AVAHO

Anyone who practices Mohs micrographic surgery is likely to know the name Hugh Greenway, MD, the longtime head of Mohs and dermatologic surgery at Scripps Clinic in San Diego, who was also recently selected as program director for cutaneous oncology at Scripps MD Anderson Cancer Center in San Diego. He is also a former president of the American College of Mohs Surgery.

After earning his medical degree from the Medical College of Georgia, Augusta, in 1974, Dr. Greenway was fellowship trained in Mohs skin cancer surgery by Frederic E. Mohs, MD, at the University of Wisconsin–Madison. He completed his dermatology residency at the Naval Medical Center San Diego and joined Scripps Clinic in 1983, where he launched the institution’s first Mohs surgery program, as well as a popular annual intensive course in superficial anatomy and cutaneous surgery that bears his name. He was also the first physician in the world to use interferon as a nonsurgical treatment of basal cell carcinoma.

Courtesy Scripps Clinic

To date, Dr. Greenway has performed more than 41,000 Mohs surgery cases and has trained 61 fellows who practice in academic and clinical settings. In 2017, he received the Frederic E. Mohs Award from the ACMS at the college’s annual meeting. He is also a past CEO of Scripps Clinic. In this Q&A, Dr. Greenway opens up about what it was like to train with Dr. Mohs, what makes a good Mohs surgeon, and why he’s excited about the future of dermatology.
 

I understand that you first became interested in a medical career after meeting Dr. Carl Jones, a friend of your father who was your Scoutmaster in the Boy Scouts in Georgia. What about Dr. Jones inspired you to pursue a career in medicine?

Dr. Jones was an internist/allergist in Atlanta, where I grew up. His three sons and I were friends. My dad had dealt with several medical problems being injured in World War II and subsequently undergoing a couple of kidney transplantations, so I developed an interest in medicine personally. Even though Dr. Jones was a specialist, he started out as a family doctor like I did, so he was interested in the whole person and all of his or her medical problems as opposed to those related to his specialty only. I traveled with the Boy Scouts to camp at places like Valley Forge in Pennsylvania, and Dr. Jones was involved with the medical set-ups of those large events. That also contributed to my interest in medicine.

As part of your 9-year service in the U.S. Navy, you spent 2 years as the flight surgeon at NAS Atlanta/Dobbins Air Force Base. What was your most memorable experience from that assignment?

Dobbins is a large facility with two Lockheed plants, and the Air Force had built the medical clinic, which was staffed by the Navy. Getting to know some of the active-duty members of the Air Force, the Navy, and the National Guard, and their commitment to our country, was memorable. Jimmy Carter was the president in those days. When he would fly in Dobbins, one of my jobs as the flight surgeon was to be on base when Air Force One landed or departed. One night, we had a DC-9 commercial aircraft coming from Huntsville, Ala., to Atlanta that got caught in a thunderstorm a little above 30,000 feet. Both engines went out and the aircraft essentially became a glider. The pilots tried to land on our runway but unfortunately, they ended up 4 miles short. We were heavily involved in responding to the crash, which was a tragic event. I also learned to fly (second seat) different types of aircraft during my assignment at NAS Atlanta/Dobbins Air Force Base, everything from the large C-5s to Navy fighter jets and helicopters. Coincidentally, Dr. Jones was involved with a couple of free health clinics in Atlanta when I was stationed there. Every Tuesday night, my wife (who is a nurse) and I would volunteer at a clinic in Cabbagetown, which was one of the poorer areas of Atlanta. It was a chance to give back to a group of people who didn’t have a whole lot.

In the middle your dermatology residency at Naval Medical Center San Diego, you were selected by Dr. Mohs for fellowship training in Mohs skin cancer surgery at the University of Wisconsin–Madison. What do you remember most about your training with Dr. Mohs?

Dr. Mohs was a kind, humble man who had this great idea about skin cancer. He was not a dermatologist; he was a general surgeon. The technique he developed was originally called chemosurgery because he put a chemical onto the skin. This was known as the fixed-tissue technique. Then we had a fresh-tissue technique, where we did not use the chemical, but we were able to use local anesthesia right away. That developed into the Mohs surgery we know today. Dr. Mohs did not name it that; he was very humble, but he was very proud of his technique. He was also a very hard worker. On the first day of my fellowship, I started at 7 in the morning and ended at 7 at night. It was the same for the last day of my fellowship. He also had an excellent office staff, many of whom had worked with him for many years. Patients with difficult skin cancers traveled to Madison from all over the world because there weren’t that many Mohs surgery clinics in those days. During the latter part of my fellowship, Michael McCall, MD, and I had the opportunity to remove a skin cancer from the nose of Dr. Mohs. We presented the case at a national conference, and I titled the talk “Mohs Surgery for Mohs’ Nose.”

Early in your career Dr. Mohs asked you to take over his practice, but you accepted an offer to establish the first Mohs surgery office at Scripps in San Diego instead. What convinced you to head West?

After my fellowship, I returned to San Diego to complete my residency with the Navy, where we opened a Mohs surgery clinic. Dr. Mohs came out for the ribbon cutting. During that time, I was taking care of several patients that he had treated in Wisconsin. Through that my wife and I ended up going to dinner with Cecil and Ida Green, philanthropists who made several financial gifts to Scripps Clinic – and for whom Scripps Green Hospital is named. Cecil cofounded Texas Instruments and was knighted by Queen Elizabeth. During dinner, he suggested that I stay in San Diego for a year and work at Scripps after my residency assignment with the Navy. I agreed and have been here ever since.

What do you find most interesting about Mohs surgery?

In Mohs surgery, you’re able to provide not only surgical care to eliminate the tumor, but also the pathology and the reconstruction. That was interesting to me. Dr. Mohs was not that interested in reconstruction. He was more focused on the tumor, in part because with the original fixed-tissue technique you could not do the reconstruction. You had to wait for an extra layer of tissue to separate. But with the fresh-tissue technique, you were able to provide the reconstruction that day. Mohs surgery deals with a subset of tumors that are challenging to treat. That also spiked my academic and clinical interest.

In your opinion, what’s been the most important advance in Mohs surgery to date?

In recent years, immunology has come into play, so now we have teams of clinicians in dermatology, medical oncology, surgery, and other subspecialties providing patients the best of care. In the arena of Mohs surgery itself, in the 1980s, the American College of Mohs Surgery developed a 1-year fellowship program, which enabled us to train many men and women to practice Mohs surgery. Most of them are dermatologists.

Please complete the sentence: “You can tell a good Mohs surgeon by the way he/she ...”

Treats patients, is willing to spend time with them, and shows an interest in them. One of the things we should strive for is to let patients know that they as a person are important; it’s not just the melanoma on their nose. We’re not only dealing with a skin cancer; we’re dealing with a patient who has skin cancer.

For the past 39 years, you have led Hugh Greenway’s Superficial Anatomy and Cutaneous Surgery course, which takes place every January in San Diego. What’s been key to sustaining this training course for nearly 4 decades?

There have been many people involved in its success, so it’s not just me. When I first started my practice, there really was not a focus on anatomy in the general dermatologic community. Dermatologic surgery textbooks contained very little content on surgical anatomy so I developed an interest a putting together a course that would cover some of this material. I met with Terence Davidson, MD, an otolaryngologist who was dean of continuing medical education at the University of California, San Diego. The course includes lectures from experts in many subspecialties and hands-on laboratories using cadavers to work on anatomy and surgical techniques. After about 16 years of doing the course Dr. Davidson told me: “When we started this course, as a group, the head and neck surgeons were the best to do the reconstructions on the face with skin flaps and grafts and layered closures. But now, as a group, the dermatologists are best at doing that.” That’s what we want to hear in medical education.

During the peak of the COVID-19 pandemic, what were your most significant challenges from both a clinical and a personal standpoint?

I’m fortunate to practice at a place like Scripps, where there are many resources to look at what was happening with COVID-19. Clinically, we had to put a lot of things on hold, but we tried our best to keep our cancer patients in particular in the forefront of care. It has been a challenge, but fortunately we have been able to take care of patients after a brief timeout. Many of us remember the polio vaccine back in the 1950s. Having worked overseas and at missionary hospital where we had children die of measles because they were not vaccinated gave me a larger appreciation for the importance of vaccines. I recommend all young physicians who work with me to read, “The Great Influenza: The Story of the Deadliest Pandemic in History,” by John M. Barry, which recounts the 1918 flu epidemic.

Who inspires you most in your work today?

I don’t view what I do as work. Dr. Jones and Dr. Mohs continue to inspire me with what they accomplished during their careers. You have to love people and love patients. Every patient who comes to see me has a story, so I try to understand their story. One of the things I really enjoy is training the young fellows. We train three Mohs fellows per year at Scripps, and it’s a great challenge every day.

What development in dermatology are you most excited about in the next 5 years?

Dermatology will continue to evolve just like all other medical specialties. We’re going to see a large growth in telemedicine, and immunotherapy is playing a key role in dermatologic oncology. What excites me the most in medicine is the young people who enter the field willing to contribute their lives to helping others.

Anyone who practices Mohs micrographic surgery is likely to know the name Hugh Greenway, MD, the longtime head of Mohs and dermatologic surgery at Scripps Clinic in San Diego, who was also recently selected as program director for cutaneous oncology at Scripps MD Anderson Cancer Center in San Diego. He is also a former president of the American College of Mohs Surgery.

After earning his medical degree from the Medical College of Georgia, Augusta, in 1974, Dr. Greenway was fellowship trained in Mohs skin cancer surgery by Frederic E. Mohs, MD, at the University of Wisconsin–Madison. He completed his dermatology residency at the Naval Medical Center San Diego and joined Scripps Clinic in 1983, where he launched the institution’s first Mohs surgery program, as well as a popular annual intensive course in superficial anatomy and cutaneous surgery that bears his name. He was also the first physician in the world to use interferon as a nonsurgical treatment of basal cell carcinoma.

Courtesy Scripps Clinic

To date, Dr. Greenway has performed more than 41,000 Mohs surgery cases and has trained 61 fellows who practice in academic and clinical settings. In 2017, he received the Frederic E. Mohs Award from the ACMS at the college’s annual meeting. He is also a past CEO of Scripps Clinic. In this Q&A, Dr. Greenway opens up about what it was like to train with Dr. Mohs, what makes a good Mohs surgeon, and why he’s excited about the future of dermatology.
 

I understand that you first became interested in a medical career after meeting Dr. Carl Jones, a friend of your father who was your Scoutmaster in the Boy Scouts in Georgia. What about Dr. Jones inspired you to pursue a career in medicine?

Dr. Jones was an internist/allergist in Atlanta, where I grew up. His three sons and I were friends. My dad had dealt with several medical problems being injured in World War II and subsequently undergoing a couple of kidney transplantations, so I developed an interest in medicine personally. Even though Dr. Jones was a specialist, he started out as a family doctor like I did, so he was interested in the whole person and all of his or her medical problems as opposed to those related to his specialty only. I traveled with the Boy Scouts to camp at places like Valley Forge in Pennsylvania, and Dr. Jones was involved with the medical set-ups of those large events. That also contributed to my interest in medicine.

As part of your 9-year service in the U.S. Navy, you spent 2 years as the flight surgeon at NAS Atlanta/Dobbins Air Force Base. What was your most memorable experience from that assignment?

Dobbins is a large facility with two Lockheed plants, and the Air Force had built the medical clinic, which was staffed by the Navy. Getting to know some of the active-duty members of the Air Force, the Navy, and the National Guard, and their commitment to our country, was memorable. Jimmy Carter was the president in those days. When he would fly in Dobbins, one of my jobs as the flight surgeon was to be on base when Air Force One landed or departed. One night, we had a DC-9 commercial aircraft coming from Huntsville, Ala., to Atlanta that got caught in a thunderstorm a little above 30,000 feet. Both engines went out and the aircraft essentially became a glider. The pilots tried to land on our runway but unfortunately, they ended up 4 miles short. We were heavily involved in responding to the crash, which was a tragic event. I also learned to fly (second seat) different types of aircraft during my assignment at NAS Atlanta/Dobbins Air Force Base, everything from the large C-5s to Navy fighter jets and helicopters. Coincidentally, Dr. Jones was involved with a couple of free health clinics in Atlanta when I was stationed there. Every Tuesday night, my wife (who is a nurse) and I would volunteer at a clinic in Cabbagetown, which was one of the poorer areas of Atlanta. It was a chance to give back to a group of people who didn’t have a whole lot.

In the middle your dermatology residency at Naval Medical Center San Diego, you were selected by Dr. Mohs for fellowship training in Mohs skin cancer surgery at the University of Wisconsin–Madison. What do you remember most about your training with Dr. Mohs?

Dr. Mohs was a kind, humble man who had this great idea about skin cancer. He was not a dermatologist; he was a general surgeon. The technique he developed was originally called chemosurgery because he put a chemical onto the skin. This was known as the fixed-tissue technique. Then we had a fresh-tissue technique, where we did not use the chemical, but we were able to use local anesthesia right away. That developed into the Mohs surgery we know today. Dr. Mohs did not name it that; he was very humble, but he was very proud of his technique. He was also a very hard worker. On the first day of my fellowship, I started at 7 in the morning and ended at 7 at night. It was the same for the last day of my fellowship. He also had an excellent office staff, many of whom had worked with him for many years. Patients with difficult skin cancers traveled to Madison from all over the world because there weren’t that many Mohs surgery clinics in those days. During the latter part of my fellowship, Michael McCall, MD, and I had the opportunity to remove a skin cancer from the nose of Dr. Mohs. We presented the case at a national conference, and I titled the talk “Mohs Surgery for Mohs’ Nose.”

Early in your career Dr. Mohs asked you to take over his practice, but you accepted an offer to establish the first Mohs surgery office at Scripps in San Diego instead. What convinced you to head West?

After my fellowship, I returned to San Diego to complete my residency with the Navy, where we opened a Mohs surgery clinic. Dr. Mohs came out for the ribbon cutting. During that time, I was taking care of several patients that he had treated in Wisconsin. Through that my wife and I ended up going to dinner with Cecil and Ida Green, philanthropists who made several financial gifts to Scripps Clinic – and for whom Scripps Green Hospital is named. Cecil cofounded Texas Instruments and was knighted by Queen Elizabeth. During dinner, he suggested that I stay in San Diego for a year and work at Scripps after my residency assignment with the Navy. I agreed and have been here ever since.

What do you find most interesting about Mohs surgery?

In Mohs surgery, you’re able to provide not only surgical care to eliminate the tumor, but also the pathology and the reconstruction. That was interesting to me. Dr. Mohs was not that interested in reconstruction. He was more focused on the tumor, in part because with the original fixed-tissue technique you could not do the reconstruction. You had to wait for an extra layer of tissue to separate. But with the fresh-tissue technique, you were able to provide the reconstruction that day. Mohs surgery deals with a subset of tumors that are challenging to treat. That also spiked my academic and clinical interest.

In your opinion, what’s been the most important advance in Mohs surgery to date?

In recent years, immunology has come into play, so now we have teams of clinicians in dermatology, medical oncology, surgery, and other subspecialties providing patients the best of care. In the arena of Mohs surgery itself, in the 1980s, the American College of Mohs Surgery developed a 1-year fellowship program, which enabled us to train many men and women to practice Mohs surgery. Most of them are dermatologists.

Please complete the sentence: “You can tell a good Mohs surgeon by the way he/she ...”

Treats patients, is willing to spend time with them, and shows an interest in them. One of the things we should strive for is to let patients know that they as a person are important; it’s not just the melanoma on their nose. We’re not only dealing with a skin cancer; we’re dealing with a patient who has skin cancer.

For the past 39 years, you have led Hugh Greenway’s Superficial Anatomy and Cutaneous Surgery course, which takes place every January in San Diego. What’s been key to sustaining this training course for nearly 4 decades?

There have been many people involved in its success, so it’s not just me. When I first started my practice, there really was not a focus on anatomy in the general dermatologic community. Dermatologic surgery textbooks contained very little content on surgical anatomy so I developed an interest a putting together a course that would cover some of this material. I met with Terence Davidson, MD, an otolaryngologist who was dean of continuing medical education at the University of California, San Diego. The course includes lectures from experts in many subspecialties and hands-on laboratories using cadavers to work on anatomy and surgical techniques. After about 16 years of doing the course Dr. Davidson told me: “When we started this course, as a group, the head and neck surgeons were the best to do the reconstructions on the face with skin flaps and grafts and layered closures. But now, as a group, the dermatologists are best at doing that.” That’s what we want to hear in medical education.

During the peak of the COVID-19 pandemic, what were your most significant challenges from both a clinical and a personal standpoint?

I’m fortunate to practice at a place like Scripps, where there are many resources to look at what was happening with COVID-19. Clinically, we had to put a lot of things on hold, but we tried our best to keep our cancer patients in particular in the forefront of care. It has been a challenge, but fortunately we have been able to take care of patients after a brief timeout. Many of us remember the polio vaccine back in the 1950s. Having worked overseas and at missionary hospital where we had children die of measles because they were not vaccinated gave me a larger appreciation for the importance of vaccines. I recommend all young physicians who work with me to read, “The Great Influenza: The Story of the Deadliest Pandemic in History,” by John M. Barry, which recounts the 1918 flu epidemic.

Who inspires you most in your work today?

I don’t view what I do as work. Dr. Jones and Dr. Mohs continue to inspire me with what they accomplished during their careers. You have to love people and love patients. Every patient who comes to see me has a story, so I try to understand their story. One of the things I really enjoy is training the young fellows. We train three Mohs fellows per year at Scripps, and it’s a great challenge every day.

What development in dermatology are you most excited about in the next 5 years?

Dermatology will continue to evolve just like all other medical specialties. We’re going to see a large growth in telemedicine, and immunotherapy is playing a key role in dermatologic oncology. What excites me the most in medicine is the young people who enter the field willing to contribute their lives to helping others.

Anyone who practices Mohs micrographic surgery is likely to know the name Hugh Greenway, MD, the longtime head of Mohs and dermatologic surgery at Scripps Clinic in San Diego, who was also recently selected as program director for cutaneous oncology at Scripps MD Anderson Cancer Center in San Diego. He is also a former president of the American College of Mohs Surgery.

After earning his medical degree from the Medical College of Georgia, Augusta, in 1974, Dr. Greenway was fellowship trained in Mohs skin cancer surgery by Frederic E. Mohs, MD, at the University of Wisconsin–Madison. He completed his dermatology residency at the Naval Medical Center San Diego and joined Scripps Clinic in 1983, where he launched the institution’s first Mohs surgery program, as well as a popular annual intensive course in superficial anatomy and cutaneous surgery that bears his name. He was also the first physician in the world to use interferon as a nonsurgical treatment of basal cell carcinoma.

Courtesy Scripps Clinic

To date, Dr. Greenway has performed more than 41,000 Mohs surgery cases and has trained 61 fellows who practice in academic and clinical settings. In 2017, he received the Frederic E. Mohs Award from the ACMS at the college’s annual meeting. He is also a past CEO of Scripps Clinic. In this Q&A, Dr. Greenway opens up about what it was like to train with Dr. Mohs, what makes a good Mohs surgeon, and why he’s excited about the future of dermatology.
 

I understand that you first became interested in a medical career after meeting Dr. Carl Jones, a friend of your father who was your Scoutmaster in the Boy Scouts in Georgia. What about Dr. Jones inspired you to pursue a career in medicine?

Dr. Jones was an internist/allergist in Atlanta, where I grew up. His three sons and I were friends. My dad had dealt with several medical problems being injured in World War II and subsequently undergoing a couple of kidney transplantations, so I developed an interest in medicine personally. Even though Dr. Jones was a specialist, he started out as a family doctor like I did, so he was interested in the whole person and all of his or her medical problems as opposed to those related to his specialty only. I traveled with the Boy Scouts to camp at places like Valley Forge in Pennsylvania, and Dr. Jones was involved with the medical set-ups of those large events. That also contributed to my interest in medicine.

As part of your 9-year service in the U.S. Navy, you spent 2 years as the flight surgeon at NAS Atlanta/Dobbins Air Force Base. What was your most memorable experience from that assignment?

Dobbins is a large facility with two Lockheed plants, and the Air Force had built the medical clinic, which was staffed by the Navy. Getting to know some of the active-duty members of the Air Force, the Navy, and the National Guard, and their commitment to our country, was memorable. Jimmy Carter was the president in those days. When he would fly in Dobbins, one of my jobs as the flight surgeon was to be on base when Air Force One landed or departed. One night, we had a DC-9 commercial aircraft coming from Huntsville, Ala., to Atlanta that got caught in a thunderstorm a little above 30,000 feet. Both engines went out and the aircraft essentially became a glider. The pilots tried to land on our runway but unfortunately, they ended up 4 miles short. We were heavily involved in responding to the crash, which was a tragic event. I also learned to fly (second seat) different types of aircraft during my assignment at NAS Atlanta/Dobbins Air Force Base, everything from the large C-5s to Navy fighter jets and helicopters. Coincidentally, Dr. Jones was involved with a couple of free health clinics in Atlanta when I was stationed there. Every Tuesday night, my wife (who is a nurse) and I would volunteer at a clinic in Cabbagetown, which was one of the poorer areas of Atlanta. It was a chance to give back to a group of people who didn’t have a whole lot.

In the middle your dermatology residency at Naval Medical Center San Diego, you were selected by Dr. Mohs for fellowship training in Mohs skin cancer surgery at the University of Wisconsin–Madison. What do you remember most about your training with Dr. Mohs?

Dr. Mohs was a kind, humble man who had this great idea about skin cancer. He was not a dermatologist; he was a general surgeon. The technique he developed was originally called chemosurgery because he put a chemical onto the skin. This was known as the fixed-tissue technique. Then we had a fresh-tissue technique, where we did not use the chemical, but we were able to use local anesthesia right away. That developed into the Mohs surgery we know today. Dr. Mohs did not name it that; he was very humble, but he was very proud of his technique. He was also a very hard worker. On the first day of my fellowship, I started at 7 in the morning and ended at 7 at night. It was the same for the last day of my fellowship. He also had an excellent office staff, many of whom had worked with him for many years. Patients with difficult skin cancers traveled to Madison from all over the world because there weren’t that many Mohs surgery clinics in those days. During the latter part of my fellowship, Michael McCall, MD, and I had the opportunity to remove a skin cancer from the nose of Dr. Mohs. We presented the case at a national conference, and I titled the talk “Mohs Surgery for Mohs’ Nose.”

Early in your career Dr. Mohs asked you to take over his practice, but you accepted an offer to establish the first Mohs surgery office at Scripps in San Diego instead. What convinced you to head West?

After my fellowship, I returned to San Diego to complete my residency with the Navy, where we opened a Mohs surgery clinic. Dr. Mohs came out for the ribbon cutting. During that time, I was taking care of several patients that he had treated in Wisconsin. Through that my wife and I ended up going to dinner with Cecil and Ida Green, philanthropists who made several financial gifts to Scripps Clinic – and for whom Scripps Green Hospital is named. Cecil cofounded Texas Instruments and was knighted by Queen Elizabeth. During dinner, he suggested that I stay in San Diego for a year and work at Scripps after my residency assignment with the Navy. I agreed and have been here ever since.

What do you find most interesting about Mohs surgery?

In Mohs surgery, you’re able to provide not only surgical care to eliminate the tumor, but also the pathology and the reconstruction. That was interesting to me. Dr. Mohs was not that interested in reconstruction. He was more focused on the tumor, in part because with the original fixed-tissue technique you could not do the reconstruction. You had to wait for an extra layer of tissue to separate. But with the fresh-tissue technique, you were able to provide the reconstruction that day. Mohs surgery deals with a subset of tumors that are challenging to treat. That also spiked my academic and clinical interest.

In your opinion, what’s been the most important advance in Mohs surgery to date?

In recent years, immunology has come into play, so now we have teams of clinicians in dermatology, medical oncology, surgery, and other subspecialties providing patients the best of care. In the arena of Mohs surgery itself, in the 1980s, the American College of Mohs Surgery developed a 1-year fellowship program, which enabled us to train many men and women to practice Mohs surgery. Most of them are dermatologists.

Please complete the sentence: “You can tell a good Mohs surgeon by the way he/she ...”

Treats patients, is willing to spend time with them, and shows an interest in them. One of the things we should strive for is to let patients know that they as a person are important; it’s not just the melanoma on their nose. We’re not only dealing with a skin cancer; we’re dealing with a patient who has skin cancer.

For the past 39 years, you have led Hugh Greenway’s Superficial Anatomy and Cutaneous Surgery course, which takes place every January in San Diego. What’s been key to sustaining this training course for nearly 4 decades?

There have been many people involved in its success, so it’s not just me. When I first started my practice, there really was not a focus on anatomy in the general dermatologic community. Dermatologic surgery textbooks contained very little content on surgical anatomy so I developed an interest a putting together a course that would cover some of this material. I met with Terence Davidson, MD, an otolaryngologist who was dean of continuing medical education at the University of California, San Diego. The course includes lectures from experts in many subspecialties and hands-on laboratories using cadavers to work on anatomy and surgical techniques. After about 16 years of doing the course Dr. Davidson told me: “When we started this course, as a group, the head and neck surgeons were the best to do the reconstructions on the face with skin flaps and grafts and layered closures. But now, as a group, the dermatologists are best at doing that.” That’s what we want to hear in medical education.

During the peak of the COVID-19 pandemic, what were your most significant challenges from both a clinical and a personal standpoint?

I’m fortunate to practice at a place like Scripps, where there are many resources to look at what was happening with COVID-19. Clinically, we had to put a lot of things on hold, but we tried our best to keep our cancer patients in particular in the forefront of care. It has been a challenge, but fortunately we have been able to take care of patients after a brief timeout. Many of us remember the polio vaccine back in the 1950s. Having worked overseas and at missionary hospital where we had children die of measles because they were not vaccinated gave me a larger appreciation for the importance of vaccines. I recommend all young physicians who work with me to read, “The Great Influenza: The Story of the Deadliest Pandemic in History,” by John M. Barry, which recounts the 1918 flu epidemic.

Who inspires you most in your work today?

I don’t view what I do as work. Dr. Jones and Dr. Mohs continue to inspire me with what they accomplished during their careers. You have to love people and love patients. Every patient who comes to see me has a story, so I try to understand their story. One of the things I really enjoy is training the young fellows. We train three Mohs fellows per year at Scripps, and it’s a great challenge every day.

What development in dermatology are you most excited about in the next 5 years?

Dermatology will continue to evolve just like all other medical specialties. We’re going to see a large growth in telemedicine, and immunotherapy is playing a key role in dermatologic oncology. What excites me the most in medicine is the young people who enter the field willing to contribute their lives to helping others.

The persistent shortage of dacarbazine has led to an “acute and unprecedented crisis” in the treatment of patients with advanced classical Hodgkin lymphoma, experts say.

Dacarbazine, an essential part of the four-drug standard of care for managing Hodgkin lymphoma, has been in short supply since last summer, prompting experts to search for a viable substitute.

In a recent review, oncologists scoured decades of data to find the best alternatives for a range of scenarios. For fit adults younger than 60, the group recommends the seven-drug regimen BEACOPP – bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone.

“Among all available regimens,” BEACOPP has “the most robust evidence” as a substitute for the four-drug standard ABVD, which includes doxorubicin, bleomycin, vinblastine, and dacarbazine, Pallawi Torka, MD, a hematologic oncologist at Roswell Park Comprehensive Cancer Center, Buffalo, N.Y., and colleagues wrote in JCO Oncology Practice.

Last October, the Food and Drug Administration posted a notice about the dacarbazine shortage. According to the notice, the shortage occurred because of “manufacturing delays” and a “demand increase” affecting three companies supplying the U.S. market – Fresenius Kabi USA, Hikma Pharmaceuticals, and Teva. In an update issued May 4, the FDA said that 100-mg and 200-mg vials of the drug are now available from Fresenius. An update from April 8 said that 200-mg vials were available from Hikma.

Dacarbazine is hardly the only oncology drug to fall into short supply. Recent data show that shortages of oncology drugs have become more common in the United States in recent years, particularly generic drugs and those targeting hematologic malignancies.

In a recent national survey of oncology pharmacists, researchers found that almost two-thirds of institutions reported at least one drug shortage in the past month, representing a 34% increase between 2018 and 2019.

“This shortage of [dacarbazine] is not the first shortage of oncolytic drugs, and it certainly will not be the last,” Nicole Soriano, PharmD, hematology/oncology clinical pharmacist at Northwestern Memorial Hospital, Chicago, and colleagues wrote in a commentary accompanying the review.

According to Dr. Soriano and coauthors, “some studies have found that shortages are significant across many oncology disciplines and may lead to delays, changes in therapy, interference with clinical research, increased risk of medication errors, adverse outcomes, and increased costs.”
 

Finding a substitute

In the current analysis, Dr. Torka and her team conducted an exhaustive literature review in which they examined studies going back decades.

The authors highlight more than 10 alternative regimens for treating advanced classical Hodgkin lymphoma. They also provide a detailed treatment algorithm to help oncologists choose the best option for their individual patients as well as strategies for reintegrating ABVD into patient care should the supply of dacarbazine return to normal.

The first considerations: Can patients tolerate intensive chemotherapy, and are patients younger than 60?

For fit adults younger than 60, Dr. Torka and colleagues conclude that the BEACOPP regimen is the “preferred” option. In trials comparing ABVD to BEACOPP, both regimens demonstrated similar overall survival. And while BEACOPP may provide slightly “better disease control,” this approach may also come with greater toxicities in the short and long term, compared with ABVD, depending on the dosing strategy.

The authors also propose an alternative treatment strategy in case the supply of dacarbazine returns to normal mid-treatment. In this scenario, patients could receive an escalated BEACOPP regimen for two cycles and then undergo an interim positron-emission tomography scan. If the scan is negative and dacarbazine is available, the patient’s regimen could be deescalated to ABVD for four cycles without affecting disease control.

For pediatric patients, the authors recommend the ABVE-PC regimen, which includes six drugs – doxorubicin, bleomycin, vincristine, etoposide, prednisone, and cyclophosphamide. Data show that the 5-year overall survival among pediatric patients receiving ABVE-PC is 95%.

Stanford V-C – cyclophosphamide, doxorubicin hydrochloride, vinblastine, vincristine, bleomycin, etoposide, and prednisone – is another “acceptable approach” for pediatric patients, the authors noted.

For older patients with advanced disease or those unfit for intensive chemotherapy, the authors suggest evaluating them for fitness for anthracyclines to determine whether doxorubicin, in particular, is an option.

The researchers suggest one of the following three strategies for those who are doxorubicin-eligible: PVAG (prednisone, vinblastine, doxorubicin, and gemcitabine), CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone), or EVA (etoposide, vinblastine, and doxorubicin).

For those unfit for anthracyclines, the options include COPP (cyclophosphamide, vincristine, procarbazine, and prednisone) or ChlVPP (chlorambucil, vinblastine, procarbazine, and prednisone).

For frail patients who are ineligible for chemotherapy, the team recommends brentuximab alone or in combination with nivolumab.

Given the limited availability of dacarbazine, the authors say that the “current supply should be triaged to prioritize patients whose therapy cannot be changed and those without alternative acceptable options.”

To stretch available dacarbazine supplies as much as possible, the researchers and editorialists advocate for rounding doses within 5%-10% of the prescribed dose.

For example, Dr. Torka and colleagues explained, rounding a dose from 750 mg down to 700 mg would save one vial of dacarbazine.

Vial sharing and using drugs beyond their use dates by compounding with closed-system transfer devices are other strategies to preserve the existing supply of dacarbazine.

The goal of this review “is to give as many patients as possible the most optimal and efficacious therapy even with the strain on supply,” the editorialists wrote.

No funding for the study was reported. Dr. Torka is an adviser for Genentech, ADC Therapeutics, and TG Therapeutics. Dr. Soriano has disclosed no relevant financial relationships.

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

The persistent shortage of dacarbazine has led to an “acute and unprecedented crisis” in the treatment of patients with advanced classical Hodgkin lymphoma, experts say.

Dacarbazine, an essential part of the four-drug standard of care for managing Hodgkin lymphoma, has been in short supply since last summer, prompting experts to search for a viable substitute.

In a recent review, oncologists scoured decades of data to find the best alternatives for a range of scenarios. For fit adults younger than 60, the group recommends the seven-drug regimen BEACOPP – bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone.

“Among all available regimens,” BEACOPP has “the most robust evidence” as a substitute for the four-drug standard ABVD, which includes doxorubicin, bleomycin, vinblastine, and dacarbazine, Pallawi Torka, MD, a hematologic oncologist at Roswell Park Comprehensive Cancer Center, Buffalo, N.Y., and colleagues wrote in JCO Oncology Practice.

Last October, the Food and Drug Administration posted a notice about the dacarbazine shortage. According to the notice, the shortage occurred because of “manufacturing delays” and a “demand increase” affecting three companies supplying the U.S. market – Fresenius Kabi USA, Hikma Pharmaceuticals, and Teva. In an update issued May 4, the FDA said that 100-mg and 200-mg vials of the drug are now available from Fresenius. An update from April 8 said that 200-mg vials were available from Hikma.

Dacarbazine is hardly the only oncology drug to fall into short supply. Recent data show that shortages of oncology drugs have become more common in the United States in recent years, particularly generic drugs and those targeting hematologic malignancies.

In a recent national survey of oncology pharmacists, researchers found that almost two-thirds of institutions reported at least one drug shortage in the past month, representing a 34% increase between 2018 and 2019.

“This shortage of [dacarbazine] is not the first shortage of oncolytic drugs, and it certainly will not be the last,” Nicole Soriano, PharmD, hematology/oncology clinical pharmacist at Northwestern Memorial Hospital, Chicago, and colleagues wrote in a commentary accompanying the review.

According to Dr. Soriano and coauthors, “some studies have found that shortages are significant across many oncology disciplines and may lead to delays, changes in therapy, interference with clinical research, increased risk of medication errors, adverse outcomes, and increased costs.”
 

Finding a substitute

In the current analysis, Dr. Torka and her team conducted an exhaustive literature review in which they examined studies going back decades.

The authors highlight more than 10 alternative regimens for treating advanced classical Hodgkin lymphoma. They also provide a detailed treatment algorithm to help oncologists choose the best option for their individual patients as well as strategies for reintegrating ABVD into patient care should the supply of dacarbazine return to normal.

The first considerations: Can patients tolerate intensive chemotherapy, and are patients younger than 60?

For fit adults younger than 60, Dr. Torka and colleagues conclude that the BEACOPP regimen is the “preferred” option. In trials comparing ABVD to BEACOPP, both regimens demonstrated similar overall survival. And while BEACOPP may provide slightly “better disease control,” this approach may also come with greater toxicities in the short and long term, compared with ABVD, depending on the dosing strategy.

The authors also propose an alternative treatment strategy in case the supply of dacarbazine returns to normal mid-treatment. In this scenario, patients could receive an escalated BEACOPP regimen for two cycles and then undergo an interim positron-emission tomography scan. If the scan is negative and dacarbazine is available, the patient’s regimen could be deescalated to ABVD for four cycles without affecting disease control.

For pediatric patients, the authors recommend the ABVE-PC regimen, which includes six drugs – doxorubicin, bleomycin, vincristine, etoposide, prednisone, and cyclophosphamide. Data show that the 5-year overall survival among pediatric patients receiving ABVE-PC is 95%.

Stanford V-C – cyclophosphamide, doxorubicin hydrochloride, vinblastine, vincristine, bleomycin, etoposide, and prednisone – is another “acceptable approach” for pediatric patients, the authors noted.

For older patients with advanced disease or those unfit for intensive chemotherapy, the authors suggest evaluating them for fitness for anthracyclines to determine whether doxorubicin, in particular, is an option.

The researchers suggest one of the following three strategies for those who are doxorubicin-eligible: PVAG (prednisone, vinblastine, doxorubicin, and gemcitabine), CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone), or EVA (etoposide, vinblastine, and doxorubicin).

For those unfit for anthracyclines, the options include COPP (cyclophosphamide, vincristine, procarbazine, and prednisone) or ChlVPP (chlorambucil, vinblastine, procarbazine, and prednisone).

For frail patients who are ineligible for chemotherapy, the team recommends brentuximab alone or in combination with nivolumab.

Given the limited availability of dacarbazine, the authors say that the “current supply should be triaged to prioritize patients whose therapy cannot be changed and those without alternative acceptable options.”

To stretch available dacarbazine supplies as much as possible, the researchers and editorialists advocate for rounding doses within 5%-10% of the prescribed dose.

For example, Dr. Torka and colleagues explained, rounding a dose from 750 mg down to 700 mg would save one vial of dacarbazine.

Vial sharing and using drugs beyond their use dates by compounding with closed-system transfer devices are other strategies to preserve the existing supply of dacarbazine.

The goal of this review “is to give as many patients as possible the most optimal and efficacious therapy even with the strain on supply,” the editorialists wrote.

No funding for the study was reported. Dr. Torka is an adviser for Genentech, ADC Therapeutics, and TG Therapeutics. Dr. Soriano has disclosed no relevant financial relationships.

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

The persistent shortage of dacarbazine has led to an “acute and unprecedented crisis” in the treatment of patients with advanced classical Hodgkin lymphoma, experts say.

Dacarbazine, an essential part of the four-drug standard of care for managing Hodgkin lymphoma, has been in short supply since last summer, prompting experts to search for a viable substitute.

In a recent review, oncologists scoured decades of data to find the best alternatives for a range of scenarios. For fit adults younger than 60, the group recommends the seven-drug regimen BEACOPP – bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone.

“Among all available regimens,” BEACOPP has “the most robust evidence” as a substitute for the four-drug standard ABVD, which includes doxorubicin, bleomycin, vinblastine, and dacarbazine, Pallawi Torka, MD, a hematologic oncologist at Roswell Park Comprehensive Cancer Center, Buffalo, N.Y., and colleagues wrote in JCO Oncology Practice.

Last October, the Food and Drug Administration posted a notice about the dacarbazine shortage. According to the notice, the shortage occurred because of “manufacturing delays” and a “demand increase” affecting three companies supplying the U.S. market – Fresenius Kabi USA, Hikma Pharmaceuticals, and Teva. In an update issued May 4, the FDA said that 100-mg and 200-mg vials of the drug are now available from Fresenius. An update from April 8 said that 200-mg vials were available from Hikma.

Dacarbazine is hardly the only oncology drug to fall into short supply. Recent data show that shortages of oncology drugs have become more common in the United States in recent years, particularly generic drugs and those targeting hematologic malignancies.

In a recent national survey of oncology pharmacists, researchers found that almost two-thirds of institutions reported at least one drug shortage in the past month, representing a 34% increase between 2018 and 2019.

“This shortage of [dacarbazine] is not the first shortage of oncolytic drugs, and it certainly will not be the last,” Nicole Soriano, PharmD, hematology/oncology clinical pharmacist at Northwestern Memorial Hospital, Chicago, and colleagues wrote in a commentary accompanying the review.

According to Dr. Soriano and coauthors, “some studies have found that shortages are significant across many oncology disciplines and may lead to delays, changes in therapy, interference with clinical research, increased risk of medication errors, adverse outcomes, and increased costs.”
 

Finding a substitute

In the current analysis, Dr. Torka and her team conducted an exhaustive literature review in which they examined studies going back decades.

The authors highlight more than 10 alternative regimens for treating advanced classical Hodgkin lymphoma. They also provide a detailed treatment algorithm to help oncologists choose the best option for their individual patients as well as strategies for reintegrating ABVD into patient care should the supply of dacarbazine return to normal.

The first considerations: Can patients tolerate intensive chemotherapy, and are patients younger than 60?

For fit adults younger than 60, Dr. Torka and colleagues conclude that the BEACOPP regimen is the “preferred” option. In trials comparing ABVD to BEACOPP, both regimens demonstrated similar overall survival. And while BEACOPP may provide slightly “better disease control,” this approach may also come with greater toxicities in the short and long term, compared with ABVD, depending on the dosing strategy.

The authors also propose an alternative treatment strategy in case the supply of dacarbazine returns to normal mid-treatment. In this scenario, patients could receive an escalated BEACOPP regimen for two cycles and then undergo an interim positron-emission tomography scan. If the scan is negative and dacarbazine is available, the patient’s regimen could be deescalated to ABVD for four cycles without affecting disease control.

For pediatric patients, the authors recommend the ABVE-PC regimen, which includes six drugs – doxorubicin, bleomycin, vincristine, etoposide, prednisone, and cyclophosphamide. Data show that the 5-year overall survival among pediatric patients receiving ABVE-PC is 95%.

Stanford V-C – cyclophosphamide, doxorubicin hydrochloride, vinblastine, vincristine, bleomycin, etoposide, and prednisone – is another “acceptable approach” for pediatric patients, the authors noted.

For older patients with advanced disease or those unfit for intensive chemotherapy, the authors suggest evaluating them for fitness for anthracyclines to determine whether doxorubicin, in particular, is an option.

The researchers suggest one of the following three strategies for those who are doxorubicin-eligible: PVAG (prednisone, vinblastine, doxorubicin, and gemcitabine), CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone), or EVA (etoposide, vinblastine, and doxorubicin).

For those unfit for anthracyclines, the options include COPP (cyclophosphamide, vincristine, procarbazine, and prednisone) or ChlVPP (chlorambucil, vinblastine, procarbazine, and prednisone).

For frail patients who are ineligible for chemotherapy, the team recommends brentuximab alone or in combination with nivolumab.

Given the limited availability of dacarbazine, the authors say that the “current supply should be triaged to prioritize patients whose therapy cannot be changed and those without alternative acceptable options.”

To stretch available dacarbazine supplies as much as possible, the researchers and editorialists advocate for rounding doses within 5%-10% of the prescribed dose.

For example, Dr. Torka and colleagues explained, rounding a dose from 750 mg down to 700 mg would save one vial of dacarbazine.

Vial sharing and using drugs beyond their use dates by compounding with closed-system transfer devices are other strategies to preserve the existing supply of dacarbazine.

The goal of this review “is to give as many patients as possible the most optimal and efficacious therapy even with the strain on supply,” the editorialists wrote.

No funding for the study was reported. Dr. Torka is an adviser for Genentech, ADC Therapeutics, and TG Therapeutics. Dr. Soriano has disclosed no relevant financial relationships.

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

When it comes to mammography recommendations state comprehensive cancer control (CCC) plans vary considerably and don’t always closely match the U.S. Preventive Services Task Force (USPSTF) recommendations for mammography frequency in women at average risk for breast cancer, according to a new cross-sectional study of CCC plans in all 50 states and the District of Columbia. The recommended age for initiation varied widely among CCC plans, and nearly one in five bore little resemblance at all to the USPTF recommendations.

According to the authors of the study, the variation among suggested ages of initiation may indicate a lack of consensus among state agencies. “For a recommendation tied to service coverage, this is a serious gap in public health policy,” they wrote in the study published online in JAMA Network Open.

CCC plans include goals, measurable objectives, and evidence-based strategies to combat cancers that are both common and preventable. They include input from multiple groups, frequently take 4-6 years to create, and should be updated regularly. Funding from the Centers for Disease Control and Prevention requires that the plans include data cancer screening prevalence rates and specific objectives and strategies.

Breast cancer is the most common cancer in women in the United States, and the second highest cause of cancer death. Regular, high-quality screening reduces breast cancer mortality by 25%-31% among women aged 50-69. As a result, the American Cancer Society, the USPSTF, the American College of Physicians, and the American Academy of Family Physicians have produced guidelines for mammography screening in women at average risk of breast cancer.

Although the benefits of screening are widely accepted, there is disagreement about the ages it should be initiated and ended. These inconsistencies stem from different evidence used to support recommendations, as well as different standards for benefits and harms from screening. Common concerns include overdiagnosis, false-positive results, and radiation damage from mammography.

Because these benefits and harms can vary based on age and values, there is an emphasis on shared decision-making between clinicians and women, especially those aged 40-49.

The most recent USPTF recommendation, issued in 2016, states that women aged 50-74 with average risk should be screened with mammography every 2 years. The choice of mammography in average-risk women under 50 should be approached on an individual basis. USPTF defines average risk as having no signs, symptoms, or previous diagnosis of breast cancer, and no family history or genetic causes for concern.

In the new study, researchers conducted a point-in-time evaluation of CCC plans from 50 states and the District of Columbia, between Nov. 1, 2019, and June 30, 2021.

Thirty-one percent of the plans included the complete USPTF recommendations of biennial mammography between ages 50 and 74; 51% included some, but not all of the USPTF recommendations; and 18% were not consistent at all with USPTF recommendations.

Overall, 59% of plans recommended initiation at age 50 and 37% at age 40, which is consistent with the older 2009 USPSTF recommendation. Eight percent of plans recommended starting at both 40 and 50, and 20% of plans had no recommended age of initiation.

Among the plans that were partially consistent with USPTF, 73% recommended initiation of mammography at age 40 and 31% at age 50. Eighty-five percent did not include an age to stop mammography; 15% did not include a recommended frequency; and 15% had an initiation age other than 40 or 50. Eighty-five percent of plans partially consistent with USPSTF included a recommendation that mammography should be conducted biennially.

The authors state that CCC plans could be improved by a unified emphasis on biennial screening of the general population of women aged 50-74, as well as clear differentiation between women at average risk and those at high risk, who could be screened at ages younger than 50 in consultation with their physician.

The study is limited by the fact that plans were reviewed a single time, while state CCC plans are updated with varying periodicity. The authors agree that implementation of population-based screening should be tailored to individual states and health care systems.

When it comes to mammography recommendations state comprehensive cancer control (CCC) plans vary considerably and don’t always closely match the U.S. Preventive Services Task Force (USPSTF) recommendations for mammography frequency in women at average risk for breast cancer, according to a new cross-sectional study of CCC plans in all 50 states and the District of Columbia. The recommended age for initiation varied widely among CCC plans, and nearly one in five bore little resemblance at all to the USPTF recommendations.

According to the authors of the study, the variation among suggested ages of initiation may indicate a lack of consensus among state agencies. “For a recommendation tied to service coverage, this is a serious gap in public health policy,” they wrote in the study published online in JAMA Network Open.

CCC plans include goals, measurable objectives, and evidence-based strategies to combat cancers that are both common and preventable. They include input from multiple groups, frequently take 4-6 years to create, and should be updated regularly. Funding from the Centers for Disease Control and Prevention requires that the plans include data cancer screening prevalence rates and specific objectives and strategies.

Breast cancer is the most common cancer in women in the United States, and the second highest cause of cancer death. Regular, high-quality screening reduces breast cancer mortality by 25%-31% among women aged 50-69. As a result, the American Cancer Society, the USPSTF, the American College of Physicians, and the American Academy of Family Physicians have produced guidelines for mammography screening in women at average risk of breast cancer.

Although the benefits of screening are widely accepted, there is disagreement about the ages it should be initiated and ended. These inconsistencies stem from different evidence used to support recommendations, as well as different standards for benefits and harms from screening. Common concerns include overdiagnosis, false-positive results, and radiation damage from mammography.

Because these benefits and harms can vary based on age and values, there is an emphasis on shared decision-making between clinicians and women, especially those aged 40-49.

The most recent USPTF recommendation, issued in 2016, states that women aged 50-74 with average risk should be screened with mammography every 2 years. The choice of mammography in average-risk women under 50 should be approached on an individual basis. USPTF defines average risk as having no signs, symptoms, or previous diagnosis of breast cancer, and no family history or genetic causes for concern.

In the new study, researchers conducted a point-in-time evaluation of CCC plans from 50 states and the District of Columbia, between Nov. 1, 2019, and June 30, 2021.

Thirty-one percent of the plans included the complete USPTF recommendations of biennial mammography between ages 50 and 74; 51% included some, but not all of the USPTF recommendations; and 18% were not consistent at all with USPTF recommendations.

Overall, 59% of plans recommended initiation at age 50 and 37% at age 40, which is consistent with the older 2009 USPSTF recommendation. Eight percent of plans recommended starting at both 40 and 50, and 20% of plans had no recommended age of initiation.

Among the plans that were partially consistent with USPTF, 73% recommended initiation of mammography at age 40 and 31% at age 50. Eighty-five percent did not include an age to stop mammography; 15% did not include a recommended frequency; and 15% had an initiation age other than 40 or 50. Eighty-five percent of plans partially consistent with USPSTF included a recommendation that mammography should be conducted biennially.

The authors state that CCC plans could be improved by a unified emphasis on biennial screening of the general population of women aged 50-74, as well as clear differentiation between women at average risk and those at high risk, who could be screened at ages younger than 50 in consultation with their physician.

The study is limited by the fact that plans were reviewed a single time, while state CCC plans are updated with varying periodicity. The authors agree that implementation of population-based screening should be tailored to individual states and health care systems.

When it comes to mammography recommendations state comprehensive cancer control (CCC) plans vary considerably and don’t always closely match the U.S. Preventive Services Task Force (USPSTF) recommendations for mammography frequency in women at average risk for breast cancer, according to a new cross-sectional study of CCC plans in all 50 states and the District of Columbia. The recommended age for initiation varied widely among CCC plans, and nearly one in five bore little resemblance at all to the USPTF recommendations.

According to the authors of the study, the variation among suggested ages of initiation may indicate a lack of consensus among state agencies. “For a recommendation tied to service coverage, this is a serious gap in public health policy,” they wrote in the study published online in JAMA Network Open.

CCC plans include goals, measurable objectives, and evidence-based strategies to combat cancers that are both common and preventable. They include input from multiple groups, frequently take 4-6 years to create, and should be updated regularly. Funding from the Centers for Disease Control and Prevention requires that the plans include data cancer screening prevalence rates and specific objectives and strategies.

Breast cancer is the most common cancer in women in the United States, and the second highest cause of cancer death. Regular, high-quality screening reduces breast cancer mortality by 25%-31% among women aged 50-69. As a result, the American Cancer Society, the USPSTF, the American College of Physicians, and the American Academy of Family Physicians have produced guidelines for mammography screening in women at average risk of breast cancer.

Although the benefits of screening are widely accepted, there is disagreement about the ages it should be initiated and ended. These inconsistencies stem from different evidence used to support recommendations, as well as different standards for benefits and harms from screening. Common concerns include overdiagnosis, false-positive results, and radiation damage from mammography.

Because these benefits and harms can vary based on age and values, there is an emphasis on shared decision-making between clinicians and women, especially those aged 40-49.

The most recent USPTF recommendation, issued in 2016, states that women aged 50-74 with average risk should be screened with mammography every 2 years. The choice of mammography in average-risk women under 50 should be approached on an individual basis. USPTF defines average risk as having no signs, symptoms, or previous diagnosis of breast cancer, and no family history or genetic causes for concern.

In the new study, researchers conducted a point-in-time evaluation of CCC plans from 50 states and the District of Columbia, between Nov. 1, 2019, and June 30, 2021.

Thirty-one percent of the plans included the complete USPTF recommendations of biennial mammography between ages 50 and 74; 51% included some, but not all of the USPTF recommendations; and 18% were not consistent at all with USPTF recommendations.

Overall, 59% of plans recommended initiation at age 50 and 37% at age 40, which is consistent with the older 2009 USPSTF recommendation. Eight percent of plans recommended starting at both 40 and 50, and 20% of plans had no recommended age of initiation.

Among the plans that were partially consistent with USPTF, 73% recommended initiation of mammography at age 40 and 31% at age 50. Eighty-five percent did not include an age to stop mammography; 15% did not include a recommended frequency; and 15% had an initiation age other than 40 or 50. Eighty-five percent of plans partially consistent with USPSTF included a recommendation that mammography should be conducted biennially.

The authors state that CCC plans could be improved by a unified emphasis on biennial screening of the general population of women aged 50-74, as well as clear differentiation between women at average risk and those at high risk, who could be screened at ages younger than 50 in consultation with their physician.

The study is limited by the fact that plans were reviewed a single time, while state CCC plans are updated with varying periodicity. The authors agree that implementation of population-based screening should be tailored to individual states and health care systems.

Burnout and other forms of psychosocial distress are common among health care professionals necessitating measures to promote well-being and reduce burnout.¹ Studies have shown that nonmedical reading is associated with low burnout and that small group study sections can promote wellness.^2,3 Narrative medicine, which proposes a model for humane and effective medical practice, advocates for the necessity of narrative competence.

Short Story Club

Narrative competence is the ability to acknowledge, interpret, and act on the stories of others. The narrative skill of close reading also encourages reflective practice, equipping practitioners to better weather the tides of illness.⁴ In our case, we formed a short story club intervention to closely read, or read and reflect, on literary fiction. We explored how reading and reflecting would result in profound changes in thinking and feeling and noted different ways by which they can cause such well-being. We describe here the 7 ways in which stories led us to increase bonding, improve empathy, and promote meaning in medicine.

Slowing Down

The short story club helped to bond us together and increase our sense of meaning in medicine by slowing us down. One member of the group likened the experience to increasing the pixels in a painting, thereby improving the resolution and seeing more clearly. Another member mentioned the experience as a form of meditation in slowing down the brain, breathing in the story, and breathing out impressions. One story by Anatole Broyard emphasized the importance of slowing down and “brooding” over a patient.⁵ The author describes his experience as a prostate cancer patient, in which his body was treated but his story was ignored. He begged his doctors to pay more attention to his story to listen and to brood over him. This story was enlightening to us; we saw how desperate our patients are to tell their stories, and for us to hear their stories.

Mirrors and Windows

Another way reading and reflecting on short stories helped was by reflecting our practices to ourselves, as though looking into a mirror to see ourselves and out of a window to see others. We found that stories mirrored our own world and allowed us to discuss issues close to us without the embarrassment or stigma of owning the story. In one session we read “The Doctor’s Visit” by Anton Chekhov.⁶ Some of the members resonated with the doctor of this story who awkwardly attended to his lady patient whose son was dying of a brain tumor. The doctor was nervous, insecure, and unable to express any empathy. He was also the father of the child who was dying and refused to admit any responsibility. One member of the group stated that he could relate to the doctor’s insecurities and mentioned that he too felt insecure and even sometimes felt like an imposter. This led to a discussion of insecurities, ways to bolster self-confidence, and ways to accept and respect limitations. This was a conversation that may not have taken place without the story as anchor to discuss insecurities that we individually may not have been willing to admit to the group.

In a different session, we discussed the story “Interpreter of Maladies” by Jhumpa Lahiri in which a settled Indian American family returns to India to tour and learn about their heritage from a guide (the interpreter of maladies) who interpreted the culture for them.⁷ The family professed to be interested in knowing about the culture but could not concentrate: the wife stayed busy flirting with the guide and revealing outrageous secrets to him, the children were engrossed in their squabbles, and the father was essentially absent taking photographs as souvenirs instead of seeing the sites firsthand. Some of the members of the group were Indian American and could relate to the alienation from their home and nostalgia for their country, while others could relate to the same alienation, albeit from other cultures and countries. This allowed us to talk about deeply personal topics, without having to own the topic or reveal personal issues. The discussion led to a deep understanding and empathy for us and our colleagues knowing the pain of alienation that some of them felt but could not discuss.

The stories also served as windows into the world of others which enabled us to see and become the other. For example, in one session we reflected on “Babylon Revisited” by F. Scott Fitzgerald.⁸ In this story, an American man returns to Paris after the Great Depression and recalls his life as a young artist in the American artist expatriate community of Paris in the 1920s and 1930s. During that time, he partied, drank in excess, lost his wife to pneumonia (for which he was at least partially responsible), lost custody of his daughter, and lost his fortune. As he returned to Paris to try to reclaim his daughter, we feel his pain as he tries but fails to overcome chronic alcoholism, sexual indiscretions, and losses. This gave rise to discussion of losses in general as we became one with the main character. This increased our empathy for others in a way that could not have been possible without this short story as anchor.

In another session we reflected on “Hills Like White Elephants” by Ernest Hemingway, in which a man is waiting for a train while proposing his girlfriend get an abortion.⁹ She agonizes over her choices and makes no decision in this story. Yet, we the reader could “become” the woman in the story faced with hard choices of having a baby but losing the man she loves, or having an abortion and maybe losing him anyway. In becoming this woman, we could experience the complex emotions and feel an experience of the other.

Exploring the Taboo

A third aspect of the club was enabling discussion of controversial topics. There were topics that arose in the group which never would have arisen in clinical practice discussions. These had to do with the taboo topics such as romantic attachments to patients. We read “The Caves of Lascaux” and reflected on the story of a young doctor who becomes enamored and obsessed with his beautiful but dying patient.¹⁰ He becomes so obsessed with her that he almost abandons his wife, family, and stable livelihood to descend with her into the caves. This story gave rise to discussions about romantic attachment to patients and how to handle and extricate one from the situation. The senior doctors explained some of their relevant experiences and how they either transferred care or sought counseling to extricate themselves from a potentially dangerous situation, especially when they too fell under the spell of forbidden romance.

Moral Grounding

These sessions also served to define the moral basis of our own practice. Much of health care psychosocial distress is related to moral injury in which health care professionals do the wrong thing or fail to do the right thing at the right time, due to external pressures related to financial or other gains. Reading and reflecting put us face-to-face with moral dilemmas and let us find our moral grounding. In reading “The Haircut” by Ring Lardner, we explored the disruptive town scoundrel who harassed and tortured his friends and neighbors but in such outrageous ways that he was considered a comedian rather than an abuser.¹¹ Despite his hurtful acts, the townspeople (including the narrator) considered him a clown and laughed at his racist and sexist statements as well as his tricks.He faced no consequences such as confrontation, until the end when fate caught up. This story gave rise to a discussion of how we handle unkind, racist, sexist, or other comments which are disguised as humor, and to what extent we tolerate such controversial behavior. Do we go along with the scoundrel and laugh, or do we confront such people and insist that they respect and honor other people? The story sensitized the group to the ways in which prejudice and racism or sexism can be masked as humor, and to consider our moral responsibilities in society.

In another session we read and reflected on “Three Questions” by Leo Tolstoy.¹² In this story, a king travels to another territory but gets distracted by helping a neighbor in need, and thereby inadvertently and fortunately avoids the trap that had been devised to kill him. The author gives us his moral basis by asking and answering 3 questions: Who is the most important person? What is the most important thing to do? What is the most important thing to do now? His answers provided his moral grounding. We discussed our answers and the basis of our moral grounding, whether it be the injunction do no harm, the more complex religious backgrounds of our childhood, or otherwise.

Symbols and Metaphors

The practice of reading and reflecting also taught us symbols and metaphors. Symbols and metaphors are the essence of storytelling, and they provide keys to understanding people. We sought out and studied the metaphors and symbols in each of the stories we read. In “I Stood There Ironing”, a woman is ironing as she is being questioned by a social worker on the upbringing of her first daughter, and its impact on her psychosocial distress.¹³ The woman remembers the hardships in raising her daughter and her neglect and abuse of the child due to circumstances beyond her control. She keeps ironing back and forth as she recounts the ways in which she neglected her child. The ironing provides a metaphor for attempting to straighten out her life and for recognizing finally at the end of the story that the daughter should not be the dress, under which her iron is pressing. This gave rise to a discussion of metaphors in our lives and the meanings they carry.

Problem-solving Guide

A sixth way the reflections helped was by serving as a guide to solving our problems. Some of the stories we read resonated deeply with members of the group and provided guides to solving problems. In one meeting we discussed “Those Are as Brothers” by Nancy Hale, a story in which a Nazi concentration camp survivor finds refuge in a country home and develops a friendship with a survivor of an abusive marriage.¹⁴ Reading and reflecting on this story enabled us to see the impact of trauma on ourselves, our life choices, professions, ways of being, philosophies, and even on our next generation. The story was personal for several members of the group, some of whom were second-generation Holocaust survivors, and for one who admitted to severe trauma as a child. Discussing our backgrounds together, we empathized with each other and helped each other heal. The story also provided a guide to healing from trauma, as its title indicates: sharing stories together can be a way to heal. The solidarity of standing together, as brothers, heals. The concentration camp survivor was mistreated in his job, but the abuse trauma victim rushes to his defense and vows her friendship and support. This soothed his soul and healed his mind. The guidance is clear: we can do the same, find friends, treat them like brothers, support each other and heal.

Bonding Through Shared Experience

The final and possibly most important way in which the club helped was by serving as an adventure to bond group members together through shared experience. We believe that literature can capture imagination in extraordinary ways and provide an opportunity to undertake remarkable journeys. As such, together we traveled to the ends of the earth from the beginning to the end of time and beyond. We traveled through the hills of Africa, meandered in the streets of Russia and Poland, watched the racetracks in Italy, toured the Taj Mahal in India, and descended into the caves of Lascaux, all while working in Little Rock, Arkansas. We shared a wide array of experiences together, which allowed us to know ourselves and others better, to share stories, and to develop a common vision, common ground, and common culture.

Conclusions

Through reading and reflecting on stories, we bonded as a group, increased our empathy for each other and others, and found meaning in medicine. Other studies have shown that participation in small study groups promote physician well-being, improve job satisfaction, and decrease burnout.³ We synergized this effort by reading nonmedical stories on a consistent basis, hoping to gain resilience to psychosocial distress.³ We chose short stories rather than novels to minimize any stress from excess reading. Combining these interventions, small group studies and nonmedical reading, into a single intervention as is typical in the practice of narrative medicine may provide a way to improve team functioning.

This pilot study showed that it is possible to form short story clubs even in a busy oncology program and that such programs benefit participants in a variety of ways with no apparent adverse effects. Further research is needed to study the impact of reading and reflecting on medical work in small study groups in larger numbers of subjects and to evaluate their impact on burnout. Further study is also needed to develop narrative medicine curricula that best address the needs of particular subspecialties and to determine the optimal conditions for implementation.

Acknowledgments

The authors acknowledge Dr. Erick Messias for inspiring and encouraging this project at the University of Arkansas for Medical Sciences where he was Associate Dean for Faculty Affairs. He is presently Chair of Psychiatry and Behavioral Neuroscience at the St. Louis University School of Medicine, St. Louis, Missouri.

Burnout and other forms of psychosocial distress are common among health care professionals necessitating measures to promote well-being and reduce burnout.¹ Studies have shown that nonmedical reading is associated with low burnout and that small group study sections can promote wellness.^2,3 Narrative medicine, which proposes a model for humane and effective medical practice, advocates for the necessity of narrative competence.

Short Story Club

Narrative competence is the ability to acknowledge, interpret, and act on the stories of others. The narrative skill of close reading also encourages reflective practice, equipping practitioners to better weather the tides of illness.⁴ In our case, we formed a short story club intervention to closely read, or read and reflect, on literary fiction. We explored how reading and reflecting would result in profound changes in thinking and feeling and noted different ways by which they can cause such well-being. We describe here the 7 ways in which stories led us to increase bonding, improve empathy, and promote meaning in medicine.

Slowing Down

The short story club helped to bond us together and increase our sense of meaning in medicine by slowing us down. One member of the group likened the experience to increasing the pixels in a painting, thereby improving the resolution and seeing more clearly. Another member mentioned the experience as a form of meditation in slowing down the brain, breathing in the story, and breathing out impressions. One story by Anatole Broyard emphasized the importance of slowing down and “brooding” over a patient.⁵ The author describes his experience as a prostate cancer patient, in which his body was treated but his story was ignored. He begged his doctors to pay more attention to his story to listen and to brood over him. This story was enlightening to us; we saw how desperate our patients are to tell their stories, and for us to hear their stories.

Mirrors and Windows

Another way reading and reflecting on short stories helped was by reflecting our practices to ourselves, as though looking into a mirror to see ourselves and out of a window to see others. We found that stories mirrored our own world and allowed us to discuss issues close to us without the embarrassment or stigma of owning the story. In one session we read “The Doctor’s Visit” by Anton Chekhov.⁶ Some of the members resonated with the doctor of this story who awkwardly attended to his lady patient whose son was dying of a brain tumor. The doctor was nervous, insecure, and unable to express any empathy. He was also the father of the child who was dying and refused to admit any responsibility. One member of the group stated that he could relate to the doctor’s insecurities and mentioned that he too felt insecure and even sometimes felt like an imposter. This led to a discussion of insecurities, ways to bolster self-confidence, and ways to accept and respect limitations. This was a conversation that may not have taken place without the story as anchor to discuss insecurities that we individually may not have been willing to admit to the group.

In a different session, we discussed the story “Interpreter of Maladies” by Jhumpa Lahiri in which a settled Indian American family returns to India to tour and learn about their heritage from a guide (the interpreter of maladies) who interpreted the culture for them.⁷ The family professed to be interested in knowing about the culture but could not concentrate: the wife stayed busy flirting with the guide and revealing outrageous secrets to him, the children were engrossed in their squabbles, and the father was essentially absent taking photographs as souvenirs instead of seeing the sites firsthand. Some of the members of the group were Indian American and could relate to the alienation from their home and nostalgia for their country, while others could relate to the same alienation, albeit from other cultures and countries. This allowed us to talk about deeply personal topics, without having to own the topic or reveal personal issues. The discussion led to a deep understanding and empathy for us and our colleagues knowing the pain of alienation that some of them felt but could not discuss.

The stories also served as windows into the world of others which enabled us to see and become the other. For example, in one session we reflected on “Babylon Revisited” by F. Scott Fitzgerald.⁸ In this story, an American man returns to Paris after the Great Depression and recalls his life as a young artist in the American artist expatriate community of Paris in the 1920s and 1930s. During that time, he partied, drank in excess, lost his wife to pneumonia (for which he was at least partially responsible), lost custody of his daughter, and lost his fortune. As he returned to Paris to try to reclaim his daughter, we feel his pain as he tries but fails to overcome chronic alcoholism, sexual indiscretions, and losses. This gave rise to discussion of losses in general as we became one with the main character. This increased our empathy for others in a way that could not have been possible without this short story as anchor.

In another session we reflected on “Hills Like White Elephants” by Ernest Hemingway, in which a man is waiting for a train while proposing his girlfriend get an abortion.⁹ She agonizes over her choices and makes no decision in this story. Yet, we the reader could “become” the woman in the story faced with hard choices of having a baby but losing the man she loves, or having an abortion and maybe losing him anyway. In becoming this woman, we could experience the complex emotions and feel an experience of the other.

Exploring the Taboo

A third aspect of the club was enabling discussion of controversial topics. There were topics that arose in the group which never would have arisen in clinical practice discussions. These had to do with the taboo topics such as romantic attachments to patients. We read “The Caves of Lascaux” and reflected on the story of a young doctor who becomes enamored and obsessed with his beautiful but dying patient.¹⁰ He becomes so obsessed with her that he almost abandons his wife, family, and stable livelihood to descend with her into the caves. This story gave rise to discussions about romantic attachment to patients and how to handle and extricate one from the situation. The senior doctors explained some of their relevant experiences and how they either transferred care or sought counseling to extricate themselves from a potentially dangerous situation, especially when they too fell under the spell of forbidden romance.

Moral Grounding

These sessions also served to define the moral basis of our own practice. Much of health care psychosocial distress is related to moral injury in which health care professionals do the wrong thing or fail to do the right thing at the right time, due to external pressures related to financial or other gains. Reading and reflecting put us face-to-face with moral dilemmas and let us find our moral grounding. In reading “The Haircut” by Ring Lardner, we explored the disruptive town scoundrel who harassed and tortured his friends and neighbors but in such outrageous ways that he was considered a comedian rather than an abuser.¹¹ Despite his hurtful acts, the townspeople (including the narrator) considered him a clown and laughed at his racist and sexist statements as well as his tricks.He faced no consequences such as confrontation, until the end when fate caught up. This story gave rise to a discussion of how we handle unkind, racist, sexist, or other comments which are disguised as humor, and to what extent we tolerate such controversial behavior. Do we go along with the scoundrel and laugh, or do we confront such people and insist that they respect and honor other people? The story sensitized the group to the ways in which prejudice and racism or sexism can be masked as humor, and to consider our moral responsibilities in society.

In another session we read and reflected on “Three Questions” by Leo Tolstoy.¹² In this story, a king travels to another territory but gets distracted by helping a neighbor in need, and thereby inadvertently and fortunately avoids the trap that had been devised to kill him. The author gives us his moral basis by asking and answering 3 questions: Who is the most important person? What is the most important thing to do? What is the most important thing to do now? His answers provided his moral grounding. We discussed our answers and the basis of our moral grounding, whether it be the injunction do no harm, the more complex religious backgrounds of our childhood, or otherwise.

Symbols and Metaphors

The practice of reading and reflecting also taught us symbols and metaphors. Symbols and metaphors are the essence of storytelling, and they provide keys to understanding people. We sought out and studied the metaphors and symbols in each of the stories we read. In “I Stood There Ironing”, a woman is ironing as she is being questioned by a social worker on the upbringing of her first daughter, and its impact on her psychosocial distress.¹³ The woman remembers the hardships in raising her daughter and her neglect and abuse of the child due to circumstances beyond her control. She keeps ironing back and forth as she recounts the ways in which she neglected her child. The ironing provides a metaphor for attempting to straighten out her life and for recognizing finally at the end of the story that the daughter should not be the dress, under which her iron is pressing. This gave rise to a discussion of metaphors in our lives and the meanings they carry.

Problem-solving Guide

A sixth way the reflections helped was by serving as a guide to solving our problems. Some of the stories we read resonated deeply with members of the group and provided guides to solving problems. In one meeting we discussed “Those Are as Brothers” by Nancy Hale, a story in which a Nazi concentration camp survivor finds refuge in a country home and develops a friendship with a survivor of an abusive marriage.¹⁴ Reading and reflecting on this story enabled us to see the impact of trauma on ourselves, our life choices, professions, ways of being, philosophies, and even on our next generation. The story was personal for several members of the group, some of whom were second-generation Holocaust survivors, and for one who admitted to severe trauma as a child. Discussing our backgrounds together, we empathized with each other and helped each other heal. The story also provided a guide to healing from trauma, as its title indicates: sharing stories together can be a way to heal. The solidarity of standing together, as brothers, heals. The concentration camp survivor was mistreated in his job, but the abuse trauma victim rushes to his defense and vows her friendship and support. This soothed his soul and healed his mind. The guidance is clear: we can do the same, find friends, treat them like brothers, support each other and heal.

Bonding Through Shared Experience

The final and possibly most important way in which the club helped was by serving as an adventure to bond group members together through shared experience. We believe that literature can capture imagination in extraordinary ways and provide an opportunity to undertake remarkable journeys. As such, together we traveled to the ends of the earth from the beginning to the end of time and beyond. We traveled through the hills of Africa, meandered in the streets of Russia and Poland, watched the racetracks in Italy, toured the Taj Mahal in India, and descended into the caves of Lascaux, all while working in Little Rock, Arkansas. We shared a wide array of experiences together, which allowed us to know ourselves and others better, to share stories, and to develop a common vision, common ground, and common culture.

Conclusions

Through reading and reflecting on stories, we bonded as a group, increased our empathy for each other and others, and found meaning in medicine. Other studies have shown that participation in small study groups promote physician well-being, improve job satisfaction, and decrease burnout.³ We synergized this effort by reading nonmedical stories on a consistent basis, hoping to gain resilience to psychosocial distress.³ We chose short stories rather than novels to minimize any stress from excess reading. Combining these interventions, small group studies and nonmedical reading, into a single intervention as is typical in the practice of narrative medicine may provide a way to improve team functioning.

This pilot study showed that it is possible to form short story clubs even in a busy oncology program and that such programs benefit participants in a variety of ways with no apparent adverse effects. Further research is needed to study the impact of reading and reflecting on medical work in small study groups in larger numbers of subjects and to evaluate their impact on burnout. Further study is also needed to develop narrative medicine curricula that best address the needs of particular subspecialties and to determine the optimal conditions for implementation.

Acknowledgments

The authors acknowledge Dr. Erick Messias for inspiring and encouraging this project at the University of Arkansas for Medical Sciences where he was Associate Dean for Faculty Affairs. He is presently Chair of Psychiatry and Behavioral Neuroscience at the St. Louis University School of Medicine, St. Louis, Missouri.

Burnout and other forms of psychosocial distress are common among health care professionals necessitating measures to promote well-being and reduce burnout.¹ Studies have shown that nonmedical reading is associated with low burnout and that small group study sections can promote wellness.^2,3 Narrative medicine, which proposes a model for humane and effective medical practice, advocates for the necessity of narrative competence.

Short Story Club

Narrative competence is the ability to acknowledge, interpret, and act on the stories of others. The narrative skill of close reading also encourages reflective practice, equipping practitioners to better weather the tides of illness.⁴ In our case, we formed a short story club intervention to closely read, or read and reflect, on literary fiction. We explored how reading and reflecting would result in profound changes in thinking and feeling and noted different ways by which they can cause such well-being. We describe here the 7 ways in which stories led us to increase bonding, improve empathy, and promote meaning in medicine.

Slowing Down

The short story club helped to bond us together and increase our sense of meaning in medicine by slowing us down. One member of the group likened the experience to increasing the pixels in a painting, thereby improving the resolution and seeing more clearly. Another member mentioned the experience as a form of meditation in slowing down the brain, breathing in the story, and breathing out impressions. One story by Anatole Broyard emphasized the importance of slowing down and “brooding” over a patient.⁵ The author describes his experience as a prostate cancer patient, in which his body was treated but his story was ignored. He begged his doctors to pay more attention to his story to listen and to brood over him. This story was enlightening to us; we saw how desperate our patients are to tell their stories, and for us to hear their stories.

Mirrors and Windows

Another way reading and reflecting on short stories helped was by reflecting our practices to ourselves, as though looking into a mirror to see ourselves and out of a window to see others. We found that stories mirrored our own world and allowed us to discuss issues close to us without the embarrassment or stigma of owning the story. In one session we read “The Doctor’s Visit” by Anton Chekhov.⁶ Some of the members resonated with the doctor of this story who awkwardly attended to his lady patient whose son was dying of a brain tumor. The doctor was nervous, insecure, and unable to express any empathy. He was also the father of the child who was dying and refused to admit any responsibility. One member of the group stated that he could relate to the doctor’s insecurities and mentioned that he too felt insecure and even sometimes felt like an imposter. This led to a discussion of insecurities, ways to bolster self-confidence, and ways to accept and respect limitations. This was a conversation that may not have taken place without the story as anchor to discuss insecurities that we individually may not have been willing to admit to the group.

In a different session, we discussed the story “Interpreter of Maladies” by Jhumpa Lahiri in which a settled Indian American family returns to India to tour and learn about their heritage from a guide (the interpreter of maladies) who interpreted the culture for them.⁷ The family professed to be interested in knowing about the culture but could not concentrate: the wife stayed busy flirting with the guide and revealing outrageous secrets to him, the children were engrossed in their squabbles, and the father was essentially absent taking photographs as souvenirs instead of seeing the sites firsthand. Some of the members of the group were Indian American and could relate to the alienation from their home and nostalgia for their country, while others could relate to the same alienation, albeit from other cultures and countries. This allowed us to talk about deeply personal topics, without having to own the topic or reveal personal issues. The discussion led to a deep understanding and empathy for us and our colleagues knowing the pain of alienation that some of them felt but could not discuss.

The stories also served as windows into the world of others which enabled us to see and become the other. For example, in one session we reflected on “Babylon Revisited” by F. Scott Fitzgerald.⁸ In this story, an American man returns to Paris after the Great Depression and recalls his life as a young artist in the American artist expatriate community of Paris in the 1920s and 1930s. During that time, he partied, drank in excess, lost his wife to pneumonia (for which he was at least partially responsible), lost custody of his daughter, and lost his fortune. As he returned to Paris to try to reclaim his daughter, we feel his pain as he tries but fails to overcome chronic alcoholism, sexual indiscretions, and losses. This gave rise to discussion of losses in general as we became one with the main character. This increased our empathy for others in a way that could not have been possible without this short story as anchor.

In another session we reflected on “Hills Like White Elephants” by Ernest Hemingway, in which a man is waiting for a train while proposing his girlfriend get an abortion.⁹ She agonizes over her choices and makes no decision in this story. Yet, we the reader could “become” the woman in the story faced with hard choices of having a baby but losing the man she loves, or having an abortion and maybe losing him anyway. In becoming this woman, we could experience the complex emotions and feel an experience of the other.

Exploring the Taboo

A third aspect of the club was enabling discussion of controversial topics. There were topics that arose in the group which never would have arisen in clinical practice discussions. These had to do with the taboo topics such as romantic attachments to patients. We read “The Caves of Lascaux” and reflected on the story of a young doctor who becomes enamored and obsessed with his beautiful but dying patient.¹⁰ He becomes so obsessed with her that he almost abandons his wife, family, and stable livelihood to descend with her into the caves. This story gave rise to discussions about romantic attachment to patients and how to handle and extricate one from the situation. The senior doctors explained some of their relevant experiences and how they either transferred care or sought counseling to extricate themselves from a potentially dangerous situation, especially when they too fell under the spell of forbidden romance.

Moral Grounding

These sessions also served to define the moral basis of our own practice. Much of health care psychosocial distress is related to moral injury in which health care professionals do the wrong thing or fail to do the right thing at the right time, due to external pressures related to financial or other gains. Reading and reflecting put us face-to-face with moral dilemmas and let us find our moral grounding. In reading “The Haircut” by Ring Lardner, we explored the disruptive town scoundrel who harassed and tortured his friends and neighbors but in such outrageous ways that he was considered a comedian rather than an abuser.¹¹ Despite his hurtful acts, the townspeople (including the narrator) considered him a clown and laughed at his racist and sexist statements as well as his tricks.He faced no consequences such as confrontation, until the end when fate caught up. This story gave rise to a discussion of how we handle unkind, racist, sexist, or other comments which are disguised as humor, and to what extent we tolerate such controversial behavior. Do we go along with the scoundrel and laugh, or do we confront such people and insist that they respect and honor other people? The story sensitized the group to the ways in which prejudice and racism or sexism can be masked as humor, and to consider our moral responsibilities in society.

In another session we read and reflected on “Three Questions” by Leo Tolstoy.¹² In this story, a king travels to another territory but gets distracted by helping a neighbor in need, and thereby inadvertently and fortunately avoids the trap that had been devised to kill him. The author gives us his moral basis by asking and answering 3 questions: Who is the most important person? What is the most important thing to do? What is the most important thing to do now? His answers provided his moral grounding. We discussed our answers and the basis of our moral grounding, whether it be the injunction do no harm, the more complex religious backgrounds of our childhood, or otherwise.

Symbols and Metaphors

The practice of reading and reflecting also taught us symbols and metaphors. Symbols and metaphors are the essence of storytelling, and they provide keys to understanding people. We sought out and studied the metaphors and symbols in each of the stories we read. In “I Stood There Ironing”, a woman is ironing as she is being questioned by a social worker on the upbringing of her first daughter, and its impact on her psychosocial distress.¹³ The woman remembers the hardships in raising her daughter and her neglect and abuse of the child due to circumstances beyond her control. She keeps ironing back and forth as she recounts the ways in which she neglected her child. The ironing provides a metaphor for attempting to straighten out her life and for recognizing finally at the end of the story that the daughter should not be the dress, under which her iron is pressing. This gave rise to a discussion of metaphors in our lives and the meanings they carry.

Problem-solving Guide

A sixth way the reflections helped was by serving as a guide to solving our problems. Some of the stories we read resonated deeply with members of the group and provided guides to solving problems. In one meeting we discussed “Those Are as Brothers” by Nancy Hale, a story in which a Nazi concentration camp survivor finds refuge in a country home and develops a friendship with a survivor of an abusive marriage.¹⁴ Reading and reflecting on this story enabled us to see the impact of trauma on ourselves, our life choices, professions, ways of being, philosophies, and even on our next generation. The story was personal for several members of the group, some of whom were second-generation Holocaust survivors, and for one who admitted to severe trauma as a child. Discussing our backgrounds together, we empathized with each other and helped each other heal. The story also provided a guide to healing from trauma, as its title indicates: sharing stories together can be a way to heal. The solidarity of standing together, as brothers, heals. The concentration camp survivor was mistreated in his job, but the abuse trauma victim rushes to his defense and vows her friendship and support. This soothed his soul and healed his mind. The guidance is clear: we can do the same, find friends, treat them like brothers, support each other and heal.

Bonding Through Shared Experience

The final and possibly most important way in which the club helped was by serving as an adventure to bond group members together through shared experience. We believe that literature can capture imagination in extraordinary ways and provide an opportunity to undertake remarkable journeys. As such, together we traveled to the ends of the earth from the beginning to the end of time and beyond. We traveled through the hills of Africa, meandered in the streets of Russia and Poland, watched the racetracks in Italy, toured the Taj Mahal in India, and descended into the caves of Lascaux, all while working in Little Rock, Arkansas. We shared a wide array of experiences together, which allowed us to know ourselves and others better, to share stories, and to develop a common vision, common ground, and common culture.

Conclusions

Through reading and reflecting on stories, we bonded as a group, increased our empathy for each other and others, and found meaning in medicine. Other studies have shown that participation in small study groups promote physician well-being, improve job satisfaction, and decrease burnout.³ We synergized this effort by reading nonmedical stories on a consistent basis, hoping to gain resilience to psychosocial distress.³ We chose short stories rather than novels to minimize any stress from excess reading. Combining these interventions, small group studies and nonmedical reading, into a single intervention as is typical in the practice of narrative medicine may provide a way to improve team functioning.

This pilot study showed that it is possible to form short story clubs even in a busy oncology program and that such programs benefit participants in a variety of ways with no apparent adverse effects. Further research is needed to study the impact of reading and reflecting on medical work in small study groups in larger numbers of subjects and to evaluate their impact on burnout. Further study is also needed to develop narrative medicine curricula that best address the needs of particular subspecialties and to determine the optimal conditions for implementation.

Acknowledgments

The authors acknowledge Dr. Erick Messias for inspiring and encouraging this project at the University of Arkansas for Medical Sciences where he was Associate Dean for Faculty Affairs. He is presently Chair of Psychiatry and Behavioral Neuroscience at the St. Louis University School of Medicine, St. Louis, Missouri.

Moderate to severe anxiety, depression, and shortness of breath indicate increased risk for nonfatal self-injury (NFSI) among patients newly diagnosed with cancer, according to a Canadian study.

In a population-based, case-control study, each of these symptoms was associated with an increase of at least 60% in the risk for NFSI in the following 180 days, the investigators report.

“Clinicians should know that self-injury is a real problem after a cancer diagnosis,” lead investigator Julie Hallet, MD, an associate scientist at Sunnybrook Health Sciences Centre in Toronto, told this news organization.

Self-injury “does not necessarily represent an attempted suicide,” she added. “While our data do not allow us to know what the intent was, we know from other work that the repercussions of distress in patients with cancer are much broader than suicide. Self-injury can be a means to cope with psychological difficulties for some patients, without intent for suicide.”

The study was published online in JAMA Oncology.
 

Nine common symptoms

The study included adults who were diagnosed with cancer between Jan. 1, 2007, and March 31, 2019, and had completed the Edmonton Symptom Assessment System (ESAS) evaluation within 36 months of their index cancer diagnosis. ESAS evaluates nine common cancer-associated symptoms, including pain, tiredness, nausea, depression, anxiety, drowsiness, appetite, well-being, and shortness of breath, on a patient-reported scale of 0 (absence of symptom) to 10 (worst possible symptom).

The analysis included 406 patients who had visited an emergency department for an NFSI within 180 days of their ESAS evaluation, as well as 1,624 matched control patients with cancer who did not have an NFSI. Case patients and control patients were matched according to age at cancer diagnosis, sex, prior self-injury within 5 years of being diagnosed with cancer, and cancer type. Nonmatched covariates included psychiatric illness and therapy received before NFSI, comorbidity burden, material deprivation, and cancer stage.
 

Toward tailored intervention

A higher proportion of case patients than control patients reported moderate to severe scores for all nine ESAS symptoms. In an adjusted analysis, moderate to severe anxiety (odds ratio, 1.61), depression (OR, 1.66), and shortness of breath (OR, 1.65) were independently associated with higher odds of subsequent NFSI. Each 10-point increase in total ESAS score also was associated with increased risk (OR, 1.51).

“These findings are important to enhance the use of screening ESAS scores to better support patients,” say the authors. “Scores from ESAS assessments can be used to identify patients at higher risk of NFSI, indicating higher level of distress, and help direct tailored assessment and intervention.”

In prior work, Dr. Hallet’s group showed that NFSI occurs in 3 of every 1,000 patients with cancer. NFSI is more frequent among younger patients and those with a history of prior mental illness. “Identifying patients at risk in clinical practice requires you to inquire about a patient’s prior history, identify high symptom scores and ask about them, and trigger intervention pathways when risk is identified,” said Dr. Hallet.

“For example, a young patient with head and neck cancer and a prior history of mental illness who reports high scores for anxiety and drowsiness would be at high risk of self-injury,” she added. Such a patient should be referred to psycho-oncology, psychiatry, or social work. “To facilitate this, we are working on prognostic scores that can be integrated in clinical practice, such as an electronic medical record, to flag patients at risk,” said Dr. Hallet. “Future work will also need to identify the optimal care pathways for at-risk patients.”
 

Self-injury vs. suicidality

Commenting on the study for this news organization, Madeline Li, MD, PhD, a psychiatrist and clinician-scientist at Toronto’s Princess Margaret Cancer Centre, said that the findings are “underwhelming” because they tell us what is already known – that “NFSI is associated with distress, and cancer is a stressor.” It would have been more interesting to ask how to distinguish patients at risk for suicide from those at risk for self-harm without suicide, she added.

“The way these authors formulated NFSI included both self-harm intent and suicidal intent,” she explained. The researchers compared patients who were at risk for these two types of events with patients without NFSI. “When we see self-harm without suicidal intent in the emergency room, it’s mostly people making cries for help,” said Dr. Li. “These are people who cut their wrists or take small overdoses on purpose without the intent to die. It would have been more interesting to see if there are different risk factors for people who are just going to self-harm vs. those who are actually going to attempt suicide.”

The study’s identification of risk factors for NSFI is important because “it does tell us that when there’s anxiety, depression, and shortness of breath, we should pay attention to these patients and do something about it,” said Dr. Li. Still, research in cancer psychiatry needs to shift its focus from identifying and addressing existing risk factors to preventing them from developing, she added.

“We need to move earlier and provide emotional and mental health support to cancer patients to prevent them from becoming suicidal, rather than intervening when somebody already is,” Dr. Li concluded.

The study was funded by the Hanna Research Award from the division of surgical oncology at the Odette Cancer Centre–Sunnybrook Health Sciences Centre and by a Sunnybrook Health Sciences Centre Alternate Funding Plan Innovation grant. It was also supported by ICES, which is funded by an annual grant from the Ontario Ministry of Health and Long-Term Care. Dr. Hallet has received personal fees from Ipsen Biopharmaceuticals Canada and AAA outside the submitted work. Dr. Li reported no relevant financial relationships.

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

Moderate to severe anxiety, depression, and shortness of breath indicate increased risk for nonfatal self-injury (NFSI) among patients newly diagnosed with cancer, according to a Canadian study.

In a population-based, case-control study, each of these symptoms was associated with an increase of at least 60% in the risk for NFSI in the following 180 days, the investigators report.

“Clinicians should know that self-injury is a real problem after a cancer diagnosis,” lead investigator Julie Hallet, MD, an associate scientist at Sunnybrook Health Sciences Centre in Toronto, told this news organization.

Self-injury “does not necessarily represent an attempted suicide,” she added. “While our data do not allow us to know what the intent was, we know from other work that the repercussions of distress in patients with cancer are much broader than suicide. Self-injury can be a means to cope with psychological difficulties for some patients, without intent for suicide.”

The study was published online in JAMA Oncology.
 

Nine common symptoms

The study included adults who were diagnosed with cancer between Jan. 1, 2007, and March 31, 2019, and had completed the Edmonton Symptom Assessment System (ESAS) evaluation within 36 months of their index cancer diagnosis. ESAS evaluates nine common cancer-associated symptoms, including pain, tiredness, nausea, depression, anxiety, drowsiness, appetite, well-being, and shortness of breath, on a patient-reported scale of 0 (absence of symptom) to 10 (worst possible symptom).

The analysis included 406 patients who had visited an emergency department for an NFSI within 180 days of their ESAS evaluation, as well as 1,624 matched control patients with cancer who did not have an NFSI. Case patients and control patients were matched according to age at cancer diagnosis, sex, prior self-injury within 5 years of being diagnosed with cancer, and cancer type. Nonmatched covariates included psychiatric illness and therapy received before NFSI, comorbidity burden, material deprivation, and cancer stage.
 

Toward tailored intervention

A higher proportion of case patients than control patients reported moderate to severe scores for all nine ESAS symptoms. In an adjusted analysis, moderate to severe anxiety (odds ratio, 1.61), depression (OR, 1.66), and shortness of breath (OR, 1.65) were independently associated with higher odds of subsequent NFSI. Each 10-point increase in total ESAS score also was associated with increased risk (OR, 1.51).

“These findings are important to enhance the use of screening ESAS scores to better support patients,” say the authors. “Scores from ESAS assessments can be used to identify patients at higher risk of NFSI, indicating higher level of distress, and help direct tailored assessment and intervention.”

In prior work, Dr. Hallet’s group showed that NFSI occurs in 3 of every 1,000 patients with cancer. NFSI is more frequent among younger patients and those with a history of prior mental illness. “Identifying patients at risk in clinical practice requires you to inquire about a patient’s prior history, identify high symptom scores and ask about them, and trigger intervention pathways when risk is identified,” said Dr. Hallet.

“For example, a young patient with head and neck cancer and a prior history of mental illness who reports high scores for anxiety and drowsiness would be at high risk of self-injury,” she added. Such a patient should be referred to psycho-oncology, psychiatry, or social work. “To facilitate this, we are working on prognostic scores that can be integrated in clinical practice, such as an electronic medical record, to flag patients at risk,” said Dr. Hallet. “Future work will also need to identify the optimal care pathways for at-risk patients.”
 

Self-injury vs. suicidality

Commenting on the study for this news organization, Madeline Li, MD, PhD, a psychiatrist and clinician-scientist at Toronto’s Princess Margaret Cancer Centre, said that the findings are “underwhelming” because they tell us what is already known – that “NFSI is associated with distress, and cancer is a stressor.” It would have been more interesting to ask how to distinguish patients at risk for suicide from those at risk for self-harm without suicide, she added.

“The way these authors formulated NFSI included both self-harm intent and suicidal intent,” she explained. The researchers compared patients who were at risk for these two types of events with patients without NFSI. “When we see self-harm without suicidal intent in the emergency room, it’s mostly people making cries for help,” said Dr. Li. “These are people who cut their wrists or take small overdoses on purpose without the intent to die. It would have been more interesting to see if there are different risk factors for people who are just going to self-harm vs. those who are actually going to attempt suicide.”

The study’s identification of risk factors for NSFI is important because “it does tell us that when there’s anxiety, depression, and shortness of breath, we should pay attention to these patients and do something about it,” said Dr. Li. Still, research in cancer psychiatry needs to shift its focus from identifying and addressing existing risk factors to preventing them from developing, she added.

“We need to move earlier and provide emotional and mental health support to cancer patients to prevent them from becoming suicidal, rather than intervening when somebody already is,” Dr. Li concluded.

The study was funded by the Hanna Research Award from the division of surgical oncology at the Odette Cancer Centre–Sunnybrook Health Sciences Centre and by a Sunnybrook Health Sciences Centre Alternate Funding Plan Innovation grant. It was also supported by ICES, which is funded by an annual grant from the Ontario Ministry of Health and Long-Term Care. Dr. Hallet has received personal fees from Ipsen Biopharmaceuticals Canada and AAA outside the submitted work. Dr. Li reported no relevant financial relationships.

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

Moderate to severe anxiety, depression, and shortness of breath indicate increased risk for nonfatal self-injury (NFSI) among patients newly diagnosed with cancer, according to a Canadian study.

In a population-based, case-control study, each of these symptoms was associated with an increase of at least 60% in the risk for NFSI in the following 180 days, the investigators report.

“Clinicians should know that self-injury is a real problem after a cancer diagnosis,” lead investigator Julie Hallet, MD, an associate scientist at Sunnybrook Health Sciences Centre in Toronto, told this news organization.

Self-injury “does not necessarily represent an attempted suicide,” she added. “While our data do not allow us to know what the intent was, we know from other work that the repercussions of distress in patients with cancer are much broader than suicide. Self-injury can be a means to cope with psychological difficulties for some patients, without intent for suicide.”

The study was published online in JAMA Oncology.
 

Nine common symptoms

The study included adults who were diagnosed with cancer between Jan. 1, 2007, and March 31, 2019, and had completed the Edmonton Symptom Assessment System (ESAS) evaluation within 36 months of their index cancer diagnosis. ESAS evaluates nine common cancer-associated symptoms, including pain, tiredness, nausea, depression, anxiety, drowsiness, appetite, well-being, and shortness of breath, on a patient-reported scale of 0 (absence of symptom) to 10 (worst possible symptom).

The analysis included 406 patients who had visited an emergency department for an NFSI within 180 days of their ESAS evaluation, as well as 1,624 matched control patients with cancer who did not have an NFSI. Case patients and control patients were matched according to age at cancer diagnosis, sex, prior self-injury within 5 years of being diagnosed with cancer, and cancer type. Nonmatched covariates included psychiatric illness and therapy received before NFSI, comorbidity burden, material deprivation, and cancer stage.
 

Toward tailored intervention

A higher proportion of case patients than control patients reported moderate to severe scores for all nine ESAS symptoms. In an adjusted analysis, moderate to severe anxiety (odds ratio, 1.61), depression (OR, 1.66), and shortness of breath (OR, 1.65) were independently associated with higher odds of subsequent NFSI. Each 10-point increase in total ESAS score also was associated with increased risk (OR, 1.51).

“These findings are important to enhance the use of screening ESAS scores to better support patients,” say the authors. “Scores from ESAS assessments can be used to identify patients at higher risk of NFSI, indicating higher level of distress, and help direct tailored assessment and intervention.”

In prior work, Dr. Hallet’s group showed that NFSI occurs in 3 of every 1,000 patients with cancer. NFSI is more frequent among younger patients and those with a history of prior mental illness. “Identifying patients at risk in clinical practice requires you to inquire about a patient’s prior history, identify high symptom scores and ask about them, and trigger intervention pathways when risk is identified,” said Dr. Hallet.

“For example, a young patient with head and neck cancer and a prior history of mental illness who reports high scores for anxiety and drowsiness would be at high risk of self-injury,” she added. Such a patient should be referred to psycho-oncology, psychiatry, or social work. “To facilitate this, we are working on prognostic scores that can be integrated in clinical practice, such as an electronic medical record, to flag patients at risk,” said Dr. Hallet. “Future work will also need to identify the optimal care pathways for at-risk patients.”
 

Self-injury vs. suicidality

Commenting on the study for this news organization, Madeline Li, MD, PhD, a psychiatrist and clinician-scientist at Toronto’s Princess Margaret Cancer Centre, said that the findings are “underwhelming” because they tell us what is already known – that “NFSI is associated with distress, and cancer is a stressor.” It would have been more interesting to ask how to distinguish patients at risk for suicide from those at risk for self-harm without suicide, she added.

“The way these authors formulated NFSI included both self-harm intent and suicidal intent,” she explained. The researchers compared patients who were at risk for these two types of events with patients without NFSI. “When we see self-harm without suicidal intent in the emergency room, it’s mostly people making cries for help,” said Dr. Li. “These are people who cut their wrists or take small overdoses on purpose without the intent to die. It would have been more interesting to see if there are different risk factors for people who are just going to self-harm vs. those who are actually going to attempt suicide.”

The study’s identification of risk factors for NSFI is important because “it does tell us that when there’s anxiety, depression, and shortness of breath, we should pay attention to these patients and do something about it,” said Dr. Li. Still, research in cancer psychiatry needs to shift its focus from identifying and addressing existing risk factors to preventing them from developing, she added.

“We need to move earlier and provide emotional and mental health support to cancer patients to prevent them from becoming suicidal, rather than intervening when somebody already is,” Dr. Li concluded.

The study was funded by the Hanna Research Award from the division of surgical oncology at the Odette Cancer Centre–Sunnybrook Health Sciences Centre and by a Sunnybrook Health Sciences Centre Alternate Funding Plan Innovation grant. It was also supported by ICES, which is funded by an annual grant from the Ontario Ministry of Health and Long-Term Care. Dr. Hallet has received personal fees from Ipsen Biopharmaceuticals Canada and AAA outside the submitted work. Dr. Li reported no relevant financial relationships.

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

The National Comprehensive Cancer Network (NCCN) has recommended a fifth COVID-19 mRNA shot for people who are immunocompromised, including many with cancer or a history of cancer.

A fifth shot of an mRNA vaccine represents a second booster, the group explained, because the primary mRNA immunization series for immunocompromised individuals involves three doses of either the Pfizer or Moderna vaccine.

The update, issued today, comes from the NCCN’s Advisory Committee on COVID-19 Vaccination and Pre-exposure Prophylaxis, which released its first vaccine guidelines for patients with cancer in January 2021. The NCCN has issued numerous updates since then as information about the virus and vaccines has evolved. 

“We know a lot more about COVID-19 and the vaccines now, and we can use that knowledge to minimize the confusion and enhance the protection we can offer to our immunocompromised patients,” said advisory committee co-leader Lindsey Baden, MD, an infectious diseases specialist at the Dana-Farber Cancer Institute, Boston.

The latest iteration of the NCCN’s COVID guidelines includes an update for patients who initially received Johnson & Johnson’s single-shot vaccine, including a recommendation that patients receive an mRNA vaccine for both the first and second booster.

The group also updated dosing recommendations for pre-exposure prevention with tixagevimab plus cilgavimab (Evusheld, AstraZeneca), suggesting 300 mg of each monoclonal antibody instead of 150 mg, based on in vitro activity against Omicron variants.

The group noted that the Moderna and Pfizer shots can be used interchangeably for boosters.

“The NCCN Committee considers both homologous and heterologous boosters to be appropriate options,” the experts wrote.

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

The National Comprehensive Cancer Network (NCCN) has recommended a fifth COVID-19 mRNA shot for people who are immunocompromised, including many with cancer or a history of cancer.

A fifth shot of an mRNA vaccine represents a second booster, the group explained, because the primary mRNA immunization series for immunocompromised individuals involves three doses of either the Pfizer or Moderna vaccine.

The update, issued today, comes from the NCCN’s Advisory Committee on COVID-19 Vaccination and Pre-exposure Prophylaxis, which released its first vaccine guidelines for patients with cancer in January 2021. The NCCN has issued numerous updates since then as information about the virus and vaccines has evolved. 

“We know a lot more about COVID-19 and the vaccines now, and we can use that knowledge to minimize the confusion and enhance the protection we can offer to our immunocompromised patients,” said advisory committee co-leader Lindsey Baden, MD, an infectious diseases specialist at the Dana-Farber Cancer Institute, Boston.

The latest iteration of the NCCN’s COVID guidelines includes an update for patients who initially received Johnson & Johnson’s single-shot vaccine, including a recommendation that patients receive an mRNA vaccine for both the first and second booster.

The group also updated dosing recommendations for pre-exposure prevention with tixagevimab plus cilgavimab (Evusheld, AstraZeneca), suggesting 300 mg of each monoclonal antibody instead of 150 mg, based on in vitro activity against Omicron variants.

The group noted that the Moderna and Pfizer shots can be used interchangeably for boosters.

“The NCCN Committee considers both homologous and heterologous boosters to be appropriate options,” the experts wrote.

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

The National Comprehensive Cancer Network (NCCN) has recommended a fifth COVID-19 mRNA shot for people who are immunocompromised, including many with cancer or a history of cancer.

A fifth shot of an mRNA vaccine represents a second booster, the group explained, because the primary mRNA immunization series for immunocompromised individuals involves three doses of either the Pfizer or Moderna vaccine.

The update, issued today, comes from the NCCN’s Advisory Committee on COVID-19 Vaccination and Pre-exposure Prophylaxis, which released its first vaccine guidelines for patients with cancer in January 2021. The NCCN has issued numerous updates since then as information about the virus and vaccines has evolved. 

“We know a lot more about COVID-19 and the vaccines now, and we can use that knowledge to minimize the confusion and enhance the protection we can offer to our immunocompromised patients,” said advisory committee co-leader Lindsey Baden, MD, an infectious diseases specialist at the Dana-Farber Cancer Institute, Boston.

The latest iteration of the NCCN’s COVID guidelines includes an update for patients who initially received Johnson & Johnson’s single-shot vaccine, including a recommendation that patients receive an mRNA vaccine for both the first and second booster.

The group also updated dosing recommendations for pre-exposure prevention with tixagevimab plus cilgavimab (Evusheld, AstraZeneca), suggesting 300 mg of each monoclonal antibody instead of 150 mg, based on in vitro activity against Omicron variants.

The group noted that the Moderna and Pfizer shots can be used interchangeably for boosters.

“The NCCN Committee considers both homologous and heterologous boosters to be appropriate options,” the experts wrote.

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

BOSTON – According to the best available data, solid organ transplant recipients (SOTRs) at highest risk for developing skin cancer are thoracic organ recipients, those aged 50 or older at the time of the transplant, and males.

White patients who meet these criteria should be screening within 2 years after transplant, while Black patients should be screened within 5 years after transplant, Ally-Khan Somani, MD, PhD, said at the annual meeting of the American Academy of Dermatology.

Dr. Somani, director of dermatologic surgery and the division of cutaneous oncology at Indiana University, Indianapolis, based his remarks on consensus screening guidelines assembled from three rounds of Delphi method surveys with 47 dermatologists and 37 transplant physicians, with the goal of establishing skin cancer screening recommendations for SOTRs. Among the dermatologists surveyed, 45% were Mohs surgeons and 55% were general dermatologists.

The panel recommended that the transplant team should perform risk assessment for SOTRs to risk stratify patients for skin cancer screening (high risk vs. low risk). They also proposed that dermatologists perform skin cancer screening by full-body skin examinations, and that SOTRs with a history of skin cancer should continue with routine skin cancer surveillance as recommended by their dermatologists.

Those at low risk for skin cancer include abdominal organ recipients, SOTR age of younger than 50 at time of transplant, and female gender. The guidelines recommend that White, Asian, and Hispanic patients who meet those criteria should be screened within 5 years after transplant, while no consensus was reached for Black patients who meet those criteria.

Based on posttransplant skin cancer incidence rates, risk is increased among males, Whites, thoracic organ recipients, and being age 50 or older, Dr. Somani said. “At our institution, we make sure there’s a good connection between our transplant teams and dermatologists. We recommend rapid referral for suspicious lesions and we educate patients and screen them within 1 year of transplant, or sooner for high-risk patients. Surveillance is increased to every 3 or 4 months for patients with a history of multiple or high-risk cancers or sooner, followed by routine surveillance as recommended by the patient’s dermatologist.”

To risk stratify patients on the development of their first skin cancer post transplantation, researchers developed the Skin and Ultraviolet Neoplasia Transplant Risk Assessment Calculator (SUNTRAC), a prediction tool with a freely available app. Data for the tool were drawn from the Transplant Skin Cancer Network study, a 5-year analysis of 6,340 adult recipients of a first solid organ transplant at 26 transplant centers in the United States. It generates a risk score for SOTRs (low, medium, high, or very high), which informs transplant care providers of a patient’s risk of skin cancer.

Dr. Somani disclosed that he has received grants and funding from Castle Biosciences. He is an adviser to Cook Biotech and a consultant to Sanara MedTech.

BOSTON – According to the best available data, solid organ transplant recipients (SOTRs) at highest risk for developing skin cancer are thoracic organ recipients, those aged 50 or older at the time of the transplant, and males.

White patients who meet these criteria should be screening within 2 years after transplant, while Black patients should be screened within 5 years after transplant, Ally-Khan Somani, MD, PhD, said at the annual meeting of the American Academy of Dermatology.

Dr. Somani, director of dermatologic surgery and the division of cutaneous oncology at Indiana University, Indianapolis, based his remarks on consensus screening guidelines assembled from three rounds of Delphi method surveys with 47 dermatologists and 37 transplant physicians, with the goal of establishing skin cancer screening recommendations for SOTRs. Among the dermatologists surveyed, 45% were Mohs surgeons and 55% were general dermatologists.

The panel recommended that the transplant team should perform risk assessment for SOTRs to risk stratify patients for skin cancer screening (high risk vs. low risk). They also proposed that dermatologists perform skin cancer screening by full-body skin examinations, and that SOTRs with a history of skin cancer should continue with routine skin cancer surveillance as recommended by their dermatologists.

Those at low risk for skin cancer include abdominal organ recipients, SOTR age of younger than 50 at time of transplant, and female gender. The guidelines recommend that White, Asian, and Hispanic patients who meet those criteria should be screened within 5 years after transplant, while no consensus was reached for Black patients who meet those criteria.

Based on posttransplant skin cancer incidence rates, risk is increased among males, Whites, thoracic organ recipients, and being age 50 or older, Dr. Somani said. “At our institution, we make sure there’s a good connection between our transplant teams and dermatologists. We recommend rapid referral for suspicious lesions and we educate patients and screen them within 1 year of transplant, or sooner for high-risk patients. Surveillance is increased to every 3 or 4 months for patients with a history of multiple or high-risk cancers or sooner, followed by routine surveillance as recommended by the patient’s dermatologist.”

To risk stratify patients on the development of their first skin cancer post transplantation, researchers developed the Skin and Ultraviolet Neoplasia Transplant Risk Assessment Calculator (SUNTRAC), a prediction tool with a freely available app. Data for the tool were drawn from the Transplant Skin Cancer Network study, a 5-year analysis of 6,340 adult recipients of a first solid organ transplant at 26 transplant centers in the United States. It generates a risk score for SOTRs (low, medium, high, or very high), which informs transplant care providers of a patient’s risk of skin cancer.

Dr. Somani disclosed that he has received grants and funding from Castle Biosciences. He is an adviser to Cook Biotech and a consultant to Sanara MedTech.

BOSTON – According to the best available data, solid organ transplant recipients (SOTRs) at highest risk for developing skin cancer are thoracic organ recipients, those aged 50 or older at the time of the transplant, and males.

White patients who meet these criteria should be screening within 2 years after transplant, while Black patients should be screened within 5 years after transplant, Ally-Khan Somani, MD, PhD, said at the annual meeting of the American Academy of Dermatology.

Dr. Somani, director of dermatologic surgery and the division of cutaneous oncology at Indiana University, Indianapolis, based his remarks on consensus screening guidelines assembled from three rounds of Delphi method surveys with 47 dermatologists and 37 transplant physicians, with the goal of establishing skin cancer screening recommendations for SOTRs. Among the dermatologists surveyed, 45% were Mohs surgeons and 55% were general dermatologists.

The panel recommended that the transplant team should perform risk assessment for SOTRs to risk stratify patients for skin cancer screening (high risk vs. low risk). They also proposed that dermatologists perform skin cancer screening by full-body skin examinations, and that SOTRs with a history of skin cancer should continue with routine skin cancer surveillance as recommended by their dermatologists.

Those at low risk for skin cancer include abdominal organ recipients, SOTR age of younger than 50 at time of transplant, and female gender. The guidelines recommend that White, Asian, and Hispanic patients who meet those criteria should be screened within 5 years after transplant, while no consensus was reached for Black patients who meet those criteria.

Based on posttransplant skin cancer incidence rates, risk is increased among males, Whites, thoracic organ recipients, and being age 50 or older, Dr. Somani said. “At our institution, we make sure there’s a good connection between our transplant teams and dermatologists. We recommend rapid referral for suspicious lesions and we educate patients and screen them within 1 year of transplant, or sooner for high-risk patients. Surveillance is increased to every 3 or 4 months for patients with a history of multiple or high-risk cancers or sooner, followed by routine surveillance as recommended by the patient’s dermatologist.”

To risk stratify patients on the development of their first skin cancer post transplantation, researchers developed the Skin and Ultraviolet Neoplasia Transplant Risk Assessment Calculator (SUNTRAC), a prediction tool with a freely available app. Data for the tool were drawn from the Transplant Skin Cancer Network study, a 5-year analysis of 6,340 adult recipients of a first solid organ transplant at 26 transplant centers in the United States. It generates a risk score for SOTRs (low, medium, high, or very high), which informs transplant care providers of a patient’s risk of skin cancer.

Dr. Somani disclosed that he has received grants and funding from Castle Biosciences. He is an adviser to Cook Biotech and a consultant to Sanara MedTech.

Bullous pemphigoid, an immune-mediated condition characterized by large, fluid-filled blisters on the skin, is a rare but serious complication of cancer therapy with immune checkpoint inhibitors (ICIs) that may result in treatment interruption or cessation.

Investigators in Boston report that among patients receiving ICIs, being aged 70 years or older and having skin cancer are both significant risk factors for bullous pemphigoid. On the plus side, ICI-induced bullous pemphigoid also appears to be a marker for improved tumor responses to therapy.

In a nested case-control study of 5,636 patients with cancer who received either a programmed death 1 inhibitor such as pembrolizumab (Keytruda) or nivolumab (Opdivo) or a cytotoxic T-lymphocyte–associated protein 4 inhibitor such as ipilimumab (Yervoy), 35 patients (0.6%) developed bullous pemphigoid. The study by Nicole R. LeBoeuf, MD, MPH, from Brigham and Women’s Hospital in Boston and colleagues was published online in JAMA Dermatology.

“What is interesting is that 0.6 is a small number, but we’re seeing bullous pemphigoid at considerably higher frequency than is expected in the general population,” Dr. LeBoeuf said in an interview.

And although bullous pemphigoid has the potential to disrupt ICI therapy, it also appears to be a marker for a favorable tumor response, the investigators found.

Their findings suggest that management of bullous pemphigoid for patients receiving ICIs should focus on early identification and management with therapies directed at the specific toxicity, Dr. LeBoeuf said.

“When you make a specific diagnosis like bullous pemphigoid, then you can treat that specific disease with very targeted therapies, such as omalizumab or dupilumab or rituximab – things that are not globally immune suppressing like steroid or other T-cell–depleting agents. Studies have shown that depleting B cells with anti-CD20 agents is not detrimental to immune checkpoint inhibitor therapy,” she said.
 

Dermatologic AEs common

About 40% of patients with cancer treated with ICIs experience immune-related dermatologic adverse events (AEs) that can range from mild rashes and hair and nail changes to uncommon but life-threatening complications, such as Stevens-Johnson syndrome, a form of toxic epidermal necrolysis, according to members of a European Academy of Dermatology and Venereology task force.

“The desirable, immune-mediated oncologic response is often achieved at the cost of immune-related adverse events (irAEs) that may potentially affect any organ system,” they wrote in a position statement on the management of ICI-derived dermatologic adverse events.

Dr. LeBoeuf and colleagues note that, while reported risk factors for idiopathic bullous pemphigoid include advanced age, type 2 diabetes, use of dipeptidyl peptidase-4 inhibitors, cerebrovascular disease, and neurocognitive disease, risk factors for bullous pemphigoid and other adverse dermatologic events associated with ICIs are less well known.
 

Study details

To identify risk factors for bullous pemphigoid in patients receiving ICI, the investigators performed a case-control study nested within a retrospective cohort study.

They evaluated records for all patients in the three Harvard-affiliated hospitals to identify patients with ICI-associated bullous pemphigoid from October 2014 through December 2020. Control persons were all patients in the Dana-Farber cancer registry who received ICIs during the study period.

The investigators chose age at ICI initiation (69 years and younger or 70 years and older), sex, ICI agents, and cancer type as potential risk factors.

They used propensity score matching based on age, cancer type, ICI agent, and number of ICI cycles to match two control persons with each case patient.

Of the 5,636 patients treated with ICIs during the study period, 35 (0.6%) developed bullous pemphigoid. The median age was 72.8 years, and 71.4% were men.

In a multivariate logistic regression model that included 2,955 patients with complete data in the cancer registry, factors significantly associated with developing bullous pemphigoid included age 70 years or older (odds ratio, 2.32; P = .01), having melanoma (OR, 3.21; P < .001), and having nonmelanoma skin cancer (OR, 8.32; P < .001).

In comparing the 35 case patients with their matched control patients, a complete or partial response at first restaging imaging was significantly associated with developing bullous pemphigoid (OR, 3.37; P = .01). In addition, there was a higher likelihood of tumor responses to ICIs among patients with bullous pemphigoid, compared with matched control patients (objective response rate, 82.9% vs. 61.4%; P = .03).
 

Prudent toxicity management

Ryan Sullivan, MD, who treats patients with skin cancer at Massachusetts General Hospital Cancer Center, Boston, but was not involved in the study, commented that the findings raise questions about the relationship between skin cancers and immune-related adverse events.

“It is compelling that bullous pemphigoid is a skin toxicity and is more common to happen in skin cancer patients,” he noted. “That’s a very interesting finding, and the reason that it’s interesting is that it’s harder to understand why a presumably antibody-mediated side effect would be more likely to have that cross-reactivity where the tumor started and where the toxicity happened,” he said in an interview.

He noted that the benefits of ICIs for patients with skin cancers far outweigh the risks of dermatologic adverse events such as bullous pemphigoid and that ICI-associated events require judicious management.

“This is true across the spectrum of toxicities: There are clear manifestations of toxicity that we should be more thoughtful about what’s driving them, more thoughtful about what it is, and more thoughtful about treating them, other than just pouring steroids into patients in industrial doses and hoping that everything’s going to be OK,” he said.

No funding source for the study was reported. Dr. LeBoeuf reported receiving grants from the National Institutes of Health National Cancer Institute during the conduct of the study and personal fees for serving as a consultant for several companies outside the study. Coauthor Arash Mostaghimi, MD, MPA, MPH, is associate editor of JAMA Dermatology but was not involved in study selection or evaluation for publication. Dr. Sullivan disclosed consulting for ICI makers Bristol-Myers Squibb and Merck.

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

Bullous pemphigoid, an immune-mediated condition characterized by large, fluid-filled blisters on the skin, is a rare but serious complication of cancer therapy with immune checkpoint inhibitors (ICIs) that may result in treatment interruption or cessation.

Investigators in Boston report that among patients receiving ICIs, being aged 70 years or older and having skin cancer are both significant risk factors for bullous pemphigoid. On the plus side, ICI-induced bullous pemphigoid also appears to be a marker for improved tumor responses to therapy.

In a nested case-control study of 5,636 patients with cancer who received either a programmed death 1 inhibitor such as pembrolizumab (Keytruda) or nivolumab (Opdivo) or a cytotoxic T-lymphocyte–associated protein 4 inhibitor such as ipilimumab (Yervoy), 35 patients (0.6%) developed bullous pemphigoid. The study by Nicole R. LeBoeuf, MD, MPH, from Brigham and Women’s Hospital in Boston and colleagues was published online in JAMA Dermatology.

“What is interesting is that 0.6 is a small number, but we’re seeing bullous pemphigoid at considerably higher frequency than is expected in the general population,” Dr. LeBoeuf said in an interview.

And although bullous pemphigoid has the potential to disrupt ICI therapy, it also appears to be a marker for a favorable tumor response, the investigators found.

Their findings suggest that management of bullous pemphigoid for patients receiving ICIs should focus on early identification and management with therapies directed at the specific toxicity, Dr. LeBoeuf said.

“When you make a specific diagnosis like bullous pemphigoid, then you can treat that specific disease with very targeted therapies, such as omalizumab or dupilumab or rituximab – things that are not globally immune suppressing like steroid or other T-cell–depleting agents. Studies have shown that depleting B cells with anti-CD20 agents is not detrimental to immune checkpoint inhibitor therapy,” she said.
 

Dermatologic AEs common

About 40% of patients with cancer treated with ICIs experience immune-related dermatologic adverse events (AEs) that can range from mild rashes and hair and nail changes to uncommon but life-threatening complications, such as Stevens-Johnson syndrome, a form of toxic epidermal necrolysis, according to members of a European Academy of Dermatology and Venereology task force.

“The desirable, immune-mediated oncologic response is often achieved at the cost of immune-related adverse events (irAEs) that may potentially affect any organ system,” they wrote in a position statement on the management of ICI-derived dermatologic adverse events.

Dr. LeBoeuf and colleagues note that, while reported risk factors for idiopathic bullous pemphigoid include advanced age, type 2 diabetes, use of dipeptidyl peptidase-4 inhibitors, cerebrovascular disease, and neurocognitive disease, risk factors for bullous pemphigoid and other adverse dermatologic events associated with ICIs are less well known.
 

Study details

To identify risk factors for bullous pemphigoid in patients receiving ICI, the investigators performed a case-control study nested within a retrospective cohort study.

They evaluated records for all patients in the three Harvard-affiliated hospitals to identify patients with ICI-associated bullous pemphigoid from October 2014 through December 2020. Control persons were all patients in the Dana-Farber cancer registry who received ICIs during the study period.

The investigators chose age at ICI initiation (69 years and younger or 70 years and older), sex, ICI agents, and cancer type as potential risk factors.

They used propensity score matching based on age, cancer type, ICI agent, and number of ICI cycles to match two control persons with each case patient.

Of the 5,636 patients treated with ICIs during the study period, 35 (0.6%) developed bullous pemphigoid. The median age was 72.8 years, and 71.4% were men.

In a multivariate logistic regression model that included 2,955 patients with complete data in the cancer registry, factors significantly associated with developing bullous pemphigoid included age 70 years or older (odds ratio, 2.32; P = .01), having melanoma (OR, 3.21; P < .001), and having nonmelanoma skin cancer (OR, 8.32; P < .001).

In comparing the 35 case patients with their matched control patients, a complete or partial response at first restaging imaging was significantly associated with developing bullous pemphigoid (OR, 3.37; P = .01). In addition, there was a higher likelihood of tumor responses to ICIs among patients with bullous pemphigoid, compared with matched control patients (objective response rate, 82.9% vs. 61.4%; P = .03).
 

Prudent toxicity management

Ryan Sullivan, MD, who treats patients with skin cancer at Massachusetts General Hospital Cancer Center, Boston, but was not involved in the study, commented that the findings raise questions about the relationship between skin cancers and immune-related adverse events.

“It is compelling that bullous pemphigoid is a skin toxicity and is more common to happen in skin cancer patients,” he noted. “That’s a very interesting finding, and the reason that it’s interesting is that it’s harder to understand why a presumably antibody-mediated side effect would be more likely to have that cross-reactivity where the tumor started and where the toxicity happened,” he said in an interview.

He noted that the benefits of ICIs for patients with skin cancers far outweigh the risks of dermatologic adverse events such as bullous pemphigoid and that ICI-associated events require judicious management.

“This is true across the spectrum of toxicities: There are clear manifestations of toxicity that we should be more thoughtful about what’s driving them, more thoughtful about what it is, and more thoughtful about treating them, other than just pouring steroids into patients in industrial doses and hoping that everything’s going to be OK,” he said.

No funding source for the study was reported. Dr. LeBoeuf reported receiving grants from the National Institutes of Health National Cancer Institute during the conduct of the study and personal fees for serving as a consultant for several companies outside the study. Coauthor Arash Mostaghimi, MD, MPA, MPH, is associate editor of JAMA Dermatology but was not involved in study selection or evaluation for publication. Dr. Sullivan disclosed consulting for ICI makers Bristol-Myers Squibb and Merck.

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

Bullous pemphigoid, an immune-mediated condition characterized by large, fluid-filled blisters on the skin, is a rare but serious complication of cancer therapy with immune checkpoint inhibitors (ICIs) that may result in treatment interruption or cessation.

Investigators in Boston report that among patients receiving ICIs, being aged 70 years or older and having skin cancer are both significant risk factors for bullous pemphigoid. On the plus side, ICI-induced bullous pemphigoid also appears to be a marker for improved tumor responses to therapy.

In a nested case-control study of 5,636 patients with cancer who received either a programmed death 1 inhibitor such as pembrolizumab (Keytruda) or nivolumab (Opdivo) or a cytotoxic T-lymphocyte–associated protein 4 inhibitor such as ipilimumab (Yervoy), 35 patients (0.6%) developed bullous pemphigoid. The study by Nicole R. LeBoeuf, MD, MPH, from Brigham and Women’s Hospital in Boston and colleagues was published online in JAMA Dermatology.

“What is interesting is that 0.6 is a small number, but we’re seeing bullous pemphigoid at considerably higher frequency than is expected in the general population,” Dr. LeBoeuf said in an interview.

And although bullous pemphigoid has the potential to disrupt ICI therapy, it also appears to be a marker for a favorable tumor response, the investigators found.

Their findings suggest that management of bullous pemphigoid for patients receiving ICIs should focus on early identification and management with therapies directed at the specific toxicity, Dr. LeBoeuf said.

“When you make a specific diagnosis like bullous pemphigoid, then you can treat that specific disease with very targeted therapies, such as omalizumab or dupilumab or rituximab – things that are not globally immune suppressing like steroid or other T-cell–depleting agents. Studies have shown that depleting B cells with anti-CD20 agents is not detrimental to immune checkpoint inhibitor therapy,” she said.
 

Dermatologic AEs common

About 40% of patients with cancer treated with ICIs experience immune-related dermatologic adverse events (AEs) that can range from mild rashes and hair and nail changes to uncommon but life-threatening complications, such as Stevens-Johnson syndrome, a form of toxic epidermal necrolysis, according to members of a European Academy of Dermatology and Venereology task force.

“The desirable, immune-mediated oncologic response is often achieved at the cost of immune-related adverse events (irAEs) that may potentially affect any organ system,” they wrote in a position statement on the management of ICI-derived dermatologic adverse events.

Dr. LeBoeuf and colleagues note that, while reported risk factors for idiopathic bullous pemphigoid include advanced age, type 2 diabetes, use of dipeptidyl peptidase-4 inhibitors, cerebrovascular disease, and neurocognitive disease, risk factors for bullous pemphigoid and other adverse dermatologic events associated with ICIs are less well known.
 

Study details

To identify risk factors for bullous pemphigoid in patients receiving ICI, the investigators performed a case-control study nested within a retrospective cohort study.

They evaluated records for all patients in the three Harvard-affiliated hospitals to identify patients with ICI-associated bullous pemphigoid from October 2014 through December 2020. Control persons were all patients in the Dana-Farber cancer registry who received ICIs during the study period.

The investigators chose age at ICI initiation (69 years and younger or 70 years and older), sex, ICI agents, and cancer type as potential risk factors.

They used propensity score matching based on age, cancer type, ICI agent, and number of ICI cycles to match two control persons with each case patient.

Of the 5,636 patients treated with ICIs during the study period, 35 (0.6%) developed bullous pemphigoid. The median age was 72.8 years, and 71.4% were men.

In a multivariate logistic regression model that included 2,955 patients with complete data in the cancer registry, factors significantly associated with developing bullous pemphigoid included age 70 years or older (odds ratio, 2.32; P = .01), having melanoma (OR, 3.21; P < .001), and having nonmelanoma skin cancer (OR, 8.32; P < .001).

In comparing the 35 case patients with their matched control patients, a complete or partial response at first restaging imaging was significantly associated with developing bullous pemphigoid (OR, 3.37; P = .01). In addition, there was a higher likelihood of tumor responses to ICIs among patients with bullous pemphigoid, compared with matched control patients (objective response rate, 82.9% vs. 61.4%; P = .03).
 

Prudent toxicity management

Ryan Sullivan, MD, who treats patients with skin cancer at Massachusetts General Hospital Cancer Center, Boston, but was not involved in the study, commented that the findings raise questions about the relationship between skin cancers and immune-related adverse events.

“It is compelling that bullous pemphigoid is a skin toxicity and is more common to happen in skin cancer patients,” he noted. “That’s a very interesting finding, and the reason that it’s interesting is that it’s harder to understand why a presumably antibody-mediated side effect would be more likely to have that cross-reactivity where the tumor started and where the toxicity happened,” he said in an interview.

He noted that the benefits of ICIs for patients with skin cancers far outweigh the risks of dermatologic adverse events such as bullous pemphigoid and that ICI-associated events require judicious management.

“This is true across the spectrum of toxicities: There are clear manifestations of toxicity that we should be more thoughtful about what’s driving them, more thoughtful about what it is, and more thoughtful about treating them, other than just pouring steroids into patients in industrial doses and hoping that everything’s going to be OK,” he said.

No funding source for the study was reported. Dr. LeBoeuf reported receiving grants from the National Institutes of Health National Cancer Institute during the conduct of the study and personal fees for serving as a consultant for several companies outside the study. Coauthor Arash Mostaghimi, MD, MPA, MPH, is associate editor of JAMA Dermatology but was not involved in study selection or evaluation for publication. Dr. Sullivan disclosed consulting for ICI makers Bristol-Myers Squibb and Merck.

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

NEW ORLEANS – For patients with resectable non–small cell lung cancer (NSCLC), further clinical data continue to show benefit from preoperative treatment with the immune checkpoint inhibitor nivolumab (Opdivo) with chemotherapy.

The combination resulted in significantly longer event-free survival and a 14-fold greater chance of having a pathological complete response compared with chemotherapy alone.

Adding immunotherapy (IO) to chemotherapy in the neoadjuvant setting represents “a quantum leap in lung cancer therapy,” commented David P. Carbone, MD, PhD, director of the James Thoracic Center at Ohio State University, Columbus.

“Combining IO with surgery I think is a new standard of care and will almost certainly improve overall survival [OS] in early-stage disease, for the first time in decades, in my entire career,” he said while discussing the new data at the annual meeting of the American Association for Cancer Research.

The data come from the phase 3 CheckMate 816 study, an open-label trial involving patients with stage IB-IIIA resectable NSCLC. The study was published in the New England Journal of Medicine to coincide with the presentation.

Results from this trial were the basis of the Food and Drug Administration’s recent approval of neoadjuvant therapy with nivolumab (Opdivo) and platinum-based chemotherapy in this population, which one expert described as “a turning point in how we treat resectable NSCLC.”

“Neoadjuvant IO has multiple theoretical advantages of over adjuvant IO,” commented Dr. Carbone. “CheckMate 816 suggests that practice will prove this theory correct.”

Importance of Neoadjuvant Immunotherapy

New details of the results were presented at the meeting by Nicolas Girard, MD, from Institut Curie in Paris.

Among 358 patients in the trial, the median event-free survival (EFS) was 31.6 months for patients randomly assigned to the combination of the immune checkpoint inhibitor nivolumab and platinum-base chemotherapy, compared with 20.8 months for patients assigned to chemotherapy alone. This translated into a hazard ratio for disease recurrence, progression, or death of 0.63 (P = .005).

In addition, 24% of patients assigned to the nivolumab plus chemotherapy arm had a pathological complete response (pCR) to neoadjuvant therapy, compared with only 2.2% of those assigned to chemotherapy alone (P < .001).

Dr. Girard said the study provided important clues to the importance of neoadjuvant therapy for improving objective responses.

“Event-free survival was improved in patients with a pathological complete response, compared with those without, suggesting pCR is a surrogate endpoint for long-term outcomes in resectable non–small cell lung cancer, and this is the first time [this has been shown] in a randomized, phase 3 study,” he said.
 

Neoadjuvant slow to catch on

About one -fourth of all patients who are diagnosed with NSCLC have resectable disease, Dr. Girard and colleagues noted. However, 30%-55% of patients who undergo surgery with curative intent ultimately experience recurrence and die from their disease.

Neoadjuvant therapy may improve chances for complete resection and prevent or delay recurrence after surgery, but the absolute difference in 5-year recurrence-free survival and OS with neoadjuvant chemotherapy alone is only about 6%, they noted.

The new results suggest that adding neoadjuvant immunotherapy to chemotherapy will improve upon this, although so far, the OS data from this trial are immature.

In an interim analysis, the median OS rate was 83% at 2 years for patients treated with nivolumab plus chemotherapy, compared with 71% for patients treated with chemotherapy alone. The published results show a significant improvement in the two primary endpoints – EFS and pCR.

In an editorial accompanying the study, Christine M. Lovly, MD, PhD, from the Vanderbilt-Ingram Cancer Center at Vanderbilt University in Nashville, Tenn., commented that the results of the trial are expected to change practice.

“However, several issues remain to be addressed,” she wrote. “First, is a pathological complete response predictive of event-free survival? Can event-free survival be used as a surrogate endpoint for overall survival? Second, although not mandated for this trial, approximately 20% of the patients received postoperative therapy. Is adjuvant therapy necessary? What criteria should be used to select patients to receive adjuvant therapy?”

Dr. Lovly also pointed out that patients with tumors harboring mutations in the genes EGFR or ALK were excluded from the trial.

“Therefore, implementation of neoadjuvant therapies requires biomarker testing for patients with early-stage disease at the time of diagnosis, a considerable alteration in the routine practice of lung-cancer medicine,” she wrote.
 

Fears of delaying surgery

In an interview, Upal Basu Roy, PhD, MPH, executive director of research at the LUNGevity Foundation, who was not involved in the study, gave a reason why neoadjuvant therapy is not more widely prescribed for patients with resectable NSCLC.

“Clinicians are always scared, and I think patients are as well, that giving a treatment before surgery would delay surgery,” he said. “When patients are diagnosed with lung cancer and they’re told that surgery offers the potential of cure and then hear that you’re giving them a treatment before surgery and that treatment may potentially delay surgery, that is a huge source of anxiety.”

In addition, clinicians until recently were unsure about which patients were most likely to benefit from neoadjuvant therapy when the only option was chemotherapy, “but that’s changing, obviously, with the recent approval of neoadjuvant nivolumab through CheckMate 816,” he said.
 

CheckMate 816 details

In the CheckMate 816 study, investigators enrolled patients with newly diagnosed resectable NSCLC (stage IB-IIIA) who had good performance status and no known sensitizing EGFR mutations or ALK alterations.

After stratification by stage, programmed death–1 status, and sex, the team randomly assigned patients to receive either nivolumab 360 mg plus platinum-based chemotherapy every 3 weeks for a total of three cycles or chemotherapy alone.

At the end of neoadjuvant therapy, patients underwent radiologic restaging and surgery within 6 weeks. Patients could also receive optional adjuvant chemotherapy with or without radiotherapy.

Of the 179 patients in each arm, 176 received the assigned treatment. In all, 149 (83%) of those assigned to the combination had definitive surgery, as did 135 (75%) of those assigned to chemotherapy alone.

In addition, 35 patients (20%) of those assigned to nivolumab-chemo and 56 (32%) assigned to chemotherapy alone received adjuvant therapy.

The coprimary endpoints of EFS and pCR favored the combination, both in the overall population and across most subgroups, including patients younger than 65, men and women, Asian patients, those with stage IIIA disease, nonsquamous histology, current smokers and never-smokers, and patients with higher levels of PD–ligand 1 expression.

The rates of grade 3 or 4 treatment-related adverse events were similar between the groups, at 33.5% with the combination and 36.9% with chemotherapy alone.

Rates of adverse events leading to study discontinuation, treatment-related adverse events, and surgery-related adverse events were similar between the groups. There were two treatment-related deaths, both in the chemotherapy-alone arm.

CheckMate 816 was funded by Bristol-Myers Squibb (manufacturer of nivolumab). Girard has consulted for and has received grant support from Bristol-Myers Squibb and other companies. Dr. Carbone has consulted for Bristol-Myers Squibb and other companies. Dr. Lovly has consulted for various companies. Dr. Roy has received grants from Bristol-Myers Squibb to the LUNGevity Foundation.

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

NEW ORLEANS – For patients with resectable non–small cell lung cancer (NSCLC), further clinical data continue to show benefit from preoperative treatment with the immune checkpoint inhibitor nivolumab (Opdivo) with chemotherapy.

The combination resulted in significantly longer event-free survival and a 14-fold greater chance of having a pathological complete response compared with chemotherapy alone.

Adding immunotherapy (IO) to chemotherapy in the neoadjuvant setting represents “a quantum leap in lung cancer therapy,” commented David P. Carbone, MD, PhD, director of the James Thoracic Center at Ohio State University, Columbus.

“Combining IO with surgery I think is a new standard of care and will almost certainly improve overall survival [OS] in early-stage disease, for the first time in decades, in my entire career,” he said while discussing the new data at the annual meeting of the American Association for Cancer Research.

The data come from the phase 3 CheckMate 816 study, an open-label trial involving patients with stage IB-IIIA resectable NSCLC. The study was published in the New England Journal of Medicine to coincide with the presentation.

Results from this trial were the basis of the Food and Drug Administration’s recent approval of neoadjuvant therapy with nivolumab (Opdivo) and platinum-based chemotherapy in this population, which one expert described as “a turning point in how we treat resectable NSCLC.”

“Neoadjuvant IO has multiple theoretical advantages of over adjuvant IO,” commented Dr. Carbone. “CheckMate 816 suggests that practice will prove this theory correct.”

Importance of Neoadjuvant Immunotherapy

New details of the results were presented at the meeting by Nicolas Girard, MD, from Institut Curie in Paris.

Among 358 patients in the trial, the median event-free survival (EFS) was 31.6 months for patients randomly assigned to the combination of the immune checkpoint inhibitor nivolumab and platinum-base chemotherapy, compared with 20.8 months for patients assigned to chemotherapy alone. This translated into a hazard ratio for disease recurrence, progression, or death of 0.63 (P = .005).

In addition, 24% of patients assigned to the nivolumab plus chemotherapy arm had a pathological complete response (pCR) to neoadjuvant therapy, compared with only 2.2% of those assigned to chemotherapy alone (P < .001).

Dr. Girard said the study provided important clues to the importance of neoadjuvant therapy for improving objective responses.

“Event-free survival was improved in patients with a pathological complete response, compared with those without, suggesting pCR is a surrogate endpoint for long-term outcomes in resectable non–small cell lung cancer, and this is the first time [this has been shown] in a randomized, phase 3 study,” he said.
 

Neoadjuvant slow to catch on

About one -fourth of all patients who are diagnosed with NSCLC have resectable disease, Dr. Girard and colleagues noted. However, 30%-55% of patients who undergo surgery with curative intent ultimately experience recurrence and die from their disease.

Neoadjuvant therapy may improve chances for complete resection and prevent or delay recurrence after surgery, but the absolute difference in 5-year recurrence-free survival and OS with neoadjuvant chemotherapy alone is only about 6%, they noted.

The new results suggest that adding neoadjuvant immunotherapy to chemotherapy will improve upon this, although so far, the OS data from this trial are immature.

In an interim analysis, the median OS rate was 83% at 2 years for patients treated with nivolumab plus chemotherapy, compared with 71% for patients treated with chemotherapy alone. The published results show a significant improvement in the two primary endpoints – EFS and pCR.

In an editorial accompanying the study, Christine M. Lovly, MD, PhD, from the Vanderbilt-Ingram Cancer Center at Vanderbilt University in Nashville, Tenn., commented that the results of the trial are expected to change practice.

“However, several issues remain to be addressed,” she wrote. “First, is a pathological complete response predictive of event-free survival? Can event-free survival be used as a surrogate endpoint for overall survival? Second, although not mandated for this trial, approximately 20% of the patients received postoperative therapy. Is adjuvant therapy necessary? What criteria should be used to select patients to receive adjuvant therapy?”

Dr. Lovly also pointed out that patients with tumors harboring mutations in the genes EGFR or ALK were excluded from the trial.

“Therefore, implementation of neoadjuvant therapies requires biomarker testing for patients with early-stage disease at the time of diagnosis, a considerable alteration in the routine practice of lung-cancer medicine,” she wrote.
 

Fears of delaying surgery

In an interview, Upal Basu Roy, PhD, MPH, executive director of research at the LUNGevity Foundation, who was not involved in the study, gave a reason why neoadjuvant therapy is not more widely prescribed for patients with resectable NSCLC.

“Clinicians are always scared, and I think patients are as well, that giving a treatment before surgery would delay surgery,” he said. “When patients are diagnosed with lung cancer and they’re told that surgery offers the potential of cure and then hear that you’re giving them a treatment before surgery and that treatment may potentially delay surgery, that is a huge source of anxiety.”

In addition, clinicians until recently were unsure about which patients were most likely to benefit from neoadjuvant therapy when the only option was chemotherapy, “but that’s changing, obviously, with the recent approval of neoadjuvant nivolumab through CheckMate 816,” he said.
 

CheckMate 816 details

In the CheckMate 816 study, investigators enrolled patients with newly diagnosed resectable NSCLC (stage IB-IIIA) who had good performance status and no known sensitizing EGFR mutations or ALK alterations.

After stratification by stage, programmed death–1 status, and sex, the team randomly assigned patients to receive either nivolumab 360 mg plus platinum-based chemotherapy every 3 weeks for a total of three cycles or chemotherapy alone.

At the end of neoadjuvant therapy, patients underwent radiologic restaging and surgery within 6 weeks. Patients could also receive optional adjuvant chemotherapy with or without radiotherapy.

Of the 179 patients in each arm, 176 received the assigned treatment. In all, 149 (83%) of those assigned to the combination had definitive surgery, as did 135 (75%) of those assigned to chemotherapy alone.

In addition, 35 patients (20%) of those assigned to nivolumab-chemo and 56 (32%) assigned to chemotherapy alone received adjuvant therapy.

The coprimary endpoints of EFS and pCR favored the combination, both in the overall population and across most subgroups, including patients younger than 65, men and women, Asian patients, those with stage IIIA disease, nonsquamous histology, current smokers and never-smokers, and patients with higher levels of PD–ligand 1 expression.

The rates of grade 3 or 4 treatment-related adverse events were similar between the groups, at 33.5% with the combination and 36.9% with chemotherapy alone.

Rates of adverse events leading to study discontinuation, treatment-related adverse events, and surgery-related adverse events were similar between the groups. There were two treatment-related deaths, both in the chemotherapy-alone arm.

CheckMate 816 was funded by Bristol-Myers Squibb (manufacturer of nivolumab). Girard has consulted for and has received grant support from Bristol-Myers Squibb and other companies. Dr. Carbone has consulted for Bristol-Myers Squibb and other companies. Dr. Lovly has consulted for various companies. Dr. Roy has received grants from Bristol-Myers Squibb to the LUNGevity Foundation.

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

NEW ORLEANS – For patients with resectable non–small cell lung cancer (NSCLC), further clinical data continue to show benefit from preoperative treatment with the immune checkpoint inhibitor nivolumab (Opdivo) with chemotherapy.

The combination resulted in significantly longer event-free survival and a 14-fold greater chance of having a pathological complete response compared with chemotherapy alone.

Adding immunotherapy (IO) to chemotherapy in the neoadjuvant setting represents “a quantum leap in lung cancer therapy,” commented David P. Carbone, MD, PhD, director of the James Thoracic Center at Ohio State University, Columbus.

“Combining IO with surgery I think is a new standard of care and will almost certainly improve overall survival [OS] in early-stage disease, for the first time in decades, in my entire career,” he said while discussing the new data at the annual meeting of the American Association for Cancer Research.

The data come from the phase 3 CheckMate 816 study, an open-label trial involving patients with stage IB-IIIA resectable NSCLC. The study was published in the New England Journal of Medicine to coincide with the presentation.

Results from this trial were the basis of the Food and Drug Administration’s recent approval of neoadjuvant therapy with nivolumab (Opdivo) and platinum-based chemotherapy in this population, which one expert described as “a turning point in how we treat resectable NSCLC.”

“Neoadjuvant IO has multiple theoretical advantages of over adjuvant IO,” commented Dr. Carbone. “CheckMate 816 suggests that practice will prove this theory correct.”

Importance of Neoadjuvant Immunotherapy

New details of the results were presented at the meeting by Nicolas Girard, MD, from Institut Curie in Paris.

Among 358 patients in the trial, the median event-free survival (EFS) was 31.6 months for patients randomly assigned to the combination of the immune checkpoint inhibitor nivolumab and platinum-base chemotherapy, compared with 20.8 months for patients assigned to chemotherapy alone. This translated into a hazard ratio for disease recurrence, progression, or death of 0.63 (P = .005).

In addition, 24% of patients assigned to the nivolumab plus chemotherapy arm had a pathological complete response (pCR) to neoadjuvant therapy, compared with only 2.2% of those assigned to chemotherapy alone (P < .001).

Dr. Girard said the study provided important clues to the importance of neoadjuvant therapy for improving objective responses.

“Event-free survival was improved in patients with a pathological complete response, compared with those without, suggesting pCR is a surrogate endpoint for long-term outcomes in resectable non–small cell lung cancer, and this is the first time [this has been shown] in a randomized, phase 3 study,” he said.
 

Neoadjuvant slow to catch on

About one -fourth of all patients who are diagnosed with NSCLC have resectable disease, Dr. Girard and colleagues noted. However, 30%-55% of patients who undergo surgery with curative intent ultimately experience recurrence and die from their disease.

Neoadjuvant therapy may improve chances for complete resection and prevent or delay recurrence after surgery, but the absolute difference in 5-year recurrence-free survival and OS with neoadjuvant chemotherapy alone is only about 6%, they noted.

The new results suggest that adding neoadjuvant immunotherapy to chemotherapy will improve upon this, although so far, the OS data from this trial are immature.

In an interim analysis, the median OS rate was 83% at 2 years for patients treated with nivolumab plus chemotherapy, compared with 71% for patients treated with chemotherapy alone. The published results show a significant improvement in the two primary endpoints – EFS and pCR.

In an editorial accompanying the study, Christine M. Lovly, MD, PhD, from the Vanderbilt-Ingram Cancer Center at Vanderbilt University in Nashville, Tenn., commented that the results of the trial are expected to change practice.

“However, several issues remain to be addressed,” she wrote. “First, is a pathological complete response predictive of event-free survival? Can event-free survival be used as a surrogate endpoint for overall survival? Second, although not mandated for this trial, approximately 20% of the patients received postoperative therapy. Is adjuvant therapy necessary? What criteria should be used to select patients to receive adjuvant therapy?”

Dr. Lovly also pointed out that patients with tumors harboring mutations in the genes EGFR or ALK were excluded from the trial.

“Therefore, implementation of neoadjuvant therapies requires biomarker testing for patients with early-stage disease at the time of diagnosis, a considerable alteration in the routine practice of lung-cancer medicine,” she wrote.
 

Fears of delaying surgery

In an interview, Upal Basu Roy, PhD, MPH, executive director of research at the LUNGevity Foundation, who was not involved in the study, gave a reason why neoadjuvant therapy is not more widely prescribed for patients with resectable NSCLC.

“Clinicians are always scared, and I think patients are as well, that giving a treatment before surgery would delay surgery,” he said. “When patients are diagnosed with lung cancer and they’re told that surgery offers the potential of cure and then hear that you’re giving them a treatment before surgery and that treatment may potentially delay surgery, that is a huge source of anxiety.”

In addition, clinicians until recently were unsure about which patients were most likely to benefit from neoadjuvant therapy when the only option was chemotherapy, “but that’s changing, obviously, with the recent approval of neoadjuvant nivolumab through CheckMate 816,” he said.
 

CheckMate 816 details

In the CheckMate 816 study, investigators enrolled patients with newly diagnosed resectable NSCLC (stage IB-IIIA) who had good performance status and no known sensitizing EGFR mutations or ALK alterations.

After stratification by stage, programmed death–1 status, and sex, the team randomly assigned patients to receive either nivolumab 360 mg plus platinum-based chemotherapy every 3 weeks for a total of three cycles or chemotherapy alone.

At the end of neoadjuvant therapy, patients underwent radiologic restaging and surgery within 6 weeks. Patients could also receive optional adjuvant chemotherapy with or without radiotherapy.

Of the 179 patients in each arm, 176 received the assigned treatment. In all, 149 (83%) of those assigned to the combination had definitive surgery, as did 135 (75%) of those assigned to chemotherapy alone.

In addition, 35 patients (20%) of those assigned to nivolumab-chemo and 56 (32%) assigned to chemotherapy alone received adjuvant therapy.

The coprimary endpoints of EFS and pCR favored the combination, both in the overall population and across most subgroups, including patients younger than 65, men and women, Asian patients, those with stage IIIA disease, nonsquamous histology, current smokers and never-smokers, and patients with higher levels of PD–ligand 1 expression.

The rates of grade 3 or 4 treatment-related adverse events were similar between the groups, at 33.5% with the combination and 36.9% with chemotherapy alone.

Rates of adverse events leading to study discontinuation, treatment-related adverse events, and surgery-related adverse events were similar between the groups. There were two treatment-related deaths, both in the chemotherapy-alone arm.

CheckMate 816 was funded by Bristol-Myers Squibb (manufacturer of nivolumab). Girard has consulted for and has received grant support from Bristol-Myers Squibb and other companies. Dr. Carbone has consulted for Bristol-Myers Squibb and other companies. Dr. Lovly has consulted for various companies. Dr. Roy has received grants from Bristol-Myers Squibb to the LUNGevity Foundation.

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

NEW ORLEANS – In just over one-third of patients with metastatic melanoma who had experienced disease progression while receiving multiple prior lines of therapy, including immunotherapy and targeted agents, objective clinical responses occurred with a customized cell therapy based on T cells extracted directly from tumor tissue.

The product, called lifileucel, is custom made for each patient and utilizes tumor-infiltrating lymphocytes (TILs) extracted from tumor lesions. This approach differs from other cell-based therapies, such as chimeric antigen receptor (CAR) T cell therapy, which utilizes T cells collected from the patient’s blood.

The new results come from a phase 2 trial conducted in 66 patients with previously treated unresectable or metastatic melanoma who received a single dose of the product. The objective response rate was 36.4%.

“Lifileucel has demonstrated efficacy and durability of response for patients with metastatic melanoma and represents a viable therapeutic option warranting further investigation,” commented Jason Alan Chesney, MD, PhD, from the James Graham Brown Cancer Center, the University of Louisville (Ky.).

He presented the new data at the virtual American Association for Cancer Research (AACR) Annual Meeting 2021.

Customized cell therapy with TILs has been explored for the treatment of melanoma for more than a decade. Some researchers have reported durable response in 25% of patients.

However, “generalizing TIL therapy has been hampered by the complex and really not absolutely defined process for generating cells,” commented Philip Greenberg, MD, professor and head of the program in immunology in the Clinical Research Division of the Fred Hutchinson Cancer Center, Seattle, who was the invited discussant.

The current study demonstrates that cell generation can be performed at a centralized facility that has the required technical expertise. The patient-specific products are then disseminated to multiple centers, he said. The study also demonstrates that TILs can be successfully generated from tumor sites other than skin or lymph nodes.

“Toxicity was, however, significant, although it was generally manageable, and it did occur early, generally within the first 2 weeks,” he noted.
 

Patient-derived product

Lifileucel is a tailor-made immunotherapy product created from melanoma tumor tissues resected from lesions in skin, lymph nodes, liver, lung, peritoneum, musculoskeletal system, breast, or other visceral organs. The cells are shipped to a central manufacturing facility, whre the TILs are isolated, cultured, expanded, and reinvigorated. The cells are then harvested and cryopreserved. The process takes about 22 days. The cryopreserved product is then shipped back to the treating facility.

Prior to receiving the expanded and rejuvenated TILs, patients undergo myeloablative conditioning with cyclophosphamide followed by fludarabine. The TILs are then delivered in a single infusion, followed by administration of up to six doses of interleukin-2 (IL-2).
 

Details from clinical trial

At the meeting, Dr. Chesney reported details on the 66 patients in the trial. They had metastatic melanoma that was progressing on treatment. The mean number of prior lines of therapy was 3.3. All of the patients had received prior anti–programmed cell death protein–1 (PD-1) or programmed cell death–ligand-1 (PD-L1) agents; 53 had received a cytotoxic T lymphocyte protein 4 (CTLA-4) inhibitor; and 15 had received a BRAF/MEK inhibitor.

These patients had a mean of six baseline target and nontarget lesions, and 28 patients had liver and/or brain metastases.

Just over a third of patients (24 of 66, 36.4%) had an objective response; three patients had a complete response; and 21 had a partial response. In addition, 29 patients had stable disease, and nine experienced disease progression. Four patients had not undergone the first assessment at the time of data cutoff.

After a median follow-up of 28.1 months, the median duration of response was not reached. It ranged from 2.2 to > 35.2 months.

Since the data cutoff in April 2020, reduction of tumor burden has occurred in 50 of 62 evaluable patients. Reductions in the target lesion sum of diameters has occurred in 11 patients. In one patient, a partial response converted to a complete response 24 months after infusion, Dr. Chesney noted.

The mean number of TILs infused was 27.3 billion (27.3 x 109). Appropriate amounts of TILs were manufactured from tumor samples acquired across all sites, and reductions in target lesion sum of diameter were seen across the range of TIL total cell doses.

All patients experienced at least one adverse event of any grade; all but two experienced grade 3 or 4 adverse events. Two patients died, one as a result of intra-abdominal hemorrhage considered possibly related to TIL therapy, and one from acute respiratory failure deemed not related to TILs.

The most common grade 3 or 4 adverse events were thrombocytopenia, anemia, febrile neutropenia, neutropenia, hypophosphatemia, and lymphopenia.

“The adverse event profile was manageable and was consistent with the underlying and the known profiles of the nonmyeloblative depletion regimen and IL-2,” Dr. Chesney said.

The decreasing frequency of adverse events over time reflects the potential benefit of the one-time infusion, and no new safety risks have been identified during more than 2 years of follow-up, he added.
 

Remaining questions, next steps

Dr. Greenberg commented that the one of the limitations of the study is that the investigators did not characterize the TIL product.

“Studies have predicted that there’s a particular type of cell, a stemlike T cell, that’s responsible for mediating the efficacy,” he commented. He referred to research from Steven Rosenberg, MD, PhD, and colleagues at the National Cancer Institute, where TILs were first used in 2002.

Dr. Greenberg also raised the question of whether high-dose IL-2 was required post infusion, given that the patients were lymphodepleted before receiving lifileucel.

Future steps for TIL therapy, he said, should include identification of biomarkers for success or failure; strategies to enhance generation and expansion of tumor-reactive T cells; postinfusion strategies, such as using vaccines and/or checkpoint inhibitors to increase therapeutic activity; genetic modifications to enhance the function of TILs in the tumor microenvironment; and research into other tumor types that may be effectively treated with TILs.

The study was supported by Iovance Biotherapeutics. Dr. Chesney has received research funding from Iovance and other companies and has consulted for Amgen and Replimune. Dr. Greenberg has served on scientific advisory boards, has received grant/research support, and owns stock in several companies that do not include Iovance.

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

NEW ORLEANS – In just over one-third of patients with metastatic melanoma who had experienced disease progression while receiving multiple prior lines of therapy, including immunotherapy and targeted agents, objective clinical responses occurred with a customized cell therapy based on T cells extracted directly from tumor tissue.

The product, called lifileucel, is custom made for each patient and utilizes tumor-infiltrating lymphocytes (TILs) extracted from tumor lesions. This approach differs from other cell-based therapies, such as chimeric antigen receptor (CAR) T cell therapy, which utilizes T cells collected from the patient’s blood.

The new results come from a phase 2 trial conducted in 66 patients with previously treated unresectable or metastatic melanoma who received a single dose of the product. The objective response rate was 36.4%.

“Lifileucel has demonstrated efficacy and durability of response for patients with metastatic melanoma and represents a viable therapeutic option warranting further investigation,” commented Jason Alan Chesney, MD, PhD, from the James Graham Brown Cancer Center, the University of Louisville (Ky.).

He presented the new data at the virtual American Association for Cancer Research (AACR) Annual Meeting 2021.

Customized cell therapy with TILs has been explored for the treatment of melanoma for more than a decade. Some researchers have reported durable response in 25% of patients.

However, “generalizing TIL therapy has been hampered by the complex and really not absolutely defined process for generating cells,” commented Philip Greenberg, MD, professor and head of the program in immunology in the Clinical Research Division of the Fred Hutchinson Cancer Center, Seattle, who was the invited discussant.

The current study demonstrates that cell generation can be performed at a centralized facility that has the required technical expertise. The patient-specific products are then disseminated to multiple centers, he said. The study also demonstrates that TILs can be successfully generated from tumor sites other than skin or lymph nodes.

“Toxicity was, however, significant, although it was generally manageable, and it did occur early, generally within the first 2 weeks,” he noted.
 

Patient-derived product

Lifileucel is a tailor-made immunotherapy product created from melanoma tumor tissues resected from lesions in skin, lymph nodes, liver, lung, peritoneum, musculoskeletal system, breast, or other visceral organs. The cells are shipped to a central manufacturing facility, whre the TILs are isolated, cultured, expanded, and reinvigorated. The cells are then harvested and cryopreserved. The process takes about 22 days. The cryopreserved product is then shipped back to the treating facility.

Prior to receiving the expanded and rejuvenated TILs, patients undergo myeloablative conditioning with cyclophosphamide followed by fludarabine. The TILs are then delivered in a single infusion, followed by administration of up to six doses of interleukin-2 (IL-2).
 

Details from clinical trial

At the meeting, Dr. Chesney reported details on the 66 patients in the trial. They had metastatic melanoma that was progressing on treatment. The mean number of prior lines of therapy was 3.3. All of the patients had received prior anti–programmed cell death protein–1 (PD-1) or programmed cell death–ligand-1 (PD-L1) agents; 53 had received a cytotoxic T lymphocyte protein 4 (CTLA-4) inhibitor; and 15 had received a BRAF/MEK inhibitor.

These patients had a mean of six baseline target and nontarget lesions, and 28 patients had liver and/or brain metastases.

Just over a third of patients (24 of 66, 36.4%) had an objective response; three patients had a complete response; and 21 had a partial response. In addition, 29 patients had stable disease, and nine experienced disease progression. Four patients had not undergone the first assessment at the time of data cutoff.

After a median follow-up of 28.1 months, the median duration of response was not reached. It ranged from 2.2 to > 35.2 months.

Since the data cutoff in April 2020, reduction of tumor burden has occurred in 50 of 62 evaluable patients. Reductions in the target lesion sum of diameters has occurred in 11 patients. In one patient, a partial response converted to a complete response 24 months after infusion, Dr. Chesney noted.

The mean number of TILs infused was 27.3 billion (27.3 x 109). Appropriate amounts of TILs were manufactured from tumor samples acquired across all sites, and reductions in target lesion sum of diameter were seen across the range of TIL total cell doses.

All patients experienced at least one adverse event of any grade; all but two experienced grade 3 or 4 adverse events. Two patients died, one as a result of intra-abdominal hemorrhage considered possibly related to TIL therapy, and one from acute respiratory failure deemed not related to TILs.

The most common grade 3 or 4 adverse events were thrombocytopenia, anemia, febrile neutropenia, neutropenia, hypophosphatemia, and lymphopenia.

“The adverse event profile was manageable and was consistent with the underlying and the known profiles of the nonmyeloblative depletion regimen and IL-2,” Dr. Chesney said.

The decreasing frequency of adverse events over time reflects the potential benefit of the one-time infusion, and no new safety risks have been identified during more than 2 years of follow-up, he added.
 

Remaining questions, next steps

Dr. Greenberg commented that the one of the limitations of the study is that the investigators did not characterize the TIL product.

“Studies have predicted that there’s a particular type of cell, a stemlike T cell, that’s responsible for mediating the efficacy,” he commented. He referred to research from Steven Rosenberg, MD, PhD, and colleagues at the National Cancer Institute, where TILs were first used in 2002.

Dr. Greenberg also raised the question of whether high-dose IL-2 was required post infusion, given that the patients were lymphodepleted before receiving lifileucel.

Future steps for TIL therapy, he said, should include identification of biomarkers for success or failure; strategies to enhance generation and expansion of tumor-reactive T cells; postinfusion strategies, such as using vaccines and/or checkpoint inhibitors to increase therapeutic activity; genetic modifications to enhance the function of TILs in the tumor microenvironment; and research into other tumor types that may be effectively treated with TILs.

The study was supported by Iovance Biotherapeutics. Dr. Chesney has received research funding from Iovance and other companies and has consulted for Amgen and Replimune. Dr. Greenberg has served on scientific advisory boards, has received grant/research support, and owns stock in several companies that do not include Iovance.

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

NEW ORLEANS – In just over one-third of patients with metastatic melanoma who had experienced disease progression while receiving multiple prior lines of therapy, including immunotherapy and targeted agents, objective clinical responses occurred with a customized cell therapy based on T cells extracted directly from tumor tissue.

The product, called lifileucel, is custom made for each patient and utilizes tumor-infiltrating lymphocytes (TILs) extracted from tumor lesions. This approach differs from other cell-based therapies, such as chimeric antigen receptor (CAR) T cell therapy, which utilizes T cells collected from the patient’s blood.

The new results come from a phase 2 trial conducted in 66 patients with previously treated unresectable or metastatic melanoma who received a single dose of the product. The objective response rate was 36.4%.

“Lifileucel has demonstrated efficacy and durability of response for patients with metastatic melanoma and represents a viable therapeutic option warranting further investigation,” commented Jason Alan Chesney, MD, PhD, from the James Graham Brown Cancer Center, the University of Louisville (Ky.).

He presented the new data at the virtual American Association for Cancer Research (AACR) Annual Meeting 2021.

Customized cell therapy with TILs has been explored for the treatment of melanoma for more than a decade. Some researchers have reported durable response in 25% of patients.

However, “generalizing TIL therapy has been hampered by the complex and really not absolutely defined process for generating cells,” commented Philip Greenberg, MD, professor and head of the program in immunology in the Clinical Research Division of the Fred Hutchinson Cancer Center, Seattle, who was the invited discussant.

The current study demonstrates that cell generation can be performed at a centralized facility that has the required technical expertise. The patient-specific products are then disseminated to multiple centers, he said. The study also demonstrates that TILs can be successfully generated from tumor sites other than skin or lymph nodes.

“Toxicity was, however, significant, although it was generally manageable, and it did occur early, generally within the first 2 weeks,” he noted.
 

Patient-derived product

Lifileucel is a tailor-made immunotherapy product created from melanoma tumor tissues resected from lesions in skin, lymph nodes, liver, lung, peritoneum, musculoskeletal system, breast, or other visceral organs. The cells are shipped to a central manufacturing facility, whre the TILs are isolated, cultured, expanded, and reinvigorated. The cells are then harvested and cryopreserved. The process takes about 22 days. The cryopreserved product is then shipped back to the treating facility.

Prior to receiving the expanded and rejuvenated TILs, patients undergo myeloablative conditioning with cyclophosphamide followed by fludarabine. The TILs are then delivered in a single infusion, followed by administration of up to six doses of interleukin-2 (IL-2).
 

Details from clinical trial

At the meeting, Dr. Chesney reported details on the 66 patients in the trial. They had metastatic melanoma that was progressing on treatment. The mean number of prior lines of therapy was 3.3. All of the patients had received prior anti–programmed cell death protein–1 (PD-1) or programmed cell death–ligand-1 (PD-L1) agents; 53 had received a cytotoxic T lymphocyte protein 4 (CTLA-4) inhibitor; and 15 had received a BRAF/MEK inhibitor.

These patients had a mean of six baseline target and nontarget lesions, and 28 patients had liver and/or brain metastases.

Just over a third of patients (24 of 66, 36.4%) had an objective response; three patients had a complete response; and 21 had a partial response. In addition, 29 patients had stable disease, and nine experienced disease progression. Four patients had not undergone the first assessment at the time of data cutoff.

After a median follow-up of 28.1 months, the median duration of response was not reached. It ranged from 2.2 to > 35.2 months.

Since the data cutoff in April 2020, reduction of tumor burden has occurred in 50 of 62 evaluable patients. Reductions in the target lesion sum of diameters has occurred in 11 patients. In one patient, a partial response converted to a complete response 24 months after infusion, Dr. Chesney noted.

The mean number of TILs infused was 27.3 billion (27.3 x 109). Appropriate amounts of TILs were manufactured from tumor samples acquired across all sites, and reductions in target lesion sum of diameter were seen across the range of TIL total cell doses.

All patients experienced at least one adverse event of any grade; all but two experienced grade 3 or 4 adverse events. Two patients died, one as a result of intra-abdominal hemorrhage considered possibly related to TIL therapy, and one from acute respiratory failure deemed not related to TILs.

The most common grade 3 or 4 adverse events were thrombocytopenia, anemia, febrile neutropenia, neutropenia, hypophosphatemia, and lymphopenia.

“The adverse event profile was manageable and was consistent with the underlying and the known profiles of the nonmyeloblative depletion regimen and IL-2,” Dr. Chesney said.

The decreasing frequency of adverse events over time reflects the potential benefit of the one-time infusion, and no new safety risks have been identified during more than 2 years of follow-up, he added.
 

Remaining questions, next steps

Dr. Greenberg commented that the one of the limitations of the study is that the investigators did not characterize the TIL product.

“Studies have predicted that there’s a particular type of cell, a stemlike T cell, that’s responsible for mediating the efficacy,” he commented. He referred to research from Steven Rosenberg, MD, PhD, and colleagues at the National Cancer Institute, where TILs were first used in 2002.

Dr. Greenberg also raised the question of whether high-dose IL-2 was required post infusion, given that the patients were lymphodepleted before receiving lifileucel.

Future steps for TIL therapy, he said, should include identification of biomarkers for success or failure; strategies to enhance generation and expansion of tumor-reactive T cells; postinfusion strategies, such as using vaccines and/or checkpoint inhibitors to increase therapeutic activity; genetic modifications to enhance the function of TILs in the tumor microenvironment; and research into other tumor types that may be effectively treated with TILs.

The study was supported by Iovance Biotherapeutics. Dr. Chesney has received research funding from Iovance and other companies and has consulted for Amgen and Replimune. Dr. Greenberg has served on scientific advisory boards, has received grant/research support, and owns stock in several companies that do not include Iovance.

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