News

Most doctors mind their manners. But surgeons are the most likely to be reported for unprofessional behavior, while physicians practicing in pediatric settings are the least likely, according to a recent study of more than 35,000 physicians.

The research, published on June 6 in JAMA Network Open, found that fewer than 10% of physicians were reported by their coworkers for at least one instance of unprofessional behavior, and only 1% showed a pattern of such reports.

Data were gathered from the Center for Patient and Professional Advocacy’s (CPPA’s) Coworker Observation Reporting System (CORS) program, a national collaborative in which 193 participating hospitals and practice sites file safety-event reports involving medical workers’ unprofessional behaviors. An algorithm that weights CORS reports based on recency and severity was used to analyze the data. The study was spearheaded by William O. Cooper, MD, MPH, director of the CPPA at Vanderbilt University Medical Center, Nashville, Tennessee.

The retrospective cohort study included deidentified data on credentialed physicians, not including residents or fellows, who practiced at a CORS site between 2018 and 2022.
 

Why Surgeons?

The authors speculated that the reason surgeons were reported for unprofessional behavior more often than their colleagues in nonsurgical specialties was because surgery is a more stressful environment than other specialties and requires more teamwork, resulting in more interactions during high-stakes events.

Daniel Katz, MD, professor and vice chair of education for the Department of Anesthesiology, Perioperative and Pain Medicine at the Icahn School of Medicine at Mount Sinai, New York City, added that part of the problem is that surgeons are expected to perform at very high levels all the time.

“When things that are outside the control of the surgeon don’t go well,” Dr. Katz said, “that can lead to increased frustration and negative emotions, which will then bring out these kinds of behaviors.”
 

Types of Unprofessional Behaviors

The most common out-of-bounds behaviors reported involved disrespectful communication or lack of professional responsibility. In one example, a physician called a coworker a “bossy cow” when the coworker reminded the physician of the need to do a timeout before beginning a bronchoscopy.

In another case involving professional responsibility, a coworker asked a physician if the team should wait for a disoriented patient’s spouse to arrive. The doctor’s response: “We’ll be here all night if we do that. If you won’t sign as a witness, I’ll get someone else who will.”

The least common reports involved unprofessionalism related to medical care or professional integrity. One cited a physician removing a Foley catheter without wearing gloves and having visible urine on his hands and not washing them before touching other things in the room. In a reported lapse of professional integrity, a physician billed at level five after spending only 4 minutes with a patient.
 

Impact of Unprofessional Behavior

Unprofessional behavior among physicians is more than just unpleasant. It can threaten the functioning of teams and increase patient complications. In addition, individuals who model unprofessional behaviors are associated with increased malpractice claims, the study’s authors wrote.

Dr. Katz agreed that unprofessional behavior is damaging to both patients and the profession as a whole.

However, this doesn’t happen because some doctors are bad, he said. Physicians today are working in a pressure cooker. The current healthcare environment, with its increased administrative burdens, lack of staffing, and other problems, has increased the overall level of stress and led to burnout among healthcare personnel.

“You have to fix the system to create a working environment that doesn’t cause somebody to explode,” Dr. Katz said.

The goal of the CORS program and this study, Dr. Cooper said, is to help physicians better weather these stresses.
 

Study Limitations

The authors noted some weaknesses in the study. Some unprofessional behavior may go unreported because of fear of retaliation or for other reasons victims or witnesses did not feel safe to report their colleagues. Also, reports were not evaluated to ensure the truth of the accusations. The records reviewed did not include the gender of the physician, though the researchers pointed out that previous studies have shown that women are less likely than men to receive CORS reports.
 

A version of this article appeared on Medscape.com.

Most doctors mind their manners. But surgeons are the most likely to be reported for unprofessional behavior, while physicians practicing in pediatric settings are the least likely, according to a recent study of more than 35,000 physicians.

The research, published on June 6 in JAMA Network Open, found that fewer than 10% of physicians were reported by their coworkers for at least one instance of unprofessional behavior, and only 1% showed a pattern of such reports.

Data were gathered from the Center for Patient and Professional Advocacy’s (CPPA’s) Coworker Observation Reporting System (CORS) program, a national collaborative in which 193 participating hospitals and practice sites file safety-event reports involving medical workers’ unprofessional behaviors. An algorithm that weights CORS reports based on recency and severity was used to analyze the data. The study was spearheaded by William O. Cooper, MD, MPH, director of the CPPA at Vanderbilt University Medical Center, Nashville, Tennessee.

The retrospective cohort study included deidentified data on credentialed physicians, not including residents or fellows, who practiced at a CORS site between 2018 and 2022.
 

Why Surgeons?

The authors speculated that the reason surgeons were reported for unprofessional behavior more often than their colleagues in nonsurgical specialties was because surgery is a more stressful environment than other specialties and requires more teamwork, resulting in more interactions during high-stakes events.

Daniel Katz, MD, professor and vice chair of education for the Department of Anesthesiology, Perioperative and Pain Medicine at the Icahn School of Medicine at Mount Sinai, New York City, added that part of the problem is that surgeons are expected to perform at very high levels all the time.

“When things that are outside the control of the surgeon don’t go well,” Dr. Katz said, “that can lead to increased frustration and negative emotions, which will then bring out these kinds of behaviors.”
 

Types of Unprofessional Behaviors

The most common out-of-bounds behaviors reported involved disrespectful communication or lack of professional responsibility. In one example, a physician called a coworker a “bossy cow” when the coworker reminded the physician of the need to do a timeout before beginning a bronchoscopy.

In another case involving professional responsibility, a coworker asked a physician if the team should wait for a disoriented patient’s spouse to arrive. The doctor’s response: “We’ll be here all night if we do that. If you won’t sign as a witness, I’ll get someone else who will.”

The least common reports involved unprofessionalism related to medical care or professional integrity. One cited a physician removing a Foley catheter without wearing gloves and having visible urine on his hands and not washing them before touching other things in the room. In a reported lapse of professional integrity, a physician billed at level five after spending only 4 minutes with a patient.
 

Impact of Unprofessional Behavior

Unprofessional behavior among physicians is more than just unpleasant. It can threaten the functioning of teams and increase patient complications. In addition, individuals who model unprofessional behaviors are associated with increased malpractice claims, the study’s authors wrote.

Dr. Katz agreed that unprofessional behavior is damaging to both patients and the profession as a whole.

However, this doesn’t happen because some doctors are bad, he said. Physicians today are working in a pressure cooker. The current healthcare environment, with its increased administrative burdens, lack of staffing, and other problems, has increased the overall level of stress and led to burnout among healthcare personnel.

“You have to fix the system to create a working environment that doesn’t cause somebody to explode,” Dr. Katz said.

The goal of the CORS program and this study, Dr. Cooper said, is to help physicians better weather these stresses.
 

Study Limitations

The authors noted some weaknesses in the study. Some unprofessional behavior may go unreported because of fear of retaliation or for other reasons victims or witnesses did not feel safe to report their colleagues. Also, reports were not evaluated to ensure the truth of the accusations. The records reviewed did not include the gender of the physician, though the researchers pointed out that previous studies have shown that women are less likely than men to receive CORS reports.
 

A version of this article appeared on Medscape.com.

Most doctors mind their manners. But surgeons are the most likely to be reported for unprofessional behavior, while physicians practicing in pediatric settings are the least likely, according to a recent study of more than 35,000 physicians.

The research, published on June 6 in JAMA Network Open, found that fewer than 10% of physicians were reported by their coworkers for at least one instance of unprofessional behavior, and only 1% showed a pattern of such reports.

Data were gathered from the Center for Patient and Professional Advocacy’s (CPPA’s) Coworker Observation Reporting System (CORS) program, a national collaborative in which 193 participating hospitals and practice sites file safety-event reports involving medical workers’ unprofessional behaviors. An algorithm that weights CORS reports based on recency and severity was used to analyze the data. The study was spearheaded by William O. Cooper, MD, MPH, director of the CPPA at Vanderbilt University Medical Center, Nashville, Tennessee.

The retrospective cohort study included deidentified data on credentialed physicians, not including residents or fellows, who practiced at a CORS site between 2018 and 2022.
 

Why Surgeons?

The authors speculated that the reason surgeons were reported for unprofessional behavior more often than their colleagues in nonsurgical specialties was because surgery is a more stressful environment than other specialties and requires more teamwork, resulting in more interactions during high-stakes events.

Daniel Katz, MD, professor and vice chair of education for the Department of Anesthesiology, Perioperative and Pain Medicine at the Icahn School of Medicine at Mount Sinai, New York City, added that part of the problem is that surgeons are expected to perform at very high levels all the time.

“When things that are outside the control of the surgeon don’t go well,” Dr. Katz said, “that can lead to increased frustration and negative emotions, which will then bring out these kinds of behaviors.”
 

Types of Unprofessional Behaviors

The most common out-of-bounds behaviors reported involved disrespectful communication or lack of professional responsibility. In one example, a physician called a coworker a “bossy cow” when the coworker reminded the physician of the need to do a timeout before beginning a bronchoscopy.

In another case involving professional responsibility, a coworker asked a physician if the team should wait for a disoriented patient’s spouse to arrive. The doctor’s response: “We’ll be here all night if we do that. If you won’t sign as a witness, I’ll get someone else who will.”

The least common reports involved unprofessionalism related to medical care or professional integrity. One cited a physician removing a Foley catheter without wearing gloves and having visible urine on his hands and not washing them before touching other things in the room. In a reported lapse of professional integrity, a physician billed at level five after spending only 4 minutes with a patient.
 

Impact of Unprofessional Behavior

Unprofessional behavior among physicians is more than just unpleasant. It can threaten the functioning of teams and increase patient complications. In addition, individuals who model unprofessional behaviors are associated with increased malpractice claims, the study’s authors wrote.

Dr. Katz agreed that unprofessional behavior is damaging to both patients and the profession as a whole.

However, this doesn’t happen because some doctors are bad, he said. Physicians today are working in a pressure cooker. The current healthcare environment, with its increased administrative burdens, lack of staffing, and other problems, has increased the overall level of stress and led to burnout among healthcare personnel.

“You have to fix the system to create a working environment that doesn’t cause somebody to explode,” Dr. Katz said.

The goal of the CORS program and this study, Dr. Cooper said, is to help physicians better weather these stresses.
 

Study Limitations

The authors noted some weaknesses in the study. Some unprofessional behavior may go unreported because of fear of retaliation or for other reasons victims or witnesses did not feel safe to report their colleagues. Also, reports were not evaluated to ensure the truth of the accusations. The records reviewed did not include the gender of the physician, though the researchers pointed out that previous studies have shown that women are less likely than men to receive CORS reports.
 

A version of this article appeared on Medscape.com.

Advances in breast cancer detection and treatment over the past decades have led to an increase in the number of women diagnosed at earlier stages and successfully treated, ushering in a new era of survivorship.

According to the American Cancer Society, there are currently roughly four million breast cancer survivors in the United States, including those still receiving treatment. The mortality rates for women with breast cancer have been decreasing since 1989, with an overall decline of 42% through 2021.

As the population of breast cancer survivors continues to grow, developing and delivering comprehensive survivorship care is crucial, Thelma Brown told attendees at the American Society of Clinical Oncology (ASCO) 2024 annual meeting. Ms. Brown’s talk was part of an educational session focused on addressing issues among early breast cancer survivors, evolving practices in breast cancer surveillance, and mitigating recurrence risk.

The challenges following breast cancer diagnosis and treatment can be both visible and invisible, said Ms. Brown, a patient advocate and member of the Breast Cancer Working Group at the University of Alabama at Birmingham.

Up to 90% of early breast cancer survivors experience long-term effects from treatment, which often include fatigue, loss of mobility, chronic pain, peripheral neuropathy, lymphedema, and infertility.

Survivors face an elevated risk for depression, anxiety, and fear of recurrence. “Fear of recurrence is a big issue, and it’s almost universal,” she noted.

Cancer treatment is also costly, leading to financial toxicity for many patients, which also “affects adherence to treatment and overall family well-being,” Ms. Brown explained. Survivors may struggle to access financial assistance due to complex eligibility requirements and a lack of awareness about available resources. 

There is a need for holistic and coordinated survivorship care that includes management of long-term effects and surveillance for recurrence to help breast cancer survivors to transition from merely surviving to thriving, said Ms. Brown.
 

Surveilling and Mitigating Recurrence

Surveillance in patients with breast cancer post treatment remains a debated area, particularly when it comes to detecting distant recurrences, David Cescon, MD, PhD, with Princess Margaret Cancer Center, University Health Network, Toronto, said in his talk.

While breast imaging standards are well established, systemic surveillance through imaging and laboratory tests for asymptomatic patients lacks consensus and uniform guidelines, he explained.

Several clinical trials conducted from the late 1980s to the early 2000s showed no survival benefit from intensive surveillance strategies, including imaging and laboratory tests, compared to routine clinical follow-up. Some studies even demonstrated a trend toward harm, given the number of false positives.

These studies formed the basis for guidelines that discourage surveillance among asymptomatic survivors. Currently, no major guideline organization — the National Comprehensive Cancer Network, ASCO, and the European Society for Medical Oncology — recommends routine (nonbreast) radiologic surveillance or laboratory tests for detecting asymptomatic distant breast cancer recurrence, Dr. Cescon said.

Yet, that may change in the coming years, he told attendees.

Ongoing prospective studies will hopefully generate high-quality evidence on the effectiveness of modern surveillance techniques, particularly detection of circulating tumor DNA (ctDNA) and its effect on survival and quality of life, said Dr. Cescon.

These liquid biopsy assays have shown promise in identifying minimal residual disease before radiographic recurrence, he explained. Retrospective studies suggest high prognostic value, with nearly all patients with detectable ctDNA post therapy experiencing recurrence. 

He cautioned, however, that while sensitive ctDNA tests exist and have clinical validity in identifying minimal residual disease, “their clinical utility has not yet been demonstrated,” Dr. Cescon said, adding that any surveillance strategy must consider the psychological effect of frequent testing and the potential for false positives or negatives.

The ultimate goal is preventing disease recurrence, said Neil M. Iyengar, MD, with Memorial Sloan Kettering Cancer Center in New York, in his talk on mitigating recurrence risk. 

Lifestyle modifications are an important targeted intervention for patients entering the survivorship phase, with a “robust level of evidence” supporting their use to mitigate adverse effects associated with cancer therapy and improve quality of life, he told attendees. Most notably, smoking cessation, healthy dietary patterns, physical activity, and reduced alcohol have been associated with improvements in breast cancer outcomes.

Going forward, it will be important to “understand the antitumor potential of lifestyle modification and how we can wield this type of intervention as a precision tool to potentially enhance the effects of cancer therapy and potentially cancer biology,” said Dr. Iyengar.

Ms. Brown disclosed relationships with AstraZeneca. Dr. Cescon disclosed relationships with AstraZeneca, Gilead Sciences, Daiichi Sankyo Europe GmbH, Eisai, GlaxoSmithKline, and other companies. Dr. Iyengar disclosed relationships with Curio Science, DAVA Oncology, Novartis, Pfizer, and others.

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

Advances in breast cancer detection and treatment over the past decades have led to an increase in the number of women diagnosed at earlier stages and successfully treated, ushering in a new era of survivorship.

According to the American Cancer Society, there are currently roughly four million breast cancer survivors in the United States, including those still receiving treatment. The mortality rates for women with breast cancer have been decreasing since 1989, with an overall decline of 42% through 2021.

As the population of breast cancer survivors continues to grow, developing and delivering comprehensive survivorship care is crucial, Thelma Brown told attendees at the American Society of Clinical Oncology (ASCO) 2024 annual meeting. Ms. Brown’s talk was part of an educational session focused on addressing issues among early breast cancer survivors, evolving practices in breast cancer surveillance, and mitigating recurrence risk.

The challenges following breast cancer diagnosis and treatment can be both visible and invisible, said Ms. Brown, a patient advocate and member of the Breast Cancer Working Group at the University of Alabama at Birmingham.

Up to 90% of early breast cancer survivors experience long-term effects from treatment, which often include fatigue, loss of mobility, chronic pain, peripheral neuropathy, lymphedema, and infertility.

Survivors face an elevated risk for depression, anxiety, and fear of recurrence. “Fear of recurrence is a big issue, and it’s almost universal,” she noted.

Cancer treatment is also costly, leading to financial toxicity for many patients, which also “affects adherence to treatment and overall family well-being,” Ms. Brown explained. Survivors may struggle to access financial assistance due to complex eligibility requirements and a lack of awareness about available resources. 

There is a need for holistic and coordinated survivorship care that includes management of long-term effects and surveillance for recurrence to help breast cancer survivors to transition from merely surviving to thriving, said Ms. Brown.
 

Surveilling and Mitigating Recurrence

Surveillance in patients with breast cancer post treatment remains a debated area, particularly when it comes to detecting distant recurrences, David Cescon, MD, PhD, with Princess Margaret Cancer Center, University Health Network, Toronto, said in his talk.

While breast imaging standards are well established, systemic surveillance through imaging and laboratory tests for asymptomatic patients lacks consensus and uniform guidelines, he explained.

Several clinical trials conducted from the late 1980s to the early 2000s showed no survival benefit from intensive surveillance strategies, including imaging and laboratory tests, compared to routine clinical follow-up. Some studies even demonstrated a trend toward harm, given the number of false positives.

These studies formed the basis for guidelines that discourage surveillance among asymptomatic survivors. Currently, no major guideline organization — the National Comprehensive Cancer Network, ASCO, and the European Society for Medical Oncology — recommends routine (nonbreast) radiologic surveillance or laboratory tests for detecting asymptomatic distant breast cancer recurrence, Dr. Cescon said.

Yet, that may change in the coming years, he told attendees.

Ongoing prospective studies will hopefully generate high-quality evidence on the effectiveness of modern surveillance techniques, particularly detection of circulating tumor DNA (ctDNA) and its effect on survival and quality of life, said Dr. Cescon.

These liquid biopsy assays have shown promise in identifying minimal residual disease before radiographic recurrence, he explained. Retrospective studies suggest high prognostic value, with nearly all patients with detectable ctDNA post therapy experiencing recurrence. 

He cautioned, however, that while sensitive ctDNA tests exist and have clinical validity in identifying minimal residual disease, “their clinical utility has not yet been demonstrated,” Dr. Cescon said, adding that any surveillance strategy must consider the psychological effect of frequent testing and the potential for false positives or negatives.

The ultimate goal is preventing disease recurrence, said Neil M. Iyengar, MD, with Memorial Sloan Kettering Cancer Center in New York, in his talk on mitigating recurrence risk. 

Lifestyle modifications are an important targeted intervention for patients entering the survivorship phase, with a “robust level of evidence” supporting their use to mitigate adverse effects associated with cancer therapy and improve quality of life, he told attendees. Most notably, smoking cessation, healthy dietary patterns, physical activity, and reduced alcohol have been associated with improvements in breast cancer outcomes.

Going forward, it will be important to “understand the antitumor potential of lifestyle modification and how we can wield this type of intervention as a precision tool to potentially enhance the effects of cancer therapy and potentially cancer biology,” said Dr. Iyengar.

Ms. Brown disclosed relationships with AstraZeneca. Dr. Cescon disclosed relationships with AstraZeneca, Gilead Sciences, Daiichi Sankyo Europe GmbH, Eisai, GlaxoSmithKline, and other companies. Dr. Iyengar disclosed relationships with Curio Science, DAVA Oncology, Novartis, Pfizer, and others.

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

Advances in breast cancer detection and treatment over the past decades have led to an increase in the number of women diagnosed at earlier stages and successfully treated, ushering in a new era of survivorship.

According to the American Cancer Society, there are currently roughly four million breast cancer survivors in the United States, including those still receiving treatment. The mortality rates for women with breast cancer have been decreasing since 1989, with an overall decline of 42% through 2021.

As the population of breast cancer survivors continues to grow, developing and delivering comprehensive survivorship care is crucial, Thelma Brown told attendees at the American Society of Clinical Oncology (ASCO) 2024 annual meeting. Ms. Brown’s talk was part of an educational session focused on addressing issues among early breast cancer survivors, evolving practices in breast cancer surveillance, and mitigating recurrence risk.

The challenges following breast cancer diagnosis and treatment can be both visible and invisible, said Ms. Brown, a patient advocate and member of the Breast Cancer Working Group at the University of Alabama at Birmingham.

Up to 90% of early breast cancer survivors experience long-term effects from treatment, which often include fatigue, loss of mobility, chronic pain, peripheral neuropathy, lymphedema, and infertility.

Survivors face an elevated risk for depression, anxiety, and fear of recurrence. “Fear of recurrence is a big issue, and it’s almost universal,” she noted.

Cancer treatment is also costly, leading to financial toxicity for many patients, which also “affects adherence to treatment and overall family well-being,” Ms. Brown explained. Survivors may struggle to access financial assistance due to complex eligibility requirements and a lack of awareness about available resources. 

There is a need for holistic and coordinated survivorship care that includes management of long-term effects and surveillance for recurrence to help breast cancer survivors to transition from merely surviving to thriving, said Ms. Brown.
 

Surveilling and Mitigating Recurrence

Surveillance in patients with breast cancer post treatment remains a debated area, particularly when it comes to detecting distant recurrences, David Cescon, MD, PhD, with Princess Margaret Cancer Center, University Health Network, Toronto, said in his talk.

While breast imaging standards are well established, systemic surveillance through imaging and laboratory tests for asymptomatic patients lacks consensus and uniform guidelines, he explained.

Several clinical trials conducted from the late 1980s to the early 2000s showed no survival benefit from intensive surveillance strategies, including imaging and laboratory tests, compared to routine clinical follow-up. Some studies even demonstrated a trend toward harm, given the number of false positives.

These studies formed the basis for guidelines that discourage surveillance among asymptomatic survivors. Currently, no major guideline organization — the National Comprehensive Cancer Network, ASCO, and the European Society for Medical Oncology — recommends routine (nonbreast) radiologic surveillance or laboratory tests for detecting asymptomatic distant breast cancer recurrence, Dr. Cescon said.

Yet, that may change in the coming years, he told attendees.

Ongoing prospective studies will hopefully generate high-quality evidence on the effectiveness of modern surveillance techniques, particularly detection of circulating tumor DNA (ctDNA) and its effect on survival and quality of life, said Dr. Cescon.

These liquid biopsy assays have shown promise in identifying minimal residual disease before radiographic recurrence, he explained. Retrospective studies suggest high prognostic value, with nearly all patients with detectable ctDNA post therapy experiencing recurrence. 

He cautioned, however, that while sensitive ctDNA tests exist and have clinical validity in identifying minimal residual disease, “their clinical utility has not yet been demonstrated,” Dr. Cescon said, adding that any surveillance strategy must consider the psychological effect of frequent testing and the potential for false positives or negatives.

The ultimate goal is preventing disease recurrence, said Neil M. Iyengar, MD, with Memorial Sloan Kettering Cancer Center in New York, in his talk on mitigating recurrence risk. 

Lifestyle modifications are an important targeted intervention for patients entering the survivorship phase, with a “robust level of evidence” supporting their use to mitigate adverse effects associated with cancer therapy and improve quality of life, he told attendees. Most notably, smoking cessation, healthy dietary patterns, physical activity, and reduced alcohol have been associated with improvements in breast cancer outcomes.

Going forward, it will be important to “understand the antitumor potential of lifestyle modification and how we can wield this type of intervention as a precision tool to potentially enhance the effects of cancer therapy and potentially cancer biology,” said Dr. Iyengar.

Ms. Brown disclosed relationships with AstraZeneca. Dr. Cescon disclosed relationships with AstraZeneca, Gilead Sciences, Daiichi Sankyo Europe GmbH, Eisai, GlaxoSmithKline, and other companies. Dr. Iyengar disclosed relationships with Curio Science, DAVA Oncology, Novartis, Pfizer, and others.

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

When she got the news that her young son had been diagnosed with the rare blood disorder known as transfusion-dependent beta thalassemia, Yusara Ahmed knew the drill. Her sister had also experienced the inherited condition and needed to undergo regular blood transfusions simply to survive.

With luck, maybe Ms. Ahmed’s son could follow in his aunt’s footsteps and get a stem cell transplant from a compatible family donor. But while little Yusuf Saeed has a twin sister of his own, she wasn’t a match. Without another treatment option, he’d face the prospect of a lifetime not only cut short but burdened by multiple monthly transfusions and severe limitations.

Then came glimpses of hope. One of Yusuf’s physicians at Cohen Children’s Medical Center in Long Island, New York, told Yusuf’s mother about a new kind of gene therapy on the horizon. But it took time to get FDA approval. Yusuf grew older, heading toward his teenage years, when regular transfusions would be a huge burden. “He’s turning 5 and 6, and there’s nothing,” Ms. Ahmed recalled, and the family worried.

Finally, the FDA approved the one-time treatment — betibeglogene autotemcel (beti-cel, Zynteglo) in 2022. By January 2024, the hospital was ready to treat Yusuf. At age 8, he became the first patient in the state of New York to undergo gene therapy for beta thalassemia.

A medical team infused Yusuf with his own stem cells, which had been genetically engineered to boost production of hemoglobin and prevent thalassemia’s devastating effects.

There are caveats about the treatment. It’s an extraordinarily expensive therapy that can be performed at only a few institutions. And it’s so brand new that caveats may not even have appeared yet. Yet, for kids like Yusuf, the gene therapy could transform a life.

“We feel like a weight has been lifted,” Ms. Ahmed said in an interview. “It’s something we’ve been waiting for.”
 

Anemia Becomes a Lifetime Threat

Among all genetic diseases, thalassemia stands alone. It’s the most common condition caused by a single gene, according to Hanny Al-Samkari, MD, a hematologist/clinical investigator at Massachusetts General Hospital and associate professor of medicine at Harvard Medical School, in Boston, Massachusetts.

Millions of people have the thalassemia trait, especially in southern Europe, the Middle East, southeast Asia, and Africa, Dr. Al-Samkari said. (Yusuf’s parents are from Pakistan.)

The trait, which appears to provide protection against malaria, may cause mild anemia in some cases but is otherwise harmless. However, a child born to parents with the same kind of trait has a high risk of developing alpha thalassemia or beta thalassemia. Like his aunt, Yusuf developed beta thalassemia, which is generally more severe. Yusuf’s bleeding disorder requires him to be transfusion-dependent.

In these patients, the disease disrupts the production of red blood cells in the bone marrow, Dr. Al-Samkari said. Hemoglobin levels can fall to 7 or 8 g/dL, compared with the normal levels of 12-16 g/dL in adults. “They’re chronically anemic, and that low hemoglobin that leads to things you associate with anemia: fatigue, reduced exercise tolerance, mind fog, challenges with work or school, and hypersomnolence.”

In addition, the bones become thinner and more brittle, he said, leading to fractures.

Transfusions are one treatment option, but they’re needed for a lifetime and cause their own problems, such as iron overload. Care of thalassemia patients “becomes quite complex and quite challenging for both families and medical institutions,” Alexis A. Thompson MD, MPH, chief of hematology at Children’s Hospital of Philadelphia, Pennsylvania, said in an interview.

Yusara Ahmed remembers her sister’s endless visits to the hospital after she was diagnosed at age 4. “We were all very traumatized by the hospital environment,” she said. But good news came in 2008, a few years later, when her sister was able to get a stem cell transplant from their brother.

But while stem cell transplants can be curative, most children don’t have a relative who can be a suitable match as a donor, Dr. Thompson said. Now, gene therapy offers another option, by turning a patient into his or her own matched donor.
 

Stem Cells Out, Stem Cells In

Last year, Yusuf went to Cohen Children’s Medical Center to donate stem cells, which were sent to a laboratory where they were genetically engineered to add copies of the beta-globin gene. Then, in January 2024, the modified stem cells were infused back into Yusuf after he underwent chemotherapy to make room for them in his bone marrow.

In April, a bald-headed Yusuf played with toy dinosaurs while his mother and clinicians met the media at a hospital press conference about his so-far-successful treatment. Early reports about the efficacy of the treatment suggest it may be the proverbial “game changer” for many of the estimated 100,000-plus people in the world who are diagnosed with transfusion-dependent beta thalassemia each year.

Over a median follow-up of 29.5 months, 20 of 22 patients treated with beti-cel no longer needed transfusions, according to a 2022 open-label phase 3 study published in the New England Journal of Medicine. Only one adverse event — thrombocytopenia in one patient — was considered both serious and related to the treatment, the industry-funded trial reported.
 

Costly Treatment Seems to Be Cost-Effective

As of 2022, gene therapy for transfusion-dependent beta thalassemia was listed as $2.8 million per treatment making it the most expensive single-treatment therapy ever approved in the United States. The price is “extraordinary,” said Dr. Thompson. “For some families, it gives them pause when they first hear about it.”

The hospital makes the case to insurers that covering the treatment is cost-effective in the long run, considering the high cost of traditional treatment, she said. “We’ve been very successful in getting coverage.”

In addition, the independent Institute for Clinical and Economic Review reported in 2022 that the treatment will be cost-effective at the “anticipated price of $2.1 million with an 80% payback option for patients who do not achieve and maintain transfusion independence over a 5-year period.”
 

Moving Forward, Clinicians Want to Reduce Complications

What’s next for transfusion-dependent beta thalassemia treatment? Earlier this year, the FDA approved a second gene therapy treatment called exagamglogene autotemcel (exa-cel, Casgevy). “We’re just beginning to evaluate individuals for the product, and we intend to make it available for families as well,” Dr. Thompson said.

In the bigger picture, she said gene therapy still has room for improvement. The need for chemotherapy is one target. According to her, it causes most of the complications related to gene therapy.

“Chemotherapy is a part of all gene therapies today because one has to make space in the bone marrow in order to have modified stem cells to come back to settle in and grow,” she said.

One strategy is to reduce the number of stem cells that are required for the therapy to work. “That would essentially eliminate the need for chemotherapy,” she said. “We’re not there yet.”

Another goal is to reduce the small risk of complications from gene therapy itself, she said. “Overall, though, this doesn’t detract us at all from being very excited about how well children are doing with the current approach. We’re very enthusiastic and very confident in recommending it to families.”
 

Back on Long Island, a Sense of Relief

Several months after his treatment, Yusuf is doing well. His hemoglobin levels are increasing, and his bone marrow has grown back, his mother said. He’s being home-schooled for the time being because he still faces a risk of infection. (Ms. Ahmed, a stay-at-home mom, has worked a teacher and mosque volunteer. Her husband runs a consumer electronics business.)

As Yusuf gets better, his parents hope they’ll soon be able to take a long trip back home to Pakistan to see relatives. They’ll be able to share their son with family along with something else: a sense of relief.

Dr. Al-Samkari discloses consulting for Agios. Dr. Thompson discloses research for Beam, Bluebird Bio, Editas, Novartis, and Novo Nordisk and consulting for Beam, Bluebird Bio, Editas, Roche, and Vertex.

When she got the news that her young son had been diagnosed with the rare blood disorder known as transfusion-dependent beta thalassemia, Yusara Ahmed knew the drill. Her sister had also experienced the inherited condition and needed to undergo regular blood transfusions simply to survive.

With luck, maybe Ms. Ahmed’s son could follow in his aunt’s footsteps and get a stem cell transplant from a compatible family donor. But while little Yusuf Saeed has a twin sister of his own, she wasn’t a match. Without another treatment option, he’d face the prospect of a lifetime not only cut short but burdened by multiple monthly transfusions and severe limitations.

Then came glimpses of hope. One of Yusuf’s physicians at Cohen Children’s Medical Center in Long Island, New York, told Yusuf’s mother about a new kind of gene therapy on the horizon. But it took time to get FDA approval. Yusuf grew older, heading toward his teenage years, when regular transfusions would be a huge burden. “He’s turning 5 and 6, and there’s nothing,” Ms. Ahmed recalled, and the family worried.

Finally, the FDA approved the one-time treatment — betibeglogene autotemcel (beti-cel, Zynteglo) in 2022. By January 2024, the hospital was ready to treat Yusuf. At age 8, he became the first patient in the state of New York to undergo gene therapy for beta thalassemia.

A medical team infused Yusuf with his own stem cells, which had been genetically engineered to boost production of hemoglobin and prevent thalassemia’s devastating effects.

There are caveats about the treatment. It’s an extraordinarily expensive therapy that can be performed at only a few institutions. And it’s so brand new that caveats may not even have appeared yet. Yet, for kids like Yusuf, the gene therapy could transform a life.

“We feel like a weight has been lifted,” Ms. Ahmed said in an interview. “It’s something we’ve been waiting for.”
 

Anemia Becomes a Lifetime Threat

Among all genetic diseases, thalassemia stands alone. It’s the most common condition caused by a single gene, according to Hanny Al-Samkari, MD, a hematologist/clinical investigator at Massachusetts General Hospital and associate professor of medicine at Harvard Medical School, in Boston, Massachusetts.

Millions of people have the thalassemia trait, especially in southern Europe, the Middle East, southeast Asia, and Africa, Dr. Al-Samkari said. (Yusuf’s parents are from Pakistan.)

The trait, which appears to provide protection against malaria, may cause mild anemia in some cases but is otherwise harmless. However, a child born to parents with the same kind of trait has a high risk of developing alpha thalassemia or beta thalassemia. Like his aunt, Yusuf developed beta thalassemia, which is generally more severe. Yusuf’s bleeding disorder requires him to be transfusion-dependent.

In these patients, the disease disrupts the production of red blood cells in the bone marrow, Dr. Al-Samkari said. Hemoglobin levels can fall to 7 or 8 g/dL, compared with the normal levels of 12-16 g/dL in adults. “They’re chronically anemic, and that low hemoglobin that leads to things you associate with anemia: fatigue, reduced exercise tolerance, mind fog, challenges with work or school, and hypersomnolence.”

In addition, the bones become thinner and more brittle, he said, leading to fractures.

Transfusions are one treatment option, but they’re needed for a lifetime and cause their own problems, such as iron overload. Care of thalassemia patients “becomes quite complex and quite challenging for both families and medical institutions,” Alexis A. Thompson MD, MPH, chief of hematology at Children’s Hospital of Philadelphia, Pennsylvania, said in an interview.

Yusara Ahmed remembers her sister’s endless visits to the hospital after she was diagnosed at age 4. “We were all very traumatized by the hospital environment,” she said. But good news came in 2008, a few years later, when her sister was able to get a stem cell transplant from their brother.

But while stem cell transplants can be curative, most children don’t have a relative who can be a suitable match as a donor, Dr. Thompson said. Now, gene therapy offers another option, by turning a patient into his or her own matched donor.
 

Stem Cells Out, Stem Cells In

Last year, Yusuf went to Cohen Children’s Medical Center to donate stem cells, which were sent to a laboratory where they were genetically engineered to add copies of the beta-globin gene. Then, in January 2024, the modified stem cells were infused back into Yusuf after he underwent chemotherapy to make room for them in his bone marrow.

In April, a bald-headed Yusuf played with toy dinosaurs while his mother and clinicians met the media at a hospital press conference about his so-far-successful treatment. Early reports about the efficacy of the treatment suggest it may be the proverbial “game changer” for many of the estimated 100,000-plus people in the world who are diagnosed with transfusion-dependent beta thalassemia each year.

Over a median follow-up of 29.5 months, 20 of 22 patients treated with beti-cel no longer needed transfusions, according to a 2022 open-label phase 3 study published in the New England Journal of Medicine. Only one adverse event — thrombocytopenia in one patient — was considered both serious and related to the treatment, the industry-funded trial reported.
 

Costly Treatment Seems to Be Cost-Effective

As of 2022, gene therapy for transfusion-dependent beta thalassemia was listed as $2.8 million per treatment making it the most expensive single-treatment therapy ever approved in the United States. The price is “extraordinary,” said Dr. Thompson. “For some families, it gives them pause when they first hear about it.”

The hospital makes the case to insurers that covering the treatment is cost-effective in the long run, considering the high cost of traditional treatment, she said. “We’ve been very successful in getting coverage.”

In addition, the independent Institute for Clinical and Economic Review reported in 2022 that the treatment will be cost-effective at the “anticipated price of $2.1 million with an 80% payback option for patients who do not achieve and maintain transfusion independence over a 5-year period.”
 

Moving Forward, Clinicians Want to Reduce Complications

What’s next for transfusion-dependent beta thalassemia treatment? Earlier this year, the FDA approved a second gene therapy treatment called exagamglogene autotemcel (exa-cel, Casgevy). “We’re just beginning to evaluate individuals for the product, and we intend to make it available for families as well,” Dr. Thompson said.

In the bigger picture, she said gene therapy still has room for improvement. The need for chemotherapy is one target. According to her, it causes most of the complications related to gene therapy.

“Chemotherapy is a part of all gene therapies today because one has to make space in the bone marrow in order to have modified stem cells to come back to settle in and grow,” she said.

One strategy is to reduce the number of stem cells that are required for the therapy to work. “That would essentially eliminate the need for chemotherapy,” she said. “We’re not there yet.”

Another goal is to reduce the small risk of complications from gene therapy itself, she said. “Overall, though, this doesn’t detract us at all from being very excited about how well children are doing with the current approach. We’re very enthusiastic and very confident in recommending it to families.”
 

Back on Long Island, a Sense of Relief

Several months after his treatment, Yusuf is doing well. His hemoglobin levels are increasing, and his bone marrow has grown back, his mother said. He’s being home-schooled for the time being because he still faces a risk of infection. (Ms. Ahmed, a stay-at-home mom, has worked a teacher and mosque volunteer. Her husband runs a consumer electronics business.)

As Yusuf gets better, his parents hope they’ll soon be able to take a long trip back home to Pakistan to see relatives. They’ll be able to share their son with family along with something else: a sense of relief.

Dr. Al-Samkari discloses consulting for Agios. Dr. Thompson discloses research for Beam, Bluebird Bio, Editas, Novartis, and Novo Nordisk and consulting for Beam, Bluebird Bio, Editas, Roche, and Vertex.

When she got the news that her young son had been diagnosed with the rare blood disorder known as transfusion-dependent beta thalassemia, Yusara Ahmed knew the drill. Her sister had also experienced the inherited condition and needed to undergo regular blood transfusions simply to survive.

With luck, maybe Ms. Ahmed’s son could follow in his aunt’s footsteps and get a stem cell transplant from a compatible family donor. But while little Yusuf Saeed has a twin sister of his own, she wasn’t a match. Without another treatment option, he’d face the prospect of a lifetime not only cut short but burdened by multiple monthly transfusions and severe limitations.

Then came glimpses of hope. One of Yusuf’s physicians at Cohen Children’s Medical Center in Long Island, New York, told Yusuf’s mother about a new kind of gene therapy on the horizon. But it took time to get FDA approval. Yusuf grew older, heading toward his teenage years, when regular transfusions would be a huge burden. “He’s turning 5 and 6, and there’s nothing,” Ms. Ahmed recalled, and the family worried.

Finally, the FDA approved the one-time treatment — betibeglogene autotemcel (beti-cel, Zynteglo) in 2022. By January 2024, the hospital was ready to treat Yusuf. At age 8, he became the first patient in the state of New York to undergo gene therapy for beta thalassemia.

A medical team infused Yusuf with his own stem cells, which had been genetically engineered to boost production of hemoglobin and prevent thalassemia’s devastating effects.

There are caveats about the treatment. It’s an extraordinarily expensive therapy that can be performed at only a few institutions. And it’s so brand new that caveats may not even have appeared yet. Yet, for kids like Yusuf, the gene therapy could transform a life.

“We feel like a weight has been lifted,” Ms. Ahmed said in an interview. “It’s something we’ve been waiting for.”
 

Anemia Becomes a Lifetime Threat

Among all genetic diseases, thalassemia stands alone. It’s the most common condition caused by a single gene, according to Hanny Al-Samkari, MD, a hematologist/clinical investigator at Massachusetts General Hospital and associate professor of medicine at Harvard Medical School, in Boston, Massachusetts.

Millions of people have the thalassemia trait, especially in southern Europe, the Middle East, southeast Asia, and Africa, Dr. Al-Samkari said. (Yusuf’s parents are from Pakistan.)

The trait, which appears to provide protection against malaria, may cause mild anemia in some cases but is otherwise harmless. However, a child born to parents with the same kind of trait has a high risk of developing alpha thalassemia or beta thalassemia. Like his aunt, Yusuf developed beta thalassemia, which is generally more severe. Yusuf’s bleeding disorder requires him to be transfusion-dependent.

In these patients, the disease disrupts the production of red blood cells in the bone marrow, Dr. Al-Samkari said. Hemoglobin levels can fall to 7 or 8 g/dL, compared with the normal levels of 12-16 g/dL in adults. “They’re chronically anemic, and that low hemoglobin that leads to things you associate with anemia: fatigue, reduced exercise tolerance, mind fog, challenges with work or school, and hypersomnolence.”

In addition, the bones become thinner and more brittle, he said, leading to fractures.

Transfusions are one treatment option, but they’re needed for a lifetime and cause their own problems, such as iron overload. Care of thalassemia patients “becomes quite complex and quite challenging for both families and medical institutions,” Alexis A. Thompson MD, MPH, chief of hematology at Children’s Hospital of Philadelphia, Pennsylvania, said in an interview.

Yusara Ahmed remembers her sister’s endless visits to the hospital after she was diagnosed at age 4. “We were all very traumatized by the hospital environment,” she said. But good news came in 2008, a few years later, when her sister was able to get a stem cell transplant from their brother.

But while stem cell transplants can be curative, most children don’t have a relative who can be a suitable match as a donor, Dr. Thompson said. Now, gene therapy offers another option, by turning a patient into his or her own matched donor.
 

Stem Cells Out, Stem Cells In

Last year, Yusuf went to Cohen Children’s Medical Center to donate stem cells, which were sent to a laboratory where they were genetically engineered to add copies of the beta-globin gene. Then, in January 2024, the modified stem cells were infused back into Yusuf after he underwent chemotherapy to make room for them in his bone marrow.

In April, a bald-headed Yusuf played with toy dinosaurs while his mother and clinicians met the media at a hospital press conference about his so-far-successful treatment. Early reports about the efficacy of the treatment suggest it may be the proverbial “game changer” for many of the estimated 100,000-plus people in the world who are diagnosed with transfusion-dependent beta thalassemia each year.

Over a median follow-up of 29.5 months, 20 of 22 patients treated with beti-cel no longer needed transfusions, according to a 2022 open-label phase 3 study published in the New England Journal of Medicine. Only one adverse event — thrombocytopenia in one patient — was considered both serious and related to the treatment, the industry-funded trial reported.
 

Costly Treatment Seems to Be Cost-Effective

As of 2022, gene therapy for transfusion-dependent beta thalassemia was listed as $2.8 million per treatment making it the most expensive single-treatment therapy ever approved in the United States. The price is “extraordinary,” said Dr. Thompson. “For some families, it gives them pause when they first hear about it.”

The hospital makes the case to insurers that covering the treatment is cost-effective in the long run, considering the high cost of traditional treatment, she said. “We’ve been very successful in getting coverage.”

In addition, the independent Institute for Clinical and Economic Review reported in 2022 that the treatment will be cost-effective at the “anticipated price of $2.1 million with an 80% payback option for patients who do not achieve and maintain transfusion independence over a 5-year period.”
 

Moving Forward, Clinicians Want to Reduce Complications

What’s next for transfusion-dependent beta thalassemia treatment? Earlier this year, the FDA approved a second gene therapy treatment called exagamglogene autotemcel (exa-cel, Casgevy). “We’re just beginning to evaluate individuals for the product, and we intend to make it available for families as well,” Dr. Thompson said.

In the bigger picture, she said gene therapy still has room for improvement. The need for chemotherapy is one target. According to her, it causes most of the complications related to gene therapy.

“Chemotherapy is a part of all gene therapies today because one has to make space in the bone marrow in order to have modified stem cells to come back to settle in and grow,” she said.

One strategy is to reduce the number of stem cells that are required for the therapy to work. “That would essentially eliminate the need for chemotherapy,” she said. “We’re not there yet.”

Another goal is to reduce the small risk of complications from gene therapy itself, she said. “Overall, though, this doesn’t detract us at all from being very excited about how well children are doing with the current approach. We’re very enthusiastic and very confident in recommending it to families.”
 

Back on Long Island, a Sense of Relief

Several months after his treatment, Yusuf is doing well. His hemoglobin levels are increasing, and his bone marrow has grown back, his mother said. He’s being home-schooled for the time being because he still faces a risk of infection. (Ms. Ahmed, a stay-at-home mom, has worked a teacher and mosque volunteer. Her husband runs a consumer electronics business.)

As Yusuf gets better, his parents hope they’ll soon be able to take a long trip back home to Pakistan to see relatives. They’ll be able to share their son with family along with something else: a sense of relief.

Dr. Al-Samkari discloses consulting for Agios. Dr. Thompson discloses research for Beam, Bluebird Bio, Editas, Novartis, and Novo Nordisk and consulting for Beam, Bluebird Bio, Editas, Roche, and Vertex.

A renowned leader in colorectal cancer research, Scott Kopetz, MD, PhD, was recently honored for helping establish new standards of care for BRAF-mutated metastatic colorectal cancer.

Dr. Kopetz received the AACR-Waun Ki Hong Award in April. The American Association for Cancer Research (AACR) granted Dr. Kopetz this award to recognize his leadership in the development of novel therapies for patients with BRAF-mutated metastatic colon cancer with poor prognoses, according to a statement from the AACR.

What led to your medical career? Growing up, did you always want to be a doctor?

Dr. Kopetz: My interest initially was in engineering. I grew up in Tennessee from a family of engineers and doctors. In college, I completed a degree in biomedical engineering and electrical engineering.

I had the opportunity to spend one summer at the National Institutes of Health, where I did some research on the structure of the HIV integrase enzyme. It was fundamental basic research with some engineering overlay and required spending 4 days a week working in the dark in a laser lab to analyze the structure of this protein.

One day a week, I was at Georgetown in the HIV/AIDS Clinic, where I collected blood samples and saw HIV/AIDS patients. At the end of the summer, I reflected and realized that I really enjoyed that 1 day out of the week, much more than the other 4. I enjoyed working with patients and interacting with people and thought I’d enjoy the more direct way to help patients, so made a pivot into medicine.
 

Was the rest of your medical training more traditional?

Dr. Kopetz: My path was a little atypical for a physician scientist. I pursued a medical degree at Johns Hopkins, did internal medicine training at Duke, and then came down to MD Anderson Cancer Center [in Houston, Texas] to do a fellowship in medical oncology, and also obtained a PhD in cancer biology, where I explored mechanisms of resistance to colorectal cancer treatment.

While a traditional physician scientist typically obtains a PhD training in the middle of their medical school, I completed my medical training and then went back to get a PhD. It was a different, nontraditional route.
 

What is your current role, and what is most inspiring about your work?

Dr. Kopetz: I’ve been at MD Anderson now for 20 years in GI medical oncology. I recently stepped into a new role of helping facilitate translational research at the institution and am now Associate VP for translational research.

I’m excited about where we are in cancer research. I think we’re moving into an era where the amount of information that we can get out of patients and the rapidity in which we can move discoveries is much greater than it has ever been.

Our ability to extract information out of patient biopsies, surgical samples, or even minimally invasive techniques to sample the tumors, such as liquid biopsy, has provided tremendous insights into how tumors are evolving and adapting to therapies and [provides us] opportunities for novel interventions. This opens up ways where I think as a field, we can more readily accelerate our understanding of cancer.

The second component is seeing the rapidity in which we’re now able to execute ideas in the drug development space compared to years before. The pace of new drug development has increased and the innovations in the chemistries have opened up new opportunities and new targets that in the past were considered undruggable. For example, the mutated oncogene, KRAS, was once an extremely challenging therapeutic target and considered undruggable. Mutations in the p53 gene, a tumor suppressor gene, were similarly challenging. I think the convergence of these two trends are going to more rapidly accelerate the advances for our patients. I’m optimistic about the future.
 

Tell us more about the novel therapies for patients with BRAF-mutated metastatic colon cancer for which you were a lead researcher.

Dr. Kopetz: A lot of [my] work goes back over 10 years, where my [research colleagues and I] were targeting the BRAF V600E oncogene in colorectal cancer melanoma and identified that this worked well in melanoma but was relatively inactive in colorectal cancer despite the same drugs and the same mutations. This led to a recognition of optimal combination drugs that really blocked some of the adaptive feedback that we saw in colorectal cancer. This was a key recognition that these tumors, after you block one node of signaling, rapidly adapt and reactivate the signaling through alternate nodes. This finding really resonated with me with my engineering background, thinking about the networks, signaling networks, and the concepts of feedback regulation of complex systems.

The strategy of blocking the primary oncogene and then blocking the feedback mechanisms that the tumors were utilizing was adopted in colorectal cancer through this work. It took us 10 years to get to an FDA approval with this strategy, but it’s really encouraging that we’re now using this strategy and applying it to the new wave of KRAS inhibitors, where the exact same feedback pathway appears to be at play.
 

Does your engineering background impact your work today?

Dr. Kopetz: Yes, I’ve found that my engineering training has provided me with complementary skills that can significantly contribute to the development of innovative technologies, computational approaches, and interdisciplinary strategies for advancing cancer research.

Today, I do a lot of work understanding and recognizing complex networks of signaling, and it’s the same network theories that we learned and developed in engineering.

These same theories are now being applied to biology. For example, we are very interested in how tumors adapt over the longer term, over multiple lines of therapy, where there is both clonal selection and clonal evolution occurring with our various standard-of-care therapies. Our hope is that application of engineering principles can help uncover new vulnerabilities in cancer that weren’t evident when we were thinking about CRC as a static tumor.
 

I understand your recently awarded AACR-Waun Ki Hong Award for Outstanding Achievement in Translational and Clinical Cancer Research has special significance to you. Can you explain why that is?

Dr. Kopetz: This holds a special meaning for me, because Dr. Hong provided a lot of guidance [to me] over the years. He was the division head for cancer medicine at MD Anderson for many years and was instrumental in helping advocate [for me] and advance my career as well as the careers of so many others in and outside of the institution. I considered him a key mentor and sponsor. He helped provide me with guidance early in my oncology career, helping me identify high-value projects and critically evaluate research directions to pursue. He also helped me think about how to balance my research portfolio and provided guidance about how to work well within a team.

It’s really humbling to have a reward bearing his name as somebody who I so deeply respected, and I’m so grateful for the impact he had on my life.

A renowned leader in colorectal cancer research, Scott Kopetz, MD, PhD, was recently honored for helping establish new standards of care for BRAF-mutated metastatic colorectal cancer.

Dr. Kopetz received the AACR-Waun Ki Hong Award in April. The American Association for Cancer Research (AACR) granted Dr. Kopetz this award to recognize his leadership in the development of novel therapies for patients with BRAF-mutated metastatic colon cancer with poor prognoses, according to a statement from the AACR.

What led to your medical career? Growing up, did you always want to be a doctor?

Dr. Kopetz: My interest initially was in engineering. I grew up in Tennessee from a family of engineers and doctors. In college, I completed a degree in biomedical engineering and electrical engineering.

I had the opportunity to spend one summer at the National Institutes of Health, where I did some research on the structure of the HIV integrase enzyme. It was fundamental basic research with some engineering overlay and required spending 4 days a week working in the dark in a laser lab to analyze the structure of this protein.

One day a week, I was at Georgetown in the HIV/AIDS Clinic, where I collected blood samples and saw HIV/AIDS patients. At the end of the summer, I reflected and realized that I really enjoyed that 1 day out of the week, much more than the other 4. I enjoyed working with patients and interacting with people and thought I’d enjoy the more direct way to help patients, so made a pivot into medicine.
 

Was the rest of your medical training more traditional?

Dr. Kopetz: My path was a little atypical for a physician scientist. I pursued a medical degree at Johns Hopkins, did internal medicine training at Duke, and then came down to MD Anderson Cancer Center [in Houston, Texas] to do a fellowship in medical oncology, and also obtained a PhD in cancer biology, where I explored mechanisms of resistance to colorectal cancer treatment.

While a traditional physician scientist typically obtains a PhD training in the middle of their medical school, I completed my medical training and then went back to get a PhD. It was a different, nontraditional route.
 

What is your current role, and what is most inspiring about your work?

Dr. Kopetz: I’ve been at MD Anderson now for 20 years in GI medical oncology. I recently stepped into a new role of helping facilitate translational research at the institution and am now Associate VP for translational research.

I’m excited about where we are in cancer research. I think we’re moving into an era where the amount of information that we can get out of patients and the rapidity in which we can move discoveries is much greater than it has ever been.

Our ability to extract information out of patient biopsies, surgical samples, or even minimally invasive techniques to sample the tumors, such as liquid biopsy, has provided tremendous insights into how tumors are evolving and adapting to therapies and [provides us] opportunities for novel interventions. This opens up ways where I think as a field, we can more readily accelerate our understanding of cancer.

The second component is seeing the rapidity in which we’re now able to execute ideas in the drug development space compared to years before. The pace of new drug development has increased and the innovations in the chemistries have opened up new opportunities and new targets that in the past were considered undruggable. For example, the mutated oncogene, KRAS, was once an extremely challenging therapeutic target and considered undruggable. Mutations in the p53 gene, a tumor suppressor gene, were similarly challenging. I think the convergence of these two trends are going to more rapidly accelerate the advances for our patients. I’m optimistic about the future.
 

Tell us more about the novel therapies for patients with BRAF-mutated metastatic colon cancer for which you were a lead researcher.

Dr. Kopetz: A lot of [my] work goes back over 10 years, where my [research colleagues and I] were targeting the BRAF V600E oncogene in colorectal cancer melanoma and identified that this worked well in melanoma but was relatively inactive in colorectal cancer despite the same drugs and the same mutations. This led to a recognition of optimal combination drugs that really blocked some of the adaptive feedback that we saw in colorectal cancer. This was a key recognition that these tumors, after you block one node of signaling, rapidly adapt and reactivate the signaling through alternate nodes. This finding really resonated with me with my engineering background, thinking about the networks, signaling networks, and the concepts of feedback regulation of complex systems.

The strategy of blocking the primary oncogene and then blocking the feedback mechanisms that the tumors were utilizing was adopted in colorectal cancer through this work. It took us 10 years to get to an FDA approval with this strategy, but it’s really encouraging that we’re now using this strategy and applying it to the new wave of KRAS inhibitors, where the exact same feedback pathway appears to be at play.
 

Does your engineering background impact your work today?

Dr. Kopetz: Yes, I’ve found that my engineering training has provided me with complementary skills that can significantly contribute to the development of innovative technologies, computational approaches, and interdisciplinary strategies for advancing cancer research.

Today, I do a lot of work understanding and recognizing complex networks of signaling, and it’s the same network theories that we learned and developed in engineering.

These same theories are now being applied to biology. For example, we are very interested in how tumors adapt over the longer term, over multiple lines of therapy, where there is both clonal selection and clonal evolution occurring with our various standard-of-care therapies. Our hope is that application of engineering principles can help uncover new vulnerabilities in cancer that weren’t evident when we were thinking about CRC as a static tumor.
 

I understand your recently awarded AACR-Waun Ki Hong Award for Outstanding Achievement in Translational and Clinical Cancer Research has special significance to you. Can you explain why that is?

Dr. Kopetz: This holds a special meaning for me, because Dr. Hong provided a lot of guidance [to me] over the years. He was the division head for cancer medicine at MD Anderson for many years and was instrumental in helping advocate [for me] and advance my career as well as the careers of so many others in and outside of the institution. I considered him a key mentor and sponsor. He helped provide me with guidance early in my oncology career, helping me identify high-value projects and critically evaluate research directions to pursue. He also helped me think about how to balance my research portfolio and provided guidance about how to work well within a team.

It’s really humbling to have a reward bearing his name as somebody who I so deeply respected, and I’m so grateful for the impact he had on my life.

A renowned leader in colorectal cancer research, Scott Kopetz, MD, PhD, was recently honored for helping establish new standards of care for BRAF-mutated metastatic colorectal cancer.

Dr. Kopetz received the AACR-Waun Ki Hong Award in April. The American Association for Cancer Research (AACR) granted Dr. Kopetz this award to recognize his leadership in the development of novel therapies for patients with BRAF-mutated metastatic colon cancer with poor prognoses, according to a statement from the AACR.

What led to your medical career? Growing up, did you always want to be a doctor?

Dr. Kopetz: My interest initially was in engineering. I grew up in Tennessee from a family of engineers and doctors. In college, I completed a degree in biomedical engineering and electrical engineering.

I had the opportunity to spend one summer at the National Institutes of Health, where I did some research on the structure of the HIV integrase enzyme. It was fundamental basic research with some engineering overlay and required spending 4 days a week working in the dark in a laser lab to analyze the structure of this protein.

One day a week, I was at Georgetown in the HIV/AIDS Clinic, where I collected blood samples and saw HIV/AIDS patients. At the end of the summer, I reflected and realized that I really enjoyed that 1 day out of the week, much more than the other 4. I enjoyed working with patients and interacting with people and thought I’d enjoy the more direct way to help patients, so made a pivot into medicine.
 

Was the rest of your medical training more traditional?

Dr. Kopetz: My path was a little atypical for a physician scientist. I pursued a medical degree at Johns Hopkins, did internal medicine training at Duke, and then came down to MD Anderson Cancer Center [in Houston, Texas] to do a fellowship in medical oncology, and also obtained a PhD in cancer biology, where I explored mechanisms of resistance to colorectal cancer treatment.

While a traditional physician scientist typically obtains a PhD training in the middle of their medical school, I completed my medical training and then went back to get a PhD. It was a different, nontraditional route.
 

What is your current role, and what is most inspiring about your work?

Dr. Kopetz: I’ve been at MD Anderson now for 20 years in GI medical oncology. I recently stepped into a new role of helping facilitate translational research at the institution and am now Associate VP for translational research.

I’m excited about where we are in cancer research. I think we’re moving into an era where the amount of information that we can get out of patients and the rapidity in which we can move discoveries is much greater than it has ever been.

Our ability to extract information out of patient biopsies, surgical samples, or even minimally invasive techniques to sample the tumors, such as liquid biopsy, has provided tremendous insights into how tumors are evolving and adapting to therapies and [provides us] opportunities for novel interventions. This opens up ways where I think as a field, we can more readily accelerate our understanding of cancer.

The second component is seeing the rapidity in which we’re now able to execute ideas in the drug development space compared to years before. The pace of new drug development has increased and the innovations in the chemistries have opened up new opportunities and new targets that in the past were considered undruggable. For example, the mutated oncogene, KRAS, was once an extremely challenging therapeutic target and considered undruggable. Mutations in the p53 gene, a tumor suppressor gene, were similarly challenging. I think the convergence of these two trends are going to more rapidly accelerate the advances for our patients. I’m optimistic about the future.
 

Tell us more about the novel therapies for patients with BRAF-mutated metastatic colon cancer for which you were a lead researcher.

Dr. Kopetz: A lot of [my] work goes back over 10 years, where my [research colleagues and I] were targeting the BRAF V600E oncogene in colorectal cancer melanoma and identified that this worked well in melanoma but was relatively inactive in colorectal cancer despite the same drugs and the same mutations. This led to a recognition of optimal combination drugs that really blocked some of the adaptive feedback that we saw in colorectal cancer. This was a key recognition that these tumors, after you block one node of signaling, rapidly adapt and reactivate the signaling through alternate nodes. This finding really resonated with me with my engineering background, thinking about the networks, signaling networks, and the concepts of feedback regulation of complex systems.

The strategy of blocking the primary oncogene and then blocking the feedback mechanisms that the tumors were utilizing was adopted in colorectal cancer through this work. It took us 10 years to get to an FDA approval with this strategy, but it’s really encouraging that we’re now using this strategy and applying it to the new wave of KRAS inhibitors, where the exact same feedback pathway appears to be at play.
 

Does your engineering background impact your work today?

Dr. Kopetz: Yes, I’ve found that my engineering training has provided me with complementary skills that can significantly contribute to the development of innovative technologies, computational approaches, and interdisciplinary strategies for advancing cancer research.

Today, I do a lot of work understanding and recognizing complex networks of signaling, and it’s the same network theories that we learned and developed in engineering.

These same theories are now being applied to biology. For example, we are very interested in how tumors adapt over the longer term, over multiple lines of therapy, where there is both clonal selection and clonal evolution occurring with our various standard-of-care therapies. Our hope is that application of engineering principles can help uncover new vulnerabilities in cancer that weren’t evident when we were thinking about CRC as a static tumor.
 

I understand your recently awarded AACR-Waun Ki Hong Award for Outstanding Achievement in Translational and Clinical Cancer Research has special significance to you. Can you explain why that is?

Dr. Kopetz: This holds a special meaning for me, because Dr. Hong provided a lot of guidance [to me] over the years. He was the division head for cancer medicine at MD Anderson for many years and was instrumental in helping advocate [for me] and advance my career as well as the careers of so many others in and outside of the institution. I considered him a key mentor and sponsor. He helped provide me with guidance early in my oncology career, helping me identify high-value projects and critically evaluate research directions to pursue. He also helped me think about how to balance my research portfolio and provided guidance about how to work well within a team.

It’s really humbling to have a reward bearing his name as somebody who I so deeply respected, and I’m so grateful for the impact he had on my life.

BOSTON — Men who stop using performance-enhancing anabolic-androgenic steroids (AAS) experience significant depression, anxiety, and diminished sexual function within the first year after quitting, new research found.

The data suggest that monitoring these men and, pending clinical trial evidence, intervening to minimize these effects could help prevent recidivism, Bonnie Grant, MBBS, a clinical research fellow at Imperial College London, London, England, told this news organization.

“Nothing has actually been studied in proper randomized controlled trials … but I think there’s going to be a role for medicine alongside psychological treatment … Clinicians often see men who have stopped [taking steroids] who report feeling low in mood … a lot of these men will just restart taking them again,” she said.

Anabolic steroids taken exogenously suppress the hypothalamic-pituitary-gonadal system, thereby suppressing endogenous testosterone secretion. While AAS do enhance muscle-building, they can also lead to enlarged hearts, hypertension, and infertility. Most of these are reversible if the man stops taking the AAS.

However, after stopping, the testosterone levels can take up to a year to return to normal. During that time, the man can experience symptoms including low libido, erectile dysfunction, low mood, and fatigue. This leads to a dependence syndrome in about 30%. About 65% of men who stop taking anabolic steroids will restart taking them within the first year, Dr. Grant said in presenting her findings at the annual meeting of the Endocrine Society.

Asked to comment, session moderator Frances Hayes, MBBCh, associate clinical chief of the Division of Reproductive Endocrinology at Massachusetts General Hospital, Boston, said, “One question is, if you intervene with an antidepressant, will that prevent the people from relapsing and going back to using? I think that’s certainly something that would need to be explored and tested.”

Dr. Hayes also noted that fertility problems may lead some men to decide to stop using the steroids. “That can be a strong motivator. If you have a motivated patient, then you add in an antidepressant or anxiolytic or link the patients with mental health services. I think that would definitely be beneficial and definitely something we need to address and see if it is worthwhile doing.”

Dr. Grant presented data from her group’s cross-sectional, observational study. Of a total 245 men, 116 were current AAS users, 84 were previous AAS users who had quit within the past year, and 45 had never used them. All completed extensive questionnaires about their substance use, mood, sexual function, and anxiety. They had morning blood tests, and urine samples were taken for toxicology testing.

The three groups didn’t differ by age (most were in their mid-30s) or ethnicity (most were White). However, the proportion who self-reported psychiatric diagnoses (mostly depression or anxiety) was significantly higher among both the current (29%) and past (25%) AAS users than among the never users (6.6%), with P = .0094.

Dr. Hayes commented, “One of the drawbacks of this study was they didn’t have baseline data. But it would make sense, I think, that the incidence of depression and anxiety was higher in the people who went on to use anabolic steroids.”

Use of other illicit drugs — mostly cocaine and cannabis — was also higher among the past (40.5%) and current (47.4%) AAS users than among the nonusers (17.7%), P = .0025.

Not surprisingly, total testosterone levels were much higher in current AAS users (62.8 nmol/L) than in past users (20.1 nmol/L) and nonusers (20.0 nmol/L), P < .001. Levels of luteinizing hormone (LH), follicle-stimulating hormone, and sex hormone-binding globulin were significantly lower in the current AAS users than in the other two groups, while estradiol levels were significantly higher (all P < .001).

There were no differences in total testosterone between the never users and previous users. However, about 25% of the men who stopped continued to have lower-than-normal testosterone levels, Dr. Grant noted.

Depression scores, as assessed by the Beck Depression Inventory-II, were highest in men who stopped using AAS, and lowest in the never users. Moderate to severe depression was present in 20% of the men who stopped using AAS, 6% of current users, and none of the nonusers.

In multivariable analysis, having a prior psychiatric diagnosis increased the risk for current depression on the Beck inventory by twofold in the current AAS users (P = .001) and threefold in the past users (P < .001). “Interestingly, testosterone levels were not associated with depression,” she noted.

Sexual function, as measured by the International Index of Erectile Function (IIEF) 15, was significantly worse among those who had stopped using AAS compared with current users and nonusers (P = .023). At the same time, total testosterone levels were only weakly correlated with IIEF scores.

In multivariate analysis, higher LH levels were associated with worse sexual function (P = .01).

Anxiety, as measured by the General Anxiety Disorder-7 assessment, was higher in previous users than in never users. Overall, 12% of the previous users had moderate or severe anxiety vs just 2% of nonusers.

The next step in the research will be to examine the urine toxicology for AAS and other illicit substances, Dr. Grant said.

“We’re hoping this information will allow for future studies to be developed to design treatments, which will help millions of men worldwide to stop and stay off anabolic steroids,” she concluded.

Dr. Grant and Dr. Hayes had no disclosures.

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

BOSTON — Men who stop using performance-enhancing anabolic-androgenic steroids (AAS) experience significant depression, anxiety, and diminished sexual function within the first year after quitting, new research found.

The data suggest that monitoring these men and, pending clinical trial evidence, intervening to minimize these effects could help prevent recidivism, Bonnie Grant, MBBS, a clinical research fellow at Imperial College London, London, England, told this news organization.

“Nothing has actually been studied in proper randomized controlled trials … but I think there’s going to be a role for medicine alongside psychological treatment … Clinicians often see men who have stopped [taking steroids] who report feeling low in mood … a lot of these men will just restart taking them again,” she said.

Anabolic steroids taken exogenously suppress the hypothalamic-pituitary-gonadal system, thereby suppressing endogenous testosterone secretion. While AAS do enhance muscle-building, they can also lead to enlarged hearts, hypertension, and infertility. Most of these are reversible if the man stops taking the AAS.

However, after stopping, the testosterone levels can take up to a year to return to normal. During that time, the man can experience symptoms including low libido, erectile dysfunction, low mood, and fatigue. This leads to a dependence syndrome in about 30%. About 65% of men who stop taking anabolic steroids will restart taking them within the first year, Dr. Grant said in presenting her findings at the annual meeting of the Endocrine Society.

Asked to comment, session moderator Frances Hayes, MBBCh, associate clinical chief of the Division of Reproductive Endocrinology at Massachusetts General Hospital, Boston, said, “One question is, if you intervene with an antidepressant, will that prevent the people from relapsing and going back to using? I think that’s certainly something that would need to be explored and tested.”

Dr. Hayes also noted that fertility problems may lead some men to decide to stop using the steroids. “That can be a strong motivator. If you have a motivated patient, then you add in an antidepressant or anxiolytic or link the patients with mental health services. I think that would definitely be beneficial and definitely something we need to address and see if it is worthwhile doing.”

Dr. Grant presented data from her group’s cross-sectional, observational study. Of a total 245 men, 116 were current AAS users, 84 were previous AAS users who had quit within the past year, and 45 had never used them. All completed extensive questionnaires about their substance use, mood, sexual function, and anxiety. They had morning blood tests, and urine samples were taken for toxicology testing.

The three groups didn’t differ by age (most were in their mid-30s) or ethnicity (most were White). However, the proportion who self-reported psychiatric diagnoses (mostly depression or anxiety) was significantly higher among both the current (29%) and past (25%) AAS users than among the never users (6.6%), with P = .0094.

Dr. Hayes commented, “One of the drawbacks of this study was they didn’t have baseline data. But it would make sense, I think, that the incidence of depression and anxiety was higher in the people who went on to use anabolic steroids.”

Use of other illicit drugs — mostly cocaine and cannabis — was also higher among the past (40.5%) and current (47.4%) AAS users than among the nonusers (17.7%), P = .0025.

Not surprisingly, total testosterone levels were much higher in current AAS users (62.8 nmol/L) than in past users (20.1 nmol/L) and nonusers (20.0 nmol/L), P < .001. Levels of luteinizing hormone (LH), follicle-stimulating hormone, and sex hormone-binding globulin were significantly lower in the current AAS users than in the other two groups, while estradiol levels were significantly higher (all P < .001).

There were no differences in total testosterone between the never users and previous users. However, about 25% of the men who stopped continued to have lower-than-normal testosterone levels, Dr. Grant noted.

Depression scores, as assessed by the Beck Depression Inventory-II, were highest in men who stopped using AAS, and lowest in the never users. Moderate to severe depression was present in 20% of the men who stopped using AAS, 6% of current users, and none of the nonusers.

In multivariable analysis, having a prior psychiatric diagnosis increased the risk for current depression on the Beck inventory by twofold in the current AAS users (P = .001) and threefold in the past users (P < .001). “Interestingly, testosterone levels were not associated with depression,” she noted.

Sexual function, as measured by the International Index of Erectile Function (IIEF) 15, was significantly worse among those who had stopped using AAS compared with current users and nonusers (P = .023). At the same time, total testosterone levels were only weakly correlated with IIEF scores.

In multivariate analysis, higher LH levels were associated with worse sexual function (P = .01).

Anxiety, as measured by the General Anxiety Disorder-7 assessment, was higher in previous users than in never users. Overall, 12% of the previous users had moderate or severe anxiety vs just 2% of nonusers.

The next step in the research will be to examine the urine toxicology for AAS and other illicit substances, Dr. Grant said.

“We’re hoping this information will allow for future studies to be developed to design treatments, which will help millions of men worldwide to stop and stay off anabolic steroids,” she concluded.

Dr. Grant and Dr. Hayes had no disclosures.

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

BOSTON — Men who stop using performance-enhancing anabolic-androgenic steroids (AAS) experience significant depression, anxiety, and diminished sexual function within the first year after quitting, new research found.

The data suggest that monitoring these men and, pending clinical trial evidence, intervening to minimize these effects could help prevent recidivism, Bonnie Grant, MBBS, a clinical research fellow at Imperial College London, London, England, told this news organization.

“Nothing has actually been studied in proper randomized controlled trials … but I think there’s going to be a role for medicine alongside psychological treatment … Clinicians often see men who have stopped [taking steroids] who report feeling low in mood … a lot of these men will just restart taking them again,” she said.

Anabolic steroids taken exogenously suppress the hypothalamic-pituitary-gonadal system, thereby suppressing endogenous testosterone secretion. While AAS do enhance muscle-building, they can also lead to enlarged hearts, hypertension, and infertility. Most of these are reversible if the man stops taking the AAS.

However, after stopping, the testosterone levels can take up to a year to return to normal. During that time, the man can experience symptoms including low libido, erectile dysfunction, low mood, and fatigue. This leads to a dependence syndrome in about 30%. About 65% of men who stop taking anabolic steroids will restart taking them within the first year, Dr. Grant said in presenting her findings at the annual meeting of the Endocrine Society.

Asked to comment, session moderator Frances Hayes, MBBCh, associate clinical chief of the Division of Reproductive Endocrinology at Massachusetts General Hospital, Boston, said, “One question is, if you intervene with an antidepressant, will that prevent the people from relapsing and going back to using? I think that’s certainly something that would need to be explored and tested.”

Dr. Hayes also noted that fertility problems may lead some men to decide to stop using the steroids. “That can be a strong motivator. If you have a motivated patient, then you add in an antidepressant or anxiolytic or link the patients with mental health services. I think that would definitely be beneficial and definitely something we need to address and see if it is worthwhile doing.”

Dr. Grant presented data from her group’s cross-sectional, observational study. Of a total 245 men, 116 were current AAS users, 84 were previous AAS users who had quit within the past year, and 45 had never used them. All completed extensive questionnaires about their substance use, mood, sexual function, and anxiety. They had morning blood tests, and urine samples were taken for toxicology testing.

The three groups didn’t differ by age (most were in their mid-30s) or ethnicity (most were White). However, the proportion who self-reported psychiatric diagnoses (mostly depression or anxiety) was significantly higher among both the current (29%) and past (25%) AAS users than among the never users (6.6%), with P = .0094.

Dr. Hayes commented, “One of the drawbacks of this study was they didn’t have baseline data. But it would make sense, I think, that the incidence of depression and anxiety was higher in the people who went on to use anabolic steroids.”

Use of other illicit drugs — mostly cocaine and cannabis — was also higher among the past (40.5%) and current (47.4%) AAS users than among the nonusers (17.7%), P = .0025.

Not surprisingly, total testosterone levels were much higher in current AAS users (62.8 nmol/L) than in past users (20.1 nmol/L) and nonusers (20.0 nmol/L), P < .001. Levels of luteinizing hormone (LH), follicle-stimulating hormone, and sex hormone-binding globulin were significantly lower in the current AAS users than in the other two groups, while estradiol levels were significantly higher (all P < .001).

There were no differences in total testosterone between the never users and previous users. However, about 25% of the men who stopped continued to have lower-than-normal testosterone levels, Dr. Grant noted.

Depression scores, as assessed by the Beck Depression Inventory-II, were highest in men who stopped using AAS, and lowest in the never users. Moderate to severe depression was present in 20% of the men who stopped using AAS, 6% of current users, and none of the nonusers.

In multivariable analysis, having a prior psychiatric diagnosis increased the risk for current depression on the Beck inventory by twofold in the current AAS users (P = .001) and threefold in the past users (P < .001). “Interestingly, testosterone levels were not associated with depression,” she noted.

Sexual function, as measured by the International Index of Erectile Function (IIEF) 15, was significantly worse among those who had stopped using AAS compared with current users and nonusers (P = .023). At the same time, total testosterone levels were only weakly correlated with IIEF scores.

In multivariate analysis, higher LH levels were associated with worse sexual function (P = .01).

Anxiety, as measured by the General Anxiety Disorder-7 assessment, was higher in previous users than in never users. Overall, 12% of the previous users had moderate or severe anxiety vs just 2% of nonusers.

The next step in the research will be to examine the urine toxicology for AAS and other illicit substances, Dr. Grant said.

“We’re hoping this information will allow for future studies to be developed to design treatments, which will help millions of men worldwide to stop and stay off anabolic steroids,” she concluded.

Dr. Grant and Dr. Hayes had no disclosures.

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

British Columbia (BC) could eliminate cervical cancer within the next 20 years if the province shifts from cytology to human papillomavirus (HPV)–based screening before the end of the decade, data suggested. To achieve this goal, the province will also need to reach historically underscreened, equity-seeking populations (ie, Black, indigenous, immigrant, LGBTQ, and disabled patients, and those with sexual trauma) through mailed self-screening HPV tests.

The adoption of both these strategies is essential, according to a modeling study that was published on June 3 in CMAJ, especially because the true impact of HPV vaccination has yet to be fully realized.

“In BC, we have a school-based program to increase vaccine coverage in boys and girls starting in grade 6,” study author Reka Pataky, PhD, a senior research health economist at the Canadian Centre for Applied Research in Cancer Control and BC Cancer in Vancouver, British Columbia, Canada, told this news organization. Dr. Pataky noted that this immunization program was launched in 2008 and that some of the initial cohorts haven›t yet reached the average age of diagnosis, which is between 30 and 59 years.

Three’s a Charm

The investigators undertook a modeling study to determine when and how BC might achieve the elimination of cervical cancer following a transition to HPV-based screening. Elimination was defined as an annual age-standardized incidence rate of < 4.0 per 100,000 women.

Modeling scenarios were developed using the Canadian Partnership Against Cancer’s priority targets, which include increasing HPV vaccination through school-based coverage from 70% to 90%, increasing the probability of ever receiving a screening test from 90% to 95%, increasing the rate of on-time screening from 70% to 90%, and improving follow-up to 95% for colposcopy (currently 88%) and HPV testing (currently 80%). Modeling simulated HPV transmission and the natural history of cervical cancer in the Canadian population and relied upon two reference scenarios: One using BC’s cytology-based screening at the time of analysis, and the other an HPV base-case scenario.

The researchers found that with the status quo (ie, cytology-based screening and no change to vaccination or screening participation rates), BC would not eliminate cervical cancer until 2045. Implementation of HPV-based screening at the current 70% participation rate would achieve elimination in 2034 and prevent 942 cases compared with cytology screening. Increasing the proportion of patients who were ever screened or increasing vaccination coverage would result in cervical cancer elimination by 2033. The time line would be shortened even further (to 2031) through a combination of three strategies (ie, improving recruitment, on-time screening, and follow-up compliance).

Low Incidence, Strained System

The incidence of cervical cancer in Canada is relatively low, accounting for 1.3% of all new female cancers and 1.1% of all female cancer deaths.

“The reason that we have such low rates is because we have organized screening programs,” explained Rachel Kupets, MD, associate professor of gynecologic oncology at the University of Toronto and Sunnybrook Hospital, Toronto. She was not involved in the study.

“We’re starting to see what happens when the system gets strained with lower participation rates. I am starting to see a lot more women with invasive cervical cancer. They’re younger, and their cancers are less curable and less treatable,” she said.

Difficulties with access, interest, and education have contributed to low cervical screening rates among equity-seeking populations, according to Dr. Pataky and Dr. Kupets.

“Self-screening is another tool that can incrementally benefit those folks who wouldn’t otherwise undergo screening or don’t want an invasive test,” said Dr. Kupets. It can also play an increasing role, while current access to primary care services in Canada is at an all-time low. Community outreach through centers, mobile coaches, and nursing stations might help ensure participation by at-risk populations. These measures also could boost follow-up for and education about positive results, said Dr. Kupets.

In a related editorial, Shannon Charlebois, MD, medical editor of CMAJ, and Sarah Kean, MD, assistant professor of gynecologic oncology at the University of Manitoba in Winnipeg, Manitoba, Canada, emphasized the need for mailed HPV self-screening kits to be paid for and integrated into provincial cervical cancer screening programs across Canada to support earlier cervical cancer detection and lower invasive cancer rates.

Dr. Pataky concurred. “There have been discussions about making the big transition from traditional cytology to implementing HPV self-screening,” she said. “We have really effective tools for preventing cervical cancer, and it’s important to not lose sight of that goal.”

The study was funded by the National Institutes of Health. Dr. Pataky and Dr. Kupets reported no relevant financial relationships.
 

A version of this article appeared on Medscape.com.

British Columbia (BC) could eliminate cervical cancer within the next 20 years if the province shifts from cytology to human papillomavirus (HPV)–based screening before the end of the decade, data suggested. To achieve this goal, the province will also need to reach historically underscreened, equity-seeking populations (ie, Black, indigenous, immigrant, LGBTQ, and disabled patients, and those with sexual trauma) through mailed self-screening HPV tests.

The adoption of both these strategies is essential, according to a modeling study that was published on June 3 in CMAJ, especially because the true impact of HPV vaccination has yet to be fully realized.

“In BC, we have a school-based program to increase vaccine coverage in boys and girls starting in grade 6,” study author Reka Pataky, PhD, a senior research health economist at the Canadian Centre for Applied Research in Cancer Control and BC Cancer in Vancouver, British Columbia, Canada, told this news organization. Dr. Pataky noted that this immunization program was launched in 2008 and that some of the initial cohorts haven›t yet reached the average age of diagnosis, which is between 30 and 59 years.

Three’s a Charm

The investigators undertook a modeling study to determine when and how BC might achieve the elimination of cervical cancer following a transition to HPV-based screening. Elimination was defined as an annual age-standardized incidence rate of < 4.0 per 100,000 women.

Modeling scenarios were developed using the Canadian Partnership Against Cancer’s priority targets, which include increasing HPV vaccination through school-based coverage from 70% to 90%, increasing the probability of ever receiving a screening test from 90% to 95%, increasing the rate of on-time screening from 70% to 90%, and improving follow-up to 95% for colposcopy (currently 88%) and HPV testing (currently 80%). Modeling simulated HPV transmission and the natural history of cervical cancer in the Canadian population and relied upon two reference scenarios: One using BC’s cytology-based screening at the time of analysis, and the other an HPV base-case scenario.

The researchers found that with the status quo (ie, cytology-based screening and no change to vaccination or screening participation rates), BC would not eliminate cervical cancer until 2045. Implementation of HPV-based screening at the current 70% participation rate would achieve elimination in 2034 and prevent 942 cases compared with cytology screening. Increasing the proportion of patients who were ever screened or increasing vaccination coverage would result in cervical cancer elimination by 2033. The time line would be shortened even further (to 2031) through a combination of three strategies (ie, improving recruitment, on-time screening, and follow-up compliance).

Low Incidence, Strained System

The incidence of cervical cancer in Canada is relatively low, accounting for 1.3% of all new female cancers and 1.1% of all female cancer deaths.

“The reason that we have such low rates is because we have organized screening programs,” explained Rachel Kupets, MD, associate professor of gynecologic oncology at the University of Toronto and Sunnybrook Hospital, Toronto. She was not involved in the study.

“We’re starting to see what happens when the system gets strained with lower participation rates. I am starting to see a lot more women with invasive cervical cancer. They’re younger, and their cancers are less curable and less treatable,” she said.

Difficulties with access, interest, and education have contributed to low cervical screening rates among equity-seeking populations, according to Dr. Pataky and Dr. Kupets.

“Self-screening is another tool that can incrementally benefit those folks who wouldn’t otherwise undergo screening or don’t want an invasive test,” said Dr. Kupets. It can also play an increasing role, while current access to primary care services in Canada is at an all-time low. Community outreach through centers, mobile coaches, and nursing stations might help ensure participation by at-risk populations. These measures also could boost follow-up for and education about positive results, said Dr. Kupets.

In a related editorial, Shannon Charlebois, MD, medical editor of CMAJ, and Sarah Kean, MD, assistant professor of gynecologic oncology at the University of Manitoba in Winnipeg, Manitoba, Canada, emphasized the need for mailed HPV self-screening kits to be paid for and integrated into provincial cervical cancer screening programs across Canada to support earlier cervical cancer detection and lower invasive cancer rates.

Dr. Pataky concurred. “There have been discussions about making the big transition from traditional cytology to implementing HPV self-screening,” she said. “We have really effective tools for preventing cervical cancer, and it’s important to not lose sight of that goal.”

The study was funded by the National Institutes of Health. Dr. Pataky and Dr. Kupets reported no relevant financial relationships.
 

A version of this article appeared on Medscape.com.

British Columbia (BC) could eliminate cervical cancer within the next 20 years if the province shifts from cytology to human papillomavirus (HPV)–based screening before the end of the decade, data suggested. To achieve this goal, the province will also need to reach historically underscreened, equity-seeking populations (ie, Black, indigenous, immigrant, LGBTQ, and disabled patients, and those with sexual trauma) through mailed self-screening HPV tests.

The adoption of both these strategies is essential, according to a modeling study that was published on June 3 in CMAJ, especially because the true impact of HPV vaccination has yet to be fully realized.

“In BC, we have a school-based program to increase vaccine coverage in boys and girls starting in grade 6,” study author Reka Pataky, PhD, a senior research health economist at the Canadian Centre for Applied Research in Cancer Control and BC Cancer in Vancouver, British Columbia, Canada, told this news organization. Dr. Pataky noted that this immunization program was launched in 2008 and that some of the initial cohorts haven›t yet reached the average age of diagnosis, which is between 30 and 59 years.

Three’s a Charm

The investigators undertook a modeling study to determine when and how BC might achieve the elimination of cervical cancer following a transition to HPV-based screening. Elimination was defined as an annual age-standardized incidence rate of < 4.0 per 100,000 women.

Modeling scenarios were developed using the Canadian Partnership Against Cancer’s priority targets, which include increasing HPV vaccination through school-based coverage from 70% to 90%, increasing the probability of ever receiving a screening test from 90% to 95%, increasing the rate of on-time screening from 70% to 90%, and improving follow-up to 95% for colposcopy (currently 88%) and HPV testing (currently 80%). Modeling simulated HPV transmission and the natural history of cervical cancer in the Canadian population and relied upon two reference scenarios: One using BC’s cytology-based screening at the time of analysis, and the other an HPV base-case scenario.

The researchers found that with the status quo (ie, cytology-based screening and no change to vaccination or screening participation rates), BC would not eliminate cervical cancer until 2045. Implementation of HPV-based screening at the current 70% participation rate would achieve elimination in 2034 and prevent 942 cases compared with cytology screening. Increasing the proportion of patients who were ever screened or increasing vaccination coverage would result in cervical cancer elimination by 2033. The time line would be shortened even further (to 2031) through a combination of three strategies (ie, improving recruitment, on-time screening, and follow-up compliance).

Low Incidence, Strained System

The incidence of cervical cancer in Canada is relatively low, accounting for 1.3% of all new female cancers and 1.1% of all female cancer deaths.

“The reason that we have such low rates is because we have organized screening programs,” explained Rachel Kupets, MD, associate professor of gynecologic oncology at the University of Toronto and Sunnybrook Hospital, Toronto. She was not involved in the study.

“We’re starting to see what happens when the system gets strained with lower participation rates. I am starting to see a lot more women with invasive cervical cancer. They’re younger, and their cancers are less curable and less treatable,” she said.

Difficulties with access, interest, and education have contributed to low cervical screening rates among equity-seeking populations, according to Dr. Pataky and Dr. Kupets.

“Self-screening is another tool that can incrementally benefit those folks who wouldn’t otherwise undergo screening or don’t want an invasive test,” said Dr. Kupets. It can also play an increasing role, while current access to primary care services in Canada is at an all-time low. Community outreach through centers, mobile coaches, and nursing stations might help ensure participation by at-risk populations. These measures also could boost follow-up for and education about positive results, said Dr. Kupets.

In a related editorial, Shannon Charlebois, MD, medical editor of CMAJ, and Sarah Kean, MD, assistant professor of gynecologic oncology at the University of Manitoba in Winnipeg, Manitoba, Canada, emphasized the need for mailed HPV self-screening kits to be paid for and integrated into provincial cervical cancer screening programs across Canada to support earlier cervical cancer detection and lower invasive cancer rates.

Dr. Pataky concurred. “There have been discussions about making the big transition from traditional cytology to implementing HPV self-screening,” she said. “We have really effective tools for preventing cervical cancer, and it’s important to not lose sight of that goal.”

The study was funded by the National Institutes of Health. Dr. Pataky and Dr. Kupets reported no relevant financial relationships.
 

A version of this article appeared on Medscape.com.

Two decades after the landmark Women’s Health Initiative (WHI) changed the way clinicians thought about hormone therapy and cancer, new findings suggest this national health study is "the gift that keeps on giving."

Follow-up from two of the WHI’s randomized trials have found that estrogen alone in women with prior hysterectomy significantly increased ovarian cancer incidence and mortality in postmenopausal women. Estrogen and progesterone together, meanwhile, did not increase ovarian cancer risk, and significantly reduced the risk of endometrial cancer. Rowan T. Chlebowski, MD, PhD, of The Lundquist Institute in Torrance, California, presented these results from the latest WHI findings, at the annual meeting of the American Society of Clinical Oncology in Chicago.

Dr. Chlebowski and his colleagues conducted an analysis from two randomized, placebo-controlled trials, which between 1993 and 1998 enrolled nearly 28,000 postmenopausal women aged 50-79 years without prior cancer from 40 centers across the United States. (The full WHI effort involved a total cohort of 161,000 patients, and included an observational study and two other non-drug trials.)

In one of the hormone therapy trials, 17,000 women with a uterus at baseline were randomized to combined equine estrogen plus medroxyprogesterone acetate, or placebo. In the other trial, about 11,000 women with prior hysterectomy were randomized to daily estrogen alone or placebo. Both trials were stopped early: the estrogen-only trial due to an increased stroke risk, and the combined therapy trial due to findings of increased breast cancer and cardiovascular risk.

Mean exposure to hormone therapy was 5.6 years for the combined therapy trial and 7.2 years for estrogen alone trial.
 

Ovarian Cancer Incidence Doubles with Estrogen

At 20 years’ follow up, with mortality information available for nearly the full cohort, Dr. Chlebowski and his colleagues could determine that ovarian cancer incidence doubled among women who had taken estrogen alone (hazard ratio = 2.04; 95% CI 1.14-3.65; P = .01), a difference that reached statistical significance at 12 years’ follow up. Ovarian cancer mortality was also significantly increased (HR = 2.79 95% CI 1.30-5.99, P = .006). Absolute numbers were small, however, with 35 cases of ovarian cancer compared with 17 in the placebo group.

Combined therapy recipients saw no increased risk for ovarian cancer and significantly lower endometrial cancer incidence (106 cases vs. 140 HR = 0.72; 95% CI, 0.56-0.92; P = .01).

Conjugated equine estrogen, Dr. Chlebowski said during his presentation at the meeting, “was introduced in US clinical practice in 1943 and used for over half a century, yet the question about hormone therapy’s influence on endometrial and ovarian cancer remains unsettled. Endometrial cancer and ovarian cancer are the fourth and fifth leading causes of cancer deaths in women ... and there’s some discordant findings from observational studies.”

Care of Ovarian Cancer Survivors Should Change

The new findings should prompt practice and guideline changes regarding the use of estrogen alone in ovarian cancer survivors, Dr. Chlebowski said.

In an interview, oncologist Eleonora Teplinsky, MD, of Valley-Mount Sinai Comprehensive Cancer Care in Paramus, New Jersey, said that apart from this subgroup of ovarian cancer survivors, the findings would not likely have much impact on how clinicians and patients approach hormone replacement therapy today.

“Twenty years ago the Women’s Health Initiative showed that hormone replacement therapy increases breast cancer risk, and everyone stopped taking HRT. And now people pushing back on it and saying wait a second – it was the estrogen plus progesterone that increased breast cancer, not estrogen alone. And now we’ve got these newer [estrogen] formulations.

“Yes, there’s a little bit of an increased risk [for ovarian cancer]. Patients should be aware. They should know the symptoms of ovarian cancer. But if they have indications and have been recommended HRT, this is not something that we would advise them against because of this very slightly increased risk,” Dr. Teplinsky said.

Oncologist Allison Kurian, MD of Stanford University in Stanford, California, who specializes in breast cancer, also noted that the duration of hormone treatment, treatment timing relative to age of menopause onset, and commonly used estrogen preparations had indeed changed since the time the WHI trials were conducted, making it harder to generalize the findings to current practice. Nonetheless, she argued, they still have real significance.

“WHI is an incredibly complex but also incredibly valuable resource,” said Dr. Kurian, who has conducted studies using WHI data. “The first big results came out in 2002, and we’re still learning from it. These are randomized trials, which offer the strongest form of scientific evidence that exists. So whenever we see results from this study, we have to take note of them,” she said.

Because the WHI trials had shown combined therapy, not estrogen alone, to be associated with breast cancer risk, clinicians have felt reassured over the years about using estrogen alone.

“You can’t give it to a person unless they have their uterus removed, because we know it will cause uterine cancer if the uterus is in place. But if the uterus is removed, the feeling was that you can give estrogen alone. I think the new piece that is going to get everyone’s attention is this signal for ovarian cancer.”

Something else the new findings show, Dr. Kurian said, is that WHI is “the gift that keeps on giving,” even after decades. “Some of the participants had a relatively short-term exposure to HRT. They took a medication for just a little while. But you didn’t see the effects until you followed people 12 years. So we’re now going to be a little more worried about ovarian cancer in this setting than we used to be. And that’s going to be something we’re all going to keep an eye on and think twice about in terms of talking to patients.”

These results help demonstrate what happens when a society invests in science on a national scale, Dr. Kurian said. “Here we have a really long-term, incredibly informative study that keeps generating knowledge to help women.”

When the WHI began, it “really was the first time that people decided it was important to systematically study women at midlife. It was a remarkable thing then that society got mobilized to do this, and we’re still seeing the benefits.”

Dr. Chlebowski disclosed receiving consulting or advisory fees from Pfizer. Dr. Teplinsky and Dr. Kurian disclosed no financial conflicts of interest.

Two decades after the landmark Women’s Health Initiative (WHI) changed the way clinicians thought about hormone therapy and cancer, new findings suggest this national health study is "the gift that keeps on giving."

Follow-up from two of the WHI’s randomized trials have found that estrogen alone in women with prior hysterectomy significantly increased ovarian cancer incidence and mortality in postmenopausal women. Estrogen and progesterone together, meanwhile, did not increase ovarian cancer risk, and significantly reduced the risk of endometrial cancer. Rowan T. Chlebowski, MD, PhD, of The Lundquist Institute in Torrance, California, presented these results from the latest WHI findings, at the annual meeting of the American Society of Clinical Oncology in Chicago.

Dr. Chlebowski and his colleagues conducted an analysis from two randomized, placebo-controlled trials, which between 1993 and 1998 enrolled nearly 28,000 postmenopausal women aged 50-79 years without prior cancer from 40 centers across the United States. (The full WHI effort involved a total cohort of 161,000 patients, and included an observational study and two other non-drug trials.)

In one of the hormone therapy trials, 17,000 women with a uterus at baseline were randomized to combined equine estrogen plus medroxyprogesterone acetate, or placebo. In the other trial, about 11,000 women with prior hysterectomy were randomized to daily estrogen alone or placebo. Both trials were stopped early: the estrogen-only trial due to an increased stroke risk, and the combined therapy trial due to findings of increased breast cancer and cardiovascular risk.

Mean exposure to hormone therapy was 5.6 years for the combined therapy trial and 7.2 years for estrogen alone trial.
 

Ovarian Cancer Incidence Doubles with Estrogen

At 20 years’ follow up, with mortality information available for nearly the full cohort, Dr. Chlebowski and his colleagues could determine that ovarian cancer incidence doubled among women who had taken estrogen alone (hazard ratio = 2.04; 95% CI 1.14-3.65; P = .01), a difference that reached statistical significance at 12 years’ follow up. Ovarian cancer mortality was also significantly increased (HR = 2.79 95% CI 1.30-5.99, P = .006). Absolute numbers were small, however, with 35 cases of ovarian cancer compared with 17 in the placebo group.

Combined therapy recipients saw no increased risk for ovarian cancer and significantly lower endometrial cancer incidence (106 cases vs. 140 HR = 0.72; 95% CI, 0.56-0.92; P = .01).

Conjugated equine estrogen, Dr. Chlebowski said during his presentation at the meeting, “was introduced in US clinical practice in 1943 and used for over half a century, yet the question about hormone therapy’s influence on endometrial and ovarian cancer remains unsettled. Endometrial cancer and ovarian cancer are the fourth and fifth leading causes of cancer deaths in women ... and there’s some discordant findings from observational studies.”

Care of Ovarian Cancer Survivors Should Change

The new findings should prompt practice and guideline changes regarding the use of estrogen alone in ovarian cancer survivors, Dr. Chlebowski said.

In an interview, oncologist Eleonora Teplinsky, MD, of Valley-Mount Sinai Comprehensive Cancer Care in Paramus, New Jersey, said that apart from this subgroup of ovarian cancer survivors, the findings would not likely have much impact on how clinicians and patients approach hormone replacement therapy today.

“Twenty years ago the Women’s Health Initiative showed that hormone replacement therapy increases breast cancer risk, and everyone stopped taking HRT. And now people pushing back on it and saying wait a second – it was the estrogen plus progesterone that increased breast cancer, not estrogen alone. And now we’ve got these newer [estrogen] formulations.

“Yes, there’s a little bit of an increased risk [for ovarian cancer]. Patients should be aware. They should know the symptoms of ovarian cancer. But if they have indications and have been recommended HRT, this is not something that we would advise them against because of this very slightly increased risk,” Dr. Teplinsky said.

Oncologist Allison Kurian, MD of Stanford University in Stanford, California, who specializes in breast cancer, also noted that the duration of hormone treatment, treatment timing relative to age of menopause onset, and commonly used estrogen preparations had indeed changed since the time the WHI trials were conducted, making it harder to generalize the findings to current practice. Nonetheless, she argued, they still have real significance.

“WHI is an incredibly complex but also incredibly valuable resource,” said Dr. Kurian, who has conducted studies using WHI data. “The first big results came out in 2002, and we’re still learning from it. These are randomized trials, which offer the strongest form of scientific evidence that exists. So whenever we see results from this study, we have to take note of them,” she said.

Because the WHI trials had shown combined therapy, not estrogen alone, to be associated with breast cancer risk, clinicians have felt reassured over the years about using estrogen alone.

“You can’t give it to a person unless they have their uterus removed, because we know it will cause uterine cancer if the uterus is in place. But if the uterus is removed, the feeling was that you can give estrogen alone. I think the new piece that is going to get everyone’s attention is this signal for ovarian cancer.”

Something else the new findings show, Dr. Kurian said, is that WHI is “the gift that keeps on giving,” even after decades. “Some of the participants had a relatively short-term exposure to HRT. They took a medication for just a little while. But you didn’t see the effects until you followed people 12 years. So we’re now going to be a little more worried about ovarian cancer in this setting than we used to be. And that’s going to be something we’re all going to keep an eye on and think twice about in terms of talking to patients.”

These results help demonstrate what happens when a society invests in science on a national scale, Dr. Kurian said. “Here we have a really long-term, incredibly informative study that keeps generating knowledge to help women.”

When the WHI began, it “really was the first time that people decided it was important to systematically study women at midlife. It was a remarkable thing then that society got mobilized to do this, and we’re still seeing the benefits.”

Dr. Chlebowski disclosed receiving consulting or advisory fees from Pfizer. Dr. Teplinsky and Dr. Kurian disclosed no financial conflicts of interest.

Two decades after the landmark Women’s Health Initiative (WHI) changed the way clinicians thought about hormone therapy and cancer, new findings suggest this national health study is "the gift that keeps on giving."

Follow-up from two of the WHI’s randomized trials have found that estrogen alone in women with prior hysterectomy significantly increased ovarian cancer incidence and mortality in postmenopausal women. Estrogen and progesterone together, meanwhile, did not increase ovarian cancer risk, and significantly reduced the risk of endometrial cancer. Rowan T. Chlebowski, MD, PhD, of The Lundquist Institute in Torrance, California, presented these results from the latest WHI findings, at the annual meeting of the American Society of Clinical Oncology in Chicago.

Dr. Chlebowski and his colleagues conducted an analysis from two randomized, placebo-controlled trials, which between 1993 and 1998 enrolled nearly 28,000 postmenopausal women aged 50-79 years without prior cancer from 40 centers across the United States. (The full WHI effort involved a total cohort of 161,000 patients, and included an observational study and two other non-drug trials.)

In one of the hormone therapy trials, 17,000 women with a uterus at baseline were randomized to combined equine estrogen plus medroxyprogesterone acetate, or placebo. In the other trial, about 11,000 women with prior hysterectomy were randomized to daily estrogen alone or placebo. Both trials were stopped early: the estrogen-only trial due to an increased stroke risk, and the combined therapy trial due to findings of increased breast cancer and cardiovascular risk.

Mean exposure to hormone therapy was 5.6 years for the combined therapy trial and 7.2 years for estrogen alone trial.
 

Ovarian Cancer Incidence Doubles with Estrogen

At 20 years’ follow up, with mortality information available for nearly the full cohort, Dr. Chlebowski and his colleagues could determine that ovarian cancer incidence doubled among women who had taken estrogen alone (hazard ratio = 2.04; 95% CI 1.14-3.65; P = .01), a difference that reached statistical significance at 12 years’ follow up. Ovarian cancer mortality was also significantly increased (HR = 2.79 95% CI 1.30-5.99, P = .006). Absolute numbers were small, however, with 35 cases of ovarian cancer compared with 17 in the placebo group.

Combined therapy recipients saw no increased risk for ovarian cancer and significantly lower endometrial cancer incidence (106 cases vs. 140 HR = 0.72; 95% CI, 0.56-0.92; P = .01).

Conjugated equine estrogen, Dr. Chlebowski said during his presentation at the meeting, “was introduced in US clinical practice in 1943 and used for over half a century, yet the question about hormone therapy’s influence on endometrial and ovarian cancer remains unsettled. Endometrial cancer and ovarian cancer are the fourth and fifth leading causes of cancer deaths in women ... and there’s some discordant findings from observational studies.”

Care of Ovarian Cancer Survivors Should Change

The new findings should prompt practice and guideline changes regarding the use of estrogen alone in ovarian cancer survivors, Dr. Chlebowski said.

In an interview, oncologist Eleonora Teplinsky, MD, of Valley-Mount Sinai Comprehensive Cancer Care in Paramus, New Jersey, said that apart from this subgroup of ovarian cancer survivors, the findings would not likely have much impact on how clinicians and patients approach hormone replacement therapy today.

“Twenty years ago the Women’s Health Initiative showed that hormone replacement therapy increases breast cancer risk, and everyone stopped taking HRT. And now people pushing back on it and saying wait a second – it was the estrogen plus progesterone that increased breast cancer, not estrogen alone. And now we’ve got these newer [estrogen] formulations.

“Yes, there’s a little bit of an increased risk [for ovarian cancer]. Patients should be aware. They should know the symptoms of ovarian cancer. But if they have indications and have been recommended HRT, this is not something that we would advise them against because of this very slightly increased risk,” Dr. Teplinsky said.

Oncologist Allison Kurian, MD of Stanford University in Stanford, California, who specializes in breast cancer, also noted that the duration of hormone treatment, treatment timing relative to age of menopause onset, and commonly used estrogen preparations had indeed changed since the time the WHI trials were conducted, making it harder to generalize the findings to current practice. Nonetheless, she argued, they still have real significance.

“WHI is an incredibly complex but also incredibly valuable resource,” said Dr. Kurian, who has conducted studies using WHI data. “The first big results came out in 2002, and we’re still learning from it. These are randomized trials, which offer the strongest form of scientific evidence that exists. So whenever we see results from this study, we have to take note of them,” she said.

Because the WHI trials had shown combined therapy, not estrogen alone, to be associated with breast cancer risk, clinicians have felt reassured over the years about using estrogen alone.

“You can’t give it to a person unless they have their uterus removed, because we know it will cause uterine cancer if the uterus is in place. But if the uterus is removed, the feeling was that you can give estrogen alone. I think the new piece that is going to get everyone’s attention is this signal for ovarian cancer.”

Something else the new findings show, Dr. Kurian said, is that WHI is “the gift that keeps on giving,” even after decades. “Some of the participants had a relatively short-term exposure to HRT. They took a medication for just a little while. But you didn’t see the effects until you followed people 12 years. So we’re now going to be a little more worried about ovarian cancer in this setting than we used to be. And that’s going to be something we’re all going to keep an eye on and think twice about in terms of talking to patients.”

These results help demonstrate what happens when a society invests in science on a national scale, Dr. Kurian said. “Here we have a really long-term, incredibly informative study that keeps generating knowledge to help women.”

When the WHI began, it “really was the first time that people decided it was important to systematically study women at midlife. It was a remarkable thing then that society got mobilized to do this, and we’re still seeing the benefits.”

Dr. Chlebowski disclosed receiving consulting or advisory fees from Pfizer. Dr. Teplinsky and Dr. Kurian disclosed no financial conflicts of interest.

TOPLINE:

High-frequency electric nerve block significantly reduced postamputation pain in a new study, presenting a potential new therapeutic option for amputees.

METHODOLOGY:

• The study enrolled 180 patients with unilateral lower limb amputations who were experiencing severe post-procedure pain.
• Participants were randomized 1:1 to receive 3 months of treatment with either a high-frequency nerve block (Altius; Neuros Medical) or an active sham.
• Effectiveness was measured by the percentage of participants achieving at least a 50% reduction in pain in more than half of the treatment sessions.
• The researchers attempted to control for variables including pain type and baseline pain intensity.

TAKEAWAY:

• A total of 24.7% of patients in the group that received the nerve block were responders at 30 minutes post-treatment, significantly higher than 7.1% in the control group (P = .002).
• The rate of response rose to 46.8% in the treatment group at 120 minutes, compared with 22.2% in the sham group (P = .001).
• Patients who received the nerve block reported a greater improvement in their score on the Brief Pain Inventory than those in the sham arm — 2.3 ± 0.29 vs 1.3 ± 0.26, respectively (P = .01).
• Use of opioids trended toward a greater reduction in the treatment group, although that finding was not statistically significant.

IN PRACTICE:

The results suggested “high-frequency electric nerve block could be a viable option for managing chronic post-amputation pain, potentially improving patients’ quality of life and reducing reliance on opioids,” the authors wrote. “The study addresses a critical gap in treatment options for amputees suffering from persistent pain, offering evidence for a novel therapeutic approach.”

“We have never seen a study of this magnitude and rigor in this patient population,” said lead author Leonardo Kapural, MD, PhD, of the Carolinas Pain Institute in Winston-Salem, North Carolina, in a press release about the data. “The data demonstrated clear and lasting benefit of treatment for pain reduction and functional outcomes at 3 months, creating great optimism for the long-term study results. These findings represent a significant advancement for an at-risk and underserved patient population in desperate need of reliable and effective treatment.”

SOURCE:

The study was led by Leonardo Kapural, MD, PhD, of the Carolinas Pain Institute in Winston-Salem, North Carolina, and was published online in the Journal of Pain Research.

LIMITATIONS:

The sample size of 180 participants may limit the generalizability of the findings to all amputees. A 3-month duration for assessing treatment efficacy may not capture long-term outcomes and effects. The active-sham control design, while rigorous, may not fully account for the placebo effects inherent in pain perception studies.

DISCLOSURES:

The QUEST study was funded by Neuros Medical Inc. Dr. Kapural reported personal fees from various medical companies, unrelated to this work. No other conflicts of interest were reported in this work.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article appeared on Medscape.com.

TOPLINE:

High-frequency electric nerve block significantly reduced postamputation pain in a new study, presenting a potential new therapeutic option for amputees.

METHODOLOGY:

• The study enrolled 180 patients with unilateral lower limb amputations who were experiencing severe post-procedure pain.
• Participants were randomized 1:1 to receive 3 months of treatment with either a high-frequency nerve block (Altius; Neuros Medical) or an active sham.
• Effectiveness was measured by the percentage of participants achieving at least a 50% reduction in pain in more than half of the treatment sessions.
• The researchers attempted to control for variables including pain type and baseline pain intensity.

TAKEAWAY:

• A total of 24.7% of patients in the group that received the nerve block were responders at 30 minutes post-treatment, significantly higher than 7.1% in the control group (P = .002).
• The rate of response rose to 46.8% in the treatment group at 120 minutes, compared with 22.2% in the sham group (P = .001).
• Patients who received the nerve block reported a greater improvement in their score on the Brief Pain Inventory than those in the sham arm — 2.3 ± 0.29 vs 1.3 ± 0.26, respectively (P = .01).
• Use of opioids trended toward a greater reduction in the treatment group, although that finding was not statistically significant.

IN PRACTICE:

The results suggested “high-frequency electric nerve block could be a viable option for managing chronic post-amputation pain, potentially improving patients’ quality of life and reducing reliance on opioids,” the authors wrote. “The study addresses a critical gap in treatment options for amputees suffering from persistent pain, offering evidence for a novel therapeutic approach.”

“We have never seen a study of this magnitude and rigor in this patient population,” said lead author Leonardo Kapural, MD, PhD, of the Carolinas Pain Institute in Winston-Salem, North Carolina, in a press release about the data. “The data demonstrated clear and lasting benefit of treatment for pain reduction and functional outcomes at 3 months, creating great optimism for the long-term study results. These findings represent a significant advancement for an at-risk and underserved patient population in desperate need of reliable and effective treatment.”

SOURCE:

The study was led by Leonardo Kapural, MD, PhD, of the Carolinas Pain Institute in Winston-Salem, North Carolina, and was published online in the Journal of Pain Research.

LIMITATIONS:

The sample size of 180 participants may limit the generalizability of the findings to all amputees. A 3-month duration for assessing treatment efficacy may not capture long-term outcomes and effects. The active-sham control design, while rigorous, may not fully account for the placebo effects inherent in pain perception studies.

DISCLOSURES:

The QUEST study was funded by Neuros Medical Inc. Dr. Kapural reported personal fees from various medical companies, unrelated to this work. No other conflicts of interest were reported in this work.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article appeared on Medscape.com.

TOPLINE:

High-frequency electric nerve block significantly reduced postamputation pain in a new study, presenting a potential new therapeutic option for amputees.

METHODOLOGY:

• The study enrolled 180 patients with unilateral lower limb amputations who were experiencing severe post-procedure pain.
• Participants were randomized 1:1 to receive 3 months of treatment with either a high-frequency nerve block (Altius; Neuros Medical) or an active sham.
• Effectiveness was measured by the percentage of participants achieving at least a 50% reduction in pain in more than half of the treatment sessions.
• The researchers attempted to control for variables including pain type and baseline pain intensity.

TAKEAWAY:

• A total of 24.7% of patients in the group that received the nerve block were responders at 30 minutes post-treatment, significantly higher than 7.1% in the control group (P = .002).
• The rate of response rose to 46.8% in the treatment group at 120 minutes, compared with 22.2% in the sham group (P = .001).
• Patients who received the nerve block reported a greater improvement in their score on the Brief Pain Inventory than those in the sham arm — 2.3 ± 0.29 vs 1.3 ± 0.26, respectively (P = .01).
• Use of opioids trended toward a greater reduction in the treatment group, although that finding was not statistically significant.

IN PRACTICE:

The results suggested “high-frequency electric nerve block could be a viable option for managing chronic post-amputation pain, potentially improving patients’ quality of life and reducing reliance on opioids,” the authors wrote. “The study addresses a critical gap in treatment options for amputees suffering from persistent pain, offering evidence for a novel therapeutic approach.”

“We have never seen a study of this magnitude and rigor in this patient population,” said lead author Leonardo Kapural, MD, PhD, of the Carolinas Pain Institute in Winston-Salem, North Carolina, in a press release about the data. “The data demonstrated clear and lasting benefit of treatment for pain reduction and functional outcomes at 3 months, creating great optimism for the long-term study results. These findings represent a significant advancement for an at-risk and underserved patient population in desperate need of reliable and effective treatment.”

SOURCE:

The study was led by Leonardo Kapural, MD, PhD, of the Carolinas Pain Institute in Winston-Salem, North Carolina, and was published online in the Journal of Pain Research.

LIMITATIONS:

The sample size of 180 participants may limit the generalizability of the findings to all amputees. A 3-month duration for assessing treatment efficacy may not capture long-term outcomes and effects. The active-sham control design, while rigorous, may not fully account for the placebo effects inherent in pain perception studies.

DISCLOSURES:

The QUEST study was funded by Neuros Medical Inc. Dr. Kapural reported personal fees from various medical companies, unrelated to this work. No other conflicts of interest were reported in this work.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article appeared on Medscape.com.

Among people diagnosed with cutaneous melanoma in the United States, those who live in rural areas have significantly lower rates of survival than those who live in urban areas, results from an analysis of data from the National Cancer Institute showed.

“Melanoma is currently the fifth most common malignancy in the United States, with approximately 106,000 new cases and 7180 reported deaths occurring in 2021,” the study’s first author, Mitchell Taylor, MD, a dermatology research fellow at the University of Nebraska, Omaha, and colleagues wrote in the abstract, which was presented during a poster session at the annual meeting of the Society for Investigative Dermatology. “Rural areas have been shown to bear a higher melanoma disease burden, yet there is a paucity of national-level studies examining these disparities.”

To characterize the rural population diagnosed with cutaneous melanoma and assess associated disparities in the United States, the researchers queried the NCI’s Surveillance, Epidemiology, and End Results database to identify individuals diagnosed with cutaneous melanoma from 2000 to 2020 (International Classification of Diseases, 3rd Edition, 8720/3 — 8780/3; Primary Site codes C44.0-C44.9). They drew from US Office of Management and Budget terminology to define and categorize rural and urban communities.

Among 391,047 patients included during the study period, binary logistic regression analysis revealed that patients in rural areas had a greater odds of being older, from ages 50 to 75 years (odds ratio [OR], 1.10; P < .001); had annual incomes < $70,000 (OR, 16.80; P < .001); had tumors located on the head and neck (OR, 1.24; P < .001); and presented with regional/distant disease (OR, 1.13; P < .001).

As for disease-specific survival, patients living in rural areas had significantly reduced survival compared with those living in urban areas (a mean of 207.3 vs 216.3 months, respectively; P < .001). Multivariate Cox regression revealed that living in a rural setting was significantly associated with reduced disease-specific survival (hazard ratio [HR], 1.10; P < .001), as was having head and neck tumors (HR, 1.41; P < .001).“Overall, this study underscores a significant decrease in disease-specific survival among rural patients diagnosed with cutaneous melanoma and establishes a significant association between rural living and high-risk primary tumor locations, particularly the head and neck,” the authors concluded.

Lucinda Kohn, MD, assistant professor of dermatology in the Centers for American Indian and Alaska Native Health at the University of Colorado at Denver, Aurora, Colorado, who was asked to comment on the results, said the findings echo the results of a recent study which characterized melanoma rates among non-Hispanic American Indian/Alaska Native individuals from 1999 to 2019.

“I suspect this decreased disease-specific survival highlights the issues our rural-residing patients face with access to dermatology care,” Dr. Kohn told this news organization. “Dermatologists are able to detect thinner melanomas than patients [and] are preferentially concentrated in metropolitan areas. Dermatologists are also the most skilled and knowledgeable to screen, diagnose, and manage melanomas. Having fewer dermatologists in rural areas impedes melanoma care for our rural-residing patients.”

Neither the researchers nor Dr. Kohn reported any relevant disclosures.

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

Among people diagnosed with cutaneous melanoma in the United States, those who live in rural areas have significantly lower rates of survival than those who live in urban areas, results from an analysis of data from the National Cancer Institute showed.

“Melanoma is currently the fifth most common malignancy in the United States, with approximately 106,000 new cases and 7180 reported deaths occurring in 2021,” the study’s first author, Mitchell Taylor, MD, a dermatology research fellow at the University of Nebraska, Omaha, and colleagues wrote in the abstract, which was presented during a poster session at the annual meeting of the Society for Investigative Dermatology. “Rural areas have been shown to bear a higher melanoma disease burden, yet there is a paucity of national-level studies examining these disparities.”

To characterize the rural population diagnosed with cutaneous melanoma and assess associated disparities in the United States, the researchers queried the NCI’s Surveillance, Epidemiology, and End Results database to identify individuals diagnosed with cutaneous melanoma from 2000 to 2020 (International Classification of Diseases, 3rd Edition, 8720/3 — 8780/3; Primary Site codes C44.0-C44.9). They drew from US Office of Management and Budget terminology to define and categorize rural and urban communities.

Among 391,047 patients included during the study period, binary logistic regression analysis revealed that patients in rural areas had a greater odds of being older, from ages 50 to 75 years (odds ratio [OR], 1.10; P < .001); had annual incomes < $70,000 (OR, 16.80; P < .001); had tumors located on the head and neck (OR, 1.24; P < .001); and presented with regional/distant disease (OR, 1.13; P < .001).

As for disease-specific survival, patients living in rural areas had significantly reduced survival compared with those living in urban areas (a mean of 207.3 vs 216.3 months, respectively; P < .001). Multivariate Cox regression revealed that living in a rural setting was significantly associated with reduced disease-specific survival (hazard ratio [HR], 1.10; P < .001), as was having head and neck tumors (HR, 1.41; P < .001).“Overall, this study underscores a significant decrease in disease-specific survival among rural patients diagnosed with cutaneous melanoma and establishes a significant association between rural living and high-risk primary tumor locations, particularly the head and neck,” the authors concluded.

Lucinda Kohn, MD, assistant professor of dermatology in the Centers for American Indian and Alaska Native Health at the University of Colorado at Denver, Aurora, Colorado, who was asked to comment on the results, said the findings echo the results of a recent study which characterized melanoma rates among non-Hispanic American Indian/Alaska Native individuals from 1999 to 2019.

“I suspect this decreased disease-specific survival highlights the issues our rural-residing patients face with access to dermatology care,” Dr. Kohn told this news organization. “Dermatologists are able to detect thinner melanomas than patients [and] are preferentially concentrated in metropolitan areas. Dermatologists are also the most skilled and knowledgeable to screen, diagnose, and manage melanomas. Having fewer dermatologists in rural areas impedes melanoma care for our rural-residing patients.”

Neither the researchers nor Dr. Kohn reported any relevant disclosures.

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

Among people diagnosed with cutaneous melanoma in the United States, those who live in rural areas have significantly lower rates of survival than those who live in urban areas, results from an analysis of data from the National Cancer Institute showed.

“Melanoma is currently the fifth most common malignancy in the United States, with approximately 106,000 new cases and 7180 reported deaths occurring in 2021,” the study’s first author, Mitchell Taylor, MD, a dermatology research fellow at the University of Nebraska, Omaha, and colleagues wrote in the abstract, which was presented during a poster session at the annual meeting of the Society for Investigative Dermatology. “Rural areas have been shown to bear a higher melanoma disease burden, yet there is a paucity of national-level studies examining these disparities.”

To characterize the rural population diagnosed with cutaneous melanoma and assess associated disparities in the United States, the researchers queried the NCI’s Surveillance, Epidemiology, and End Results database to identify individuals diagnosed with cutaneous melanoma from 2000 to 2020 (International Classification of Diseases, 3rd Edition, 8720/3 — 8780/3; Primary Site codes C44.0-C44.9). They drew from US Office of Management and Budget terminology to define and categorize rural and urban communities.

Among 391,047 patients included during the study period, binary logistic regression analysis revealed that patients in rural areas had a greater odds of being older, from ages 50 to 75 years (odds ratio [OR], 1.10; P < .001); had annual incomes < $70,000 (OR, 16.80; P < .001); had tumors located on the head and neck (OR, 1.24; P < .001); and presented with regional/distant disease (OR, 1.13; P < .001).

As for disease-specific survival, patients living in rural areas had significantly reduced survival compared with those living in urban areas (a mean of 207.3 vs 216.3 months, respectively; P < .001). Multivariate Cox regression revealed that living in a rural setting was significantly associated with reduced disease-specific survival (hazard ratio [HR], 1.10; P < .001), as was having head and neck tumors (HR, 1.41; P < .001).“Overall, this study underscores a significant decrease in disease-specific survival among rural patients diagnosed with cutaneous melanoma and establishes a significant association between rural living and high-risk primary tumor locations, particularly the head and neck,” the authors concluded.

Lucinda Kohn, MD, assistant professor of dermatology in the Centers for American Indian and Alaska Native Health at the University of Colorado at Denver, Aurora, Colorado, who was asked to comment on the results, said the findings echo the results of a recent study which characterized melanoma rates among non-Hispanic American Indian/Alaska Native individuals from 1999 to 2019.

“I suspect this decreased disease-specific survival highlights the issues our rural-residing patients face with access to dermatology care,” Dr. Kohn told this news organization. “Dermatologists are able to detect thinner melanomas than patients [and] are preferentially concentrated in metropolitan areas. Dermatologists are also the most skilled and knowledgeable to screen, diagnose, and manage melanomas. Having fewer dermatologists in rural areas impedes melanoma care for our rural-residing patients.”

Neither the researchers nor Dr. Kohn reported any relevant disclosures.

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

TOPLINE:

Some vulnerable older patients with untreated metastatic pancreatic cancer can benefit from chemotherapy, but only if they can tolerate enough cycles of treatment, according to results of the randomized phase 2 GIANT study.

METHODOLOGY:

Pancreatic cancer is most often diagnosed in adults aged 65 years or older. Providing cancer treatment for this older, often vulnerable, population comes with significant challenges and can lead to worse survival.

To examine real-world outcomes of older adults with untreated metastatic pancreatic cancer, researchers recruited patients aged 70 years or older and performed a geriatric assessment to identify comorbidities, cognitive issues, and other geriatric abnormalities.

Those who were deemed “fit” (ie, with no geriatric abnormalities) were assigned to receive off-study standard-of-care treatment, whereas those classified as “frail” (ie, with severe abnormalities) received off-study supportive care.

The remaining 176 “vulnerable” patients with mild to moderate geriatric abnormalities completed a geriatric and quality-of-life assessment and were then randomly assigned to receive either dose-reduced 5-fluorouracil (5-FU), leucovorin plus liposomal irinotecan (n = 88) or modified gemcitabine plus nab-paclitaxel (n = 88) every 2 weeks. Ultimately, 79 patients started the 5-FU combination and 75 received gemcitabine plus nab-paclitaxel. Patients were assessed every 8 weeks until disease progression or intolerance.

Overall, patients had a median age of 77 years; 61.9% were aged 75 years or older. About half were female, and 81.5% were White. The majority (87.5%) had a performance status of 0 or 1.

TAKEAWAY:

• Median overall survival was 4.7 months in the gemcitabine plus nab-paclitaxel arm and 4.4 months in the 5-FU combination group, with no significant survival difference observed between the two arms (P = .72).
• When the overall survival analysis was restricted to patients who received at least 4 weeks, or two cycles, of treatment (about 62% of patients), the median overall survival across the two treatment arms reached 8.0 months, in line with expectations for these regimens.
• Patient stratification revealed that those with a performance status of 2 had significantly worse overall survival than those with a status of 0: 1.4 months vs 6.9 months, respectively (hazard ratio [HR], 2.77; P < .001). A similar divide was seen when patients were stratified by physical/functional status and well-being. Age, however, did not significantly influence the results.
• Overall, more than half of patients experienced grade 3 or higher adverse events. Just over 38% of patients received only one to three cycles of therapy, whereas 26% remained on treatment for 12 or more cycles. The adverse event rates were similar between the two regimens, but the toxicity profile was slightly different — the researchers, for instance, observed more peripheral neuropathy with gemcitabine plus nab-paclitaxel and more diarrhea in the 5-FU combination arm.

IN PRACTICE:

• Overall, the “survival outcomes among vulnerable older patients were lower than expected, with high percentage of patients not able to start treatment, or complete one month of therapy due to clinical deterioration,” said study presenter Efrat Dotan, MD, chief, Division of Gastrointestinal Medical Oncology, Fox Chase Cancer Center, Philadelphia. 
• “For vulnerable older adults who can tolerate treatment, these two regimens provide clinicians with options for tailoring therapy based on toxicity profile,” Dr. Dotan added. But “tools are needed to better identify patients who can benefit from treatment.”
• The results underline the need to perform geriatric assessments, as opposed to merely looking at performance status, commented David F. Chang, PhD, MS, MBBS, professor of Surgical Oncology, University of Glasgow, Scotland, who was not involved in the study. 

SOURCE:

The research, presented at the 2024 annual meeting of the American Society of Clinical Oncology, was funded by the National Cancer Institute and the Eastern Cooperative Oncology Group.

LIMITATIONS:

Dr. Chang noted that the study did not reveal which treatment regimen was more effective.

DISCLOSURES:

Dr. Dotan declared relationships with Agenus, Amgen, G1 Therapeutics, Incyte, Olympus, and Taiho Pharmaceutical and institutional relationships with Dragonfly Therapeutics, Gilead Sciences, Ipsen, Kinnate Biopharma, Leap Therapeutics, Lilly, Lutris, NGM Biopharmaceuticals, Relay Therapeutics, and Zymeworks. Dr. Chang declared relationships with Immodulon Therapeutics and Mylan and institutional relationships with AstraZeneca, BMS GmbH & Co. KG, Immodulon Therapeutics, and Merck.

A version of this article appeared on Medscape.com.

TOPLINE:

Some vulnerable older patients with untreated metastatic pancreatic cancer can benefit from chemotherapy, but only if they can tolerate enough cycles of treatment, according to results of the randomized phase 2 GIANT study.

METHODOLOGY:

Pancreatic cancer is most often diagnosed in adults aged 65 years or older. Providing cancer treatment for this older, often vulnerable, population comes with significant challenges and can lead to worse survival.

To examine real-world outcomes of older adults with untreated metastatic pancreatic cancer, researchers recruited patients aged 70 years or older and performed a geriatric assessment to identify comorbidities, cognitive issues, and other geriatric abnormalities.

Those who were deemed “fit” (ie, with no geriatric abnormalities) were assigned to receive off-study standard-of-care treatment, whereas those classified as “frail” (ie, with severe abnormalities) received off-study supportive care.

The remaining 176 “vulnerable” patients with mild to moderate geriatric abnormalities completed a geriatric and quality-of-life assessment and were then randomly assigned to receive either dose-reduced 5-fluorouracil (5-FU), leucovorin plus liposomal irinotecan (n = 88) or modified gemcitabine plus nab-paclitaxel (n = 88) every 2 weeks. Ultimately, 79 patients started the 5-FU combination and 75 received gemcitabine plus nab-paclitaxel. Patients were assessed every 8 weeks until disease progression or intolerance.

Overall, patients had a median age of 77 years; 61.9% were aged 75 years or older. About half were female, and 81.5% were White. The majority (87.5%) had a performance status of 0 or 1.

TAKEAWAY:

• Median overall survival was 4.7 months in the gemcitabine plus nab-paclitaxel arm and 4.4 months in the 5-FU combination group, with no significant survival difference observed between the two arms (P = .72).
• When the overall survival analysis was restricted to patients who received at least 4 weeks, or two cycles, of treatment (about 62% of patients), the median overall survival across the two treatment arms reached 8.0 months, in line with expectations for these regimens.
• Patient stratification revealed that those with a performance status of 2 had significantly worse overall survival than those with a status of 0: 1.4 months vs 6.9 months, respectively (hazard ratio [HR], 2.77; P < .001). A similar divide was seen when patients were stratified by physical/functional status and well-being. Age, however, did not significantly influence the results.
• Overall, more than half of patients experienced grade 3 or higher adverse events. Just over 38% of patients received only one to three cycles of therapy, whereas 26% remained on treatment for 12 or more cycles. The adverse event rates were similar between the two regimens, but the toxicity profile was slightly different — the researchers, for instance, observed more peripheral neuropathy with gemcitabine plus nab-paclitaxel and more diarrhea in the 5-FU combination arm.

IN PRACTICE:

• Overall, the “survival outcomes among vulnerable older patients were lower than expected, with high percentage of patients not able to start treatment, or complete one month of therapy due to clinical deterioration,” said study presenter Efrat Dotan, MD, chief, Division of Gastrointestinal Medical Oncology, Fox Chase Cancer Center, Philadelphia. 
• “For vulnerable older adults who can tolerate treatment, these two regimens provide clinicians with options for tailoring therapy based on toxicity profile,” Dr. Dotan added. But “tools are needed to better identify patients who can benefit from treatment.”
• The results underline the need to perform geriatric assessments, as opposed to merely looking at performance status, commented David F. Chang, PhD, MS, MBBS, professor of Surgical Oncology, University of Glasgow, Scotland, who was not involved in the study. 

SOURCE:

The research, presented at the 2024 annual meeting of the American Society of Clinical Oncology, was funded by the National Cancer Institute and the Eastern Cooperative Oncology Group.

LIMITATIONS:

Dr. Chang noted that the study did not reveal which treatment regimen was more effective.

DISCLOSURES:

Dr. Dotan declared relationships with Agenus, Amgen, G1 Therapeutics, Incyte, Olympus, and Taiho Pharmaceutical and institutional relationships with Dragonfly Therapeutics, Gilead Sciences, Ipsen, Kinnate Biopharma, Leap Therapeutics, Lilly, Lutris, NGM Biopharmaceuticals, Relay Therapeutics, and Zymeworks. Dr. Chang declared relationships with Immodulon Therapeutics and Mylan and institutional relationships with AstraZeneca, BMS GmbH & Co. KG, Immodulon Therapeutics, and Merck.

A version of this article appeared on Medscape.com.

TOPLINE:

Some vulnerable older patients with untreated metastatic pancreatic cancer can benefit from chemotherapy, but only if they can tolerate enough cycles of treatment, according to results of the randomized phase 2 GIANT study.

METHODOLOGY:

Pancreatic cancer is most often diagnosed in adults aged 65 years or older. Providing cancer treatment for this older, often vulnerable, population comes with significant challenges and can lead to worse survival.

To examine real-world outcomes of older adults with untreated metastatic pancreatic cancer, researchers recruited patients aged 70 years or older and performed a geriatric assessment to identify comorbidities, cognitive issues, and other geriatric abnormalities.

Those who were deemed “fit” (ie, with no geriatric abnormalities) were assigned to receive off-study standard-of-care treatment, whereas those classified as “frail” (ie, with severe abnormalities) received off-study supportive care.

The remaining 176 “vulnerable” patients with mild to moderate geriatric abnormalities completed a geriatric and quality-of-life assessment and were then randomly assigned to receive either dose-reduced 5-fluorouracil (5-FU), leucovorin plus liposomal irinotecan (n = 88) or modified gemcitabine plus nab-paclitaxel (n = 88) every 2 weeks. Ultimately, 79 patients started the 5-FU combination and 75 received gemcitabine plus nab-paclitaxel. Patients were assessed every 8 weeks until disease progression or intolerance.

Overall, patients had a median age of 77 years; 61.9% were aged 75 years or older. About half were female, and 81.5% were White. The majority (87.5%) had a performance status of 0 or 1.

TAKEAWAY:

• Median overall survival was 4.7 months in the gemcitabine plus nab-paclitaxel arm and 4.4 months in the 5-FU combination group, with no significant survival difference observed between the two arms (P = .72).
• When the overall survival analysis was restricted to patients who received at least 4 weeks, or two cycles, of treatment (about 62% of patients), the median overall survival across the two treatment arms reached 8.0 months, in line with expectations for these regimens.
• Patient stratification revealed that those with a performance status of 2 had significantly worse overall survival than those with a status of 0: 1.4 months vs 6.9 months, respectively (hazard ratio [HR], 2.77; P < .001). A similar divide was seen when patients were stratified by physical/functional status and well-being. Age, however, did not significantly influence the results.
• Overall, more than half of patients experienced grade 3 or higher adverse events. Just over 38% of patients received only one to three cycles of therapy, whereas 26% remained on treatment for 12 or more cycles. The adverse event rates were similar between the two regimens, but the toxicity profile was slightly different — the researchers, for instance, observed more peripheral neuropathy with gemcitabine plus nab-paclitaxel and more diarrhea in the 5-FU combination arm.

IN PRACTICE:

• Overall, the “survival outcomes among vulnerable older patients were lower than expected, with high percentage of patients not able to start treatment, or complete one month of therapy due to clinical deterioration,” said study presenter Efrat Dotan, MD, chief, Division of Gastrointestinal Medical Oncology, Fox Chase Cancer Center, Philadelphia. 
• “For vulnerable older adults who can tolerate treatment, these two regimens provide clinicians with options for tailoring therapy based on toxicity profile,” Dr. Dotan added. But “tools are needed to better identify patients who can benefit from treatment.”
• The results underline the need to perform geriatric assessments, as opposed to merely looking at performance status, commented David F. Chang, PhD, MS, MBBS, professor of Surgical Oncology, University of Glasgow, Scotland, who was not involved in the study. 

SOURCE:

The research, presented at the 2024 annual meeting of the American Society of Clinical Oncology, was funded by the National Cancer Institute and the Eastern Cooperative Oncology Group.

LIMITATIONS:

Dr. Chang noted that the study did not reveal which treatment regimen was more effective.

DISCLOSURES:

Dr. Dotan declared relationships with Agenus, Amgen, G1 Therapeutics, Incyte, Olympus, and Taiho Pharmaceutical and institutional relationships with Dragonfly Therapeutics, Gilead Sciences, Ipsen, Kinnate Biopharma, Leap Therapeutics, Lilly, Lutris, NGM Biopharmaceuticals, Relay Therapeutics, and Zymeworks. Dr. Chang declared relationships with Immodulon Therapeutics and Mylan and institutional relationships with AstraZeneca, BMS GmbH & Co. KG, Immodulon Therapeutics, and Merck.

A version of this article appeared on Medscape.com.