Ob.Gyn. News

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

TOPLINE: 

Despite the risk of worsening acne with progestin-only long-acting reversible contraception (LARC) in a study of adolescents and young adults, acne alone was not a common reason for discontinuation.

METHODOLOGY:

• Progestin-only LARC may increase the risk for acne, but this has not been well studied in adolescents and young adults.
• In the study, researchers evaluated the incidence of acne, acne as a reason for removal, and strategies used to manage acne after insertion of a progestin-only intrauterine device (IUD) or contraceptive implant in 1319 adolescents and young adults across four Adolescent Medicine LARC Collaborative study sites from January 2017 to June 2021.The mean age at insertion was 18.6 years.
• Overall, 24% of participants had acne at the time of LARC insertion.
• Worsening acne was defined as new patient reports of concern about acne, observations of acne, or addition of an acne medication after insertion; increased severity noted on an exam during follow-up or at the time of LARC removal; or acne reported as a side effect and/or reason for LARC removal.

TAKEAWAY: 

• During the study period, 376 participants (28.5%) experienced worsening acne after LARC insertion, and 17% reported acne as a new concern, with no differences between those who received an IUD or an implant.
• Only 44 of the 376 participants (11.7%) who reported worsening acne were being treated with an oral agent at follow-up.
• Of the 542 individuals (41% of the total) who had the LARC device removed, 40 (7.4%) cited concerns about acne for removing the device, although just 5 (0.92%) said that acne was the only reason for removal. Of the 40 with concerns about acne when the device was removed, 18 (45%) had documented acne at the time of insertion.

IN PRACTICE:

The authors recommend that clinicians prescribing progestin-only LARC should counsel patients that acne may be a side effect, reassuring them that if they develop acne, “it typically is not problematic enough to warrant discontinuation,” and concluded that “concerns about the development or worsening of acne should not be cause to avoid these forms of contraception.”

SOURCE:

The study, led by Markus D. Boos, MD, PhD, of the division of dermatology in the Department of Pediatrics, University of Washington in Seattle and Seattle Children’s Hospital, was published in Pediatric Dermatology.

LIMITATIONS:

Individuals without documented acne were assumed to be acne-free, creating potential bias. Acne evaluation and treatment were not standardized and were not performed by dermatologists; acne severity was not recorded for many participants, possibly underestimating severity, and excluding LARC insertions without follow-up or with removal within 8 weeks may have underestimated the percentage of participants who developed new or worsening acne.

DISCLOSURES: 

The study was supported by Investigator-Initiated Studies Program of Organon and by the Health Resources and Services Administration of the US Department of Health and Human Services. Many authors received grants for this work. The authors did not disclose any other competing interests.

A version of this article appeared on Medscape.com.

TOPLINE: 

Despite the risk of worsening acne with progestin-only long-acting reversible contraception (LARC) in a study of adolescents and young adults, acne alone was not a common reason for discontinuation.

METHODOLOGY:

• Progestin-only LARC may increase the risk for acne, but this has not been well studied in adolescents and young adults.
• In the study, researchers evaluated the incidence of acne, acne as a reason for removal, and strategies used to manage acne after insertion of a progestin-only intrauterine device (IUD) or contraceptive implant in 1319 adolescents and young adults across four Adolescent Medicine LARC Collaborative study sites from January 2017 to June 2021.The mean age at insertion was 18.6 years.
• Overall, 24% of participants had acne at the time of LARC insertion.
• Worsening acne was defined as new patient reports of concern about acne, observations of acne, or addition of an acne medication after insertion; increased severity noted on an exam during follow-up or at the time of LARC removal; or acne reported as a side effect and/or reason for LARC removal.

TAKEAWAY: 

• During the study period, 376 participants (28.5%) experienced worsening acne after LARC insertion, and 17% reported acne as a new concern, with no differences between those who received an IUD or an implant.
• Only 44 of the 376 participants (11.7%) who reported worsening acne were being treated with an oral agent at follow-up.
• Of the 542 individuals (41% of the total) who had the LARC device removed, 40 (7.4%) cited concerns about acne for removing the device, although just 5 (0.92%) said that acne was the only reason for removal. Of the 40 with concerns about acne when the device was removed, 18 (45%) had documented acne at the time of insertion.

IN PRACTICE:

The authors recommend that clinicians prescribing progestin-only LARC should counsel patients that acne may be a side effect, reassuring them that if they develop acne, “it typically is not problematic enough to warrant discontinuation,” and concluded that “concerns about the development or worsening of acne should not be cause to avoid these forms of contraception.”

SOURCE:

The study, led by Markus D. Boos, MD, PhD, of the division of dermatology in the Department of Pediatrics, University of Washington in Seattle and Seattle Children’s Hospital, was published in Pediatric Dermatology.

LIMITATIONS:

Individuals without documented acne were assumed to be acne-free, creating potential bias. Acne evaluation and treatment were not standardized and were not performed by dermatologists; acne severity was not recorded for many participants, possibly underestimating severity, and excluding LARC insertions without follow-up or with removal within 8 weeks may have underestimated the percentage of participants who developed new or worsening acne.

DISCLOSURES: 

The study was supported by Investigator-Initiated Studies Program of Organon and by the Health Resources and Services Administration of the US Department of Health and Human Services. Many authors received grants for this work. The authors did not disclose any other competing interests.

A version of this article appeared on Medscape.com.

TOPLINE: 

Despite the risk of worsening acne with progestin-only long-acting reversible contraception (LARC) in a study of adolescents and young adults, acne alone was not a common reason for discontinuation.

METHODOLOGY:

• Progestin-only LARC may increase the risk for acne, but this has not been well studied in adolescents and young adults.
• In the study, researchers evaluated the incidence of acne, acne as a reason for removal, and strategies used to manage acne after insertion of a progestin-only intrauterine device (IUD) or contraceptive implant in 1319 adolescents and young adults across four Adolescent Medicine LARC Collaborative study sites from January 2017 to June 2021.The mean age at insertion was 18.6 years.
• Overall, 24% of participants had acne at the time of LARC insertion.
• Worsening acne was defined as new patient reports of concern about acne, observations of acne, or addition of an acne medication after insertion; increased severity noted on an exam during follow-up or at the time of LARC removal; or acne reported as a side effect and/or reason for LARC removal.

TAKEAWAY: 

• During the study period, 376 participants (28.5%) experienced worsening acne after LARC insertion, and 17% reported acne as a new concern, with no differences between those who received an IUD or an implant.
• Only 44 of the 376 participants (11.7%) who reported worsening acne were being treated with an oral agent at follow-up.
• Of the 542 individuals (41% of the total) who had the LARC device removed, 40 (7.4%) cited concerns about acne for removing the device, although just 5 (0.92%) said that acne was the only reason for removal. Of the 40 with concerns about acne when the device was removed, 18 (45%) had documented acne at the time of insertion.

IN PRACTICE:

The authors recommend that clinicians prescribing progestin-only LARC should counsel patients that acne may be a side effect, reassuring them that if they develop acne, “it typically is not problematic enough to warrant discontinuation,” and concluded that “concerns about the development or worsening of acne should not be cause to avoid these forms of contraception.”

SOURCE:

The study, led by Markus D. Boos, MD, PhD, of the division of dermatology in the Department of Pediatrics, University of Washington in Seattle and Seattle Children’s Hospital, was published in Pediatric Dermatology.

LIMITATIONS:

Individuals without documented acne were assumed to be acne-free, creating potential bias. Acne evaluation and treatment were not standardized and were not performed by dermatologists; acne severity was not recorded for many participants, possibly underestimating severity, and excluding LARC insertions without follow-up or with removal within 8 weeks may have underestimated the percentage of participants who developed new or worsening acne.

DISCLOSURES: 

The study was supported by Investigator-Initiated Studies Program of Organon and by the Health Resources and Services Administration of the US Department of Health and Human Services. Many authors received grants for this work. The authors did not disclose any other competing interests.

A version of this article appeared on Medscape.com.

Circulating tumor DNA (ctDNA) testing may serve as an early predictor of response to radiotherapy or chemoradiotherapy in patients with gynecologic cancers, results of a small study suggest.

Among 15 patients with vulvar, cervical, or endometrial malignancies who had serum ctDNA draws prior to, during, and after radiation therapy (RT) or chemoradiotherapy (CRT), both persistence or clearance of residual ctDNA were prognostic of patient outcomes from 3 to 6 months after the end of radiation therapy, reported A. Gabriella Wernicke, MD, MSc, a radiation oncologist at Lenox Hill Hospital in New York City.

“Our early findings in this limited cohort suggest that a mid-treatment ctDNA draw identified responders to radiation, and that may potentially serve as an early predictive biomarker of response. And clearly, these findings need to be validated in a prospective manner, a trial which will be starting in our center soon,” she said in an oral abstract session at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer, held in San Diego, California.

Gynecologic malignancies are challenging to manage with radiotherapy because of the treatment’s toxicities and because outcomes may not be known until several months after the end of therapy. Early identification of responses to radiation therapy with simple blood draws has the potential to help clinicians identify those patients whose tumors are responding to radiation early in the course of therapy, she said.
 

Correlating treatment with responses

Dr. Wernicke and colleagues tested their hypothesis that the ctDNA is predictive of treatment response in patients receiving RT or CRT by retrospectively assessing the correlation of clinical responses to ctDNA detection and dynamics.

Their sample included 15 women with vulvar, cervical, or recurrent endometrial cancer who were treated with RT or CRT in 2022 and 2023.

The samples were collected prior to radiation therapy, mid-treatment, prior to boost dose with brachytherapy or stereotactic body radiation therapy, at the end of treatment, and at follow-up at 1, 3, and 6 months after the end of therapy and every 6 months thereafter.

The ctDNA analysis was performed with a personalized assay consisting of multiplex polymerase chain reaction and next-generation sequencing. The assays assessed clonal mutations found in the tumors of each patient.

Of the 15 patients, 5 had vulvar/vaginal tumors, all of squamous cell carcinoma histology. Six patients had squamous cell carcinoma of the cervix, and one had neuroendocrine cervical tumors. The two remaining patients had recurrent endometrial adenocarcinomas.

Eight of the patients had stage III disease, four had stage I or II, one had stage IV, and two had recurrent disease.
 

Results

At baseline 13 of the patients had detectable ctDNA, measured as greater than 0.00 mean tumor molecules per milliliter of plasma (MTM/mL).

There was a strong correlation between elevated ctDNA and measurable disease evaluated by standardized uptake values (SUV) on imaging pre treatment (correlation coefficient = 0.87, P less than .0001).

All patients had reductions in ctDNA from baseline to post-RT/CRT, with 2 having a reduction (partial metabolic response) and 13 having undetectable ctDNA (complete metabolic response) at the end of RT/CRT.

From the mid-treatment blood draw to the posttreatment draw 33% of patients had a partial metabolic response, and 67% had a complete response.

Reduction or clearance of ctDNA also correlated with a decrease in disease burden on MRI during the pre-boost phase of RT.

“Patients with undetectable ctDNA, meaning a complete metabolic response, at mid-radiation and at the end of radiation continued to be clinically without evidence of disease and with undetectable ctDNA at follow-up,” Dr. Wernicke said.

In contrast, the two patients who had partial metabolic responses had disease progression at the end of treatment. Dr. Wernicke noted that one of these patients, who was treated for a neuroendocrine carcinoma of the cervix and had undergone both systemic therapy and CRT, was found to have disease metastatic to the liver and lungs at the 3-month follow-up.
 

How to Use It?

Invited discussant Casey M. Cosgrove, MD, a gynecologic oncologist at Ohio State University Comprehensive Cancer Centers facility in Hilliard, Ohio, said that the reduction of ctDNA levels in all patients was “great,” but the question remains about how the information from ctDNA might be used to guide care in patients undergoing radiation therapy.

“The main questions I have are: If I don’t clear the ctDNA do I need to do more therapy? If I do clear does that mean I need to do less therapy? And if I have negative ctDNA to start what do I do?” he said.

The answers will be found only with further prospective studies, he emphasized.

“These technologies are only going to get better, and better, and better, and this is going to be a conversation that our patients are going to be bringing up, and this is going to be technology that we’re going to be using in our clinics in the very near future,” he added.

Session comoderator Michael Bookman, MD, a gynecology oncologist at Kaiser Permanente in San Francisco, said “it’s worth remembering that FDA approval of a diagnostic test can be obtained prior to showing any clinical benefit. So these are tests that measure what they say they’re measuring, but they haven’t been validated as improving clinical outcomes, which is the task that clearly lies ahead of us.”

The study was internally funded. Dr. Wernicke reported no relevant disclosures. Dr. Cosgrove reported a consulting or advisory role for Intuitive Ltd., GlaxoSmithKline, AstraZeneca, ImmunoGen, and Merck, and research fees from GSK. Dr. Bookman reported clinical trial advising/monitoring for Immunogen and Clovis Oncology, with fees paid to his institution.

Circulating tumor DNA (ctDNA) testing may serve as an early predictor of response to radiotherapy or chemoradiotherapy in patients with gynecologic cancers, results of a small study suggest.

Among 15 patients with vulvar, cervical, or endometrial malignancies who had serum ctDNA draws prior to, during, and after radiation therapy (RT) or chemoradiotherapy (CRT), both persistence or clearance of residual ctDNA were prognostic of patient outcomes from 3 to 6 months after the end of radiation therapy, reported A. Gabriella Wernicke, MD, MSc, a radiation oncologist at Lenox Hill Hospital in New York City.

“Our early findings in this limited cohort suggest that a mid-treatment ctDNA draw identified responders to radiation, and that may potentially serve as an early predictive biomarker of response. And clearly, these findings need to be validated in a prospective manner, a trial which will be starting in our center soon,” she said in an oral abstract session at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer, held in San Diego, California.

Gynecologic malignancies are challenging to manage with radiotherapy because of the treatment’s toxicities and because outcomes may not be known until several months after the end of therapy. Early identification of responses to radiation therapy with simple blood draws has the potential to help clinicians identify those patients whose tumors are responding to radiation early in the course of therapy, she said.
 

Correlating treatment with responses

Dr. Wernicke and colleagues tested their hypothesis that the ctDNA is predictive of treatment response in patients receiving RT or CRT by retrospectively assessing the correlation of clinical responses to ctDNA detection and dynamics.

Their sample included 15 women with vulvar, cervical, or recurrent endometrial cancer who were treated with RT or CRT in 2022 and 2023.

The samples were collected prior to radiation therapy, mid-treatment, prior to boost dose with brachytherapy or stereotactic body radiation therapy, at the end of treatment, and at follow-up at 1, 3, and 6 months after the end of therapy and every 6 months thereafter.

The ctDNA analysis was performed with a personalized assay consisting of multiplex polymerase chain reaction and next-generation sequencing. The assays assessed clonal mutations found in the tumors of each patient.

Of the 15 patients, 5 had vulvar/vaginal tumors, all of squamous cell carcinoma histology. Six patients had squamous cell carcinoma of the cervix, and one had neuroendocrine cervical tumors. The two remaining patients had recurrent endometrial adenocarcinomas.

Eight of the patients had stage III disease, four had stage I or II, one had stage IV, and two had recurrent disease.
 

Results

At baseline 13 of the patients had detectable ctDNA, measured as greater than 0.00 mean tumor molecules per milliliter of plasma (MTM/mL).

There was a strong correlation between elevated ctDNA and measurable disease evaluated by standardized uptake values (SUV) on imaging pre treatment (correlation coefficient = 0.87, P less than .0001).

All patients had reductions in ctDNA from baseline to post-RT/CRT, with 2 having a reduction (partial metabolic response) and 13 having undetectable ctDNA (complete metabolic response) at the end of RT/CRT.

From the mid-treatment blood draw to the posttreatment draw 33% of patients had a partial metabolic response, and 67% had a complete response.

Reduction or clearance of ctDNA also correlated with a decrease in disease burden on MRI during the pre-boost phase of RT.

“Patients with undetectable ctDNA, meaning a complete metabolic response, at mid-radiation and at the end of radiation continued to be clinically without evidence of disease and with undetectable ctDNA at follow-up,” Dr. Wernicke said.

In contrast, the two patients who had partial metabolic responses had disease progression at the end of treatment. Dr. Wernicke noted that one of these patients, who was treated for a neuroendocrine carcinoma of the cervix and had undergone both systemic therapy and CRT, was found to have disease metastatic to the liver and lungs at the 3-month follow-up.
 

How to Use It?

Invited discussant Casey M. Cosgrove, MD, a gynecologic oncologist at Ohio State University Comprehensive Cancer Centers facility in Hilliard, Ohio, said that the reduction of ctDNA levels in all patients was “great,” but the question remains about how the information from ctDNA might be used to guide care in patients undergoing radiation therapy.

“The main questions I have are: If I don’t clear the ctDNA do I need to do more therapy? If I do clear does that mean I need to do less therapy? And if I have negative ctDNA to start what do I do?” he said.

The answers will be found only with further prospective studies, he emphasized.

“These technologies are only going to get better, and better, and better, and this is going to be a conversation that our patients are going to be bringing up, and this is going to be technology that we’re going to be using in our clinics in the very near future,” he added.

Session comoderator Michael Bookman, MD, a gynecology oncologist at Kaiser Permanente in San Francisco, said “it’s worth remembering that FDA approval of a diagnostic test can be obtained prior to showing any clinical benefit. So these are tests that measure what they say they’re measuring, but they haven’t been validated as improving clinical outcomes, which is the task that clearly lies ahead of us.”

The study was internally funded. Dr. Wernicke reported no relevant disclosures. Dr. Cosgrove reported a consulting or advisory role for Intuitive Ltd., GlaxoSmithKline, AstraZeneca, ImmunoGen, and Merck, and research fees from GSK. Dr. Bookman reported clinical trial advising/monitoring for Immunogen and Clovis Oncology, with fees paid to his institution.

Circulating tumor DNA (ctDNA) testing may serve as an early predictor of response to radiotherapy or chemoradiotherapy in patients with gynecologic cancers, results of a small study suggest.

Among 15 patients with vulvar, cervical, or endometrial malignancies who had serum ctDNA draws prior to, during, and after radiation therapy (RT) or chemoradiotherapy (CRT), both persistence or clearance of residual ctDNA were prognostic of patient outcomes from 3 to 6 months after the end of radiation therapy, reported A. Gabriella Wernicke, MD, MSc, a radiation oncologist at Lenox Hill Hospital in New York City.

“Our early findings in this limited cohort suggest that a mid-treatment ctDNA draw identified responders to radiation, and that may potentially serve as an early predictive biomarker of response. And clearly, these findings need to be validated in a prospective manner, a trial which will be starting in our center soon,” she said in an oral abstract session at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer, held in San Diego, California.

Gynecologic malignancies are challenging to manage with radiotherapy because of the treatment’s toxicities and because outcomes may not be known until several months after the end of therapy. Early identification of responses to radiation therapy with simple blood draws has the potential to help clinicians identify those patients whose tumors are responding to radiation early in the course of therapy, she said.
 

Correlating treatment with responses

Dr. Wernicke and colleagues tested their hypothesis that the ctDNA is predictive of treatment response in patients receiving RT or CRT by retrospectively assessing the correlation of clinical responses to ctDNA detection and dynamics.

Their sample included 15 women with vulvar, cervical, or recurrent endometrial cancer who were treated with RT or CRT in 2022 and 2023.

The samples were collected prior to radiation therapy, mid-treatment, prior to boost dose with brachytherapy or stereotactic body radiation therapy, at the end of treatment, and at follow-up at 1, 3, and 6 months after the end of therapy and every 6 months thereafter.

The ctDNA analysis was performed with a personalized assay consisting of multiplex polymerase chain reaction and next-generation sequencing. The assays assessed clonal mutations found in the tumors of each patient.

Of the 15 patients, 5 had vulvar/vaginal tumors, all of squamous cell carcinoma histology. Six patients had squamous cell carcinoma of the cervix, and one had neuroendocrine cervical tumors. The two remaining patients had recurrent endometrial adenocarcinomas.

Eight of the patients had stage III disease, four had stage I or II, one had stage IV, and two had recurrent disease.
 

Results

At baseline 13 of the patients had detectable ctDNA, measured as greater than 0.00 mean tumor molecules per milliliter of plasma (MTM/mL).

There was a strong correlation between elevated ctDNA and measurable disease evaluated by standardized uptake values (SUV) on imaging pre treatment (correlation coefficient = 0.87, P less than .0001).

All patients had reductions in ctDNA from baseline to post-RT/CRT, with 2 having a reduction (partial metabolic response) and 13 having undetectable ctDNA (complete metabolic response) at the end of RT/CRT.

From the mid-treatment blood draw to the posttreatment draw 33% of patients had a partial metabolic response, and 67% had a complete response.

Reduction or clearance of ctDNA also correlated with a decrease in disease burden on MRI during the pre-boost phase of RT.

“Patients with undetectable ctDNA, meaning a complete metabolic response, at mid-radiation and at the end of radiation continued to be clinically without evidence of disease and with undetectable ctDNA at follow-up,” Dr. Wernicke said.

In contrast, the two patients who had partial metabolic responses had disease progression at the end of treatment. Dr. Wernicke noted that one of these patients, who was treated for a neuroendocrine carcinoma of the cervix and had undergone both systemic therapy and CRT, was found to have disease metastatic to the liver and lungs at the 3-month follow-up.
 

How to Use It?

Invited discussant Casey M. Cosgrove, MD, a gynecologic oncologist at Ohio State University Comprehensive Cancer Centers facility in Hilliard, Ohio, said that the reduction of ctDNA levels in all patients was “great,” but the question remains about how the information from ctDNA might be used to guide care in patients undergoing radiation therapy.

“The main questions I have are: If I don’t clear the ctDNA do I need to do more therapy? If I do clear does that mean I need to do less therapy? And if I have negative ctDNA to start what do I do?” he said.

The answers will be found only with further prospective studies, he emphasized.

“These technologies are only going to get better, and better, and better, and this is going to be a conversation that our patients are going to be bringing up, and this is going to be technology that we’re going to be using in our clinics in the very near future,” he added.

Session comoderator Michael Bookman, MD, a gynecology oncologist at Kaiser Permanente in San Francisco, said “it’s worth remembering that FDA approval of a diagnostic test can be obtained prior to showing any clinical benefit. So these are tests that measure what they say they’re measuring, but they haven’t been validated as improving clinical outcomes, which is the task that clearly lies ahead of us.”

The study was internally funded. Dr. Wernicke reported no relevant disclosures. Dr. Cosgrove reported a consulting or advisory role for Intuitive Ltd., GlaxoSmithKline, AstraZeneca, ImmunoGen, and Merck, and research fees from GSK. Dr. Bookman reported clinical trial advising/monitoring for Immunogen and Clovis Oncology, with fees paid to his institution.

This transcript has been edited for clarity.

Rachel S. Rubin, MD: We are here at the Harvard Continuing Medical Education Course in Orlando, Florida. It’s all about testosterone therapy and sexual medicine. I have with me today the wonderful Dr. Marianne Brandon, who is an amazing sex therapist. Could you introduce yourself?

Marianne Brandon, PhD: I am a clinical psychologist and sex therapist. I’ve been in practice for more than 25 years. I’m currently located in Sarasota. I have a Psychology Today blog called The Future of Intimacy, which I have a lot of fun with.

Dr. Rubin: It’s very important, when taking care of patients, that we work in a biopsychosocial model. Yes, we can fix erectile dysfunction. We can help with menopause symptoms and that helps sexual function. But what I find makes my patients able to live their best lives is when they have a team, including a mental health professional — often a sex therapist or a couples’ therapist — where they can learn communication skills. Why is it important for primary care doctors to talk to their patients about sex? My primary care doctor has never asked me about sex.  

Dr. Brandon: For most people, sexual intimacy is critical for their experience of life. It correlates with their relationship satisfaction and life satisfaction. It’s much bigger than what’s happening in the bedroom. People have more struggles than you realize. Sexual dysfunction correlates with emotional issues such as depression and anxiety, with medical problems, and with medication use. Chances are that your patients have some kind of sexual concern, even if that’s not to the degree that it would be classified as a sexual dysfunction.

But sexual concerns wreak havoc. Believing they have a sexual problem, they stop touching, they stop relating to their partner. It becomes a really big deal in their lives. If you can open the door for a conversation about sex with your patients, it could do them a great deal of good. It’s also good for the practitioner, because if your patients think they can talk with you about anything, that’s going to establish your relationship with them. Practitioners avoid these conversations because they don’t have the time or the training to offer help.

Dr. Rubin: You don’t have to know all the answers. You just have to show empathy and compassion and say, “I hear you.” That’s the magic in the doctor-patient relationship. We refer patients to specialists when we don’t know what to do. What happens when I send a patient to a sex therapist? Do they watch them have sex? Of course not, but everyone thinks that is what sex therapists do.

Dr. Brandon: Sex therapy is just like any other type of therapy, but we discuss sexual issues. And because just about anything that’s happening in your patient’s life can trickle down into the bedroom, we end up talking about a lot of stuff that’s not directly related to sex but ultimately impacts the patient’s sex life.

Dr. Rubin: It’s true. Most medical conditions that we treat — from diabetes, hypertension, high cholesterol, and obesity to depression and anxiety — are strongly correlated with sexual health. We treat the underlying condition, but our patients don’t care about their A1c levels. They care about the fact that they cannot get aroused; their genitals don’t feel the same way they used to.

Dr. Brandon: I love that point because people make meaning out of their sexual concerns and dysfunction. Suddenly their body isn’t responding the way it used to. They think something’s wrong with them, or maybe they are with the wrong partner. This meaning becomes very powerful in their mind and perpetuates the sexual problem.

Dr. Rubin: First and foremost, we are educators. We can say, “You have pretty out-of-control diabetes,” or, “You’re a smoker, which can affect the health of your genitals. Have you noticed any issues going on there?” If you don’t ask, patients will not bring up their concerns with their doctors.

So how do people find a sex therapist?

Dr. Brandon: There are a few fabulous organizations that provide on their websites ways to find a therapist: the American Association of Sex Educators, Counselors and Therapists (AASECT) and Sex Therapy and Research (STAR). Giving patients this information is a huge intervention.

Other places to find a therapist include the International Society for Sexual Medicine, and the International Society for the Study of Women’s Sexual Health.

Since COVID, many therapists have gone virtual. Encourage your patients to look within their states to find options for therapists and psychologists. Recent legislation allows psychologists who have signed up for PSYPACT to practice almost throughout the entire United States. We used to think if we didn’t have a therapist in the community, we couldn’t make a referral. That›s not the case anymore.

Dr. Rubin: All doctors are really sexual medicine doctors. We can change the whole world by giving our patients a better quality of life.
 

Dr. Rubin, Assistant Clinical Professor, Department of Urology, Georgetown University, Washington, disclosed ties to Sprout, Maternal Medical, Absorption Pharmaceuticals, GlaxoSmithKline, and Endo.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

Rachel S. Rubin, MD: We are here at the Harvard Continuing Medical Education Course in Orlando, Florida. It’s all about testosterone therapy and sexual medicine. I have with me today the wonderful Dr. Marianne Brandon, who is an amazing sex therapist. Could you introduce yourself?

Marianne Brandon, PhD: I am a clinical psychologist and sex therapist. I’ve been in practice for more than 25 years. I’m currently located in Sarasota. I have a Psychology Today blog called The Future of Intimacy, which I have a lot of fun with.

Dr. Rubin: It’s very important, when taking care of patients, that we work in a biopsychosocial model. Yes, we can fix erectile dysfunction. We can help with menopause symptoms and that helps sexual function. But what I find makes my patients able to live their best lives is when they have a team, including a mental health professional — often a sex therapist or a couples’ therapist — where they can learn communication skills. Why is it important for primary care doctors to talk to their patients about sex? My primary care doctor has never asked me about sex.  

Dr. Brandon: For most people, sexual intimacy is critical for their experience of life. It correlates with their relationship satisfaction and life satisfaction. It’s much bigger than what’s happening in the bedroom. People have more struggles than you realize. Sexual dysfunction correlates with emotional issues such as depression and anxiety, with medical problems, and with medication use. Chances are that your patients have some kind of sexual concern, even if that’s not to the degree that it would be classified as a sexual dysfunction.

But sexual concerns wreak havoc. Believing they have a sexual problem, they stop touching, they stop relating to their partner. It becomes a really big deal in their lives. If you can open the door for a conversation about sex with your patients, it could do them a great deal of good. It’s also good for the practitioner, because if your patients think they can talk with you about anything, that’s going to establish your relationship with them. Practitioners avoid these conversations because they don’t have the time or the training to offer help.

Dr. Rubin: You don’t have to know all the answers. You just have to show empathy and compassion and say, “I hear you.” That’s the magic in the doctor-patient relationship. We refer patients to specialists when we don’t know what to do. What happens when I send a patient to a sex therapist? Do they watch them have sex? Of course not, but everyone thinks that is what sex therapists do.

Dr. Brandon: Sex therapy is just like any other type of therapy, but we discuss sexual issues. And because just about anything that’s happening in your patient’s life can trickle down into the bedroom, we end up talking about a lot of stuff that’s not directly related to sex but ultimately impacts the patient’s sex life.

Dr. Rubin: It’s true. Most medical conditions that we treat — from diabetes, hypertension, high cholesterol, and obesity to depression and anxiety — are strongly correlated with sexual health. We treat the underlying condition, but our patients don’t care about their A1c levels. They care about the fact that they cannot get aroused; their genitals don’t feel the same way they used to.

Dr. Brandon: I love that point because people make meaning out of their sexual concerns and dysfunction. Suddenly their body isn’t responding the way it used to. They think something’s wrong with them, or maybe they are with the wrong partner. This meaning becomes very powerful in their mind and perpetuates the sexual problem.

Dr. Rubin: First and foremost, we are educators. We can say, “You have pretty out-of-control diabetes,” or, “You’re a smoker, which can affect the health of your genitals. Have you noticed any issues going on there?” If you don’t ask, patients will not bring up their concerns with their doctors.

So how do people find a sex therapist?

Dr. Brandon: There are a few fabulous organizations that provide on their websites ways to find a therapist: the American Association of Sex Educators, Counselors and Therapists (AASECT) and Sex Therapy and Research (STAR). Giving patients this information is a huge intervention.

Other places to find a therapist include the International Society for Sexual Medicine, and the International Society for the Study of Women’s Sexual Health.

Since COVID, many therapists have gone virtual. Encourage your patients to look within their states to find options for therapists and psychologists. Recent legislation allows psychologists who have signed up for PSYPACT to practice almost throughout the entire United States. We used to think if we didn’t have a therapist in the community, we couldn’t make a referral. That›s not the case anymore.

Dr. Rubin: All doctors are really sexual medicine doctors. We can change the whole world by giving our patients a better quality of life.
 

Dr. Rubin, Assistant Clinical Professor, Department of Urology, Georgetown University, Washington, disclosed ties to Sprout, Maternal Medical, Absorption Pharmaceuticals, GlaxoSmithKline, and Endo.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

Rachel S. Rubin, MD: We are here at the Harvard Continuing Medical Education Course in Orlando, Florida. It’s all about testosterone therapy and sexual medicine. I have with me today the wonderful Dr. Marianne Brandon, who is an amazing sex therapist. Could you introduce yourself?

Marianne Brandon, PhD: I am a clinical psychologist and sex therapist. I’ve been in practice for more than 25 years. I’m currently located in Sarasota. I have a Psychology Today blog called The Future of Intimacy, which I have a lot of fun with.

Dr. Rubin: It’s very important, when taking care of patients, that we work in a biopsychosocial model. Yes, we can fix erectile dysfunction. We can help with menopause symptoms and that helps sexual function. But what I find makes my patients able to live their best lives is when they have a team, including a mental health professional — often a sex therapist or a couples’ therapist — where they can learn communication skills. Why is it important for primary care doctors to talk to their patients about sex? My primary care doctor has never asked me about sex.  

Dr. Brandon: For most people, sexual intimacy is critical for their experience of life. It correlates with their relationship satisfaction and life satisfaction. It’s much bigger than what’s happening in the bedroom. People have more struggles than you realize. Sexual dysfunction correlates with emotional issues such as depression and anxiety, with medical problems, and with medication use. Chances are that your patients have some kind of sexual concern, even if that’s not to the degree that it would be classified as a sexual dysfunction.

But sexual concerns wreak havoc. Believing they have a sexual problem, they stop touching, they stop relating to their partner. It becomes a really big deal in their lives. If you can open the door for a conversation about sex with your patients, it could do them a great deal of good. It’s also good for the practitioner, because if your patients think they can talk with you about anything, that’s going to establish your relationship with them. Practitioners avoid these conversations because they don’t have the time or the training to offer help.

Dr. Rubin: You don’t have to know all the answers. You just have to show empathy and compassion and say, “I hear you.” That’s the magic in the doctor-patient relationship. We refer patients to specialists when we don’t know what to do. What happens when I send a patient to a sex therapist? Do they watch them have sex? Of course not, but everyone thinks that is what sex therapists do.

Dr. Brandon: Sex therapy is just like any other type of therapy, but we discuss sexual issues. And because just about anything that’s happening in your patient’s life can trickle down into the bedroom, we end up talking about a lot of stuff that’s not directly related to sex but ultimately impacts the patient’s sex life.

Dr. Rubin: It’s true. Most medical conditions that we treat — from diabetes, hypertension, high cholesterol, and obesity to depression and anxiety — are strongly correlated with sexual health. We treat the underlying condition, but our patients don’t care about their A1c levels. They care about the fact that they cannot get aroused; their genitals don’t feel the same way they used to.

Dr. Brandon: I love that point because people make meaning out of their sexual concerns and dysfunction. Suddenly their body isn’t responding the way it used to. They think something’s wrong with them, or maybe they are with the wrong partner. This meaning becomes very powerful in their mind and perpetuates the sexual problem.

Dr. Rubin: First and foremost, we are educators. We can say, “You have pretty out-of-control diabetes,” or, “You’re a smoker, which can affect the health of your genitals. Have you noticed any issues going on there?” If you don’t ask, patients will not bring up their concerns with their doctors.

So how do people find a sex therapist?

Dr. Brandon: There are a few fabulous organizations that provide on their websites ways to find a therapist: the American Association of Sex Educators, Counselors and Therapists (AASECT) and Sex Therapy and Research (STAR). Giving patients this information is a huge intervention.

Other places to find a therapist include the International Society for Sexual Medicine, and the International Society for the Study of Women’s Sexual Health.

Since COVID, many therapists have gone virtual. Encourage your patients to look within their states to find options for therapists and psychologists. Recent legislation allows psychologists who have signed up for PSYPACT to practice almost throughout the entire United States. We used to think if we didn’t have a therapist in the community, we couldn’t make a referral. That›s not the case anymore.

Dr. Rubin: All doctors are really sexual medicine doctors. We can change the whole world by giving our patients a better quality of life.
 

Dr. Rubin, Assistant Clinical Professor, Department of Urology, Georgetown University, Washington, disclosed ties to Sprout, Maternal Medical, Absorption Pharmaceuticals, GlaxoSmithKline, and Endo.

A version of this article appeared on Medscape.com.

For early-stage cervical cancer, non-radical surgery (simple hysterectomy or cone biopsy plus pelvic lymphadenectomy) appears safe with no lasting negative impact on quality of life, according to results of the GOG-278 trial.

In fact, patients’ quality of life was improved after surgery in both groups, and their concerns about cancer recurrence decreased, especially for those undergoing simple hysterectomy, said Allan Covens, MD, in his late-breaking abstract presentation at the Society of Gynecologic Oncology (SGO)’s Annual Meeting on Women’s Cancer. 

“Cone biopsy patients reported less concerns about reproductive fertility after surgery and over time compared to preop assessments,” he added.

Due to screening in developed countries, a large proportion of cervical cancers are discovered at an early stage. Treatment of these cancers with radical surgery is associated with high cure rates but significant adverse effects on quality of life, said Dr. Covens, who is with the University of Toronto, Toronto, Ontario, Canada.

He and his colleagues wanted to see if non-radical surgery could be safely used instead. “Multiple case series have indicated that non-radical surgery is associated with less morbidity and improved quality of life,” he explained. “If this can be proven in a prospective evaluation, it will change future practice.”

GOG-278 was a prospective cohort study of women with stage IA1 (lymph-vascular space invasion+) and IA2-IB1 (≤ 2 cm) carcinoma of the cervix who underwent non-radical surgery (simple hysterectomy or fertility-preserving cone biopsy) and pelvic lymphadenectomy. Criteria included ≤ 10 mm stromal invasion and negative margins on the final cone biopsy.

The primary objectives were to assess changes in functional outcomes of quality of life (bladder/bowel function, sexual function, cancer worry, and reproductive concerns), using validated instruments. Findings were based on 55 patients who underwent cone biopsy and 113 who underwent simple hysterectomy.

Both simple hysterectomy and cone biopsy were associated with “small” declines in sexual function and bladder/bowel function at 4-6 weeks after surgery, but function “quickly” recovered to baseline by 6 months, Dr. Covens reported.

Twelve patients reported a diagnosis of lymphedema, with a Gynecologic Cancer Lymphedema Questionnaire score change of 4 or higher on at least two consecutive evaluations from baseline. This occurred in six cone biopsy and six simple hysterectomy patients.

In a separate presentation, Dr. Covens reported secondary oncologic outcomes from GOG-278, which suggest that non-radical surgery for early-stage cervical cancer is safe, with low perioperative morbidity, although longer follow-up is needed.

He also reported 16 pregnancies in 15 patients who had undergone cone biopsies; 12 of these were successful, and there were four early pregnancy losses.
 

‘Impressive’ Data

Study discussant Kristin Bixel, MD, with The Ohio State University, Columbus, Ohio, said the data are “impressive” and clearly show that non-radical surgery has “minimal impact on bladder/bowel function, with no long-term differences from baseline.”

She added that the incidence of lymphedema was “honestly significantly lower than what I typically counsel patients about” and wondered if the percentage of patients with lymphedema would increase over time.

Dr. Bixel particularly noted the decrease in cancer worry scores after surgery, as sometimes patients who have less radical procedures fear that this comes with an increased risk for recurrence.

The “growing body of data suggests that less radical surgery is safe and effective for early-stage low-risk cervical cancer and highlights the potential reproductive success,” she concluded.

Funding for the study was provided by grants from NRG Oncology. Dr. Covens had no disclosures. Dr. Bixel has received research funding from the Intuitive Foundation.

A version of this article appeared on Medscape.com.

For early-stage cervical cancer, non-radical surgery (simple hysterectomy or cone biopsy plus pelvic lymphadenectomy) appears safe with no lasting negative impact on quality of life, according to results of the GOG-278 trial.

In fact, patients’ quality of life was improved after surgery in both groups, and their concerns about cancer recurrence decreased, especially for those undergoing simple hysterectomy, said Allan Covens, MD, in his late-breaking abstract presentation at the Society of Gynecologic Oncology (SGO)’s Annual Meeting on Women’s Cancer. 

“Cone biopsy patients reported less concerns about reproductive fertility after surgery and over time compared to preop assessments,” he added.

Due to screening in developed countries, a large proportion of cervical cancers are discovered at an early stage. Treatment of these cancers with radical surgery is associated with high cure rates but significant adverse effects on quality of life, said Dr. Covens, who is with the University of Toronto, Toronto, Ontario, Canada.

He and his colleagues wanted to see if non-radical surgery could be safely used instead. “Multiple case series have indicated that non-radical surgery is associated with less morbidity and improved quality of life,” he explained. “If this can be proven in a prospective evaluation, it will change future practice.”

GOG-278 was a prospective cohort study of women with stage IA1 (lymph-vascular space invasion+) and IA2-IB1 (≤ 2 cm) carcinoma of the cervix who underwent non-radical surgery (simple hysterectomy or fertility-preserving cone biopsy) and pelvic lymphadenectomy. Criteria included ≤ 10 mm stromal invasion and negative margins on the final cone biopsy.

The primary objectives were to assess changes in functional outcomes of quality of life (bladder/bowel function, sexual function, cancer worry, and reproductive concerns), using validated instruments. Findings were based on 55 patients who underwent cone biopsy and 113 who underwent simple hysterectomy.

Both simple hysterectomy and cone biopsy were associated with “small” declines in sexual function and bladder/bowel function at 4-6 weeks after surgery, but function “quickly” recovered to baseline by 6 months, Dr. Covens reported.

Twelve patients reported a diagnosis of lymphedema, with a Gynecologic Cancer Lymphedema Questionnaire score change of 4 or higher on at least two consecutive evaluations from baseline. This occurred in six cone biopsy and six simple hysterectomy patients.

In a separate presentation, Dr. Covens reported secondary oncologic outcomes from GOG-278, which suggest that non-radical surgery for early-stage cervical cancer is safe, with low perioperative morbidity, although longer follow-up is needed.

He also reported 16 pregnancies in 15 patients who had undergone cone biopsies; 12 of these were successful, and there were four early pregnancy losses.
 

‘Impressive’ Data

Study discussant Kristin Bixel, MD, with The Ohio State University, Columbus, Ohio, said the data are “impressive” and clearly show that non-radical surgery has “minimal impact on bladder/bowel function, with no long-term differences from baseline.”

She added that the incidence of lymphedema was “honestly significantly lower than what I typically counsel patients about” and wondered if the percentage of patients with lymphedema would increase over time.

Dr. Bixel particularly noted the decrease in cancer worry scores after surgery, as sometimes patients who have less radical procedures fear that this comes with an increased risk for recurrence.

The “growing body of data suggests that less radical surgery is safe and effective for early-stage low-risk cervical cancer and highlights the potential reproductive success,” she concluded.

Funding for the study was provided by grants from NRG Oncology. Dr. Covens had no disclosures. Dr. Bixel has received research funding from the Intuitive Foundation.

A version of this article appeared on Medscape.com.

For early-stage cervical cancer, non-radical surgery (simple hysterectomy or cone biopsy plus pelvic lymphadenectomy) appears safe with no lasting negative impact on quality of life, according to results of the GOG-278 trial.

In fact, patients’ quality of life was improved after surgery in both groups, and their concerns about cancer recurrence decreased, especially for those undergoing simple hysterectomy, said Allan Covens, MD, in his late-breaking abstract presentation at the Society of Gynecologic Oncology (SGO)’s Annual Meeting on Women’s Cancer. 

“Cone biopsy patients reported less concerns about reproductive fertility after surgery and over time compared to preop assessments,” he added.

Due to screening in developed countries, a large proportion of cervical cancers are discovered at an early stage. Treatment of these cancers with radical surgery is associated with high cure rates but significant adverse effects on quality of life, said Dr. Covens, who is with the University of Toronto, Toronto, Ontario, Canada.

He and his colleagues wanted to see if non-radical surgery could be safely used instead. “Multiple case series have indicated that non-radical surgery is associated with less morbidity and improved quality of life,” he explained. “If this can be proven in a prospective evaluation, it will change future practice.”

GOG-278 was a prospective cohort study of women with stage IA1 (lymph-vascular space invasion+) and IA2-IB1 (≤ 2 cm) carcinoma of the cervix who underwent non-radical surgery (simple hysterectomy or fertility-preserving cone biopsy) and pelvic lymphadenectomy. Criteria included ≤ 10 mm stromal invasion and negative margins on the final cone biopsy.

The primary objectives were to assess changes in functional outcomes of quality of life (bladder/bowel function, sexual function, cancer worry, and reproductive concerns), using validated instruments. Findings were based on 55 patients who underwent cone biopsy and 113 who underwent simple hysterectomy.

Both simple hysterectomy and cone biopsy were associated with “small” declines in sexual function and bladder/bowel function at 4-6 weeks after surgery, but function “quickly” recovered to baseline by 6 months, Dr. Covens reported.

Twelve patients reported a diagnosis of lymphedema, with a Gynecologic Cancer Lymphedema Questionnaire score change of 4 or higher on at least two consecutive evaluations from baseline. This occurred in six cone biopsy and six simple hysterectomy patients.

In a separate presentation, Dr. Covens reported secondary oncologic outcomes from GOG-278, which suggest that non-radical surgery for early-stage cervical cancer is safe, with low perioperative morbidity, although longer follow-up is needed.

He also reported 16 pregnancies in 15 patients who had undergone cone biopsies; 12 of these were successful, and there were four early pregnancy losses.
 

‘Impressive’ Data

Study discussant Kristin Bixel, MD, with The Ohio State University, Columbus, Ohio, said the data are “impressive” and clearly show that non-radical surgery has “minimal impact on bladder/bowel function, with no long-term differences from baseline.”

She added that the incidence of lymphedema was “honestly significantly lower than what I typically counsel patients about” and wondered if the percentage of patients with lymphedema would increase over time.

Dr. Bixel particularly noted the decrease in cancer worry scores after surgery, as sometimes patients who have less radical procedures fear that this comes with an increased risk for recurrence.

The “growing body of data suggests that less radical surgery is safe and effective for early-stage low-risk cervical cancer and highlights the potential reproductive success,” she concluded.

Funding for the study was provided by grants from NRG Oncology. Dr. Covens had no disclosures. Dr. Bixel has received research funding from the Intuitive Foundation.

A version of this article appeared on Medscape.com.

The transplantation of ovarian tissue is often performed to extend fertility among women and adolescents with cancer. But some reproductive specialists believe the procedure may have another role to play with much wider application: delaying, or even preventing, menopause in healthy women.

Kutluk Oktay, MD, director of the Laboratory of Molecular Reproduction and Fertility Preservation at the Yale School of Medicine in New Haven, Connecticut, has used ovarian tissue transplantation (OTT) in his own practice — Innovation Fertility Preservation & IVF — for several years. He said the approach can reduce health risks associated with menopause, such as the loss of bone density and cardiovascular disease.

“We have started offering [ovarian tissue transplantation] in carefully selected candidates, but the pace will accelerate now that we have a way to better inform the candidates on the potential of the procedure,” Dr. Oktay said. To date, he said he has performed the procedure on approximately 20 patients.

But Dr. Oktay’s vision of the future for OTT remains on the fringe of reproductive medicine.

“I think there are ethical considerations to take into account here,” said Stephanie Faubion, MD, Medical Director for the North American Menopause Society. “You’re taking a perfectly healthy 25- to 30-year-old woman and putting her through surgery to take out a healthy organ. Let’s just think about that.”
 

The Promise and Risks of OTT

OTT involves removing part of the ovarian tissue, cryopreservation, and then transplanting it back into the body. The procedure has reversed early menopause in women who underwent cancer treatment and resulted in over 140 live births worldwide.

Dr. Oktay recently published a nonclinical study in the American Journal of Obstetrics & Gynecology using a mathematical model based on decades of clinical research on cancer patients and ovarian follicle counts in cadaver to forecast how OTT can delay the onset of menopause through restored ovarian function and hormonal shifts.

The model forecasts a delay in menopause of up to 47 years, depending on factors such as the age of tissue removal, a woman’s ovarian reserve, and an estimated number of primordial follicles — where tens to hundreds of thousands of undeveloped eggs can live — that survive the process of removal, freezing, and reimplantation.

OTT is currently associated with a survival rate of 40% for follicles, Dr. Oktay said. But technological advancements, including revascularization drugs and robotic surgery, are likely to extend the survival rate to 80% by the time reimplantation occurs, potentially 15-20 years after tissue removal, he said.

Prospective patients at Dr. Oktay’s practice can use an interactive tool to receive an estimate of their potential menopausal delay. Patients receive a clinical assessment, including tests for ovarian reserve markers, to determine their potential for the procedure.

The model predicted that harvesting tissue before age 30 could delay menopause significantly. A 25-year-old woman with an average ovarian reserve who preserved a quarter of one ovary would have a delay in menopause of 11.8 years if 40% of the follicles survived. Women around age 40, and especially those with a low ovarian reserve, would need a follicle survival rate of close to 100% to result in a delay significant enough to justify the procedure.

The procedure also comes with risks. Removing ovarian tissue can bring on early menopause, Dr. Oktay said. Removing part or all of the ovarian cortex — the outer part of the ovary that contains the follicles — can start menopause about 1.5 years earlier. But as long as the tissue is transplanted, a woman would gain many more years of fertility before menopause.

While potentially promising, some obstetrics and gynecology experts question the procedure, with no proven benefits.

“While theoretically possible, my biggest question is, how is this better than egg freezing in your 20s or 30s combined with hormone replacement for the aging benefits, given the risks associated with potentially multiple surgeries?” said Paula Amato, MD, professor of obstetrics and gynecology at Oregon Health & Science University in Portland, Oregon.

Any risks associated with receiving hormone therapy through OTT rather than traditional hormone replacement therapy are also unknown, Dr. Amato said.

A UK clinic, ProFam, based in Birmingham, also offered the procedure but faced criticism in 2020 for being unnecessary and experimental. This news organization could not confirm if the clinic is still in operation.
 

Why Delay Menopause?

While the procedure may extend fertility, the goal of the procedure is not to enable patients to become pregnant at ages that are not safe, Dr. Oktay said. Rather, he said postponing menopause is medically beneficial.

Some research shows that women who have late menopause have a lower risk for all-cause mortality and cardiovascular disease but a higher risk for breast, endometrial, and ovarian cancers.

Dr. Oktay said that delaying menopause could improve the quality of life for women by reducing menopausal symptoms like anxiety and depression. Clinicians could also use the procedure as preventive care for those who are at high risk for conditions associated with menopause, such as osteoporosis and dementia.

But Dr. Faubion is unconvinced that delaying menopause through OTT carries health benefits.

“Just because we can do this, should we?” she said. “And will it do the things that we think it will? Does preventing or delaying menopause delay the aging process? I think that’s what they’re trying to imply, and we don’t have evidence that that’s true.”

The study was funded by the National Science Foundation, U-Anschutz Department of Obstetrics and Gynecology Research Funds, SF Faculty Early Career Development Program, and the National Institutes of Health awards. The authors reported no disclosures.

A version of this article appeared on Medscape.com.

The transplantation of ovarian tissue is often performed to extend fertility among women and adolescents with cancer. But some reproductive specialists believe the procedure may have another role to play with much wider application: delaying, or even preventing, menopause in healthy women.

Kutluk Oktay, MD, director of the Laboratory of Molecular Reproduction and Fertility Preservation at the Yale School of Medicine in New Haven, Connecticut, has used ovarian tissue transplantation (OTT) in his own practice — Innovation Fertility Preservation & IVF — for several years. He said the approach can reduce health risks associated with menopause, such as the loss of bone density and cardiovascular disease.

“We have started offering [ovarian tissue transplantation] in carefully selected candidates, but the pace will accelerate now that we have a way to better inform the candidates on the potential of the procedure,” Dr. Oktay said. To date, he said he has performed the procedure on approximately 20 patients.

But Dr. Oktay’s vision of the future for OTT remains on the fringe of reproductive medicine.

“I think there are ethical considerations to take into account here,” said Stephanie Faubion, MD, Medical Director for the North American Menopause Society. “You’re taking a perfectly healthy 25- to 30-year-old woman and putting her through surgery to take out a healthy organ. Let’s just think about that.”
 

The Promise and Risks of OTT

OTT involves removing part of the ovarian tissue, cryopreservation, and then transplanting it back into the body. The procedure has reversed early menopause in women who underwent cancer treatment and resulted in over 140 live births worldwide.

Dr. Oktay recently published a nonclinical study in the American Journal of Obstetrics & Gynecology using a mathematical model based on decades of clinical research on cancer patients and ovarian follicle counts in cadaver to forecast how OTT can delay the onset of menopause through restored ovarian function and hormonal shifts.

The model forecasts a delay in menopause of up to 47 years, depending on factors such as the age of tissue removal, a woman’s ovarian reserve, and an estimated number of primordial follicles — where tens to hundreds of thousands of undeveloped eggs can live — that survive the process of removal, freezing, and reimplantation.

OTT is currently associated with a survival rate of 40% for follicles, Dr. Oktay said. But technological advancements, including revascularization drugs and robotic surgery, are likely to extend the survival rate to 80% by the time reimplantation occurs, potentially 15-20 years after tissue removal, he said.

Prospective patients at Dr. Oktay’s practice can use an interactive tool to receive an estimate of their potential menopausal delay. Patients receive a clinical assessment, including tests for ovarian reserve markers, to determine their potential for the procedure.

The model predicted that harvesting tissue before age 30 could delay menopause significantly. A 25-year-old woman with an average ovarian reserve who preserved a quarter of one ovary would have a delay in menopause of 11.8 years if 40% of the follicles survived. Women around age 40, and especially those with a low ovarian reserve, would need a follicle survival rate of close to 100% to result in a delay significant enough to justify the procedure.

The procedure also comes with risks. Removing ovarian tissue can bring on early menopause, Dr. Oktay said. Removing part or all of the ovarian cortex — the outer part of the ovary that contains the follicles — can start menopause about 1.5 years earlier. But as long as the tissue is transplanted, a woman would gain many more years of fertility before menopause.

While potentially promising, some obstetrics and gynecology experts question the procedure, with no proven benefits.

“While theoretically possible, my biggest question is, how is this better than egg freezing in your 20s or 30s combined with hormone replacement for the aging benefits, given the risks associated with potentially multiple surgeries?” said Paula Amato, MD, professor of obstetrics and gynecology at Oregon Health & Science University in Portland, Oregon.

Any risks associated with receiving hormone therapy through OTT rather than traditional hormone replacement therapy are also unknown, Dr. Amato said.

A UK clinic, ProFam, based in Birmingham, also offered the procedure but faced criticism in 2020 for being unnecessary and experimental. This news organization could not confirm if the clinic is still in operation.
 

Why Delay Menopause?

While the procedure may extend fertility, the goal of the procedure is not to enable patients to become pregnant at ages that are not safe, Dr. Oktay said. Rather, he said postponing menopause is medically beneficial.

Some research shows that women who have late menopause have a lower risk for all-cause mortality and cardiovascular disease but a higher risk for breast, endometrial, and ovarian cancers.

Dr. Oktay said that delaying menopause could improve the quality of life for women by reducing menopausal symptoms like anxiety and depression. Clinicians could also use the procedure as preventive care for those who are at high risk for conditions associated with menopause, such as osteoporosis and dementia.

But Dr. Faubion is unconvinced that delaying menopause through OTT carries health benefits.

“Just because we can do this, should we?” she said. “And will it do the things that we think it will? Does preventing or delaying menopause delay the aging process? I think that’s what they’re trying to imply, and we don’t have evidence that that’s true.”

The study was funded by the National Science Foundation, U-Anschutz Department of Obstetrics and Gynecology Research Funds, SF Faculty Early Career Development Program, and the National Institutes of Health awards. The authors reported no disclosures.

A version of this article appeared on Medscape.com.

The transplantation of ovarian tissue is often performed to extend fertility among women and adolescents with cancer. But some reproductive specialists believe the procedure may have another role to play with much wider application: delaying, or even preventing, menopause in healthy women.

Kutluk Oktay, MD, director of the Laboratory of Molecular Reproduction and Fertility Preservation at the Yale School of Medicine in New Haven, Connecticut, has used ovarian tissue transplantation (OTT) in his own practice — Innovation Fertility Preservation & IVF — for several years. He said the approach can reduce health risks associated with menopause, such as the loss of bone density and cardiovascular disease.

“We have started offering [ovarian tissue transplantation] in carefully selected candidates, but the pace will accelerate now that we have a way to better inform the candidates on the potential of the procedure,” Dr. Oktay said. To date, he said he has performed the procedure on approximately 20 patients.

But Dr. Oktay’s vision of the future for OTT remains on the fringe of reproductive medicine.

“I think there are ethical considerations to take into account here,” said Stephanie Faubion, MD, Medical Director for the North American Menopause Society. “You’re taking a perfectly healthy 25- to 30-year-old woman and putting her through surgery to take out a healthy organ. Let’s just think about that.”
 

The Promise and Risks of OTT

OTT involves removing part of the ovarian tissue, cryopreservation, and then transplanting it back into the body. The procedure has reversed early menopause in women who underwent cancer treatment and resulted in over 140 live births worldwide.

Dr. Oktay recently published a nonclinical study in the American Journal of Obstetrics & Gynecology using a mathematical model based on decades of clinical research on cancer patients and ovarian follicle counts in cadaver to forecast how OTT can delay the onset of menopause through restored ovarian function and hormonal shifts.

The model forecasts a delay in menopause of up to 47 years, depending on factors such as the age of tissue removal, a woman’s ovarian reserve, and an estimated number of primordial follicles — where tens to hundreds of thousands of undeveloped eggs can live — that survive the process of removal, freezing, and reimplantation.

OTT is currently associated with a survival rate of 40% for follicles, Dr. Oktay said. But technological advancements, including revascularization drugs and robotic surgery, are likely to extend the survival rate to 80% by the time reimplantation occurs, potentially 15-20 years after tissue removal, he said.

Prospective patients at Dr. Oktay’s practice can use an interactive tool to receive an estimate of their potential menopausal delay. Patients receive a clinical assessment, including tests for ovarian reserve markers, to determine their potential for the procedure.

The model predicted that harvesting tissue before age 30 could delay menopause significantly. A 25-year-old woman with an average ovarian reserve who preserved a quarter of one ovary would have a delay in menopause of 11.8 years if 40% of the follicles survived. Women around age 40, and especially those with a low ovarian reserve, would need a follicle survival rate of close to 100% to result in a delay significant enough to justify the procedure.

The procedure also comes with risks. Removing ovarian tissue can bring on early menopause, Dr. Oktay said. Removing part or all of the ovarian cortex — the outer part of the ovary that contains the follicles — can start menopause about 1.5 years earlier. But as long as the tissue is transplanted, a woman would gain many more years of fertility before menopause.

While potentially promising, some obstetrics and gynecology experts question the procedure, with no proven benefits.

“While theoretically possible, my biggest question is, how is this better than egg freezing in your 20s or 30s combined with hormone replacement for the aging benefits, given the risks associated with potentially multiple surgeries?” said Paula Amato, MD, professor of obstetrics and gynecology at Oregon Health & Science University in Portland, Oregon.

Any risks associated with receiving hormone therapy through OTT rather than traditional hormone replacement therapy are also unknown, Dr. Amato said.

A UK clinic, ProFam, based in Birmingham, also offered the procedure but faced criticism in 2020 for being unnecessary and experimental. This news organization could not confirm if the clinic is still in operation.
 

Why Delay Menopause?

While the procedure may extend fertility, the goal of the procedure is not to enable patients to become pregnant at ages that are not safe, Dr. Oktay said. Rather, he said postponing menopause is medically beneficial.

Some research shows that women who have late menopause have a lower risk for all-cause mortality and cardiovascular disease but a higher risk for breast, endometrial, and ovarian cancers.

Dr. Oktay said that delaying menopause could improve the quality of life for women by reducing menopausal symptoms like anxiety and depression. Clinicians could also use the procedure as preventive care for those who are at high risk for conditions associated with menopause, such as osteoporosis and dementia.

But Dr. Faubion is unconvinced that delaying menopause through OTT carries health benefits.

“Just because we can do this, should we?” she said. “And will it do the things that we think it will? Does preventing or delaying menopause delay the aging process? I think that’s what they’re trying to imply, and we don’t have evidence that that’s true.”

The study was funded by the National Science Foundation, U-Anschutz Department of Obstetrics and Gynecology Research Funds, SF Faculty Early Career Development Program, and the National Institutes of Health awards. The authors reported no disclosures.

A version of this article appeared on Medscape.com.

The following scenario was discussed during a forum at a meeting recently:

Two employees managing the front desk are clock watchers, always the first to leave at 11:59 a.m. for lunch and at 4:59 p.m. for the end of the day no matter what is happening. This leaves the other employees stuck with their work.

I have seen clock watching often enough to know that it is widely practiced, and widely reviled by coworkers and managers alike. Generally, clock watchers — sometimes referred to in modern parlance as “quiet quitters” — radiate a palpable sense of “I don’t want to be here.”

Physicians typically can’t identify with clock watching behavior, because we learned early on that patient-care tasks must be pursued to completion; if that involves working past the usual “quitting time,” so be it. So your first task in dealing with this problem is to determine its cause. The clock watcher label may be unfair. There may be legitimate reasons for certain employees to leave work at precisely 4:59 every day. Perhaps they must pick up children, or they have a second job to get to. The label usually comes from a pattern of consistent, repeated behavior. And if more than one employee is exhibiting the same behavior in the same office, the likelihood of a valid explanation decreases proportionally.

Utamaru Kido/Moment/Getty Images

A common cause of clock watching is a lack of employees’ commitment to their jobs. They don’t see the point in putting in extra effort, so they run out the door as soon as possible. There are many reasons why this might be the case. For example, the workload in your office may be too large to be accomplished in the time available by the number of people you employ. The solution might be to simply hire additional personnel.

Another common cause is a lack of communication between physicians, managers, and lower-level employees. If staffers are raising concerns or potential solutions, and management is not listening to their opinions or ideas, they will stop offering them. Alternatively, other staff members may not be pulling their weight. When there is a large imbalance in the contribution of team members, the higher performers will stop trying.

Over my 40 plus years in practice, I have had my share of clock watchers. I try the best I can not to let employees’ time commitment practices impact my valuation of their work. I always attempt to focus on quality and productivity. It isn’t easy, but I always try to address the issues behind clock watching behavior. As such, I can’t recall ever having to fire anyone for clock watching. Here are some of the strategies that have worked for me over the years:

1. Set clear expectations. Clearly communicate job responsibilities and expectations regarding time management and patient care. Ensure that all staff understand the importance of dedicating the necessary time to each patient, regardless of the time of day.

2. Foster a patient-centered culture. Cultivate a work environment that prioritizes patient care above all. This can help shift the focus from watching the clock to ensuring high-quality patient care.

3. Provide adequate breaks. Ensure that staff schedules include sufficient breaks. Overworked staff are more likely to watch the clock. Adequate rest periods can help alleviate this issue.

4. Offer flexibility where possible. If feasible, offer some degree of scheduling flexibility. This can help staff manage their personal time more effectively, potentially reducing the tendency to watch the clock.

5. Implement time management training. Offer training sessions focused on time management and efficiency. This can help staff manage their duties more effectively, reducing the need to constantly check the time.

6. Encourage open communication. Create an environment where staff feel comfortable discussing their concerns, including issues related to workload and time management. This can help identify and address specific factors contributing to clock watching.

7. Monitor and provide feedback. Regularly monitor staff performance and provide constructive feedback. If clock watching is observed, discuss it directly with the employee, focusing on the impact on patient care and the work environment.

8. Recognize and reward. Acknowledge and reward staff who consistently provide high-quality care and demonstrate effective time management. Recognition can motivate others to adjust their behavior.

9. Evaluate workloads. Regularly assess staff workloads to ensure they are manageable. Overburdened employees are more likely to engage in clock watching.

10. Lead by example. Management should model the behavior they wish to see in their staff. Demonstrating a commitment to patient care and effective time management can set a positive example.

Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at [email protected].

The following scenario was discussed during a forum at a meeting recently:

Two employees managing the front desk are clock watchers, always the first to leave at 11:59 a.m. for lunch and at 4:59 p.m. for the end of the day no matter what is happening. This leaves the other employees stuck with their work.

I have seen clock watching often enough to know that it is widely practiced, and widely reviled by coworkers and managers alike. Generally, clock watchers — sometimes referred to in modern parlance as “quiet quitters” — radiate a palpable sense of “I don’t want to be here.”

Physicians typically can’t identify with clock watching behavior, because we learned early on that patient-care tasks must be pursued to completion; if that involves working past the usual “quitting time,” so be it. So your first task in dealing with this problem is to determine its cause. The clock watcher label may be unfair. There may be legitimate reasons for certain employees to leave work at precisely 4:59 every day. Perhaps they must pick up children, or they have a second job to get to. The label usually comes from a pattern of consistent, repeated behavior. And if more than one employee is exhibiting the same behavior in the same office, the likelihood of a valid explanation decreases proportionally.

Utamaru Kido/Moment/Getty Images

A common cause of clock watching is a lack of employees’ commitment to their jobs. They don’t see the point in putting in extra effort, so they run out the door as soon as possible. There are many reasons why this might be the case. For example, the workload in your office may be too large to be accomplished in the time available by the number of people you employ. The solution might be to simply hire additional personnel.

Another common cause is a lack of communication between physicians, managers, and lower-level employees. If staffers are raising concerns or potential solutions, and management is not listening to their opinions or ideas, they will stop offering them. Alternatively, other staff members may not be pulling their weight. When there is a large imbalance in the contribution of team members, the higher performers will stop trying.

Over my 40 plus years in practice, I have had my share of clock watchers. I try the best I can not to let employees’ time commitment practices impact my valuation of their work. I always attempt to focus on quality and productivity. It isn’t easy, but I always try to address the issues behind clock watching behavior. As such, I can’t recall ever having to fire anyone for clock watching. Here are some of the strategies that have worked for me over the years:

1. Set clear expectations. Clearly communicate job responsibilities and expectations regarding time management and patient care. Ensure that all staff understand the importance of dedicating the necessary time to each patient, regardless of the time of day.

2. Foster a patient-centered culture. Cultivate a work environment that prioritizes patient care above all. This can help shift the focus from watching the clock to ensuring high-quality patient care.

3. Provide adequate breaks. Ensure that staff schedules include sufficient breaks. Overworked staff are more likely to watch the clock. Adequate rest periods can help alleviate this issue.

4. Offer flexibility where possible. If feasible, offer some degree of scheduling flexibility. This can help staff manage their personal time more effectively, potentially reducing the tendency to watch the clock.

5. Implement time management training. Offer training sessions focused on time management and efficiency. This can help staff manage their duties more effectively, reducing the need to constantly check the time.

6. Encourage open communication. Create an environment where staff feel comfortable discussing their concerns, including issues related to workload and time management. This can help identify and address specific factors contributing to clock watching.

7. Monitor and provide feedback. Regularly monitor staff performance and provide constructive feedback. If clock watching is observed, discuss it directly with the employee, focusing on the impact on patient care and the work environment.

8. Recognize and reward. Acknowledge and reward staff who consistently provide high-quality care and demonstrate effective time management. Recognition can motivate others to adjust their behavior.

9. Evaluate workloads. Regularly assess staff workloads to ensure they are manageable. Overburdened employees are more likely to engage in clock watching.

10. Lead by example. Management should model the behavior they wish to see in their staff. Demonstrating a commitment to patient care and effective time management can set a positive example.

Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at [email protected].

The following scenario was discussed during a forum at a meeting recently:

Two employees managing the front desk are clock watchers, always the first to leave at 11:59 a.m. for lunch and at 4:59 p.m. for the end of the day no matter what is happening. This leaves the other employees stuck with their work.

I have seen clock watching often enough to know that it is widely practiced, and widely reviled by coworkers and managers alike. Generally, clock watchers — sometimes referred to in modern parlance as “quiet quitters” — radiate a palpable sense of “I don’t want to be here.”

Physicians typically can’t identify with clock watching behavior, because we learned early on that patient-care tasks must be pursued to completion; if that involves working past the usual “quitting time,” so be it. So your first task in dealing with this problem is to determine its cause. The clock watcher label may be unfair. There may be legitimate reasons for certain employees to leave work at precisely 4:59 every day. Perhaps they must pick up children, or they have a second job to get to. The label usually comes from a pattern of consistent, repeated behavior. And if more than one employee is exhibiting the same behavior in the same office, the likelihood of a valid explanation decreases proportionally.

Utamaru Kido/Moment/Getty Images

A common cause of clock watching is a lack of employees’ commitment to their jobs. They don’t see the point in putting in extra effort, so they run out the door as soon as possible. There are many reasons why this might be the case. For example, the workload in your office may be too large to be accomplished in the time available by the number of people you employ. The solution might be to simply hire additional personnel.

Another common cause is a lack of communication between physicians, managers, and lower-level employees. If staffers are raising concerns or potential solutions, and management is not listening to their opinions or ideas, they will stop offering them. Alternatively, other staff members may not be pulling their weight. When there is a large imbalance in the contribution of team members, the higher performers will stop trying.

Over my 40 plus years in practice, I have had my share of clock watchers. I try the best I can not to let employees’ time commitment practices impact my valuation of their work. I always attempt to focus on quality and productivity. It isn’t easy, but I always try to address the issues behind clock watching behavior. As such, I can’t recall ever having to fire anyone for clock watching. Here are some of the strategies that have worked for me over the years:

1. Set clear expectations. Clearly communicate job responsibilities and expectations regarding time management and patient care. Ensure that all staff understand the importance of dedicating the necessary time to each patient, regardless of the time of day.

2. Foster a patient-centered culture. Cultivate a work environment that prioritizes patient care above all. This can help shift the focus from watching the clock to ensuring high-quality patient care.

3. Provide adequate breaks. Ensure that staff schedules include sufficient breaks. Overworked staff are more likely to watch the clock. Adequate rest periods can help alleviate this issue.

4. Offer flexibility where possible. If feasible, offer some degree of scheduling flexibility. This can help staff manage their personal time more effectively, potentially reducing the tendency to watch the clock.

5. Implement time management training. Offer training sessions focused on time management and efficiency. This can help staff manage their duties more effectively, reducing the need to constantly check the time.

6. Encourage open communication. Create an environment where staff feel comfortable discussing their concerns, including issues related to workload and time management. This can help identify and address specific factors contributing to clock watching.

7. Monitor and provide feedback. Regularly monitor staff performance and provide constructive feedback. If clock watching is observed, discuss it directly with the employee, focusing on the impact on patient care and the work environment.

8. Recognize and reward. Acknowledge and reward staff who consistently provide high-quality care and demonstrate effective time management. Recognition can motivate others to adjust their behavior.

9. Evaluate workloads. Regularly assess staff workloads to ensure they are manageable. Overburdened employees are more likely to engage in clock watching.

10. Lead by example. Management should model the behavior they wish to see in their staff. Demonstrating a commitment to patient care and effective time management can set a positive example.

Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at [email protected].

Unwanted weight gain is a common problem for women after menopause. Primary care clinicians have likely heard from patients that attempts at shedding extra pounds are not working.

Nearly three fourths of women aged 60 years and older in the United States are overweight. Some may blame menopause for this trend. But the life stage itself does not cause weight gain. Aging does: Women gain about 1.5 pounds per year on average starting almost a decade prior to menopause to a decade after their final menstrual cycle, according to research.

“A lot of women are in tears because they have gained 10 or 15 pounds,” said Stephanie Faubion, MD, medical director of The Menopause Society and director of the Mayo Clinic Center for Women’s Health in Jacksonville, Florida.

A shortage of obesity and menopause specialists means primary care clinicians must understand the intersection of weight management and how the body functions after menopause.

“The importance of weight management in midlife cannot be overemphasized,” Dr. Faubion said. “Excess weight around the middle increases the risk of diabetes and heart disease and that is directly related to the loss of estrogen.”

The loss of estrogen due to menopause also causes the redistribution of fat from the thighs, hips, and buttocks to the midsection, which can be more difficult to trim. And women naturally lose muscle mass as they age, in part because the hormone is important to muscle functioning, according to Maria Daniela Hurtado Andrade, MD, PhD, assistant professor of medicine at Mayo Clinic Alix School of Medicine in Jacksonville, Florida.

“Menopause compounds the changes associated with aging: It makes them worse,” Dr. Hurtado Andrade said.

Mounting evidence has linked obesity-related systemic inflammation with an increased risk for cardiovascular disease, including heart attacks and vascular damage.

Michael Knight, MD, clinical associate professor of medicine and a weight loss specialist at the George Washington University in Washington, DC, estimated that more than half of his patients are postmenopausal women.

He recommended clinicians look for adipose tissue dysfunction, which can cause localized insulin resistance and affect metabolic health. Research suggests clinicians can perform a basic metabolic panel, in addition to testing for triglyceride, low-density lipoprotein, and renal function levels. Several other recent studies have pointed to using waist circumference, insulin resistance, or presence of metabolic syndrome to diagnose adipose tissue dysfunction.

Beyond Diet and Exercise

Physicians should ask their patients about physical activity, the type of foods they are eating, and changes in day-to-day movement, Dr. Knight advised.

Pharmacotherapy or surgical options should be considered for some patients, according to Karen Adams, MD, clinical professor of obstetrics and gynecology and a lifestyle medicine specialist at Stanford Medicine in Palo Alto, California. Postmenopausal women who want to lose more than 5%-10% of their body weight likely will need another modality in addition to diet and exercise.

“What’s important is transitioning the patient from feeling like they’ve failed to a mindset of seeking help or seeking care for this condition,” she said. Dr. Adams, a certified menopause specialist, uses the idea of “good enough” with her patients and suggests they think of weight loss as a journey, which may require different tools at various points.

Glucagon-like peptide 1 receptor agonists like semaglutide or tirzepatide are some of the most effective drugs for obesity, according to Dr. Knight.

In addition to these drugs, hormone replacement therapy in combination with the weight loss drug semaglutide may improve weight loss and reduce cardiometabolic risk in postmenopausal women compared with semaglutide alone, as reported in a study Dr. Hurtado Andrade and Dr. Faubion recently coauthored. Improving vasomotor symptoms improved sleep, physical activity, and quality of life, which all can affect efforts to lose weight.

Most patients who struggle to lose weight using diet and exercise methods alone usually do not maintain a healthy weight long term, according to Knight. Physicians need a comprehensive strategy to introduce options like medications or surgery when indicated for long-term, weight management solutions.

Tips for primary care clinicians in helping postmenopausal women lose weight:

• Develop an effective solution that works for your patient’s lifestyle. If you don’t have one, make a referral to a weight loss specialist.
• Educate patients about obesity and postmenopausal weight loss challenges, to help destigmatize the condition. Explain that obesity is a chronic disease, like hypertension or diabetes.
• Exercise suggestions should consider issues like walkable neighborhoods, access and affordability of gym membership, and home broadband access.
• Strength training should be recommended to counter loss of muscle mass that comes with aging.
• Consider a patient’s culture when discussing healthier alternatives to their usual diet.
• Suggest simple changes to start, like eliminating simple carbohydrates — white bread, pasta, and white rice — as a good place to start.

Body mass index was not designed to be a clinical tool and does not fully assess weight in many populations. Risk for chronic diseases and obesity varies depending on whether a person carries weight centrally or on the hips and thighs.

But well before menopause, clinicians can educate their female patients on what body changes to expect and be more mindful about which medications to not prescribe.

People in menopause or perimenopause are frequently prescribed weight-promoting drugs like antidepressants for mood swings or gabapentin for hot flashes. Clinicians should conduct a medication review and look for alternatives to drugs that are associated with weight gain.

The best approach is to try to avoid weight gain in the first place, which can be easier than trying to lose later, Dr. Faubion said. “You can’t just exercise your way out of it,” she said.

Dr. Adams, Dr. Faubion, and Dr. Hurtado Andrade reported no disclosures. Dr. Knight is a former consultant with Novo Nordisk.

A version of this article appeared on Medscape.com.

Unwanted weight gain is a common problem for women after menopause. Primary care clinicians have likely heard from patients that attempts at shedding extra pounds are not working.

Nearly three fourths of women aged 60 years and older in the United States are overweight. Some may blame menopause for this trend. But the life stage itself does not cause weight gain. Aging does: Women gain about 1.5 pounds per year on average starting almost a decade prior to menopause to a decade after their final menstrual cycle, according to research.

“A lot of women are in tears because they have gained 10 or 15 pounds,” said Stephanie Faubion, MD, medical director of The Menopause Society and director of the Mayo Clinic Center for Women’s Health in Jacksonville, Florida.

A shortage of obesity and menopause specialists means primary care clinicians must understand the intersection of weight management and how the body functions after menopause.

“The importance of weight management in midlife cannot be overemphasized,” Dr. Faubion said. “Excess weight around the middle increases the risk of diabetes and heart disease and that is directly related to the loss of estrogen.”

The loss of estrogen due to menopause also causes the redistribution of fat from the thighs, hips, and buttocks to the midsection, which can be more difficult to trim. And women naturally lose muscle mass as they age, in part because the hormone is important to muscle functioning, according to Maria Daniela Hurtado Andrade, MD, PhD, assistant professor of medicine at Mayo Clinic Alix School of Medicine in Jacksonville, Florida.

“Menopause compounds the changes associated with aging: It makes them worse,” Dr. Hurtado Andrade said.

Mounting evidence has linked obesity-related systemic inflammation with an increased risk for cardiovascular disease, including heart attacks and vascular damage.

Michael Knight, MD, clinical associate professor of medicine and a weight loss specialist at the George Washington University in Washington, DC, estimated that more than half of his patients are postmenopausal women.

He recommended clinicians look for adipose tissue dysfunction, which can cause localized insulin resistance and affect metabolic health. Research suggests clinicians can perform a basic metabolic panel, in addition to testing for triglyceride, low-density lipoprotein, and renal function levels. Several other recent studies have pointed to using waist circumference, insulin resistance, or presence of metabolic syndrome to diagnose adipose tissue dysfunction.

Beyond Diet and Exercise

Physicians should ask their patients about physical activity, the type of foods they are eating, and changes in day-to-day movement, Dr. Knight advised.

Pharmacotherapy or surgical options should be considered for some patients, according to Karen Adams, MD, clinical professor of obstetrics and gynecology and a lifestyle medicine specialist at Stanford Medicine in Palo Alto, California. Postmenopausal women who want to lose more than 5%-10% of their body weight likely will need another modality in addition to diet and exercise.

“What’s important is transitioning the patient from feeling like they’ve failed to a mindset of seeking help or seeking care for this condition,” she said. Dr. Adams, a certified menopause specialist, uses the idea of “good enough” with her patients and suggests they think of weight loss as a journey, which may require different tools at various points.

Glucagon-like peptide 1 receptor agonists like semaglutide or tirzepatide are some of the most effective drugs for obesity, according to Dr. Knight.

In addition to these drugs, hormone replacement therapy in combination with the weight loss drug semaglutide may improve weight loss and reduce cardiometabolic risk in postmenopausal women compared with semaglutide alone, as reported in a study Dr. Hurtado Andrade and Dr. Faubion recently coauthored. Improving vasomotor symptoms improved sleep, physical activity, and quality of life, which all can affect efforts to lose weight.

Most patients who struggle to lose weight using diet and exercise methods alone usually do not maintain a healthy weight long term, according to Knight. Physicians need a comprehensive strategy to introduce options like medications or surgery when indicated for long-term, weight management solutions.

Tips for primary care clinicians in helping postmenopausal women lose weight:

• Develop an effective solution that works for your patient’s lifestyle. If you don’t have one, make a referral to a weight loss specialist.
• Educate patients about obesity and postmenopausal weight loss challenges, to help destigmatize the condition. Explain that obesity is a chronic disease, like hypertension or diabetes.
• Exercise suggestions should consider issues like walkable neighborhoods, access and affordability of gym membership, and home broadband access.
• Strength training should be recommended to counter loss of muscle mass that comes with aging.
• Consider a patient’s culture when discussing healthier alternatives to their usual diet.
• Suggest simple changes to start, like eliminating simple carbohydrates — white bread, pasta, and white rice — as a good place to start.

Body mass index was not designed to be a clinical tool and does not fully assess weight in many populations. Risk for chronic diseases and obesity varies depending on whether a person carries weight centrally or on the hips and thighs.

But well before menopause, clinicians can educate their female patients on what body changes to expect and be more mindful about which medications to not prescribe.

People in menopause or perimenopause are frequently prescribed weight-promoting drugs like antidepressants for mood swings or gabapentin for hot flashes. Clinicians should conduct a medication review and look for alternatives to drugs that are associated with weight gain.

The best approach is to try to avoid weight gain in the first place, which can be easier than trying to lose later, Dr. Faubion said. “You can’t just exercise your way out of it,” she said.

Dr. Adams, Dr. Faubion, and Dr. Hurtado Andrade reported no disclosures. Dr. Knight is a former consultant with Novo Nordisk.

A version of this article appeared on Medscape.com.

Unwanted weight gain is a common problem for women after menopause. Primary care clinicians have likely heard from patients that attempts at shedding extra pounds are not working.

Nearly three fourths of women aged 60 years and older in the United States are overweight. Some may blame menopause for this trend. But the life stage itself does not cause weight gain. Aging does: Women gain about 1.5 pounds per year on average starting almost a decade prior to menopause to a decade after their final menstrual cycle, according to research.

“A lot of women are in tears because they have gained 10 or 15 pounds,” said Stephanie Faubion, MD, medical director of The Menopause Society and director of the Mayo Clinic Center for Women’s Health in Jacksonville, Florida.

A shortage of obesity and menopause specialists means primary care clinicians must understand the intersection of weight management and how the body functions after menopause.

“The importance of weight management in midlife cannot be overemphasized,” Dr. Faubion said. “Excess weight around the middle increases the risk of diabetes and heart disease and that is directly related to the loss of estrogen.”

The loss of estrogen due to menopause also causes the redistribution of fat from the thighs, hips, and buttocks to the midsection, which can be more difficult to trim. And women naturally lose muscle mass as they age, in part because the hormone is important to muscle functioning, according to Maria Daniela Hurtado Andrade, MD, PhD, assistant professor of medicine at Mayo Clinic Alix School of Medicine in Jacksonville, Florida.

“Menopause compounds the changes associated with aging: It makes them worse,” Dr. Hurtado Andrade said.

Mounting evidence has linked obesity-related systemic inflammation with an increased risk for cardiovascular disease, including heart attacks and vascular damage.

Michael Knight, MD, clinical associate professor of medicine and a weight loss specialist at the George Washington University in Washington, DC, estimated that more than half of his patients are postmenopausal women.

He recommended clinicians look for adipose tissue dysfunction, which can cause localized insulin resistance and affect metabolic health. Research suggests clinicians can perform a basic metabolic panel, in addition to testing for triglyceride, low-density lipoprotein, and renal function levels. Several other recent studies have pointed to using waist circumference, insulin resistance, or presence of metabolic syndrome to diagnose adipose tissue dysfunction.

Beyond Diet and Exercise

Physicians should ask their patients about physical activity, the type of foods they are eating, and changes in day-to-day movement, Dr. Knight advised.

Pharmacotherapy or surgical options should be considered for some patients, according to Karen Adams, MD, clinical professor of obstetrics and gynecology and a lifestyle medicine specialist at Stanford Medicine in Palo Alto, California. Postmenopausal women who want to lose more than 5%-10% of their body weight likely will need another modality in addition to diet and exercise.

“What’s important is transitioning the patient from feeling like they’ve failed to a mindset of seeking help or seeking care for this condition,” she said. Dr. Adams, a certified menopause specialist, uses the idea of “good enough” with her patients and suggests they think of weight loss as a journey, which may require different tools at various points.

Glucagon-like peptide 1 receptor agonists like semaglutide or tirzepatide are some of the most effective drugs for obesity, according to Dr. Knight.

In addition to these drugs, hormone replacement therapy in combination with the weight loss drug semaglutide may improve weight loss and reduce cardiometabolic risk in postmenopausal women compared with semaglutide alone, as reported in a study Dr. Hurtado Andrade and Dr. Faubion recently coauthored. Improving vasomotor symptoms improved sleep, physical activity, and quality of life, which all can affect efforts to lose weight.

Most patients who struggle to lose weight using diet and exercise methods alone usually do not maintain a healthy weight long term, according to Knight. Physicians need a comprehensive strategy to introduce options like medications or surgery when indicated for long-term, weight management solutions.

Tips for primary care clinicians in helping postmenopausal women lose weight:

• Develop an effective solution that works for your patient’s lifestyle. If you don’t have one, make a referral to a weight loss specialist.
• Educate patients about obesity and postmenopausal weight loss challenges, to help destigmatize the condition. Explain that obesity is a chronic disease, like hypertension or diabetes.
• Exercise suggestions should consider issues like walkable neighborhoods, access and affordability of gym membership, and home broadband access.
• Strength training should be recommended to counter loss of muscle mass that comes with aging.
• Consider a patient’s culture when discussing healthier alternatives to their usual diet.
• Suggest simple changes to start, like eliminating simple carbohydrates — white bread, pasta, and white rice — as a good place to start.

Body mass index was not designed to be a clinical tool and does not fully assess weight in many populations. Risk for chronic diseases and obesity varies depending on whether a person carries weight centrally or on the hips and thighs.

But well before menopause, clinicians can educate their female patients on what body changes to expect and be more mindful about which medications to not prescribe.

People in menopause or perimenopause are frequently prescribed weight-promoting drugs like antidepressants for mood swings or gabapentin for hot flashes. Clinicians should conduct a medication review and look for alternatives to drugs that are associated with weight gain.

The best approach is to try to avoid weight gain in the first place, which can be easier than trying to lose later, Dr. Faubion said. “You can’t just exercise your way out of it,” she said.

Dr. Adams, Dr. Faubion, and Dr. Hurtado Andrade reported no disclosures. Dr. Knight is a former consultant with Novo Nordisk.

A version of this article appeared on Medscape.com.

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

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

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

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


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

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


How did that experience impact your aspirations?

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


What led to your interest in cancer treatment?

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


Were there patients who inspired your research?

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

Was the second patient’s case as impressive?

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


From there, how did your work evolve?

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


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

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

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


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

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

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

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

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

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


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

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


How did that experience impact your aspirations?

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


What led to your interest in cancer treatment?

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


Were there patients who inspired your research?

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

Was the second patient’s case as impressive?

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


From there, how did your work evolve?

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


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

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

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


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

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

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

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

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

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


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

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


How did that experience impact your aspirations?

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


What led to your interest in cancer treatment?

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


Were there patients who inspired your research?

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

Was the second patient’s case as impressive?

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


From there, how did your work evolve?