Jim Kling

A new international consensus paper is recommending that eosinophilic GI diseases (EGIDs) should be named according to more specific criteria. The paper seeks to update nomenclature to improve research and bolster clinical clarity.

The involved part of the GI tract should be specifically named, and the abbreviation “Eo” should be used. Furthermore, the umbrella term should be EGID instead of the currently used “eosinophilic gastroenteritis,” according to the statement published in Clinical Gastroenterology and Hepatology. The statement included 91 authors from five continents who filled out two rounds of surveys. In total, 93% completed the first and 90% completed the second. The paper produced 22 statements, with a consensus reached on all but 2.

EGIDs are chronic, immune-driven disorders that produce gastrointestinal symptoms and are characterized by eosinophil-dominant inflammation in specific GI regions. Although eosinophilic esophagitis (EoE) is the most well known of these conditions, other EGIDs have become more commonly recognized in recent years and are the subject of intense study. Other affected areas include the stomach, small bowel, and colon, where it can occur individually or in combination.

Efforts are underway to develop guidelines for diagnosis and treatment of EGIDs, but there was initial confusion surrounding the term eosinophilic gastroenteritis since its definition varied significantly in different clinical and research settings, according to the authors. That term varyingly referred to stomach alone, small bowel alone, stomach and small bowel, or any region of the GI tract.

“This nonstandardized use of nomenclature highlighted a need for a common language for non-EoE eosinophilic GI disease names, not only for clinical practice, but also for the consistent data collection required for research to continue to advance the field,” co–first authors Evan S. Dellon, MD, MPH, AGAF, from the University of North Carolina at Chapel Hill, and Nirmala Gonsalves, MD, from Northwestern University, Chicago, and colleagues wrote. “This step, while seemingly rudimentary, was essential to inform the guideline efforts that are now underway.”

After responses to the surveys were analyzed, respondents participated in one of two scheduled meetings held on a video conferencing platform in May 2021. Feedback from these meetings was then used to create a second round of 29 statements which were again distributed, and participants were asked to either agree or disagree with each statement. Agreement was set a priori at 70%. In all, 38% of the participants were women, and 91% worked in academic or university settings.

In routine clinical practice, conditions with eosinophil-dominant inflammation in the absence of secondary causes outside of the esophagus can collectively be referred to clinically as non-EoE EGID. Stomach involvement should be called eosinophilic gastritis (EoG), small bowel involvement eosinophilic enteritis (EoN), and colon involvement eosinophilic colitis (EoC).

For research use, and clinical use if desired, the authors called for greater granularity in description of the conditions, with each location named. For example, if the stomach and small bowel are both involved, the condition should be termed eosinophilic gastritis and enteritis. The authors could not reach a consensus for terminology when the esophagus is also involved, leading to the recommendation that it can be included using the phrase “with esophageal involvement” or by using EoE, although they note that this could be confusing since EoE is the current term for eosinophilia isolated in the esophagus.

The authors came to universal agreement in many areas, but there were exceptions that mostly centered on how to name conditions that affect multiple areas of the GI tract. It remains uncertain whether eosinophilia in different regions is caused by the same pathogenesis. Some experts felt that a “primary” location of EGID should be identified using predominant symptoms, endoscopic features, and complications. However, the authors anticipate that this nomenclature will change over time.

The authors noted that the clinical manifestation of the disease should remain the driving factor behind classification. Testing should be driven by clinically relevant questions, and overtesting should be avoided. More details on this are likely to be forthcoming in future guidelines.

The consensus statement is limited by the fact that most participants were from academic settings. These recommendations do not apply to eosinophilic disorders of the gallbladder, liver, or pancreas. Application of the recommendations to the small bowel may be too general or specific, but are meant primarily as a starting point for further refinement.

These limitations should help to drive further research. For example, molecular and pathogenic data could help distinguish EoE from “esophageal involvement” by determining if pathogenic mechanisms are the same or different, which would in turn lead to lumping the conditions into a single term or keeping them separate.

“The iterative and collaborative process led to agreement on nearly all aspects of the proposed nomenclature framework, and has identified future research directions. It is expected that as more data are collected, the nomenclature will again be updated to reflect best practices and the underlying pathogenesis of these disorders,” the authors concluded.

The authors disclosed relationships with various industry companies, including AstraZeneca, Celgene, GlaxoSmithKline, Regeneron, Sanofi, and Takeda.

A new international consensus paper is recommending that eosinophilic GI diseases (EGIDs) should be named according to more specific criteria. The paper seeks to update nomenclature to improve research and bolster clinical clarity.

The involved part of the GI tract should be specifically named, and the abbreviation “Eo” should be used. Furthermore, the umbrella term should be EGID instead of the currently used “eosinophilic gastroenteritis,” according to the statement published in Clinical Gastroenterology and Hepatology. The statement included 91 authors from five continents who filled out two rounds of surveys. In total, 93% completed the first and 90% completed the second. The paper produced 22 statements, with a consensus reached on all but 2.

EGIDs are chronic, immune-driven disorders that produce gastrointestinal symptoms and are characterized by eosinophil-dominant inflammation in specific GI regions. Although eosinophilic esophagitis (EoE) is the most well known of these conditions, other EGIDs have become more commonly recognized in recent years and are the subject of intense study. Other affected areas include the stomach, small bowel, and colon, where it can occur individually or in combination.

Efforts are underway to develop guidelines for diagnosis and treatment of EGIDs, but there was initial confusion surrounding the term eosinophilic gastroenteritis since its definition varied significantly in different clinical and research settings, according to the authors. That term varyingly referred to stomach alone, small bowel alone, stomach and small bowel, or any region of the GI tract.

“This nonstandardized use of nomenclature highlighted a need for a common language for non-EoE eosinophilic GI disease names, not only for clinical practice, but also for the consistent data collection required for research to continue to advance the field,” co–first authors Evan S. Dellon, MD, MPH, AGAF, from the University of North Carolina at Chapel Hill, and Nirmala Gonsalves, MD, from Northwestern University, Chicago, and colleagues wrote. “This step, while seemingly rudimentary, was essential to inform the guideline efforts that are now underway.”

After responses to the surveys were analyzed, respondents participated in one of two scheduled meetings held on a video conferencing platform in May 2021. Feedback from these meetings was then used to create a second round of 29 statements which were again distributed, and participants were asked to either agree or disagree with each statement. Agreement was set a priori at 70%. In all, 38% of the participants were women, and 91% worked in academic or university settings.

In routine clinical practice, conditions with eosinophil-dominant inflammation in the absence of secondary causes outside of the esophagus can collectively be referred to clinically as non-EoE EGID. Stomach involvement should be called eosinophilic gastritis (EoG), small bowel involvement eosinophilic enteritis (EoN), and colon involvement eosinophilic colitis (EoC).

For research use, and clinical use if desired, the authors called for greater granularity in description of the conditions, with each location named. For example, if the stomach and small bowel are both involved, the condition should be termed eosinophilic gastritis and enteritis. The authors could not reach a consensus for terminology when the esophagus is also involved, leading to the recommendation that it can be included using the phrase “with esophageal involvement” or by using EoE, although they note that this could be confusing since EoE is the current term for eosinophilia isolated in the esophagus.

The authors came to universal agreement in many areas, but there were exceptions that mostly centered on how to name conditions that affect multiple areas of the GI tract. It remains uncertain whether eosinophilia in different regions is caused by the same pathogenesis. Some experts felt that a “primary” location of EGID should be identified using predominant symptoms, endoscopic features, and complications. However, the authors anticipate that this nomenclature will change over time.

The authors noted that the clinical manifestation of the disease should remain the driving factor behind classification. Testing should be driven by clinically relevant questions, and overtesting should be avoided. More details on this are likely to be forthcoming in future guidelines.

The consensus statement is limited by the fact that most participants were from academic settings. These recommendations do not apply to eosinophilic disorders of the gallbladder, liver, or pancreas. Application of the recommendations to the small bowel may be too general or specific, but are meant primarily as a starting point for further refinement.

These limitations should help to drive further research. For example, molecular and pathogenic data could help distinguish EoE from “esophageal involvement” by determining if pathogenic mechanisms are the same or different, which would in turn lead to lumping the conditions into a single term or keeping them separate.

“The iterative and collaborative process led to agreement on nearly all aspects of the proposed nomenclature framework, and has identified future research directions. It is expected that as more data are collected, the nomenclature will again be updated to reflect best practices and the underlying pathogenesis of these disorders,” the authors concluded.

The authors disclosed relationships with various industry companies, including AstraZeneca, Celgene, GlaxoSmithKline, Regeneron, Sanofi, and Takeda.

A new international consensus paper is recommending that eosinophilic GI diseases (EGIDs) should be named according to more specific criteria. The paper seeks to update nomenclature to improve research and bolster clinical clarity.

The involved part of the GI tract should be specifically named, and the abbreviation “Eo” should be used. Furthermore, the umbrella term should be EGID instead of the currently used “eosinophilic gastroenteritis,” according to the statement published in Clinical Gastroenterology and Hepatology. The statement included 91 authors from five continents who filled out two rounds of surveys. In total, 93% completed the first and 90% completed the second. The paper produced 22 statements, with a consensus reached on all but 2.

EGIDs are chronic, immune-driven disorders that produce gastrointestinal symptoms and are characterized by eosinophil-dominant inflammation in specific GI regions. Although eosinophilic esophagitis (EoE) is the most well known of these conditions, other EGIDs have become more commonly recognized in recent years and are the subject of intense study. Other affected areas include the stomach, small bowel, and colon, where it can occur individually or in combination.

Efforts are underway to develop guidelines for diagnosis and treatment of EGIDs, but there was initial confusion surrounding the term eosinophilic gastroenteritis since its definition varied significantly in different clinical and research settings, according to the authors. That term varyingly referred to stomach alone, small bowel alone, stomach and small bowel, or any region of the GI tract.

“This nonstandardized use of nomenclature highlighted a need for a common language for non-EoE eosinophilic GI disease names, not only for clinical practice, but also for the consistent data collection required for research to continue to advance the field,” co–first authors Evan S. Dellon, MD, MPH, AGAF, from the University of North Carolina at Chapel Hill, and Nirmala Gonsalves, MD, from Northwestern University, Chicago, and colleagues wrote. “This step, while seemingly rudimentary, was essential to inform the guideline efforts that are now underway.”

After responses to the surveys were analyzed, respondents participated in one of two scheduled meetings held on a video conferencing platform in May 2021. Feedback from these meetings was then used to create a second round of 29 statements which were again distributed, and participants were asked to either agree or disagree with each statement. Agreement was set a priori at 70%. In all, 38% of the participants were women, and 91% worked in academic or university settings.

In routine clinical practice, conditions with eosinophil-dominant inflammation in the absence of secondary causes outside of the esophagus can collectively be referred to clinically as non-EoE EGID. Stomach involvement should be called eosinophilic gastritis (EoG), small bowel involvement eosinophilic enteritis (EoN), and colon involvement eosinophilic colitis (EoC).

For research use, and clinical use if desired, the authors called for greater granularity in description of the conditions, with each location named. For example, if the stomach and small bowel are both involved, the condition should be termed eosinophilic gastritis and enteritis. The authors could not reach a consensus for terminology when the esophagus is also involved, leading to the recommendation that it can be included using the phrase “with esophageal involvement” or by using EoE, although they note that this could be confusing since EoE is the current term for eosinophilia isolated in the esophagus.

The authors came to universal agreement in many areas, but there were exceptions that mostly centered on how to name conditions that affect multiple areas of the GI tract. It remains uncertain whether eosinophilia in different regions is caused by the same pathogenesis. Some experts felt that a “primary” location of EGID should be identified using predominant symptoms, endoscopic features, and complications. However, the authors anticipate that this nomenclature will change over time.

The authors noted that the clinical manifestation of the disease should remain the driving factor behind classification. Testing should be driven by clinically relevant questions, and overtesting should be avoided. More details on this are likely to be forthcoming in future guidelines.

The consensus statement is limited by the fact that most participants were from academic settings. These recommendations do not apply to eosinophilic disorders of the gallbladder, liver, or pancreas. Application of the recommendations to the small bowel may be too general or specific, but are meant primarily as a starting point for further refinement.

These limitations should help to drive further research. For example, molecular and pathogenic data could help distinguish EoE from “esophageal involvement” by determining if pathogenic mechanisms are the same or different, which would in turn lead to lumping the conditions into a single term or keeping them separate.

“The iterative and collaborative process led to agreement on nearly all aspects of the proposed nomenclature framework, and has identified future research directions. It is expected that as more data are collected, the nomenclature will again be updated to reflect best practices and the underlying pathogenesis of these disorders,” the authors concluded.

The authors disclosed relationships with various industry companies, including AstraZeneca, Celgene, GlaxoSmithKline, Regeneron, Sanofi, and Takeda.

A new international consensus paper is recommending that eosinophilic GI diseases (EGIDs) should be named according to more specific criteria. The paper seeks to update nomenclature to improve research and bolster clinical clarity.

The involved part of the GI tract should be specifically named, and the abbreviation “Eo” should be used. Furthermore, the umbrella term should be EGID instead of the currently used “eosinophilic gastroenteritis,” according to the statement published in Clinical Gastroenterology and Hepatology. The statement included 91 authors from five continents who filled out two rounds of surveys. In total, 93% completed the first and 90% completed the second. The paper produced 22 statements, with a consensus reached on all but 2.

EGIDs are chronic, immune-driven disorders that produce gastrointestinal symptoms and are characterized by eosinophil-dominant inflammation in specific GI regions. Although eosinophilic esophagitis (EoE) is the most well known of these conditions, other EGIDs have become more commonly recognized in recent years and are the subject of intense study. Other affected areas include the stomach, small bowel, and colon, where it can occur individually or in combination.

Efforts are underway to develop guidelines for diagnosis and treatment of EGIDs, but there was initial confusion surrounding the term eosinophilic gastroenteritis since its definition varied significantly in different clinical and research settings, according to the authors. That term varyingly referred to stomach alone, small bowel alone, stomach and small bowel, or any region of the GI tract.

“This nonstandardized use of nomenclature highlighted a need for a common language for non-EoE eosinophilic GI disease names, not only for clinical practice, but also for the consistent data collection required for research to continue to advance the field,” co–first authors Evan S. Dellon, MD, MPH, AGAF, from the University of North Carolina at Chapel Hill, and Nirmala Gonsalves, MD, from Northwestern University, Chicago, and colleagues wrote. “This step, while seemingly rudimentary, was essential to inform the guideline efforts that are now underway.”

After responses to the surveys were analyzed, respondents participated in one of two scheduled meetings held on a video conferencing platform in May 2021. Feedback from these meetings was then used to create a second round of 29 statements which were again distributed, and participants were asked to either agree or disagree with each statement. Agreement was set a priori at 70%. In all, 38% of the participants were women, and 91% worked in academic or university settings.

In routine clinical practice, conditions with eosinophil-dominant inflammation in the absence of secondary causes outside of the esophagus can collectively be referred to clinically as non-EoE EGID. Stomach involvement should be called eosinophilic gastritis (EoG), small bowel involvement eosinophilic enteritis (EoN), and colon involvement eosinophilic colitis (EoC).

For research use, and clinical use if desired, the authors called for greater granularity in description of the conditions, with each location named. For example, if the stomach and small bowel are both involved, the condition should be termed eosinophilic gastritis and enteritis. The authors could not reach a consensus for terminology when the esophagus is also involved, leading to the recommendation that it can be included using the phrase “with esophageal involvement” or by using EoE, although they note that this could be confusing since EoE is the current term for eosinophilia isolated in the esophagus.

The authors came to universal agreement in many areas, but there were exceptions that mostly centered on how to name conditions that affect multiple areas of the GI tract. It remains uncertain whether eosinophilia in different regions is caused by the same pathogenesis. Some experts felt that a “primary” location of EGID should be identified using predominant symptoms, endoscopic features, and complications. However, the authors anticipate that this nomenclature will change over time.

The authors noted that the clinical manifestation of the disease should remain the driving factor behind classification. Testing should be driven by clinically relevant questions and overtesting should be avoided. More details on this are likely to be forthcoming in future guidelines.

The consensus statement is limited by the fact that most participants were from academic settings. These recommendations do not apply to eosinophilic disorders of gallbladder, liver, or pancreas. Application of the recommendations to the small bowel may be too general or specific, but are meant primarily as a starting point for further refinement.

These limitations should help to drive further research. For example, molecular and pathogenic data could help distinguish EoE from “esophageal involvement” by determining if pathogenic mechanisms are the same or different, which would in turn lead to lumping the conditions into a single term or keeping them separate.

“The iterative and collaborative process led to agreement on nearly all aspects of the proposed nomenclature framework, and has identified future research directions. It is expected that as more data are collected, the nomenclature will again be updated to reflect best practices and the underlying pathogenesis of these disorders,” the authors concluded.

The authors disclosed relationships with various industry companies, include AstraZeneca, Celgene, GlaxoSmithKline, Regeneron, Sanofi, and Takeda.

A new international consensus paper is recommending that eosinophilic GI diseases (EGIDs) should be named according to more specific criteria. The paper seeks to update nomenclature to improve research and bolster clinical clarity.

The involved part of the GI tract should be specifically named, and the abbreviation “Eo” should be used. Furthermore, the umbrella term should be EGID instead of the currently used “eosinophilic gastroenteritis,” according to the statement published in Clinical Gastroenterology and Hepatology. The statement included 91 authors from five continents who filled out two rounds of surveys. In total, 93% completed the first and 90% completed the second. The paper produced 22 statements, with a consensus reached on all but 2.

EGIDs are chronic, immune-driven disorders that produce gastrointestinal symptoms and are characterized by eosinophil-dominant inflammation in specific GI regions. Although eosinophilic esophagitis (EoE) is the most well known of these conditions, other EGIDs have become more commonly recognized in recent years and are the subject of intense study. Other affected areas include the stomach, small bowel, and colon, where it can occur individually or in combination.

Efforts are underway to develop guidelines for diagnosis and treatment of EGIDs, but there was initial confusion surrounding the term eosinophilic gastroenteritis since its definition varied significantly in different clinical and research settings, according to the authors. That term varyingly referred to stomach alone, small bowel alone, stomach and small bowel, or any region of the GI tract.

“This nonstandardized use of nomenclature highlighted a need for a common language for non-EoE eosinophilic GI disease names, not only for clinical practice, but also for the consistent data collection required for research to continue to advance the field,” co–first authors Evan S. Dellon, MD, MPH, AGAF, from the University of North Carolina at Chapel Hill, and Nirmala Gonsalves, MD, from Northwestern University, Chicago, and colleagues wrote. “This step, while seemingly rudimentary, was essential to inform the guideline efforts that are now underway.”

After responses to the surveys were analyzed, respondents participated in one of two scheduled meetings held on a video conferencing platform in May 2021. Feedback from these meetings was then used to create a second round of 29 statements which were again distributed, and participants were asked to either agree or disagree with each statement. Agreement was set a priori at 70%. In all, 38% of the participants were women, and 91% worked in academic or university settings.

In routine clinical practice, conditions with eosinophil-dominant inflammation in the absence of secondary causes outside of the esophagus can collectively be referred to clinically as non-EoE EGID. Stomach involvement should be called eosinophilic gastritis (EoG), small bowel involvement eosinophilic enteritis (EoN), and colon involvement eosinophilic colitis (EoC).

For research use, and clinical use if desired, the authors called for greater granularity in description of the conditions, with each location named. For example, if the stomach and small bowel are both involved, the condition should be termed eosinophilic gastritis and enteritis. The authors could not reach a consensus for terminology when the esophagus is also involved, leading to the recommendation that it can be included using the phrase “with esophageal involvement” or by using EoE, although they note that this could be confusing since EoE is the current term for eosinophilia isolated in the esophagus.

The authors came to universal agreement in many areas, but there were exceptions that mostly centered on how to name conditions that affect multiple areas of the GI tract. It remains uncertain whether eosinophilia in different regions is caused by the same pathogenesis. Some experts felt that a “primary” location of EGID should be identified using predominant symptoms, endoscopic features, and complications. However, the authors anticipate that this nomenclature will change over time.

The authors noted that the clinical manifestation of the disease should remain the driving factor behind classification. Testing should be driven by clinically relevant questions and overtesting should be avoided. More details on this are likely to be forthcoming in future guidelines.

The consensus statement is limited by the fact that most participants were from academic settings. These recommendations do not apply to eosinophilic disorders of gallbladder, liver, or pancreas. Application of the recommendations to the small bowel may be too general or specific, but are meant primarily as a starting point for further refinement.

These limitations should help to drive further research. For example, molecular and pathogenic data could help distinguish EoE from “esophageal involvement” by determining if pathogenic mechanisms are the same or different, which would in turn lead to lumping the conditions into a single term or keeping them separate.

“The iterative and collaborative process led to agreement on nearly all aspects of the proposed nomenclature framework, and has identified future research directions. It is expected that as more data are collected, the nomenclature will again be updated to reflect best practices and the underlying pathogenesis of these disorders,” the authors concluded.

The authors disclosed relationships with various industry companies, include AstraZeneca, Celgene, GlaxoSmithKline, Regeneron, Sanofi, and Takeda.

A new international consensus paper is recommending that eosinophilic GI diseases (EGIDs) should be named according to more specific criteria. The paper seeks to update nomenclature to improve research and bolster clinical clarity.

The involved part of the GI tract should be specifically named, and the abbreviation “Eo” should be used. Furthermore, the umbrella term should be EGID instead of the currently used “eosinophilic gastroenteritis,” according to the statement published in Clinical Gastroenterology and Hepatology. The statement included 91 authors from five continents who filled out two rounds of surveys. In total, 93% completed the first and 90% completed the second. The paper produced 22 statements, with a consensus reached on all but 2.

EGIDs are chronic, immune-driven disorders that produce gastrointestinal symptoms and are characterized by eosinophil-dominant inflammation in specific GI regions. Although eosinophilic esophagitis (EoE) is the most well known of these conditions, other EGIDs have become more commonly recognized in recent years and are the subject of intense study. Other affected areas include the stomach, small bowel, and colon, where it can occur individually or in combination.

Efforts are underway to develop guidelines for diagnosis and treatment of EGIDs, but there was initial confusion surrounding the term eosinophilic gastroenteritis since its definition varied significantly in different clinical and research settings, according to the authors. That term varyingly referred to stomach alone, small bowel alone, stomach and small bowel, or any region of the GI tract.

“This nonstandardized use of nomenclature highlighted a need for a common language for non-EoE eosinophilic GI disease names, not only for clinical practice, but also for the consistent data collection required for research to continue to advance the field,” co–first authors Evan S. Dellon, MD, MPH, AGAF, from the University of North Carolina at Chapel Hill, and Nirmala Gonsalves, MD, from Northwestern University, Chicago, and colleagues wrote. “This step, while seemingly rudimentary, was essential to inform the guideline efforts that are now underway.”

After responses to the surveys were analyzed, respondents participated in one of two scheduled meetings held on a video conferencing platform in May 2021. Feedback from these meetings was then used to create a second round of 29 statements which were again distributed, and participants were asked to either agree or disagree with each statement. Agreement was set a priori at 70%. In all, 38% of the participants were women, and 91% worked in academic or university settings.

In routine clinical practice, conditions with eosinophil-dominant inflammation in the absence of secondary causes outside of the esophagus can collectively be referred to clinically as non-EoE EGID. Stomach involvement should be called eosinophilic gastritis (EoG), small bowel involvement eosinophilic enteritis (EoN), and colon involvement eosinophilic colitis (EoC).

For research use, and clinical use if desired, the authors called for greater granularity in description of the conditions, with each location named. For example, if the stomach and small bowel are both involved, the condition should be termed eosinophilic gastritis and enteritis. The authors could not reach a consensus for terminology when the esophagus is also involved, leading to the recommendation that it can be included using the phrase “with esophageal involvement” or by using EoE, although they note that this could be confusing since EoE is the current term for eosinophilia isolated in the esophagus.

The authors came to universal agreement in many areas, but there were exceptions that mostly centered on how to name conditions that affect multiple areas of the GI tract. It remains uncertain whether eosinophilia in different regions is caused by the same pathogenesis. Some experts felt that a “primary” location of EGID should be identified using predominant symptoms, endoscopic features, and complications. However, the authors anticipate that this nomenclature will change over time.

The authors noted that the clinical manifestation of the disease should remain the driving factor behind classification. Testing should be driven by clinically relevant questions and overtesting should be avoided. More details on this are likely to be forthcoming in future guidelines.

The consensus statement is limited by the fact that most participants were from academic settings. These recommendations do not apply to eosinophilic disorders of gallbladder, liver, or pancreas. Application of the recommendations to the small bowel may be too general or specific, but are meant primarily as a starting point for further refinement.

These limitations should help to drive further research. For example, molecular and pathogenic data could help distinguish EoE from “esophageal involvement” by determining if pathogenic mechanisms are the same or different, which would in turn lead to lumping the conditions into a single term or keeping them separate.

“The iterative and collaborative process led to agreement on nearly all aspects of the proposed nomenclature framework, and has identified future research directions. It is expected that as more data are collected, the nomenclature will again be updated to reflect best practices and the underlying pathogenesis of these disorders,” the authors concluded.

The authors disclosed relationships with various industry companies, include AstraZeneca, Celgene, GlaxoSmithKline, Regeneron, Sanofi, and Takeda.

Among patients with locally advanced head and neck squamous cell carcinoma who are ineligible to receive cisplatin, carboplatin-based chemoradiotherapy (CRT) may be a better option than cetuximab-based chemoradiotherapy, according to a new cohort study of U.S. veterans.

Although cisplatin is the favored treatment choice for these patients, kidney dysfunction, hearing loss, neuropathy, advanced age, and performance status can be contraindications. As radiosensitizing agents, both cetuximab and carboplatin-fluorouracil combined with radiotherapy have increased survival compared to radiotherapy alone in randomized, controlled trials.

Previous studies have demonstrated that cisplatin outperforms cetuximab in CRT regimens with a particular focus on cancers linked to human papillomavirus (HPV), but no prospective trials have compared cetuximab and carboplatin-based radiosensitization, according to the authors of the new report, published online in JAMA Otolaryngology – Head & Neck Surgery.

Some small retrospective studies, generally performed at one or two institutions, found that carboplatin outperformed cetuximab with respect to progression-free and overall survival, but these were subject to natural biases as well as imbalances between the two treatment groups.

To address this literature gap, the authors conducted a nationwide retrospective analysis of 8,290 U.S. veterans, who have a high rate of frailty and comorbidities such as heart disease and tobacco use that could make them ineligible for treatment with cisplatin. Among the veterans, 5,566 were treated with cisplatin, 1,231 with carboplatin, and 1,493 with cetuximab. The overall median age was 63 years, 98.9% were male, 82.6% were White, 15.8% were Black or African American, 68.5% were current smokers, 13.0% were former smokers, and 18.5% had never smoked.

Patients treated with carboplatin and cetuximab were older and had more comorbidities than those treated with cisplatin. Sixty-five percent of patients treated with carboplatin also received paclitaxel. Fifty-eight percent had a primary oropharynx cancer.

Median overall survival was 59.3 months among all patients (interquartile range [IQR, 18.5-140.9 months]. Median OS was 74.4 months in the cisplatin group (IQR, 22.3-162.2), 43.4 months in the carboplatin group (IQR, 15.3-123.8), and 31.1 months in the cetuximab group (IQR, 12.4-87.8). There was a lower inverse probability weighted cause-specific hazard ratio (csHR) of death associated with carboplatin (csHR, 0.85; 95% confidence interval [CI], 0.78-0.93). The researchers compared survival associations in oropharynx and nonoropharynx subgroups and found a significant association in the oropharynx group (csHR, 0.82; 95% CI, 0.72-0.94) but only a trend in the nonoropharynx group (csHR, 0.88; 95% CI, 0.78-1.00).

Given that most oropharynx cancers are likely related to HPV, the authors speculate that the finding of an association in the oropharynx group but not the nonoropharynx group may be attributable to differences in treatment efficacy due to HPV status, since there is evidence beginning to mount that cetuximab may have lower efficacy in these cancers. “For patients who are ineligible for treatment with cisplatin, carboplatin-based radiosensitization may provide better oncologic outcomes than cetuximab, particularly for oropharynx cancer,” the authors wrote.

The study is limited by its retrospective nature and a lack of patient-level data on HPV status. The researchers did not have information on neuropathy, hearing loss, treatment toxicity, or disease progression.

Among patients with locally advanced head and neck squamous cell carcinoma who are ineligible to receive cisplatin, carboplatin-based chemoradiotherapy (CRT) may be a better option than cetuximab-based chemoradiotherapy, according to a new cohort study of U.S. veterans.

Although cisplatin is the favored treatment choice for these patients, kidney dysfunction, hearing loss, neuropathy, advanced age, and performance status can be contraindications. As radiosensitizing agents, both cetuximab and carboplatin-fluorouracil combined with radiotherapy have increased survival compared to radiotherapy alone in randomized, controlled trials.

Previous studies have demonstrated that cisplatin outperforms cetuximab in CRT regimens with a particular focus on cancers linked to human papillomavirus (HPV), but no prospective trials have compared cetuximab and carboplatin-based radiosensitization, according to the authors of the new report, published online in JAMA Otolaryngology – Head & Neck Surgery.

Some small retrospective studies, generally performed at one or two institutions, found that carboplatin outperformed cetuximab with respect to progression-free and overall survival, but these were subject to natural biases as well as imbalances between the two treatment groups.

To address this literature gap, the authors conducted a nationwide retrospective analysis of 8,290 U.S. veterans, who have a high rate of frailty and comorbidities such as heart disease and tobacco use that could make them ineligible for treatment with cisplatin. Among the veterans, 5,566 were treated with cisplatin, 1,231 with carboplatin, and 1,493 with cetuximab. The overall median age was 63 years, 98.9% were male, 82.6% were White, 15.8% were Black or African American, 68.5% were current smokers, 13.0% were former smokers, and 18.5% had never smoked.

Patients treated with carboplatin and cetuximab were older and had more comorbidities than those treated with cisplatin. Sixty-five percent of patients treated with carboplatin also received paclitaxel. Fifty-eight percent had a primary oropharynx cancer.

Median overall survival was 59.3 months among all patients (interquartile range [IQR, 18.5-140.9 months]. Median OS was 74.4 months in the cisplatin group (IQR, 22.3-162.2), 43.4 months in the carboplatin group (IQR, 15.3-123.8), and 31.1 months in the cetuximab group (IQR, 12.4-87.8). There was a lower inverse probability weighted cause-specific hazard ratio (csHR) of death associated with carboplatin (csHR, 0.85; 95% confidence interval [CI], 0.78-0.93). The researchers compared survival associations in oropharynx and nonoropharynx subgroups and found a significant association in the oropharynx group (csHR, 0.82; 95% CI, 0.72-0.94) but only a trend in the nonoropharynx group (csHR, 0.88; 95% CI, 0.78-1.00).

Given that most oropharynx cancers are likely related to HPV, the authors speculate that the finding of an association in the oropharynx group but not the nonoropharynx group may be attributable to differences in treatment efficacy due to HPV status, since there is evidence beginning to mount that cetuximab may have lower efficacy in these cancers. “For patients who are ineligible for treatment with cisplatin, carboplatin-based radiosensitization may provide better oncologic outcomes than cetuximab, particularly for oropharynx cancer,” the authors wrote.

The study is limited by its retrospective nature and a lack of patient-level data on HPV status. The researchers did not have information on neuropathy, hearing loss, treatment toxicity, or disease progression.

Among patients with locally advanced head and neck squamous cell carcinoma who are ineligible to receive cisplatin, carboplatin-based chemoradiotherapy (CRT) may be a better option than cetuximab-based chemoradiotherapy, according to a new cohort study of U.S. veterans.

Although cisplatin is the favored treatment choice for these patients, kidney dysfunction, hearing loss, neuropathy, advanced age, and performance status can be contraindications. As radiosensitizing agents, both cetuximab and carboplatin-fluorouracil combined with radiotherapy have increased survival compared to radiotherapy alone in randomized, controlled trials.

Previous studies have demonstrated that cisplatin outperforms cetuximab in CRT regimens with a particular focus on cancers linked to human papillomavirus (HPV), but no prospective trials have compared cetuximab and carboplatin-based radiosensitization, according to the authors of the new report, published online in JAMA Otolaryngology – Head & Neck Surgery.

Some small retrospective studies, generally performed at one or two institutions, found that carboplatin outperformed cetuximab with respect to progression-free and overall survival, but these were subject to natural biases as well as imbalances between the two treatment groups.

To address this literature gap, the authors conducted a nationwide retrospective analysis of 8,290 U.S. veterans, who have a high rate of frailty and comorbidities such as heart disease and tobacco use that could make them ineligible for treatment with cisplatin. Among the veterans, 5,566 were treated with cisplatin, 1,231 with carboplatin, and 1,493 with cetuximab. The overall median age was 63 years, 98.9% were male, 82.6% were White, 15.8% were Black or African American, 68.5% were current smokers, 13.0% were former smokers, and 18.5% had never smoked.

Patients treated with carboplatin and cetuximab were older and had more comorbidities than those treated with cisplatin. Sixty-five percent of patients treated with carboplatin also received paclitaxel. Fifty-eight percent had a primary oropharynx cancer.

Median overall survival was 59.3 months among all patients (interquartile range [IQR, 18.5-140.9 months]. Median OS was 74.4 months in the cisplatin group (IQR, 22.3-162.2), 43.4 months in the carboplatin group (IQR, 15.3-123.8), and 31.1 months in the cetuximab group (IQR, 12.4-87.8). There was a lower inverse probability weighted cause-specific hazard ratio (csHR) of death associated with carboplatin (csHR, 0.85; 95% confidence interval [CI], 0.78-0.93). The researchers compared survival associations in oropharynx and nonoropharynx subgroups and found a significant association in the oropharynx group (csHR, 0.82; 95% CI, 0.72-0.94) but only a trend in the nonoropharynx group (csHR, 0.88; 95% CI, 0.78-1.00).

Given that most oropharynx cancers are likely related to HPV, the authors speculate that the finding of an association in the oropharynx group but not the nonoropharynx group may be attributable to differences in treatment efficacy due to HPV status, since there is evidence beginning to mount that cetuximab may have lower efficacy in these cancers. “For patients who are ineligible for treatment with cisplatin, carboplatin-based radiosensitization may provide better oncologic outcomes than cetuximab, particularly for oropharynx cancer,” the authors wrote.

The study is limited by its retrospective nature and a lack of patient-level data on HPV status. The researchers did not have information on neuropathy, hearing loss, treatment toxicity, or disease progression.

FROM JAMA ONCOLOGY

A new study finds that high levels of tumor mutation burden (TMB) in non–small cell lung cancer (NSCLC) were associated with better outcomes after treatment with PD-1 and PD-L1 inhibitors. The findings could supplement other biomarkers, and suggest that chemotherapy could be avoided in some patients.

“We found a TMB value … of 19 mutations per megabase was a strong discriminator of response and nonresponse, and that corresponds to approximately the 90th percentile for TMB in our dataset. That is a higher threshold than has been previously proposed to be used for a TMB cutoff across different datasets or in lung cancer, but it did seem to be a strong discriminator of response, and that also translated into an improvement in progression free survival and overall survival in patients treated with immunotherapy,” said study coauthor Mark Awad, MD, PhD, in a podcast hosted by JAMA. He is a cancer researcher at Harvard Medical School, Boston. The research was published online in JAMA Oncology.

The value was reinforced when the team looked at deciles of TMB, from the lowest 10%, 20%, up to 90%. “It did seem like there was an inflection point, but only at the really higher levels of TMB – above the 80th, or especially the 90th percentile for TMB. That’s where it seemed to make a big difference in terms of improvements in response rate, progression-free, and overall survival,” Dr. Awad said.

The values of TMB and levels of PD-L1 expression also interacted in a useful way. “If you’re looking at PD-L1 on one axis and TMB on the other, it does seem that higher PD-L1 and the higher TMB can really identify patients with strong and great outcomes to immune checkpoint inhibitors. By contrast, low PD-L1 and low TMB really identifies patients that are not likely to benefit from immunotherapy alone and obviously might need to escalate it or more intensified therapy,” he said.

The results could help inform clinical decisions, though Dr. Awad included a caveat that the study was retrospective. In particular, patients with high TMB levels who might not tolerate chemotherapy well could be candidates for immunotherapy alone, “if you feel like there would be time to try immunotherapy alone rather than chemoimmunotherapy, and hopefully spare or avoid some of the chemotherapy toxicities, with the understanding that you wouldn’t want a patient’s disease to rapidly progress. You have to choose these cases carefully,” he said.

Dr. Awad suggested that TMB can be used alongside other factors such as PD-L1 mutations, KRAS mutation status, STK-11, and KEAP1 mutations. “I think all of these features will start to tip the scales one way or the other in terms of using immunotherapy alone or immunotherapy in combination with chemotherapy, and hopefully as new trials are developed, TMB and other predictive biomarkers can be used to stratify populations within a trial to hopefully ensure balance between treatment arms, and also to identify cancers that are less likely to respond to immune checkpoint inhibitors, such that we can really develop more tailored regimens for patients that will or won’t be as likely to respond to immunotherapy.”

The study included 1,552 patients with advanced NSCLC, with a median age of 66; 53.5% were women. The median TMB was 9.82 mutations per megabase. The researchers categorized patients as low TMB (fewer than 19 mutations per megabase) or high TMB (19 or more mutations). The high TMB group associated with better outcomes after treatment with PD-1/PD-L1 inhibitors, including overall response rate, progression-free survival, and overall survival. The associations occurred in the discovery cohort as well as two other independent cohorts. The same relationship occurred in all PD-L1 tumor proportion score subgroups.

Patients with NSCLCs with high TMB as well as PD-L1 expression of 50% or higher had an overall response rate of 57% and had the longest PFS and OS with ICI treatment (18.1 months and 47.7 months, respectively). On the other hand, patients with low TMB and PD-L1–negative NSCLC had the lowest ORR at 8.7% and the shortest PFS and OS (2.1 months and 10.4 months, respectively).

Dr. Awad has consulted for Achilles, AbbVie, Neon, Maverick, Nektar, and Hegrui. He has received grants and personal fees from Genentech, Bristol-Myers Squibb, Merck, AstraZeneca, and Lilly. He has received personal fees from Maverick, Blueprint Medicine, Syndax, Ariad, Nektar, Gritstone, ArcherDx, Mirati, NextCure, Novartis, EMD Serono, and NovaRx.

FROM JAMA ONCOLOGY

A new study finds that high levels of tumor mutation burden (TMB) in non–small cell lung cancer (NSCLC) were associated with better outcomes after treatment with PD-1 and PD-L1 inhibitors. The findings could supplement other biomarkers, and suggest that chemotherapy could be avoided in some patients.

“We found a TMB value … of 19 mutations per megabase was a strong discriminator of response and nonresponse, and that corresponds to approximately the 90th percentile for TMB in our dataset. That is a higher threshold than has been previously proposed to be used for a TMB cutoff across different datasets or in lung cancer, but it did seem to be a strong discriminator of response, and that also translated into an improvement in progression free survival and overall survival in patients treated with immunotherapy,” said study coauthor Mark Awad, MD, PhD, in a podcast hosted by JAMA. He is a cancer researcher at Harvard Medical School, Boston. The research was published online in JAMA Oncology.

The value was reinforced when the team looked at deciles of TMB, from the lowest 10%, 20%, up to 90%. “It did seem like there was an inflection point, but only at the really higher levels of TMB – above the 80th, or especially the 90th percentile for TMB. That’s where it seemed to make a big difference in terms of improvements in response rate, progression-free, and overall survival,” Dr. Awad said.

The values of TMB and levels of PD-L1 expression also interacted in a useful way. “If you’re looking at PD-L1 on one axis and TMB on the other, it does seem that higher PD-L1 and the higher TMB can really identify patients with strong and great outcomes to immune checkpoint inhibitors. By contrast, low PD-L1 and low TMB really identifies patients that are not likely to benefit from immunotherapy alone and obviously might need to escalate it or more intensified therapy,” he said.

The results could help inform clinical decisions, though Dr. Awad included a caveat that the study was retrospective. In particular, patients with high TMB levels who might not tolerate chemotherapy well could be candidates for immunotherapy alone, “if you feel like there would be time to try immunotherapy alone rather than chemoimmunotherapy, and hopefully spare or avoid some of the chemotherapy toxicities, with the understanding that you wouldn’t want a patient’s disease to rapidly progress. You have to choose these cases carefully,” he said.

Dr. Awad suggested that TMB can be used alongside other factors such as PD-L1 mutations, KRAS mutation status, STK-11, and KEAP1 mutations. “I think all of these features will start to tip the scales one way or the other in terms of using immunotherapy alone or immunotherapy in combination with chemotherapy, and hopefully as new trials are developed, TMB and other predictive biomarkers can be used to stratify populations within a trial to hopefully ensure balance between treatment arms, and also to identify cancers that are less likely to respond to immune checkpoint inhibitors, such that we can really develop more tailored regimens for patients that will or won’t be as likely to respond to immunotherapy.”

The study included 1,552 patients with advanced NSCLC, with a median age of 66; 53.5% were women. The median TMB was 9.82 mutations per megabase. The researchers categorized patients as low TMB (fewer than 19 mutations per megabase) or high TMB (19 or more mutations). The high TMB group associated with better outcomes after treatment with PD-1/PD-L1 inhibitors, including overall response rate, progression-free survival, and overall survival. The associations occurred in the discovery cohort as well as two other independent cohorts. The same relationship occurred in all PD-L1 tumor proportion score subgroups.

Patients with NSCLCs with high TMB as well as PD-L1 expression of 50% or higher had an overall response rate of 57% and had the longest PFS and OS with ICI treatment (18.1 months and 47.7 months, respectively). On the other hand, patients with low TMB and PD-L1–negative NSCLC had the lowest ORR at 8.7% and the shortest PFS and OS (2.1 months and 10.4 months, respectively).

Dr. Awad has consulted for Achilles, AbbVie, Neon, Maverick, Nektar, and Hegrui. He has received grants and personal fees from Genentech, Bristol-Myers Squibb, Merck, AstraZeneca, and Lilly. He has received personal fees from Maverick, Blueprint Medicine, Syndax, Ariad, Nektar, Gritstone, ArcherDx, Mirati, NextCure, Novartis, EMD Serono, and NovaRx.

FROM JAMA ONCOLOGY

A new study finds that high levels of tumor mutation burden (TMB) in non–small cell lung cancer (NSCLC) were associated with better outcomes after treatment with PD-1 and PD-L1 inhibitors. The findings could supplement other biomarkers, and suggest that chemotherapy could be avoided in some patients.

“We found a TMB value … of 19 mutations per megabase was a strong discriminator of response and nonresponse, and that corresponds to approximately the 90th percentile for TMB in our dataset. That is a higher threshold than has been previously proposed to be used for a TMB cutoff across different datasets or in lung cancer, but it did seem to be a strong discriminator of response, and that also translated into an improvement in progression free survival and overall survival in patients treated with immunotherapy,” said study coauthor Mark Awad, MD, PhD, in a podcast hosted by JAMA. He is a cancer researcher at Harvard Medical School, Boston. The research was published online in JAMA Oncology.

The value was reinforced when the team looked at deciles of TMB, from the lowest 10%, 20%, up to 90%. “It did seem like there was an inflection point, but only at the really higher levels of TMB – above the 80th, or especially the 90th percentile for TMB. That’s where it seemed to make a big difference in terms of improvements in response rate, progression-free, and overall survival,” Dr. Awad said.

The values of TMB and levels of PD-L1 expression also interacted in a useful way. “If you’re looking at PD-L1 on one axis and TMB on the other, it does seem that higher PD-L1 and the higher TMB can really identify patients with strong and great outcomes to immune checkpoint inhibitors. By contrast, low PD-L1 and low TMB really identifies patients that are not likely to benefit from immunotherapy alone and obviously might need to escalate it or more intensified therapy,” he said.

The results could help inform clinical decisions, though Dr. Awad included a caveat that the study was retrospective. In particular, patients with high TMB levels who might not tolerate chemotherapy well could be candidates for immunotherapy alone, “if you feel like there would be time to try immunotherapy alone rather than chemoimmunotherapy, and hopefully spare or avoid some of the chemotherapy toxicities, with the understanding that you wouldn’t want a patient’s disease to rapidly progress. You have to choose these cases carefully,” he said.

Dr. Awad suggested that TMB can be used alongside other factors such as PD-L1 mutations, KRAS mutation status, STK-11, and KEAP1 mutations. “I think all of these features will start to tip the scales one way or the other in terms of using immunotherapy alone or immunotherapy in combination with chemotherapy, and hopefully as new trials are developed, TMB and other predictive biomarkers can be used to stratify populations within a trial to hopefully ensure balance between treatment arms, and also to identify cancers that are less likely to respond to immune checkpoint inhibitors, such that we can really develop more tailored regimens for patients that will or won’t be as likely to respond to immunotherapy.”

The study included 1,552 patients with advanced NSCLC, with a median age of 66; 53.5% were women. The median TMB was 9.82 mutations per megabase. The researchers categorized patients as low TMB (fewer than 19 mutations per megabase) or high TMB (19 or more mutations). The high TMB group associated with better outcomes after treatment with PD-1/PD-L1 inhibitors, including overall response rate, progression-free survival, and overall survival. The associations occurred in the discovery cohort as well as two other independent cohorts. The same relationship occurred in all PD-L1 tumor proportion score subgroups.

Patients with NSCLCs with high TMB as well as PD-L1 expression of 50% or higher had an overall response rate of 57% and had the longest PFS and OS with ICI treatment (18.1 months and 47.7 months, respectively). On the other hand, patients with low TMB and PD-L1–negative NSCLC had the lowest ORR at 8.7% and the shortest PFS and OS (2.1 months and 10.4 months, respectively).

Dr. Awad has consulted for Achilles, AbbVie, Neon, Maverick, Nektar, and Hegrui. He has received grants and personal fees from Genentech, Bristol-Myers Squibb, Merck, AstraZeneca, and Lilly. He has received personal fees from Maverick, Blueprint Medicine, Syndax, Ariad, Nektar, Gritstone, ArcherDx, Mirati, NextCure, Novartis, EMD Serono, and NovaRx.

Among patients with constipation, reduced rectoanal gradient found during high-resolution anorectal manometry (HR-ARM) is the strongest parameter for predicting how a patient is likely to perform on a rectal balloon expulsion test (BET). Findings of both reduced rectoanal gradient and abnormal BET should be considered diagnostic for a defecatory disorder.

Those are the findings of a study out of the Mayo Clinic in Rochester, Minn., which was published in Gastroenterology. The research could help streamline diagnosis of defecatory disorders: Currently there is a lack of consensus on what tests should be performed and in what order to achieve a reliable diagnosis, according to the authors.

The authors recommend that, in patients with a suggestive history, a prolonged time on BET or reduced rectoanal gradient individually indicate a probable defecatory disorder, while the presence of both could be considered diagnostic even in the absence of defecography.

The research should provide clarity about the findings from HR-ARM, which can be complex, according to Kyle Staller, MD, who was asked to comment on the study. “You get lots of different numbers, you get lots of different parameters [with HR-ARM], and figuring out which ones are really relevant is somewhat difficult. [This study] is really a tour de force that distills down many of these parameters into some that we might want to pay attention to more than others,” said Dr. Staller, who is director of the GI Motility Laboratory at Massachusetts General Hospital and a professor of medicine at Harvard Medical School, both in Boston.

He pointed out that one limitation of the study is it didn’t attempt to answer the question of what parameters predict benefit from biofeedback therapy.

“I think the practice right now is that we tend to put the most weight on the balloon expulsion test. I think what this paper convincingly argues is that maybe someone who has an abnormal rectoanal gradient and a normal balloon expulsion test should also be referred for biofeedback with the caveat that we still don’t know if they’re going to do well on biofeedback or not,” said Dr. Staller.

The study included 658 patients, 474 with constipation and 184 healthy controls. In addition to HR-ARM and BET, 158 underwent defecography. Females made up 89% of constipated patients and 73% of healthy individuals. Healthy individuals were younger than constipated individuals (median age 35 versus 49 years).

Overall, 11% of healthy patients and 32% of constipated patients had prolonged BET time (P < .001) and 11% and 21% had a reduced rectoanal gradient on HR-ARM (P = .003). Among those with a normal BET time, 13% had a reduced rectoanal gradient, compared with 34% of those with a prolonged BET time (P < .001).

The authors report that HR-ARM variables had good specificity but worse sensitivity for predicting prolonged BET. The rectoanal gradient was the best-performing variable, with a specificity of 85% and a sensitivity of 36%.

HR-ARM and BET findings were associated with reduced rectal evacuation found on defecography. The median rectal evacuation was 79% if both BET and rectoanal gradient were normal, 35% if either one was abnormal, and 3% if both were abnormal (P < .001). Having either prolonged BET time or reduced anorectal gradient alone had a 73% sensitivity and specificity of 72% for incomplete evacuation on defecography. If both abnormalities were present, the sensitivity was 31% but the specificity was 95%.

A reduced rectoanal gradient was associated with incomplete rectal evacuation (odds ratio, 4.35; P = .002); prolonged BET time showed a similar association (OR, 4.57; P < .001).

The authors proposed terminology to help differentiate the findings: “probable defecatory disorder,” or “probable DD,” to describe patients with one abnormal result from the three tests and “definite DD” for those with two abnormal test results. “Although a single abnormal finding may be a false-positive result, pursuing a trial of biofeedback therapy for patients with a probable DD may be reasonable, especially when defecography is not feasible. However, this approach should be confirmed by prospective studies that assess the response to anorectal biofeedback therapy in patients with probable and definite DD, as defined above.”

The authors disclosed no conflicts of interest. Dr. Staller has consulted for GI Supply.

Among patients with constipation, reduced rectoanal gradient found during high-resolution anorectal manometry (HR-ARM) is the strongest parameter for predicting how a patient is likely to perform on a rectal balloon expulsion test (BET). Findings of both reduced rectoanal gradient and abnormal BET should be considered diagnostic for a defecatory disorder.

Those are the findings of a study out of the Mayo Clinic in Rochester, Minn., which was published in Gastroenterology. The research could help streamline diagnosis of defecatory disorders: Currently there is a lack of consensus on what tests should be performed and in what order to achieve a reliable diagnosis, according to the authors.

The authors recommend that, in patients with a suggestive history, a prolonged time on BET or reduced rectoanal gradient individually indicate a probable defecatory disorder, while the presence of both could be considered diagnostic even in the absence of defecography.

The research should provide clarity about the findings from HR-ARM, which can be complex, according to Kyle Staller, MD, who was asked to comment on the study. “You get lots of different numbers, you get lots of different parameters [with HR-ARM], and figuring out which ones are really relevant is somewhat difficult. [This study] is really a tour de force that distills down many of these parameters into some that we might want to pay attention to more than others,” said Dr. Staller, who is director of the GI Motility Laboratory at Massachusetts General Hospital and a professor of medicine at Harvard Medical School, both in Boston.

He pointed out that one limitation of the study is it didn’t attempt to answer the question of what parameters predict benefit from biofeedback therapy.

“I think the practice right now is that we tend to put the most weight on the balloon expulsion test. I think what this paper convincingly argues is that maybe someone who has an abnormal rectoanal gradient and a normal balloon expulsion test should also be referred for biofeedback with the caveat that we still don’t know if they’re going to do well on biofeedback or not,” said Dr. Staller.

The study included 658 patients, 474 with constipation and 184 healthy controls. In addition to HR-ARM and BET, 158 underwent defecography. Females made up 89% of constipated patients and 73% of healthy individuals. Healthy individuals were younger than constipated individuals (median age 35 versus 49 years).

Overall, 11% of healthy patients and 32% of constipated patients had prolonged BET time (P < .001) and 11% and 21% had a reduced rectoanal gradient on HR-ARM (P = .003). Among those with a normal BET time, 13% had a reduced rectoanal gradient, compared with 34% of those with a prolonged BET time (P < .001).

The authors report that HR-ARM variables had good specificity but worse sensitivity for predicting prolonged BET. The rectoanal gradient was the best-performing variable, with a specificity of 85% and a sensitivity of 36%.

HR-ARM and BET findings were associated with reduced rectal evacuation found on defecography. The median rectal evacuation was 79% if both BET and rectoanal gradient were normal, 35% if either one was abnormal, and 3% if both were abnormal (P < .001). Having either prolonged BET time or reduced anorectal gradient alone had a 73% sensitivity and specificity of 72% for incomplete evacuation on defecography. If both abnormalities were present, the sensitivity was 31% but the specificity was 95%.

A reduced rectoanal gradient was associated with incomplete rectal evacuation (odds ratio, 4.35; P = .002); prolonged BET time showed a similar association (OR, 4.57; P < .001).

The authors proposed terminology to help differentiate the findings: “probable defecatory disorder,” or “probable DD,” to describe patients with one abnormal result from the three tests and “definite DD” for those with two abnormal test results. “Although a single abnormal finding may be a false-positive result, pursuing a trial of biofeedback therapy for patients with a probable DD may be reasonable, especially when defecography is not feasible. However, this approach should be confirmed by prospective studies that assess the response to anorectal biofeedback therapy in patients with probable and definite DD, as defined above.”

The authors disclosed no conflicts of interest. Dr. Staller has consulted for GI Supply.

Among patients with constipation, reduced rectoanal gradient found during high-resolution anorectal manometry (HR-ARM) is the strongest parameter for predicting how a patient is likely to perform on a rectal balloon expulsion test (BET). Findings of both reduced rectoanal gradient and abnormal BET should be considered diagnostic for a defecatory disorder.

Those are the findings of a study out of the Mayo Clinic in Rochester, Minn., which was published in Gastroenterology. The research could help streamline diagnosis of defecatory disorders: Currently there is a lack of consensus on what tests should be performed and in what order to achieve a reliable diagnosis, according to the authors.

The authors recommend that, in patients with a suggestive history, a prolonged time on BET or reduced rectoanal gradient individually indicate a probable defecatory disorder, while the presence of both could be considered diagnostic even in the absence of defecography.

The research should provide clarity about the findings from HR-ARM, which can be complex, according to Kyle Staller, MD, who was asked to comment on the study. “You get lots of different numbers, you get lots of different parameters [with HR-ARM], and figuring out which ones are really relevant is somewhat difficult. [This study] is really a tour de force that distills down many of these parameters into some that we might want to pay attention to more than others,” said Dr. Staller, who is director of the GI Motility Laboratory at Massachusetts General Hospital and a professor of medicine at Harvard Medical School, both in Boston.

He pointed out that one limitation of the study is it didn’t attempt to answer the question of what parameters predict benefit from biofeedback therapy.

“I think the practice right now is that we tend to put the most weight on the balloon expulsion test. I think what this paper convincingly argues is that maybe someone who has an abnormal rectoanal gradient and a normal balloon expulsion test should also be referred for biofeedback with the caveat that we still don’t know if they’re going to do well on biofeedback or not,” said Dr. Staller.

The study included 658 patients, 474 with constipation and 184 healthy controls. In addition to HR-ARM and BET, 158 underwent defecography. Females made up 89% of constipated patients and 73% of healthy individuals. Healthy individuals were younger than constipated individuals (median age 35 versus 49 years).

Overall, 11% of healthy patients and 32% of constipated patients had prolonged BET time (P < .001) and 11% and 21% had a reduced rectoanal gradient on HR-ARM (P = .003). Among those with a normal BET time, 13% had a reduced rectoanal gradient, compared with 34% of those with a prolonged BET time (P < .001).

The authors report that HR-ARM variables had good specificity but worse sensitivity for predicting prolonged BET. The rectoanal gradient was the best-performing variable, with a specificity of 85% and a sensitivity of 36%.

HR-ARM and BET findings were associated with reduced rectal evacuation found on defecography. The median rectal evacuation was 79% if both BET and rectoanal gradient were normal, 35% if either one was abnormal, and 3% if both were abnormal (P < .001). Having either prolonged BET time or reduced anorectal gradient alone had a 73% sensitivity and specificity of 72% for incomplete evacuation on defecography. If both abnormalities were present, the sensitivity was 31% but the specificity was 95%.

A reduced rectoanal gradient was associated with incomplete rectal evacuation (odds ratio, 4.35; P = .002); prolonged BET time showed a similar association (OR, 4.57; P < .001).

The authors proposed terminology to help differentiate the findings: “probable defecatory disorder,” or “probable DD,” to describe patients with one abnormal result from the three tests and “definite DD” for those with two abnormal test results. “Although a single abnormal finding may be a false-positive result, pursuing a trial of biofeedback therapy for patients with a probable DD may be reasonable, especially when defecography is not feasible. However, this approach should be confirmed by prospective studies that assess the response to anorectal biofeedback therapy in patients with probable and definite DD, as defined above.”

The authors disclosed no conflicts of interest. Dr. Staller has consulted for GI Supply.

Among patients with American Joint Committee on Cancer IIIA early-stage melanoma metastases, the presence of sentinel node (SN) tumor deposits of 0.3 mm or higher is associated with a greater risk of disease progression, and these individuals may be well served by adjuvant systemic therapy. It suggests that those with smaller tumor deposits can be managed in a similar way to AJCC IB patients who are SN negative.

Those are the conclusions from a new prospective analysis of melanoma patients drawn from nine high-volume cancer centers in Australia, Europe, and North America. It was published online in the Journal of Clinical Oncology.

Classification of stage III melanoma is difficult since it comprises a heterogeneous group of patients with divergent prognoses. That complexity has resulted in four subcategories of stage III, ranging from high-risk primaries with synchronous nodal metastases (IIID) to patients with early-stage primary tumors with low burden at the SN (IIIA). The latter patients have excellent prognoses, with close to 90% 5-year survival. In fact, they have a better survival rate than some stage II patients with SN-negative, high-risk primary tumors (AJCC IIB-IIC).

Recent phase 3 trials have produced standardized protocols for treating stage III patients with intermediate to high risk (IIIB-IIID), but there is little evidence for the best approach to treat stage IIIA.

To fill that gap, the researchers examined data from 3,607 patients with low-risk primaries, defined as AJCC pT1b-pT2a. About 11.3% were AJCC IIIA and the rest were AJCC IB with no SN tumors: They served as a comparison group. The median follow-up was 34 months.

The researchers conducted a survival analysis that identified 0.3 mm as the optimal size to stratify outcomes. Among those with SN tumors 0.3 mm or higher, 5-year disease-specific survival was 80.3%. For those with smaller tumors, the rate was 94.1% (hazard ratio, 1.26; P < .0001). For distant metastasis-free survival the rates were 72.4% and 92.1% (HR, 1.27; P < .0001). Survival rates were similar between AJCC IB and low-risk AJCC IIIA patients.

The researchers found no differences between the AJCC IB patients and low-risk (< 0.3 mm) AJCC IIIA patients.

Other factors were associated with the presence of high-risk SN tumor size, including male sex (chi-squared, 4.97; df, 1; P = .034), and mitotic rates higher than 1/mm² (chi-squared, 4.92; df, 1; P = .035), although only mitotic rate remained a statistically significant risk factor after multivariate analysis (HR, 1.59; P = .050).

Where extracapsular spread was present, the median maximum tumor deposit size was 3.0 mm versus 0.5 mm in the absence of ECS (Kruskal-Wallis; F, 17.78; df, 1; P < .0001). High-risk nodal disease trended towards an association with N2a stage nodal metastases, compared with N1a stage disease (22.6% vs. 13.8%; chi-squared, 4.31; df, 1; P = .052).

The results of the study suggest that guidelines from the National Comprehensive Cancer Network and The National Institute for Health and Care Excellence could be missing up to one-third of patients with stage IIIA disease with high risk of distance recurrence or death, who may benefit from adjuvant systemic therapy. “We suggest that early-stage, AJCC IIIA patients with micrometastases of maximum tumor dimension [of at least] 0.3 mm should be considered for adjuvant systemic therapy or enrollment into a clinical trial, whereas patients with micrometastases of maximum tumor dimension less than 0.3 mm can be managed in a similar fashion to their SN-negative, AJCC IB counterparts,” the authors wrote.

Eight coauthors reported various conflicts of interest with pharmaceutical companies; the other coauthors reported no conflicts of interest.

Among patients with American Joint Committee on Cancer IIIA early-stage melanoma metastases, the presence of sentinel node (SN) tumor deposits of 0.3 mm or higher is associated with a greater risk of disease progression, and these individuals may be well served by adjuvant systemic therapy. It suggests that those with smaller tumor deposits can be managed in a similar way to AJCC IB patients who are SN negative.

Those are the conclusions from a new prospective analysis of melanoma patients drawn from nine high-volume cancer centers in Australia, Europe, and North America. It was published online in the Journal of Clinical Oncology.

Classification of stage III melanoma is difficult since it comprises a heterogeneous group of patients with divergent prognoses. That complexity has resulted in four subcategories of stage III, ranging from high-risk primaries with synchronous nodal metastases (IIID) to patients with early-stage primary tumors with low burden at the SN (IIIA). The latter patients have excellent prognoses, with close to 90% 5-year survival. In fact, they have a better survival rate than some stage II patients with SN-negative, high-risk primary tumors (AJCC IIB-IIC).

Recent phase 3 trials have produced standardized protocols for treating stage III patients with intermediate to high risk (IIIB-IIID), but there is little evidence for the best approach to treat stage IIIA.

To fill that gap, the researchers examined data from 3,607 patients with low-risk primaries, defined as AJCC pT1b-pT2a. About 11.3% were AJCC IIIA and the rest were AJCC IB with no SN tumors: They served as a comparison group. The median follow-up was 34 months.

The researchers conducted a survival analysis that identified 0.3 mm as the optimal size to stratify outcomes. Among those with SN tumors 0.3 mm or higher, 5-year disease-specific survival was 80.3%. For those with smaller tumors, the rate was 94.1% (hazard ratio, 1.26; P < .0001). For distant metastasis-free survival the rates were 72.4% and 92.1% (HR, 1.27; P < .0001). Survival rates were similar between AJCC IB and low-risk AJCC IIIA patients.

The researchers found no differences between the AJCC IB patients and low-risk (< 0.3 mm) AJCC IIIA patients.

Other factors were associated with the presence of high-risk SN tumor size, including male sex (chi-squared, 4.97; df, 1; P = .034), and mitotic rates higher than 1/mm² (chi-squared, 4.92; df, 1; P = .035), although only mitotic rate remained a statistically significant risk factor after multivariate analysis (HR, 1.59; P = .050).

Where extracapsular spread was present, the median maximum tumor deposit size was 3.0 mm versus 0.5 mm in the absence of ECS (Kruskal-Wallis; F, 17.78; df, 1; P < .0001). High-risk nodal disease trended towards an association with N2a stage nodal metastases, compared with N1a stage disease (22.6% vs. 13.8%; chi-squared, 4.31; df, 1; P = .052).

The results of the study suggest that guidelines from the National Comprehensive Cancer Network and The National Institute for Health and Care Excellence could be missing up to one-third of patients with stage IIIA disease with high risk of distance recurrence or death, who may benefit from adjuvant systemic therapy. “We suggest that early-stage, AJCC IIIA patients with micrometastases of maximum tumor dimension [of at least] 0.3 mm should be considered for adjuvant systemic therapy or enrollment into a clinical trial, whereas patients with micrometastases of maximum tumor dimension less than 0.3 mm can be managed in a similar fashion to their SN-negative, AJCC IB counterparts,” the authors wrote.

Eight coauthors reported various conflicts of interest with pharmaceutical companies; the other coauthors reported no conflicts of interest.

Among patients with American Joint Committee on Cancer IIIA early-stage melanoma metastases, the presence of sentinel node (SN) tumor deposits of 0.3 mm or higher is associated with a greater risk of disease progression, and these individuals may be well served by adjuvant systemic therapy. It suggests that those with smaller tumor deposits can be managed in a similar way to AJCC IB patients who are SN negative.

Those are the conclusions from a new prospective analysis of melanoma patients drawn from nine high-volume cancer centers in Australia, Europe, and North America. It was published online in the Journal of Clinical Oncology.

Classification of stage III melanoma is difficult since it comprises a heterogeneous group of patients with divergent prognoses. That complexity has resulted in four subcategories of stage III, ranging from high-risk primaries with synchronous nodal metastases (IIID) to patients with early-stage primary tumors with low burden at the SN (IIIA). The latter patients have excellent prognoses, with close to 90% 5-year survival. In fact, they have a better survival rate than some stage II patients with SN-negative, high-risk primary tumors (AJCC IIB-IIC).

Recent phase 3 trials have produced standardized protocols for treating stage III patients with intermediate to high risk (IIIB-IIID), but there is little evidence for the best approach to treat stage IIIA.

To fill that gap, the researchers examined data from 3,607 patients with low-risk primaries, defined as AJCC pT1b-pT2a. About 11.3% were AJCC IIIA and the rest were AJCC IB with no SN tumors: They served as a comparison group. The median follow-up was 34 months.

The researchers conducted a survival analysis that identified 0.3 mm as the optimal size to stratify outcomes. Among those with SN tumors 0.3 mm or higher, 5-year disease-specific survival was 80.3%. For those with smaller tumors, the rate was 94.1% (hazard ratio, 1.26; P < .0001). For distant metastasis-free survival the rates were 72.4% and 92.1% (HR, 1.27; P < .0001). Survival rates were similar between AJCC IB and low-risk AJCC IIIA patients.

The researchers found no differences between the AJCC IB patients and low-risk (< 0.3 mm) AJCC IIIA patients.

Other factors were associated with the presence of high-risk SN tumor size, including male sex (chi-squared, 4.97; df, 1; P = .034), and mitotic rates higher than 1/mm² (chi-squared, 4.92; df, 1; P = .035), although only mitotic rate remained a statistically significant risk factor after multivariate analysis (HR, 1.59; P = .050).

Where extracapsular spread was present, the median maximum tumor deposit size was 3.0 mm versus 0.5 mm in the absence of ECS (Kruskal-Wallis; F, 17.78; df, 1; P < .0001). High-risk nodal disease trended towards an association with N2a stage nodal metastases, compared with N1a stage disease (22.6% vs. 13.8%; chi-squared, 4.31; df, 1; P = .052).

The results of the study suggest that guidelines from the National Comprehensive Cancer Network and The National Institute for Health and Care Excellence could be missing up to one-third of patients with stage IIIA disease with high risk of distance recurrence or death, who may benefit from adjuvant systemic therapy. “We suggest that early-stage, AJCC IIIA patients with micrometastases of maximum tumor dimension [of at least] 0.3 mm should be considered for adjuvant systemic therapy or enrollment into a clinical trial, whereas patients with micrometastases of maximum tumor dimension less than 0.3 mm can be managed in a similar fashion to their SN-negative, AJCC IB counterparts,” the authors wrote.

Eight coauthors reported various conflicts of interest with pharmaceutical companies; the other coauthors reported no conflicts of interest.

Neoadjuvant immunotherapy for stage II-IV cutaneous squamous cell carcinoma (CSCC) led to a strong pathological complete response rate, according to results from a stage 2 clinical trial.

CSCC hasn’t received much attention from pharmaceutical companies, in part because it so often responds well to surgery or local therapy. Still, some patients develop more advanced cancer that requires surgery, often on exposed surfaces like the scalp, face, or neck. That can lead to cosmetic and functional impairment.

“Having witnessed the toxicity of treatments over time has really kind of kind of pushed me for a long time to seek better ways to treat this,” lead author Neil Gross, MD, said in an interview. Dr. Gross is director of clinical research in the department of head and neck surgery at the University of Texas MD Anderson Cancer Center, Houston. The study was presented at the annual meeting of the European Society for Medical Oncology and published simultaneously in the New England Journal of Medicine.

Dr. Gross and colleagues conducted a pilot study that examined neoadjuvant immunotherapy with cemiplimab (Libtayo, Regeneron). It received Food and Drug Administration approval in 2018 for metastatic cutaneous squamous cell carcinoma. The aim of the study was to determine how cells responded to the therapy and learn more about the biology, but the results turned heads. “We were surprised to learn just how well the patients responded, Over half of the patients had a complete pathologic response to treatment, and another 4 patients out of 20 had a near-complete pathological response. It prompted a multicenter trial to confirm whether or not what we’re seeing was real,” Dr. Gross said.

The new phase 2 study, conducted in 79 patients at centers in Australia, Germany, and the United States, was encouraging. “The results were very, very similar. About 63% overall had this really impressive pathologic response to treatment. And, it may even be an underestimation of the responses because there were several patients in the trial who responded so well that they refused surgery. Those patients were counted as nonresponders just to be most conservative,” Dr. Gross said.

“I think it will change practice. The results are just so dramatic that it’s hard to imagine it’s not going to influence how patients are treated,” he said.
 

Dramatic results and an attractive option

Among 79 patients in the new trial, the median age was 73 years, 85% were male, and 87% were White. About 91% of primary tumors were head and neck; 6% were stage II, 48% stage III, and 46% stage IV. All patients received four doses of 350 mg cemiplimab at 3-week intervals.

After a median follow-up of 9.7 months (range, 1.3-19.6 months), 51% achieved a pathological complete response (95% confidence interval, 39%-62%). The null hypothesis was that 25% would achieve a pathologic response. An additional 13% had a pathological major response (95% CI, 6%-22%). 25% did not achieve a pathological complete or pathological major response, which was defined as viable tumor cells representing at least 10% of the surgical specimen.

72% of patients experienced an adverse event considered by the investigator to be related to treatment, most commonly fatigue (28%), maculopapular rash (14%), and diarrhea (11%). 15% of patients experienced immune-related adverse events. 4% experienced a grade 3 immune-related adverse event.

Despite the encouraging results, more research needs to be done. One key question is the optimal number of treatments prior to surgery. The pilot study used two doses while the phase 2 study used four doses. Another is whether the surgical excision can be safely reduced after treatment to reduce morbidity, and still another is whether some patients can avoid radiation. “There are lots of unanswered questions that are really important to how this gets rolled out into clinical practice, but I do think that there’s no turning back. The results are so dramatic that it’s a very attractive option to patients and providers. We will have to figure out how to learn the best way to use this in practice while it’s being used,” Dr. Gross said.

Additional studies are in the planning phase, though the results are so encouraging that they might hinder future research. “Will patients be willing in the future to be randomized to the current standard of care, which would be upfront surgery and radiation for advanced disease? I don’t know. There’s a lot of thought being put into the best way to design these studies moving forward that are really advantageous to patients, but still answer these some of these fundamental questions,” Dr. Gross said.

He also noted that these studies looked at pathological responses, not overall survival or clinical outcomes. “We believe that these responses will be durable, but this has to be borne out as the data matures.”

The study was funded by Regeneron. Dr. Gross has consulted for DragonFly Therapeutics, Intuitive Surgical, Regeneron, and Sanofi/Genzyme. He has been on scientific advisory boards for PDS Biotechnology and Shattuck Labs.

Neoadjuvant immunotherapy for stage II-IV cutaneous squamous cell carcinoma (CSCC) led to a strong pathological complete response rate, according to results from a stage 2 clinical trial.

CSCC hasn’t received much attention from pharmaceutical companies, in part because it so often responds well to surgery or local therapy. Still, some patients develop more advanced cancer that requires surgery, often on exposed surfaces like the scalp, face, or neck. That can lead to cosmetic and functional impairment.

“Having witnessed the toxicity of treatments over time has really kind of kind of pushed me for a long time to seek better ways to treat this,” lead author Neil Gross, MD, said in an interview. Dr. Gross is director of clinical research in the department of head and neck surgery at the University of Texas MD Anderson Cancer Center, Houston. The study was presented at the annual meeting of the European Society for Medical Oncology and published simultaneously in the New England Journal of Medicine.

Dr. Gross and colleagues conducted a pilot study that examined neoadjuvant immunotherapy with cemiplimab (Libtayo, Regeneron). It received Food and Drug Administration approval in 2018 for metastatic cutaneous squamous cell carcinoma. The aim of the study was to determine how cells responded to the therapy and learn more about the biology, but the results turned heads. “We were surprised to learn just how well the patients responded, Over half of the patients had a complete pathologic response to treatment, and another 4 patients out of 20 had a near-complete pathological response. It prompted a multicenter trial to confirm whether or not what we’re seeing was real,” Dr. Gross said.

The new phase 2 study, conducted in 79 patients at centers in Australia, Germany, and the United States, was encouraging. “The results were very, very similar. About 63% overall had this really impressive pathologic response to treatment. And, it may even be an underestimation of the responses because there were several patients in the trial who responded so well that they refused surgery. Those patients were counted as nonresponders just to be most conservative,” Dr. Gross said.

“I think it will change practice. The results are just so dramatic that it’s hard to imagine it’s not going to influence how patients are treated,” he said.
 

Dramatic results and an attractive option

Among 79 patients in the new trial, the median age was 73 years, 85% were male, and 87% were White. About 91% of primary tumors were head and neck; 6% were stage II, 48% stage III, and 46% stage IV. All patients received four doses of 350 mg cemiplimab at 3-week intervals.

After a median follow-up of 9.7 months (range, 1.3-19.6 months), 51% achieved a pathological complete response (95% confidence interval, 39%-62%). The null hypothesis was that 25% would achieve a pathologic response. An additional 13% had a pathological major response (95% CI, 6%-22%). 25% did not achieve a pathological complete or pathological major response, which was defined as viable tumor cells representing at least 10% of the surgical specimen.

72% of patients experienced an adverse event considered by the investigator to be related to treatment, most commonly fatigue (28%), maculopapular rash (14%), and diarrhea (11%). 15% of patients experienced immune-related adverse events. 4% experienced a grade 3 immune-related adverse event.

Despite the encouraging results, more research needs to be done. One key question is the optimal number of treatments prior to surgery. The pilot study used two doses while the phase 2 study used four doses. Another is whether the surgical excision can be safely reduced after treatment to reduce morbidity, and still another is whether some patients can avoid radiation. “There are lots of unanswered questions that are really important to how this gets rolled out into clinical practice, but I do think that there’s no turning back. The results are so dramatic that it’s a very attractive option to patients and providers. We will have to figure out how to learn the best way to use this in practice while it’s being used,” Dr. Gross said.

Additional studies are in the planning phase, though the results are so encouraging that they might hinder future research. “Will patients be willing in the future to be randomized to the current standard of care, which would be upfront surgery and radiation for advanced disease? I don’t know. There’s a lot of thought being put into the best way to design these studies moving forward that are really advantageous to patients, but still answer these some of these fundamental questions,” Dr. Gross said.

He also noted that these studies looked at pathological responses, not overall survival or clinical outcomes. “We believe that these responses will be durable, but this has to be borne out as the data matures.”

The study was funded by Regeneron. Dr. Gross has consulted for DragonFly Therapeutics, Intuitive Surgical, Regeneron, and Sanofi/Genzyme. He has been on scientific advisory boards for PDS Biotechnology and Shattuck Labs.

Neoadjuvant immunotherapy for stage II-IV cutaneous squamous cell carcinoma (CSCC) led to a strong pathological complete response rate, according to results from a stage 2 clinical trial.

CSCC hasn’t received much attention from pharmaceutical companies, in part because it so often responds well to surgery or local therapy. Still, some patients develop more advanced cancer that requires surgery, often on exposed surfaces like the scalp, face, or neck. That can lead to cosmetic and functional impairment.

“Having witnessed the toxicity of treatments over time has really kind of kind of pushed me for a long time to seek better ways to treat this,” lead author Neil Gross, MD, said in an interview. Dr. Gross is director of clinical research in the department of head and neck surgery at the University of Texas MD Anderson Cancer Center, Houston. The study was presented at the annual meeting of the European Society for Medical Oncology and published simultaneously in the New England Journal of Medicine.

Dr. Gross and colleagues conducted a pilot study that examined neoadjuvant immunotherapy with cemiplimab (Libtayo, Regeneron). It received Food and Drug Administration approval in 2018 for metastatic cutaneous squamous cell carcinoma. The aim of the study was to determine how cells responded to the therapy and learn more about the biology, but the results turned heads. “We were surprised to learn just how well the patients responded, Over half of the patients had a complete pathologic response to treatment, and another 4 patients out of 20 had a near-complete pathological response. It prompted a multicenter trial to confirm whether or not what we’re seeing was real,” Dr. Gross said.

The new phase 2 study, conducted in 79 patients at centers in Australia, Germany, and the United States, was encouraging. “The results were very, very similar. About 63% overall had this really impressive pathologic response to treatment. And, it may even be an underestimation of the responses because there were several patients in the trial who responded so well that they refused surgery. Those patients were counted as nonresponders just to be most conservative,” Dr. Gross said.

“I think it will change practice. The results are just so dramatic that it’s hard to imagine it’s not going to influence how patients are treated,” he said.
 

Dramatic results and an attractive option

Among 79 patients in the new trial, the median age was 73 years, 85% were male, and 87% were White. About 91% of primary tumors were head and neck; 6% were stage II, 48% stage III, and 46% stage IV. All patients received four doses of 350 mg cemiplimab at 3-week intervals.

After a median follow-up of 9.7 months (range, 1.3-19.6 months), 51% achieved a pathological complete response (95% confidence interval, 39%-62%). The null hypothesis was that 25% would achieve a pathologic response. An additional 13% had a pathological major response (95% CI, 6%-22%). 25% did not achieve a pathological complete or pathological major response, which was defined as viable tumor cells representing at least 10% of the surgical specimen.

72% of patients experienced an adverse event considered by the investigator to be related to treatment, most commonly fatigue (28%), maculopapular rash (14%), and diarrhea (11%). 15% of patients experienced immune-related adverse events. 4% experienced a grade 3 immune-related adverse event.

Despite the encouraging results, more research needs to be done. One key question is the optimal number of treatments prior to surgery. The pilot study used two doses while the phase 2 study used four doses. Another is whether the surgical excision can be safely reduced after treatment to reduce morbidity, and still another is whether some patients can avoid radiation. “There are lots of unanswered questions that are really important to how this gets rolled out into clinical practice, but I do think that there’s no turning back. The results are so dramatic that it’s a very attractive option to patients and providers. We will have to figure out how to learn the best way to use this in practice while it’s being used,” Dr. Gross said.

Additional studies are in the planning phase, though the results are so encouraging that they might hinder future research. “Will patients be willing in the future to be randomized to the current standard of care, which would be upfront surgery and radiation for advanced disease? I don’t know. There’s a lot of thought being put into the best way to design these studies moving forward that are really advantageous to patients, but still answer these some of these fundamental questions,” Dr. Gross said.

He also noted that these studies looked at pathological responses, not overall survival or clinical outcomes. “We believe that these responses will be durable, but this has to be borne out as the data matures.”

The study was funded by Regeneron. Dr. Gross has consulted for DragonFly Therapeutics, Intuitive Surgical, Regeneron, and Sanofi/Genzyme. He has been on scientific advisory boards for PDS Biotechnology and Shattuck Labs.

Cancer cachexia is a syndrome of weight loss that frequently occurs during cancer treatment. Consequences can include skeletal muscle loss, fatigue, functional impairment, worse quality of life, and worse survival. On the other hand, weight gain during cancer treatment has been tied to better survival.

A new study shows that, among patients with non–small cell lung cancer (NSCLC), weight gain over the course of treatment with standard of care chemotherapy was associated with improved survival in both men and women. Few studies have examined the relationship between weight gain and outcomes by sex.

“The finding that weight gain occurred in subsets of males and females is a new observation. The fact that weight gain occurs in cancer patients during anticancer treatment could confound results of clinical [trials] evaluating novel anticachexia treatments. Simultaneously studying longitudinal body weights and serum and cellular biomarkers in cancer patients might provide insights into mechanisms involved in cachexia. Increased understanding of mechanisms driving cachexia could lead to new therapeutic strategies,” said study coauthor Philip Bonomi, MD, who is an oncologist at Rush Medical College, Chicago.

“This data, although it appears to be very basic, is critically important, especially as we consider our novel interventions in the treatment of cancer cachexia,” said Eric Roeland, MD, during his presentation of the study at the annual meeting of European Society for Medical Oncology. Dr. Roeland is a medical oncologist at Oregon Health & Science University, Portland.

Dr. Roeland is also the lead author of cancer cachexia guidelines published by the American Society of Clinical Oncology in 2020. The guidelines suggest that dietary counseling can be offered to patients, but warns against routine use of enteral feeding tubes and parenteral nutrition. Although no specific drug can be recommended for cancer cachexia, progesterone analogs and corticosteroids used over the short term (weeks) can be used on a trial base to improve appetite and weight gain. While not approved in the United States, anamorelin was approved in 2020 in Japan for cancer cachexia in NSCLC, gastric cancer, pancreatic cancer, and colorectal cancer.

The new study should raise awareness of the importance of adverse effects of cancer treatments, said Karin Jordan, MD, University Hospital Heidelberg (Germany). She served as a discussant following the presentation. “As a medical oncologist, we focus a bit too much on the benefits of antineoplastic therapy, both on cure and on the survival benefit. But what is also very, very important to do is a balanced oncology treatment to focus on the risks of oncology therapies,” she said.

The study is limited by its retrospective nature and potential for bias. “The hypothesis that weight gain leads to improved survival is not really proven as it likewise may be the other way around,” Dr. Jordan said.

However, in oncology research, a phenomenon called the “obesity paradox” is increasingly catching the interest of investigators. Observational studies have shown that overweight patients with certain cancers (specifically, colorectal, endometrial and lung cancer). actually have improved overall survival as compared with normal-weight patients.
 

Details from the new study

The researchers pooled data 1,030 patients who participated in three phase 3 clinical trials conducted between 2005 and 2011. The patients all received platinum-based chemotherapy as part of control arms. 304 were female and 726 were male. The median age was 62. 16.7% were Asian, the mean body mass index was 24.6 kg/m², 88.5% had stage 4 disease, 36.9% had adenocarcinoma, and 86.3% were current or former smokers.

Males and females had similar magnitudes and rate of weight gain over the course of treatment. Any weight gain was associated with improved overall survival in both males (12.7 vs. 8.0 months; hazard ratio, 0.60; P < .001) and females (16.2 vs. 10.1 months; HR, 0.65; P = .0028). Patients who had a weight gain of 2.5% of body weight or more saw an improvement in overall survival in both males (14.0 vs. 8.2 months; HR, 0.57; P < .001) and females (16.7 vs. 11.3 months; HR, 0.61; P = .0041).

Patients with a weight gain of 5% or more was associated with improved survival in males (13.6 vs. 8.9 months; HR, 0.62; P = .0001), but there was no statistically significant association in females (16.7 vs. 12.6 months; HR, 0.69; P = .1107).

Regardless of weight-gain status, males had lower survival rates than females. All of the associations were independent of smoking status.

The study was funded by Pfizer. Dr. Bonomi has received honoraria from Pfizer and Helsinn for participation in scientific advisory boards. Dr. Jordan has consulted for Amgen, Hexal, Riemser, Helsinn, Voluntis, Pfizer, and BD Solution. She has received research funding from Deutsche Krebshilfe. She has received honoraria from MSD, Merck, Amgen, Hexal, Riemser, Helsinn, Voluntis, Pfizer, Pomme-med, PharmaMar, arttemoi, OnkoUpdate, Stemline, and Roche.

Cancer cachexia is a syndrome of weight loss that frequently occurs during cancer treatment. Consequences can include skeletal muscle loss, fatigue, functional impairment, worse quality of life, and worse survival. On the other hand, weight gain during cancer treatment has been tied to better survival.

A new study shows that, among patients with non–small cell lung cancer (NSCLC), weight gain over the course of treatment with standard of care chemotherapy was associated with improved survival in both men and women. Few studies have examined the relationship between weight gain and outcomes by sex.

“The finding that weight gain occurred in subsets of males and females is a new observation. The fact that weight gain occurs in cancer patients during anticancer treatment could confound results of clinical [trials] evaluating novel anticachexia treatments. Simultaneously studying longitudinal body weights and serum and cellular biomarkers in cancer patients might provide insights into mechanisms involved in cachexia. Increased understanding of mechanisms driving cachexia could lead to new therapeutic strategies,” said study coauthor Philip Bonomi, MD, who is an oncologist at Rush Medical College, Chicago.

“This data, although it appears to be very basic, is critically important, especially as we consider our novel interventions in the treatment of cancer cachexia,” said Eric Roeland, MD, during his presentation of the study at the annual meeting of European Society for Medical Oncology. Dr. Roeland is a medical oncologist at Oregon Health & Science University, Portland.

Dr. Roeland is also the lead author of cancer cachexia guidelines published by the American Society of Clinical Oncology in 2020. The guidelines suggest that dietary counseling can be offered to patients, but warns against routine use of enteral feeding tubes and parenteral nutrition. Although no specific drug can be recommended for cancer cachexia, progesterone analogs and corticosteroids used over the short term (weeks) can be used on a trial base to improve appetite and weight gain. While not approved in the United States, anamorelin was approved in 2020 in Japan for cancer cachexia in NSCLC, gastric cancer, pancreatic cancer, and colorectal cancer.

The new study should raise awareness of the importance of adverse effects of cancer treatments, said Karin Jordan, MD, University Hospital Heidelberg (Germany). She served as a discussant following the presentation. “As a medical oncologist, we focus a bit too much on the benefits of antineoplastic therapy, both on cure and on the survival benefit. But what is also very, very important to do is a balanced oncology treatment to focus on the risks of oncology therapies,” she said.

The study is limited by its retrospective nature and potential for bias. “The hypothesis that weight gain leads to improved survival is not really proven as it likewise may be the other way around,” Dr. Jordan said.

However, in oncology research, a phenomenon called the “obesity paradox” is increasingly catching the interest of investigators. Observational studies have shown that overweight patients with certain cancers (specifically, colorectal, endometrial and lung cancer). actually have improved overall survival as compared with normal-weight patients.
 

Details from the new study

The researchers pooled data 1,030 patients who participated in three phase 3 clinical trials conducted between 2005 and 2011. The patients all received platinum-based chemotherapy as part of control arms. 304 were female and 726 were male. The median age was 62. 16.7% were Asian, the mean body mass index was 24.6 kg/m², 88.5% had stage 4 disease, 36.9% had adenocarcinoma, and 86.3% were current or former smokers.

Males and females had similar magnitudes and rate of weight gain over the course of treatment. Any weight gain was associated with improved overall survival in both males (12.7 vs. 8.0 months; hazard ratio, 0.60; P < .001) and females (16.2 vs. 10.1 months; HR, 0.65; P = .0028). Patients who had a weight gain of 2.5% of body weight or more saw an improvement in overall survival in both males (14.0 vs. 8.2 months; HR, 0.57; P < .001) and females (16.7 vs. 11.3 months; HR, 0.61; P = .0041).

Patients with a weight gain of 5% or more was associated with improved survival in males (13.6 vs. 8.9 months; HR, 0.62; P = .0001), but there was no statistically significant association in females (16.7 vs. 12.6 months; HR, 0.69; P = .1107).

Regardless of weight-gain status, males had lower survival rates than females. All of the associations were independent of smoking status.

The study was funded by Pfizer. Dr. Bonomi has received honoraria from Pfizer and Helsinn for participation in scientific advisory boards. Dr. Jordan has consulted for Amgen, Hexal, Riemser, Helsinn, Voluntis, Pfizer, and BD Solution. She has received research funding from Deutsche Krebshilfe. She has received honoraria from MSD, Merck, Amgen, Hexal, Riemser, Helsinn, Voluntis, Pfizer, Pomme-med, PharmaMar, arttemoi, OnkoUpdate, Stemline, and Roche.

Cancer cachexia is a syndrome of weight loss that frequently occurs during cancer treatment. Consequences can include skeletal muscle loss, fatigue, functional impairment, worse quality of life, and worse survival. On the other hand, weight gain during cancer treatment has been tied to better survival.

A new study shows that, among patients with non–small cell lung cancer (NSCLC), weight gain over the course of treatment with standard of care chemotherapy was associated with improved survival in both men and women. Few studies have examined the relationship between weight gain and outcomes by sex.

“The finding that weight gain occurred in subsets of males and females is a new observation. The fact that weight gain occurs in cancer patients during anticancer treatment could confound results of clinical [trials] evaluating novel anticachexia treatments. Simultaneously studying longitudinal body weights and serum and cellular biomarkers in cancer patients might provide insights into mechanisms involved in cachexia. Increased understanding of mechanisms driving cachexia could lead to new therapeutic strategies,” said study coauthor Philip Bonomi, MD, who is an oncologist at Rush Medical College, Chicago.

“This data, although it appears to be very basic, is critically important, especially as we consider our novel interventions in the treatment of cancer cachexia,” said Eric Roeland, MD, during his presentation of the study at the annual meeting of European Society for Medical Oncology. Dr. Roeland is a medical oncologist at Oregon Health & Science University, Portland.

Dr. Roeland is also the lead author of cancer cachexia guidelines published by the American Society of Clinical Oncology in 2020. The guidelines suggest that dietary counseling can be offered to patients, but warns against routine use of enteral feeding tubes and parenteral nutrition. Although no specific drug can be recommended for cancer cachexia, progesterone analogs and corticosteroids used over the short term (weeks) can be used on a trial base to improve appetite and weight gain. While not approved in the United States, anamorelin was approved in 2020 in Japan for cancer cachexia in NSCLC, gastric cancer, pancreatic cancer, and colorectal cancer.

The new study should raise awareness of the importance of adverse effects of cancer treatments, said Karin Jordan, MD, University Hospital Heidelberg (Germany). She served as a discussant following the presentation. “As a medical oncologist, we focus a bit too much on the benefits of antineoplastic therapy, both on cure and on the survival benefit. But what is also very, very important to do is a balanced oncology treatment to focus on the risks of oncology therapies,” she said.

The study is limited by its retrospective nature and potential for bias. “The hypothesis that weight gain leads to improved survival is not really proven as it likewise may be the other way around,” Dr. Jordan said.

However, in oncology research, a phenomenon called the “obesity paradox” is increasingly catching the interest of investigators. Observational studies have shown that overweight patients with certain cancers (specifically, colorectal, endometrial and lung cancer). actually have improved overall survival as compared with normal-weight patients.
 

Details from the new study

The researchers pooled data 1,030 patients who participated in three phase 3 clinical trials conducted between 2005 and 2011. The patients all received platinum-based chemotherapy as part of control arms. 304 were female and 726 were male. The median age was 62. 16.7% were Asian, the mean body mass index was 24.6 kg/m², 88.5% had stage 4 disease, 36.9% had adenocarcinoma, and 86.3% were current or former smokers.

Males and females had similar magnitudes and rate of weight gain over the course of treatment. Any weight gain was associated with improved overall survival in both males (12.7 vs. 8.0 months; hazard ratio, 0.60; P < .001) and females (16.2 vs. 10.1 months; HR, 0.65; P = .0028). Patients who had a weight gain of 2.5% of body weight or more saw an improvement in overall survival in both males (14.0 vs. 8.2 months; HR, 0.57; P < .001) and females (16.7 vs. 11.3 months; HR, 0.61; P = .0041).

Patients with a weight gain of 5% or more was associated with improved survival in males (13.6 vs. 8.9 months; HR, 0.62; P = .0001), but there was no statistically significant association in females (16.7 vs. 12.6 months; HR, 0.69; P = .1107).

Regardless of weight-gain status, males had lower survival rates than females. All of the associations were independent of smoking status.

The study was funded by Pfizer. Dr. Bonomi has received honoraria from Pfizer and Helsinn for participation in scientific advisory boards. Dr. Jordan has consulted for Amgen, Hexal, Riemser, Helsinn, Voluntis, Pfizer, and BD Solution. She has received research funding from Deutsche Krebshilfe. She has received honoraria from MSD, Merck, Amgen, Hexal, Riemser, Helsinn, Voluntis, Pfizer, Pomme-med, PharmaMar, arttemoi, OnkoUpdate, Stemline, and Roche.

High body mass index (BMI) values are associated with higher survival among metastatic cancer patients treated with first- and second-line immune checkpoint inhibitors (ICIs), but the relationship was only present in males.

That is the conclusion of a new retrospective analysis presented during a poster session given at the annual meeting of the European Society for Medical Oncology. The study sought to better understand ICI outcomes. “These are complex new treatments and, because they harness the immune system, no two patients are likely to respond in the same way. BMI has previously been associated with improved survival in patients with advanced lung cancer treated with immunotherapy. However, the reasons behind this observation, and the implications for treatment are unknown, as is whether this observation is specific for patients with only certain types of cancers,” study author Dwight Owen, MD, said in an email.

He pointed out that the retrospective nature of the findings means that they have no immediate clinical implications. “The reason for the discrepancy in males remains unclear. Although our study included a relatively large number of patients, it is a heterogenous cohort and there may be confounding factors that we haven’t recognized, so these findings need to be replicated in larger cohorts,” said Dr. Owen, a medical oncologist with The Ohio State University Comprehensive Cancer Center, Columbus.

Asked if there is a potential biological explanation for a difference between males and females, Dr. Owen said that this is an area of intense research. One recent study examined whether androgen could help explain why men are more likely than women to both develop and have more aggressive nonreproductive cancers. They concluded that androgen receptor signaling may be leading to loss of effector and proliferative potential of CD8+ T cells in the tumor microenvironment. Once exhausted, these cells do not respond well to stimulation that can occur after ICI treatment.

On the opposite end of the spectrum, cancer cachexia is also a key subject of study. It is characterized by weight loss and is associated with worse clinical outcomes. A cachexia mouse model found that weight loss can lead to more clearance of immune checkpoint antibodies.

Still, much more work needs to be done. “For now, how BMI, obesity, and cachexia relate to other factors, for instance the microbiome and tumor immunogenicity, are still not fully understood,” Dr. Owen said.
 

The study data

The researchers analyzed data from 688 patients with metastatic cancer treated at their center between 2011 and 2017. 94% were White and 5% were Black. 41% were female and the mean age was 61.9 years. The mean BMI was 28.8 kg/m²; 40% of patients had melanoma, 23% had non–small cell lung cancer, 10% had renal cancer, and 27% had another form of cancer.

For every unit decrease in BMI, the researchers observed a 1.8% decrease in mortality (hazard ratio, 0.982; P = .007). Patients with a BMI of 40 or above had better survival than all other patients grouped by 5 BMI increments (that is, 35-40, 30-35, etc.). When separated by sex, males had a significant decrease in mortality for every increase in BMI unit (HR, 0.964; P = .004), but there was no significant difference among women (HR, 1.003; P = .706). The relationship in men held up after adjustment for Eastern Cooperative Oncology Group score, line of therapy, and cancer type (HR, 0.979; P = .0308). The researchers also looked at a separate cohort of 185 normal weight and 15 obese (BMI ≥ 40) NSCLC patients. Median survival was 27.5 months in the obese group and 9.1 months in the normal weight group (HR, 0.474; 95% CI, 0.232-0.969).

Dr. Owen has received research funding through his institution from Bristol-Myers Squibb, Genentech, Pfizer, Palobiofarma, and Onc.AI.

High body mass index (BMI) values are associated with higher survival among metastatic cancer patients treated with first- and second-line immune checkpoint inhibitors (ICIs), but the relationship was only present in males.

That is the conclusion of a new retrospective analysis presented during a poster session given at the annual meeting of the European Society for Medical Oncology. The study sought to better understand ICI outcomes. “These are complex new treatments and, because they harness the immune system, no two patients are likely to respond in the same way. BMI has previously been associated with improved survival in patients with advanced lung cancer treated with immunotherapy. However, the reasons behind this observation, and the implications for treatment are unknown, as is whether this observation is specific for patients with only certain types of cancers,” study author Dwight Owen, MD, said in an email.

He pointed out that the retrospective nature of the findings means that they have no immediate clinical implications. “The reason for the discrepancy in males remains unclear. Although our study included a relatively large number of patients, it is a heterogenous cohort and there may be confounding factors that we haven’t recognized, so these findings need to be replicated in larger cohorts,” said Dr. Owen, a medical oncologist with The Ohio State University Comprehensive Cancer Center, Columbus.

Asked if there is a potential biological explanation for a difference between males and females, Dr. Owen said that this is an area of intense research. One recent study examined whether androgen could help explain why men are more likely than women to both develop and have more aggressive nonreproductive cancers. They concluded that androgen receptor signaling may be leading to loss of effector and proliferative potential of CD8+ T cells in the tumor microenvironment. Once exhausted, these cells do not respond well to stimulation that can occur after ICI treatment.

On the opposite end of the spectrum, cancer cachexia is also a key subject of study. It is characterized by weight loss and is associated with worse clinical outcomes. A cachexia mouse model found that weight loss can lead to more clearance of immune checkpoint antibodies.

Still, much more work needs to be done. “For now, how BMI, obesity, and cachexia relate to other factors, for instance the microbiome and tumor immunogenicity, are still not fully understood,” Dr. Owen said.
 

The study data

The researchers analyzed data from 688 patients with metastatic cancer treated at their center between 2011 and 2017. 94% were White and 5% were Black. 41% were female and the mean age was 61.9 years. The mean BMI was 28.8 kg/m²; 40% of patients had melanoma, 23% had non–small cell lung cancer, 10% had renal cancer, and 27% had another form of cancer.

For every unit decrease in BMI, the researchers observed a 1.8% decrease in mortality (hazard ratio, 0.982; P = .007). Patients with a BMI of 40 or above had better survival than all other patients grouped by 5 BMI increments (that is, 35-40, 30-35, etc.). When separated by sex, males had a significant decrease in mortality for every increase in BMI unit (HR, 0.964; P = .004), but there was no significant difference among women (HR, 1.003; P = .706). The relationship in men held up after adjustment for Eastern Cooperative Oncology Group score, line of therapy, and cancer type (HR, 0.979; P = .0308). The researchers also looked at a separate cohort of 185 normal weight and 15 obese (BMI ≥ 40) NSCLC patients. Median survival was 27.5 months in the obese group and 9.1 months in the normal weight group (HR, 0.474; 95% CI, 0.232-0.969).

Dr. Owen has received research funding through his institution from Bristol-Myers Squibb, Genentech, Pfizer, Palobiofarma, and Onc.AI.

High body mass index (BMI) values are associated with higher survival among metastatic cancer patients treated with first- and second-line immune checkpoint inhibitors (ICIs), but the relationship was only present in males.

That is the conclusion of a new retrospective analysis presented during a poster session given at the annual meeting of the European Society for Medical Oncology. The study sought to better understand ICI outcomes. “These are complex new treatments and, because they harness the immune system, no two patients are likely to respond in the same way. BMI has previously been associated with improved survival in patients with advanced lung cancer treated with immunotherapy. However, the reasons behind this observation, and the implications for treatment are unknown, as is whether this observation is specific for patients with only certain types of cancers,” study author Dwight Owen, MD, said in an email.

He pointed out that the retrospective nature of the findings means that they have no immediate clinical implications. “The reason for the discrepancy in males remains unclear. Although our study included a relatively large number of patients, it is a heterogenous cohort and there may be confounding factors that we haven’t recognized, so these findings need to be replicated in larger cohorts,” said Dr. Owen, a medical oncologist with The Ohio State University Comprehensive Cancer Center, Columbus.

Asked if there is a potential biological explanation for a difference between males and females, Dr. Owen said that this is an area of intense research. One recent study examined whether androgen could help explain why men are more likely than women to both develop and have more aggressive nonreproductive cancers. They concluded that androgen receptor signaling may be leading to loss of effector and proliferative potential of CD8+ T cells in the tumor microenvironment. Once exhausted, these cells do not respond well to stimulation that can occur after ICI treatment.

On the opposite end of the spectrum, cancer cachexia is also a key subject of study. It is characterized by weight loss and is associated with worse clinical outcomes. A cachexia mouse model found that weight loss can lead to more clearance of immune checkpoint antibodies.

Still, much more work needs to be done. “For now, how BMI, obesity, and cachexia relate to other factors, for instance the microbiome and tumor immunogenicity, are still not fully understood,” Dr. Owen said.
 

The study data

The researchers analyzed data from 688 patients with metastatic cancer treated at their center between 2011 and 2017. 94% were White and 5% were Black. 41% were female and the mean age was 61.9 years. The mean BMI was 28.8 kg/m²; 40% of patients had melanoma, 23% had non–small cell lung cancer, 10% had renal cancer, and 27% had another form of cancer.

For every unit decrease in BMI, the researchers observed a 1.8% decrease in mortality (hazard ratio, 0.982; P = .007). Patients with a BMI of 40 or above had better survival than all other patients grouped by 5 BMI increments (that is, 35-40, 30-35, etc.). When separated by sex, males had a significant decrease in mortality for every increase in BMI unit (HR, 0.964; P = .004), but there was no significant difference among women (HR, 1.003; P = .706). The relationship in men held up after adjustment for Eastern Cooperative Oncology Group score, line of therapy, and cancer type (HR, 0.979; P = .0308). The researchers also looked at a separate cohort of 185 normal weight and 15 obese (BMI ≥ 40) NSCLC patients. Median survival was 27.5 months in the obese group and 9.1 months in the normal weight group (HR, 0.474; 95% CI, 0.232-0.969).

Dr. Owen has received research funding through his institution from Bristol-Myers Squibb, Genentech, Pfizer, Palobiofarma, and Onc.AI.

Postoperative radiotherapy is a mainstay in the treatment of uterine cancer, but the typical 5-week regimen can be time-consuming and expensive. A pilot study found that delivery of approximately the same dose over just 2.5 weeks, known as hypofractionation, had good short-term toxicity outcomes.

It isn’t yet clear if the protocol will be as effective as the standard course, and long-term side effects may still be an issue.

Nevertheless, shortening the duration of radiotherapy could have benefits, especially in advanced uterine cancer, where chemotherapy is employed against distant metastases. Following surgery, there is a risk of both local recurrence and distant metastasis, complicating the choice of initial treatment. “Chemo can be several months long and radiation is typically several weeks. Therefore a shortened radiation schedule may have potential benefits, especially if there is an opportunity for this to be delivered earlier without delaying or interrupting chemotherapy, for example,” said lead study author Eric Leung, MD, who is an associate professor of radiation oncology at the University of Toronto’s Sunnybrook Health Sciences Centre.

The research was published in JAMA Oncology.

Delivery of hypofractionation is tricky, according to Dr. Leung. “Gynecological cancer patients were treated with hypofractionation radiation to the pelvis which included the vagina, paravaginal tissues, and pelvic lymph nodes. With this relatively large pelvic volume with surrounding normal tissues, this requires a highly focused radiation treatment with advanced technology,” said Dr. Leung. The study protocol employed stereotactic technique to deliver 30 Gy in 5 fractions.

Hypofractionation could be beneficial in reduction of travel time and time spent in the hospital, as well as reducing financial burden and increasing quality of life. These benefits have taken on a larger role in the context of the COVID-19 pandemic.

Although the findings are encouraging, they are preliminary, according to Vonetta Williams, MD, PhD, who wrote an accompanying editorial. “I would caution that all they’ve done is presented preliminary toxicity data, so we don’t have any proof yet that it is equally effective [compared to standard protocol], and their study cannot answer that at any rate because it was not designed to answer that question,” said Dr. Williams in an interview. She also noted that long-term follow-up is needed to measure bowel dysfunction, sexual dysfunction, vaginal stenosis, and other side effects.

It is also uncertain whether hypofractionated doses are actually equivalent to the standard dose. “We know that they’re roughly equivalent, but that is very much a question if they are equivalent in terms of efficacy. I don’t know that I would be confident that they are. That’s probably what would give most radiation oncologists pause, because we don’t have any data to say that it is [equivalent]. Although it would be nice to shorten treatment, and I think it would certainly be better for patients, I want to caution that we want to do so once we know what the toxicity and the outcomes really are,” Dr. Williams said.
 

The study’s findings

The researchers enrolled 61 patients with a median age of 66 years. Thirty-nine had endometrioid adenocarcinoma, 15 serous or clear cell, 3 carcinosarcoma, and 4 had dedifferentiated disease. Sixteen patients underwent sequential chemotherapy, and 9 underwent additional vault brachytherapy. Over a median follow-up of 9 months, 54% had a worst gastrointestinal side effect of grade 1, while 13% had a worst side effect of grade 2. Among worst genitourinary side effects, 41% had grade 1 and 3% had grade 2. One patient had acute grade 3 diarrhea at fraction 5, but this resolved at follow-up. One patient had diarrhea scores that were both clinically and statistically significantly worse than baseline at fraction 5, and this improved at follow-up.

Patient-reported quality of life outcomes were generally good. Of all measures, only diarrhea was clinically and statistically worse by fraction 5, and improvement was seen at 6 weeks and 3 months. Global health status was consistent throughout treatment and follow-up. There was no change in sexual and vaginal symptoms.

Postoperative radiotherapy is a mainstay in the treatment of uterine cancer, but the typical 5-week regimen can be time-consuming and expensive. A pilot study found that delivery of approximately the same dose over just 2.5 weeks, known as hypofractionation, had good short-term toxicity outcomes.

It isn’t yet clear if the protocol will be as effective as the standard course, and long-term side effects may still be an issue.

Nevertheless, shortening the duration of radiotherapy could have benefits, especially in advanced uterine cancer, where chemotherapy is employed against distant metastases. Following surgery, there is a risk of both local recurrence and distant metastasis, complicating the choice of initial treatment. “Chemo can be several months long and radiation is typically several weeks. Therefore a shortened radiation schedule may have potential benefits, especially if there is an opportunity for this to be delivered earlier without delaying or interrupting chemotherapy, for example,” said lead study author Eric Leung, MD, who is an associate professor of radiation oncology at the University of Toronto’s Sunnybrook Health Sciences Centre.

The research was published in JAMA Oncology.

Delivery of hypofractionation is tricky, according to Dr. Leung. “Gynecological cancer patients were treated with hypofractionation radiation to the pelvis which included the vagina, paravaginal tissues, and pelvic lymph nodes. With this relatively large pelvic volume with surrounding normal tissues, this requires a highly focused radiation treatment with advanced technology,” said Dr. Leung. The study protocol employed stereotactic technique to deliver 30 Gy in 5 fractions.

Hypofractionation could be beneficial in reduction of travel time and time spent in the hospital, as well as reducing financial burden and increasing quality of life. These benefits have taken on a larger role in the context of the COVID-19 pandemic.

Although the findings are encouraging, they are preliminary, according to Vonetta Williams, MD, PhD, who wrote an accompanying editorial. “I would caution that all they’ve done is presented preliminary toxicity data, so we don’t have any proof yet that it is equally effective [compared to standard protocol], and their study cannot answer that at any rate because it was not designed to answer that question,” said Dr. Williams in an interview. She also noted that long-term follow-up is needed to measure bowel dysfunction, sexual dysfunction, vaginal stenosis, and other side effects.

It is also uncertain whether hypofractionated doses are actually equivalent to the standard dose. “We know that they’re roughly equivalent, but that is very much a question if they are equivalent in terms of efficacy. I don’t know that I would be confident that they are. That’s probably what would give most radiation oncologists pause, because we don’t have any data to say that it is [equivalent]. Although it would be nice to shorten treatment, and I think it would certainly be better for patients, I want to caution that we want to do so once we know what the toxicity and the outcomes really are,” Dr. Williams said.
 

The study’s findings

The researchers enrolled 61 patients with a median age of 66 years. Thirty-nine had endometrioid adenocarcinoma, 15 serous or clear cell, 3 carcinosarcoma, and 4 had dedifferentiated disease. Sixteen patients underwent sequential chemotherapy, and 9 underwent additional vault brachytherapy. Over a median follow-up of 9 months, 54% had a worst gastrointestinal side effect of grade 1, while 13% had a worst side effect of grade 2. Among worst genitourinary side effects, 41% had grade 1 and 3% had grade 2. One patient had acute grade 3 diarrhea at fraction 5, but this resolved at follow-up. One patient had diarrhea scores that were both clinically and statistically significantly worse than baseline at fraction 5, and this improved at follow-up.

Patient-reported quality of life outcomes were generally good. Of all measures, only diarrhea was clinically and statistically worse by fraction 5, and improvement was seen at 6 weeks and 3 months. Global health status was consistent throughout treatment and follow-up. There was no change in sexual and vaginal symptoms.

Postoperative radiotherapy is a mainstay in the treatment of uterine cancer, but the typical 5-week regimen can be time-consuming and expensive. A pilot study found that delivery of approximately the same dose over just 2.5 weeks, known as hypofractionation, had good short-term toxicity outcomes.

It isn’t yet clear if the protocol will be as effective as the standard course, and long-term side effects may still be an issue.

Nevertheless, shortening the duration of radiotherapy could have benefits, especially in advanced uterine cancer, where chemotherapy is employed against distant metastases. Following surgery, there is a risk of both local recurrence and distant metastasis, complicating the choice of initial treatment. “Chemo can be several months long and radiation is typically several weeks. Therefore a shortened radiation schedule may have potential benefits, especially if there is an opportunity for this to be delivered earlier without delaying or interrupting chemotherapy, for example,” said lead study author Eric Leung, MD, who is an associate professor of radiation oncology at the University of Toronto’s Sunnybrook Health Sciences Centre.

The research was published in JAMA Oncology.

Delivery of hypofractionation is tricky, according to Dr. Leung. “Gynecological cancer patients were treated with hypofractionation radiation to the pelvis which included the vagina, paravaginal tissues, and pelvic lymph nodes. With this relatively large pelvic volume with surrounding normal tissues, this requires a highly focused radiation treatment with advanced technology,” said Dr. Leung. The study protocol employed stereotactic technique to deliver 30 Gy in 5 fractions.

Hypofractionation could be beneficial in reduction of travel time and time spent in the hospital, as well as reducing financial burden and increasing quality of life. These benefits have taken on a larger role in the context of the COVID-19 pandemic.

Although the findings are encouraging, they are preliminary, according to Vonetta Williams, MD, PhD, who wrote an accompanying editorial. “I would caution that all they’ve done is presented preliminary toxicity data, so we don’t have any proof yet that it is equally effective [compared to standard protocol], and their study cannot answer that at any rate because it was not designed to answer that question,” said Dr. Williams in an interview. She also noted that long-term follow-up is needed to measure bowel dysfunction, sexual dysfunction, vaginal stenosis, and other side effects.

It is also uncertain whether hypofractionated doses are actually equivalent to the standard dose. “We know that they’re roughly equivalent, but that is very much a question if they are equivalent in terms of efficacy. I don’t know that I would be confident that they are. That’s probably what would give most radiation oncologists pause, because we don’t have any data to say that it is [equivalent]. Although it would be nice to shorten treatment, and I think it would certainly be better for patients, I want to caution that we want to do so once we know what the toxicity and the outcomes really are,” Dr. Williams said.
 

The study’s findings

The researchers enrolled 61 patients with a median age of 66 years. Thirty-nine had endometrioid adenocarcinoma, 15 serous or clear cell, 3 carcinosarcoma, and 4 had dedifferentiated disease. Sixteen patients underwent sequential chemotherapy, and 9 underwent additional vault brachytherapy. Over a median follow-up of 9 months, 54% had a worst gastrointestinal side effect of grade 1, while 13% had a worst side effect of grade 2. Among worst genitourinary side effects, 41% had grade 1 and 3% had grade 2. One patient had acute grade 3 diarrhea at fraction 5, but this resolved at follow-up. One patient had diarrhea scores that were both clinically and statistically significantly worse than baseline at fraction 5, and this improved at follow-up.

Patient-reported quality of life outcomes were generally good. Of all measures, only diarrhea was clinically and statistically worse by fraction 5, and improvement was seen at 6 weeks and 3 months. Global health status was consistent throughout treatment and follow-up. There was no change in sexual and vaginal symptoms.