CHEST Physician

Most major cancer trial centers in the United States are located closer to populations with higher proportions of White, affluent individuals, a new study finds.

This inequity may be potentiating the underrepresentation of racially minoritized and socioeconomically disadvantaged populations in clinical trials, suggesting that employment of satellite hospitals is needed to expand access to investigational therapies, reported lead author Hassal Lee, MD, PhD, of Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, and colleagues.

“Minoritized and socioeconomically disadvantaged populations are underrepresented in clinical trials,” the investigators wrote in JAMA Oncology. “This may reduce the generalizability of trial results and propagate health disparities. Contributors to inequitable trial participation include individual-level factors and structural factors.”

Specifically, travel time to trial centers, as well as socioeconomic deprivation, can reduce likelihood of trial participation.

“Data on these parameters and population data on self-identified race exist, but their interrelation with clinical research facilities has not been systematically analyzed,” they wrote.

To try to draw comparisons between the distribution of patients of different races and socioeconomic statuses and the locations of clinical research facilities, Dr. Lee and colleagues aggregated data from the US Census, National Trial registry, Nature Index of Cancer Research Health Institutions, OpenStreetMap, National Cancer Institute–designated Cancer Centers list, and National Homeland Infrastructure Foundation. They then characterized catchment population demographics within 30-, 60-, and 120-minute driving commute times of all US hospitals, along with a more focused look at centers capable of conducting phase 1, phase 2, and phase 3 trials.

These efforts revealed broad geographic inequity.The 78 major centers that conduct 94% of all US cancer trials are located within 30 minutes of populations that have a 10.1% higher proportion of self-identified White individuals than the average US county, and a median income $18,900 higher than average (unpaired mean differences).

The publication also includes several maps characterizing racial and socioeconomic demographics within various catchment areas. For example, centers in New York City, Houston, and Chicago have the most diverse catchment populations within a 30-minute commute. Maps of all cities in the United States with populations greater than 500,000 are available in a supplementary index.

“This study indicates that geographical population distributions may present barriers to equitable clinical trial access and that data are available to proactively strategize about reduction of such barriers,” Dr. Lee and colleagues wrote.

The findings call attention to modifiable socioeconomic factors associated with trial participation, they added, like financial toxicity and affordable transportation, noting that ethnic and racial groups consent to trials at similar rates after controlling for income.

In addition, Dr. Lee and colleagues advised clinical trial designers to enlist satellite hospitals to increase participant diversity, since long commutes exacerbate “socioeconomic burdens associated with clinical trial participation,” with trial participation decreasing as commute time increases.

“Existing clinical trial centers may build collaborative efforts with nearby hospitals closer to underrepresented populations or set up community centers to support new collaborative networks to improve geographical access equity,” they wrote. “Methodologically, our approach is transferable to any country, region, or global effort with sufficient source data and can inform decision-making along the continuum of cancer care, from screening to implementing specialist care.”

A coauthor disclosed relationships with Flagship Therapeutics, Leidos Holding Ltd, Pershing Square Foundation, and others.

Most major cancer trial centers in the United States are located closer to populations with higher proportions of White, affluent individuals, a new study finds.

This inequity may be potentiating the underrepresentation of racially minoritized and socioeconomically disadvantaged populations in clinical trials, suggesting that employment of satellite hospitals is needed to expand access to investigational therapies, reported lead author Hassal Lee, MD, PhD, of Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, and colleagues.

“Minoritized and socioeconomically disadvantaged populations are underrepresented in clinical trials,” the investigators wrote in JAMA Oncology. “This may reduce the generalizability of trial results and propagate health disparities. Contributors to inequitable trial participation include individual-level factors and structural factors.”

Specifically, travel time to trial centers, as well as socioeconomic deprivation, can reduce likelihood of trial participation.

“Data on these parameters and population data on self-identified race exist, but their interrelation with clinical research facilities has not been systematically analyzed,” they wrote.

To try to draw comparisons between the distribution of patients of different races and socioeconomic statuses and the locations of clinical research facilities, Dr. Lee and colleagues aggregated data from the US Census, National Trial registry, Nature Index of Cancer Research Health Institutions, OpenStreetMap, National Cancer Institute–designated Cancer Centers list, and National Homeland Infrastructure Foundation. They then characterized catchment population demographics within 30-, 60-, and 120-minute driving commute times of all US hospitals, along with a more focused look at centers capable of conducting phase 1, phase 2, and phase 3 trials.

These efforts revealed broad geographic inequity.The 78 major centers that conduct 94% of all US cancer trials are located within 30 minutes of populations that have a 10.1% higher proportion of self-identified White individuals than the average US county, and a median income $18,900 higher than average (unpaired mean differences).

The publication also includes several maps characterizing racial and socioeconomic demographics within various catchment areas. For example, centers in New York City, Houston, and Chicago have the most diverse catchment populations within a 30-minute commute. Maps of all cities in the United States with populations greater than 500,000 are available in a supplementary index.

“This study indicates that geographical population distributions may present barriers to equitable clinical trial access and that data are available to proactively strategize about reduction of such barriers,” Dr. Lee and colleagues wrote.

The findings call attention to modifiable socioeconomic factors associated with trial participation, they added, like financial toxicity and affordable transportation, noting that ethnic and racial groups consent to trials at similar rates after controlling for income.

In addition, Dr. Lee and colleagues advised clinical trial designers to enlist satellite hospitals to increase participant diversity, since long commutes exacerbate “socioeconomic burdens associated with clinical trial participation,” with trial participation decreasing as commute time increases.

“Existing clinical trial centers may build collaborative efforts with nearby hospitals closer to underrepresented populations or set up community centers to support new collaborative networks to improve geographical access equity,” they wrote. “Methodologically, our approach is transferable to any country, region, or global effort with sufficient source data and can inform decision-making along the continuum of cancer care, from screening to implementing specialist care.”

A coauthor disclosed relationships with Flagship Therapeutics, Leidos Holding Ltd, Pershing Square Foundation, and others.

Most major cancer trial centers in the United States are located closer to populations with higher proportions of White, affluent individuals, a new study finds.

This inequity may be potentiating the underrepresentation of racially minoritized and socioeconomically disadvantaged populations in clinical trials, suggesting that employment of satellite hospitals is needed to expand access to investigational therapies, reported lead author Hassal Lee, MD, PhD, of Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, and colleagues.

“Minoritized and socioeconomically disadvantaged populations are underrepresented in clinical trials,” the investigators wrote in JAMA Oncology. “This may reduce the generalizability of trial results and propagate health disparities. Contributors to inequitable trial participation include individual-level factors and structural factors.”

Specifically, travel time to trial centers, as well as socioeconomic deprivation, can reduce likelihood of trial participation.

“Data on these parameters and population data on self-identified race exist, but their interrelation with clinical research facilities has not been systematically analyzed,” they wrote.

To try to draw comparisons between the distribution of patients of different races and socioeconomic statuses and the locations of clinical research facilities, Dr. Lee and colleagues aggregated data from the US Census, National Trial registry, Nature Index of Cancer Research Health Institutions, OpenStreetMap, National Cancer Institute–designated Cancer Centers list, and National Homeland Infrastructure Foundation. They then characterized catchment population demographics within 30-, 60-, and 120-minute driving commute times of all US hospitals, along with a more focused look at centers capable of conducting phase 1, phase 2, and phase 3 trials.

These efforts revealed broad geographic inequity.The 78 major centers that conduct 94% of all US cancer trials are located within 30 minutes of populations that have a 10.1% higher proportion of self-identified White individuals than the average US county, and a median income $18,900 higher than average (unpaired mean differences).

The publication also includes several maps characterizing racial and socioeconomic demographics within various catchment areas. For example, centers in New York City, Houston, and Chicago have the most diverse catchment populations within a 30-minute commute. Maps of all cities in the United States with populations greater than 500,000 are available in a supplementary index.

“This study indicates that geographical population distributions may present barriers to equitable clinical trial access and that data are available to proactively strategize about reduction of such barriers,” Dr. Lee and colleagues wrote.

The findings call attention to modifiable socioeconomic factors associated with trial participation, they added, like financial toxicity and affordable transportation, noting that ethnic and racial groups consent to trials at similar rates after controlling for income.

In addition, Dr. Lee and colleagues advised clinical trial designers to enlist satellite hospitals to increase participant diversity, since long commutes exacerbate “socioeconomic burdens associated with clinical trial participation,” with trial participation decreasing as commute time increases.

“Existing clinical trial centers may build collaborative efforts with nearby hospitals closer to underrepresented populations or set up community centers to support new collaborative networks to improve geographical access equity,” they wrote. “Methodologically, our approach is transferable to any country, region, or global effort with sufficient source data and can inform decision-making along the continuum of cancer care, from screening to implementing specialist care.”

A coauthor disclosed relationships with Flagship Therapeutics, Leidos Holding Ltd, Pershing Square Foundation, and others.

Informing patients of a dire diagnosis — or even one that will require significant lifestyle changes — is never easy. But what’s even more challenging is when patients don’t accept their medical condition or a future that might include a difficult treatment protocol or even new medications or surgery.

“This is a challenging space to be in because this isn’t an exact science,” said Jack Jacoub, MD, medical director of MemorialCare Cancer Institute at Orange Coast Memorial in Fountain Valley, California. “There’s no formal training to deal with this — experience is your best teacher.”

Ultimately, helping a person reconceptualize what their future looks like is at the heart of every one of these conversations, said Sourav Sengupta, MD, MPH, associate professor of psychiatry and pediatrics at the Jacobs School of Medicine and Biomedical Sciences at the University at Buffalo, Buffalo, New York. “As physicians, we’re charged with helping our patients navigate a difficult and challenging time in their life,” he told this news organization.

“It’s not infrequent that patients are struggling to rethink what it will be like to be a person with an illness that might be chronic and how this will change their life,” he said.

And because denial is commonly the initial way a patient might cope with absorbing news that’s hard to hear, you’ll need to be extremely patient and empathetic.

“The goal is to build trust with this person, including trust in you, the hospital itself, and the entire team treating the patient,” Dr. Jacoub said.

“A diagnosis, especially in my field of oncology, can be scary. Spending time explaining their prognosis is very important. This can’t be a rushed scenario.”

More advice on helping patients who are in denial about their medical condition:
 

Make Sure They Understand What’s Going on

In cardiology, it’s common for patients to be hospitalized when they first learn that they have a disease they must manage for the rest of their life, said Stephanie Saucier, MD, a noninvasive cardiologist and codirector of the Women’s Heart Wellness Program at Hartford Healthcare’s Heart and Vascular Institute.

“Especially after someone has had a heart attack, a stroke, or they had bypass or stents placed, I like to see what their understanding of the disease is,” Dr. Saucier said. “I ask them, ‘What do you understand about what happened to you’. It can get confusing when you’re in the hospital and are told a lot of information in a short period of time.”
 

Share the Data

If a patient remains resistant to the news of a diagnosis, sharing test results can be beneficial. “I’ll often say, ‘here are the scans; this is the path report; this is the bloodwork; this is your biopsy report; these are the things we have’,” Dr. Jacoub said.

“Yes, this is clinical, but it helps to communicate the information you have and do it with data. For example, I might add, ‘Would you like to see some of the things [results, scans, tests] we’re talking about today?’ This also helps establish trust.”
 

Help Them Wrap Their Mind Around a Lifelong Condition

It’s often challenging for patients to accept that what they think is a one-time health issue will affect them for a lifetime. “I use juvenile diabetes as a way to explain this,” Dr. Saucier said. “I ask them what they would do if, say, their child was diagnosed with juvenile diabetes.”

Of course, patients agree that they wouldn’t give a child insulin for only a brief period. They understand that the condition must be treated in the long term. This kind of analogy can help patients understand that they, too, have a disorder requiring lifelong treatment.
 

Be Ready to Respond

Dr. Sengupta says that it’s important to be prepared with an answer if your patient is challenging or suggests that the diagnosis is fake or that you don’t have their best interests in mind.

“It’s understandable that patients might feel frustrated and upset,” he said. “It’s challenging when somehow a patient doesn’t assume my best intent.”

They might say something like, “You’re trying to make more money” or “you’re a shill for a pharma company.” In that case, you must listen. Patiently explain, “I’m your doctor; I work for you; I’m most interested in you feeling healthy and well.”

Occasionally, you’ll need a thick skin when it comes to inaccurate, controversial, or conspiratorial conversations with patients.
 

Acknowledge Differences

News of an illness may clash with a person’s take on the world. “A cancer diagnosis, for example, may clash with religious beliefs or faith-based ideology about the healthcare system,” said Aaron Fletcher, MD, a board-certified otolaryngologist specializing in head and neck surgery at the Georgia Center for Ear, Nose, Throat, and Facial Plastic Surgery in Atlanta, Georgia.

“If you have a patient who is coming to you with these beliefs, you need to have a lot of empathy, patience, and good communication skills. It’s up to you to break through the initial doubt and do your best to explain things in layman’s terms.”
 

Find Mutual Ground

If your patient still denies their health issues, try to find one thing you can agree on regarding a long-term game plan. “I’ll say, ‘Can we at least agree to discuss this with other family members or people who care about you’?” Dr. Jacoub said.

“I always tell patients that loved ones are welcome to call me so long as they [the patient] give permission. Sometimes, this is all that it takes to get them to accept their health situation.”
 

Seven Ways to Cope With Diagnosis  Denial

This news organization asked David Cutler, MD, a board-certified family medicine physician at Providence Saint John›s Health Center in Santa Monica, California, for tips in helping patients who are having a challenging time accepting their condition:

• Listen Actively. Allow the patient to express their feelings and concerns without judgment. Active listening can help them feel heard and understood, which may open the door to discussing their condition more openly.
• Provide Information. Offer factual information about their medical condition, treatment options, and the potential consequences of denial. Provide resources such as pamphlets, websites, or books that they can review at their own pace.
• Encourage Professional Help. You may want to suggest that your patient seek professional help from a therapist, counselor, or support group. A mental health professional can assist patients in processing their emotions and addressing their denial constructively.
• Involve Trusted Individuals. Enlist the support of trusted friends, family members, or healthcare professionals who can help reinforce the importance of facing their medical condition.
• Respect Autonomy. While it’s essential to encourage the person to accept their diagnosis, ultimately, the decision to get treatment lies with them. Respect their autonomy and avoid pushing them too hard, which could lead to resistance or further denial.
• Be Patient and Persistent. Overcoming denial is often a gradual process. Be patient and persistent in supporting the person, even if progress seems slow.
• Set Boundaries. It’s essential to set boundaries to protect your well-being. While you can offer support and encouragement, you cannot force someone to accept their medical condition. Recognize when your efforts are not being productive and take care of yourself in the process.

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

Informing patients of a dire diagnosis — or even one that will require significant lifestyle changes — is never easy. But what’s even more challenging is when patients don’t accept their medical condition or a future that might include a difficult treatment protocol or even new medications or surgery.

“This is a challenging space to be in because this isn’t an exact science,” said Jack Jacoub, MD, medical director of MemorialCare Cancer Institute at Orange Coast Memorial in Fountain Valley, California. “There’s no formal training to deal with this — experience is your best teacher.”

Ultimately, helping a person reconceptualize what their future looks like is at the heart of every one of these conversations, said Sourav Sengupta, MD, MPH, associate professor of psychiatry and pediatrics at the Jacobs School of Medicine and Biomedical Sciences at the University at Buffalo, Buffalo, New York. “As physicians, we’re charged with helping our patients navigate a difficult and challenging time in their life,” he told this news organization.

“It’s not infrequent that patients are struggling to rethink what it will be like to be a person with an illness that might be chronic and how this will change their life,” he said.

And because denial is commonly the initial way a patient might cope with absorbing news that’s hard to hear, you’ll need to be extremely patient and empathetic.

“The goal is to build trust with this person, including trust in you, the hospital itself, and the entire team treating the patient,” Dr. Jacoub said.

“A diagnosis, especially in my field of oncology, can be scary. Spending time explaining their prognosis is very important. This can’t be a rushed scenario.”

More advice on helping patients who are in denial about their medical condition:
 

Make Sure They Understand What’s Going on

In cardiology, it’s common for patients to be hospitalized when they first learn that they have a disease they must manage for the rest of their life, said Stephanie Saucier, MD, a noninvasive cardiologist and codirector of the Women’s Heart Wellness Program at Hartford Healthcare’s Heart and Vascular Institute.

“Especially after someone has had a heart attack, a stroke, or they had bypass or stents placed, I like to see what their understanding of the disease is,” Dr. Saucier said. “I ask them, ‘What do you understand about what happened to you’. It can get confusing when you’re in the hospital and are told a lot of information in a short period of time.”
 

Share the Data

If a patient remains resistant to the news of a diagnosis, sharing test results can be beneficial. “I’ll often say, ‘here are the scans; this is the path report; this is the bloodwork; this is your biopsy report; these are the things we have’,” Dr. Jacoub said.

“Yes, this is clinical, but it helps to communicate the information you have and do it with data. For example, I might add, ‘Would you like to see some of the things [results, scans, tests] we’re talking about today?’ This also helps establish trust.”
 

Help Them Wrap Their Mind Around a Lifelong Condition

It’s often challenging for patients to accept that what they think is a one-time health issue will affect them for a lifetime. “I use juvenile diabetes as a way to explain this,” Dr. Saucier said. “I ask them what they would do if, say, their child was diagnosed with juvenile diabetes.”

Of course, patients agree that they wouldn’t give a child insulin for only a brief period. They understand that the condition must be treated in the long term. This kind of analogy can help patients understand that they, too, have a disorder requiring lifelong treatment.
 

Be Ready to Respond

Dr. Sengupta says that it’s important to be prepared with an answer if your patient is challenging or suggests that the diagnosis is fake or that you don’t have their best interests in mind.

“It’s understandable that patients might feel frustrated and upset,” he said. “It’s challenging when somehow a patient doesn’t assume my best intent.”

They might say something like, “You’re trying to make more money” or “you’re a shill for a pharma company.” In that case, you must listen. Patiently explain, “I’m your doctor; I work for you; I’m most interested in you feeling healthy and well.”

Occasionally, you’ll need a thick skin when it comes to inaccurate, controversial, or conspiratorial conversations with patients.
 

Acknowledge Differences

News of an illness may clash with a person’s take on the world. “A cancer diagnosis, for example, may clash with religious beliefs or faith-based ideology about the healthcare system,” said Aaron Fletcher, MD, a board-certified otolaryngologist specializing in head and neck surgery at the Georgia Center for Ear, Nose, Throat, and Facial Plastic Surgery in Atlanta, Georgia.

“If you have a patient who is coming to you with these beliefs, you need to have a lot of empathy, patience, and good communication skills. It’s up to you to break through the initial doubt and do your best to explain things in layman’s terms.”
 

Find Mutual Ground

If your patient still denies their health issues, try to find one thing you can agree on regarding a long-term game plan. “I’ll say, ‘Can we at least agree to discuss this with other family members or people who care about you’?” Dr. Jacoub said.

“I always tell patients that loved ones are welcome to call me so long as they [the patient] give permission. Sometimes, this is all that it takes to get them to accept their health situation.”
 

Seven Ways to Cope With Diagnosis  Denial

This news organization asked David Cutler, MD, a board-certified family medicine physician at Providence Saint John›s Health Center in Santa Monica, California, for tips in helping patients who are having a challenging time accepting their condition:

• Listen Actively. Allow the patient to express their feelings and concerns without judgment. Active listening can help them feel heard and understood, which may open the door to discussing their condition more openly.
• Provide Information. Offer factual information about their medical condition, treatment options, and the potential consequences of denial. Provide resources such as pamphlets, websites, or books that they can review at their own pace.
• Encourage Professional Help. You may want to suggest that your patient seek professional help from a therapist, counselor, or support group. A mental health professional can assist patients in processing their emotions and addressing their denial constructively.
• Involve Trusted Individuals. Enlist the support of trusted friends, family members, or healthcare professionals who can help reinforce the importance of facing their medical condition.
• Respect Autonomy. While it’s essential to encourage the person to accept their diagnosis, ultimately, the decision to get treatment lies with them. Respect their autonomy and avoid pushing them too hard, which could lead to resistance or further denial.
• Be Patient and Persistent. Overcoming denial is often a gradual process. Be patient and persistent in supporting the person, even if progress seems slow.
• Set Boundaries. It’s essential to set boundaries to protect your well-being. While you can offer support and encouragement, you cannot force someone to accept their medical condition. Recognize when your efforts are not being productive and take care of yourself in the process.

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

Informing patients of a dire diagnosis — or even one that will require significant lifestyle changes — is never easy. But what’s even more challenging is when patients don’t accept their medical condition or a future that might include a difficult treatment protocol or even new medications or surgery.

“This is a challenging space to be in because this isn’t an exact science,” said Jack Jacoub, MD, medical director of MemorialCare Cancer Institute at Orange Coast Memorial in Fountain Valley, California. “There’s no formal training to deal with this — experience is your best teacher.”

Ultimately, helping a person reconceptualize what their future looks like is at the heart of every one of these conversations, said Sourav Sengupta, MD, MPH, associate professor of psychiatry and pediatrics at the Jacobs School of Medicine and Biomedical Sciences at the University at Buffalo, Buffalo, New York. “As physicians, we’re charged with helping our patients navigate a difficult and challenging time in their life,” he told this news organization.

“It’s not infrequent that patients are struggling to rethink what it will be like to be a person with an illness that might be chronic and how this will change their life,” he said.

And because denial is commonly the initial way a patient might cope with absorbing news that’s hard to hear, you’ll need to be extremely patient and empathetic.

“The goal is to build trust with this person, including trust in you, the hospital itself, and the entire team treating the patient,” Dr. Jacoub said.

“A diagnosis, especially in my field of oncology, can be scary. Spending time explaining their prognosis is very important. This can’t be a rushed scenario.”

More advice on helping patients who are in denial about their medical condition:
 

Make Sure They Understand What’s Going on

In cardiology, it’s common for patients to be hospitalized when they first learn that they have a disease they must manage for the rest of their life, said Stephanie Saucier, MD, a noninvasive cardiologist and codirector of the Women’s Heart Wellness Program at Hartford Healthcare’s Heart and Vascular Institute.

“Especially after someone has had a heart attack, a stroke, or they had bypass or stents placed, I like to see what their understanding of the disease is,” Dr. Saucier said. “I ask them, ‘What do you understand about what happened to you’. It can get confusing when you’re in the hospital and are told a lot of information in a short period of time.”
 

Share the Data

If a patient remains resistant to the news of a diagnosis, sharing test results can be beneficial. “I’ll often say, ‘here are the scans; this is the path report; this is the bloodwork; this is your biopsy report; these are the things we have’,” Dr. Jacoub said.

“Yes, this is clinical, but it helps to communicate the information you have and do it with data. For example, I might add, ‘Would you like to see some of the things [results, scans, tests] we’re talking about today?’ This also helps establish trust.”
 

Help Them Wrap Their Mind Around a Lifelong Condition

It’s often challenging for patients to accept that what they think is a one-time health issue will affect them for a lifetime. “I use juvenile diabetes as a way to explain this,” Dr. Saucier said. “I ask them what they would do if, say, their child was diagnosed with juvenile diabetes.”

Of course, patients agree that they wouldn’t give a child insulin for only a brief period. They understand that the condition must be treated in the long term. This kind of analogy can help patients understand that they, too, have a disorder requiring lifelong treatment.
 

Be Ready to Respond

Dr. Sengupta says that it’s important to be prepared with an answer if your patient is challenging or suggests that the diagnosis is fake or that you don’t have their best interests in mind.

“It’s understandable that patients might feel frustrated and upset,” he said. “It’s challenging when somehow a patient doesn’t assume my best intent.”

They might say something like, “You’re trying to make more money” or “you’re a shill for a pharma company.” In that case, you must listen. Patiently explain, “I’m your doctor; I work for you; I’m most interested in you feeling healthy and well.”

Occasionally, you’ll need a thick skin when it comes to inaccurate, controversial, or conspiratorial conversations with patients.
 

Acknowledge Differences

News of an illness may clash with a person’s take on the world. “A cancer diagnosis, for example, may clash with religious beliefs or faith-based ideology about the healthcare system,” said Aaron Fletcher, MD, a board-certified otolaryngologist specializing in head and neck surgery at the Georgia Center for Ear, Nose, Throat, and Facial Plastic Surgery in Atlanta, Georgia.

“If you have a patient who is coming to you with these beliefs, you need to have a lot of empathy, patience, and good communication skills. It’s up to you to break through the initial doubt and do your best to explain things in layman’s terms.”
 

Find Mutual Ground

If your patient still denies their health issues, try to find one thing you can agree on regarding a long-term game plan. “I’ll say, ‘Can we at least agree to discuss this with other family members or people who care about you’?” Dr. Jacoub said.

“I always tell patients that loved ones are welcome to call me so long as they [the patient] give permission. Sometimes, this is all that it takes to get them to accept their health situation.”
 

Seven Ways to Cope With Diagnosis  Denial

This news organization asked David Cutler, MD, a board-certified family medicine physician at Providence Saint John›s Health Center in Santa Monica, California, for tips in helping patients who are having a challenging time accepting their condition:

• Listen Actively. Allow the patient to express their feelings and concerns without judgment. Active listening can help them feel heard and understood, which may open the door to discussing their condition more openly.
• Provide Information. Offer factual information about their medical condition, treatment options, and the potential consequences of denial. Provide resources such as pamphlets, websites, or books that they can review at their own pace.
• Encourage Professional Help. You may want to suggest that your patient seek professional help from a therapist, counselor, or support group. A mental health professional can assist patients in processing their emotions and addressing their denial constructively.
• Involve Trusted Individuals. Enlist the support of trusted friends, family members, or healthcare professionals who can help reinforce the importance of facing their medical condition.
• Respect Autonomy. While it’s essential to encourage the person to accept their diagnosis, ultimately, the decision to get treatment lies with them. Respect their autonomy and avoid pushing them too hard, which could lead to resistance or further denial.
• Be Patient and Persistent. Overcoming denial is often a gradual process. Be patient and persistent in supporting the person, even if progress seems slow.
• Set Boundaries. It’s essential to set boundaries to protect your well-being. While you can offer support and encouragement, you cannot force someone to accept their medical condition. Recognize when your efforts are not being productive and take care of yourself in the process.

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

A new study raises a cautionary note on time-restricted eating (TRE), a type of intermittent fasting that is gaining popularity.

The observational analysis of over 20,000 US adults showed that those who limited their eating to a period of less than 8 hours per day had a higher risk for cardiovascular mortality compared with peers who ate across the typical 12-16 hours per day. This was the case in the overall sample and in those with cardiovascular disease (CVD) or cancer.

Lead author Victor Wenze Zhong, PhD, cautioned that the findings “require replication and we cannot demonstrate 8-hour TRE causes cardiovascular death in this observational study.

“However, it’s important for patients, particularly those with existing heart conditions or cancer, to be aware of the positive association between an 8-hour eating window and cardiovascular death,” Dr. Zhong, professor and chair, Department of Epidemiology and Biostatistics, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China, told this news organization. 

The results (Abstract P192) were presented March 18 at the American Heart Association (AHA) Epidemiology and Prevention/Lifestyle and Cardiometabolic Health Scientific Sessions 2024.
 

‘Provocative’ Results 

Short-term randomized controlled trials have suggested that 8-hour TRE may improve cardiometabolic risk profiles, but the potential long-term effects of this eating pattern are unknown. 

The observation that TRE may have short-term benefits but long-term adverse effects is “interesting and provocative” and needs further study, Christopher D. Gardner, PhD, professor of medicine at Stanford University in California, who wasn’t involved in the study, said in a conference statement, and he agreed that much more research is needed. 

The researchers analyzed data on dietary patterns for 20,078 adults (mean age, 48 years; 50% men; 73% non-Hispanic White) who participated in the 2003-2018 National Health and Nutrition Examination Surveys (NHANES). All of them completed two 24-hour dietary recall questionnaires within the first year of enrollment. Deaths through the end of 2019 were determined via the National Death Index.

During a median follow-up of 8 years, there were 2797 deaths due to any cause, including 840 CV deaths and 643 cancer deaths. 

In the overall sample, compared with an eating duration of 12-16 hours, 8-hour TRE was significantly associated with an increased risk for CV mortality (hazard ratio [HR], 1.91; 95% CI, 1.20-3.03).

This association was also observed in adults with CVD (HR, 2.07; 95% CI, 1.14-3.78) and adults with cancer (HR, 3.04; 95% CI, 1.44-6.41). 

Other eating durations were not associated with CV mortality, except for eating duration of 8 to less than 10 hours in people with CVD (HR, 1.66; 95% CI, 1.03-2.67). 

No significant associations were found between eating duration and all-cause or cancer mortality in the overall sample and CVD/cancer subsamples, except that eating duration of more than 16 hours was associated with a lower risk for cancer mortality in people with cancer (HR, 0.47; 95% CI, 0.23-0.95).
 

Quality More Important Than Timing 

Dr. Zhong noted that the study doesn’t address the underlying mechanisms driving the observed association between 8-hour TRE and CV death. 

“However, we did observe that people who restricted eating to a period less than 8 hours per day had less lean muscle mass compared with those with typical eating duration of 12-16 hours. Loss of lean body mass has been linked to higher risk of cardiovascular mortality,” Dr. Zhong said. 

“Based on the evidence as of now, focusing on what people eat appears to be more important than focusing on the time when they eat. There are certain dietary approaches with compelling health benefits to choose, such as DASH diet and Mediterranean diet,” Dr. Zhong said.

Intermittent fasting is “certainly an interesting concept and one on which the potential mechanisms underlying the improvements in short outcome studies and preclinical studies in animals are strongly being pursued,” Sean P. Heffron, MD, cardiologist at the Center for the Prevention of Cardiovascular Disease at NYU Langone Heart, New York, who wasn’t involved in the study, told this news organization. 

Dr. Heffron expressed skepticism about the study results calling them “far from complete” and noted that data on diet was based on only 2-day diet records without correction for confounding variables. 

Dr. Heffron also noted that the restricted diet group has more smokers and more men. “I would “strongly anticipate that once appropriate corrections are made, the findings will no longer persist in statistical significance,” Dr. Heffron said.

He emphasized the need for more rigorous research before making clinical recommendations. When patients ask about intermittent fasting, Dr. Heffron said he tells them, “If it works for you, that’s fine,” but he doesn’t provide a recommendation for or against it. 

Funding for the study was provided by the National Key Research and Development Program of China and the National Science Foundation of China. Zhong, Dr. Heffron and Dr. Gardner have no relevant disclosures.
 

A version of this article appeared on Medscape.com.

A new study raises a cautionary note on time-restricted eating (TRE), a type of intermittent fasting that is gaining popularity.

The observational analysis of over 20,000 US adults showed that those who limited their eating to a period of less than 8 hours per day had a higher risk for cardiovascular mortality compared with peers who ate across the typical 12-16 hours per day. This was the case in the overall sample and in those with cardiovascular disease (CVD) or cancer.

Lead author Victor Wenze Zhong, PhD, cautioned that the findings “require replication and we cannot demonstrate 8-hour TRE causes cardiovascular death in this observational study.

“However, it’s important for patients, particularly those with existing heart conditions or cancer, to be aware of the positive association between an 8-hour eating window and cardiovascular death,” Dr. Zhong, professor and chair, Department of Epidemiology and Biostatistics, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China, told this news organization. 

The results (Abstract P192) were presented March 18 at the American Heart Association (AHA) Epidemiology and Prevention/Lifestyle and Cardiometabolic Health Scientific Sessions 2024.
 

‘Provocative’ Results 

Short-term randomized controlled trials have suggested that 8-hour TRE may improve cardiometabolic risk profiles, but the potential long-term effects of this eating pattern are unknown. 

The observation that TRE may have short-term benefits but long-term adverse effects is “interesting and provocative” and needs further study, Christopher D. Gardner, PhD, professor of medicine at Stanford University in California, who wasn’t involved in the study, said in a conference statement, and he agreed that much more research is needed. 

The researchers analyzed data on dietary patterns for 20,078 adults (mean age, 48 years; 50% men; 73% non-Hispanic White) who participated in the 2003-2018 National Health and Nutrition Examination Surveys (NHANES). All of them completed two 24-hour dietary recall questionnaires within the first year of enrollment. Deaths through the end of 2019 were determined via the National Death Index.

During a median follow-up of 8 years, there were 2797 deaths due to any cause, including 840 CV deaths and 643 cancer deaths. 

In the overall sample, compared with an eating duration of 12-16 hours, 8-hour TRE was significantly associated with an increased risk for CV mortality (hazard ratio [HR], 1.91; 95% CI, 1.20-3.03).

This association was also observed in adults with CVD (HR, 2.07; 95% CI, 1.14-3.78) and adults with cancer (HR, 3.04; 95% CI, 1.44-6.41). 

Other eating durations were not associated with CV mortality, except for eating duration of 8 to less than 10 hours in people with CVD (HR, 1.66; 95% CI, 1.03-2.67). 

No significant associations were found between eating duration and all-cause or cancer mortality in the overall sample and CVD/cancer subsamples, except that eating duration of more than 16 hours was associated with a lower risk for cancer mortality in people with cancer (HR, 0.47; 95% CI, 0.23-0.95).
 

Quality More Important Than Timing 

Dr. Zhong noted that the study doesn’t address the underlying mechanisms driving the observed association between 8-hour TRE and CV death. 

“However, we did observe that people who restricted eating to a period less than 8 hours per day had less lean muscle mass compared with those with typical eating duration of 12-16 hours. Loss of lean body mass has been linked to higher risk of cardiovascular mortality,” Dr. Zhong said. 

“Based on the evidence as of now, focusing on what people eat appears to be more important than focusing on the time when they eat. There are certain dietary approaches with compelling health benefits to choose, such as DASH diet and Mediterranean diet,” Dr. Zhong said.

Intermittent fasting is “certainly an interesting concept and one on which the potential mechanisms underlying the improvements in short outcome studies and preclinical studies in animals are strongly being pursued,” Sean P. Heffron, MD, cardiologist at the Center for the Prevention of Cardiovascular Disease at NYU Langone Heart, New York, who wasn’t involved in the study, told this news organization. 

Dr. Heffron expressed skepticism about the study results calling them “far from complete” and noted that data on diet was based on only 2-day diet records without correction for confounding variables. 

Dr. Heffron also noted that the restricted diet group has more smokers and more men. “I would “strongly anticipate that once appropriate corrections are made, the findings will no longer persist in statistical significance,” Dr. Heffron said.

He emphasized the need for more rigorous research before making clinical recommendations. When patients ask about intermittent fasting, Dr. Heffron said he tells them, “If it works for you, that’s fine,” but he doesn’t provide a recommendation for or against it. 

Funding for the study was provided by the National Key Research and Development Program of China and the National Science Foundation of China. Zhong, Dr. Heffron and Dr. Gardner have no relevant disclosures.
 

A version of this article appeared on Medscape.com.

A new study raises a cautionary note on time-restricted eating (TRE), a type of intermittent fasting that is gaining popularity.

The observational analysis of over 20,000 US adults showed that those who limited their eating to a period of less than 8 hours per day had a higher risk for cardiovascular mortality compared with peers who ate across the typical 12-16 hours per day. This was the case in the overall sample and in those with cardiovascular disease (CVD) or cancer.

Lead author Victor Wenze Zhong, PhD, cautioned that the findings “require replication and we cannot demonstrate 8-hour TRE causes cardiovascular death in this observational study.

“However, it’s important for patients, particularly those with existing heart conditions or cancer, to be aware of the positive association between an 8-hour eating window and cardiovascular death,” Dr. Zhong, professor and chair, Department of Epidemiology and Biostatistics, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China, told this news organization. 

The results (Abstract P192) were presented March 18 at the American Heart Association (AHA) Epidemiology and Prevention/Lifestyle and Cardiometabolic Health Scientific Sessions 2024.
 

‘Provocative’ Results 

Short-term randomized controlled trials have suggested that 8-hour TRE may improve cardiometabolic risk profiles, but the potential long-term effects of this eating pattern are unknown. 

The observation that TRE may have short-term benefits but long-term adverse effects is “interesting and provocative” and needs further study, Christopher D. Gardner, PhD, professor of medicine at Stanford University in California, who wasn’t involved in the study, said in a conference statement, and he agreed that much more research is needed. 

The researchers analyzed data on dietary patterns for 20,078 adults (mean age, 48 years; 50% men; 73% non-Hispanic White) who participated in the 2003-2018 National Health and Nutrition Examination Surveys (NHANES). All of them completed two 24-hour dietary recall questionnaires within the first year of enrollment. Deaths through the end of 2019 were determined via the National Death Index.

During a median follow-up of 8 years, there were 2797 deaths due to any cause, including 840 CV deaths and 643 cancer deaths. 

In the overall sample, compared with an eating duration of 12-16 hours, 8-hour TRE was significantly associated with an increased risk for CV mortality (hazard ratio [HR], 1.91; 95% CI, 1.20-3.03).

This association was also observed in adults with CVD (HR, 2.07; 95% CI, 1.14-3.78) and adults with cancer (HR, 3.04; 95% CI, 1.44-6.41). 

Other eating durations were not associated with CV mortality, except for eating duration of 8 to less than 10 hours in people with CVD (HR, 1.66; 95% CI, 1.03-2.67). 

No significant associations were found between eating duration and all-cause or cancer mortality in the overall sample and CVD/cancer subsamples, except that eating duration of more than 16 hours was associated with a lower risk for cancer mortality in people with cancer (HR, 0.47; 95% CI, 0.23-0.95).
 

Quality More Important Than Timing 

Dr. Zhong noted that the study doesn’t address the underlying mechanisms driving the observed association between 8-hour TRE and CV death. 

“However, we did observe that people who restricted eating to a period less than 8 hours per day had less lean muscle mass compared with those with typical eating duration of 12-16 hours. Loss of lean body mass has been linked to higher risk of cardiovascular mortality,” Dr. Zhong said. 

“Based on the evidence as of now, focusing on what people eat appears to be more important than focusing on the time when they eat. There are certain dietary approaches with compelling health benefits to choose, such as DASH diet and Mediterranean diet,” Dr. Zhong said.

Intermittent fasting is “certainly an interesting concept and one on which the potential mechanisms underlying the improvements in short outcome studies and preclinical studies in animals are strongly being pursued,” Sean P. Heffron, MD, cardiologist at the Center for the Prevention of Cardiovascular Disease at NYU Langone Heart, New York, who wasn’t involved in the study, told this news organization. 

Dr. Heffron expressed skepticism about the study results calling them “far from complete” and noted that data on diet was based on only 2-day diet records without correction for confounding variables. 

Dr. Heffron also noted that the restricted diet group has more smokers and more men. “I would “strongly anticipate that once appropriate corrections are made, the findings will no longer persist in statistical significance,” Dr. Heffron said.

He emphasized the need for more rigorous research before making clinical recommendations. When patients ask about intermittent fasting, Dr. Heffron said he tells them, “If it works for you, that’s fine,” but he doesn’t provide a recommendation for or against it. 

Funding for the study was provided by the National Key Research and Development Program of China and the National Science Foundation of China. Zhong, Dr. Heffron and Dr. Gardner have no relevant disclosures.
 

A version of this article appeared on Medscape.com.

Widely considered the father of cancer immunotherapy, Steven A. Rosenberg MD, PhD, FAACR, has spent nearly 50 years analyzing the link between patients’ immune reaction and their cancer response.

His pioneering research established interleukin-2 (IL-2) as the first U.S. Food and Drug Administration–approved cancer immunotherapy in 1992.

To recognize his trailblazing work and other achievements, the American Association for Cancer Research (AACR) will award Dr. Rosenberg with the 2024 AACR Award for Lifetime Achievement in Cancer Research at its annual meeting in April.

Dr. Rosenberg: I grew up in the Bronx. My parents both immigrated to the United States from Poland as teenagers.


As a young boy, did you always want to become a doctor?

Dr. Rosenberg: I think some defining moments on why I decided to go into medicine occurred when I was 6 or 7 years old. The second world war was over, and many of the horrors of the Holocaust became apparent to me. I was brought up as an Orthodox Jew. My parents were quite religious, and I remember postcards coming in one after another about relatives that had died in the death camps. That had a profound influence on me.


How did that experience impact your aspirations?

Dr. Rosenberg: It was an example to me of how evil certain people and groups can be toward one another. I decided at that point, that I wanted to do something good for people, and medicine seemed the most likely way to do that. But also, I was developing a broad scientific interest. I ended up at the Bronx High School of Science and knew that I not only wanted to practice the medicine of today, but I wanted to play a role in helping develop the medicine.


What led to your interest in cancer treatment?

Dr. Rosenberg: Well, as a medical student and resident, it became clear that the field of cancer needed major improvement. We had three major ways to treat cancer: surgery, radiation therapy, and chemotherapy. That could cure about half of the people [who] had cancer. But despite the best application of those three specialties, there were over 600,000 deaths from cancer each year in the United States alone. It was clear to me that new approaches were needed, and I became very interested in taking advantage of the body’s immune system as a source of information to try to make progress.


Were there patients who inspired your research?

Dr. Rosenberg: There were two patients that I saw early in my career that impressed me a great deal. One was a patient that I saw when working in the emergency ward as a resident. A patient came in with right upper quadrant pain that looked like a gallbladder attack. That’s what it was. But when I went through his chart, I saw that he had been at that hospital 12 years earlier with a metastatic gastric cancer. The surgeons had operated. They saw tumor had spread to the liver and could not be removed. They closed the belly, not expecting him to survive. Yet he kept showing up for follow-up visits.
Here he was 12 years later. When I helped operate to take out his gallbladder, there was no evidence of any cancer. The cancer had disappeared in the absence of any external treatment. One of the rarest events in medicine, the spontaneous regression of a cancer. Somehow his body had learned how to destroy the tumor.
 

Was the second patient’s case as impressive?

Dr. Rosenberg: This patient had received a kidney transplant from a gentleman who died in an auto accident. [The donor’s] kidney contained a cancer deposit, a kidney cancer, unbeknownst to the transplant surgeons. [When the kidney was transplanted], the recipient developed widespread metastatic kidney cancer.
[The recipient] was on immunosuppressive drugs, and so the drugs had to be stopped. [When the immunosuppressive drugs were stopped], the patient’s body rejected the kidney and his cancer disappeared.
That showed me that, in fact, if you could stimulate a strong enough immune reaction, in this case, an [allogeneic] reaction, against foreign tissues from a different individual, that you could make large vascularized, invasive cancers disappear based on immune reactivities. Those were clues that led me toward studying the immune system’s impact on cancer.


From there, how did your work evolve?

Dr. Rosenberg: As chief of the surgery branch at NIH, I began doing research. It was very difficult to manipulate immune cells in the laboratory. They wouldn’t stay alive. But I tried to study immune reactions in patients with cancer to see if there was such a thing as an immune reaction against the cancer. There was no such thing known at the time. There were no cancer antigens and no known immune reactions against the disease in the human.


Around this time, investigators were publishing studies about interleukin-2 (IL-2), or white blood cells known as leukocytes. How did interleukin-2 further your research?

Dr. Rosenberg: The advent of interleukin-2 enabled scientists to grow lymphocytes outside the body. [This] enabled us to grow t-lymphocytes, which are some of the major warriors of the immune system against foreign tissue. After [studying] 66 patients in which we studied interleukin-2 and cells that would develop from it, we finally saw a disappearance of melanoma in a patient that received interleukin-2. And we went on to treat hundreds of patients with that hormone, interleukin-2. In fact, interleukin-2 became the first immunotherapy ever approved by the Food and Drug Administration for the treatment of cancer in humans.

Dr. Rosenberg: [It] led to studies of the mechanism of action of interleukin-2 and to do that, we identified a kind of cell called a tumor infiltrating lymphocyte. What better place, intuitively to look for cells doing battle against the cancer than within the cancer itself?
In 1988, we demonstrated for the first time that transfer of lymphocytes with antitumor activity could cause the regression of melanoma. This was a living drug obtained from melanoma deposits that could be grown outside the body and then readministered to the patient under suitable conditions. Interestingly, [in February the FDA approved that drug as treatment for patients with melanoma]. A company developed it to the point where in multi-institutional studies, they reproduced our results.
And we’ve now emphasized the value of using T cell therapy, t cell transfer, for the treatment of patients with the common solid cancers, the cancers that start anywhere from the colon up through the intestine, the stomach, the pancreas, and the esophagus. Solid tumors such as ovarian cancer, uterine cancer and so on, are also potentially susceptible to this T cell therapy.
We’ve published several papers showing in isolated patients that you could cause major regressions, if not complete regressions, of these solid cancers in the liver, in the breast, the cervix, the colon. That’s a major aspect of what we’re doing now.
I think immunotherapy has come to be recognized as a major fourth arm that can be used to attack cancers, adding to surgery, radiation, and chemotherapy.


What guidance would you have for other physician-investigators or young doctors who want to follow in your path?

Dr. Rosenberg: You have to have a broad base of knowledge. You have to be willing to immerse yourself in a problem so that your mind is working on it when you’re doing things where you can only think. [When] you’re taking a shower, [or] waiting at a red light, your mind is working on this problem because you’re immersed in trying to understand it.
You need to have a laser focus on the goals that you have and not get sidetracked by issues that may be interesting but not directly related to the goals that you’re attempting to achieve.

Widely considered the father of cancer immunotherapy, Steven A. Rosenberg MD, PhD, FAACR, has spent nearly 50 years analyzing the link between patients’ immune reaction and their cancer response.

His pioneering research established interleukin-2 (IL-2) as the first U.S. Food and Drug Administration–approved cancer immunotherapy in 1992.

To recognize his trailblazing work and other achievements, the American Association for Cancer Research (AACR) will award Dr. Rosenberg with the 2024 AACR Award for Lifetime Achievement in Cancer Research at its annual meeting in April.

Dr. Rosenberg: I grew up in the Bronx. My parents both immigrated to the United States from Poland as teenagers.


As a young boy, did you always want to become a doctor?

Dr. Rosenberg: I think some defining moments on why I decided to go into medicine occurred when I was 6 or 7 years old. The second world war was over, and many of the horrors of the Holocaust became apparent to me. I was brought up as an Orthodox Jew. My parents were quite religious, and I remember postcards coming in one after another about relatives that had died in the death camps. That had a profound influence on me.


How did that experience impact your aspirations?

Dr. Rosenberg: It was an example to me of how evil certain people and groups can be toward one another. I decided at that point, that I wanted to do something good for people, and medicine seemed the most likely way to do that. But also, I was developing a broad scientific interest. I ended up at the Bronx High School of Science and knew that I not only wanted to practice the medicine of today, but I wanted to play a role in helping develop the medicine.


What led to your interest in cancer treatment?

Dr. Rosenberg: Well, as a medical student and resident, it became clear that the field of cancer needed major improvement. We had three major ways to treat cancer: surgery, radiation therapy, and chemotherapy. That could cure about half of the people [who] had cancer. But despite the best application of those three specialties, there were over 600,000 deaths from cancer each year in the United States alone. It was clear to me that new approaches were needed, and I became very interested in taking advantage of the body’s immune system as a source of information to try to make progress.


Were there patients who inspired your research?

Dr. Rosenberg: There were two patients that I saw early in my career that impressed me a great deal. One was a patient that I saw when working in the emergency ward as a resident. A patient came in with right upper quadrant pain that looked like a gallbladder attack. That’s what it was. But when I went through his chart, I saw that he had been at that hospital 12 years earlier with a metastatic gastric cancer. The surgeons had operated. They saw tumor had spread to the liver and could not be removed. They closed the belly, not expecting him to survive. Yet he kept showing up for follow-up visits.
Here he was 12 years later. When I helped operate to take out his gallbladder, there was no evidence of any cancer. The cancer had disappeared in the absence of any external treatment. One of the rarest events in medicine, the spontaneous regression of a cancer. Somehow his body had learned how to destroy the tumor.
 

Was the second patient’s case as impressive?

Dr. Rosenberg: This patient had received a kidney transplant from a gentleman who died in an auto accident. [The donor’s] kidney contained a cancer deposit, a kidney cancer, unbeknownst to the transplant surgeons. [When the kidney was transplanted], the recipient developed widespread metastatic kidney cancer.
[The recipient] was on immunosuppressive drugs, and so the drugs had to be stopped. [When the immunosuppressive drugs were stopped], the patient’s body rejected the kidney and his cancer disappeared.
That showed me that, in fact, if you could stimulate a strong enough immune reaction, in this case, an [allogeneic] reaction, against foreign tissues from a different individual, that you could make large vascularized, invasive cancers disappear based on immune reactivities. Those were clues that led me toward studying the immune system’s impact on cancer.


From there, how did your work evolve?

Dr. Rosenberg: As chief of the surgery branch at NIH, I began doing research. It was very difficult to manipulate immune cells in the laboratory. They wouldn’t stay alive. But I tried to study immune reactions in patients with cancer to see if there was such a thing as an immune reaction against the cancer. There was no such thing known at the time. There were no cancer antigens and no known immune reactions against the disease in the human.


Around this time, investigators were publishing studies about interleukin-2 (IL-2), or white blood cells known as leukocytes. How did interleukin-2 further your research?

Dr. Rosenberg: The advent of interleukin-2 enabled scientists to grow lymphocytes outside the body. [This] enabled us to grow t-lymphocytes, which are some of the major warriors of the immune system against foreign tissue. After [studying] 66 patients in which we studied interleukin-2 and cells that would develop from it, we finally saw a disappearance of melanoma in a patient that received interleukin-2. And we went on to treat hundreds of patients with that hormone, interleukin-2. In fact, interleukin-2 became the first immunotherapy ever approved by the Food and Drug Administration for the treatment of cancer in humans.

Dr. Rosenberg: [It] led to studies of the mechanism of action of interleukin-2 and to do that, we identified a kind of cell called a tumor infiltrating lymphocyte. What better place, intuitively to look for cells doing battle against the cancer than within the cancer itself?
In 1988, we demonstrated for the first time that transfer of lymphocytes with antitumor activity could cause the regression of melanoma. This was a living drug obtained from melanoma deposits that could be grown outside the body and then readministered to the patient under suitable conditions. Interestingly, [in February the FDA approved that drug as treatment for patients with melanoma]. A company developed it to the point where in multi-institutional studies, they reproduced our results.
And we’ve now emphasized the value of using T cell therapy, t cell transfer, for the treatment of patients with the common solid cancers, the cancers that start anywhere from the colon up through the intestine, the stomach, the pancreas, and the esophagus. Solid tumors such as ovarian cancer, uterine cancer and so on, are also potentially susceptible to this T cell therapy.
We’ve published several papers showing in isolated patients that you could cause major regressions, if not complete regressions, of these solid cancers in the liver, in the breast, the cervix, the colon. That’s a major aspect of what we’re doing now.
I think immunotherapy has come to be recognized as a major fourth arm that can be used to attack cancers, adding to surgery, radiation, and chemotherapy.


What guidance would you have for other physician-investigators or young doctors who want to follow in your path?

Dr. Rosenberg: You have to have a broad base of knowledge. You have to be willing to immerse yourself in a problem so that your mind is working on it when you’re doing things where you can only think. [When] you’re taking a shower, [or] waiting at a red light, your mind is working on this problem because you’re immersed in trying to understand it.
You need to have a laser focus on the goals that you have and not get sidetracked by issues that may be interesting but not directly related to the goals that you’re attempting to achieve.

Widely considered the father of cancer immunotherapy, Steven A. Rosenberg MD, PhD, FAACR, has spent nearly 50 years analyzing the link between patients’ immune reaction and their cancer response.

His pioneering research established interleukin-2 (IL-2) as the first U.S. Food and Drug Administration–approved cancer immunotherapy in 1992.

To recognize his trailblazing work and other achievements, the American Association for Cancer Research (AACR) will award Dr. Rosenberg with the 2024 AACR Award for Lifetime Achievement in Cancer Research at its annual meeting in April.

Dr. Rosenberg: I grew up in the Bronx. My parents both immigrated to the United States from Poland as teenagers.


As a young boy, did you always want to become a doctor?

Dr. Rosenberg: I think some defining moments on why I decided to go into medicine occurred when I was 6 or 7 years old. The second world war was over, and many of the horrors of the Holocaust became apparent to me. I was brought up as an Orthodox Jew. My parents were quite religious, and I remember postcards coming in one after another about relatives that had died in the death camps. That had a profound influence on me.


How did that experience impact your aspirations?

Dr. Rosenberg: It was an example to me of how evil certain people and groups can be toward one another. I decided at that point, that I wanted to do something good for people, and medicine seemed the most likely way to do that. But also, I was developing a broad scientific interest. I ended up at the Bronx High School of Science and knew that I not only wanted to practice the medicine of today, but I wanted to play a role in helping develop the medicine.


What led to your interest in cancer treatment?

Dr. Rosenberg: Well, as a medical student and resident, it became clear that the field of cancer needed major improvement. We had three major ways to treat cancer: surgery, radiation therapy, and chemotherapy. That could cure about half of the people [who] had cancer. But despite the best application of those three specialties, there were over 600,000 deaths from cancer each year in the United States alone. It was clear to me that new approaches were needed, and I became very interested in taking advantage of the body’s immune system as a source of information to try to make progress.


Were there patients who inspired your research?

Dr. Rosenberg: There were two patients that I saw early in my career that impressed me a great deal. One was a patient that I saw when working in the emergency ward as a resident. A patient came in with right upper quadrant pain that looked like a gallbladder attack. That’s what it was. But when I went through his chart, I saw that he had been at that hospital 12 years earlier with a metastatic gastric cancer. The surgeons had operated. They saw tumor had spread to the liver and could not be removed. They closed the belly, not expecting him to survive. Yet he kept showing up for follow-up visits.
Here he was 12 years later. When I helped operate to take out his gallbladder, there was no evidence of any cancer. The cancer had disappeared in the absence of any external treatment. One of the rarest events in medicine, the spontaneous regression of a cancer. Somehow his body had learned how to destroy the tumor.
 

Was the second patient’s case as impressive?

Dr. Rosenberg: This patient had received a kidney transplant from a gentleman who died in an auto accident. [The donor’s] kidney contained a cancer deposit, a kidney cancer, unbeknownst to the transplant surgeons. [When the kidney was transplanted], the recipient developed widespread metastatic kidney cancer.
[The recipient] was on immunosuppressive drugs, and so the drugs had to be stopped. [When the immunosuppressive drugs were stopped], the patient’s body rejected the kidney and his cancer disappeared.
That showed me that, in fact, if you could stimulate a strong enough immune reaction, in this case, an [allogeneic] reaction, against foreign tissues from a different individual, that you could make large vascularized, invasive cancers disappear based on immune reactivities. Those were clues that led me toward studying the immune system’s impact on cancer.


From there, how did your work evolve?

Dr. Rosenberg: As chief of the surgery branch at NIH, I began doing research. It was very difficult to manipulate immune cells in the laboratory. They wouldn’t stay alive. But I tried to study immune reactions in patients with cancer to see if there was such a thing as an immune reaction against the cancer. There was no such thing known at the time. There were no cancer antigens and no known immune reactions against the disease in the human.


Around this time, investigators were publishing studies about interleukin-2 (IL-2), or white blood cells known as leukocytes. How did interleukin-2 further your research?

Dr. Rosenberg: The advent of interleukin-2 enabled scientists to grow lymphocytes outside the body. [This] enabled us to grow t-lymphocytes, which are some of the major warriors of the immune system against foreign tissue. After [studying] 66 patients in which we studied interleukin-2 and cells that would develop from it, we finally saw a disappearance of melanoma in a patient that received interleukin-2. And we went on to treat hundreds of patients with that hormone, interleukin-2. In fact, interleukin-2 became the first immunotherapy ever approved by the Food and Drug Administration for the treatment of cancer in humans.

Dr. Rosenberg: [It] led to studies of the mechanism of action of interleukin-2 and to do that, we identified a kind of cell called a tumor infiltrating lymphocyte. What better place, intuitively to look for cells doing battle against the cancer than within the cancer itself?
In 1988, we demonstrated for the first time that transfer of lymphocytes with antitumor activity could cause the regression of melanoma. This was a living drug obtained from melanoma deposits that could be grown outside the body and then readministered to the patient under suitable conditions. Interestingly, [in February the FDA approved that drug as treatment for patients with melanoma]. A company developed it to the point where in multi-institutional studies, they reproduced our results.
And we’ve now emphasized the value of using T cell therapy, t cell transfer, for the treatment of patients with the common solid cancers, the cancers that start anywhere from the colon up through the intestine, the stomach, the pancreas, and the esophagus. Solid tumors such as ovarian cancer, uterine cancer and so on, are also potentially susceptible to this T cell therapy.
We’ve published several papers showing in isolated patients that you could cause major regressions, if not complete regressions, of these solid cancers in the liver, in the breast, the cervix, the colon. That’s a major aspect of what we’re doing now.
I think immunotherapy has come to be recognized as a major fourth arm that can be used to attack cancers, adding to surgery, radiation, and chemotherapy.


What guidance would you have for other physician-investigators or young doctors who want to follow in your path?

Dr. Rosenberg: You have to have a broad base of knowledge. You have to be willing to immerse yourself in a problem so that your mind is working on it when you’re doing things where you can only think. [When] you’re taking a shower, [or] waiting at a red light, your mind is working on this problem because you’re immersed in trying to understand it.
You need to have a laser focus on the goals that you have and not get sidetracked by issues that may be interesting but not directly related to the goals that you’re attempting to achieve.

TOPLINE:

Depression is linked to a significantly increased risk for cardiovascular disease (CVD), particularly in women, new data from a large retrospective cohort study show. Researchers suggest that screening and treating patients for depression may lead to a decreased incidence of CVD.

METHODOLOGY:

• Researchers analyzed health insurance claims from more than 4 million Japanese patients filed between 2005 and 2022.
• Participants were 18-75 (median age, 44) without a history of CVD or stroke, heart failure, or atrial fibrillation.
• Investigators followed participants for a mean period of 2.5-3.5 years to observe the number of CVD events in those who had a diagnosis of depression.
• During the follow-up period, there were 119,000 CVD events in men (14 per 10,000 person-years) and 61,800 CVD events in women (111 per 10,000 person-years).

TAKEAWAY:

• Compared with women without depression, those with depression had a 64% higher risk for CVD (hazard ratio [HR], 1.64), while men with depression had a 39% higher risk for CVD vs their counterparts without depression (HR, 1.39; P < .001).
• This association was significant even after controlling for various factors such as body mass index, diabetes, smoking, alcohol consumption, and physical inactivity.
• Investigators offered several theories about the increased risk for CVD in women with depression, including how depression during hormonal shifts can contribute to a greater impact on cardiovascular health.

IN PRACTICE:

“Healthcare professionals must recognize the important role of depression in the development of CVD and emphasize the importance of a comprehensive, patient-centered approach to its prevention and management,” study author Hidehiro Kaneko, MD, said in a press release. “Assessing the risk of CVD in depressed patients and treating and preventing depression may lead to a decrease of CVD cases.”

SOURCE:

Keitaro Senoo, MD, of the Kyoto Prefectural University of Medicine, Kyoto, Japan, led the study, which was published online on March 12 in JACC: Asia.

LIMITATIONS:

The study is observational, so causality between depression and subsequent CVD events cannot be established. In addition, depression severity is unknown.

DISCLOSURES:

The study was funded by the Ministry of Health, Labour, and Welfare, Japan, and the Ministry of Education, Culture, Sports, Science, and Technology, Japan. There were no disclosures reported.

A version of this article appeared on Medscape.com.

TOPLINE:

Depression is linked to a significantly increased risk for cardiovascular disease (CVD), particularly in women, new data from a large retrospective cohort study show. Researchers suggest that screening and treating patients for depression may lead to a decreased incidence of CVD.

METHODOLOGY:

• Researchers analyzed health insurance claims from more than 4 million Japanese patients filed between 2005 and 2022.
• Participants were 18-75 (median age, 44) without a history of CVD or stroke, heart failure, or atrial fibrillation.
• Investigators followed participants for a mean period of 2.5-3.5 years to observe the number of CVD events in those who had a diagnosis of depression.
• During the follow-up period, there were 119,000 CVD events in men (14 per 10,000 person-years) and 61,800 CVD events in women (111 per 10,000 person-years).

TAKEAWAY:

• Compared with women without depression, those with depression had a 64% higher risk for CVD (hazard ratio [HR], 1.64), while men with depression had a 39% higher risk for CVD vs their counterparts without depression (HR, 1.39; P < .001).
• This association was significant even after controlling for various factors such as body mass index, diabetes, smoking, alcohol consumption, and physical inactivity.
• Investigators offered several theories about the increased risk for CVD in women with depression, including how depression during hormonal shifts can contribute to a greater impact on cardiovascular health.

IN PRACTICE:

“Healthcare professionals must recognize the important role of depression in the development of CVD and emphasize the importance of a comprehensive, patient-centered approach to its prevention and management,” study author Hidehiro Kaneko, MD, said in a press release. “Assessing the risk of CVD in depressed patients and treating and preventing depression may lead to a decrease of CVD cases.”

SOURCE:

Keitaro Senoo, MD, of the Kyoto Prefectural University of Medicine, Kyoto, Japan, led the study, which was published online on March 12 in JACC: Asia.

LIMITATIONS:

The study is observational, so causality between depression and subsequent CVD events cannot be established. In addition, depression severity is unknown.

DISCLOSURES:

The study was funded by the Ministry of Health, Labour, and Welfare, Japan, and the Ministry of Education, Culture, Sports, Science, and Technology, Japan. There were no disclosures reported.

A version of this article appeared on Medscape.com.

TOPLINE:

Depression is linked to a significantly increased risk for cardiovascular disease (CVD), particularly in women, new data from a large retrospective cohort study show. Researchers suggest that screening and treating patients for depression may lead to a decreased incidence of CVD.

METHODOLOGY:

• Researchers analyzed health insurance claims from more than 4 million Japanese patients filed between 2005 and 2022.
• Participants were 18-75 (median age, 44) without a history of CVD or stroke, heart failure, or atrial fibrillation.
• Investigators followed participants for a mean period of 2.5-3.5 years to observe the number of CVD events in those who had a diagnosis of depression.
• During the follow-up period, there were 119,000 CVD events in men (14 per 10,000 person-years) and 61,800 CVD events in women (111 per 10,000 person-years).

TAKEAWAY:

• Compared with women without depression, those with depression had a 64% higher risk for CVD (hazard ratio [HR], 1.64), while men with depression had a 39% higher risk for CVD vs their counterparts without depression (HR, 1.39; P < .001).
• This association was significant even after controlling for various factors such as body mass index, diabetes, smoking, alcohol consumption, and physical inactivity.
• Investigators offered several theories about the increased risk for CVD in women with depression, including how depression during hormonal shifts can contribute to a greater impact on cardiovascular health.

IN PRACTICE:

“Healthcare professionals must recognize the important role of depression in the development of CVD and emphasize the importance of a comprehensive, patient-centered approach to its prevention and management,” study author Hidehiro Kaneko, MD, said in a press release. “Assessing the risk of CVD in depressed patients and treating and preventing depression may lead to a decrease of CVD cases.”

SOURCE:

Keitaro Senoo, MD, of the Kyoto Prefectural University of Medicine, Kyoto, Japan, led the study, which was published online on March 12 in JACC: Asia.

LIMITATIONS:

The study is observational, so causality between depression and subsequent CVD events cannot be established. In addition, depression severity is unknown.

DISCLOSURES:

The study was funded by the Ministry of Health, Labour, and Welfare, Japan, and the Ministry of Education, Culture, Sports, Science, and Technology, Japan. There were no disclosures reported.

A version of this article appeared on Medscape.com.

Cells in the human body chat with each other all the time. One major way they communicate is by releasing tiny spheres called exosomes. These carry fats, proteins, and genetic material that help regulate everything from pregnancy and immune responses to heart health and kidney function.

Now, a new Columbia University study in Nature Nanotechnology demonstrated that these «nanobubbles» can deliver potent immunotherapy directly to tough-to-treat lung cancer tumors via inhalation.

“Exosomes work like text messages between cells , sending and receiving information,” said lead researcher Ke Cheng, PhD, professor of biomedical engineering at Columbia. “The significance of this study is that exosomes can bring mRNA-based treatment to lung cancer cells locally, unlike systemic chemotherapy that can have side effects throughout the body. And inhalation is totally noninvasive. You don’t need a nurse to use an IV needle to pierce your skin.”

Dr. Cheng expects a human trial could launch within 5 years. For now, his study is attracting attention because it marks an advance in three areas of intense interest by researchers and biotech companies alike: Therapeutic uses of exosomes, inhalable treatments for lung conditions, and the safe delivery of powerful interleukin-12 (IL-12) immunotherapy.

Inside the Study

Dr. Cheng, who has been developing exosome and stem cell therapies for more than 15 years, and his lab team focused on lung cancer because the disease, often detected in later stages, “has a huge mortality rate,” he said. “Therapies have been suboptimal and leave the organ so damaged.”

He wanted to explore new alternatives to systemic treatments. Most are given intravenously, but Dr. Cheng thinks exosomes — also called extracellular vesicles (EVs) — could change that.

“One of the advantages of exosomes is that they are naturally secreted by the body or cultured cells,” he noted. “They have low toxicity and have multiple ways of getting their message into cells.”

The scientists borrowed an approach that captured public attention during the pandemic: Using messenger RNA, which directs cells to make proteins for tasks — including boosting immune response.

IL-12 has shown promise against cancer for decades, but early human trials triggered serious side effects and several deaths. Researchers are now trying new delivery methods that target tumor cells without affecting healthy tissue. Dr. Cheng’s team took a new approach, inserting mRNA for IL-12 into exosomes.

One aim of the study was to compare the effectiveness of inhaled exosomes vs inhaled liposomes, engineered fat droplets also under investigation as drug carriers. The team’s question: Which would work better at introducing IL-12 to the lungs to affect cancer, without triggering side effects?

After lab mice inhaled the particles through the nose, the researchers found that exosomes delivered more mRNA into cancer cells in the lungs and fought lung cancer with few side effects. Three days after treatment, researchers saw an influx of cancer-fighting T cells within tumors — with higher levels for exosome-based treatment. Plus, the exosomes led to more cancer-destroying nature killer cells and more monocytes, a sign of immune-system activation.

Researchers also found the treatment acted as a vaccine, training the immune system to battle newly introduced cancers. Little of the exosome-delivered drug escaped into the bloodstream, and the study found minimal side effects. Inhalation didn’t affect normal breathing, Dr. Cheng added.

The study’s use of inhaled exosomes makes it significant, said Raghu Kalluri, MD, PhD, professor and chair of the Department of Cancer Biology at MD Anderson Cancer Center. “This is an interesting study that explores the inhalable delivery of engineered EVs for the treatment of lung cancer and offers insights into focused delivery of EV-based drugs…with implications for diseases beyond cancer,” he said. Dr. Kalluri is also an exosome researcher.

New Frontiers

Once seen as a “quirky biological phenomenon” or just cellular trash, exosomes are now the subject of intense medical research for their potential as drug carriers, as treatments in their own right for everything from wound healing and pneumonia to heart attacks and bowel disorders, and as measurable biological markers that could lead to new tests for cancer and other conditions. One exosome-based prostate cancer test, the ExoDx Prostate Test, is already on the market.

The explosion in exosome research — the number of published studies has grown from just a handful in the early 1980s to more than 9000  — spotlights a particular focus on cancer. According to a 2021 paper in Annals of Oncology, clinical trials for exosomes in cancer treatments and tests far out-paces those for diabetes, heart disease, or neurologic conditions. Currently, 52 clinical trials using exosomes in cancer diagnosis or treatment have been completed, are underway, or are looking for participants, according to clinicaltrials.gov.

Dr. Cheng’s approach could also be used to deliver other drugs to the lungs and other organs via inhalation. “We’re testing inhalation for a different type of lung disease, acute lung injury,” Dr. Cheng said. Other potential targets include lung disorders like pulmonary hypertension. Inhaled exosomes could potentially reach the brain via the olfactory bulb or the heart as it receives oxygenated blood from the lungs.

Breathing in Medicine

So far, inhalable cancer treatments are not available outside research studies in the United States or Europe , said Remi Rosiere, PhD, a lecturer at the Université libre de Bruxelles in Brussels, Belgium, and chief scientific officer of InhaTarget Therapeutics, a company developing its own inhaled treatments for severe respiratory diseases. “Oncologists are very interested,” he said. “If you concentrate the drug on the tumor site, you can avoid distribution to the body.”

Early research into inhalable chemotherapy began in the 1960s but was unsuccessful because breathing equipment dispersed toxic cancer drugs into the air or delivered only small amounts to the lungs, he said.

New delivery techniques aim to change that. Dr. Rosiere’s company is starting a human trial of a dry powder inhaler with the chemotherapy drug cisplatin for lung cancer. Also in the pipeline is an immunotherapy treatment for lung cancer inserted in lipid nanoparticles, which are tiny fat particles similar to liposomes.

He said Dr. Cheng’s study shows the advantages of sending in exosomes. “The data are very persuasive,” Dr. Rosier said of the study. “Exosomes have a good safety profile and are able to remain in the lung for quite a long time. This prolongs exposure to the drug for greater effectiveness, without causing toxicities.”

Getting from a mouse study to a human trial will take time. “You need to understand this is very early stage,” Dr. Rosiere added. “There will be many challenges to overcome.”

One is purely practical: If the drug approaches human trials, he said, regulators will ask whether the exosomes can be produced in large quantities to meet the huge demand for new lung cancer treatments. “Lung cancer is the number one fatal cancer in the world,” Dr. Rosiere said.

A New Route for ‘Powerful’ Cancer Treatment

Meanwhile, the Columbia University study showed that inhalable exosomes are a unique delivery method for IL-12 — and could help solve a major problem that’s plagued this promising cancer treatment for decades.

Called “one of the most powerful immunotherapy agents ever discovered” in a 2022 literature review, IL-12 showed serious side effects that stalled research in the 1980s , sparking an ongoing search for new delivery methods that continues today. In 2022 and 2023, Big Pharma companies including AstraZenca, Moderna, and Bristol Myers Squib reduced their involvement with IL-12 treatment research, leaving the field open to smaller biotech companies working on a variety of drug-delivery approaches that could make IL-12 safe and effective in humans.

These include injecting it directly into tumors, encasing it in various types of particles, masking the drug so it is activated only in cancer cells, and using IL-12 mRNA, which essentially turns tumor cells into IL-12–producing factories. Another IL-12 mRNA drug, from Pittsburgh-based Krystal Biotech, received a fast-track designation from the US Food and Drug Administration in February 2024 for an inhaled lung cancer treatment that packages mRNA for IL-12 and IL-2 inside an engineered virus.

And of course, there is Dr. Cheng’s inhalable treatment, culminating decades of work across three burgeoning fields.

A version of this article appeared on Medscape.com.

Cells in the human body chat with each other all the time. One major way they communicate is by releasing tiny spheres called exosomes. These carry fats, proteins, and genetic material that help regulate everything from pregnancy and immune responses to heart health and kidney function.

Now, a new Columbia University study in Nature Nanotechnology demonstrated that these «nanobubbles» can deliver potent immunotherapy directly to tough-to-treat lung cancer tumors via inhalation.

“Exosomes work like text messages between cells , sending and receiving information,” said lead researcher Ke Cheng, PhD, professor of biomedical engineering at Columbia. “The significance of this study is that exosomes can bring mRNA-based treatment to lung cancer cells locally, unlike systemic chemotherapy that can have side effects throughout the body. And inhalation is totally noninvasive. You don’t need a nurse to use an IV needle to pierce your skin.”

Dr. Cheng expects a human trial could launch within 5 years. For now, his study is attracting attention because it marks an advance in three areas of intense interest by researchers and biotech companies alike: Therapeutic uses of exosomes, inhalable treatments for lung conditions, and the safe delivery of powerful interleukin-12 (IL-12) immunotherapy.

Inside the Study

Dr. Cheng, who has been developing exosome and stem cell therapies for more than 15 years, and his lab team focused on lung cancer because the disease, often detected in later stages, “has a huge mortality rate,” he said. “Therapies have been suboptimal and leave the organ so damaged.”

He wanted to explore new alternatives to systemic treatments. Most are given intravenously, but Dr. Cheng thinks exosomes — also called extracellular vesicles (EVs) — could change that.

“One of the advantages of exosomes is that they are naturally secreted by the body or cultured cells,” he noted. “They have low toxicity and have multiple ways of getting their message into cells.”

The scientists borrowed an approach that captured public attention during the pandemic: Using messenger RNA, which directs cells to make proteins for tasks — including boosting immune response.

IL-12 has shown promise against cancer for decades, but early human trials triggered serious side effects and several deaths. Researchers are now trying new delivery methods that target tumor cells without affecting healthy tissue. Dr. Cheng’s team took a new approach, inserting mRNA for IL-12 into exosomes.

One aim of the study was to compare the effectiveness of inhaled exosomes vs inhaled liposomes, engineered fat droplets also under investigation as drug carriers. The team’s question: Which would work better at introducing IL-12 to the lungs to affect cancer, without triggering side effects?

After lab mice inhaled the particles through the nose, the researchers found that exosomes delivered more mRNA into cancer cells in the lungs and fought lung cancer with few side effects. Three days after treatment, researchers saw an influx of cancer-fighting T cells within tumors — with higher levels for exosome-based treatment. Plus, the exosomes led to more cancer-destroying nature killer cells and more monocytes, a sign of immune-system activation.

Researchers also found the treatment acted as a vaccine, training the immune system to battle newly introduced cancers. Little of the exosome-delivered drug escaped into the bloodstream, and the study found minimal side effects. Inhalation didn’t affect normal breathing, Dr. Cheng added.

The study’s use of inhaled exosomes makes it significant, said Raghu Kalluri, MD, PhD, professor and chair of the Department of Cancer Biology at MD Anderson Cancer Center. “This is an interesting study that explores the inhalable delivery of engineered EVs for the treatment of lung cancer and offers insights into focused delivery of EV-based drugs…with implications for diseases beyond cancer,” he said. Dr. Kalluri is also an exosome researcher.

New Frontiers

Once seen as a “quirky biological phenomenon” or just cellular trash, exosomes are now the subject of intense medical research for their potential as drug carriers, as treatments in their own right for everything from wound healing and pneumonia to heart attacks and bowel disorders, and as measurable biological markers that could lead to new tests for cancer and other conditions. One exosome-based prostate cancer test, the ExoDx Prostate Test, is already on the market.

The explosion in exosome research — the number of published studies has grown from just a handful in the early 1980s to more than 9000  — spotlights a particular focus on cancer. According to a 2021 paper in Annals of Oncology, clinical trials for exosomes in cancer treatments and tests far out-paces those for diabetes, heart disease, or neurologic conditions. Currently, 52 clinical trials using exosomes in cancer diagnosis or treatment have been completed, are underway, or are looking for participants, according to clinicaltrials.gov.

Dr. Cheng’s approach could also be used to deliver other drugs to the lungs and other organs via inhalation. “We’re testing inhalation for a different type of lung disease, acute lung injury,” Dr. Cheng said. Other potential targets include lung disorders like pulmonary hypertension. Inhaled exosomes could potentially reach the brain via the olfactory bulb or the heart as it receives oxygenated blood from the lungs.

Breathing in Medicine

So far, inhalable cancer treatments are not available outside research studies in the United States or Europe , said Remi Rosiere, PhD, a lecturer at the Université libre de Bruxelles in Brussels, Belgium, and chief scientific officer of InhaTarget Therapeutics, a company developing its own inhaled treatments for severe respiratory diseases. “Oncologists are very interested,” he said. “If you concentrate the drug on the tumor site, you can avoid distribution to the body.”

Early research into inhalable chemotherapy began in the 1960s but was unsuccessful because breathing equipment dispersed toxic cancer drugs into the air or delivered only small amounts to the lungs, he said.

New delivery techniques aim to change that. Dr. Rosiere’s company is starting a human trial of a dry powder inhaler with the chemotherapy drug cisplatin for lung cancer. Also in the pipeline is an immunotherapy treatment for lung cancer inserted in lipid nanoparticles, which are tiny fat particles similar to liposomes.

He said Dr. Cheng’s study shows the advantages of sending in exosomes. “The data are very persuasive,” Dr. Rosier said of the study. “Exosomes have a good safety profile and are able to remain in the lung for quite a long time. This prolongs exposure to the drug for greater effectiveness, without causing toxicities.”

Getting from a mouse study to a human trial will take time. “You need to understand this is very early stage,” Dr. Rosiere added. “There will be many challenges to overcome.”

One is purely practical: If the drug approaches human trials, he said, regulators will ask whether the exosomes can be produced in large quantities to meet the huge demand for new lung cancer treatments. “Lung cancer is the number one fatal cancer in the world,” Dr. Rosiere said.

A New Route for ‘Powerful’ Cancer Treatment

Meanwhile, the Columbia University study showed that inhalable exosomes are a unique delivery method for IL-12 — and could help solve a major problem that’s plagued this promising cancer treatment for decades.

Called “one of the most powerful immunotherapy agents ever discovered” in a 2022 literature review, IL-12 showed serious side effects that stalled research in the 1980s , sparking an ongoing search for new delivery methods that continues today. In 2022 and 2023, Big Pharma companies including AstraZenca, Moderna, and Bristol Myers Squib reduced their involvement with IL-12 treatment research, leaving the field open to smaller biotech companies working on a variety of drug-delivery approaches that could make IL-12 safe and effective in humans.

These include injecting it directly into tumors, encasing it in various types of particles, masking the drug so it is activated only in cancer cells, and using IL-12 mRNA, which essentially turns tumor cells into IL-12–producing factories. Another IL-12 mRNA drug, from Pittsburgh-based Krystal Biotech, received a fast-track designation from the US Food and Drug Administration in February 2024 for an inhaled lung cancer treatment that packages mRNA for IL-12 and IL-2 inside an engineered virus.

And of course, there is Dr. Cheng’s inhalable treatment, culminating decades of work across three burgeoning fields.

A version of this article appeared on Medscape.com.

Cells in the human body chat with each other all the time. One major way they communicate is by releasing tiny spheres called exosomes. These carry fats, proteins, and genetic material that help regulate everything from pregnancy and immune responses to heart health and kidney function.

Now, a new Columbia University study in Nature Nanotechnology demonstrated that these «nanobubbles» can deliver potent immunotherapy directly to tough-to-treat lung cancer tumors via inhalation.

“Exosomes work like text messages between cells , sending and receiving information,” said lead researcher Ke Cheng, PhD, professor of biomedical engineering at Columbia. “The significance of this study is that exosomes can bring mRNA-based treatment to lung cancer cells locally, unlike systemic chemotherapy that can have side effects throughout the body. And inhalation is totally noninvasive. You don’t need a nurse to use an IV needle to pierce your skin.”

Dr. Cheng expects a human trial could launch within 5 years. For now, his study is attracting attention because it marks an advance in three areas of intense interest by researchers and biotech companies alike: Therapeutic uses of exosomes, inhalable treatments for lung conditions, and the safe delivery of powerful interleukin-12 (IL-12) immunotherapy.

Inside the Study

Dr. Cheng, who has been developing exosome and stem cell therapies for more than 15 years, and his lab team focused on lung cancer because the disease, often detected in later stages, “has a huge mortality rate,” he said. “Therapies have been suboptimal and leave the organ so damaged.”

He wanted to explore new alternatives to systemic treatments. Most are given intravenously, but Dr. Cheng thinks exosomes — also called extracellular vesicles (EVs) — could change that.

“One of the advantages of exosomes is that they are naturally secreted by the body or cultured cells,” he noted. “They have low toxicity and have multiple ways of getting their message into cells.”

The scientists borrowed an approach that captured public attention during the pandemic: Using messenger RNA, which directs cells to make proteins for tasks — including boosting immune response.

IL-12 has shown promise against cancer for decades, but early human trials triggered serious side effects and several deaths. Researchers are now trying new delivery methods that target tumor cells without affecting healthy tissue. Dr. Cheng’s team took a new approach, inserting mRNA for IL-12 into exosomes.

One aim of the study was to compare the effectiveness of inhaled exosomes vs inhaled liposomes, engineered fat droplets also under investigation as drug carriers. The team’s question: Which would work better at introducing IL-12 to the lungs to affect cancer, without triggering side effects?

After lab mice inhaled the particles through the nose, the researchers found that exosomes delivered more mRNA into cancer cells in the lungs and fought lung cancer with few side effects. Three days after treatment, researchers saw an influx of cancer-fighting T cells within tumors — with higher levels for exosome-based treatment. Plus, the exosomes led to more cancer-destroying nature killer cells and more monocytes, a sign of immune-system activation.

Researchers also found the treatment acted as a vaccine, training the immune system to battle newly introduced cancers. Little of the exosome-delivered drug escaped into the bloodstream, and the study found minimal side effects. Inhalation didn’t affect normal breathing, Dr. Cheng added.

The study’s use of inhaled exosomes makes it significant, said Raghu Kalluri, MD, PhD, professor and chair of the Department of Cancer Biology at MD Anderson Cancer Center. “This is an interesting study that explores the inhalable delivery of engineered EVs for the treatment of lung cancer and offers insights into focused delivery of EV-based drugs…with implications for diseases beyond cancer,” he said. Dr. Kalluri is also an exosome researcher.

New Frontiers

Once seen as a “quirky biological phenomenon” or just cellular trash, exosomes are now the subject of intense medical research for their potential as drug carriers, as treatments in their own right for everything from wound healing and pneumonia to heart attacks and bowel disorders, and as measurable biological markers that could lead to new tests for cancer and other conditions. One exosome-based prostate cancer test, the ExoDx Prostate Test, is already on the market.

The explosion in exosome research — the number of published studies has grown from just a handful in the early 1980s to more than 9000  — spotlights a particular focus on cancer. According to a 2021 paper in Annals of Oncology, clinical trials for exosomes in cancer treatments and tests far out-paces those for diabetes, heart disease, or neurologic conditions. Currently, 52 clinical trials using exosomes in cancer diagnosis or treatment have been completed, are underway, or are looking for participants, according to clinicaltrials.gov.

Dr. Cheng’s approach could also be used to deliver other drugs to the lungs and other organs via inhalation. “We’re testing inhalation for a different type of lung disease, acute lung injury,” Dr. Cheng said. Other potential targets include lung disorders like pulmonary hypertension. Inhaled exosomes could potentially reach the brain via the olfactory bulb or the heart as it receives oxygenated blood from the lungs.

Breathing in Medicine

So far, inhalable cancer treatments are not available outside research studies in the United States or Europe , said Remi Rosiere, PhD, a lecturer at the Université libre de Bruxelles in Brussels, Belgium, and chief scientific officer of InhaTarget Therapeutics, a company developing its own inhaled treatments for severe respiratory diseases. “Oncologists are very interested,” he said. “If you concentrate the drug on the tumor site, you can avoid distribution to the body.”

Early research into inhalable chemotherapy began in the 1960s but was unsuccessful because breathing equipment dispersed toxic cancer drugs into the air or delivered only small amounts to the lungs, he said.

New delivery techniques aim to change that. Dr. Rosiere’s company is starting a human trial of a dry powder inhaler with the chemotherapy drug cisplatin for lung cancer. Also in the pipeline is an immunotherapy treatment for lung cancer inserted in lipid nanoparticles, which are tiny fat particles similar to liposomes.

He said Dr. Cheng’s study shows the advantages of sending in exosomes. “The data are very persuasive,” Dr. Rosier said of the study. “Exosomes have a good safety profile and are able to remain in the lung for quite a long time. This prolongs exposure to the drug for greater effectiveness, without causing toxicities.”

Getting from a mouse study to a human trial will take time. “You need to understand this is very early stage,” Dr. Rosiere added. “There will be many challenges to overcome.”

One is purely practical: If the drug approaches human trials, he said, regulators will ask whether the exosomes can be produced in large quantities to meet the huge demand for new lung cancer treatments. “Lung cancer is the number one fatal cancer in the world,” Dr. Rosiere said.

A New Route for ‘Powerful’ Cancer Treatment

Meanwhile, the Columbia University study showed that inhalable exosomes are a unique delivery method for IL-12 — and could help solve a major problem that’s plagued this promising cancer treatment for decades.

Called “one of the most powerful immunotherapy agents ever discovered” in a 2022 literature review, IL-12 showed serious side effects that stalled research in the 1980s , sparking an ongoing search for new delivery methods that continues today. In 2022 and 2023, Big Pharma companies including AstraZenca, Moderna, and Bristol Myers Squib reduced their involvement with IL-12 treatment research, leaving the field open to smaller biotech companies working on a variety of drug-delivery approaches that could make IL-12 safe and effective in humans.

These include injecting it directly into tumors, encasing it in various types of particles, masking the drug so it is activated only in cancer cells, and using IL-12 mRNA, which essentially turns tumor cells into IL-12–producing factories. Another IL-12 mRNA drug, from Pittsburgh-based Krystal Biotech, received a fast-track designation from the US Food and Drug Administration in February 2024 for an inhaled lung cancer treatment that packages mRNA for IL-12 and IL-2 inside an engineered virus.

And of course, there is Dr. Cheng’s inhalable treatment, culminating decades of work across three burgeoning fields.

A version of this article appeared on Medscape.com.

Silence Therapeutics shared positive topline 36-week data from its ongoing phase 2 study of zerlasiran, a long-acting agent directed at lowering Lp(a) levels. 

In a statement, the company said the study shows a highly significant reduction from baseline in Lp(a) levels with zerlasiran compared with placebo at 36 weeks, the primary endpoint.

Zerlasiran (formerly known as SLN360), is a short interfering RNA (siRNA) agent, or “ gene silencing” therapy. It binds to and temporarily blocks the action of the LPA gene which encodes for apolipoprotein(a), a dominant and a rate-limiting component in the hepatic synthesis of the Lp(a) particle.

A previous phase 1 study showed that single subcutaneous doses of the drug, ranging from 30 mg to 600 mg, produced a dose-dependent reduction in Lp(a) plasma levels at 45-60 days.

The current double-blind placebo-controlled phase 2 trial — known as ALPACAR-360 — enrolled 178 patients at high risk for atherosclerotic cardiovascular events who had elevated levels of Lp(a), ie, ≥ 125 nmol/L (median baseline Lp(a) was approximately 215 nmol/L). They were randomized to zerlasiran or placebo. 

Zerlasiran was administered at 300 mg subcutaneously every 16 or 24 weeks or at 450 mg every 24 weeks. 

Results reported by the company show a median percentage reduction in Lp(a) of ≥ 90% for both doses at week 36, with no new safety concerns identified during this treatment period.

The 60-week study is ongoing, and secondary endpoints, including change in Lp(a) from baseline to 48 weeks (end of treatment period) and 60 weeks (end of study) and potential effects on other lipids/lipoproteins, will be evaluated.

Silence says it plans to report topline 48-week data from the ALPACAR-360 study in the second quarter of this year.

Elevated levels of Lp(a) represent a genetic risk factor for cardiovascular disease, which is believed to affect approximately 20% of the population. Although there are currently no approved Lp(a)-lowering therapies, several drug candidates are in late-stage clinical testing.

A version of this article appeared on Medscape.com.

Silence Therapeutics shared positive topline 36-week data from its ongoing phase 2 study of zerlasiran, a long-acting agent directed at lowering Lp(a) levels. 

In a statement, the company said the study shows a highly significant reduction from baseline in Lp(a) levels with zerlasiran compared with placebo at 36 weeks, the primary endpoint.

Zerlasiran (formerly known as SLN360), is a short interfering RNA (siRNA) agent, or “ gene silencing” therapy. It binds to and temporarily blocks the action of the LPA gene which encodes for apolipoprotein(a), a dominant and a rate-limiting component in the hepatic synthesis of the Lp(a) particle.

A previous phase 1 study showed that single subcutaneous doses of the drug, ranging from 30 mg to 600 mg, produced a dose-dependent reduction in Lp(a) plasma levels at 45-60 days.

The current double-blind placebo-controlled phase 2 trial — known as ALPACAR-360 — enrolled 178 patients at high risk for atherosclerotic cardiovascular events who had elevated levels of Lp(a), ie, ≥ 125 nmol/L (median baseline Lp(a) was approximately 215 nmol/L). They were randomized to zerlasiran or placebo. 

Zerlasiran was administered at 300 mg subcutaneously every 16 or 24 weeks or at 450 mg every 24 weeks. 

Results reported by the company show a median percentage reduction in Lp(a) of ≥ 90% for both doses at week 36, with no new safety concerns identified during this treatment period.

The 60-week study is ongoing, and secondary endpoints, including change in Lp(a) from baseline to 48 weeks (end of treatment period) and 60 weeks (end of study) and potential effects on other lipids/lipoproteins, will be evaluated.

Silence says it plans to report topline 48-week data from the ALPACAR-360 study in the second quarter of this year.

Elevated levels of Lp(a) represent a genetic risk factor for cardiovascular disease, which is believed to affect approximately 20% of the population. Although there are currently no approved Lp(a)-lowering therapies, several drug candidates are in late-stage clinical testing.

A version of this article appeared on Medscape.com.

Silence Therapeutics shared positive topline 36-week data from its ongoing phase 2 study of zerlasiran, a long-acting agent directed at lowering Lp(a) levels. 

In a statement, the company said the study shows a highly significant reduction from baseline in Lp(a) levels with zerlasiran compared with placebo at 36 weeks, the primary endpoint.

Zerlasiran (formerly known as SLN360), is a short interfering RNA (siRNA) agent, or “ gene silencing” therapy. It binds to and temporarily blocks the action of the LPA gene which encodes for apolipoprotein(a), a dominant and a rate-limiting component in the hepatic synthesis of the Lp(a) particle.

A previous phase 1 study showed that single subcutaneous doses of the drug, ranging from 30 mg to 600 mg, produced a dose-dependent reduction in Lp(a) plasma levels at 45-60 days.

The current double-blind placebo-controlled phase 2 trial — known as ALPACAR-360 — enrolled 178 patients at high risk for atherosclerotic cardiovascular events who had elevated levels of Lp(a), ie, ≥ 125 nmol/L (median baseline Lp(a) was approximately 215 nmol/L). They were randomized to zerlasiran or placebo. 

Zerlasiran was administered at 300 mg subcutaneously every 16 or 24 weeks or at 450 mg every 24 weeks. 

Results reported by the company show a median percentage reduction in Lp(a) of ≥ 90% for both doses at week 36, with no new safety concerns identified during this treatment period.

The 60-week study is ongoing, and secondary endpoints, including change in Lp(a) from baseline to 48 weeks (end of treatment period) and 60 weeks (end of study) and potential effects on other lipids/lipoproteins, will be evaluated.

Silence says it plans to report topline 48-week data from the ALPACAR-360 study in the second quarter of this year.

Elevated levels of Lp(a) represent a genetic risk factor for cardiovascular disease, which is believed to affect approximately 20% of the population. Although there are currently no approved Lp(a)-lowering therapies, several drug candidates are in late-stage clinical testing.

A version of this article appeared on Medscape.com.

The new RSV antibody treatment for babies has been highly effective in its first season, according to a first look at data from four children’s hospitals.

Babies who received the new preventive treatment for RSV shortly after birth were 90% less likely to be severely sickened with the potentially deadly respiratory illness, according to the new estimate published by the Centers for Disease Control and Prevention. It is the first real-world evaluation of Beyfortus (the generic name is nirsevimab), which was approved by the Food and Drug Administration last July.

RSV is a seasonal illness that affects more people — particularly infants and the elderly — in the fall and winter. Symptoms are usually mild in healthy adults, but infants are particularly at risk of getting bronchiolitis, which results in exhausting wheezing and coughing in babies due to swelling in their airways and lungs. Babies who are hospitalized may need fluids and medical devices to help them breathe.

RSV peaked this season from November to January, with more than 10,000 monthly diagnoses reported to the CDC. 

The new CDC analysis was conducted among about 700 babies hospitalized for severe respiratory problems from October to the end of February. Among the babies in the study, 407 were diagnosed with RSV and 292 tested negative. The researchers found that 1% of babies in the study who were diagnosed with RSV had received Beyfortus, while the remaining babies who were positive for the virus had not. 

Among the babies hospitalized for other severe respiratory problems, 18% had received Beyfortus. Overall, just 59 babies among the nearly 700 in the study received Beyfortus, perhaps reflecting the short supply of the medicine the first season it was available. The report authors noted that babies in the study who did receive Beyfortus also tended to have high-risk medical conditions.

The number of babies nationwide who received Beyfortus during this first season of availability is unclear, but a January CDC survey showed that 4 in 10 parents said their babies under 8 months old had received the treatment. The Wall Street Journal reported recently that a shortage last fall resulted from underestimated demand and from production plans that were set before the CDC decided to recommend that all infants under 8 months old receive Beyfortus if their mothers did not get a maternal vaccine that can protect infants from RSV.

Both the antibody treatment for infants and the maternal vaccine were shown in clinical trials to be about 80% effective at preventing severe illness stemming from RSV.

The authors of the latest CDC report concluded that “this early estimate supports the current nirsevimab recommendation for the prevention of severe RSV disease in infants. Infants should be protected by maternal RSV vaccination or infant receipt of nirsevimab.”

A version of this article appeared on WebMD.com.

The new RSV antibody treatment for babies has been highly effective in its first season, according to a first look at data from four children’s hospitals.

Babies who received the new preventive treatment for RSV shortly after birth were 90% less likely to be severely sickened with the potentially deadly respiratory illness, according to the new estimate published by the Centers for Disease Control and Prevention. It is the first real-world evaluation of Beyfortus (the generic name is nirsevimab), which was approved by the Food and Drug Administration last July.

RSV is a seasonal illness that affects more people — particularly infants and the elderly — in the fall and winter. Symptoms are usually mild in healthy adults, but infants are particularly at risk of getting bronchiolitis, which results in exhausting wheezing and coughing in babies due to swelling in their airways and lungs. Babies who are hospitalized may need fluids and medical devices to help them breathe.

RSV peaked this season from November to January, with more than 10,000 monthly diagnoses reported to the CDC. 

The new CDC analysis was conducted among about 700 babies hospitalized for severe respiratory problems from October to the end of February. Among the babies in the study, 407 were diagnosed with RSV and 292 tested negative. The researchers found that 1% of babies in the study who were diagnosed with RSV had received Beyfortus, while the remaining babies who were positive for the virus had not. 

Among the babies hospitalized for other severe respiratory problems, 18% had received Beyfortus. Overall, just 59 babies among the nearly 700 in the study received Beyfortus, perhaps reflecting the short supply of the medicine the first season it was available. The report authors noted that babies in the study who did receive Beyfortus also tended to have high-risk medical conditions.

The number of babies nationwide who received Beyfortus during this first season of availability is unclear, but a January CDC survey showed that 4 in 10 parents said their babies under 8 months old had received the treatment. The Wall Street Journal reported recently that a shortage last fall resulted from underestimated demand and from production plans that were set before the CDC decided to recommend that all infants under 8 months old receive Beyfortus if their mothers did not get a maternal vaccine that can protect infants from RSV.

Both the antibody treatment for infants and the maternal vaccine were shown in clinical trials to be about 80% effective at preventing severe illness stemming from RSV.

The authors of the latest CDC report concluded that “this early estimate supports the current nirsevimab recommendation for the prevention of severe RSV disease in infants. Infants should be protected by maternal RSV vaccination or infant receipt of nirsevimab.”

A version of this article appeared on WebMD.com.

The new RSV antibody treatment for babies has been highly effective in its first season, according to a first look at data from four children’s hospitals.

Babies who received the new preventive treatment for RSV shortly after birth were 90% less likely to be severely sickened with the potentially deadly respiratory illness, according to the new estimate published by the Centers for Disease Control and Prevention. It is the first real-world evaluation of Beyfortus (the generic name is nirsevimab), which was approved by the Food and Drug Administration last July.

RSV is a seasonal illness that affects more people — particularly infants and the elderly — in the fall and winter. Symptoms are usually mild in healthy adults, but infants are particularly at risk of getting bronchiolitis, which results in exhausting wheezing and coughing in babies due to swelling in their airways and lungs. Babies who are hospitalized may need fluids and medical devices to help them breathe.

RSV peaked this season from November to January, with more than 10,000 monthly diagnoses reported to the CDC. 

The new CDC analysis was conducted among about 700 babies hospitalized for severe respiratory problems from October to the end of February. Among the babies in the study, 407 were diagnosed with RSV and 292 tested negative. The researchers found that 1% of babies in the study who were diagnosed with RSV had received Beyfortus, while the remaining babies who were positive for the virus had not. 

Among the babies hospitalized for other severe respiratory problems, 18% had received Beyfortus. Overall, just 59 babies among the nearly 700 in the study received Beyfortus, perhaps reflecting the short supply of the medicine the first season it was available. The report authors noted that babies in the study who did receive Beyfortus also tended to have high-risk medical conditions.

The number of babies nationwide who received Beyfortus during this first season of availability is unclear, but a January CDC survey showed that 4 in 10 parents said their babies under 8 months old had received the treatment. The Wall Street Journal reported recently that a shortage last fall resulted from underestimated demand and from production plans that were set before the CDC decided to recommend that all infants under 8 months old receive Beyfortus if their mothers did not get a maternal vaccine that can protect infants from RSV.

Both the antibody treatment for infants and the maternal vaccine were shown in clinical trials to be about 80% effective at preventing severe illness stemming from RSV.

The authors of the latest CDC report concluded that “this early estimate supports the current nirsevimab recommendation for the prevention of severe RSV disease in infants. Infants should be protected by maternal RSV vaccination or infant receipt of nirsevimab.”

A version of this article appeared on WebMD.com.

The American College of Cardiology has published a new update to its consensus decision pathway for the treatment of heart failure with reduced ejection fraction (HFrEF).

Chair of the consensus document Writing Committee Thomas M. Maddox, MD, explained to this news organization that this new Decision Pathway provides a practical, streamlined update to frontline clinicians treating patients with heart failure and incorporates evidence from the 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure.

The authors said that the treatment of heart failure can feel overwhelming, and many opportunities to improve patient outcomes are being missed.

“While the AHA/ACC/HFSA Guidelines are wonderful in that they collate all the latest scientific evidence, they don’t speak as much to the practicalities of delivering the care. This is what this Decision Pathway document comes in — it is designed to help frontline clinicians with the practical reality of managing these patients,” Dr. Maddox, who is director of the Healthcare Innovation Lab at BJC HealthCare and the Washington University School of Medicine in St Louis, Missouri, commented.

The document, “Expert Consensus Decision Pathway for Optimization of Heart Failure Treatment: Answers to 10 Pivotal Issues About Heart Failure With Reduced Ejection Fraction,” was published online on March 8 in the Journal of the American College of Cardiology.

The authors provided guidance on introducing the numerous evidence-based therapies now available for HFrEF, improving adherence, overcoming treatment barriers, acknowledging contraindications and situations for which few data exist, affording expensive therapies, treating special cohorts, and making the transition to palliative care.

Rather than focusing on extensive text, the document provided practical tips, tables, and figures to make clear the steps, tools, and provisos needed to treat patients with heart failure successfully and expeditiously, they added.

Dr. Maddox reported that there are three main updated areas of advice on the treatment of heart failure in the new document.
 

Valsartan/Sacubitril First Line

One of the major changes involves an elevation for the status of the angiotensin receptor-neprilysin inhibitor (ARNI), Entresto (valsartan/sacubitril).

“It is now clear that this agent is superior to ACE-inhibitors or angiotensin receptor blockers in terms of reducing heart failure hospitalization and death, whereas previously it was seen as somewhat equivalent,” Dr. Maddox said. “So, barring a contraindication or another problem with getting the medication, this agent should be one of the first line medicines for all patients with heart failure and a reduced ejection fraction.”
 

Dual Sodium-Glucose Cotransporter 1/2 (SGLT1/2) Inhibitor

A second update involves the addition of sotagliflozin (a dual inhibitor of both SGLT1 and SGLT2) to the SGLT2 inhibitors as another first-line medication for patients with heart failure and reduced ejection fraction.

“We now have evidence that both SGLT2 and SGLT1 inhibitors are beneficial in reducing heart failure hospitalization and death. Previously we only had evidence on SGLT2 inhibitors — dapagliflozin and empagliflozin. Sotagliflozin is a newer agent, which inhibits both SGLT1 and SGLT2, and it turns out that inhibiting both are beneficial in heart failure. So, this gives us a third med in this category,” Dr. Maddox noted.
 

Rapid Initiation of the Four Pillars of Therapy

The document stated that more data have emerged recently to support early and rapid initiation and titration of the “four pillars” of medical therapy in heart failure to maximize the benefits of patient-reported outcomes and reduction in hospitalizations and mortality.

The four pillars of therapy are ARNI, a beta-blocker, a mineralocorticoid antagonist, and an SGLT inhibitor.

As an example, four-class medication initiation reduced the hazard of cardiovascular death or hospital admission for heart failure significantly (hazard ratio, 0.38) compared with therapy with just an angiotensin-converting enzyme inhibitor/angiotensin receptor blocker plus a beta-blocker, the document reported.

“What we realize now is that the more quickly we can get patients on all four of these drug classes and escalate to target doses or maximally tolerated doses ideally within 3 months, the better the outcome,” Dr. Maddox said.

“Unfortunately, right now there is very incomplete realization and recognition of that in clinical practice. So, we are trying to highlight the importance of this to encourage clinicians to be more aggressive in making this happen.”

“In all patients with heart failure and reduced ejection fraction, getting them on all four of these medicines as quickly as possible will give the best outcome. We’ve seen evidence in support of this from several broad population trials,” he added. “There are times when they can’t take all four but we should do our best to get there.”
 

Practical Considerations

Dr. Maddox pointed out that the Consensus Document is also trying to account for practical realities and barriers to heart failure treatment.

“When we think about these recommendations — and evidence that getting patients on all these medicines is valuable, we also focus on the fact that there are three major barriers that can get in the way of this and how to think about overcoming those barriers,” he said.

The barriers are comorbidities/side effects of medications, costs of the medicines, and systems of care that are needed to ensure patients can be treated with multiple medications in a timely fashion.

In terms of comorbidities/side effects, Dr. Maddox explained that patients with heart failure are generally older and are likely to have other comorbidities. “The more medicines we give, the more likely we are to run into side effects. So, we have produced some guidance on how to monitor for adverse effects and ways to mitigate these effects so the guideline recommended therapies can be continued without creating new harms.”

He gave the example of mineralocorticoid antagonists, which can sometimes elevate potassium levels, particularly if there is some underlying kidney disease, so clinicians are advised to recommend a low-potassium diet for these patients or the use of potassium binding agents that will also lower the amount of potassium in the blood stream; in this way, patients are able to continue the mineralocorticoid antagonist.

On costs, Dr. Maddox noted that the valsartan/sacubitril combination drug and SGLT inhibitors are new medicines and are expensive.

“They can be prohibitively expensive for patients who have suboptimal pharmacy benefits or who are uninsured.”

The Consensus Document therefore provided some guidance on ways to identify rebate programs, access insurance, and find different pathways to obtaining those drugs at a more reasonable price. It also advocated for policy changes to allow these medicines to be more accessible to more people.
 

More Use of Digital Tools

On the issue of systems of care, Dr. Maddox noted that the preexisting model of delivering care, which almost always involves the patient coming into the doctor’s office, invokes a high burden on both the system and most especially, the patient.

“Patients do not want to come back and forth to the doctor’s office multiple times in a few weeks. This is often a nonstarter, particularly for patients with busy lives,” he commented.

The Consensus Document advised more use of digital tools to provide remote care and contact with patients including sensors that can measure variables such as heart rate and blood pressure and video appointments.

“We are still working out what are the right models of care and how they can be performed safely and how they can be funded. But I think at the end of the day, this will give us more practical ways of getting people on multiple heart failure medicines and monitoring them safely without causing an undue burden for them logistically,” Dr. Maddox said.

He pointed out that there are a record number of medicines now available to treat heart failure, and while this is welcome, many of these patients are also on multiple other medications for other comorbidities as well.

“If you start giving patients seven, eight, or nine different medicines that they have to take every day, sometimes multiple times a day — that’s complicated medically, logistically, and financially. The potential for interaction and complications increases with every additional medication.”

Dr. Maddox also noted that patients have limits on how many medications they will accept. “It really helps if we have an engaged patient who has a good relationship with the care team to try to develop the right treatment plan that is going to meet their needs and give them the best possible health outcomes.”

It can take many visits to get the patient on all these medications and then up-titrate to target doses.

“We try and do a couple of things in each appointment. Often, we tend to start one or maybe two drugs at a time at a relatively low dose to avoid side effects, so we can be talking about 12-16 different encounters in total,” he said.

He recommended making a plan and the use of new technologies to manage each incremental step.
 

A Team Approach

Another issue that is discussed in the document is the use of a healthcare team to manage all the necessary appointments.

“It is no longer practical that one person can be the engineer for all this. It should be a team effort,” Dr. Maddox stated.

Responsibilities can be allocated across physicians, nurses, pharmacists, and even case managers, so that the team can take more of a population approach and develop a system to get patients on the multiple medications as quickly as possible.

“While this can still be quite a big burden for the patient, we need to figure out a system to make this as palatable as possible for them. Practices need to tailor this themselves according to what resources they have,” he added.

While most new patients will be routed to cardiologists to start their treatment plans, once on their initial medications and these have been up titrated to target levels, they should be able to be managed by primary care doctors, who will have the most holistic view of the patient and their other comorbidities, Dr. Maddox advised.

“Following this guidance should lead to more patients receiving evidence-based care which leads to better health outcomes, but delivered in a practical way that fits with their life reality and logistical needs,” he concluded.

A version of this article appeared on Medscape.com.

The American College of Cardiology has published a new update to its consensus decision pathway for the treatment of heart failure with reduced ejection fraction (HFrEF).

Chair of the consensus document Writing Committee Thomas M. Maddox, MD, explained to this news organization that this new Decision Pathway provides a practical, streamlined update to frontline clinicians treating patients with heart failure and incorporates evidence from the 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure.

The authors said that the treatment of heart failure can feel overwhelming, and many opportunities to improve patient outcomes are being missed.

“While the AHA/ACC/HFSA Guidelines are wonderful in that they collate all the latest scientific evidence, they don’t speak as much to the practicalities of delivering the care. This is what this Decision Pathway document comes in — it is designed to help frontline clinicians with the practical reality of managing these patients,” Dr. Maddox, who is director of the Healthcare Innovation Lab at BJC HealthCare and the Washington University School of Medicine in St Louis, Missouri, commented.

The document, “Expert Consensus Decision Pathway for Optimization of Heart Failure Treatment: Answers to 10 Pivotal Issues About Heart Failure With Reduced Ejection Fraction,” was published online on March 8 in the Journal of the American College of Cardiology.

The authors provided guidance on introducing the numerous evidence-based therapies now available for HFrEF, improving adherence, overcoming treatment barriers, acknowledging contraindications and situations for which few data exist, affording expensive therapies, treating special cohorts, and making the transition to palliative care.

Rather than focusing on extensive text, the document provided practical tips, tables, and figures to make clear the steps, tools, and provisos needed to treat patients with heart failure successfully and expeditiously, they added.

Dr. Maddox reported that there are three main updated areas of advice on the treatment of heart failure in the new document.
 

Valsartan/Sacubitril First Line

One of the major changes involves an elevation for the status of the angiotensin receptor-neprilysin inhibitor (ARNI), Entresto (valsartan/sacubitril).

“It is now clear that this agent is superior to ACE-inhibitors or angiotensin receptor blockers in terms of reducing heart failure hospitalization and death, whereas previously it was seen as somewhat equivalent,” Dr. Maddox said. “So, barring a contraindication or another problem with getting the medication, this agent should be one of the first line medicines for all patients with heart failure and a reduced ejection fraction.”
 

Dual Sodium-Glucose Cotransporter 1/2 (SGLT1/2) Inhibitor

A second update involves the addition of sotagliflozin (a dual inhibitor of both SGLT1 and SGLT2) to the SGLT2 inhibitors as another first-line medication for patients with heart failure and reduced ejection fraction.

“We now have evidence that both SGLT2 and SGLT1 inhibitors are beneficial in reducing heart failure hospitalization and death. Previously we only had evidence on SGLT2 inhibitors — dapagliflozin and empagliflozin. Sotagliflozin is a newer agent, which inhibits both SGLT1 and SGLT2, and it turns out that inhibiting both are beneficial in heart failure. So, this gives us a third med in this category,” Dr. Maddox noted.
 

Rapid Initiation of the Four Pillars of Therapy

The document stated that more data have emerged recently to support early and rapid initiation and titration of the “four pillars” of medical therapy in heart failure to maximize the benefits of patient-reported outcomes and reduction in hospitalizations and mortality.

The four pillars of therapy are ARNI, a beta-blocker, a mineralocorticoid antagonist, and an SGLT inhibitor.

As an example, four-class medication initiation reduced the hazard of cardiovascular death or hospital admission for heart failure significantly (hazard ratio, 0.38) compared with therapy with just an angiotensin-converting enzyme inhibitor/angiotensin receptor blocker plus a beta-blocker, the document reported.

“What we realize now is that the more quickly we can get patients on all four of these drug classes and escalate to target doses or maximally tolerated doses ideally within 3 months, the better the outcome,” Dr. Maddox said.

“Unfortunately, right now there is very incomplete realization and recognition of that in clinical practice. So, we are trying to highlight the importance of this to encourage clinicians to be more aggressive in making this happen.”

“In all patients with heart failure and reduced ejection fraction, getting them on all four of these medicines as quickly as possible will give the best outcome. We’ve seen evidence in support of this from several broad population trials,” he added. “There are times when they can’t take all four but we should do our best to get there.”
 

Practical Considerations

Dr. Maddox pointed out that the Consensus Document is also trying to account for practical realities and barriers to heart failure treatment.

“When we think about these recommendations — and evidence that getting patients on all these medicines is valuable, we also focus on the fact that there are three major barriers that can get in the way of this and how to think about overcoming those barriers,” he said.

The barriers are comorbidities/side effects of medications, costs of the medicines, and systems of care that are needed to ensure patients can be treated with multiple medications in a timely fashion.

In terms of comorbidities/side effects, Dr. Maddox explained that patients with heart failure are generally older and are likely to have other comorbidities. “The more medicines we give, the more likely we are to run into side effects. So, we have produced some guidance on how to monitor for adverse effects and ways to mitigate these effects so the guideline recommended therapies can be continued without creating new harms.”

He gave the example of mineralocorticoid antagonists, which can sometimes elevate potassium levels, particularly if there is some underlying kidney disease, so clinicians are advised to recommend a low-potassium diet for these patients or the use of potassium binding agents that will also lower the amount of potassium in the blood stream; in this way, patients are able to continue the mineralocorticoid antagonist.

On costs, Dr. Maddox noted that the valsartan/sacubitril combination drug and SGLT inhibitors are new medicines and are expensive.

“They can be prohibitively expensive for patients who have suboptimal pharmacy benefits or who are uninsured.”

The Consensus Document therefore provided some guidance on ways to identify rebate programs, access insurance, and find different pathways to obtaining those drugs at a more reasonable price. It also advocated for policy changes to allow these medicines to be more accessible to more people.
 

More Use of Digital Tools

On the issue of systems of care, Dr. Maddox noted that the preexisting model of delivering care, which almost always involves the patient coming into the doctor’s office, invokes a high burden on both the system and most especially, the patient.

“Patients do not want to come back and forth to the doctor’s office multiple times in a few weeks. This is often a nonstarter, particularly for patients with busy lives,” he commented.

The Consensus Document advised more use of digital tools to provide remote care and contact with patients including sensors that can measure variables such as heart rate and blood pressure and video appointments.

“We are still working out what are the right models of care and how they can be performed safely and how they can be funded. But I think at the end of the day, this will give us more practical ways of getting people on multiple heart failure medicines and monitoring them safely without causing an undue burden for them logistically,” Dr. Maddox said.

He pointed out that there are a record number of medicines now available to treat heart failure, and while this is welcome, many of these patients are also on multiple other medications for other comorbidities as well.

“If you start giving patients seven, eight, or nine different medicines that they have to take every day, sometimes multiple times a day — that’s complicated medically, logistically, and financially. The potential for interaction and complications increases with every additional medication.”

Dr. Maddox also noted that patients have limits on how many medications they will accept. “It really helps if we have an engaged patient who has a good relationship with the care team to try to develop the right treatment plan that is going to meet their needs and give them the best possible health outcomes.”

It can take many visits to get the patient on all these medications and then up-titrate to target doses.

“We try and do a couple of things in each appointment. Often, we tend to start one or maybe two drugs at a time at a relatively low dose to avoid side effects, so we can be talking about 12-16 different encounters in total,” he said.

He recommended making a plan and the use of new technologies to manage each incremental step.
 

A Team Approach

Another issue that is discussed in the document is the use of a healthcare team to manage all the necessary appointments.

“It is no longer practical that one person can be the engineer for all this. It should be a team effort,” Dr. Maddox stated.

Responsibilities can be allocated across physicians, nurses, pharmacists, and even case managers, so that the team can take more of a population approach and develop a system to get patients on the multiple medications as quickly as possible.

“While this can still be quite a big burden for the patient, we need to figure out a system to make this as palatable as possible for them. Practices need to tailor this themselves according to what resources they have,” he added.

While most new patients will be routed to cardiologists to start their treatment plans, once on their initial medications and these have been up titrated to target levels, they should be able to be managed by primary care doctors, who will have the most holistic view of the patient and their other comorbidities, Dr. Maddox advised.

“Following this guidance should lead to more patients receiving evidence-based care which leads to better health outcomes, but delivered in a practical way that fits with their life reality and logistical needs,” he concluded.

A version of this article appeared on Medscape.com.

The American College of Cardiology has published a new update to its consensus decision pathway for the treatment of heart failure with reduced ejection fraction (HFrEF).

Chair of the consensus document Writing Committee Thomas M. Maddox, MD, explained to this news organization that this new Decision Pathway provides a practical, streamlined update to frontline clinicians treating patients with heart failure and incorporates evidence from the 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure.

The authors said that the treatment of heart failure can feel overwhelming, and many opportunities to improve patient outcomes are being missed.

“While the AHA/ACC/HFSA Guidelines are wonderful in that they collate all the latest scientific evidence, they don’t speak as much to the practicalities of delivering the care. This is what this Decision Pathway document comes in — it is designed to help frontline clinicians with the practical reality of managing these patients,” Dr. Maddox, who is director of the Healthcare Innovation Lab at BJC HealthCare and the Washington University School of Medicine in St Louis, Missouri, commented.

The document, “Expert Consensus Decision Pathway for Optimization of Heart Failure Treatment: Answers to 10 Pivotal Issues About Heart Failure With Reduced Ejection Fraction,” was published online on March 8 in the Journal of the American College of Cardiology.

The authors provided guidance on introducing the numerous evidence-based therapies now available for HFrEF, improving adherence, overcoming treatment barriers, acknowledging contraindications and situations for which few data exist, affording expensive therapies, treating special cohorts, and making the transition to palliative care.

Rather than focusing on extensive text, the document provided practical tips, tables, and figures to make clear the steps, tools, and provisos needed to treat patients with heart failure successfully and expeditiously, they added.

Dr. Maddox reported that there are three main updated areas of advice on the treatment of heart failure in the new document.
 

Valsartan/Sacubitril First Line

One of the major changes involves an elevation for the status of the angiotensin receptor-neprilysin inhibitor (ARNI), Entresto (valsartan/sacubitril).

“It is now clear that this agent is superior to ACE-inhibitors or angiotensin receptor blockers in terms of reducing heart failure hospitalization and death, whereas previously it was seen as somewhat equivalent,” Dr. Maddox said. “So, barring a contraindication or another problem with getting the medication, this agent should be one of the first line medicines for all patients with heart failure and a reduced ejection fraction.”
 

Dual Sodium-Glucose Cotransporter 1/2 (SGLT1/2) Inhibitor

A second update involves the addition of sotagliflozin (a dual inhibitor of both SGLT1 and SGLT2) to the SGLT2 inhibitors as another first-line medication for patients with heart failure and reduced ejection fraction.

“We now have evidence that both SGLT2 and SGLT1 inhibitors are beneficial in reducing heart failure hospitalization and death. Previously we only had evidence on SGLT2 inhibitors — dapagliflozin and empagliflozin. Sotagliflozin is a newer agent, which inhibits both SGLT1 and SGLT2, and it turns out that inhibiting both are beneficial in heart failure. So, this gives us a third med in this category,” Dr. Maddox noted.
 

Rapid Initiation of the Four Pillars of Therapy

The document stated that more data have emerged recently to support early and rapid initiation and titration of the “four pillars” of medical therapy in heart failure to maximize the benefits of patient-reported outcomes and reduction in hospitalizations and mortality.

The four pillars of therapy are ARNI, a beta-blocker, a mineralocorticoid antagonist, and an SGLT inhibitor.

As an example, four-class medication initiation reduced the hazard of cardiovascular death or hospital admission for heart failure significantly (hazard ratio, 0.38) compared with therapy with just an angiotensin-converting enzyme inhibitor/angiotensin receptor blocker plus a beta-blocker, the document reported.

“What we realize now is that the more quickly we can get patients on all four of these drug classes and escalate to target doses or maximally tolerated doses ideally within 3 months, the better the outcome,” Dr. Maddox said.

“Unfortunately, right now there is very incomplete realization and recognition of that in clinical practice. So, we are trying to highlight the importance of this to encourage clinicians to be more aggressive in making this happen.”

“In all patients with heart failure and reduced ejection fraction, getting them on all four of these medicines as quickly as possible will give the best outcome. We’ve seen evidence in support of this from several broad population trials,” he added. “There are times when they can’t take all four but we should do our best to get there.”
 

Practical Considerations

Dr. Maddox pointed out that the Consensus Document is also trying to account for practical realities and barriers to heart failure treatment.

“When we think about these recommendations — and evidence that getting patients on all these medicines is valuable, we also focus on the fact that there are three major barriers that can get in the way of this and how to think about overcoming those barriers,” he said.

The barriers are comorbidities/side effects of medications, costs of the medicines, and systems of care that are needed to ensure patients can be treated with multiple medications in a timely fashion.

In terms of comorbidities/side effects, Dr. Maddox explained that patients with heart failure are generally older and are likely to have other comorbidities. “The more medicines we give, the more likely we are to run into side effects. So, we have produced some guidance on how to monitor for adverse effects and ways to mitigate these effects so the guideline recommended therapies can be continued without creating new harms.”

He gave the example of mineralocorticoid antagonists, which can sometimes elevate potassium levels, particularly if there is some underlying kidney disease, so clinicians are advised to recommend a low-potassium diet for these patients or the use of potassium binding agents that will also lower the amount of potassium in the blood stream; in this way, patients are able to continue the mineralocorticoid antagonist.

On costs, Dr. Maddox noted that the valsartan/sacubitril combination drug and SGLT inhibitors are new medicines and are expensive.

“They can be prohibitively expensive for patients who have suboptimal pharmacy benefits or who are uninsured.”

The Consensus Document therefore provided some guidance on ways to identify rebate programs, access insurance, and find different pathways to obtaining those drugs at a more reasonable price. It also advocated for policy changes to allow these medicines to be more accessible to more people.
 

More Use of Digital Tools

On the issue of systems of care, Dr. Maddox noted that the preexisting model of delivering care, which almost always involves the patient coming into the doctor’s office, invokes a high burden on both the system and most especially, the patient.

“Patients do not want to come back and forth to the doctor’s office multiple times in a few weeks. This is often a nonstarter, particularly for patients with busy lives,” he commented.

The Consensus Document advised more use of digital tools to provide remote care and contact with patients including sensors that can measure variables such as heart rate and blood pressure and video appointments.

“We are still working out what are the right models of care and how they can be performed safely and how they can be funded. But I think at the end of the day, this will give us more practical ways of getting people on multiple heart failure medicines and monitoring them safely without causing an undue burden for them logistically,” Dr. Maddox said.

He pointed out that there are a record number of medicines now available to treat heart failure, and while this is welcome, many of these patients are also on multiple other medications for other comorbidities as well.

“If you start giving patients seven, eight, or nine different medicines that they have to take every day, sometimes multiple times a day — that’s complicated medically, logistically, and financially. The potential for interaction and complications increases with every additional medication.”

Dr. Maddox also noted that patients have limits on how many medications they will accept. “It really helps if we have an engaged patient who has a good relationship with the care team to try to develop the right treatment plan that is going to meet their needs and give them the best possible health outcomes.”

It can take many visits to get the patient on all these medications and then up-titrate to target doses.

“We try and do a couple of things in each appointment. Often, we tend to start one or maybe two drugs at a time at a relatively low dose to avoid side effects, so we can be talking about 12-16 different encounters in total,” he said.

He recommended making a plan and the use of new technologies to manage each incremental step.
 

A Team Approach

Another issue that is discussed in the document is the use of a healthcare team to manage all the necessary appointments.

“It is no longer practical that one person can be the engineer for all this. It should be a team effort,” Dr. Maddox stated.

Responsibilities can be allocated across physicians, nurses, pharmacists, and even case managers, so that the team can take more of a population approach and develop a system to get patients on the multiple medications as quickly as possible.

“While this can still be quite a big burden for the patient, we need to figure out a system to make this as palatable as possible for them. Practices need to tailor this themselves according to what resources they have,” he added.

While most new patients will be routed to cardiologists to start their treatment plans, once on their initial medications and these have been up titrated to target levels, they should be able to be managed by primary care doctors, who will have the most holistic view of the patient and their other comorbidities, Dr. Maddox advised.

“Following this guidance should lead to more patients receiving evidence-based care which leads to better health outcomes, but delivered in a practical way that fits with their life reality and logistical needs,” he concluded.

A version of this article appeared on Medscape.com.

President Joe Biden on March 9 signed into law a measure that softened — but did not completely eliminate — a 2024 cut in a key rate used to determine how physicians are paid for treating Medicare patients.

While physician groups hailed the move as partial relief, they say they’ll continue to press for broader changes in the Medicare physician fee schedule.

The Medicare provision was tucked into a larger spending package approved by the US House and Senate.

The American Academy of Family Physicians (AAFP), the American Medical Association (AMA), and other groups have lobbied Congress for months to undo a 3.4% cut in the base rate, or conversion factor, in the physician fee schedule for 2024.

The conversion factor is used in calculations to determine reimbursement for myriad other services. Federal Medicare officials said the cut would mean a 1.25% decrease in overall payments in 2024, compared with 2023.

“With the passage of this legislation, Congress has offset 2.93% of that payment cut,” said Steven P. Furr, MD, AAFP’s president in a statement. “We appreciate this temporary measure but continue to urge Congress to advance comprehensive, long-term Medicare payment reform.”

In a statement, Representative Larry Bucshon, MD (R-IN), said the payment cut could not be completely eliminated because of budget constraints.

The Medicare physician fee schedule covers much of the care clinicians provide to people older than 65 and those with disabilities. It covers about 8000 different types of services, ranging from office visits to surgical procedures, imaging, and tests, according to the Medicare Payment Advisory Commission (MedPAC).

Along with physicians, the fee schedule sets payments for nurse practitioners, physician assistants, podiatrists, physical therapists, psychologists, and other clinicians.

In 2021, the Medicare program and its beneficiaries paid $92.8 billion for services provided by almost 1.3 million clinicians, MedPAC said.
 

Larger Changes Ahead?

Rep. Bucshon is among the physicians serving in the House who are pressing for a permanent revamp of the Medicare physician fee schedule. He cosponsored a bill (HR 2474) that would peg future annual increases in the physician fee schedule to the Medicare Economic Index, which would reflect inflation’s effect.

In April, more than 120 state and national medical groups signed onto an AMA-led letter urging Congress to pass this bill.

The measure is a key priority for the AMA. The organization reached out repeatedly last year to federal officials about it through its own in-house lobbyists, this news organization found through a review of congressional lobbying forms submitted by AMA.

These required disclosure forms reveal how much AMA and other organizations spend each quarter to appeal to members of Congress and federal agencies on specific issues. The disclosure forms do not include a detailed accounting of spending on each issue.

But they do show which issues are priorities for an organization. AMA’s in-house lobbyists reported raising dozens of issues in 2024 within contacts in Congress and federal agencies. These issues included abortion access, maternal health, physician burnout, and potential for bias in clinical use of algorithms, as well as Medicare payment for physicians.

AMA reported spending estimated cost of $20.6 million. (AMA spent $6.7 million in the first quarter, $4.75 million in the second quarter, $3.42 million in the third quarter, and $5.74 million in the fourth quarter.)

In a March 6 statement, Jesse M. Ehrenfeld, MD, MPH, AMA president, urged Congress to turn to more serious consideration of Medicare physician pay beyond short-term tweaks attached to other larger bills.

“As physicians, we are trained to run toward emergencies. We urge Congress to do the same,” Dr. Ehrenfeld said. “We encourage Congress to act if this policy decision is an emergency because — in fact — it is. It is well past time to put an end to stopgap measures that fail to address the underlying causes of the continuing decline in Medicare physician payments.”

There’s bipartisan interest in a revamp of the physician fee schedule amid widespread criticism of the last such overhaul, the Medicare Access and CHIP Reauthorization Act of 2015.

For example, Senate Budget Chairman Sheldon Whitehouse (D-RI) has proposed the creation of a technical advisory committee to improve how Medicare sets the physician fee schedule. The existing fee schedule provides too little money for primary care services and primary care provider pay, contributing to shortages, Sen. Whitehouse said.

Sen. Whitehouse on March 6 held a hearing on ways to beef up US primary care. Among the experts who appeared was Amol Navathe, MD, PhD, of the University of Pennsylvania, Philadelphia, Pennsylvania.

Dr. Navathe said the current Medicare physician fee schedule tilts in favor of procedural services, leading to “underinvestment in cognitive, diagnostic, and supportive services such as primary care.”

In addition, much of what primary care clinicians do, “such as addressing social challenges, is not included in the codes of the fee schedule itself,” said Dr. Navathe, who also serves as the vice chairman of MedPAC.

It’s unclear when Congress will attempt a serious revision to the Medicare physician fee schedule. Lawmakers are unlikely to take on such a major challenge in this election year.

There would be significant opposition and challenges for lawmakers in trying to clear a bill that added an inflation adjustment for what’s already seen as an imperfect physician fee schedule, said Mark E. Miller, PhD, executive vice president of healthcare at the philanthropy Arnold Ventures, which studies how payment decisions affect medical care.

“That bill could cost a lot of money and raise a lot of questions,” Dr. Miller said.

A version of this article appeared on Medscape.com.

President Joe Biden on March 9 signed into law a measure that softened — but did not completely eliminate — a 2024 cut in a key rate used to determine how physicians are paid for treating Medicare patients.

While physician groups hailed the move as partial relief, they say they’ll continue to press for broader changes in the Medicare physician fee schedule.

The Medicare provision was tucked into a larger spending package approved by the US House and Senate.

The American Academy of Family Physicians (AAFP), the American Medical Association (AMA), and other groups have lobbied Congress for months to undo a 3.4% cut in the base rate, or conversion factor, in the physician fee schedule for 2024.

The conversion factor is used in calculations to determine reimbursement for myriad other services. Federal Medicare officials said the cut would mean a 1.25% decrease in overall payments in 2024, compared with 2023.

“With the passage of this legislation, Congress has offset 2.93% of that payment cut,” said Steven P. Furr, MD, AAFP’s president in a statement. “We appreciate this temporary measure but continue to urge Congress to advance comprehensive, long-term Medicare payment reform.”

In a statement, Representative Larry Bucshon, MD (R-IN), said the payment cut could not be completely eliminated because of budget constraints.

The Medicare physician fee schedule covers much of the care clinicians provide to people older than 65 and those with disabilities. It covers about 8000 different types of services, ranging from office visits to surgical procedures, imaging, and tests, according to the Medicare Payment Advisory Commission (MedPAC).

Along with physicians, the fee schedule sets payments for nurse practitioners, physician assistants, podiatrists, physical therapists, psychologists, and other clinicians.

In 2021, the Medicare program and its beneficiaries paid $92.8 billion for services provided by almost 1.3 million clinicians, MedPAC said.
 

Larger Changes Ahead?

Rep. Bucshon is among the physicians serving in the House who are pressing for a permanent revamp of the Medicare physician fee schedule. He cosponsored a bill (HR 2474) that would peg future annual increases in the physician fee schedule to the Medicare Economic Index, which would reflect inflation’s effect.

In April, more than 120 state and national medical groups signed onto an AMA-led letter urging Congress to pass this bill.

The measure is a key priority for the AMA. The organization reached out repeatedly last year to federal officials about it through its own in-house lobbyists, this news organization found through a review of congressional lobbying forms submitted by AMA.

These required disclosure forms reveal how much AMA and other organizations spend each quarter to appeal to members of Congress and federal agencies on specific issues. The disclosure forms do not include a detailed accounting of spending on each issue.

But they do show which issues are priorities for an organization. AMA’s in-house lobbyists reported raising dozens of issues in 2024 within contacts in Congress and federal agencies. These issues included abortion access, maternal health, physician burnout, and potential for bias in clinical use of algorithms, as well as Medicare payment for physicians.

AMA reported spending estimated cost of $20.6 million. (AMA spent $6.7 million in the first quarter, $4.75 million in the second quarter, $3.42 million in the third quarter, and $5.74 million in the fourth quarter.)

In a March 6 statement, Jesse M. Ehrenfeld, MD, MPH, AMA president, urged Congress to turn to more serious consideration of Medicare physician pay beyond short-term tweaks attached to other larger bills.

“As physicians, we are trained to run toward emergencies. We urge Congress to do the same,” Dr. Ehrenfeld said. “We encourage Congress to act if this policy decision is an emergency because — in fact — it is. It is well past time to put an end to stopgap measures that fail to address the underlying causes of the continuing decline in Medicare physician payments.”

There’s bipartisan interest in a revamp of the physician fee schedule amid widespread criticism of the last such overhaul, the Medicare Access and CHIP Reauthorization Act of 2015.

For example, Senate Budget Chairman Sheldon Whitehouse (D-RI) has proposed the creation of a technical advisory committee to improve how Medicare sets the physician fee schedule. The existing fee schedule provides too little money for primary care services and primary care provider pay, contributing to shortages, Sen. Whitehouse said.

Sen. Whitehouse on March 6 held a hearing on ways to beef up US primary care. Among the experts who appeared was Amol Navathe, MD, PhD, of the University of Pennsylvania, Philadelphia, Pennsylvania.

Dr. Navathe said the current Medicare physician fee schedule tilts in favor of procedural services, leading to “underinvestment in cognitive, diagnostic, and supportive services such as primary care.”

In addition, much of what primary care clinicians do, “such as addressing social challenges, is not included in the codes of the fee schedule itself,” said Dr. Navathe, who also serves as the vice chairman of MedPAC.

It’s unclear when Congress will attempt a serious revision to the Medicare physician fee schedule. Lawmakers are unlikely to take on such a major challenge in this election year.

There would be significant opposition and challenges for lawmakers in trying to clear a bill that added an inflation adjustment for what’s already seen as an imperfect physician fee schedule, said Mark E. Miller, PhD, executive vice president of healthcare at the philanthropy Arnold Ventures, which studies how payment decisions affect medical care.

“That bill could cost a lot of money and raise a lot of questions,” Dr. Miller said.

A version of this article appeared on Medscape.com.

President Joe Biden on March 9 signed into law a measure that softened — but did not completely eliminate — a 2024 cut in a key rate used to determine how physicians are paid for treating Medicare patients.

While physician groups hailed the move as partial relief, they say they’ll continue to press for broader changes in the Medicare physician fee schedule.

The Medicare provision was tucked into a larger spending package approved by the US House and Senate.

The American Academy of Family Physicians (AAFP), the American Medical Association (AMA), and other groups have lobbied Congress for months to undo a 3.4% cut in the base rate, or conversion factor, in the physician fee schedule for 2024.

The conversion factor is used in calculations to determine reimbursement for myriad other services. Federal Medicare officials said the cut would mean a 1.25% decrease in overall payments in 2024, compared with 2023.

“With the passage of this legislation, Congress has offset 2.93% of that payment cut,” said Steven P. Furr, MD, AAFP’s president in a statement. “We appreciate this temporary measure but continue to urge Congress to advance comprehensive, long-term Medicare payment reform.”

In a statement, Representative Larry Bucshon, MD (R-IN), said the payment cut could not be completely eliminated because of budget constraints.

The Medicare physician fee schedule covers much of the care clinicians provide to people older than 65 and those with disabilities. It covers about 8000 different types of services, ranging from office visits to surgical procedures, imaging, and tests, according to the Medicare Payment Advisory Commission (MedPAC).

Along with physicians, the fee schedule sets payments for nurse practitioners, physician assistants, podiatrists, physical therapists, psychologists, and other clinicians.

In 2021, the Medicare program and its beneficiaries paid $92.8 billion for services provided by almost 1.3 million clinicians, MedPAC said.
 

Larger Changes Ahead?

Rep. Bucshon is among the physicians serving in the House who are pressing for a permanent revamp of the Medicare physician fee schedule. He cosponsored a bill (HR 2474) that would peg future annual increases in the physician fee schedule to the Medicare Economic Index, which would reflect inflation’s effect.

In April, more than 120 state and national medical groups signed onto an AMA-led letter urging Congress to pass this bill.

The measure is a key priority for the AMA. The organization reached out repeatedly last year to federal officials about it through its own in-house lobbyists, this news organization found through a review of congressional lobbying forms submitted by AMA.

These required disclosure forms reveal how much AMA and other organizations spend each quarter to appeal to members of Congress and federal agencies on specific issues. The disclosure forms do not include a detailed accounting of spending on each issue.

But they do show which issues are priorities for an organization. AMA’s in-house lobbyists reported raising dozens of issues in 2024 within contacts in Congress and federal agencies. These issues included abortion access, maternal health, physician burnout, and potential for bias in clinical use of algorithms, as well as Medicare payment for physicians.

AMA reported spending estimated cost of $20.6 million. (AMA spent $6.7 million in the first quarter, $4.75 million in the second quarter, $3.42 million in the third quarter, and $5.74 million in the fourth quarter.)

In a March 6 statement, Jesse M. Ehrenfeld, MD, MPH, AMA president, urged Congress to turn to more serious consideration of Medicare physician pay beyond short-term tweaks attached to other larger bills.

“As physicians, we are trained to run toward emergencies. We urge Congress to do the same,” Dr. Ehrenfeld said. “We encourage Congress to act if this policy decision is an emergency because — in fact — it is. It is well past time to put an end to stopgap measures that fail to address the underlying causes of the continuing decline in Medicare physician payments.”

There’s bipartisan interest in a revamp of the physician fee schedule amid widespread criticism of the last such overhaul, the Medicare Access and CHIP Reauthorization Act of 2015.

For example, Senate Budget Chairman Sheldon Whitehouse (D-RI) has proposed the creation of a technical advisory committee to improve how Medicare sets the physician fee schedule. The existing fee schedule provides too little money for primary care services and primary care provider pay, contributing to shortages, Sen. Whitehouse said.

Sen. Whitehouse on March 6 held a hearing on ways to beef up US primary care. Among the experts who appeared was Amol Navathe, MD, PhD, of the University of Pennsylvania, Philadelphia, Pennsylvania.

Dr. Navathe said the current Medicare physician fee schedule tilts in favor of procedural services, leading to “underinvestment in cognitive, diagnostic, and supportive services such as primary care.”

In addition, much of what primary care clinicians do, “such as addressing social challenges, is not included in the codes of the fee schedule itself,” said Dr. Navathe, who also serves as the vice chairman of MedPAC.

It’s unclear when Congress will attempt a serious revision to the Medicare physician fee schedule. Lawmakers are unlikely to take on such a major challenge in this election year.

There would be significant opposition and challenges for lawmakers in trying to clear a bill that added an inflation adjustment for what’s already seen as an imperfect physician fee schedule, said Mark E. Miller, PhD, executive vice president of healthcare at the philanthropy Arnold Ventures, which studies how payment decisions affect medical care.

“That bill could cost a lot of money and raise a lot of questions,” Dr. Miller said.

A version of this article appeared on Medscape.com.