures varies from state to state, he added.

“So the take-home point is to provide excellent training and appropriate supervision, and if you’re the owner of that practice, you are liable in the event of negligence even though you never were part of the treatment,” Dr. Avram said.

Ins and Outs of Informed Consent

When a patient outcome is less than desirable, or at least less than what the patient expected, a transparent and thorough informed consent process can protect the practice and physician, Dr. Avram said at the meeting.

“Malpractice and consent have nothing to do with each other,” he said. “Consent is getting permission to do a procedure. It’s needed actually for any medical intervention that you perform. What you need to do is to provide information to enable the patient or guardian or to choose knowledgeably among reasonable medical alternatives. This places the patient in control of the course of their medical treatment.”

The information conveyed to the patient should include the diagnosis, the medical causes, the nature and purpose of the treatment, and the risks and alternatives of procedure, “particularly if they’re high risk,” Dr. Avram said.

“Failure to obtain informed consent constitutes a civil battery, and the physician is liable for civil damages,” he said. “The patient need only show that he or she was not informed of the medical nature of the medical touching; physical injury is not necessary.”

A battery could occur if a procedure extends beyond the scope or area of treatment the patient agreed to — for example, extending a liposuction to an area that wasn’t originally targeted, or extending a laser procedure to an area of the body as a presumed favor to the patient. “It does not require a standard of care or an expert witness,” Dr. Avram said. “One only needs to show nonconsensual touching.”

Informed consents should include plain language, he said. “The whole idea is the patient understands what the risks and benefits are,” Dr. Avram said. “You don’t need to use medical jargon.” As an example, he suggested using the term “blisters” instead of “bullae.” If the treatment involves an off-label procedure, include that too, he said.

He also advised avoiding blanket authorizations. “Courts disfavor them,” he noted. “They need more specificity. So those are not valid.”

Dr. Stratman added that providers should think about the setting in which they obtain informed consent. “It’s really important that providers are consenting their patients in private and quiet places, free from distractions, that they accommodate patients who might have disabilities or limitations in English proficiency, using a teach-back method to help patients understand or demonstrate their understanding of the procedure in order to gauge comprehension,” he said.

Both Dr. Avram and Dr. Stratman pointed out that another strategy to prevent malpractice is to build trusting patient-provider relationships. “The patient-provider relationship is paramount not only to the success of the procedure but to the clinical visit as a whole,” Dr. Stratman said.

That’s a two-way street, he added. Patients should be able to trust that their provider provides them with the best treatment based on their own history, and providers should also be able to trust that patients are providing them with an accurate history, asking relevant questions, or expressing any level of apprehension about the procedure or visit. “The patient-provider relationship is everything,” Dr. Stratman said.

Dr. Stratman and Dr. Avram had no relevant disclosures.
 

A version of this article appeared on Medscape.com.

Nonphysician operators (NPOs) using laser and energy-based devices are accounting for an increasing share of malpractice lawsuits in dermatology, and when they use these devices in a dermatologic practice or a dermatologist-owned medical spa, the dermatologist can be on the hook for liability. Dermatologists can protect themselves by understanding malpractice trends and taking preventive steps, such as making sure NPOs have appropriate training and using a rigorous informed consent process, according to a dermatology resident and a dermatologist who have researched recent trends in dermatology lawsuits.

“It’s really important that physicians recognize their responsibility when delegating procedures to nonphysician operators and the physician’s role in supervision of these procedures,” Scott Stratman, MD, MPH, a dermatology resident at the Icahn School of Medicine at Mount Sinai, New York City, told this news organization. He led a  study recently published in the Journal of the American Academy of Dermatology, which found that the majority (52%) of malpractice cases for cutaneous energy-based device procedures in the LexisNexis database from 1985 to September 2023 involved NPOs. The study did not break the data down between different types of NPOs.

Dr. Stratman

Trends in Dermatology Malpractice

This follows a similar trend reported in a 2014 study led by Mathew M. Avram, MD, JD, director of the MGH Dermatology Laser and Cosmetic Center at Massachusetts General Hospital, Boston. The study analyzed liability claims related to cutaneous laser surgery performed by nonphysicians from January 1999 to December 2012.

“With nonphysician litigation data, we saw trend lines beginning in 2008 where the proportion of cases began to increase,” Dr. Avram said at the American Society for Laser Medicine and Surgery (ASLMS) meeting on April 12, 2024. “Over a period of 2008-2012, it went from 36% of cases to about 78%,” he said.

About a quarter (23.4%) of those were in medical offices; 76.6% were in nontraditional settings such as medical spas, he added. The proportion of NPOs was similar in a 2022 study that looked at causes of litigation in cutaneous laser surgery from 2012 to 2020, Dr. Avram said. Again, neither study broke down cases involving NPOs by specific type, but the 2014 study reported that 64% of cases by NPOs occurred outside of a traditional medical setting.

“So it seems that the location and potentially the supervision are issues that are important to patient safety,” Dr. Avram said at the meeting. While state laws regarding laser delegation vary widely, “depending on where you practice, it’s incumbent upon you to know that.”

Dr. Avram and colleagues were also the authors of a study published in June in Dermatologic Surgery that looked at the reasons behind ligations involving dermatologists in a retrospective analysis of 48 state and federal cases between 2011 and 2022. The majority of cases — 54.2% — were for unexpected harm, followed by wrong or delayed diagnoses, which accounted for a third of litigations.

Dr. Stratman’s study found that laser hair removal was the most common procedure for malpractice claims in dermatology among cutaneous energy-based device procedures. Complications from energy-based devices included burns, scarring, and pigmentation changes.

The growth of malpractice suits involving NPOs could be because NPOs are performing a greater proportion of dermatologic procedures, “particularly those practicing without direct supervision, such as in the context of a medical spa,” Dr. Stratman said in the interview. “Again, this highlights a physician’s responsibility in delegating these kinds of procedures to NPOs.”
 

Training Is a Must — But Not Standardized

Comprehensive training for physicians, staff, NPOs, and physicians “is all necessary and paramount in order to diminish adverse outcomes and legal risk, and then, of course, all these practitioners, be it staff or [NPOs], and, of course, physicians, are all held to the same standard of care,” Dr. Stratman said.

However, he added, “There is really no standardized training to operate these devices. That being said, it’s really important to know that both providers and facility owners have a significant obligation to their patients to make sure that their staff in their centers are appropriately trained.”

Training not only involves protocols and procedures but also how to handle patient interactions, Dr. Stratman said.

The legal concept of respondeat superior applies when nonphysicians participate in a patient’s care, Dr. Avram said at the ASLMS meeting. The physician is held liable for a nonphysician’s “negligence provided he or she is an employee receiving a salary [and] benefits and is performing within the scope of his or her duty,” regardless of whether the physician saw the patient or not at that visit, he said. Again, supervision of nonphysician laser procedures varies from state to state, he added.

“So the take-home point is to provide excellent training and appropriate supervision, and if you’re the owner of that practice, you are liable in the event of negligence even though you never were part of the treatment,” Dr. Avram said.

Ins and Outs of Informed Consent

When a patient outcome is less than desirable, or at least less than what the patient expected, a transparent and thorough informed consent process can protect the practice and physician, Dr. Avram said at the meeting.

“Malpractice and consent have nothing to do with each other,” he said. “Consent is getting permission to do a procedure. It’s needed actually for any medical intervention that you perform. What you need to do is to provide information to enable the patient or guardian or to choose knowledgeably among reasonable medical alternatives. This places the patient in control of the course of their medical treatment.”

The information conveyed to the patient should include the diagnosis, the medical causes, the nature and purpose of the treatment, and the risks and alternatives of procedure, “particularly if they’re high risk,” Dr. Avram said.

“Failure to obtain informed consent constitutes a civil battery, and the physician is liable for civil damages,” he said. “The patient need only show that he or she was not informed of the medical nature of the medical touching; physical injury is not necessary.”

A battery could occur if a procedure extends beyond the scope or area of treatment the patient agreed to — for example, extending a liposuction to an area that wasn’t originally targeted, or extending a laser procedure to an area of the body as a presumed favor to the patient. “It does not require a standard of care or an expert witness,” Dr. Avram said. “One only needs to show nonconsensual touching.”

Informed consents should include plain language, he said. “The whole idea is the patient understands what the risks and benefits are,” Dr. Avram said. “You don’t need to use medical jargon.” As an example, he suggested using the term “blisters” instead of “bullae.” If the treatment involves an off-label procedure, include that too, he said.

He also advised avoiding blanket authorizations. “Courts disfavor them,” he noted. “They need more specificity. So those are not valid.”

Dr. Stratman added that providers should think about the setting in which they obtain informed consent. “It’s really important that providers are consenting their patients in private and quiet places, free from distractions, that they accommodate patients who might have disabilities or limitations in English proficiency, using a teach-back method to help patients understand or demonstrate their understanding of the procedure in order to gauge comprehension,” he said.

Both Dr. Avram and Dr. Stratman pointed out that another strategy to prevent malpractice is to build trusting patient-provider relationships. “The patient-provider relationship is paramount not only to the success of the procedure but to the clinical visit as a whole,” Dr. Stratman said.

That’s a two-way street, he added. Patients should be able to trust that their provider provides them with the best treatment based on their own history, and providers should also be able to trust that patients are providing them with an accurate history, asking relevant questions, or expressing any level of apprehension about the procedure or visit. “The patient-provider relationship is everything,” Dr. Stratman said.

Dr. Stratman and Dr. Avram had no relevant disclosures.
 

A version of this article appeared on Medscape.com.

Nonphysician operators (NPOs) using laser and energy-based devices are accounting for an increasing share of malpractice lawsuits in dermatology, and when they use these devices in a dermatologic practice or a dermatologist-owned medical spa, the dermatologist can be on the hook for liability. Dermatologists can protect themselves by understanding malpractice trends and taking preventive steps, such as making sure NPOs have appropriate training and using a rigorous informed consent process, according to a dermatology resident and a dermatologist who have researched recent trends in dermatology lawsuits.

“It’s really important that physicians recognize their responsibility when delegating procedures to nonphysician operators and the physician’s role in supervision of these procedures,” Scott Stratman, MD, MPH, a dermatology resident at the Icahn School of Medicine at Mount Sinai, New York City, told this news organization. He led a  study recently published in the Journal of the American Academy of Dermatology, which found that the majority (52%) of malpractice cases for cutaneous energy-based device procedures in the LexisNexis database from 1985 to September 2023 involved NPOs. The study did not break the data down between different types of NPOs.

Dr. Stratman

Trends in Dermatology Malpractice

This follows a similar trend reported in a 2014 study led by Mathew M. Avram, MD, JD, director of the MGH Dermatology Laser and Cosmetic Center at Massachusetts General Hospital, Boston. The study analyzed liability claims related to cutaneous laser surgery performed by nonphysicians from January 1999 to December 2012.

“With nonphysician litigation data, we saw trend lines beginning in 2008 where the proportion of cases began to increase,” Dr. Avram said at the American Society for Laser Medicine and Surgery (ASLMS) meeting on April 12, 2024. “Over a period of 2008-2012, it went from 36% of cases to about 78%,” he said.

About a quarter (23.4%) of those were in medical offices; 76.6% were in nontraditional settings such as medical spas, he added. The proportion of NPOs was similar in a 2022 study that looked at causes of litigation in cutaneous laser surgery from 2012 to 2020, Dr. Avram said. Again, neither study broke down cases involving NPOs by specific type, but the 2014 study reported that 64% of cases by NPOs occurred outside of a traditional medical setting.

“So it seems that the location and potentially the supervision are issues that are important to patient safety,” Dr. Avram said at the meeting. While state laws regarding laser delegation vary widely, “depending on where you practice, it’s incumbent upon you to know that.”

Dr. Avram and colleagues were also the authors of a study published in June in Dermatologic Surgery that looked at the reasons behind ligations involving dermatologists in a retrospective analysis of 48 state and federal cases between 2011 and 2022. The majority of cases — 54.2% — were for unexpected harm, followed by wrong or delayed diagnoses, which accounted for a third of litigations.

Dr. Stratman’s study found that laser hair removal was the most common procedure for malpractice claims in dermatology among cutaneous energy-based device procedures. Complications from energy-based devices included burns, scarring, and pigmentation changes.

The growth of malpractice suits involving NPOs could be because NPOs are performing a greater proportion of dermatologic procedures, “particularly those practicing without direct supervision, such as in the context of a medical spa,” Dr. Stratman said in the interview. “Again, this highlights a physician’s responsibility in delegating these kinds of procedures to NPOs.”
 

Training Is a Must — But Not Standardized

Comprehensive training for physicians, staff, NPOs, and physicians “is all necessary and paramount in order to diminish adverse outcomes and legal risk, and then, of course, all these practitioners, be it staff or [NPOs], and, of course, physicians, are all held to the same standard of care,” Dr. Stratman said.

However, he added, “There is really no standardized training to operate these devices. That being said, it’s really important to know that both providers and facility owners have a significant obligation to their patients to make sure that their staff in their centers are appropriately trained.”

Training not only involves protocols and procedures but also how to handle patient interactions, Dr. Stratman said.

The legal concept of respondeat superior applies when nonphysicians participate in a patient’s care, Dr. Avram said at the ASLMS meeting. The physician is held liable for a nonphysician’s “negligence provided he or she is an employee receiving a salary [and] benefits and is performing within the scope of his or her duty,” regardless of whether the physician saw the patient or not at that visit, he said. Again, supervision of nonphysician laser procedures varies from state to state, he added.

“So the take-home point is to provide excellent training and appropriate supervision, and if you’re the owner of that practice, you are liable in the event of negligence even though you never were part of the treatment,” Dr. Avram said.

Ins and Outs of Informed Consent

When a patient outcome is less than desirable, or at least less than what the patient expected, a transparent and thorough informed consent process can protect the practice and physician, Dr. Avram said at the meeting.

“Malpractice and consent have nothing to do with each other,” he said. “Consent is getting permission to do a procedure. It’s needed actually for any medical intervention that you perform. What you need to do is to provide information to enable the patient or guardian or to choose knowledgeably among reasonable medical alternatives. This places the patient in control of the course of their medical treatment.”

The information conveyed to the patient should include the diagnosis, the medical causes, the nature and purpose of the treatment, and the risks and alternatives of procedure, “particularly if they’re high risk,” Dr. Avram said.

“Failure to obtain informed consent constitutes a civil battery, and the physician is liable for civil damages,” he said. “The patient need only show that he or she was not informed of the medical nature of the medical touching; physical injury is not necessary.”

A battery could occur if a procedure extends beyond the scope or area of treatment the patient agreed to — for example, extending a liposuction to an area that wasn’t originally targeted, or extending a laser procedure to an area of the body as a presumed favor to the patient. “It does not require a standard of care or an expert witness,” Dr. Avram said. “One only needs to show nonconsensual touching.”

Informed consents should include plain language, he said. “The whole idea is the patient understands what the risks and benefits are,” Dr. Avram said. “You don’t need to use medical jargon.” As an example, he suggested using the term “blisters” instead of “bullae.” If the treatment involves an off-label procedure, include that too, he said.

He also advised avoiding blanket authorizations. “Courts disfavor them,” he noted. “They need more specificity. So those are not valid.”

Dr. Stratman added that providers should think about the setting in which they obtain informed consent. “It’s really important that providers are consenting their patients in private and quiet places, free from distractions, that they accommodate patients who might have disabilities or limitations in English proficiency, using a teach-back method to help patients understand or demonstrate their understanding of the procedure in order to gauge comprehension,” he said.

Both Dr. Avram and Dr. Stratman pointed out that another strategy to prevent malpractice is to build trusting patient-provider relationships. “The patient-provider relationship is paramount not only to the success of the procedure but to the clinical visit as a whole,” Dr. Stratman said.

That’s a two-way street, he added. Patients should be able to trust that their provider provides them with the best treatment based on their own history, and providers should also be able to trust that patients are providing them with an accurate history, asking relevant questions, or expressing any level of apprehension about the procedure or visit. “The patient-provider relationship is everything,” Dr. Stratman said.

Dr. Stratman and Dr. Avram had no relevant disclosures.
 

A version of this article appeared on Medscape.com.

Should 5 mg of tamoxifen — known as “baby TAM” — or the usual 20 mg dose be standard of care for breast cancer prevention in high-risk women?

Research to date clearly shows that tamoxifen can reduce the risk for breast cancer in high-risk individuals by 30%-50%. Recent evidence also indicates that this chemoprevention approach can reduce the risk of dying from breast cancer by as much as 57%.

In 2019, the US Preventive Services Task Force issued updated recommendations that clinicians offer risk-reducing medications, such as tamoxifen, raloxifene, or aromatase inhibitors, to women at an increased risk for breast cancer and a low risk for adverse medication effects.

However, this prophylactic strategy remains underused.

A major roadblock: The drugs’ side effects, which include venous thromboembolic events and endometrial cancer as well as symptoms of menopause, such as hot flashes and sexual issues, have made uptake and adherence a challenge.

Offering women a lower dose of tamoxifen could allay fears about toxicities and improve uptake as well as reduce side effects and boost long-term adherence among those receiving baby TAM.

However, experts remain uncertain about whether patients need the standard dose to experience the full prevention benefit.
 

The Debate

Years ago, Andrea De Censi, MD, a breast cancer researcher at the Galliera Hospital in Genova, Italy, and his colleagues reasoned that, because tamoxifen is a competitive estrogen receptor inhibitor, it may indeed have a minimal effective dose below 20 mg/d.

The fruits of that line of thought were presented to the world in the TAM-01 trial, first published in 2019, which pitted tamoxifen 5 mg/d for 3 years against placebo in 500 women with high-risk lesions, including lobular and ductal carcinoma in situ.

Dr. De Censi and colleagues found that baby TAM reduced the risk for invasive breast cancer by 52% and the risk for contralateral breast cancer by 75%.

Treatment adherence was slightly higher in the baby TAM group at 65% vs 61% in the placebo group.

A recent 10-year follow-up showed ongoing benefits associated with baby TAM vs placebo — a 42% reduction in breast cancer and a 64% drop in contralateral lesions.

The baby TAM group vs placebo experienced a slight increase in hot flashes but no significant increase in other common side effects.

Regarding serious adverse events, the baby TAM arm had one case of stage 1 endometrial cancer (0.4% of patients) and 20 cases of endometrial polyps (5%) vs 13 cases of endometrial polyps in the placebo arm. But there were no significant differences in thrombosis, cataracts, bone fractures, and other serious events.

Dr. De Censi said he’s surprised the baby TAM vs tamoxifen topic is still being debated. “Baby TAM, in my opinion, is a new standard of care for endocrine prevention of breast cancer in high-risk [women],” and baby TAM over 3 years is enough, said Dr. De Censi during a debate on the topic at the 2024 European Society for Medical Oncology Breast Cancer Congress in Berlin.

Gareth Evans, MD, a cancer genetics and prevention specialist at the University of Manchester, Manchester, England, however, isn’t convinced.

During the debate, Dr. Evans explained that  his main concern was that the baby TAM trial was limited to women with high-risk lesions, not other common reasons for tamoxifen prophylaxis, such as a positive family history or BRCA mutations.

“In Manchester, we have put over a thousand women on tamoxifen who have a family history or other risk factors, not high-risk lesions,” and there simply isn’t definitive evidence for baby TAM in these women, Dr. Evans said.

The vast weight of evidence for tamoxifen prophylaxis, he added, is in trials involving tens of thousands of women, followed in some cases for 20 years, who received the 20 mg dose for 5 years.

As a result, women in Manchester are started on 20 mg and dropped down to 5 mg only for side effects. That way, Evans explained, we are not taking away the benefit among women who can tolerate 20 mg.

Meanwhile, there’s no evidence that baby TAM improves medication adherence, he noted. Trials have reported similar adherence rates to baby TAM and standard dose tamoxifen as well as no definitive evidence that the risk for cancer and thrombosis is less with baby TAM, he said.

In fact, Dr. Evans noted, “many women take tamoxifen 20 mg for 5 years with no side effects.”

Overall, “I don’t think we’ve got the evidence yet to drop” dosages, particularly in women without high-risk lesions, Dr. Evans said. A real concern, he added, is poor metabolizers for whom 5 mg won’t be enough to have a preventive effect.

Dr. De Censi noted, however, that there will likely never be a definitive answer to the question of baby TAM vs standard dosing because industry has no financial incentive to do a head-to-head trial; tamoxifen went off patent over 30 years ago.

Still, a poll of the audience favored Evans’ approach — 80% said they would start high-risk women on 20 mg for breast cancer prophylaxis and reduce for side effects as needed.

Dr. De Censi didn’t have any disclosures. Dr. Evans is a consultant/advisor for AstraZeneca, SpringWorks, Recursion, Everything Genetic, and Syantra.

A version of this article first appeared on Medscape.com.

Should 5 mg of tamoxifen — known as “baby TAM” — or the usual 20 mg dose be standard of care for breast cancer prevention in high-risk women?

Research to date clearly shows that tamoxifen can reduce the risk for breast cancer in high-risk individuals by 30%-50%. Recent evidence also indicates that this chemoprevention approach can reduce the risk of dying from breast cancer by as much as 57%.

In 2019, the US Preventive Services Task Force issued updated recommendations that clinicians offer risk-reducing medications, such as tamoxifen, raloxifene, or aromatase inhibitors, to women at an increased risk for breast cancer and a low risk for adverse medication effects.

However, this prophylactic strategy remains underused.

A major roadblock: The drugs’ side effects, which include venous thromboembolic events and endometrial cancer as well as symptoms of menopause, such as hot flashes and sexual issues, have made uptake and adherence a challenge.

Offering women a lower dose of tamoxifen could allay fears about toxicities and improve uptake as well as reduce side effects and boost long-term adherence among those receiving baby TAM.

However, experts remain uncertain about whether patients need the standard dose to experience the full prevention benefit.
 

The Debate

Years ago, Andrea De Censi, MD, a breast cancer researcher at the Galliera Hospital in Genova, Italy, and his colleagues reasoned that, because tamoxifen is a competitive estrogen receptor inhibitor, it may indeed have a minimal effective dose below 20 mg/d.

The fruits of that line of thought were presented to the world in the TAM-01 trial, first published in 2019, which pitted tamoxifen 5 mg/d for 3 years against placebo in 500 women with high-risk lesions, including lobular and ductal carcinoma in situ.

Dr. De Censi and colleagues found that baby TAM reduced the risk for invasive breast cancer by 52% and the risk for contralateral breast cancer by 75%.

Treatment adherence was slightly higher in the baby TAM group at 65% vs 61% in the placebo group.

A recent 10-year follow-up showed ongoing benefits associated with baby TAM vs placebo — a 42% reduction in breast cancer and a 64% drop in contralateral lesions.

The baby TAM group vs placebo experienced a slight increase in hot flashes but no significant increase in other common side effects.

Regarding serious adverse events, the baby TAM arm had one case of stage 1 endometrial cancer (0.4% of patients) and 20 cases of endometrial polyps (5%) vs 13 cases of endometrial polyps in the placebo arm. But there were no significant differences in thrombosis, cataracts, bone fractures, and other serious events.

Dr. De Censi said he’s surprised the baby TAM vs tamoxifen topic is still being debated. “Baby TAM, in my opinion, is a new standard of care for endocrine prevention of breast cancer in high-risk [women],” and baby TAM over 3 years is enough, said Dr. De Censi during a debate on the topic at the 2024 European Society for Medical Oncology Breast Cancer Congress in Berlin.

Gareth Evans, MD, a cancer genetics and prevention specialist at the University of Manchester, Manchester, England, however, isn’t convinced.

During the debate, Dr. Evans explained that  his main concern was that the baby TAM trial was limited to women with high-risk lesions, not other common reasons for tamoxifen prophylaxis, such as a positive family history or BRCA mutations.

“In Manchester, we have put over a thousand women on tamoxifen who have a family history or other risk factors, not high-risk lesions,” and there simply isn’t definitive evidence for baby TAM in these women, Dr. Evans said.

The vast weight of evidence for tamoxifen prophylaxis, he added, is in trials involving tens of thousands of women, followed in some cases for 20 years, who received the 20 mg dose for 5 years.

As a result, women in Manchester are started on 20 mg and dropped down to 5 mg only for side effects. That way, Evans explained, we are not taking away the benefit among women who can tolerate 20 mg.

Meanwhile, there’s no evidence that baby TAM improves medication adherence, he noted. Trials have reported similar adherence rates to baby TAM and standard dose tamoxifen as well as no definitive evidence that the risk for cancer and thrombosis is less with baby TAM, he said.

In fact, Dr. Evans noted, “many women take tamoxifen 20 mg for 5 years with no side effects.”

Overall, “I don’t think we’ve got the evidence yet to drop” dosages, particularly in women without high-risk lesions, Dr. Evans said. A real concern, he added, is poor metabolizers for whom 5 mg won’t be enough to have a preventive effect.

Dr. De Censi noted, however, that there will likely never be a definitive answer to the question of baby TAM vs standard dosing because industry has no financial incentive to do a head-to-head trial; tamoxifen went off patent over 30 years ago.

Still, a poll of the audience favored Evans’ approach — 80% said they would start high-risk women on 20 mg for breast cancer prophylaxis and reduce for side effects as needed.

Dr. De Censi didn’t have any disclosures. Dr. Evans is a consultant/advisor for AstraZeneca, SpringWorks, Recursion, Everything Genetic, and Syantra.

A version of this article first appeared on Medscape.com.

Should 5 mg of tamoxifen — known as “baby TAM” — or the usual 20 mg dose be standard of care for breast cancer prevention in high-risk women?

Research to date clearly shows that tamoxifen can reduce the risk for breast cancer in high-risk individuals by 30%-50%. Recent evidence also indicates that this chemoprevention approach can reduce the risk of dying from breast cancer by as much as 57%.

In 2019, the US Preventive Services Task Force issued updated recommendations that clinicians offer risk-reducing medications, such as tamoxifen, raloxifene, or aromatase inhibitors, to women at an increased risk for breast cancer and a low risk for adverse medication effects.

However, this prophylactic strategy remains underused.

A major roadblock: The drugs’ side effects, which include venous thromboembolic events and endometrial cancer as well as symptoms of menopause, such as hot flashes and sexual issues, have made uptake and adherence a challenge.

Offering women a lower dose of tamoxifen could allay fears about toxicities and improve uptake as well as reduce side effects and boost long-term adherence among those receiving baby TAM.

However, experts remain uncertain about whether patients need the standard dose to experience the full prevention benefit.
 

The Debate

Years ago, Andrea De Censi, MD, a breast cancer researcher at the Galliera Hospital in Genova, Italy, and his colleagues reasoned that, because tamoxifen is a competitive estrogen receptor inhibitor, it may indeed have a minimal effective dose below 20 mg/d.

The fruits of that line of thought were presented to the world in the TAM-01 trial, first published in 2019, which pitted tamoxifen 5 mg/d for 3 years against placebo in 500 women with high-risk lesions, including lobular and ductal carcinoma in situ.

Dr. De Censi and colleagues found that baby TAM reduced the risk for invasive breast cancer by 52% and the risk for contralateral breast cancer by 75%.

Treatment adherence was slightly higher in the baby TAM group at 65% vs 61% in the placebo group.

A recent 10-year follow-up showed ongoing benefits associated with baby TAM vs placebo — a 42% reduction in breast cancer and a 64% drop in contralateral lesions.

The baby TAM group vs placebo experienced a slight increase in hot flashes but no significant increase in other common side effects.

Regarding serious adverse events, the baby TAM arm had one case of stage 1 endometrial cancer (0.4% of patients) and 20 cases of endometrial polyps (5%) vs 13 cases of endometrial polyps in the placebo arm. But there were no significant differences in thrombosis, cataracts, bone fractures, and other serious events.

Dr. De Censi said he’s surprised the baby TAM vs tamoxifen topic is still being debated. “Baby TAM, in my opinion, is a new standard of care for endocrine prevention of breast cancer in high-risk [women],” and baby TAM over 3 years is enough, said Dr. De Censi during a debate on the topic at the 2024 European Society for Medical Oncology Breast Cancer Congress in Berlin.

Gareth Evans, MD, a cancer genetics and prevention specialist at the University of Manchester, Manchester, England, however, isn’t convinced.

During the debate, Dr. Evans explained that  his main concern was that the baby TAM trial was limited to women with high-risk lesions, not other common reasons for tamoxifen prophylaxis, such as a positive family history or BRCA mutations.

“In Manchester, we have put over a thousand women on tamoxifen who have a family history or other risk factors, not high-risk lesions,” and there simply isn’t definitive evidence for baby TAM in these women, Dr. Evans said.

The vast weight of evidence for tamoxifen prophylaxis, he added, is in trials involving tens of thousands of women, followed in some cases for 20 years, who received the 20 mg dose for 5 years.

As a result, women in Manchester are started on 20 mg and dropped down to 5 mg only for side effects. That way, Evans explained, we are not taking away the benefit among women who can tolerate 20 mg.

Meanwhile, there’s no evidence that baby TAM improves medication adherence, he noted. Trials have reported similar adherence rates to baby TAM and standard dose tamoxifen as well as no definitive evidence that the risk for cancer and thrombosis is less with baby TAM, he said.

In fact, Dr. Evans noted, “many women take tamoxifen 20 mg for 5 years with no side effects.”

Overall, “I don’t think we’ve got the evidence yet to drop” dosages, particularly in women without high-risk lesions, Dr. Evans said. A real concern, he added, is poor metabolizers for whom 5 mg won’t be enough to have a preventive effect.

Dr. De Censi noted, however, that there will likely never be a definitive answer to the question of baby TAM vs standard dosing because industry has no financial incentive to do a head-to-head trial; tamoxifen went off patent over 30 years ago.

Still, a poll of the audience favored Evans’ approach — 80% said they would start high-risk women on 20 mg for breast cancer prophylaxis and reduce for side effects as needed.

Dr. De Censi didn’t have any disclosures. Dr. Evans is a consultant/advisor for AstraZeneca, SpringWorks, Recursion, Everything Genetic, and Syantra.

A version of this article first appeared on Medscape.com.

An elderly gentleman was truly suffering, so his doctor decided to try something new.

“He’d had a number of cumulative side effects after almost two years of IV chemotherapy for his metastatic colon cancer,” said Anuj Patel, MD, a senior physician at Dana-Farber Cancer Institute in Boston, recalling his patient. “When we switched him to combination treatment with trifluridine/tipiracil and bevacizumab, he constantly remarked on how well he now felt. He described no side effects from this new regimen.”

Nearly a year after the US Food and Drug Administration (FDA) approved trifluridine/tipiracil combined with bevacizumab for refractory mCRC, the tremendous value of its results in practice are clear.

Trifluridine/tipiracil (Lonsurf) had been used to treat advanced gastric cancer, while bevacizumab had been therapeutic for a wider range of diseases, including cervical, brain, liver, kidney, gynecological and lung cancers. Used together for treating refractory mCRC, well-known initial findings about their effectiveness have been proven true over time.

“Patients taking both drugs can experience, on average, a life extension of three months,” said Richard M. Goldberg, MD, professor emeritus of the West Virginia University Cancer Institute and director of Fight Colorectal Cancer.
 

The History of the Combined Therapy’s Approval

The FDA originally approved trifluridine/tipiracil in September 2015 for use in patients with metastatic colorectal cancer. Patients eligible to take it had to have been treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, an anti-vascular endothelial growth factor (VEGF) biological therapy, and—if RAS wild-type—an anti-epidermal growth factor receptor (EGFR) therapy, according to data published by the National Center for Biotechnology Information. The FDA’s August 2023 approval of the trifluridine/tipiracil and bevacizumab combination regimen is for patients meeting the same eligibility requirements.

Another drug, regorafenib, had already been approved by the FDA in September 2012 to treat mCRC. The drug has a wide range of potential side effects, however, including complications relating to the limbs.

“One of my patients tried regorafenib as his initial third- line treatment,” Dr. Goldberg said. “I checked in on him at his farm, and he was sitting in the barn near his tractor.

He had such severe hand-foot syndrome that he could barely walk.”

Trifluridine/tipiracil alone proved to be very helpful in this case. “We switched him to it, and he tolerated it well,” Dr. Goldberg continued. “He got his fields plowed and was on it for months before he passed away. We both felt it kept him going longer.”

A new research review confirms the regimen’s success, determining that trifluridine/tipiracil plus bevacizumab was associated with improved outcomes compared to therapy solely with trifluridine/tipiracil.
 

A True Practice Changer

Now that the regimen has been on the market for more than half a year, there are longer-term data available.

Patients on average live within the same timeframe as the patients in the SUNLIGHT study, and many feel physically better on the therapy. “The combination has very quickly shifted the standard of care,” Dr. Goldberg said.

The regimen can also provide significant psychological benefits to patients.

“As patients can maintain good performance status for longer with the combination, it increases the perception of quality of life,” said Jacobo Hincapie-Echeverri, MD, a GI and geriatric oncologist at Orlando Health Cancer Institute in Orlando, Florida.

The regimen is unique too, in that it can help doctors plan additional treatment strategies.

“This current approval, for the combination of trifluridine/tipiracil and bevacizumab, is practice-changing in that it helps clarify the sequence for later treatments for patients with mCRC,” said Dr. Patel, who is also clinical director of the Center for Esophageal and Gastric Cancer and assistant professor of medicine at Harvard Medical School, Boston. “Previously, it had been difficult to decide between trifluridine/tipiracil and regorafenib in this setting.”

The fact that the regimen has been shown to give time and improved quality of life to patients in ways regorafenib does not is clarifying. “Now, with the improved outcomes seen, I do think that trifluridine/tipiracil plus bevacizumab is the better option for most mCRC patients after IV chemotherapies,” Dr. Patel added.

When it comes to his specific experience with prescribing the regimen for his patients, Dr. Patel reported that it’s easier on his patients than other therapies.

“I find that it is generally well tolerated,” he elaborated. “As an oral agent, it is also usually somewhat easier to take (than other delivery methods of medication). These factors are critical for patients who have likely already had at least 2 or 3 prior lines of chemotherapy. I have had many patients with mCRC who, after disease progression on prior IV chemotherapy regimens, have had periods of meaningful disease control – often with fewer and manageable side effects.”

Dr. Goldberg mentioned another benefit.

“The nice thing about the combination of trifluridine/tipiracil and bevacizumab is that in terms of toxicity, there’s very little difference compared to the toxicity of trifluridine/tipiracil used alone.”
 

Are There Downsides to the Regimen?

The pros are obvious, but the regimen has some cons as well. Medically, patients should have a platelet count over 75,000/mm³ and absolute neutrophil count (ANC) over 1,500/mm³ prior to the start of each cycle, and their liver and renal function should be monitored.

Patients with metastatic colorectal cancer must be also carefully monitored for hematologic adverse events (AEs) , including chemotherapy-associated neutropenia. Biweekly treatments may reduce the risk of AEs as a whole, however, according to research.

The regimen is also expensive – an approximate cost of $8,191 for a 28-day supply. According to a new study, patients managing both AE expenses along with the cost of trifluridine/tipiracil-bevacizumab face a monthly bill of about $17,179.

Some very good news, though: 100% of Medicare drug plans cover trifluridine/tipiracil, with an average copay of $57-$292. Bevacizumab is also covered by Medicare, with a copay as low as $0-$25.

Private insurers do cover the drugs, depending on a patient’s specific plan. However, if a patient’s claim is denied, financial assistance for trifluridine/tipiracil through the drug’s manufacturers may be available for some patients, reducing prescriptions to a zero cost in some cases. Bevacizumab can be made available to patients who may not have health insurance at all, too. Patients can use a financial assistance tool through the drug’s manufacturer to receive up to $25,000 in yearly copay assistance.
 

What Does the Latest Research on the Regimen Indicate?

In May 2024, two abstracts were presented at the annual meeting of the American Society of Clinical Oncology (ASCO) that explored expanded possible use of trifluridine/tipiracil plus bevacizumab as a treatment for metastatic colorectal cancer.

The first abstract studied trifluridine/tipiracil plus bevacizumab as upfront treatment for mCRC, adding capecitabine to the regimen.

“It’s a phase 1 study looking at dose findings for the three-drug combination, where the active drug is a chemotherapy agent classified as a fluoropyrimidine ... I would characterize this as a study combining two [fluoropyrimidines] with a single targeted therapy,” Dr. Goldberg said.

“Combining two fluoropyrimidines is an unusual approach, because they tend to have overlapping side effects, and the potential is there for either innate drug resistance to the class of drugs or that the combination of two agents that work by a similar mechanism of action could hasten the development of acquired drug resistance. There is apparently a signal that combining the two chemotherapy agents enhances each other’s activity in cell culture and animal models,” he added.

Ultimately, Dr. Goldberg said he thinks more evidence is needed to prove the regimen’s effectiveness.

“This is a very early study and really provides no information about its potential given that no response data was presented,” he added. “While this is an interesting idea, it is unclear if it will pan out until we see the data on the Phase II study in progress.”

The other abstract looked at the impact of colorectal liver metastases in patients with mCRC who in phase 3 of the SUNLIGHT trial received trifluridine/tipiracil with or without bevacizumab.

“There is not much that is novel here,” Dr. Goldberg said. “The retrospective analysis shows that trifluridine/tipiracil plus bevacizumab is better than trifluridine/tipiracil alone in the subset of patients with liver metastases, as it was shown to be in the entire patient population. While this is reassuring, it’s not unexpected, especially since the vast majority of people enrolled in the SUNLIGHT trial had liver metastases.”

The Bottom Line

In the future, the potential exists for trifluridine/tipiracil combined with bevacizumab to work in first-line and second-line patients.

“Seventy percent of colorectal cancer patients reach second line treatment right now, but only 30% reach third line treatment — either they become too sick to continue, or choose not to,” Dr. Goldberg said. “The hope is that using these drugs earlier can help more patients reach and prolong treatment.”

It’s also possible that the regimen can be applied in new ways.

“Further research combining trifluridine/tipiracil and bevacizumab with other targeted therapies could yield additional advances for refractory mCRC patients,” Dr. Hincapie-Echeverri said. “The survival benefit of this therapy reinforces the importance of continuing to develop new therapies to improve outcomes in the refractory mCRC setting.”

Dr. Patel’s patient felt lucky to simply live a longer life.

Because of the regimen, “his cancer remained stable for approximately 8 months. Upon its progression, he chose not to pursue any further chemotherapy. He instead expressed his gratitude at having been able to feel more like himself for nearly a year.”

Dr. Patel received research funding in 2017 from Taiho, which manufactures trifluridine/tipiracil. He receives no current funding from Taiho and has no additional conflicts of interest. Dr. Goldberg helped represent Taiho in a patent law dispute regarding Lonsurf for which he was paid, but he is no longer paid by the company. Dr. Hincapie-Echeverri is a speaker for Astellas Pharma, which does not manufacture trifluridine/tipiracil or bevacizumab, and he has no additional conflicts of interest.

An elderly gentleman was truly suffering, so his doctor decided to try something new.

“He’d had a number of cumulative side effects after almost two years of IV chemotherapy for his metastatic colon cancer,” said Anuj Patel, MD, a senior physician at Dana-Farber Cancer Institute in Boston, recalling his patient. “When we switched him to combination treatment with trifluridine/tipiracil and bevacizumab, he constantly remarked on how well he now felt. He described no side effects from this new regimen.”

Nearly a year after the US Food and Drug Administration (FDA) approved trifluridine/tipiracil combined with bevacizumab for refractory mCRC, the tremendous value of its results in practice are clear.

Trifluridine/tipiracil (Lonsurf) had been used to treat advanced gastric cancer, while bevacizumab had been therapeutic for a wider range of diseases, including cervical, brain, liver, kidney, gynecological and lung cancers. Used together for treating refractory mCRC, well-known initial findings about their effectiveness have been proven true over time.

“Patients taking both drugs can experience, on average, a life extension of three months,” said Richard M. Goldberg, MD, professor emeritus of the West Virginia University Cancer Institute and director of Fight Colorectal Cancer.
 

The History of the Combined Therapy’s Approval

The FDA originally approved trifluridine/tipiracil in September 2015 for use in patients with metastatic colorectal cancer. Patients eligible to take it had to have been treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, an anti-vascular endothelial growth factor (VEGF) biological therapy, and—if RAS wild-type—an anti-epidermal growth factor receptor (EGFR) therapy, according to data published by the National Center for Biotechnology Information. The FDA’s August 2023 approval of the trifluridine/tipiracil and bevacizumab combination regimen is for patients meeting the same eligibility requirements.

Another drug, regorafenib, had already been approved by the FDA in September 2012 to treat mCRC. The drug has a wide range of potential side effects, however, including complications relating to the limbs.

“One of my patients tried regorafenib as his initial third- line treatment,” Dr. Goldberg said. “I checked in on him at his farm, and he was sitting in the barn near his tractor.

He had such severe hand-foot syndrome that he could barely walk.”

Trifluridine/tipiracil alone proved to be very helpful in this case. “We switched him to it, and he tolerated it well,” Dr. Goldberg continued. “He got his fields plowed and was on it for months before he passed away. We both felt it kept him going longer.”

A new research review confirms the regimen’s success, determining that trifluridine/tipiracil plus bevacizumab was associated with improved outcomes compared to therapy solely with trifluridine/tipiracil.
 

A True Practice Changer

Now that the regimen has been on the market for more than half a year, there are longer-term data available.

Patients on average live within the same timeframe as the patients in the SUNLIGHT study, and many feel physically better on the therapy. “The combination has very quickly shifted the standard of care,” Dr. Goldberg said.

The regimen can also provide significant psychological benefits to patients.

“As patients can maintain good performance status for longer with the combination, it increases the perception of quality of life,” said Jacobo Hincapie-Echeverri, MD, a GI and geriatric oncologist at Orlando Health Cancer Institute in Orlando, Florida.

The regimen is unique too, in that it can help doctors plan additional treatment strategies.

“This current approval, for the combination of trifluridine/tipiracil and bevacizumab, is practice-changing in that it helps clarify the sequence for later treatments for patients with mCRC,” said Dr. Patel, who is also clinical director of the Center for Esophageal and Gastric Cancer and assistant professor of medicine at Harvard Medical School, Boston. “Previously, it had been difficult to decide between trifluridine/tipiracil and regorafenib in this setting.”

The fact that the regimen has been shown to give time and improved quality of life to patients in ways regorafenib does not is clarifying. “Now, with the improved outcomes seen, I do think that trifluridine/tipiracil plus bevacizumab is the better option for most mCRC patients after IV chemotherapies,” Dr. Patel added.

When it comes to his specific experience with prescribing the regimen for his patients, Dr. Patel reported that it’s easier on his patients than other therapies.

“I find that it is generally well tolerated,” he elaborated. “As an oral agent, it is also usually somewhat easier to take (than other delivery methods of medication). These factors are critical for patients who have likely already had at least 2 or 3 prior lines of chemotherapy. I have had many patients with mCRC who, after disease progression on prior IV chemotherapy regimens, have had periods of meaningful disease control – often with fewer and manageable side effects.”

Dr. Goldberg mentioned another benefit.

“The nice thing about the combination of trifluridine/tipiracil and bevacizumab is that in terms of toxicity, there’s very little difference compared to the toxicity of trifluridine/tipiracil used alone.”
 

Are There Downsides to the Regimen?

The pros are obvious, but the regimen has some cons as well. Medically, patients should have a platelet count over 75,000/mm³ and absolute neutrophil count (ANC) over 1,500/mm³ prior to the start of each cycle, and their liver and renal function should be monitored.

Patients with metastatic colorectal cancer must be also carefully monitored for hematologic adverse events (AEs) , including chemotherapy-associated neutropenia. Biweekly treatments may reduce the risk of AEs as a whole, however, according to research.

The regimen is also expensive – an approximate cost of $8,191 for a 28-day supply. According to a new study, patients managing both AE expenses along with the cost of trifluridine/tipiracil-bevacizumab face a monthly bill of about $17,179.

Some very good news, though: 100% of Medicare drug plans cover trifluridine/tipiracil, with an average copay of $57-$292. Bevacizumab is also covered by Medicare, with a copay as low as $0-$25.

Private insurers do cover the drugs, depending on a patient’s specific plan. However, if a patient’s claim is denied, financial assistance for trifluridine/tipiracil through the drug’s manufacturers may be available for some patients, reducing prescriptions to a zero cost in some cases. Bevacizumab can be made available to patients who may not have health insurance at all, too. Patients can use a financial assistance tool through the drug’s manufacturer to receive up to $25,000 in yearly copay assistance.
 

What Does the Latest Research on the Regimen Indicate?

In May 2024, two abstracts were presented at the annual meeting of the American Society of Clinical Oncology (ASCO) that explored expanded possible use of trifluridine/tipiracil plus bevacizumab as a treatment for metastatic colorectal cancer.

The first abstract studied trifluridine/tipiracil plus bevacizumab as upfront treatment for mCRC, adding capecitabine to the regimen.

“It’s a phase 1 study looking at dose findings for the three-drug combination, where the active drug is a chemotherapy agent classified as a fluoropyrimidine ... I would characterize this as a study combining two [fluoropyrimidines] with a single targeted therapy,” Dr. Goldberg said.

“Combining two fluoropyrimidines is an unusual approach, because they tend to have overlapping side effects, and the potential is there for either innate drug resistance to the class of drugs or that the combination of two agents that work by a similar mechanism of action could hasten the development of acquired drug resistance. There is apparently a signal that combining the two chemotherapy agents enhances each other’s activity in cell culture and animal models,” he added.

Ultimately, Dr. Goldberg said he thinks more evidence is needed to prove the regimen’s effectiveness.

“This is a very early study and really provides no information about its potential given that no response data was presented,” he added. “While this is an interesting idea, it is unclear if it will pan out until we see the data on the Phase II study in progress.”

The other abstract looked at the impact of colorectal liver metastases in patients with mCRC who in phase 3 of the SUNLIGHT trial received trifluridine/tipiracil with or without bevacizumab.

“There is not much that is novel here,” Dr. Goldberg said. “The retrospective analysis shows that trifluridine/tipiracil plus bevacizumab is better than trifluridine/tipiracil alone in the subset of patients with liver metastases, as it was shown to be in the entire patient population. While this is reassuring, it’s not unexpected, especially since the vast majority of people enrolled in the SUNLIGHT trial had liver metastases.”

The Bottom Line

In the future, the potential exists for trifluridine/tipiracil combined with bevacizumab to work in first-line and second-line patients.

“Seventy percent of colorectal cancer patients reach second line treatment right now, but only 30% reach third line treatment — either they become too sick to continue, or choose not to,” Dr. Goldberg said. “The hope is that using these drugs earlier can help more patients reach and prolong treatment.”

It’s also possible that the regimen can be applied in new ways.

“Further research combining trifluridine/tipiracil and bevacizumab with other targeted therapies could yield additional advances for refractory mCRC patients,” Dr. Hincapie-Echeverri said. “The survival benefit of this therapy reinforces the importance of continuing to develop new therapies to improve outcomes in the refractory mCRC setting.”

Dr. Patel’s patient felt lucky to simply live a longer life.

Because of the regimen, “his cancer remained stable for approximately 8 months. Upon its progression, he chose not to pursue any further chemotherapy. He instead expressed his gratitude at having been able to feel more like himself for nearly a year.”

Dr. Patel received research funding in 2017 from Taiho, which manufactures trifluridine/tipiracil. He receives no current funding from Taiho and has no additional conflicts of interest. Dr. Goldberg helped represent Taiho in a patent law dispute regarding Lonsurf for which he was paid, but he is no longer paid by the company. Dr. Hincapie-Echeverri is a speaker for Astellas Pharma, which does not manufacture trifluridine/tipiracil or bevacizumab, and he has no additional conflicts of interest.

An elderly gentleman was truly suffering, so his doctor decided to try something new.

“He’d had a number of cumulative side effects after almost two years of IV chemotherapy for his metastatic colon cancer,” said Anuj Patel, MD, a senior physician at Dana-Farber Cancer Institute in Boston, recalling his patient. “When we switched him to combination treatment with trifluridine/tipiracil and bevacizumab, he constantly remarked on how well he now felt. He described no side effects from this new regimen.”

Nearly a year after the US Food and Drug Administration (FDA) approved trifluridine/tipiracil combined with bevacizumab for refractory mCRC, the tremendous value of its results in practice are clear.

Trifluridine/tipiracil (Lonsurf) had been used to treat advanced gastric cancer, while bevacizumab had been therapeutic for a wider range of diseases, including cervical, brain, liver, kidney, gynecological and lung cancers. Used together for treating refractory mCRC, well-known initial findings about their effectiveness have been proven true over time.

“Patients taking both drugs can experience, on average, a life extension of three months,” said Richard M. Goldberg, MD, professor emeritus of the West Virginia University Cancer Institute and director of Fight Colorectal Cancer.
 

The History of the Combined Therapy’s Approval

The FDA originally approved trifluridine/tipiracil in September 2015 for use in patients with metastatic colorectal cancer. Patients eligible to take it had to have been treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, an anti-vascular endothelial growth factor (VEGF) biological therapy, and—if RAS wild-type—an anti-epidermal growth factor receptor (EGFR) therapy, according to data published by the National Center for Biotechnology Information. The FDA’s August 2023 approval of the trifluridine/tipiracil and bevacizumab combination regimen is for patients meeting the same eligibility requirements.

Another drug, regorafenib, had already been approved by the FDA in September 2012 to treat mCRC. The drug has a wide range of potential side effects, however, including complications relating to the limbs.

“One of my patients tried regorafenib as his initial third- line treatment,” Dr. Goldberg said. “I checked in on him at his farm, and he was sitting in the barn near his tractor.

He had such severe hand-foot syndrome that he could barely walk.”

Trifluridine/tipiracil alone proved to be very helpful in this case. “We switched him to it, and he tolerated it well,” Dr. Goldberg continued. “He got his fields plowed and was on it for months before he passed away. We both felt it kept him going longer.”

A new research review confirms the regimen’s success, determining that trifluridine/tipiracil plus bevacizumab was associated with improved outcomes compared to therapy solely with trifluridine/tipiracil.
 

A True Practice Changer

Now that the regimen has been on the market for more than half a year, there are longer-term data available.

Patients on average live within the same timeframe as the patients in the SUNLIGHT study, and many feel physically better on the therapy. “The combination has very quickly shifted the standard of care,” Dr. Goldberg said.

The regimen can also provide significant psychological benefits to patients.

“As patients can maintain good performance status for longer with the combination, it increases the perception of quality of life,” said Jacobo Hincapie-Echeverri, MD, a GI and geriatric oncologist at Orlando Health Cancer Institute in Orlando, Florida.

The regimen is unique too, in that it can help doctors plan additional treatment strategies.

“This current approval, for the combination of trifluridine/tipiracil and bevacizumab, is practice-changing in that it helps clarify the sequence for later treatments for patients with mCRC,” said Dr. Patel, who is also clinical director of the Center for Esophageal and Gastric Cancer and assistant professor of medicine at Harvard Medical School, Boston. “Previously, it had been difficult to decide between trifluridine/tipiracil and regorafenib in this setting.”

The fact that the regimen has been shown to give time and improved quality of life to patients in ways regorafenib does not is clarifying. “Now, with the improved outcomes seen, I do think that trifluridine/tipiracil plus bevacizumab is the better option for most mCRC patients after IV chemotherapies,” Dr. Patel added.

When it comes to his specific experience with prescribing the regimen for his patients, Dr. Patel reported that it’s easier on his patients than other therapies.

“I find that it is generally well tolerated,” he elaborated. “As an oral agent, it is also usually somewhat easier to take (than other delivery methods of medication). These factors are critical for patients who have likely already had at least 2 or 3 prior lines of chemotherapy. I have had many patients with mCRC who, after disease progression on prior IV chemotherapy regimens, have had periods of meaningful disease control – often with fewer and manageable side effects.”

Dr. Goldberg mentioned another benefit.

“The nice thing about the combination of trifluridine/tipiracil and bevacizumab is that in terms of toxicity, there’s very little difference compared to the toxicity of trifluridine/tipiracil used alone.”
 

Are There Downsides to the Regimen?

The pros are obvious, but the regimen has some cons as well. Medically, patients should have a platelet count over 75,000/mm³ and absolute neutrophil count (ANC) over 1,500/mm³ prior to the start of each cycle, and their liver and renal function should be monitored.

Patients with metastatic colorectal cancer must be also carefully monitored for hematologic adverse events (AEs) , including chemotherapy-associated neutropenia. Biweekly treatments may reduce the risk of AEs as a whole, however, according to research.

The regimen is also expensive – an approximate cost of $8,191 for a 28-day supply. According to a new study, patients managing both AE expenses along with the cost of trifluridine/tipiracil-bevacizumab face a monthly bill of about $17,179.

Some very good news, though: 100% of Medicare drug plans cover trifluridine/tipiracil, with an average copay of $57-$292. Bevacizumab is also covered by Medicare, with a copay as low as $0-$25.

Private insurers do cover the drugs, depending on a patient’s specific plan. However, if a patient’s claim is denied, financial assistance for trifluridine/tipiracil through the drug’s manufacturers may be available for some patients, reducing prescriptions to a zero cost in some cases. Bevacizumab can be made available to patients who may not have health insurance at all, too. Patients can use a financial assistance tool through the drug’s manufacturer to receive up to $25,000 in yearly copay assistance.
 

What Does the Latest Research on the Regimen Indicate?

In May 2024, two abstracts were presented at the annual meeting of the American Society of Clinical Oncology (ASCO) that explored expanded possible use of trifluridine/tipiracil plus bevacizumab as a treatment for metastatic colorectal cancer.

The first abstract studied trifluridine/tipiracil plus bevacizumab as upfront treatment for mCRC, adding capecitabine to the regimen.

“It’s a phase 1 study looking at dose findings for the three-drug combination, where the active drug is a chemotherapy agent classified as a fluoropyrimidine ... I would characterize this as a study combining two [fluoropyrimidines] with a single targeted therapy,” Dr. Goldberg said.

“Combining two fluoropyrimidines is an unusual approach, because they tend to have overlapping side effects, and the potential is there for either innate drug resistance to the class of drugs or that the combination of two agents that work by a similar mechanism of action could hasten the development of acquired drug resistance. There is apparently a signal that combining the two chemotherapy agents enhances each other’s activity in cell culture and animal models,” he added.

Ultimately, Dr. Goldberg said he thinks more evidence is needed to prove the regimen’s effectiveness.

“This is a very early study and really provides no information about its potential given that no response data was presented,” he added. “While this is an interesting idea, it is unclear if it will pan out until we see the data on the Phase II study in progress.”

The other abstract looked at the impact of colorectal liver metastases in patients with mCRC who in phase 3 of the SUNLIGHT trial received trifluridine/tipiracil with or without bevacizumab.

“There is not much that is novel here,” Dr. Goldberg said. “The retrospective analysis shows that trifluridine/tipiracil plus bevacizumab is better than trifluridine/tipiracil alone in the subset of patients with liver metastases, as it was shown to be in the entire patient population. While this is reassuring, it’s not unexpected, especially since the vast majority of people enrolled in the SUNLIGHT trial had liver metastases.”

The Bottom Line

In the future, the potential exists for trifluridine/tipiracil combined with bevacizumab to work in first-line and second-line patients.

“Seventy percent of colorectal cancer patients reach second line treatment right now, but only 30% reach third line treatment — either they become too sick to continue, or choose not to,” Dr. Goldberg said. “The hope is that using these drugs earlier can help more patients reach and prolong treatment.”

It’s also possible that the regimen can be applied in new ways.

“Further research combining trifluridine/tipiracil and bevacizumab with other targeted therapies could yield additional advances for refractory mCRC patients,” Dr. Hincapie-Echeverri said. “The survival benefit of this therapy reinforces the importance of continuing to develop new therapies to improve outcomes in the refractory mCRC setting.”

Dr. Patel’s patient felt lucky to simply live a longer life.

Because of the regimen, “his cancer remained stable for approximately 8 months. Upon its progression, he chose not to pursue any further chemotherapy. He instead expressed his gratitude at having been able to feel more like himself for nearly a year.”

Dr. Patel received research funding in 2017 from Taiho, which manufactures trifluridine/tipiracil. He receives no current funding from Taiho and has no additional conflicts of interest. Dr. Goldberg helped represent Taiho in a patent law dispute regarding Lonsurf for which he was paid, but he is no longer paid by the company. Dr. Hincapie-Echeverri is a speaker for Astellas Pharma, which does not manufacture trifluridine/tipiracil or bevacizumab, and he has no additional conflicts of interest.