AVAHO

A safety analysis following a landmark randomized phase 3 trial confirms that vomiting and nausea are quite common in patients who take the drug trastuzumab deruxtecan (T-DXd; Enhertu) to treat HER2-low metastatic breast cancer. Interstitial lung disease (ILD) also remains a concern, and it’s not clear if retreatment after resolution is warranted.

In general, however, “T-DXd demonstrates a manageable safety profile consistent with prior reports. Results from this safety analysis continued to support its use as a new standard of care in patients with HER2-low metastatic breast cancer,” said report lead author Hope Rugo, MD, of the University of California, San Francisco, during a presentation at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress.

T-DXd, an antibody-drug conjugate, received FDA approval in August 2022 for patients with HER2-low disease. The drug has been touted as “practice changing” and a “new standard of care.”

However, physicians have noted that the benefits of the drug come at the cost of significant adverse effects, including some that can cause hospitalization. There’s special concern about high-grade interstitial lung disease/pneumonitis, and an FDA boxed warning cautions clinicians about this possible side effect.

For the new analysis, researchers presented additional safety data from the industry-funded DESTINY-Breast04 trial, whose results was published in July 2022 in the New England Journal of Medicine. That study randomized 373 patients to T-DXd and 184 to physician’s choice of treatment. It found that, “among all patients, the median progression-free survival was 9.9 months in the trastuzumab deruxtecan group and 5.1 months in the physician’s choice group (hazard ratio for disease progression or death, 0.50; P < .001), and overall survival was 23.4 months and 16.8 months, respectively (hazard ratio for death, 0.64; P = .001).”

Exposure-adjusted incidence rates for any-grade treatment-emergent adverse events were lower for T-DXd versus physician’s choice of treatment (1.30 vs. 2.66). However, nausea and vomiting events were more than twice as common in patients who took T-DXd versus the physician’s choice (79.5% vs. 35.5%).

A total of 50.9% of patients in the T-DXd arm received antiemetic prophylaxis versus 37.2% in the physician’s choice arm. A single patient discontinued T-DXd treatment because of vomiting, and a single patient discontinued treatment because of nausea. No patients in the physician choice group discontinued treatment because of nausea or vomiting.

Neutropenia and febrile neutropenia were less frequent in the T-DXd arm versus physician’s choice (12.9% vs. 18.0% and 0.3% vs. 2.9%, respectively.)

ILD occurred in 45 patients (12.1%) of those in the T-DXd arm versus 1 (0.6%) in the physician choice arm. Ten patients of the patients in the T-DXd arm had not recovered by the data cutoff point.

Six patients with ILD were retreated following resolution; one discontinued because of an adverse event, two discontinued because of progressive disease, and three remained on the drug. “Given that there was only a small number of patients who were retreated with T-DXd, it’s difficult to make clinically meaningful conclusions on the effect of retreatment following grade IDL events that have resolved,” Dr. Rugo said.

In the big picture, “ILD pneumonitis remains an important identified risk and an adverse event of interest associated with T-DXd,” Dr. Rugo said. “It’s important that we adhere to management guidelines and updated toxicity management guidelines.”

In a discussion, Dr. Rugo said she prescribes three antiemetic drugs to help patients tolerate T-DXd therapy: “It makes a big difference. Anecdotally, it really has improved management of nausea. Start more and back down [as symptoms fade].”

Gustavo Werutsky, MD, PhD, of Moinhos de Vento Hospital, Porto Alegre, Brazil, the discussant for the presentation, also emphasized the importance of prevention and said he prescribes two or three prophylactic drugs. “In the beginning, we didn’t know these events were so important. A big part of the message is that patients from the beginning need to have a good prophylaxis for the nausea and vomiting.”

The researchers also presented a related report at the conference, an analysis of patient-reported outcomes from DESTINY-Breast02, a randomized phase 3 study of T-DXd (n = 406) versus physician’s choice of treatment (n = 202) in patients with HER2-positive metastatic breast cancer who were resistant/refractory to trastuzumab emtansine.

The analysis, led by Tanja Fehm, MD, of University Hospital Düsseldorf (Germany), found that the median time to definitive deterioration was longer with T-DXd versus the other arm per the EORTC QLQ-C30 global health status/quality of life score (14.1 vs. 5.9 months; HR, 0.56; 95% confidence interval, 0.44-0.71).

The studies were funded by Daiichi Sankyo and AstraZeneca, which make T-DXd. Dr. Hugo discloses relationships with Puma, NAPO, Blueprint, Scorpion Therapeutics, Merck, AstraZeneca, Gilead, Astellas, Daiichi Sankyo, F. Hoffmann–La Roche/Genentech, GlaxoSmithKline, Lilly, Novartis, OBI, Pfizer, Pionyr, Sermonix, Taiho Oncology, and Veru. Multiple other authors of both studies have various disclosures.

A safety analysis following a landmark randomized phase 3 trial confirms that vomiting and nausea are quite common in patients who take the drug trastuzumab deruxtecan (T-DXd; Enhertu) to treat HER2-low metastatic breast cancer. Interstitial lung disease (ILD) also remains a concern, and it’s not clear if retreatment after resolution is warranted.

In general, however, “T-DXd demonstrates a manageable safety profile consistent with prior reports. Results from this safety analysis continued to support its use as a new standard of care in patients with HER2-low metastatic breast cancer,” said report lead author Hope Rugo, MD, of the University of California, San Francisco, during a presentation at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress.

T-DXd, an antibody-drug conjugate, received FDA approval in August 2022 for patients with HER2-low disease. The drug has been touted as “practice changing” and a “new standard of care.”

However, physicians have noted that the benefits of the drug come at the cost of significant adverse effects, including some that can cause hospitalization. There’s special concern about high-grade interstitial lung disease/pneumonitis, and an FDA boxed warning cautions clinicians about this possible side effect.

For the new analysis, researchers presented additional safety data from the industry-funded DESTINY-Breast04 trial, whose results was published in July 2022 in the New England Journal of Medicine. That study randomized 373 patients to T-DXd and 184 to physician’s choice of treatment. It found that, “among all patients, the median progression-free survival was 9.9 months in the trastuzumab deruxtecan group and 5.1 months in the physician’s choice group (hazard ratio for disease progression or death, 0.50; P < .001), and overall survival was 23.4 months and 16.8 months, respectively (hazard ratio for death, 0.64; P = .001).”

Exposure-adjusted incidence rates for any-grade treatment-emergent adverse events were lower for T-DXd versus physician’s choice of treatment (1.30 vs. 2.66). However, nausea and vomiting events were more than twice as common in patients who took T-DXd versus the physician’s choice (79.5% vs. 35.5%).

A total of 50.9% of patients in the T-DXd arm received antiemetic prophylaxis versus 37.2% in the physician’s choice arm. A single patient discontinued T-DXd treatment because of vomiting, and a single patient discontinued treatment because of nausea. No patients in the physician choice group discontinued treatment because of nausea or vomiting.

Neutropenia and febrile neutropenia were less frequent in the T-DXd arm versus physician’s choice (12.9% vs. 18.0% and 0.3% vs. 2.9%, respectively.)

ILD occurred in 45 patients (12.1%) of those in the T-DXd arm versus 1 (0.6%) in the physician choice arm. Ten patients of the patients in the T-DXd arm had not recovered by the data cutoff point.

Six patients with ILD were retreated following resolution; one discontinued because of an adverse event, two discontinued because of progressive disease, and three remained on the drug. “Given that there was only a small number of patients who were retreated with T-DXd, it’s difficult to make clinically meaningful conclusions on the effect of retreatment following grade IDL events that have resolved,” Dr. Rugo said.

In the big picture, “ILD pneumonitis remains an important identified risk and an adverse event of interest associated with T-DXd,” Dr. Rugo said. “It’s important that we adhere to management guidelines and updated toxicity management guidelines.”

In a discussion, Dr. Rugo said she prescribes three antiemetic drugs to help patients tolerate T-DXd therapy: “It makes a big difference. Anecdotally, it really has improved management of nausea. Start more and back down [as symptoms fade].”

Gustavo Werutsky, MD, PhD, of Moinhos de Vento Hospital, Porto Alegre, Brazil, the discussant for the presentation, also emphasized the importance of prevention and said he prescribes two or three prophylactic drugs. “In the beginning, we didn’t know these events were so important. A big part of the message is that patients from the beginning need to have a good prophylaxis for the nausea and vomiting.”

The researchers also presented a related report at the conference, an analysis of patient-reported outcomes from DESTINY-Breast02, a randomized phase 3 study of T-DXd (n = 406) versus physician’s choice of treatment (n = 202) in patients with HER2-positive metastatic breast cancer who were resistant/refractory to trastuzumab emtansine.

The analysis, led by Tanja Fehm, MD, of University Hospital Düsseldorf (Germany), found that the median time to definitive deterioration was longer with T-DXd versus the other arm per the EORTC QLQ-C30 global health status/quality of life score (14.1 vs. 5.9 months; HR, 0.56; 95% confidence interval, 0.44-0.71).

The studies were funded by Daiichi Sankyo and AstraZeneca, which make T-DXd. Dr. Hugo discloses relationships with Puma, NAPO, Blueprint, Scorpion Therapeutics, Merck, AstraZeneca, Gilead, Astellas, Daiichi Sankyo, F. Hoffmann–La Roche/Genentech, GlaxoSmithKline, Lilly, Novartis, OBI, Pfizer, Pionyr, Sermonix, Taiho Oncology, and Veru. Multiple other authors of both studies have various disclosures.

A safety analysis following a landmark randomized phase 3 trial confirms that vomiting and nausea are quite common in patients who take the drug trastuzumab deruxtecan (T-DXd; Enhertu) to treat HER2-low metastatic breast cancer. Interstitial lung disease (ILD) also remains a concern, and it’s not clear if retreatment after resolution is warranted.

In general, however, “T-DXd demonstrates a manageable safety profile consistent with prior reports. Results from this safety analysis continued to support its use as a new standard of care in patients with HER2-low metastatic breast cancer,” said report lead author Hope Rugo, MD, of the University of California, San Francisco, during a presentation at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress.

T-DXd, an antibody-drug conjugate, received FDA approval in August 2022 for patients with HER2-low disease. The drug has been touted as “practice changing” and a “new standard of care.”

However, physicians have noted that the benefits of the drug come at the cost of significant adverse effects, including some that can cause hospitalization. There’s special concern about high-grade interstitial lung disease/pneumonitis, and an FDA boxed warning cautions clinicians about this possible side effect.

For the new analysis, researchers presented additional safety data from the industry-funded DESTINY-Breast04 trial, whose results was published in July 2022 in the New England Journal of Medicine. That study randomized 373 patients to T-DXd and 184 to physician’s choice of treatment. It found that, “among all patients, the median progression-free survival was 9.9 months in the trastuzumab deruxtecan group and 5.1 months in the physician’s choice group (hazard ratio for disease progression or death, 0.50; P < .001), and overall survival was 23.4 months and 16.8 months, respectively (hazard ratio for death, 0.64; P = .001).”

Exposure-adjusted incidence rates for any-grade treatment-emergent adverse events were lower for T-DXd versus physician’s choice of treatment (1.30 vs. 2.66). However, nausea and vomiting events were more than twice as common in patients who took T-DXd versus the physician’s choice (79.5% vs. 35.5%).

A total of 50.9% of patients in the T-DXd arm received antiemetic prophylaxis versus 37.2% in the physician’s choice arm. A single patient discontinued T-DXd treatment because of vomiting, and a single patient discontinued treatment because of nausea. No patients in the physician choice group discontinued treatment because of nausea or vomiting.

Neutropenia and febrile neutropenia were less frequent in the T-DXd arm versus physician’s choice (12.9% vs. 18.0% and 0.3% vs. 2.9%, respectively.)

ILD occurred in 45 patients (12.1%) of those in the T-DXd arm versus 1 (0.6%) in the physician choice arm. Ten patients of the patients in the T-DXd arm had not recovered by the data cutoff point.

Six patients with ILD were retreated following resolution; one discontinued because of an adverse event, two discontinued because of progressive disease, and three remained on the drug. “Given that there was only a small number of patients who were retreated with T-DXd, it’s difficult to make clinically meaningful conclusions on the effect of retreatment following grade IDL events that have resolved,” Dr. Rugo said.

In the big picture, “ILD pneumonitis remains an important identified risk and an adverse event of interest associated with T-DXd,” Dr. Rugo said. “It’s important that we adhere to management guidelines and updated toxicity management guidelines.”

In a discussion, Dr. Rugo said she prescribes three antiemetic drugs to help patients tolerate T-DXd therapy: “It makes a big difference. Anecdotally, it really has improved management of nausea. Start more and back down [as symptoms fade].”

Gustavo Werutsky, MD, PhD, of Moinhos de Vento Hospital, Porto Alegre, Brazil, the discussant for the presentation, also emphasized the importance of prevention and said he prescribes two or three prophylactic drugs. “In the beginning, we didn’t know these events were so important. A big part of the message is that patients from the beginning need to have a good prophylaxis for the nausea and vomiting.”

The researchers also presented a related report at the conference, an analysis of patient-reported outcomes from DESTINY-Breast02, a randomized phase 3 study of T-DXd (n = 406) versus physician’s choice of treatment (n = 202) in patients with HER2-positive metastatic breast cancer who were resistant/refractory to trastuzumab emtansine.

The analysis, led by Tanja Fehm, MD, of University Hospital Düsseldorf (Germany), found that the median time to definitive deterioration was longer with T-DXd versus the other arm per the EORTC QLQ-C30 global health status/quality of life score (14.1 vs. 5.9 months; HR, 0.56; 95% confidence interval, 0.44-0.71).

The studies were funded by Daiichi Sankyo and AstraZeneca, which make T-DXd. Dr. Hugo discloses relationships with Puma, NAPO, Blueprint, Scorpion Therapeutics, Merck, AstraZeneca, Gilead, Astellas, Daiichi Sankyo, F. Hoffmann–La Roche/Genentech, GlaxoSmithKline, Lilly, Novartis, OBI, Pfizer, Pionyr, Sermonix, Taiho Oncology, and Veru. Multiple other authors of both studies have various disclosures.

In postmenopausal women with hormone receptor–positive breast cancer, overweight and obesity were overall predictors of lower disease-free survival, but body mass index had no apparent association with the effect of extended endocrine therapy on disease-free survival, new data suggest.

Obesity is a well-known risk factor for breast cancer in postmenopausal women and has been associated with adverse prognosis, said Senna W.M. Lammers, MD, of Maastricht (the Netherlands) University during a presentation at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress. In addition, some studies suggest that patients with higher body mass index (BMI) experience reduced benefits from endocrine therapy, she said.

Dr. Lammers and colleagues conducted a study to determine the prognostic and predictive effect of BMI on disease-free survival in postmenopausal women with hormone receptor–positive (HR+) breast cancer who were treated with extended endocrine therapy.

The study population included participants in the randomized, phase III DATA trial, which evaluated the use of 6 years vs. 3 years of anastrozole in postmenopausal women with HR+ breast cancer who were disease-free after 2-3 years of adjuvant tamoxifen therapy.

Patients were categorized based on BMI as having normal weight (18.5-24.9 kg/m²), overweight (25-29.9 kg/m²), or obese (30 kg/m² or higher). The primary outcome was disease-free survival (DFS); the median follow-up period was 13.1 years.

DFS for patients with normal weight, overweight, and obesity was 66.2%, 59.5%, and 52.4%, with a P value of less than .001 for the trend, Dr. Lammers said. “These results were confirmed in multivariable analysis,” she said. Overall, patients with overweight and obesity had a worse DFS when compared with patients with normal weight (hazard ratio, 1.16; P = .10, for patients with overweight and HR, 1.26; P = .03 for patients with obesity).

“Next, we aimed to determine whether the prognostic effect of BMI differed by age,” Dr. Lammers said.

In women younger than 60 years, overweight and obesity were significantly associated with worse DFS (HR, 1.29; P = .05 and HR 1.83, P less than .001, respectively). However, this effect was not observed in women aged 60 years and older.

The researchers also examined the treatment effect of extended anastrozole on adapted DFS by weight, and found no significant differences among patients with normal weight, overweight, and obesity (HR, 1.00; HR, 0.74; and HR, 0.97, respectively), said Dr. Lammers.

In the question and answer session, Dr. Lammers was asked about possible explanations for the difference in DFS by age. Potential explanations include possible survival bias “as only the healthier [patients with obesity] survive to old age,” she said. Other potential explanations are biological, such as the potentially higher levels of bone density in older [patients with obesity], she said.

When asked about additional clinical implications, Dr. Lammers emphasized the importance of maintaining a healthy BMI for breast cancer patients of all ages. Other research areas might involve the use of lifestyle interventions, although these are challenging to implement, she noted.
 

Data draw attention to quality of life and lifestyle factors

The need to “look at drug development with new eyes” is particularly important when reviewing patient-reported outcomes, said Otto Metzger, MD, of the Dana Farber Cancer Institute, Boston, who served as the discussant for the session.

Dr. Metzger brought up the association between age and the effect of BMI on DFS, specifically.

Based on data from multiple studies and meta-analyses, “I do believe that obesity does play a role in prognosis,” he said, but the question is how long will researchers continue to simply record data without acting to add lifestyle interventions while also trying to develop new drugs, he said. Although convincing patients to make lifestyle changes remains a challenge, patients are often more motivated to make such changes after a cancer diagnosis, Dr. Metzger noted.

“I am a firm believer in the use of digital therapeutics in the context of clinical trials,” said Dr. Metzger. Digital technology offers great potential to educate patients on [adverse effects] and also to improve treatment adherence and quality of life, he concluded.

The study was supported by AstraZeneca, and Dr. Lammers disclosed financial relationships with AstraZeneca and Eli Lilly. Dr. Metzger disclosed receiving research funding to his institution from Pfizer, Genentech/Roche, and Sanofi, and serving as an adviser/consultant to AstraZeneca, Merck, Oncoclinicas, Resilience, and Roche.

In postmenopausal women with hormone receptor–positive breast cancer, overweight and obesity were overall predictors of lower disease-free survival, but body mass index had no apparent association with the effect of extended endocrine therapy on disease-free survival, new data suggest.

Obesity is a well-known risk factor for breast cancer in postmenopausal women and has been associated with adverse prognosis, said Senna W.M. Lammers, MD, of Maastricht (the Netherlands) University during a presentation at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress. In addition, some studies suggest that patients with higher body mass index (BMI) experience reduced benefits from endocrine therapy, she said.

Dr. Lammers and colleagues conducted a study to determine the prognostic and predictive effect of BMI on disease-free survival in postmenopausal women with hormone receptor–positive (HR+) breast cancer who were treated with extended endocrine therapy.

The study population included participants in the randomized, phase III DATA trial, which evaluated the use of 6 years vs. 3 years of anastrozole in postmenopausal women with HR+ breast cancer who were disease-free after 2-3 years of adjuvant tamoxifen therapy.

Patients were categorized based on BMI as having normal weight (18.5-24.9 kg/m²), overweight (25-29.9 kg/m²), or obese (30 kg/m² or higher). The primary outcome was disease-free survival (DFS); the median follow-up period was 13.1 years.

DFS for patients with normal weight, overweight, and obesity was 66.2%, 59.5%, and 52.4%, with a P value of less than .001 for the trend, Dr. Lammers said. “These results were confirmed in multivariable analysis,” she said. Overall, patients with overweight and obesity had a worse DFS when compared with patients with normal weight (hazard ratio, 1.16; P = .10, for patients with overweight and HR, 1.26; P = .03 for patients with obesity).

“Next, we aimed to determine whether the prognostic effect of BMI differed by age,” Dr. Lammers said.

In women younger than 60 years, overweight and obesity were significantly associated with worse DFS (HR, 1.29; P = .05 and HR 1.83, P less than .001, respectively). However, this effect was not observed in women aged 60 years and older.

The researchers also examined the treatment effect of extended anastrozole on adapted DFS by weight, and found no significant differences among patients with normal weight, overweight, and obesity (HR, 1.00; HR, 0.74; and HR, 0.97, respectively), said Dr. Lammers.

In the question and answer session, Dr. Lammers was asked about possible explanations for the difference in DFS by age. Potential explanations include possible survival bias “as only the healthier [patients with obesity] survive to old age,” she said. Other potential explanations are biological, such as the potentially higher levels of bone density in older [patients with obesity], she said.

When asked about additional clinical implications, Dr. Lammers emphasized the importance of maintaining a healthy BMI for breast cancer patients of all ages. Other research areas might involve the use of lifestyle interventions, although these are challenging to implement, she noted.
 

Data draw attention to quality of life and lifestyle factors

The need to “look at drug development with new eyes” is particularly important when reviewing patient-reported outcomes, said Otto Metzger, MD, of the Dana Farber Cancer Institute, Boston, who served as the discussant for the session.

Dr. Metzger brought up the association between age and the effect of BMI on DFS, specifically.

Based on data from multiple studies and meta-analyses, “I do believe that obesity does play a role in prognosis,” he said, but the question is how long will researchers continue to simply record data without acting to add lifestyle interventions while also trying to develop new drugs, he said. Although convincing patients to make lifestyle changes remains a challenge, patients are often more motivated to make such changes after a cancer diagnosis, Dr. Metzger noted.

“I am a firm believer in the use of digital therapeutics in the context of clinical trials,” said Dr. Metzger. Digital technology offers great potential to educate patients on [adverse effects] and also to improve treatment adherence and quality of life, he concluded.

The study was supported by AstraZeneca, and Dr. Lammers disclosed financial relationships with AstraZeneca and Eli Lilly. Dr. Metzger disclosed receiving research funding to his institution from Pfizer, Genentech/Roche, and Sanofi, and serving as an adviser/consultant to AstraZeneca, Merck, Oncoclinicas, Resilience, and Roche.

In postmenopausal women with hormone receptor–positive breast cancer, overweight and obesity were overall predictors of lower disease-free survival, but body mass index had no apparent association with the effect of extended endocrine therapy on disease-free survival, new data suggest.

Obesity is a well-known risk factor for breast cancer in postmenopausal women and has been associated with adverse prognosis, said Senna W.M. Lammers, MD, of Maastricht (the Netherlands) University during a presentation at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress. In addition, some studies suggest that patients with higher body mass index (BMI) experience reduced benefits from endocrine therapy, she said.

Dr. Lammers and colleagues conducted a study to determine the prognostic and predictive effect of BMI on disease-free survival in postmenopausal women with hormone receptor–positive (HR+) breast cancer who were treated with extended endocrine therapy.

The study population included participants in the randomized, phase III DATA trial, which evaluated the use of 6 years vs. 3 years of anastrozole in postmenopausal women with HR+ breast cancer who were disease-free after 2-3 years of adjuvant tamoxifen therapy.

Patients were categorized based on BMI as having normal weight (18.5-24.9 kg/m²), overweight (25-29.9 kg/m²), or obese (30 kg/m² or higher). The primary outcome was disease-free survival (DFS); the median follow-up period was 13.1 years.

DFS for patients with normal weight, overweight, and obesity was 66.2%, 59.5%, and 52.4%, with a P value of less than .001 for the trend, Dr. Lammers said. “These results were confirmed in multivariable analysis,” she said. Overall, patients with overweight and obesity had a worse DFS when compared with patients with normal weight (hazard ratio, 1.16; P = .10, for patients with overweight and HR, 1.26; P = .03 for patients with obesity).

“Next, we aimed to determine whether the prognostic effect of BMI differed by age,” Dr. Lammers said.

In women younger than 60 years, overweight and obesity were significantly associated with worse DFS (HR, 1.29; P = .05 and HR 1.83, P less than .001, respectively). However, this effect was not observed in women aged 60 years and older.

The researchers also examined the treatment effect of extended anastrozole on adapted DFS by weight, and found no significant differences among patients with normal weight, overweight, and obesity (HR, 1.00; HR, 0.74; and HR, 0.97, respectively), said Dr. Lammers.

In the question and answer session, Dr. Lammers was asked about possible explanations for the difference in DFS by age. Potential explanations include possible survival bias “as only the healthier [patients with obesity] survive to old age,” she said. Other potential explanations are biological, such as the potentially higher levels of bone density in older [patients with obesity], she said.

When asked about additional clinical implications, Dr. Lammers emphasized the importance of maintaining a healthy BMI for breast cancer patients of all ages. Other research areas might involve the use of lifestyle interventions, although these are challenging to implement, she noted.
 

Data draw attention to quality of life and lifestyle factors

The need to “look at drug development with new eyes” is particularly important when reviewing patient-reported outcomes, said Otto Metzger, MD, of the Dana Farber Cancer Institute, Boston, who served as the discussant for the session.

Dr. Metzger brought up the association between age and the effect of BMI on DFS, specifically.

Based on data from multiple studies and meta-analyses, “I do believe that obesity does play a role in prognosis,” he said, but the question is how long will researchers continue to simply record data without acting to add lifestyle interventions while also trying to develop new drugs, he said. Although convincing patients to make lifestyle changes remains a challenge, patients are often more motivated to make such changes after a cancer diagnosis, Dr. Metzger noted.

“I am a firm believer in the use of digital therapeutics in the context of clinical trials,” said Dr. Metzger. Digital technology offers great potential to educate patients on [adverse effects] and also to improve treatment adherence and quality of life, he concluded.

The study was supported by AstraZeneca, and Dr. Lammers disclosed financial relationships with AstraZeneca and Eli Lilly. Dr. Metzger disclosed receiving research funding to his institution from Pfizer, Genentech/Roche, and Sanofi, and serving as an adviser/consultant to AstraZeneca, Merck, Oncoclinicas, Resilience, and Roche.

Venetoclax combinations – especially a novel combination of venetoclax, ibrutinib, and obinutuzumab – outperform first-line chemoimmunotherapy for chronic lymphocytic leukemia in otherwise fit adults with few comorbidities, according to a phase 3 trial published in the New England Journal of Medicine.

The trial, dubbed GAIA–CLL13, “is a remarkable demonstration of the quality of fixed-duration therapies for younger, fit patients, and it challenges us to continue to work to develop therapeutic strategies that will ultimately cure patients with CLL,” two hematologic cancer specialists said in an accompanying editorial.

In short, “venetoclax-obinutuzumab and venetoclax-obinutuzumab-ibrutinib were superior to chemoimmunotherapy with respect to both the minimal residual disease end point and progression-free survival, but venetoclax-rituximab was not,” Jennifer Woyach, MD, of Ohio State University, Columbus, and John Byrd, MD, University of Cincinnati, said in their commentary.

Noting that randomized trials involving venetoclax combinations in fit CLL patients “have been lacking,” the investigators compared 6 cycles of chemoimmunotherapy (fludarabine-cyclophosphamide-rituximab or bendamustine-rituximab) with 12 cycles of venetoclax plus the anti-CD20 antibody rituximab, venetoclax plus the third generation anti-CD20 antibody obinutuzumab, and venetoclax combined with both obinutuzumab and the Bruton’s tyrosine kinase inhibitor ibrutinib in a novel triple-therapy regimen.

The 926 patients in the study were a mean of 61 years old and split about evenly among the four treatment arms. Ibrutinib was discontinued after two consecutive measurements if patients had undetectable minimal residual disease (uMRD). Subjects did not have TP53 aberrations, a marker of poor prognosis in CLL.

At 15 months, the percentage of patients with uMRD was significantly higher in the triple-therapy arm (92.2%) and the venetoclax-obinutuzumab group (86.5%) than in the chemoimmunotherapy group (52.0%), but there was no statistical difference with venetoclax-rituximab (57%, P = .32).

The three-year progression-free survival (PFS) was 90.5% in the triple-therapy arm versus 87.7% with venetoclax-obinutuzumab. The 3-year PFS with venetoclax-rituximab (80.8%) was again not statistically different than the 75.5% with chemoimmunotherapy (P = .18).
 

Not ready for prime time

The benefits of triple therapy and venetoclax-obinutuzumab held only in patients with unmutated IgVH. “The high efficacy of the fludarabine, cyclophosphamide, and rituximab regimen in young, fit patients with mutated IgVH may be difficult to improve on,” noted the investigators, led by Barbara Eichhorst, MD, a hematologic malignancy specialist at the University of Cologne (Germany).

Also, although triple-therapy results were impressive, some of the benefits “are neutralized by the need for dose reductions and early treatment discontinuation owing to adverse events,” they said.

For instance, triple therapy had the highest incidence of both grade 3 and 4 infections (21.2%) and atrial fibrillation (7.8%).

The editorialists noted that there has been “a flurry of interest” in trials combining ibrutinib and venetoclax – as was done in the triple-therapy arm – since both emerged as powerful tools against CLL in recent years. However, even with the study results, they said “the use of triplet therapy should be viewed as investigational.”

For one thing, rates of uMRD were not “dramatically different” between triple therapy and venetoclax-obinutuzumab, and longer follow-up is better gauge differences in PFS and long-term toxicities.

Also, ibrutinib is being eclipsed by the second-generation Bruton’s tyrosine kinase inhibitors acalabrutinib and zanubrutinib, because they have better safety profiles, and they are being assessed in CLL combination trials. For now, there are too many unknowns for routine use of triple therapy in fit CLL patients, they said.

The investigators and editorialists both noted that improved uMRD in the study translated into superior PFS, raising the possibility that uMRD might be a valid alternative endpoint to PFS in CLL trials.

With “median remissions in CLL lasting far in excess of 5 years, designing studies that take 8-10 years” to reach a PFS endpoint is simply too slow. Moving to an alternative endpoint such a uMRD would preserve “the momentum that has been generated” with recent advances, Dr. Woyach and Dr. Byrd said.

The work was funded by the companies that market venetoclax, ibrutinib, and obinutuzumab: AbbVie, Janssen, and Roche. Dr. Eichhorst is a consultant and/or speaker for the companies and also reported grants from them. Dr. Byrd is a consultant/adviser for Eilean Therapeutics, Kurome Therapeutics, Newave, and Orbimed. Dr. Woyach disclosed ties with AbbVie, AstraZeneca, Lilly, and other companies.

Venetoclax combinations – especially a novel combination of venetoclax, ibrutinib, and obinutuzumab – outperform first-line chemoimmunotherapy for chronic lymphocytic leukemia in otherwise fit adults with few comorbidities, according to a phase 3 trial published in the New England Journal of Medicine.

The trial, dubbed GAIA–CLL13, “is a remarkable demonstration of the quality of fixed-duration therapies for younger, fit patients, and it challenges us to continue to work to develop therapeutic strategies that will ultimately cure patients with CLL,” two hematologic cancer specialists said in an accompanying editorial.

In short, “venetoclax-obinutuzumab and venetoclax-obinutuzumab-ibrutinib were superior to chemoimmunotherapy with respect to both the minimal residual disease end point and progression-free survival, but venetoclax-rituximab was not,” Jennifer Woyach, MD, of Ohio State University, Columbus, and John Byrd, MD, University of Cincinnati, said in their commentary.

Noting that randomized trials involving venetoclax combinations in fit CLL patients “have been lacking,” the investigators compared 6 cycles of chemoimmunotherapy (fludarabine-cyclophosphamide-rituximab or bendamustine-rituximab) with 12 cycles of venetoclax plus the anti-CD20 antibody rituximab, venetoclax plus the third generation anti-CD20 antibody obinutuzumab, and venetoclax combined with both obinutuzumab and the Bruton’s tyrosine kinase inhibitor ibrutinib in a novel triple-therapy regimen.

The 926 patients in the study were a mean of 61 years old and split about evenly among the four treatment arms. Ibrutinib was discontinued after two consecutive measurements if patients had undetectable minimal residual disease (uMRD). Subjects did not have TP53 aberrations, a marker of poor prognosis in CLL.

At 15 months, the percentage of patients with uMRD was significantly higher in the triple-therapy arm (92.2%) and the venetoclax-obinutuzumab group (86.5%) than in the chemoimmunotherapy group (52.0%), but there was no statistical difference with venetoclax-rituximab (57%, P = .32).

The three-year progression-free survival (PFS) was 90.5% in the triple-therapy arm versus 87.7% with venetoclax-obinutuzumab. The 3-year PFS with venetoclax-rituximab (80.8%) was again not statistically different than the 75.5% with chemoimmunotherapy (P = .18).
 

Not ready for prime time

The benefits of triple therapy and venetoclax-obinutuzumab held only in patients with unmutated IgVH. “The high efficacy of the fludarabine, cyclophosphamide, and rituximab regimen in young, fit patients with mutated IgVH may be difficult to improve on,” noted the investigators, led by Barbara Eichhorst, MD, a hematologic malignancy specialist at the University of Cologne (Germany).

Also, although triple-therapy results were impressive, some of the benefits “are neutralized by the need for dose reductions and early treatment discontinuation owing to adverse events,” they said.

For instance, triple therapy had the highest incidence of both grade 3 and 4 infections (21.2%) and atrial fibrillation (7.8%).

The editorialists noted that there has been “a flurry of interest” in trials combining ibrutinib and venetoclax – as was done in the triple-therapy arm – since both emerged as powerful tools against CLL in recent years. However, even with the study results, they said “the use of triplet therapy should be viewed as investigational.”

For one thing, rates of uMRD were not “dramatically different” between triple therapy and venetoclax-obinutuzumab, and longer follow-up is better gauge differences in PFS and long-term toxicities.

Also, ibrutinib is being eclipsed by the second-generation Bruton’s tyrosine kinase inhibitors acalabrutinib and zanubrutinib, because they have better safety profiles, and they are being assessed in CLL combination trials. For now, there are too many unknowns for routine use of triple therapy in fit CLL patients, they said.

The investigators and editorialists both noted that improved uMRD in the study translated into superior PFS, raising the possibility that uMRD might be a valid alternative endpoint to PFS in CLL trials.

With “median remissions in CLL lasting far in excess of 5 years, designing studies that take 8-10 years” to reach a PFS endpoint is simply too slow. Moving to an alternative endpoint such a uMRD would preserve “the momentum that has been generated” with recent advances, Dr. Woyach and Dr. Byrd said.

The work was funded by the companies that market venetoclax, ibrutinib, and obinutuzumab: AbbVie, Janssen, and Roche. Dr. Eichhorst is a consultant and/or speaker for the companies and also reported grants from them. Dr. Byrd is a consultant/adviser for Eilean Therapeutics, Kurome Therapeutics, Newave, and Orbimed. Dr. Woyach disclosed ties with AbbVie, AstraZeneca, Lilly, and other companies.

Venetoclax combinations – especially a novel combination of venetoclax, ibrutinib, and obinutuzumab – outperform first-line chemoimmunotherapy for chronic lymphocytic leukemia in otherwise fit adults with few comorbidities, according to a phase 3 trial published in the New England Journal of Medicine.

The trial, dubbed GAIA–CLL13, “is a remarkable demonstration of the quality of fixed-duration therapies for younger, fit patients, and it challenges us to continue to work to develop therapeutic strategies that will ultimately cure patients with CLL,” two hematologic cancer specialists said in an accompanying editorial.

In short, “venetoclax-obinutuzumab and venetoclax-obinutuzumab-ibrutinib were superior to chemoimmunotherapy with respect to both the minimal residual disease end point and progression-free survival, but venetoclax-rituximab was not,” Jennifer Woyach, MD, of Ohio State University, Columbus, and John Byrd, MD, University of Cincinnati, said in their commentary.

Noting that randomized trials involving venetoclax combinations in fit CLL patients “have been lacking,” the investigators compared 6 cycles of chemoimmunotherapy (fludarabine-cyclophosphamide-rituximab or bendamustine-rituximab) with 12 cycles of venetoclax plus the anti-CD20 antibody rituximab, venetoclax plus the third generation anti-CD20 antibody obinutuzumab, and venetoclax combined with both obinutuzumab and the Bruton’s tyrosine kinase inhibitor ibrutinib in a novel triple-therapy regimen.

The 926 patients in the study were a mean of 61 years old and split about evenly among the four treatment arms. Ibrutinib was discontinued after two consecutive measurements if patients had undetectable minimal residual disease (uMRD). Subjects did not have TP53 aberrations, a marker of poor prognosis in CLL.

At 15 months, the percentage of patients with uMRD was significantly higher in the triple-therapy arm (92.2%) and the venetoclax-obinutuzumab group (86.5%) than in the chemoimmunotherapy group (52.0%), but there was no statistical difference with venetoclax-rituximab (57%, P = .32).

The three-year progression-free survival (PFS) was 90.5% in the triple-therapy arm versus 87.7% with venetoclax-obinutuzumab. The 3-year PFS with venetoclax-rituximab (80.8%) was again not statistically different than the 75.5% with chemoimmunotherapy (P = .18).
 

Not ready for prime time

The benefits of triple therapy and venetoclax-obinutuzumab held only in patients with unmutated IgVH. “The high efficacy of the fludarabine, cyclophosphamide, and rituximab regimen in young, fit patients with mutated IgVH may be difficult to improve on,” noted the investigators, led by Barbara Eichhorst, MD, a hematologic malignancy specialist at the University of Cologne (Germany).

Also, although triple-therapy results were impressive, some of the benefits “are neutralized by the need for dose reductions and early treatment discontinuation owing to adverse events,” they said.

For instance, triple therapy had the highest incidence of both grade 3 and 4 infections (21.2%) and atrial fibrillation (7.8%).

The editorialists noted that there has been “a flurry of interest” in trials combining ibrutinib and venetoclax – as was done in the triple-therapy arm – since both emerged as powerful tools against CLL in recent years. However, even with the study results, they said “the use of triplet therapy should be viewed as investigational.”

For one thing, rates of uMRD were not “dramatically different” between triple therapy and venetoclax-obinutuzumab, and longer follow-up is better gauge differences in PFS and long-term toxicities.

Also, ibrutinib is being eclipsed by the second-generation Bruton’s tyrosine kinase inhibitors acalabrutinib and zanubrutinib, because they have better safety profiles, and they are being assessed in CLL combination trials. For now, there are too many unknowns for routine use of triple therapy in fit CLL patients, they said.

The investigators and editorialists both noted that improved uMRD in the study translated into superior PFS, raising the possibility that uMRD might be a valid alternative endpoint to PFS in CLL trials.

With “median remissions in CLL lasting far in excess of 5 years, designing studies that take 8-10 years” to reach a PFS endpoint is simply too slow. Moving to an alternative endpoint such a uMRD would preserve “the momentum that has been generated” with recent advances, Dr. Woyach and Dr. Byrd said.

The work was funded by the companies that market venetoclax, ibrutinib, and obinutuzumab: AbbVie, Janssen, and Roche. Dr. Eichhorst is a consultant and/or speaker for the companies and also reported grants from them. Dr. Byrd is a consultant/adviser for Eilean Therapeutics, Kurome Therapeutics, Newave, and Orbimed. Dr. Woyach disclosed ties with AbbVie, AstraZeneca, Lilly, and other companies.

The number of cancer survivors who report functional limitation has more than doubled in 20 years, according to a research letter published in JAMA Oncology.

Vishal Patel, BS, a student at the Dell Medical School at The University of Texas at Austin, and colleagues identified 51,258 cancer survivors from the National Health Interview Survey, representing a weighted population of approximately 178.8 million from 1999 to 2018.

Most survivors were women (60.2%) and were at least 65 years old (55.4%). In 1999, 3.6 million weighted survivors reported functional limitation. In 2018, the number increased to 8.2 million, a 2.25-fold increase.

The number of survivors who reported no limitations also increased, but not by as much. That group grew 1.34-fold during the study period.

For context, “the 70% prevalence of functional limitation among survivors in 2018 is nearly twice that of the general population,” the authors wrote.
 

Patients surveyed on function

Functional limitation was defined as “self-reported difficulty performing any of 12 routine physical or social activities without assistance.” Examples of the activities included difficulty sitting for more than 2 hours, difficulty participating in social activities or difficulty pushing or pulling an object the size of a living room chair.

Over the 2 decades analyzed, the adjusted prevalence of functional limitation was highest among survivors of pancreatic cancer (80.3%) and lung cancer (76.5%). Prevalence was lowest for survivors of melanoma (62.2%), breast (61.8%) and prostate (59.5%) cancers.
 

Not just a result of living longer

Mr. Patel told this publication that one assumption people might make when they read these results is that people are just living longer with cancer and losing functional ability accordingly.

“But, in fact, we found that the youngest [– those less than 65 years–] actually contributed to this trend more than the oldest people, which means it’s not just [happening], because people are getting older,” he said.

Hispanic and Black individuals had disproportionately higher increases in functional limitation; percentage point increases over the 2 decades were 19.5 for Black people, 25.1 for Hispanic people and 12.5 for White people. There may be a couple of reasons for that, Mr. Patel noted.

Those who are Black or Hispanic tend to have less access to cancer survivorship care for reasons including insurance status and historic health care inequities, he noted.

“The other potential reason is that they have had less access to cancer care historically. And if, 20 years ago Black and Hispanic individuals didn’t have access to some chemotherapies, and now they do, maybe it’s the increased access to care that’s causing these functional limitations. Because chemotherapy can sometimes be very toxic. It may be sort of a catch-up toxicity,” he said.
 

Quality of life beyond survivorship

Mr. Patel said the results seem to call for building on improved survival rates by tracking and improving function.

“It’s good to celebrate that there are more survivors. But now that we can keep people alive longer, maybe we can shift gears to improving their quality of life,” he said.

The more-than-doubling of functional limitations over 2 decades “is a very sobering trend,” he noted, while pointing out that the functional limitations applied to 8 million people in the United States – people whose needs are not being met.

There’s no sign of the trend stopping, he continued. “We saw no downward trend, only an upward trend.”

Increasingly, including functionality as an endpoint in cancer trials, in addition to improvements in mortality, is one place to start, he added.

“Our findings suggest an urgent need for care teams to understand and address function, for researchers to evaluate function as a core outcome in trials, and for health systems and policy makers to reimagine survivorship care, recognizing the burden of cancer and its treatment on physical, psychosocial, and cognitive function,” the authors wrote in their paper. Limitations of the study include the potential for recall bias, lack of cancer staging or treatment information, and the subjective perception of function.

A coauthor reported personal fees from Astellas, AstraZeneca, AAA, Blue Earth, Janssen, Lantheus, Myovant, Myriad Genetics, Novartis, Telix, and Sanofi, as well as grants from Pfizer and Bayer during the conduct of the study. No other disclosures were reported.

The number of cancer survivors who report functional limitation has more than doubled in 20 years, according to a research letter published in JAMA Oncology.

Vishal Patel, BS, a student at the Dell Medical School at The University of Texas at Austin, and colleagues identified 51,258 cancer survivors from the National Health Interview Survey, representing a weighted population of approximately 178.8 million from 1999 to 2018.

Most survivors were women (60.2%) and were at least 65 years old (55.4%). In 1999, 3.6 million weighted survivors reported functional limitation. In 2018, the number increased to 8.2 million, a 2.25-fold increase.

The number of survivors who reported no limitations also increased, but not by as much. That group grew 1.34-fold during the study period.

For context, “the 70% prevalence of functional limitation among survivors in 2018 is nearly twice that of the general population,” the authors wrote.
 

Patients surveyed on function

Functional limitation was defined as “self-reported difficulty performing any of 12 routine physical or social activities without assistance.” Examples of the activities included difficulty sitting for more than 2 hours, difficulty participating in social activities or difficulty pushing or pulling an object the size of a living room chair.

Over the 2 decades analyzed, the adjusted prevalence of functional limitation was highest among survivors of pancreatic cancer (80.3%) and lung cancer (76.5%). Prevalence was lowest for survivors of melanoma (62.2%), breast (61.8%) and prostate (59.5%) cancers.
 

Not just a result of living longer

Mr. Patel told this publication that one assumption people might make when they read these results is that people are just living longer with cancer and losing functional ability accordingly.

“But, in fact, we found that the youngest [– those less than 65 years–] actually contributed to this trend more than the oldest people, which means it’s not just [happening], because people are getting older,” he said.

Hispanic and Black individuals had disproportionately higher increases in functional limitation; percentage point increases over the 2 decades were 19.5 for Black people, 25.1 for Hispanic people and 12.5 for White people. There may be a couple of reasons for that, Mr. Patel noted.

Those who are Black or Hispanic tend to have less access to cancer survivorship care for reasons including insurance status and historic health care inequities, he noted.

“The other potential reason is that they have had less access to cancer care historically. And if, 20 years ago Black and Hispanic individuals didn’t have access to some chemotherapies, and now they do, maybe it’s the increased access to care that’s causing these functional limitations. Because chemotherapy can sometimes be very toxic. It may be sort of a catch-up toxicity,” he said.
 

Quality of life beyond survivorship

Mr. Patel said the results seem to call for building on improved survival rates by tracking and improving function.

“It’s good to celebrate that there are more survivors. But now that we can keep people alive longer, maybe we can shift gears to improving their quality of life,” he said.

The more-than-doubling of functional limitations over 2 decades “is a very sobering trend,” he noted, while pointing out that the functional limitations applied to 8 million people in the United States – people whose needs are not being met.

There’s no sign of the trend stopping, he continued. “We saw no downward trend, only an upward trend.”

Increasingly, including functionality as an endpoint in cancer trials, in addition to improvements in mortality, is one place to start, he added.

“Our findings suggest an urgent need for care teams to understand and address function, for researchers to evaluate function as a core outcome in trials, and for health systems and policy makers to reimagine survivorship care, recognizing the burden of cancer and its treatment on physical, psychosocial, and cognitive function,” the authors wrote in their paper. Limitations of the study include the potential for recall bias, lack of cancer staging or treatment information, and the subjective perception of function.

A coauthor reported personal fees from Astellas, AstraZeneca, AAA, Blue Earth, Janssen, Lantheus, Myovant, Myriad Genetics, Novartis, Telix, and Sanofi, as well as grants from Pfizer and Bayer during the conduct of the study. No other disclosures were reported.

The number of cancer survivors who report functional limitation has more than doubled in 20 years, according to a research letter published in JAMA Oncology.

Vishal Patel, BS, a student at the Dell Medical School at The University of Texas at Austin, and colleagues identified 51,258 cancer survivors from the National Health Interview Survey, representing a weighted population of approximately 178.8 million from 1999 to 2018.

Most survivors were women (60.2%) and were at least 65 years old (55.4%). In 1999, 3.6 million weighted survivors reported functional limitation. In 2018, the number increased to 8.2 million, a 2.25-fold increase.

The number of survivors who reported no limitations also increased, but not by as much. That group grew 1.34-fold during the study period.

For context, “the 70% prevalence of functional limitation among survivors in 2018 is nearly twice that of the general population,” the authors wrote.
 

Patients surveyed on function

Functional limitation was defined as “self-reported difficulty performing any of 12 routine physical or social activities without assistance.” Examples of the activities included difficulty sitting for more than 2 hours, difficulty participating in social activities or difficulty pushing or pulling an object the size of a living room chair.

Over the 2 decades analyzed, the adjusted prevalence of functional limitation was highest among survivors of pancreatic cancer (80.3%) and lung cancer (76.5%). Prevalence was lowest for survivors of melanoma (62.2%), breast (61.8%) and prostate (59.5%) cancers.
 

Not just a result of living longer

Mr. Patel told this publication that one assumption people might make when they read these results is that people are just living longer with cancer and losing functional ability accordingly.

“But, in fact, we found that the youngest [– those less than 65 years–] actually contributed to this trend more than the oldest people, which means it’s not just [happening], because people are getting older,” he said.

Hispanic and Black individuals had disproportionately higher increases in functional limitation; percentage point increases over the 2 decades were 19.5 for Black people, 25.1 for Hispanic people and 12.5 for White people. There may be a couple of reasons for that, Mr. Patel noted.

Those who are Black or Hispanic tend to have less access to cancer survivorship care for reasons including insurance status and historic health care inequities, he noted.

“The other potential reason is that they have had less access to cancer care historically. And if, 20 years ago Black and Hispanic individuals didn’t have access to some chemotherapies, and now they do, maybe it’s the increased access to care that’s causing these functional limitations. Because chemotherapy can sometimes be very toxic. It may be sort of a catch-up toxicity,” he said.
 

Quality of life beyond survivorship

Mr. Patel said the results seem to call for building on improved survival rates by tracking and improving function.

“It’s good to celebrate that there are more survivors. But now that we can keep people alive longer, maybe we can shift gears to improving their quality of life,” he said.

The more-than-doubling of functional limitations over 2 decades “is a very sobering trend,” he noted, while pointing out that the functional limitations applied to 8 million people in the United States – people whose needs are not being met.

There’s no sign of the trend stopping, he continued. “We saw no downward trend, only an upward trend.”

Increasingly, including functionality as an endpoint in cancer trials, in addition to improvements in mortality, is one place to start, he added.

“Our findings suggest an urgent need for care teams to understand and address function, for researchers to evaluate function as a core outcome in trials, and for health systems and policy makers to reimagine survivorship care, recognizing the burden of cancer and its treatment on physical, psychosocial, and cognitive function,” the authors wrote in their paper. Limitations of the study include the potential for recall bias, lack of cancer staging or treatment information, and the subjective perception of function.

A coauthor reported personal fees from Astellas, AstraZeneca, AAA, Blue Earth, Janssen, Lantheus, Myovant, Myriad Genetics, Novartis, Telix, and Sanofi, as well as grants from Pfizer and Bayer during the conduct of the study. No other disclosures were reported.

Researchers have developed an artificial intelligence (AI) machine-learning platform that can predict the prognosis and likely treatment response of patients with colorectal cancer (CRC) using histopathology images, according to a new study published in Nature Communications.
 

Specifically, the tool can aid doctors in identifying a “molecular diagnosis” based on a patient’s tumor and cancer characteristics, Kun-Hsing Yu, MD, PhD, the study’s senior author and an assistant professor of biomedical informatics at Harvard Medical School, Boston, said in an interview.

The Multi-omics Multi-cohort Assessment (MOMA) “successfully identified indicators of how aggressive a tumor was and how likely it was to behave in response to a particular treatment,” as well as patients’ overall and disease-free survival, noted Harvard Medical School in a press release. “Based on an image alone, the model also pinpointed characteristics associated with the presence or absence of specific genetic mutations – something that typically requires genomic sequencing of the tumor.”

The researchers designed the tool to offer “transparent reasoning,” so that if a clinician asks it why it made a certain prediction, it would be able to explain its reasoning and the variables it used, the press release noted.

“We first allow AI to explore any correlation, and then we try to explain those correlations using existing pathology terms that experts will be able to understand,” Dr. Yu said in an interview.

Although the tool is freely available to clinicians and researchers, it’s not yet ready for clinical use. When it is, the tool has the potential to provide timely, accurate decision support based on tumor imaging.

Colorectal cancer is the second most common cause of death from cancer in the United States, with more than 53,000 deaths each year, and the patient population has been gradually skewing younger over the past 2 decades.

Although clinicians already use histopathology and genetic analysis to guide treatment, the process can take several days or weeks in some areas, and these services may not be available in all parts of the world.

“Currently, a clinician has to send a [tissue] sample from the tumor specimen to genomic sequencing labs and wait for a week, sometimes up to 3 or more weeks, to get genomic sequencing results,” Dr. Yu said. That means a patient’s anxiety grows as they wait to find out which treatments might benefit them or how they might respond to a particular treatment.

Additionally, current knowledge for predicting patient survival, beyond considering the patient’s cancer stage, age, and general health status, is limited, Dr. Yu said.
 

Predictive ability

The MOMA platform was trained on information from 1,888 patients with colorectal cancer from three national cohorts: 628 patients from The Cancer Genome Atlas (TCGA) program, 927 patients from the Nurses’ Health Study with Health Professionals Follow-Up Study (NHS-HPFS), and 333 patients from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial.

During the training, they fed the model information about the patients’ age, sex, cancer stage, and outcomes, as well as their tumors’ “multi-omic” information: the cancers’ genomic, epigenetic, protein, and metabolic profiles. Researchers showed the AI model digital, whole-slide histopathology images of tumor samples and asked it to look for visual markers related to tumor types, genetic mutations, epigenetic alterations, disease progression, and patient survival with the goal of enabling the platform to detect patterns that are indiscernible to the human eye.

They then tested the MOMA platform’s ability to interpret images by feeding it new tumor sample images from different patients and asking it to predict their survival and progression-free survival.

The researchers found that the tool successfully identified overall survival outcomes in patients with stage I or II cancer in the TCGA cohort, which they further validated with the NHS-HPFS and PLCO cohorts. The platform revealed that “dense clusters of adenocarcinoma cells are highly indicative of worse overall survival outcomes” and that the interaction of cancer cells with smooth muscle cells in cancerous areas predicted poorer overall survival.

MOMA was slightly more effective in predicting progression-free survival for stage I and stage II colorectal cancer across all three cohorts.

“Compared with the overall survival prediction, our progression-free survival model puts more emphasis on infiltrating lymphocytes and regions associated with extracellular mucin in its prediction,” the authors noted.

Prediction of overall survival and progression-free survival for stage III colorectal cancer showed similar levels of accuracy, they noted.

The tool also successfully assessed patients’ likely response to immunotherapy using predictions of microsatellite instability, since high MSI indicates a better response to immune checkpoint inhibitors.

MOMA outperformed a different machine-learning algorithm in predicting the copy number alterations and other features related to cancer development, and it predicted the likelihood of a BRAF mutation, which is linked to poorer prognosis.
 

Pushing the envelope?

MOMA presents an “intriguing new avenue of adding to how we think about and assess someone who has cancer,” Stacey Cohen, MD, an associate professor in the clinical research division of Fred Hutchinson Cancer Center at the University of Washington Medicine, Seattle, said in an interview.

However, the tool as it’s currently described appears primarily to duplicate what clinicians already are doing, which is considering a wide range of factors – including pathologic features, patient features and demographics, and the patient’s other medical illnesses – to develop a treatment plan within the context of current guidelines, noted Dr. Cohen, who was not involved in the project.

“I’m looking for these types of models to not just prognosticate an outcome but to really predict how someone should be treated, and to do that better than [using] standard clinical features,” Dr. Cohen said. “To some degree, they’re taking this AI model and trying to catch up to what we’re currently doing. Clearly, if they could do that, they can then push the envelope.”

Dr. Cohen acknowledged that a strength of using an AI platform is the speed at which it can provide its predictions in areas with few medical resources and few health care professionals – as long as the necessary imaging is available and physicians have a way to use the platform.

“On the one hand, I do see this as an opportunity to share the wealth of knowledge in a more rapid fashion, but I don’t think anybody is going to let a computer program dictate their treatment without a human medical oncologist being able to interpret that information,” Dr. Cohen said. “It still will require a lot of education by the users and not just by the people who are designing the study.”

Although the MOMA platform looked at multiple pathologic features in multiple cohorts, the results remain limited by the fact that the patients in those cohorts were treated decades ago, before many current treatments may have been available, Dr. Cohen said.

She also added that the cohorts did not have much ethnic diversity. In the NHS-HPFS, the largest cohort, 57% of the patients were White, and researchers lacked data on race for 42% of patients, so only about 1% of participants were of a known non-White race. Similarly, 47% of the TCGA patients were White and 41% had no data on race, leaving only 12% of patients from known, non-White racial backgrounds, including 10% Black or African American.

Additional studies that focus on specific patient populations are needed to evaluate the model’s applicability in clinical settings, the investigators note. More research is required to “identify the optimal prognostic prediction methods and enable personalized treatments and advance care planning,” they added.

These are the early days for this type of technology, Dr. Cohen noted.

“I’m very excited to see how this technology develops and how it could be potentially additive or improve upon our current treatment planning for patients,” she said.

Dr. Yu developed the invention “Quantitative Pathology Analysis and Diagnosis using Neural Networks,” whose patent is held by Harvard University, and has consulted for Curatio. One coauthor is a stakeholder and employee of Vertex Pharmaceuticals. The study’s funding sources included the National Institute of General Medical Sciences, the Google Research Scholar Award, the Blavatnik Center for Computational Biomedicine Award, the National Science and Technology Council Taiwan, and the National Center for High-performance Computing Taiwan. Dr. Cohen has advised or consulted for Natera.

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

Researchers have developed an artificial intelligence (AI) machine-learning platform that can predict the prognosis and likely treatment response of patients with colorectal cancer (CRC) using histopathology images, according to a new study published in Nature Communications.
 

Specifically, the tool can aid doctors in identifying a “molecular diagnosis” based on a patient’s tumor and cancer characteristics, Kun-Hsing Yu, MD, PhD, the study’s senior author and an assistant professor of biomedical informatics at Harvard Medical School, Boston, said in an interview.

The Multi-omics Multi-cohort Assessment (MOMA) “successfully identified indicators of how aggressive a tumor was and how likely it was to behave in response to a particular treatment,” as well as patients’ overall and disease-free survival, noted Harvard Medical School in a press release. “Based on an image alone, the model also pinpointed characteristics associated with the presence or absence of specific genetic mutations – something that typically requires genomic sequencing of the tumor.”

The researchers designed the tool to offer “transparent reasoning,” so that if a clinician asks it why it made a certain prediction, it would be able to explain its reasoning and the variables it used, the press release noted.

“We first allow AI to explore any correlation, and then we try to explain those correlations using existing pathology terms that experts will be able to understand,” Dr. Yu said in an interview.

Although the tool is freely available to clinicians and researchers, it’s not yet ready for clinical use. When it is, the tool has the potential to provide timely, accurate decision support based on tumor imaging.

Colorectal cancer is the second most common cause of death from cancer in the United States, with more than 53,000 deaths each year, and the patient population has been gradually skewing younger over the past 2 decades.

Although clinicians already use histopathology and genetic analysis to guide treatment, the process can take several days or weeks in some areas, and these services may not be available in all parts of the world.

“Currently, a clinician has to send a [tissue] sample from the tumor specimen to genomic sequencing labs and wait for a week, sometimes up to 3 or more weeks, to get genomic sequencing results,” Dr. Yu said. That means a patient’s anxiety grows as they wait to find out which treatments might benefit them or how they might respond to a particular treatment.

Additionally, current knowledge for predicting patient survival, beyond considering the patient’s cancer stage, age, and general health status, is limited, Dr. Yu said.
 

Predictive ability

The MOMA platform was trained on information from 1,888 patients with colorectal cancer from three national cohorts: 628 patients from The Cancer Genome Atlas (TCGA) program, 927 patients from the Nurses’ Health Study with Health Professionals Follow-Up Study (NHS-HPFS), and 333 patients from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial.

During the training, they fed the model information about the patients’ age, sex, cancer stage, and outcomes, as well as their tumors’ “multi-omic” information: the cancers’ genomic, epigenetic, protein, and metabolic profiles. Researchers showed the AI model digital, whole-slide histopathology images of tumor samples and asked it to look for visual markers related to tumor types, genetic mutations, epigenetic alterations, disease progression, and patient survival with the goal of enabling the platform to detect patterns that are indiscernible to the human eye.

They then tested the MOMA platform’s ability to interpret images by feeding it new tumor sample images from different patients and asking it to predict their survival and progression-free survival.

The researchers found that the tool successfully identified overall survival outcomes in patients with stage I or II cancer in the TCGA cohort, which they further validated with the NHS-HPFS and PLCO cohorts. The platform revealed that “dense clusters of adenocarcinoma cells are highly indicative of worse overall survival outcomes” and that the interaction of cancer cells with smooth muscle cells in cancerous areas predicted poorer overall survival.

MOMA was slightly more effective in predicting progression-free survival for stage I and stage II colorectal cancer across all three cohorts.

“Compared with the overall survival prediction, our progression-free survival model puts more emphasis on infiltrating lymphocytes and regions associated with extracellular mucin in its prediction,” the authors noted.

Prediction of overall survival and progression-free survival for stage III colorectal cancer showed similar levels of accuracy, they noted.

The tool also successfully assessed patients’ likely response to immunotherapy using predictions of microsatellite instability, since high MSI indicates a better response to immune checkpoint inhibitors.

MOMA outperformed a different machine-learning algorithm in predicting the copy number alterations and other features related to cancer development, and it predicted the likelihood of a BRAF mutation, which is linked to poorer prognosis.
 

Pushing the envelope?

MOMA presents an “intriguing new avenue of adding to how we think about and assess someone who has cancer,” Stacey Cohen, MD, an associate professor in the clinical research division of Fred Hutchinson Cancer Center at the University of Washington Medicine, Seattle, said in an interview.

However, the tool as it’s currently described appears primarily to duplicate what clinicians already are doing, which is considering a wide range of factors – including pathologic features, patient features and demographics, and the patient’s other medical illnesses – to develop a treatment plan within the context of current guidelines, noted Dr. Cohen, who was not involved in the project.

“I’m looking for these types of models to not just prognosticate an outcome but to really predict how someone should be treated, and to do that better than [using] standard clinical features,” Dr. Cohen said. “To some degree, they’re taking this AI model and trying to catch up to what we’re currently doing. Clearly, if they could do that, they can then push the envelope.”

Dr. Cohen acknowledged that a strength of using an AI platform is the speed at which it can provide its predictions in areas with few medical resources and few health care professionals – as long as the necessary imaging is available and physicians have a way to use the platform.

“On the one hand, I do see this as an opportunity to share the wealth of knowledge in a more rapid fashion, but I don’t think anybody is going to let a computer program dictate their treatment without a human medical oncologist being able to interpret that information,” Dr. Cohen said. “It still will require a lot of education by the users and not just by the people who are designing the study.”

Although the MOMA platform looked at multiple pathologic features in multiple cohorts, the results remain limited by the fact that the patients in those cohorts were treated decades ago, before many current treatments may have been available, Dr. Cohen said.

She also added that the cohorts did not have much ethnic diversity. In the NHS-HPFS, the largest cohort, 57% of the patients were White, and researchers lacked data on race for 42% of patients, so only about 1% of participants were of a known non-White race. Similarly, 47% of the TCGA patients were White and 41% had no data on race, leaving only 12% of patients from known, non-White racial backgrounds, including 10% Black or African American.

Additional studies that focus on specific patient populations are needed to evaluate the model’s applicability in clinical settings, the investigators note. More research is required to “identify the optimal prognostic prediction methods and enable personalized treatments and advance care planning,” they added.

These are the early days for this type of technology, Dr. Cohen noted.

“I’m very excited to see how this technology develops and how it could be potentially additive or improve upon our current treatment planning for patients,” she said.

Dr. Yu developed the invention “Quantitative Pathology Analysis and Diagnosis using Neural Networks,” whose patent is held by Harvard University, and has consulted for Curatio. One coauthor is a stakeholder and employee of Vertex Pharmaceuticals. The study’s funding sources included the National Institute of General Medical Sciences, the Google Research Scholar Award, the Blavatnik Center for Computational Biomedicine Award, the National Science and Technology Council Taiwan, and the National Center for High-performance Computing Taiwan. Dr. Cohen has advised or consulted for Natera.

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

Researchers have developed an artificial intelligence (AI) machine-learning platform that can predict the prognosis and likely treatment response of patients with colorectal cancer (CRC) using histopathology images, according to a new study published in Nature Communications.
 

Specifically, the tool can aid doctors in identifying a “molecular diagnosis” based on a patient’s tumor and cancer characteristics, Kun-Hsing Yu, MD, PhD, the study’s senior author and an assistant professor of biomedical informatics at Harvard Medical School, Boston, said in an interview.

The Multi-omics Multi-cohort Assessment (MOMA) “successfully identified indicators of how aggressive a tumor was and how likely it was to behave in response to a particular treatment,” as well as patients’ overall and disease-free survival, noted Harvard Medical School in a press release. “Based on an image alone, the model also pinpointed characteristics associated with the presence or absence of specific genetic mutations – something that typically requires genomic sequencing of the tumor.”

The researchers designed the tool to offer “transparent reasoning,” so that if a clinician asks it why it made a certain prediction, it would be able to explain its reasoning and the variables it used, the press release noted.

“We first allow AI to explore any correlation, and then we try to explain those correlations using existing pathology terms that experts will be able to understand,” Dr. Yu said in an interview.

Although the tool is freely available to clinicians and researchers, it’s not yet ready for clinical use. When it is, the tool has the potential to provide timely, accurate decision support based on tumor imaging.

Colorectal cancer is the second most common cause of death from cancer in the United States, with more than 53,000 deaths each year, and the patient population has been gradually skewing younger over the past 2 decades.

Although clinicians already use histopathology and genetic analysis to guide treatment, the process can take several days or weeks in some areas, and these services may not be available in all parts of the world.

“Currently, a clinician has to send a [tissue] sample from the tumor specimen to genomic sequencing labs and wait for a week, sometimes up to 3 or more weeks, to get genomic sequencing results,” Dr. Yu said. That means a patient’s anxiety grows as they wait to find out which treatments might benefit them or how they might respond to a particular treatment.

Additionally, current knowledge for predicting patient survival, beyond considering the patient’s cancer stage, age, and general health status, is limited, Dr. Yu said.
 

Predictive ability

The MOMA platform was trained on information from 1,888 patients with colorectal cancer from three national cohorts: 628 patients from The Cancer Genome Atlas (TCGA) program, 927 patients from the Nurses’ Health Study with Health Professionals Follow-Up Study (NHS-HPFS), and 333 patients from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial.

During the training, they fed the model information about the patients’ age, sex, cancer stage, and outcomes, as well as their tumors’ “multi-omic” information: the cancers’ genomic, epigenetic, protein, and metabolic profiles. Researchers showed the AI model digital, whole-slide histopathology images of tumor samples and asked it to look for visual markers related to tumor types, genetic mutations, epigenetic alterations, disease progression, and patient survival with the goal of enabling the platform to detect patterns that are indiscernible to the human eye.

They then tested the MOMA platform’s ability to interpret images by feeding it new tumor sample images from different patients and asking it to predict their survival and progression-free survival.

The researchers found that the tool successfully identified overall survival outcomes in patients with stage I or II cancer in the TCGA cohort, which they further validated with the NHS-HPFS and PLCO cohorts. The platform revealed that “dense clusters of adenocarcinoma cells are highly indicative of worse overall survival outcomes” and that the interaction of cancer cells with smooth muscle cells in cancerous areas predicted poorer overall survival.

MOMA was slightly more effective in predicting progression-free survival for stage I and stage II colorectal cancer across all three cohorts.

“Compared with the overall survival prediction, our progression-free survival model puts more emphasis on infiltrating lymphocytes and regions associated with extracellular mucin in its prediction,” the authors noted.

Prediction of overall survival and progression-free survival for stage III colorectal cancer showed similar levels of accuracy, they noted.

The tool also successfully assessed patients’ likely response to immunotherapy using predictions of microsatellite instability, since high MSI indicates a better response to immune checkpoint inhibitors.

MOMA outperformed a different machine-learning algorithm in predicting the copy number alterations and other features related to cancer development, and it predicted the likelihood of a BRAF mutation, which is linked to poorer prognosis.
 

Pushing the envelope?

MOMA presents an “intriguing new avenue of adding to how we think about and assess someone who has cancer,” Stacey Cohen, MD, an associate professor in the clinical research division of Fred Hutchinson Cancer Center at the University of Washington Medicine, Seattle, said in an interview.

However, the tool as it’s currently described appears primarily to duplicate what clinicians already are doing, which is considering a wide range of factors – including pathologic features, patient features and demographics, and the patient’s other medical illnesses – to develop a treatment plan within the context of current guidelines, noted Dr. Cohen, who was not involved in the project.

“I’m looking for these types of models to not just prognosticate an outcome but to really predict how someone should be treated, and to do that better than [using] standard clinical features,” Dr. Cohen said. “To some degree, they’re taking this AI model and trying to catch up to what we’re currently doing. Clearly, if they could do that, they can then push the envelope.”

Dr. Cohen acknowledged that a strength of using an AI platform is the speed at which it can provide its predictions in areas with few medical resources and few health care professionals – as long as the necessary imaging is available and physicians have a way to use the platform.

“On the one hand, I do see this as an opportunity to share the wealth of knowledge in a more rapid fashion, but I don’t think anybody is going to let a computer program dictate their treatment without a human medical oncologist being able to interpret that information,” Dr. Cohen said. “It still will require a lot of education by the users and not just by the people who are designing the study.”

Although the MOMA platform looked at multiple pathologic features in multiple cohorts, the results remain limited by the fact that the patients in those cohorts were treated decades ago, before many current treatments may have been available, Dr. Cohen said.

She also added that the cohorts did not have much ethnic diversity. In the NHS-HPFS, the largest cohort, 57% of the patients were White, and researchers lacked data on race for 42% of patients, so only about 1% of participants were of a known non-White race. Similarly, 47% of the TCGA patients were White and 41% had no data on race, leaving only 12% of patients from known, non-White racial backgrounds, including 10% Black or African American.

Additional studies that focus on specific patient populations are needed to evaluate the model’s applicability in clinical settings, the investigators note. More research is required to “identify the optimal prognostic prediction methods and enable personalized treatments and advance care planning,” they added.

These are the early days for this type of technology, Dr. Cohen noted.

“I’m very excited to see how this technology develops and how it could be potentially additive or improve upon our current treatment planning for patients,” she said.

Dr. Yu developed the invention “Quantitative Pathology Analysis and Diagnosis using Neural Networks,” whose patent is held by Harvard University, and has consulted for Curatio. One coauthor is a stakeholder and employee of Vertex Pharmaceuticals. The study’s funding sources included the National Institute of General Medical Sciences, the Google Research Scholar Award, the Blavatnik Center for Computational Biomedicine Award, the National Science and Technology Council Taiwan, and the National Center for High-performance Computing Taiwan. Dr. Cohen has advised or consulted for Natera.

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

SEATTLE – The use of Mohs surgery may improve survival for patients with early-stage Merkel cell carcinoma (MCC), results from a large, retrospective study show.

Compared with conventional wide local excision, survival was significantly improved among patients treated with Mohs, and a subgroup analysis showed that the survival benefit remained for patients with risk factors.

“At 10 years, overall survival was about 21% higher for those treated with Mohs surgery versus those treated with conventional surgery,” said lead author Shayan Cheraghlou, MD, a dermatology resident at the New York University School of Medicine. “On multivariable analysis, which controlled for tumor and patient factors, Mohs was associated with an over 40% reduction in the hazard for death.”

The findings were presented at the annual meeting of the American College of Mohs Surgery.

MCC is a rare, aggressive, neuroendocrine cutaneous malignancy that carries a high mortality rate. The estimated 5-year survival for patients with localized disease is about 50%, Dr. Cheraghlou noted. “That extrapolates to about 55% for T1 tumors and down to about 30% for T4 tumors.”

Although it’s considered to be a rare cancer, the incidence of MCC has been rapidly rising, and in fact it doubled during the period from the 1990s to the 2010s.

Most commonly treated with wide local excision with or without adjuvant radiation therapy, Mohs as monotherapy may offer an alternative treatment option for patients with MCC. It is generally accepted that the optimal treatment for tumors without regional lymph node involvement is surgical, but the data regarding the optimal surgical approach are mixed. Current National Comprehensive Cancer Network guidelines state that either Mohs surgery or wide local excision can be used.

“However, these guidelines do not indicate a preference for one modality over the other,” said Dr. Cheraghlou, “and present them as interchangeable treatment options.”

A growing body of literature supports Mohs surgery for many types of rare tumors, including MCC. For example, as previously reported at the 2021 ACMS meeting, one study found that Mohs surgery compared favorably with the standard treatment approach when it came to recurrence rates for patients with MCC. The 5-year disease-specific survival rate was 91.2% for patients with stage I disease and 68.6% for patients with stage IIa. These rates were comparable with rates for historical control patients who were treated with wide local excision, with or without radiation (81%-87% for stage I disease, and 63%-67% for stage II).

Study details

In the current study, Dr. Cheraghlou and colleagues sought to evaluate the association of the type of surgical approach with patient survival after excision of early-stage MCC. They conducted a retrospective cohort study using the National Cancer Database to identify cases of MCC with T1/T2 tumors. A total of 2,313 patients who were diagnosed from 2004 to 2018 with pathologically confirmed negative lymph node involvement and who were treated with Mohs surgery or wide lesion excision were included in the analysis.

“About 90% were T1 tumors, about 40% were located on the head and neck, and the vast majority – about 60% – were treated with wide local excision,” he explained. “Only about 5% received Mohs surgery for treatment of the primary tumor.”

But when the researchers assessed survival outcomes, they found that treatment with Mohs surgery was associated with significantly improved overall survival.

The unadjusted 3-, 5-, and 10-year survival rates for patients treated with Mohs was 87.4% (SE: 3.4%), 84.5% (SE: 3.9%), and 81.8% (SE: 4.6%), respectively, while for wide lesion excision, the rates were 86.1% (SE: 0.9%), 76.9% (SE: 1.2%), and 60.9% (SE: 2.0%), respectively.

For patients who underwent treatment with narrow margin excision, survival rates were similar as for those treated with wide lesion excision, with 3-, 5-, and 10-year survival rates of 84.8% (SE: 1.4%), 78.3% (SE: 1.7%), and 60.8% (SE: 3.6%), respectively.

On multivariable survival analysis, Mohs surgery was associated with significantly improved survival, compared with wide lesion excision (hazard ratio, 0.594; P = .038). This was also true after multivariable analysis for patients who had one or more NCCN risk factors, for whom improved survival was also seen with Mohs (HR, 0.530; P = .026).

The results did not differ after a sensitivity analysis that included T3 and T4 tumors.

Given that the use of Mohs was so infrequent, compared with standard surgery, the researchers investigated the factors that were associated with the use of Mohs. High-volume MCC centers were significantly more likely to utilize Mohs than wide lesion excision (odds ratio, 1.993; P < .001), compared with other facilities.

“This study has important implications going forward,” Dr. Cheraghlou concluded. “We think it’s important how few patients were treated with Mohs for Merkel cell, and it was slightly more likely to happen in a high-volume center.”

The reasoning for that may be that high-volume centers are more likely to have a surgeon trained to perform Mohs surgery for MCC. “Or perhaps they are more attuned to the benefits of this procedure,” he said. “We can’t tell that from our data, but its notable that it’s such a small proportion of patients – especially when we consider that it is associated with improved survival for the patients who receive it.”

He added that efforts to increase the utilization of Mohs may yield improved local control and overall survival for these patients. “And perhaps with more data, future versions of guidelines may indicate a preference for Mohs over conventional incisions.”
 

No changes to current practice

Asked to comment on the study, Anthony J. Olszanski, RPh, MD, associate professor, department of hematology/oncology, Fox Chase Cancer Center, Philadelphia, noted that while the results are intriguing, they must be interpreted with caution.

“This study was retrospective in nature, and unrecognized biases can influence results,” he said. “Additionally, given the relative rarity of Merkel cell carcinoma, the sample size is expectantly small.”

But importantly, Dr. Olszanski emphasized, Mohs may more often have been recommended for patients with lesions that appear less aggressive. “Many patients undergoing wide lesion excision may have been referred by Mohs surgeons secondary to features or characteristics of lesions which were worrisome,” he explained. “The results of this study do not opine on why Mohs would impact overall survival over wide lesion excision, a point worthy of consideration. Presently, both modalities can be considered for patients with T1/T2 MCC. The results of this study should not change current practice and would lend themselves to a more robust study.”

No external funding of the study was reported. Dr. Cheraghlou has disclosed no relevant financial relationships. Dr. Olszanski has received financial support from Merck and BMS for participated on advisory boards.

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

SEATTLE – The use of Mohs surgery may improve survival for patients with early-stage Merkel cell carcinoma (MCC), results from a large, retrospective study show.

Compared with conventional wide local excision, survival was significantly improved among patients treated with Mohs, and a subgroup analysis showed that the survival benefit remained for patients with risk factors.

“At 10 years, overall survival was about 21% higher for those treated with Mohs surgery versus those treated with conventional surgery,” said lead author Shayan Cheraghlou, MD, a dermatology resident at the New York University School of Medicine. “On multivariable analysis, which controlled for tumor and patient factors, Mohs was associated with an over 40% reduction in the hazard for death.”

The findings were presented at the annual meeting of the American College of Mohs Surgery.

MCC is a rare, aggressive, neuroendocrine cutaneous malignancy that carries a high mortality rate. The estimated 5-year survival for patients with localized disease is about 50%, Dr. Cheraghlou noted. “That extrapolates to about 55% for T1 tumors and down to about 30% for T4 tumors.”

Although it’s considered to be a rare cancer, the incidence of MCC has been rapidly rising, and in fact it doubled during the period from the 1990s to the 2010s.

Most commonly treated with wide local excision with or without adjuvant radiation therapy, Mohs as monotherapy may offer an alternative treatment option for patients with MCC. It is generally accepted that the optimal treatment for tumors without regional lymph node involvement is surgical, but the data regarding the optimal surgical approach are mixed. Current National Comprehensive Cancer Network guidelines state that either Mohs surgery or wide local excision can be used.

“However, these guidelines do not indicate a preference for one modality over the other,” said Dr. Cheraghlou, “and present them as interchangeable treatment options.”

A growing body of literature supports Mohs surgery for many types of rare tumors, including MCC. For example, as previously reported at the 2021 ACMS meeting, one study found that Mohs surgery compared favorably with the standard treatment approach when it came to recurrence rates for patients with MCC. The 5-year disease-specific survival rate was 91.2% for patients with stage I disease and 68.6% for patients with stage IIa. These rates were comparable with rates for historical control patients who were treated with wide local excision, with or without radiation (81%-87% for stage I disease, and 63%-67% for stage II).

Study details

In the current study, Dr. Cheraghlou and colleagues sought to evaluate the association of the type of surgical approach with patient survival after excision of early-stage MCC. They conducted a retrospective cohort study using the National Cancer Database to identify cases of MCC with T1/T2 tumors. A total of 2,313 patients who were diagnosed from 2004 to 2018 with pathologically confirmed negative lymph node involvement and who were treated with Mohs surgery or wide lesion excision were included in the analysis.

“About 90% were T1 tumors, about 40% were located on the head and neck, and the vast majority – about 60% – were treated with wide local excision,” he explained. “Only about 5% received Mohs surgery for treatment of the primary tumor.”

But when the researchers assessed survival outcomes, they found that treatment with Mohs surgery was associated with significantly improved overall survival.

The unadjusted 3-, 5-, and 10-year survival rates for patients treated with Mohs was 87.4% (SE: 3.4%), 84.5% (SE: 3.9%), and 81.8% (SE: 4.6%), respectively, while for wide lesion excision, the rates were 86.1% (SE: 0.9%), 76.9% (SE: 1.2%), and 60.9% (SE: 2.0%), respectively.

For patients who underwent treatment with narrow margin excision, survival rates were similar as for those treated with wide lesion excision, with 3-, 5-, and 10-year survival rates of 84.8% (SE: 1.4%), 78.3% (SE: 1.7%), and 60.8% (SE: 3.6%), respectively.

On multivariable survival analysis, Mohs surgery was associated with significantly improved survival, compared with wide lesion excision (hazard ratio, 0.594; P = .038). This was also true after multivariable analysis for patients who had one or more NCCN risk factors, for whom improved survival was also seen with Mohs (HR, 0.530; P = .026).

The results did not differ after a sensitivity analysis that included T3 and T4 tumors.

Given that the use of Mohs was so infrequent, compared with standard surgery, the researchers investigated the factors that were associated with the use of Mohs. High-volume MCC centers were significantly more likely to utilize Mohs than wide lesion excision (odds ratio, 1.993; P < .001), compared with other facilities.

“This study has important implications going forward,” Dr. Cheraghlou concluded. “We think it’s important how few patients were treated with Mohs for Merkel cell, and it was slightly more likely to happen in a high-volume center.”

The reasoning for that may be that high-volume centers are more likely to have a surgeon trained to perform Mohs surgery for MCC. “Or perhaps they are more attuned to the benefits of this procedure,” he said. “We can’t tell that from our data, but its notable that it’s such a small proportion of patients – especially when we consider that it is associated with improved survival for the patients who receive it.”

He added that efforts to increase the utilization of Mohs may yield improved local control and overall survival for these patients. “And perhaps with more data, future versions of guidelines may indicate a preference for Mohs over conventional incisions.”
 

No changes to current practice

Asked to comment on the study, Anthony J. Olszanski, RPh, MD, associate professor, department of hematology/oncology, Fox Chase Cancer Center, Philadelphia, noted that while the results are intriguing, they must be interpreted with caution.

“This study was retrospective in nature, and unrecognized biases can influence results,” he said. “Additionally, given the relative rarity of Merkel cell carcinoma, the sample size is expectantly small.”

But importantly, Dr. Olszanski emphasized, Mohs may more often have been recommended for patients with lesions that appear less aggressive. “Many patients undergoing wide lesion excision may have been referred by Mohs surgeons secondary to features or characteristics of lesions which were worrisome,” he explained. “The results of this study do not opine on why Mohs would impact overall survival over wide lesion excision, a point worthy of consideration. Presently, both modalities can be considered for patients with T1/T2 MCC. The results of this study should not change current practice and would lend themselves to a more robust study.”

No external funding of the study was reported. Dr. Cheraghlou has disclosed no relevant financial relationships. Dr. Olszanski has received financial support from Merck and BMS for participated on advisory boards.

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

SEATTLE – The use of Mohs surgery may improve survival for patients with early-stage Merkel cell carcinoma (MCC), results from a large, retrospective study show.

Compared with conventional wide local excision, survival was significantly improved among patients treated with Mohs, and a subgroup analysis showed that the survival benefit remained for patients with risk factors.

“At 10 years, overall survival was about 21% higher for those treated with Mohs surgery versus those treated with conventional surgery,” said lead author Shayan Cheraghlou, MD, a dermatology resident at the New York University School of Medicine. “On multivariable analysis, which controlled for tumor and patient factors, Mohs was associated with an over 40% reduction in the hazard for death.”

The findings were presented at the annual meeting of the American College of Mohs Surgery.

MCC is a rare, aggressive, neuroendocrine cutaneous malignancy that carries a high mortality rate. The estimated 5-year survival for patients with localized disease is about 50%, Dr. Cheraghlou noted. “That extrapolates to about 55% for T1 tumors and down to about 30% for T4 tumors.”

Although it’s considered to be a rare cancer, the incidence of MCC has been rapidly rising, and in fact it doubled during the period from the 1990s to the 2010s.

Most commonly treated with wide local excision with or without adjuvant radiation therapy, Mohs as monotherapy may offer an alternative treatment option for patients with MCC. It is generally accepted that the optimal treatment for tumors without regional lymph node involvement is surgical, but the data regarding the optimal surgical approach are mixed. Current National Comprehensive Cancer Network guidelines state that either Mohs surgery or wide local excision can be used.

“However, these guidelines do not indicate a preference for one modality over the other,” said Dr. Cheraghlou, “and present them as interchangeable treatment options.”

A growing body of literature supports Mohs surgery for many types of rare tumors, including MCC. For example, as previously reported at the 2021 ACMS meeting, one study found that Mohs surgery compared favorably with the standard treatment approach when it came to recurrence rates for patients with MCC. The 5-year disease-specific survival rate was 91.2% for patients with stage I disease and 68.6% for patients with stage IIa. These rates were comparable with rates for historical control patients who were treated with wide local excision, with or without radiation (81%-87% for stage I disease, and 63%-67% for stage II).

Study details

In the current study, Dr. Cheraghlou and colleagues sought to evaluate the association of the type of surgical approach with patient survival after excision of early-stage MCC. They conducted a retrospective cohort study using the National Cancer Database to identify cases of MCC with T1/T2 tumors. A total of 2,313 patients who were diagnosed from 2004 to 2018 with pathologically confirmed negative lymph node involvement and who were treated with Mohs surgery or wide lesion excision were included in the analysis.

“About 90% were T1 tumors, about 40% were located on the head and neck, and the vast majority – about 60% – were treated with wide local excision,” he explained. “Only about 5% received Mohs surgery for treatment of the primary tumor.”

But when the researchers assessed survival outcomes, they found that treatment with Mohs surgery was associated with significantly improved overall survival.

The unadjusted 3-, 5-, and 10-year survival rates for patients treated with Mohs was 87.4% (SE: 3.4%), 84.5% (SE: 3.9%), and 81.8% (SE: 4.6%), respectively, while for wide lesion excision, the rates were 86.1% (SE: 0.9%), 76.9% (SE: 1.2%), and 60.9% (SE: 2.0%), respectively.

For patients who underwent treatment with narrow margin excision, survival rates were similar as for those treated with wide lesion excision, with 3-, 5-, and 10-year survival rates of 84.8% (SE: 1.4%), 78.3% (SE: 1.7%), and 60.8% (SE: 3.6%), respectively.

On multivariable survival analysis, Mohs surgery was associated with significantly improved survival, compared with wide lesion excision (hazard ratio, 0.594; P = .038). This was also true after multivariable analysis for patients who had one or more NCCN risk factors, for whom improved survival was also seen with Mohs (HR, 0.530; P = .026).

The results did not differ after a sensitivity analysis that included T3 and T4 tumors.

Given that the use of Mohs was so infrequent, compared with standard surgery, the researchers investigated the factors that were associated with the use of Mohs. High-volume MCC centers were significantly more likely to utilize Mohs than wide lesion excision (odds ratio, 1.993; P < .001), compared with other facilities.

“This study has important implications going forward,” Dr. Cheraghlou concluded. “We think it’s important how few patients were treated with Mohs for Merkel cell, and it was slightly more likely to happen in a high-volume center.”

The reasoning for that may be that high-volume centers are more likely to have a surgeon trained to perform Mohs surgery for MCC. “Or perhaps they are more attuned to the benefits of this procedure,” he said. “We can’t tell that from our data, but its notable that it’s such a small proportion of patients – especially when we consider that it is associated with improved survival for the patients who receive it.”

He added that efforts to increase the utilization of Mohs may yield improved local control and overall survival for these patients. “And perhaps with more data, future versions of guidelines may indicate a preference for Mohs over conventional incisions.”
 

No changes to current practice

Asked to comment on the study, Anthony J. Olszanski, RPh, MD, associate professor, department of hematology/oncology, Fox Chase Cancer Center, Philadelphia, noted that while the results are intriguing, they must be interpreted with caution.

“This study was retrospective in nature, and unrecognized biases can influence results,” he said. “Additionally, given the relative rarity of Merkel cell carcinoma, the sample size is expectantly small.”

But importantly, Dr. Olszanski emphasized, Mohs may more often have been recommended for patients with lesions that appear less aggressive. “Many patients undergoing wide lesion excision may have been referred by Mohs surgeons secondary to features or characteristics of lesions which were worrisome,” he explained. “The results of this study do not opine on why Mohs would impact overall survival over wide lesion excision, a point worthy of consideration. Presently, both modalities can be considered for patients with T1/T2 MCC. The results of this study should not change current practice and would lend themselves to a more robust study.”

No external funding of the study was reported. Dr. Cheraghlou has disclosed no relevant financial relationships. Dr. Olszanski has received financial support from Merck and BMS for participated on advisory boards.

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

Primary hepatic lymphoma (PHL) is a rare, malignant lymphoma of the liver. It differs from the predominantly lymph nodal or splenic involvement associated with other types of lymphoma. It is usually detected incidentally on imaging examination, commonly computed tomography (CT), for nonspecific clinical presentation. However, it has important clinical implications for early diagnosis and treatment as indicated in our case.

Case Presentation

An 84-year-old man presented to the emergency department for evaluation of upper back pain. The patient had a history of hypertension, diabetes mellitus, and was a former smoker. He had normal vital signs, an unremarkable physical examination, and a body mass index of 25. His laboratory studies showed a normal blood cell count and serum chemistry, including serum calcium level and α-fetoprotein, but mildly elevated liver function tests.

The patient’s chest CT angiography showed no evidence of thoracic aortic dissection, penetrating atherosclerotic ulceration, or pulmonary artery embolism. Besides emphysematous changes in the lung, the chest CT was within normal limits.

Discussion

Lymphoma is a tumor that originates from hematopoietic cells typically presented as a circumscribed solid tumor of lymphoid cells.¹ Lymphomas are usually seen in the lymph nodes, spleen, blood, bone marrow, brain, gastrointestinal tract, skin, or other normal structures where lymphoreticular cells exist but very rarely in the liver.² PHL is extremely rare due to the lack of abundant lymphoid tissue in the normal liver.³ It accounts for 0.4% of extra-nodal lymphomas and 0.016% of non-Hodgkin lymphoma.^4-6 The etiology of PHL is unknown but usually it develops in patients with previous liver disease: viral infection (hepatitis B and C, Epstein-Barr, and HIV), autoimmune disease, immunosuppression, or liver cirrhosis.^5-7

The diagnosis of PHL can be challenging due to its rarity, vague clinical features, and nonspecific radiologic findings. The common presenting symptoms are usually vague and include abdominal pain or discomfort, fatigue, jaundice, weight loss, and fever.⁵ Liver biopsy is essential to its diagnosis. The disease course is usually indolent among most patients with PHL. In our case, the patient presented with upper back pain but his condition deteriorated rapidly, likely due to the advanced stage of the disease. Diagnosis of liver lymphoma depends on a liver biopsy that should be compatible with the lymphoma. The criteria for diagnosis of PHL defined by Lei include (1) symptoms caused mainly by liver involvement at presentation; (2) absence of distant lymphadenopathy, palpable clinically at presentation or detected during staging radiologic studies; and (3) absence of leukemic blood involvement in the peripheral blood smear.⁷ Other authors define PHL as having major liver involvement without evidence of extrahepatic involvement for at least 6 months.⁸ In our case, the multiple large lesions of the liver are consistent with advanced stage PHL with retroperitoneal lymph nodes and right lung metastasis. DLBCL is the most common histopathological type of lymphoma (65.9%). Other types have been described less commonly, including diffuse mixed large- and small-cell, lymphoblastic, diffuse histiocytic, mantle cell, and small noncleaved or Burkitt lymphoma.^5-7

Currently, there is no consensus on PHL treatment. The therapeutic options include surgery, chemotherapy, radiation therapy, or a combination of therapies.⁷ Most evidence regarding treatment and tumor response comes from case series, as PHLs are rare. Surgical resection in a series of 8 patients showed a cumulative 1- and 2-year survival rate of 66.7% and 55.6%, respectively.⁹ Chemotherapy is the recommended treatment option for extra-nodal DLBCL, making it a choice also for the treatment of PHL.¹⁰ Page and colleagues demonstrated that combination chemotherapy regimens helped achieve remission for 83.3% of patients.¹¹ Since PHL is chemo-sensitive, most patients are treated with chemotherapy alone or in combination with surgery and radiotherapy. The most common chemotherapy regimen is R-CHOP for CD20-positive B-cell lymphoma. The use of the R-CHOP regimen has been reported to achieve complete remission in primary DLBCL of the liver.¹²

Conclusions

Primary DLBCL of the liver is a very rare disease without specific clinical manifestations, biochemical indicators, or radiologic features except for space-occupying liver lesions. However, patients’ conditions can deteriorate rapidly at an advanced stage, as demonstrated in our case. DLBCL requires a high level of suspicion for its early diagnosis and treatment and should be considered in the differential diagnosis for any hepatic space-occupying lesions.

Acknowledgments

We appreciate Lynne Dryer, ARNP, for her clinical assistance with this patient and in the preparation of the manuscript.

Primary hepatic lymphoma (PHL) is a rare, malignant lymphoma of the liver. It differs from the predominantly lymph nodal or splenic involvement associated with other types of lymphoma. It is usually detected incidentally on imaging examination, commonly computed tomography (CT), for nonspecific clinical presentation. However, it has important clinical implications for early diagnosis and treatment as indicated in our case.

Case Presentation

An 84-year-old man presented to the emergency department for evaluation of upper back pain. The patient had a history of hypertension, diabetes mellitus, and was a former smoker. He had normal vital signs, an unremarkable physical examination, and a body mass index of 25. His laboratory studies showed a normal blood cell count and serum chemistry, including serum calcium level and α-fetoprotein, but mildly elevated liver function tests.

The patient’s chest CT angiography showed no evidence of thoracic aortic dissection, penetrating atherosclerotic ulceration, or pulmonary artery embolism. Besides emphysematous changes in the lung, the chest CT was within normal limits.

Discussion

Lymphoma is a tumor that originates from hematopoietic cells typically presented as a circumscribed solid tumor of lymphoid cells.¹ Lymphomas are usually seen in the lymph nodes, spleen, blood, bone marrow, brain, gastrointestinal tract, skin, or other normal structures where lymphoreticular cells exist but very rarely in the liver.² PHL is extremely rare due to the lack of abundant lymphoid tissue in the normal liver.³ It accounts for 0.4% of extra-nodal lymphomas and 0.016% of non-Hodgkin lymphoma.^4-6 The etiology of PHL is unknown but usually it develops in patients with previous liver disease: viral infection (hepatitis B and C, Epstein-Barr, and HIV), autoimmune disease, immunosuppression, or liver cirrhosis.^5-7

The diagnosis of PHL can be challenging due to its rarity, vague clinical features, and nonspecific radiologic findings. The common presenting symptoms are usually vague and include abdominal pain or discomfort, fatigue, jaundice, weight loss, and fever.⁵ Liver biopsy is essential to its diagnosis. The disease course is usually indolent among most patients with PHL. In our case, the patient presented with upper back pain but his condition deteriorated rapidly, likely due to the advanced stage of the disease. Diagnosis of liver lymphoma depends on a liver biopsy that should be compatible with the lymphoma. The criteria for diagnosis of PHL defined by Lei include (1) symptoms caused mainly by liver involvement at presentation; (2) absence of distant lymphadenopathy, palpable clinically at presentation or detected during staging radiologic studies; and (3) absence of leukemic blood involvement in the peripheral blood smear.⁷ Other authors define PHL as having major liver involvement without evidence of extrahepatic involvement for at least 6 months.⁸ In our case, the multiple large lesions of the liver are consistent with advanced stage PHL with retroperitoneal lymph nodes and right lung metastasis. DLBCL is the most common histopathological type of lymphoma (65.9%). Other types have been described less commonly, including diffuse mixed large- and small-cell, lymphoblastic, diffuse histiocytic, mantle cell, and small noncleaved or Burkitt lymphoma.^5-7

Currently, there is no consensus on PHL treatment. The therapeutic options include surgery, chemotherapy, radiation therapy, or a combination of therapies.⁷ Most evidence regarding treatment and tumor response comes from case series, as PHLs are rare. Surgical resection in a series of 8 patients showed a cumulative 1- and 2-year survival rate of 66.7% and 55.6%, respectively.⁹ Chemotherapy is the recommended treatment option for extra-nodal DLBCL, making it a choice also for the treatment of PHL.¹⁰ Page and colleagues demonstrated that combination chemotherapy regimens helped achieve remission for 83.3% of patients.¹¹ Since PHL is chemo-sensitive, most patients are treated with chemotherapy alone or in combination with surgery and radiotherapy. The most common chemotherapy regimen is R-CHOP for CD20-positive B-cell lymphoma. The use of the R-CHOP regimen has been reported to achieve complete remission in primary DLBCL of the liver.¹²

Conclusions

Primary DLBCL of the liver is a very rare disease without specific clinical manifestations, biochemical indicators, or radiologic features except for space-occupying liver lesions. However, patients’ conditions can deteriorate rapidly at an advanced stage, as demonstrated in our case. DLBCL requires a high level of suspicion for its early diagnosis and treatment and should be considered in the differential diagnosis for any hepatic space-occupying lesions.

Acknowledgments

We appreciate Lynne Dryer, ARNP, for her clinical assistance with this patient and in the preparation of the manuscript.

Primary hepatic lymphoma (PHL) is a rare, malignant lymphoma of the liver. It differs from the predominantly lymph nodal or splenic involvement associated with other types of lymphoma. It is usually detected incidentally on imaging examination, commonly computed tomography (CT), for nonspecific clinical presentation. However, it has important clinical implications for early diagnosis and treatment as indicated in our case.

Case Presentation

An 84-year-old man presented to the emergency department for evaluation of upper back pain. The patient had a history of hypertension, diabetes mellitus, and was a former smoker. He had normal vital signs, an unremarkable physical examination, and a body mass index of 25. His laboratory studies showed a normal blood cell count and serum chemistry, including serum calcium level and α-fetoprotein, but mildly elevated liver function tests.

The patient’s chest CT angiography showed no evidence of thoracic aortic dissection, penetrating atherosclerotic ulceration, or pulmonary artery embolism. Besides emphysematous changes in the lung, the chest CT was within normal limits.

Discussion

Lymphoma is a tumor that originates from hematopoietic cells typically presented as a circumscribed solid tumor of lymphoid cells.¹ Lymphomas are usually seen in the lymph nodes, spleen, blood, bone marrow, brain, gastrointestinal tract, skin, or other normal structures where lymphoreticular cells exist but very rarely in the liver.² PHL is extremely rare due to the lack of abundant lymphoid tissue in the normal liver.³ It accounts for 0.4% of extra-nodal lymphomas and 0.016% of non-Hodgkin lymphoma.^4-6 The etiology of PHL is unknown but usually it develops in patients with previous liver disease: viral infection (hepatitis B and C, Epstein-Barr, and HIV), autoimmune disease, immunosuppression, or liver cirrhosis.^5-7

The diagnosis of PHL can be challenging due to its rarity, vague clinical features, and nonspecific radiologic findings. The common presenting symptoms are usually vague and include abdominal pain or discomfort, fatigue, jaundice, weight loss, and fever.⁵ Liver biopsy is essential to its diagnosis. The disease course is usually indolent among most patients with PHL. In our case, the patient presented with upper back pain but his condition deteriorated rapidly, likely due to the advanced stage of the disease. Diagnosis of liver lymphoma depends on a liver biopsy that should be compatible with the lymphoma. The criteria for diagnosis of PHL defined by Lei include (1) symptoms caused mainly by liver involvement at presentation; (2) absence of distant lymphadenopathy, palpable clinically at presentation or detected during staging radiologic studies; and (3) absence of leukemic blood involvement in the peripheral blood smear.⁷ Other authors define PHL as having major liver involvement without evidence of extrahepatic involvement for at least 6 months.⁸ In our case, the multiple large lesions of the liver are consistent with advanced stage PHL with retroperitoneal lymph nodes and right lung metastasis. DLBCL is the most common histopathological type of lymphoma (65.9%). Other types have been described less commonly, including diffuse mixed large- and small-cell, lymphoblastic, diffuse histiocytic, mantle cell, and small noncleaved or Burkitt lymphoma.^5-7

Currently, there is no consensus on PHL treatment. The therapeutic options include surgery, chemotherapy, radiation therapy, or a combination of therapies.⁷ Most evidence regarding treatment and tumor response comes from case series, as PHLs are rare. Surgical resection in a series of 8 patients showed a cumulative 1- and 2-year survival rate of 66.7% and 55.6%, respectively.⁹ Chemotherapy is the recommended treatment option for extra-nodal DLBCL, making it a choice also for the treatment of PHL.¹⁰ Page and colleagues demonstrated that combination chemotherapy regimens helped achieve remission for 83.3% of patients.¹¹ Since PHL is chemo-sensitive, most patients are treated with chemotherapy alone or in combination with surgery and radiotherapy. The most common chemotherapy regimen is R-CHOP for CD20-positive B-cell lymphoma. The use of the R-CHOP regimen has been reported to achieve complete remission in primary DLBCL of the liver.¹²

Conclusions

Primary DLBCL of the liver is a very rare disease without specific clinical manifestations, biochemical indicators, or radiologic features except for space-occupying liver lesions. However, patients’ conditions can deteriorate rapidly at an advanced stage, as demonstrated in our case. DLBCL requires a high level of suspicion for its early diagnosis and treatment and should be considered in the differential diagnosis for any hepatic space-occupying lesions.

Acknowledgments

We appreciate Lynne Dryer, ARNP, for her clinical assistance with this patient and in the preparation of the manuscript.

In patients with gastrointestinal (GI) malignancies, malnutrition is common. In addition, it has various negative implications, including high risk for surgical complications, prolonged hospitalization, decreased quality of life (QOL), increased mortality, and poor tolerance for treatments such as chemotherapy and radiotherapy.¹

A 2014 French study of 1903 patients hospitalized for cancer reported a 39% overall prevalence of malnutrition; 39% in patients with cancers of the colon/rectum, 60% for pancreatic cancer, and 67% for cancers of the esophagus/stomach.² Malnutrition was defined as body mass index (BMI) < 18.5 for individuals aged < 75 years or BMI < 21 for individuals aged ≥ 75 years, and/or weight loss > 10% since disease onset. Malnutrition also was strongly associated with worsened performance status.

The etiology of malnutrition in GI cancers is often multifactorial. It includes systemic tumor effects, such as inflammatory mediators contributing to hypermetabolism and cachexia, local tumor-associated mechanical obstruction, GI toxicities caused by antineoplastic therapy or other medications, and psychological factors that contribute to anorexia.³ Patient-related risk factors such as older age, other chronic diseases, and history of other GI surgeries also play a role.¹

Other studies have demonstrated that malnutrition in patients with GI malignancies undergoing surgical resection is associated with high rates of severe postoperative complications, increased length of stay (LOS) and time on a ventilator for patients treated in the intensive care unit, and poor QOL in the postoperative survival period.^4-6 Several randomized controlled trials conducted in patients with GI cancers have shown that enteral and parenteral nutrition supplementations in the perioperative period improve various outcomes, such as reduction of postoperative complication rates, fewer readmissions, improved chemotherapy tolerance, and improved QOL.^7-10 Thus, in the management of patients with GI malignancies, it is highly important to implement early nutritional screening and establish a diagnosis of malnutrition to intervene and reduce postoperative morbidity and mortality.¹

However, tools and predictors of malnutrition are often imperfect. The Academy of Nutrition and Dietetics and the American Society for Parenteral and Enteral Nutrition (AND/ASPEN) weight-based criteria define malnutrition and nutritionally-at-risk as BMI < 18.5, involuntary loss of at least 10% of body weight within 6 months or 5% within 1 month, or loss of 10 lb within 6 months.¹¹ While the ASPEN criteria are often used to define malnourishment, they may not fully capture the population at risk, and there does not exist a gold-standard tool for nutritional screening. A 2002 study that performed a critical appraisal of 44 nutritional screening tools found that no single tool was fully sufficient for application, development, evaluation, and consistent screening.¹² As such, consistently screening for malnutrition to target interventions in the perioperative period for GI surgical oncology has been challenging.¹³ More recent tools such as the perioperative nutrition screen (PONS) have been validated as rapid, effective screening tools to predict postoperative outcomes.¹⁴ Additionally, implementation of perioperative nutritional protocols, such as enhanced recovery after surgery (ERAS) in colon cancer (CC) surgery, also has shown improved perioperative care and outcomes.¹⁵

Preoperative nutritional interventions have been implemented in practice and have focused mostly on the immediate perioperative period. This has been shown to improve surgical outcomes. The Veterans Health Administration (VHA) provides comprehensive care to patients in a single-payer system, allowing for capture of perioperative data and the opportunity for focused preoperative interventions to improve outcomes.

Methods

This was a retrospective record review of colorectal malignancies treated with curative intent at the Veterans Affairs Ann Arbor Healthcare System (VAAAHS) in Michigan between January 1, 2015, and December 31, 2019. We examined nutritional status, degree of longitudinal weight loss, and subsequent clinical outcomes, including delayed postoperative recovery and delays in chemotherapy in 115 patients with CC and 33 patients with rectal cancer (RC) undergoing curative surgical resection at VAAAHS. To avoid additional confounding effects of advanced cancer, only early-stage, curable disease was included. This study was approved by the VAAAHS Institutional Review Board.

Analysis

The data were described using mean (SD) for continuous variables and number and percentages for categorical variables. Where appropriate, Fisher exact test, Pearson χ² test, Spearman ρ, and Mann-Whitney U test were used for tests of significance. SAS (SAS Institute) was utilized for multivariable analysis. The significance level was P = .05 for all tests.

Results

There were 115 patients in the CC cohort and 33 in the RC cohort. The mean (SD) age at diagnosis was 70 (9.1) for CC group and 59 (1.4) for RC group (Table 1). 

Weight Trends

From 1 year to 6 months before diagnosis, 40 of 80 patients lost weight in the CC cohort (mean change, +1.9%) and 6 of 22 patients lost weight in the RC cohort (mean change, + 0.5%). From 6 months before diagnosis to time of diagnosis, 47 of 74 patients lost weight in the CC cohort (mean change, -1.5%) and 14 of 21 patients lost weight in the RC cohort (mean change, -2.5%). From time of diagnosis to time of surgery, 36 of 104 patients with CC and 14 of 32 patients with RC lost weight with a mean weight change of and +0.1% and -0.3%, respectively. In the 6 months before surgery, any amount of weight loss was observed in 58 patients (66%) in the CC group and in 12 patients (57%) in the RC group. In this time frame, in the CC cohort, 32 patients (36%) were observed to have at least 3% weight loss, and 23 (26%) were observed to have at least 5% weight loss (Table 3). 

Nutrition Consultations

In the CC group, preoperative nutrition consultations (either inpatient or outpatient) occurred in 17 patients (15%). Inpatient postoperative nutrition evaluations occurred in 110 patients (96%) (Table 5). 

In the RC group, preoperative inpatient or outpatient nutrition consultations occurred in 12 patients (36%). Eight of those occurred before initiation of neoadjuvant chemoradiotherapy. All 33 patients received an inpatient postoperative nutrition evaluation during admission. Oral or enteral nutrition supplements were prescribed 19 times (58%). Postoperative outpatient nutrition consultations occurred for 24 patients (73%). Of the 19 patients who were readmitted to the hospital, 3 (16%) had a nutrition reconsultation on readmission.

Outcomes

The primary outcomes observed were delayed recovery, hospital readmission and LOS, and completion of adjuvant chemotherapy as indicated. Delayed recovery was observed in 35 patients with CC (40%) and 21 patients with RC (64%). Multivariable analysis in the CC cohort demonstrated that weight change was significantly associated with delayed recovery. Among those with ≥ 3% weight loss in the 6-month preoperative period (the weight measurement 6 months prior to diagnosis to date of surgery), 20 patients (63%) had delayed recovery compared with 15 patients (27%) without ≥ 3% weight loss who experienced delayed recovery (χ² = 10.84; P < .001).

Weight loss of ≥ 3% in the 6-month preoperative period also was significantly associated with complications. Of patients with at least 3% preoperative weight loss, 16 (50%) experienced complications, while 8 (14%) with < 3% preoperative weight loss experienced complications (χ² = 11.20; P < .001). Notably, ≥ 3% weight loss in the 1-year preoperative period before surgery was not significantly associated with delayed recovery. Any degree of 30-day postoperative weight loss was not correlated with delayed recovery. Finally, low preoperative albumin also was not correlated with delayed recovery (Fisher exact; P = .13). Table 3 displays differences based on presence of delayed recovery in the 88 patients with CC 6 months before surgery. Of note, ≥ 10-lb weight loss in the 6 months preceding surgery also correlated with delayed recovery (P = .01).In our cohort, 3% weight loss over 6 months had a sensitivity of 57%, specificity of 77%, positive predictive value 63%, and negative predictive value 73% for delayed recovery. By comparison, a 10-lb weight loss in 6 months per ASPEN criteria had a sensitivity of 40%, specificity of 85%, positive predictive value 64%, and negative predictive value 68% for delayed recovery.

Hospital Readmissions and LOS

Hospital readmissions occurred within the first 30 days in 11 patients (10%) in the CC cohort and 12 patients (36%) in the RC cohort. Readmissions occurred between 31 and 60 days in 4 (3%) and 7 (21%) of CC and RC cohorts, respectively. The presence of ≥ 3% weight loss in the 6-month preoperative period was significantly associated with 60-day readmissions. Among those with ≥ 3% preoperative weight loss, 8 patients (25%) had readmissions within 60 days vs 3 patients (5%) without 3% preoperative weight loss who had readmissions within 60 days (Fisher exact; P = .02).

Mean (SD) LOS was 6.4 (4.7) days (range, 1-28) for patients with CC and 8.8 (5.1) days (range, 3-23) for patients with RC. Mean (SD) LOS increased to 10.2 (4.3) days and 9.7 (6.0) days in patients with delayed recovery in the CC and RC cohorts, respectively. The mean (SD) LOS was 5.2 (2.8) days and 6.3 (2.2) days in patients without delayed recovery in the CC and RC cohorts, respectively. There was no significant difference when examining association between percent weight change and LOS for either initial admission (r_s= -0.1409; 2-tailed P = .19) or for initial and readmission combined (r_s = -0.13532; 2-tailed P = .21) within the CC cohort.

Chemotherapy

Within the CC cohort, 31 patients (27%) had an indication for adjuvant chemotherapy. Of these, 25 of 31 (81%) started chemotherapy within 12 weeks of surgical resection, and of these, 17 of 25 patients (68%) completed chemotherapy as indicated. Within the RC cohort all 33 patients had an indication for adjuvant chemotherapy, of these 18 of 33 patients (55%) began within 12 weeks of surgical resection, and 10 of 18 (56%) completed chemotherapy as indicated.

Among the CC cohort who began but did not complete adjuvant chemotherapy, there was no significant association between completion of chemotherapy and preoperative weight loss. Of patients with ≥ 3% preoperative weight loss, 3 (43%) did not complete chemotherapy vs 3 patients (27%) without preoperative weight loss who did not complete chemotherapy as indicated (Fisher exact; P = .63). Finally, low preoperative albumin did not significantly correlate with lack of completion of adjuvant chemotherapy (Fisher exact; P = .99).

Discussion

This study highlights several important findings. There were no patients in our cohort that met ASPEN malnourishment criteria with a BMI < 18.5. Twenty percent of patients lost at least 10 lb in 6 months before the operation. Notably, patients had significant associations with adverse outcomes with less pronounced weight loss than previously noted. As has been established previously, malnourishment can be difficult to screen for, and BMI also is often an imprecise tool.¹² In the CC cohort, weight loss ≥ 3% from 6 months before surgery was significantly associated with delayed recovery, complications, and hospital readmissions. We did not identify a statistically significant effect on chemotherapy completion. However, the numerical difference was suggestive of a difference, and a type 2 error is possible due to our limited sample size.

Our findings imply that the effects of even mild malnutrition are even more profound than previously thought. Significantly, this applies to overweight and obese patients as well, as these constituted a significant fraction of our cohort. A finding of ≥ 3% weight loss at the time of CC diagnosis may provide an opportunity for a focused nutrition intervention up to the time of surgery. Second, although nutrition consultation was frequent in the inpatient setting during the hospital admission (96%-100%), rates of nutrition evaluation were as low as 15% before surgery and 12% after surgery, representing a key area for improvement and focused intervention. An optimal time for intervention and nutrition prehabilitation would be at time of diagnosis before surgery with plans for continued aggressive monitoring and subsequent follow-up. Our finding seems to provide a more sensitive tool to identify patients at risk for delayed recovery compared with the ASPEN-driven assessment. Given the simplicity and the clinical significance, our test consisting of 3% weight loss over 6 months, with its sensitivity of 57%, may be superior to the ASPEN 10-lb weight loss, with its sensitivity of 40% in our cohort.

Previous Studies

Our findings are consistent with previous studies that have demonstrated that perioperative weight loss and malnutrition are correlated with delayed recovery and complications, such as wound healing, in patients with GI cancer.^2,4,5,8 In a retrospective study of more than 7000 patients with CC, those who were overweight or obese were found to have an improved overall survival compared with other BMI categories, and those who were underweight had an increased 30-day mortality and postoperative complications.¹⁶

In another retrospective study of 3799 patients with CC, those who were overweight and obese had an improved 5-year survival rate compared with patients whose weight was normal or underweight. Outcomes were found to be stage dependent.¹⁷ In this study cohort, all patients were either overweight or obese and remained in that category even with weight loss. This may have contributed to overall improved outcomes.

Implications and Next Steps

Our study has several implications. One is that BMI criteria < 18.5 may not be a good measure for malnutrition given that about 75% of the patients in our cohort were overweight or obese and none were underweight. We also show a concrete, easily identifiable finding of percent weight change that could be addressed as an automated electronic notification and potentially identify a patient at risk and serve as a trigger for both timely and early nutrition intervention. It seems to be more sensitive than the ASPEN criterion of 10-lb weight loss in 6 months before surgery. Sensitivity is especially appealing given the ease and potential of embedding this tool in an electronic health record and the clinical importance of the consequent intervention. Preoperative as opposed to perioperative nutrition optimization at time of CC diagnosis is essential, as it may help improve postsurgical outcomes as well as oncologic outcomes, including completion of adjuvant chemotherapy. Finally, although our study found that rates of inpatient postoperative nutrition consultation were high, rates of outpatient nutrition consultation in the preoperative period were low. This represents a missed opportunity for intervention before surgery. Similarly, rates of postoperative nutrition follow-up period were low, which points to an area for improvement in longitudinal and holistic care.

We suggest modifications to nutrition intervention protocols, such as ERAS, which should start at the time of GI malignancy diagnosis.¹⁸ Other suggestions include standard involvement of nutritionists in inpatient and outpatient settings with longitudinal follow-up in the preoperative and postoperative periods and patient enrollment in a nutrition program with monitoring at time of diagnosis at the VHA. Our findings as well as previous literature suggest that the preoperative period is the most important time to intervene with regard to nutrition optimization and represents an opportunity for intensive prehabilitation. Future areas of research include incorporating other important measures of malnourishment independent of BMI into future study designs, such as sarcopenia and adipose tissue density, to better assess body composition and predict prognostic risk in CC.^18,19

Strengths and Limitations

This study is limited by its single-center, retrospective design and small sample sizes, and we acknowledge the limitations of our data set. However, the strength of this VHA-based study is that the single-payer system allows for complete capture of perioperative data as well as the opportunity for focused preoperative interventions to improve outcomes. To our knowledge, there is no currently existing literature on improving nutrition protocols at the VHA for patients with a GI malignancy. These retrospective data will help inform current gaps in quality improvement and supportive oncology as it relates to optimizing malnourishment in veterans undergoing surgical resection for their cancer.

Conclusions

In the CC cohort, weight loss of ≥ 3% from 6 months prior to time of surgery was significantly associated with delayed recovery, complications, and hospital readmissions. Our findings suggest that patients with CC undergoing surgery may benefit from an intensive, early nutrition prehabilitation. Preoperative nutrition optimization may help improve postsurgical outcomes as well as oncologic outcomes, including completion of adjuvant chemotherapy. Further research would be able to clarify these hypotheses.

In patients with gastrointestinal (GI) malignancies, malnutrition is common. In addition, it has various negative implications, including high risk for surgical complications, prolonged hospitalization, decreased quality of life (QOL), increased mortality, and poor tolerance for treatments such as chemotherapy and radiotherapy.¹

A 2014 French study of 1903 patients hospitalized for cancer reported a 39% overall prevalence of malnutrition; 39% in patients with cancers of the colon/rectum, 60% for pancreatic cancer, and 67% for cancers of the esophagus/stomach.² Malnutrition was defined as body mass index (BMI) < 18.5 for individuals aged < 75 years or BMI < 21 for individuals aged ≥ 75 years, and/or weight loss > 10% since disease onset. Malnutrition also was strongly associated with worsened performance status.

The etiology of malnutrition in GI cancers is often multifactorial. It includes systemic tumor effects, such as inflammatory mediators contributing to hypermetabolism and cachexia, local tumor-associated mechanical obstruction, GI toxicities caused by antineoplastic therapy or other medications, and psychological factors that contribute to anorexia.³ Patient-related risk factors such as older age, other chronic diseases, and history of other GI surgeries also play a role.¹

Other studies have demonstrated that malnutrition in patients with GI malignancies undergoing surgical resection is associated with high rates of severe postoperative complications, increased length of stay (LOS) and time on a ventilator for patients treated in the intensive care unit, and poor QOL in the postoperative survival period.^4-6 Several randomized controlled trials conducted in patients with GI cancers have shown that enteral and parenteral nutrition supplementations in the perioperative period improve various outcomes, such as reduction of postoperative complication rates, fewer readmissions, improved chemotherapy tolerance, and improved QOL.^7-10 Thus, in the management of patients with GI malignancies, it is highly important to implement early nutritional screening and establish a diagnosis of malnutrition to intervene and reduce postoperative morbidity and mortality.¹

However, tools and predictors of malnutrition are often imperfect. The Academy of Nutrition and Dietetics and the American Society for Parenteral and Enteral Nutrition (AND/ASPEN) weight-based criteria define malnutrition and nutritionally-at-risk as BMI < 18.5, involuntary loss of at least 10% of body weight within 6 months or 5% within 1 month, or loss of 10 lb within 6 months.¹¹ While the ASPEN criteria are often used to define malnourishment, they may not fully capture the population at risk, and there does not exist a gold-standard tool for nutritional screening. A 2002 study that performed a critical appraisal of 44 nutritional screening tools found that no single tool was fully sufficient for application, development, evaluation, and consistent screening.¹² As such, consistently screening for malnutrition to target interventions in the perioperative period for GI surgical oncology has been challenging.¹³ More recent tools such as the perioperative nutrition screen (PONS) have been validated as rapid, effective screening tools to predict postoperative outcomes.¹⁴ Additionally, implementation of perioperative nutritional protocols, such as enhanced recovery after surgery (ERAS) in colon cancer (CC) surgery, also has shown improved perioperative care and outcomes.¹⁵

Preoperative nutritional interventions have been implemented in practice and have focused mostly on the immediate perioperative period. This has been shown to improve surgical outcomes. The Veterans Health Administration (VHA) provides comprehensive care to patients in a single-payer system, allowing for capture of perioperative data and the opportunity for focused preoperative interventions to improve outcomes.

Methods

This was a retrospective record review of colorectal malignancies treated with curative intent at the Veterans Affairs Ann Arbor Healthcare System (VAAAHS) in Michigan between January 1, 2015, and December 31, 2019. We examined nutritional status, degree of longitudinal weight loss, and subsequent clinical outcomes, including delayed postoperative recovery and delays in chemotherapy in 115 patients with CC and 33 patients with rectal cancer (RC) undergoing curative surgical resection at VAAAHS. To avoid additional confounding effects of advanced cancer, only early-stage, curable disease was included. This study was approved by the VAAAHS Institutional Review Board.

Analysis

The data were described using mean (SD) for continuous variables and number and percentages for categorical variables. Where appropriate, Fisher exact test, Pearson χ² test, Spearman ρ, and Mann-Whitney U test were used for tests of significance. SAS (SAS Institute) was utilized for multivariable analysis. The significance level was P = .05 for all tests.

Results

There were 115 patients in the CC cohort and 33 in the RC cohort. The mean (SD) age at diagnosis was 70 (9.1) for CC group and 59 (1.4) for RC group (Table 1). 

Weight Trends

From 1 year to 6 months before diagnosis, 40 of 80 patients lost weight in the CC cohort (mean change, +1.9%) and 6 of 22 patients lost weight in the RC cohort (mean change, + 0.5%). From 6 months before diagnosis to time of diagnosis, 47 of 74 patients lost weight in the CC cohort (mean change, -1.5%) and 14 of 21 patients lost weight in the RC cohort (mean change, -2.5%). From time of diagnosis to time of surgery, 36 of 104 patients with CC and 14 of 32 patients with RC lost weight with a mean weight change of and +0.1% and -0.3%, respectively. In the 6 months before surgery, any amount of weight loss was observed in 58 patients (66%) in the CC group and in 12 patients (57%) in the RC group. In this time frame, in the CC cohort, 32 patients (36%) were observed to have at least 3% weight loss, and 23 (26%) were observed to have at least 5% weight loss (Table 3). 

Nutrition Consultations

In the CC group, preoperative nutrition consultations (either inpatient or outpatient) occurred in 17 patients (15%). Inpatient postoperative nutrition evaluations occurred in 110 patients (96%) (Table 5). 

In the RC group, preoperative inpatient or outpatient nutrition consultations occurred in 12 patients (36%). Eight of those occurred before initiation of neoadjuvant chemoradiotherapy. All 33 patients received an inpatient postoperative nutrition evaluation during admission. Oral or enteral nutrition supplements were prescribed 19 times (58%). Postoperative outpatient nutrition consultations occurred for 24 patients (73%). Of the 19 patients who were readmitted to the hospital, 3 (16%) had a nutrition reconsultation on readmission.

Outcomes

The primary outcomes observed were delayed recovery, hospital readmission and LOS, and completion of adjuvant chemotherapy as indicated. Delayed recovery was observed in 35 patients with CC (40%) and 21 patients with RC (64%). Multivariable analysis in the CC cohort demonstrated that weight change was significantly associated with delayed recovery. Among those with ≥ 3% weight loss in the 6-month preoperative period (the weight measurement 6 months prior to diagnosis to date of surgery), 20 patients (63%) had delayed recovery compared with 15 patients (27%) without ≥ 3% weight loss who experienced delayed recovery (χ² = 10.84; P < .001).

Weight loss of ≥ 3% in the 6-month preoperative period also was significantly associated with complications. Of patients with at least 3% preoperative weight loss, 16 (50%) experienced complications, while 8 (14%) with < 3% preoperative weight loss experienced complications (χ² = 11.20; P < .001). Notably, ≥ 3% weight loss in the 1-year preoperative period before surgery was not significantly associated with delayed recovery. Any degree of 30-day postoperative weight loss was not correlated with delayed recovery. Finally, low preoperative albumin also was not correlated with delayed recovery (Fisher exact; P = .13). Table 3 displays differences based on presence of delayed recovery in the 88 patients with CC 6 months before surgery. Of note, ≥ 10-lb weight loss in the 6 months preceding surgery also correlated with delayed recovery (P = .01).In our cohort, 3% weight loss over 6 months had a sensitivity of 57%, specificity of 77%, positive predictive value 63%, and negative predictive value 73% for delayed recovery. By comparison, a 10-lb weight loss in 6 months per ASPEN criteria had a sensitivity of 40%, specificity of 85%, positive predictive value 64%, and negative predictive value 68% for delayed recovery.

Hospital Readmissions and LOS

Hospital readmissions occurred within the first 30 days in 11 patients (10%) in the CC cohort and 12 patients (36%) in the RC cohort. Readmissions occurred between 31 and 60 days in 4 (3%) and 7 (21%) of CC and RC cohorts, respectively. The presence of ≥ 3% weight loss in the 6-month preoperative period was significantly associated with 60-day readmissions. Among those with ≥ 3% preoperative weight loss, 8 patients (25%) had readmissions within 60 days vs 3 patients (5%) without 3% preoperative weight loss who had readmissions within 60 days (Fisher exact; P = .02).

Mean (SD) LOS was 6.4 (4.7) days (range, 1-28) for patients with CC and 8.8 (5.1) days (range, 3-23) for patients with RC. Mean (SD) LOS increased to 10.2 (4.3) days and 9.7 (6.0) days in patients with delayed recovery in the CC and RC cohorts, respectively. The mean (SD) LOS was 5.2 (2.8) days and 6.3 (2.2) days in patients without delayed recovery in the CC and RC cohorts, respectively. There was no significant difference when examining association between percent weight change and LOS for either initial admission (r_s= -0.1409; 2-tailed P = .19) or for initial and readmission combined (r_s = -0.13532; 2-tailed P = .21) within the CC cohort.

Chemotherapy

Within the CC cohort, 31 patients (27%) had an indication for adjuvant chemotherapy. Of these, 25 of 31 (81%) started chemotherapy within 12 weeks of surgical resection, and of these, 17 of 25 patients (68%) completed chemotherapy as indicated. Within the RC cohort all 33 patients had an indication for adjuvant chemotherapy, of these 18 of 33 patients (55%) began within 12 weeks of surgical resection, and 10 of 18 (56%) completed chemotherapy as indicated.

Among the CC cohort who began but did not complete adjuvant chemotherapy, there was no significant association between completion of chemotherapy and preoperative weight loss. Of patients with ≥ 3% preoperative weight loss, 3 (43%) did not complete chemotherapy vs 3 patients (27%) without preoperative weight loss who did not complete chemotherapy as indicated (Fisher exact; P = .63). Finally, low preoperative albumin did not significantly correlate with lack of completion of adjuvant chemotherapy (Fisher exact; P = .99).

Discussion

This study highlights several important findings. There were no patients in our cohort that met ASPEN malnourishment criteria with a BMI < 18.5. Twenty percent of patients lost at least 10 lb in 6 months before the operation. Notably, patients had significant associations with adverse outcomes with less pronounced weight loss than previously noted. As has been established previously, malnourishment can be difficult to screen for, and BMI also is often an imprecise tool.¹² In the CC cohort, weight loss ≥ 3% from 6 months before surgery was significantly associated with delayed recovery, complications, and hospital readmissions. We did not identify a statistically significant effect on chemotherapy completion. However, the numerical difference was suggestive of a difference, and a type 2 error is possible due to our limited sample size.

Our findings imply that the effects of even mild malnutrition are even more profound than previously thought. Significantly, this applies to overweight and obese patients as well, as these constituted a significant fraction of our cohort. A finding of ≥ 3% weight loss at the time of CC diagnosis may provide an opportunity for a focused nutrition intervention up to the time of surgery. Second, although nutrition consultation was frequent in the inpatient setting during the hospital admission (96%-100%), rates of nutrition evaluation were as low as 15% before surgery and 12% after surgery, representing a key area for improvement and focused intervention. An optimal time for intervention and nutrition prehabilitation would be at time of diagnosis before surgery with plans for continued aggressive monitoring and subsequent follow-up. Our finding seems to provide a more sensitive tool to identify patients at risk for delayed recovery compared with the ASPEN-driven assessment. Given the simplicity and the clinical significance, our test consisting of 3% weight loss over 6 months, with its sensitivity of 57%, may be superior to the ASPEN 10-lb weight loss, with its sensitivity of 40% in our cohort.

Previous Studies

Our findings are consistent with previous studies that have demonstrated that perioperative weight loss and malnutrition are correlated with delayed recovery and complications, such as wound healing, in patients with GI cancer.^2,4,5,8 In a retrospective study of more than 7000 patients with CC, those who were overweight or obese were found to have an improved overall survival compared with other BMI categories, and those who were underweight had an increased 30-day mortality and postoperative complications.¹⁶

In another retrospective study of 3799 patients with CC, those who were overweight and obese had an improved 5-year survival rate compared with patients whose weight was normal or underweight. Outcomes were found to be stage dependent.¹⁷ In this study cohort, all patients were either overweight or obese and remained in that category even with weight loss. This may have contributed to overall improved outcomes.

Implications and Next Steps

Our study has several implications. One is that BMI criteria < 18.5 may not be a good measure for malnutrition given that about 75% of the patients in our cohort were overweight or obese and none were underweight. We also show a concrete, easily identifiable finding of percent weight change that could be addressed as an automated electronic notification and potentially identify a patient at risk and serve as a trigger for both timely and early nutrition intervention. It seems to be more sensitive than the ASPEN criterion of 10-lb weight loss in 6 months before surgery. Sensitivity is especially appealing given the ease and potential of embedding this tool in an electronic health record and the clinical importance of the consequent intervention. Preoperative as opposed to perioperative nutrition optimization at time of CC diagnosis is essential, as it may help improve postsurgical outcomes as well as oncologic outcomes, including completion of adjuvant chemotherapy. Finally, although our study found that rates of inpatient postoperative nutrition consultation were high, rates of outpatient nutrition consultation in the preoperative period were low. This represents a missed opportunity for intervention before surgery. Similarly, rates of postoperative nutrition follow-up period were low, which points to an area for improvement in longitudinal and holistic care.

We suggest modifications to nutrition intervention protocols, such as ERAS, which should start at the time of GI malignancy diagnosis.¹⁸ Other suggestions include standard involvement of nutritionists in inpatient and outpatient settings with longitudinal follow-up in the preoperative and postoperative periods and patient enrollment in a nutrition program with monitoring at time of diagnosis at the VHA. Our findings as well as previous literature suggest that the preoperative period is the most important time to intervene with regard to nutrition optimization and represents an opportunity for intensive prehabilitation. Future areas of research include incorporating other important measures of malnourishment independent of BMI into future study designs, such as sarcopenia and adipose tissue density, to better assess body composition and predict prognostic risk in CC.^18,19

Strengths and Limitations

This study is limited by its single-center, retrospective design and small sample sizes, and we acknowledge the limitations of our data set. However, the strength of this VHA-based study is that the single-payer system allows for complete capture of perioperative data as well as the opportunity for focused preoperative interventions to improve outcomes. To our knowledge, there is no currently existing literature on improving nutrition protocols at the VHA for patients with a GI malignancy. These retrospective data will help inform current gaps in quality improvement and supportive oncology as it relates to optimizing malnourishment in veterans undergoing surgical resection for their cancer.

Conclusions

In the CC cohort, weight loss of ≥ 3% from 6 months prior to time of surgery was significantly associated with delayed recovery, complications, and hospital readmissions. Our findings suggest that patients with CC undergoing surgery may benefit from an intensive, early nutrition prehabilitation. Preoperative nutrition optimization may help improve postsurgical outcomes as well as oncologic outcomes, including completion of adjuvant chemotherapy. Further research would be able to clarify these hypotheses.

In patients with gastrointestinal (GI) malignancies, malnutrition is common. In addition, it has various negative implications, including high risk for surgical complications, prolonged hospitalization, decreased quality of life (QOL), increased mortality, and poor tolerance for treatments such as chemotherapy and radiotherapy.¹

A 2014 French study of 1903 patients hospitalized for cancer reported a 39% overall prevalence of malnutrition; 39% in patients with cancers of the colon/rectum, 60% for pancreatic cancer, and 67% for cancers of the esophagus/stomach.² Malnutrition was defined as body mass index (BMI) < 18.5 for individuals aged < 75 years or BMI < 21 for individuals aged ≥ 75 years, and/or weight loss > 10% since disease onset. Malnutrition also was strongly associated with worsened performance status.

The etiology of malnutrition in GI cancers is often multifactorial. It includes systemic tumor effects, such as inflammatory mediators contributing to hypermetabolism and cachexia, local tumor-associated mechanical obstruction, GI toxicities caused by antineoplastic therapy or other medications, and psychological factors that contribute to anorexia.³ Patient-related risk factors such as older age, other chronic diseases, and history of other GI surgeries also play a role.¹

Other studies have demonstrated that malnutrition in patients with GI malignancies undergoing surgical resection is associated with high rates of severe postoperative complications, increased length of stay (LOS) and time on a ventilator for patients treated in the intensive care unit, and poor QOL in the postoperative survival period.^4-6 Several randomized controlled trials conducted in patients with GI cancers have shown that enteral and parenteral nutrition supplementations in the perioperative period improve various outcomes, such as reduction of postoperative complication rates, fewer readmissions, improved chemotherapy tolerance, and improved QOL.^7-10 Thus, in the management of patients with GI malignancies, it is highly important to implement early nutritional screening and establish a diagnosis of malnutrition to intervene and reduce postoperative morbidity and mortality.¹

However, tools and predictors of malnutrition are often imperfect. The Academy of Nutrition and Dietetics and the American Society for Parenteral and Enteral Nutrition (AND/ASPEN) weight-based criteria define malnutrition and nutritionally-at-risk as BMI < 18.5, involuntary loss of at least 10% of body weight within 6 months or 5% within 1 month, or loss of 10 lb within 6 months.¹¹ While the ASPEN criteria are often used to define malnourishment, they may not fully capture the population at risk, and there does not exist a gold-standard tool for nutritional screening. A 2002 study that performed a critical appraisal of 44 nutritional screening tools found that no single tool was fully sufficient for application, development, evaluation, and consistent screening.¹² As such, consistently screening for malnutrition to target interventions in the perioperative period for GI surgical oncology has been challenging.¹³ More recent tools such as the perioperative nutrition screen (PONS) have been validated as rapid, effective screening tools to predict postoperative outcomes.¹⁴ Additionally, implementation of perioperative nutritional protocols, such as enhanced recovery after surgery (ERAS) in colon cancer (CC) surgery, also has shown improved perioperative care and outcomes.¹⁵

Preoperative nutritional interventions have been implemented in practice and have focused mostly on the immediate perioperative period. This has been shown to improve surgical outcomes. The Veterans Health Administration (VHA) provides comprehensive care to patients in a single-payer system, allowing for capture of perioperative data and the opportunity for focused preoperative interventions to improve outcomes.

Methods

This was a retrospective record review of colorectal malignancies treated with curative intent at the Veterans Affairs Ann Arbor Healthcare System (VAAAHS) in Michigan between January 1, 2015, and December 31, 2019. We examined nutritional status, degree of longitudinal weight loss, and subsequent clinical outcomes, including delayed postoperative recovery and delays in chemotherapy in 115 patients with CC and 33 patients with rectal cancer (RC) undergoing curative surgical resection at VAAAHS. To avoid additional confounding effects of advanced cancer, only early-stage, curable disease was included. This study was approved by the VAAAHS Institutional Review Board.

Analysis

The data were described using mean (SD) for continuous variables and number and percentages for categorical variables. Where appropriate, Fisher exact test, Pearson χ² test, Spearman ρ, and Mann-Whitney U test were used for tests of significance. SAS (SAS Institute) was utilized for multivariable analysis. The significance level was P = .05 for all tests.

Results

There were 115 patients in the CC cohort and 33 in the RC cohort. The mean (SD) age at diagnosis was 70 (9.1) for CC group and 59 (1.4) for RC group (Table 1). 

Weight Trends

From 1 year to 6 months before diagnosis, 40 of 80 patients lost weight in the CC cohort (mean change, +1.9%) and 6 of 22 patients lost weight in the RC cohort (mean change, + 0.5%). From 6 months before diagnosis to time of diagnosis, 47 of 74 patients lost weight in the CC cohort (mean change, -1.5%) and 14 of 21 patients lost weight in the RC cohort (mean change, -2.5%). From time of diagnosis to time of surgery, 36 of 104 patients with CC and 14 of 32 patients with RC lost weight with a mean weight change of and +0.1% and -0.3%, respectively. In the 6 months before surgery, any amount of weight loss was observed in 58 patients (66%) in the CC group and in 12 patients (57%) in the RC group. In this time frame, in the CC cohort, 32 patients (36%) were observed to have at least 3% weight loss, and 23 (26%) were observed to have at least 5% weight loss (Table 3). 

Nutrition Consultations

In the CC group, preoperative nutrition consultations (either inpatient or outpatient) occurred in 17 patients (15%). Inpatient postoperative nutrition evaluations occurred in 110 patients (96%) (Table 5). 

In the RC group, preoperative inpatient or outpatient nutrition consultations occurred in 12 patients (36%). Eight of those occurred before initiation of neoadjuvant chemoradiotherapy. All 33 patients received an inpatient postoperative nutrition evaluation during admission. Oral or enteral nutrition supplements were prescribed 19 times (58%). Postoperative outpatient nutrition consultations occurred for 24 patients (73%). Of the 19 patients who were readmitted to the hospital, 3 (16%) had a nutrition reconsultation on readmission.

Outcomes

The primary outcomes observed were delayed recovery, hospital readmission and LOS, and completion of adjuvant chemotherapy as indicated. Delayed recovery was observed in 35 patients with CC (40%) and 21 patients with RC (64%). Multivariable analysis in the CC cohort demonstrated that weight change was significantly associated with delayed recovery. Among those with ≥ 3% weight loss in the 6-month preoperative period (the weight measurement 6 months prior to diagnosis to date of surgery), 20 patients (63%) had delayed recovery compared with 15 patients (27%) without ≥ 3% weight loss who experienced delayed recovery (χ² = 10.84; P < .001).

Weight loss of ≥ 3% in the 6-month preoperative period also was significantly associated with complications. Of patients with at least 3% preoperative weight loss, 16 (50%) experienced complications, while 8 (14%) with < 3% preoperative weight loss experienced complications (χ² = 11.20; P < .001). Notably, ≥ 3% weight loss in the 1-year preoperative period before surgery was not significantly associated with delayed recovery. Any degree of 30-day postoperative weight loss was not correlated with delayed recovery. Finally, low preoperative albumin also was not correlated with delayed recovery (Fisher exact; P = .13). Table 3 displays differences based on presence of delayed recovery in the 88 patients with CC 6 months before surgery. Of note, ≥ 10-lb weight loss in the 6 months preceding surgery also correlated with delayed recovery (P = .01).In our cohort, 3% weight loss over 6 months had a sensitivity of 57%, specificity of 77%, positive predictive value 63%, and negative predictive value 73% for delayed recovery. By comparison, a 10-lb weight loss in 6 months per ASPEN criteria had a sensitivity of 40%, specificity of 85%, positive predictive value 64%, and negative predictive value 68% for delayed recovery.

Hospital Readmissions and LOS

Hospital readmissions occurred within the first 30 days in 11 patients (10%) in the CC cohort and 12 patients (36%) in the RC cohort. Readmissions occurred between 31 and 60 days in 4 (3%) and 7 (21%) of CC and RC cohorts, respectively. The presence of ≥ 3% weight loss in the 6-month preoperative period was significantly associated with 60-day readmissions. Among those with ≥ 3% preoperative weight loss, 8 patients (25%) had readmissions within 60 days vs 3 patients (5%) without 3% preoperative weight loss who had readmissions within 60 days (Fisher exact; P = .02).

Mean (SD) LOS was 6.4 (4.7) days (range, 1-28) for patients with CC and 8.8 (5.1) days (range, 3-23) for patients with RC. Mean (SD) LOS increased to 10.2 (4.3) days and 9.7 (6.0) days in patients with delayed recovery in the CC and RC cohorts, respectively. The mean (SD) LOS was 5.2 (2.8) days and 6.3 (2.2) days in patients without delayed recovery in the CC and RC cohorts, respectively. There was no significant difference when examining association between percent weight change and LOS for either initial admission (r_s= -0.1409; 2-tailed P = .19) or for initial and readmission combined (r_s = -0.13532; 2-tailed P = .21) within the CC cohort.

Chemotherapy

Within the CC cohort, 31 patients (27%) had an indication for adjuvant chemotherapy. Of these, 25 of 31 (81%) started chemotherapy within 12 weeks of surgical resection, and of these, 17 of 25 patients (68%) completed chemotherapy as indicated. Within the RC cohort all 33 patients had an indication for adjuvant chemotherapy, of these 18 of 33 patients (55%) began within 12 weeks of surgical resection, and 10 of 18 (56%) completed chemotherapy as indicated.

Among the CC cohort who began but did not complete adjuvant chemotherapy, there was no significant association between completion of chemotherapy and preoperative weight loss. Of patients with ≥ 3% preoperative weight loss, 3 (43%) did not complete chemotherapy vs 3 patients (27%) without preoperative weight loss who did not complete chemotherapy as indicated (Fisher exact; P = .63). Finally, low preoperative albumin did not significantly correlate with lack of completion of adjuvant chemotherapy (Fisher exact; P = .99).

Discussion

This study highlights several important findings. There were no patients in our cohort that met ASPEN malnourishment criteria with a BMI < 18.5. Twenty percent of patients lost at least 10 lb in 6 months before the operation. Notably, patients had significant associations with adverse outcomes with less pronounced weight loss than previously noted. As has been established previously, malnourishment can be difficult to screen for, and BMI also is often an imprecise tool.¹² In the CC cohort, weight loss ≥ 3% from 6 months before surgery was significantly associated with delayed recovery, complications, and hospital readmissions. We did not identify a statistically significant effect on chemotherapy completion. However, the numerical difference was suggestive of a difference, and a type 2 error is possible due to our limited sample size.

Our findings imply that the effects of even mild malnutrition are even more profound than previously thought. Significantly, this applies to overweight and obese patients as well, as these constituted a significant fraction of our cohort. A finding of ≥ 3% weight loss at the time of CC diagnosis may provide an opportunity for a focused nutrition intervention up to the time of surgery. Second, although nutrition consultation was frequent in the inpatient setting during the hospital admission (96%-100%), rates of nutrition evaluation were as low as 15% before surgery and 12% after surgery, representing a key area for improvement and focused intervention. An optimal time for intervention and nutrition prehabilitation would be at time of diagnosis before surgery with plans for continued aggressive monitoring and subsequent follow-up. Our finding seems to provide a more sensitive tool to identify patients at risk for delayed recovery compared with the ASPEN-driven assessment. Given the simplicity and the clinical significance, our test consisting of 3% weight loss over 6 months, with its sensitivity of 57%, may be superior to the ASPEN 10-lb weight loss, with its sensitivity of 40% in our cohort.

Previous Studies

Our findings are consistent with previous studies that have demonstrated that perioperative weight loss and malnutrition are correlated with delayed recovery and complications, such as wound healing, in patients with GI cancer.^2,4,5,8 In a retrospective study of more than 7000 patients with CC, those who were overweight or obese were found to have an improved overall survival compared with other BMI categories, and those who were underweight had an increased 30-day mortality and postoperative complications.¹⁶

In another retrospective study of 3799 patients with CC, those who were overweight and obese had an improved 5-year survival rate compared with patients whose weight was normal or underweight. Outcomes were found to be stage dependent.¹⁷ In this study cohort, all patients were either overweight or obese and remained in that category even with weight loss. This may have contributed to overall improved outcomes.

Implications and Next Steps

Our study has several implications. One is that BMI criteria < 18.5 may not be a good measure for malnutrition given that about 75% of the patients in our cohort were overweight or obese and none were underweight. We also show a concrete, easily identifiable finding of percent weight change that could be addressed as an automated electronic notification and potentially identify a patient at risk and serve as a trigger for both timely and early nutrition intervention. It seems to be more sensitive than the ASPEN criterion of 10-lb weight loss in 6 months before surgery. Sensitivity is especially appealing given the ease and potential of embedding this tool in an electronic health record and the clinical importance of the consequent intervention. Preoperative as opposed to perioperative nutrition optimization at time of CC diagnosis is essential, as it may help improve postsurgical outcomes as well as oncologic outcomes, including completion of adjuvant chemotherapy. Finally, although our study found that rates of inpatient postoperative nutrition consultation were high, rates of outpatient nutrition consultation in the preoperative period were low. This represents a missed opportunity for intervention before surgery. Similarly, rates of postoperative nutrition follow-up period were low, which points to an area for improvement in longitudinal and holistic care.

We suggest modifications to nutrition intervention protocols, such as ERAS, which should start at the time of GI malignancy diagnosis.¹⁸ Other suggestions include standard involvement of nutritionists in inpatient and outpatient settings with longitudinal follow-up in the preoperative and postoperative periods and patient enrollment in a nutrition program with monitoring at time of diagnosis at the VHA. Our findings as well as previous literature suggest that the preoperative period is the most important time to intervene with regard to nutrition optimization and represents an opportunity for intensive prehabilitation. Future areas of research include incorporating other important measures of malnourishment independent of BMI into future study designs, such as sarcopenia and adipose tissue density, to better assess body composition and predict prognostic risk in CC.^18,19

Strengths and Limitations

This study is limited by its single-center, retrospective design and small sample sizes, and we acknowledge the limitations of our data set. However, the strength of this VHA-based study is that the single-payer system allows for complete capture of perioperative data as well as the opportunity for focused preoperative interventions to improve outcomes. To our knowledge, there is no currently existing literature on improving nutrition protocols at the VHA for patients with a GI malignancy. These retrospective data will help inform current gaps in quality improvement and supportive oncology as it relates to optimizing malnourishment in veterans undergoing surgical resection for their cancer.

Conclusions

In the CC cohort, weight loss of ≥ 3% from 6 months prior to time of surgery was significantly associated with delayed recovery, complications, and hospital readmissions. Our findings suggest that patients with CC undergoing surgery may benefit from an intensive, early nutrition prehabilitation. Preoperative nutrition optimization may help improve postsurgical outcomes as well as oncologic outcomes, including completion of adjuvant chemotherapy. Further research would be able to clarify these hypotheses.

The VA MISSION Act of 2018 expanded options for veterans to receive government-paid health care from private sector community health care practitioners. The act tasked the US Department of Veterans Affairs (VA) to develop rules that determine eligibility for outside care based on appointment wait times or distance to the nearest VA facility. As a part of those standards, VA opted not to include the availability of VA telehealth in its wait time calculations—a decision that we believe was a gross misjudgment with far-reaching consequences for veterans. Excluding telehealth from the guidelines has unnecessarily restricted veterans’ access to high-quality health care and has squandered large sums of taxpayer dollars.

The VA has reviewed its initial MISSION Act eligibility standards and proposed a correction that recognizes telehealth as a valid means of providing health care to veterans who prefer that option.¹ Telehealth may not have been an essential component of health care before the COVID-19 pandemic, but now it is clear that the best action VA can take is to swiftly enact its recommended change, stipulating that both VA telehealth and in-person health care constitute access to treatment. If implemented, this correction would save taxpayers an astronomical sum—according to a VA reportto Congress, about $1.1 billion in fiscal year 2021 alone.² The cost savings from this proposed correction is reason enough to implement it. But just as importantly, increased use of VA telehealth also means higher quality, quicker, and more convenient care for veterans.

The VA is the recognized world leader in providing telehealth that is effective, timely, and veteran centric. Veterans across the country have access to telehealth services in more than 30 specialties.³ To ensure accessibility, the VA has established partnerships with major mobile broadband carriers so that veterans can receive telehealth at home without additional charges.⁴ The VA project Accessing Telehealth through Local Area Stations (ATLAS) brings VA telehealth to areas where existing internet infrastructure may not be adequate to support video telehealth. ATLAS is a collaboration with private organizations, including Veterans of Foreign Wars, The American Legion, and Walmart.⁴The agency also provides tablets to veterans who might not have access to telehealth, fostering higher access and patient satisfaction.⁴

The VA can initiate telehealth care rapidly. The “Anywhere to Anywhere” VA Health Care initiative and telecare hubs eliminate geographic constraints, allowing clinicians to provide team-based services across county and state lines to veterans’ homes and communities.

VA’s telehealth effort maximizes convenience for veterans. It reduces travel time, travel expenses, depletion of sick leave, and the need for childcare. Veterans with posttraumatic stress disorder or military sexual trauma who are triggered by traffic and waiting rooms, those with mobility issues, or those facing the stigma of mental health treatment often prefer to receive care in the familiarity of their home. Nonetheless, any veteran who desires an in-person appointment would continue to have that option under the proposed VA rule change.

VA telehealth is often used for mental health care, using the same evidence-based psychotherapies that VA has championed and are superior to that available in the private sector.^5,6 This advantage is largely due to VA’s rigorous training, consultation, case review, care delivery, measurement standards, and integrated care model. In a recent survey of veterans engaged in mental health care, 80% reported that VA virtual care via video and/or telephone is as helpful or more helpful than in‐person services.⁷And yet, because of existing regulations, VA telemental health (TMH) does not qualify as access, resulting in hundreds of thousands of TMH visits being outsourced yearly to community practitioners that could be quickly and beneficially furnished by VA clinicians.

Telehealth has been shown to be as clinically effective as in-person care. A recent review of 38 meta-analyses covering telehealth with 10 medical disciplines found that for all disciplines, telehealth was as effective, if not more so, than conventional care.⁸ And because the likelihood of not showing up for telehealth appointments is lower than for in-person appointments, continuity of care is uninterrupted, and health care outcomes are improved.

Telehealth is health care. The VA must end the double standard that has handicapped it from including telehealth availability in determinations of eligibility for community care. The VA has voiced its intention to seek stakeholder input before implementing its proposed correction. The change is long overdue. It will save the VA a billion dollars annually while ensuring that veterans have quicker access to better treatment.

The VA MISSION Act of 2018 expanded options for veterans to receive government-paid health care from private sector community health care practitioners. The act tasked the US Department of Veterans Affairs (VA) to develop rules that determine eligibility for outside care based on appointment wait times or distance to the nearest VA facility. As a part of those standards, VA opted not to include the availability of VA telehealth in its wait time calculations—a decision that we believe was a gross misjudgment with far-reaching consequences for veterans. Excluding telehealth from the guidelines has unnecessarily restricted veterans’ access to high-quality health care and has squandered large sums of taxpayer dollars.

The VA has reviewed its initial MISSION Act eligibility standards and proposed a correction that recognizes telehealth as a valid means of providing health care to veterans who prefer that option.¹ Telehealth may not have been an essential component of health care before the COVID-19 pandemic, but now it is clear that the best action VA can take is to swiftly enact its recommended change, stipulating that both VA telehealth and in-person health care constitute access to treatment. If implemented, this correction would save taxpayers an astronomical sum—according to a VA reportto Congress, about $1.1 billion in fiscal year 2021 alone.² The cost savings from this proposed correction is reason enough to implement it. But just as importantly, increased use of VA telehealth also means higher quality, quicker, and more convenient care for veterans.

The VA is the recognized world leader in providing telehealth that is effective, timely, and veteran centric. Veterans across the country have access to telehealth services in more than 30 specialties.³ To ensure accessibility, the VA has established partnerships with major mobile broadband carriers so that veterans can receive telehealth at home without additional charges.⁴ The VA project Accessing Telehealth through Local Area Stations (ATLAS) brings VA telehealth to areas where existing internet infrastructure may not be adequate to support video telehealth. ATLAS is a collaboration with private organizations, including Veterans of Foreign Wars, The American Legion, and Walmart.⁴The agency also provides tablets to veterans who might not have access to telehealth, fostering higher access and patient satisfaction.⁴

The VA can initiate telehealth care rapidly. The “Anywhere to Anywhere” VA Health Care initiative and telecare hubs eliminate geographic constraints, allowing clinicians to provide team-based services across county and state lines to veterans’ homes and communities.

VA’s telehealth effort maximizes convenience for veterans. It reduces travel time, travel expenses, depletion of sick leave, and the need for childcare. Veterans with posttraumatic stress disorder or military sexual trauma who are triggered by traffic and waiting rooms, those with mobility issues, or those facing the stigma of mental health treatment often prefer to receive care in the familiarity of their home. Nonetheless, any veteran who desires an in-person appointment would continue to have that option under the proposed VA rule change.

VA telehealth is often used for mental health care, using the same evidence-based psychotherapies that VA has championed and are superior to that available in the private sector.^5,6 This advantage is largely due to VA’s rigorous training, consultation, case review, care delivery, measurement standards, and integrated care model. In a recent survey of veterans engaged in mental health care, 80% reported that VA virtual care via video and/or telephone is as helpful or more helpful than in‐person services.⁷And yet, because of existing regulations, VA telemental health (TMH) does not qualify as access, resulting in hundreds of thousands of TMH visits being outsourced yearly to community practitioners that could be quickly and beneficially furnished by VA clinicians.

Telehealth has been shown to be as clinically effective as in-person care. A recent review of 38 meta-analyses covering telehealth with 10 medical disciplines found that for all disciplines, telehealth was as effective, if not more so, than conventional care.⁸ And because the likelihood of not showing up for telehealth appointments is lower than for in-person appointments, continuity of care is uninterrupted, and health care outcomes are improved.

Telehealth is health care. The VA must end the double standard that has handicapped it from including telehealth availability in determinations of eligibility for community care. The VA has voiced its intention to seek stakeholder input before implementing its proposed correction. The change is long overdue. It will save the VA a billion dollars annually while ensuring that veterans have quicker access to better treatment.

The VA MISSION Act of 2018 expanded options for veterans to receive government-paid health care from private sector community health care practitioners. The act tasked the US Department of Veterans Affairs (VA) to develop rules that determine eligibility for outside care based on appointment wait times or distance to the nearest VA facility. As a part of those standards, VA opted not to include the availability of VA telehealth in its wait time calculations—a decision that we believe was a gross misjudgment with far-reaching consequences for veterans. Excluding telehealth from the guidelines has unnecessarily restricted veterans’ access to high-quality health care and has squandered large sums of taxpayer dollars.

The VA has reviewed its initial MISSION Act eligibility standards and proposed a correction that recognizes telehealth as a valid means of providing health care to veterans who prefer that option.¹ Telehealth may not have been an essential component of health care before the COVID-19 pandemic, but now it is clear that the best action VA can take is to swiftly enact its recommended change, stipulating that both VA telehealth and in-person health care constitute access to treatment. If implemented, this correction would save taxpayers an astronomical sum—according to a VA reportto Congress, about $1.1 billion in fiscal year 2021 alone.² The cost savings from this proposed correction is reason enough to implement it. But just as importantly, increased use of VA telehealth also means higher quality, quicker, and more convenient care for veterans.

The VA is the recognized world leader in providing telehealth that is effective, timely, and veteran centric. Veterans across the country have access to telehealth services in more than 30 specialties.³ To ensure accessibility, the VA has established partnerships with major mobile broadband carriers so that veterans can receive telehealth at home without additional charges.⁴ The VA project Accessing Telehealth through Local Area Stations (ATLAS) brings VA telehealth to areas where existing internet infrastructure may not be adequate to support video telehealth. ATLAS is a collaboration with private organizations, including Veterans of Foreign Wars, The American Legion, and Walmart.⁴The agency also provides tablets to veterans who might not have access to telehealth, fostering higher access and patient satisfaction.⁴

The VA can initiate telehealth care rapidly. The “Anywhere to Anywhere” VA Health Care initiative and telecare hubs eliminate geographic constraints, allowing clinicians to provide team-based services across county and state lines to veterans’ homes and communities.

VA’s telehealth effort maximizes convenience for veterans. It reduces travel time, travel expenses, depletion of sick leave, and the need for childcare. Veterans with posttraumatic stress disorder or military sexual trauma who are triggered by traffic and waiting rooms, those with mobility issues, or those facing the stigma of mental health treatment often prefer to receive care in the familiarity of their home. Nonetheless, any veteran who desires an in-person appointment would continue to have that option under the proposed VA rule change.

VA telehealth is often used for mental health care, using the same evidence-based psychotherapies that VA has championed and are superior to that available in the private sector.^5,6 This advantage is largely due to VA’s rigorous training, consultation, case review, care delivery, measurement standards, and integrated care model. In a recent survey of veterans engaged in mental health care, 80% reported that VA virtual care via video and/or telephone is as helpful or more helpful than in‐person services.⁷And yet, because of existing regulations, VA telemental health (TMH) does not qualify as access, resulting in hundreds of thousands of TMH visits being outsourced yearly to community practitioners that could be quickly and beneficially furnished by VA clinicians.

Telehealth has been shown to be as clinically effective as in-person care. A recent review of 38 meta-analyses covering telehealth with 10 medical disciplines found that for all disciplines, telehealth was as effective, if not more so, than conventional care.⁸ And because the likelihood of not showing up for telehealth appointments is lower than for in-person appointments, continuity of care is uninterrupted, and health care outcomes are improved.

Telehealth is health care. The VA must end the double standard that has handicapped it from including telehealth availability in determinations of eligibility for community care. The VA has voiced its intention to seek stakeholder input before implementing its proposed correction. The change is long overdue. It will save the VA a billion dollars annually while ensuring that veterans have quicker access to better treatment.

A primary care physician at the Veterans Affairs Medical Center in Decatur, Georgia, has been indicted on several counts of sexual assault of veteran patients. Rajesh Motibhai Patel is accused of violating his patients’ constitutional right to bodily integrity while acting under color of law and of engaging in unwanted sexual contact.

According to US Attorney Ryan Buchanan, Patel allegedly “violated his oath to do no harm to patients under his care.” He allegedly sexually touched 4 female patients during routine examinations.

Patel’s alleged crimes were “horrific and unacceptable,” US Department of Veterans Affairs (VA) press secretary Terrence Hayes said in a statement. “As soon as VA learned of these allegations, we removed this clinician from patient care and reassigned him to a role that had no patient interaction. Whenever a patient comes to VA, they deserve to know that they will be treated with care, compassion, and respect.”

The case is being investigated by the VA Office of Inspector General. Although Patel is only charged at present, not convicted, investigators believe he may have victimized other patients as well. Anyone with information is asked to call the VA-OIG tipline at (770) 758-6646.

A primary care physician at the Veterans Affairs Medical Center in Decatur, Georgia, has been indicted on several counts of sexual assault of veteran patients. Rajesh Motibhai Patel is accused of violating his patients’ constitutional right to bodily integrity while acting under color of law and of engaging in unwanted sexual contact.

According to US Attorney Ryan Buchanan, Patel allegedly “violated his oath to do no harm to patients under his care.” He allegedly sexually touched 4 female patients during routine examinations.

Patel’s alleged crimes were “horrific and unacceptable,” US Department of Veterans Affairs (VA) press secretary Terrence Hayes said in a statement. “As soon as VA learned of these allegations, we removed this clinician from patient care and reassigned him to a role that had no patient interaction. Whenever a patient comes to VA, they deserve to know that they will be treated with care, compassion, and respect.”

The case is being investigated by the VA Office of Inspector General. Although Patel is only charged at present, not convicted, investigators believe he may have victimized other patients as well. Anyone with information is asked to call the VA-OIG tipline at (770) 758-6646.

A primary care physician at the Veterans Affairs Medical Center in Decatur, Georgia, has been indicted on several counts of sexual assault of veteran patients. Rajesh Motibhai Patel is accused of violating his patients’ constitutional right to bodily integrity while acting under color of law and of engaging in unwanted sexual contact.

According to US Attorney Ryan Buchanan, Patel allegedly “violated his oath to do no harm to patients under his care.” He allegedly sexually touched 4 female patients during routine examinations.

Patel’s alleged crimes were “horrific and unacceptable,” US Department of Veterans Affairs (VA) press secretary Terrence Hayes said in a statement. “As soon as VA learned of these allegations, we removed this clinician from patient care and reassigned him to a role that had no patient interaction. Whenever a patient comes to VA, they deserve to know that they will be treated with care, compassion, and respect.”

The case is being investigated by the VA Office of Inspector General. Although Patel is only charged at present, not convicted, investigators believe he may have victimized other patients as well. Anyone with information is asked to call the VA-OIG tipline at (770) 758-6646.