Federal Practitioner

Introduction

Hematologists and oncologists (HO) face mortality daily. “Death Cafe” (DC) is a safe space set aside for open dialogue about death and dying. Despite origins outside the healthcare setting, DC has been used as a framework to help health care students and workers process death and dying. We aim to assess if DC sessions are perceived to have value by HO trainees and faculty.

Methods

HO fellows from Baylor College of Medicine (BCM) and HO Faculty from BCM, mostly those at the Houston Michael E. DeBakey Veterans Affairs Hospital (VA), were offered the opportunity to participate in the DC sessions. Our VA Cancer Center Chaplain was present for all sessions and helped facilitate the conversation. HO fellows who were invited to a DC and attended were emailed a survey questionnaire after the activity via survey monkey. The sessions and the surveys were not compulsory. Their participation in the session and completion of surveys implied informed consent. After IRB approval, we reviewed responses for the study groups. Sessions were held in person pre-pandemic in 2019 and virtually during the COVID-19 pandemic in 2022.

Results

Five fellows responded to our survey in 2019 and 7 in 2022 for a total of 12 respondents. 100% of respondents had been emotionally affected by a patient’s death. 82% had been emotionally affected by a patient’s death during the preceding 3 months. 90% had previously discussed their emotions relating to patient death with others. 83% would participate in DC again and 92% would recommend DC to a colleague. One 2019 participant commented that they thought attendings needed the session more than fellows, 2 2022 participants commented that they believe the meeting would be better in person. One 2022 participant commented they thought DC “is a good platform to vent emotions, identify self-destructive thoughts and better coping mechanisms.”

Conclusions 

DC provides a framework for HC to share personal and professional experience with mortality from a human perspective and support each other. This approach may be useful for HO departments or fellowships to offer as an opportunity to process end-of-life matters experienced as providers and finite humans.

Introduction

Hematologists and oncologists (HO) face mortality daily. “Death Cafe” (DC) is a safe space set aside for open dialogue about death and dying. Despite origins outside the healthcare setting, DC has been used as a framework to help health care students and workers process death and dying. We aim to assess if DC sessions are perceived to have value by HO trainees and faculty.

Methods

HO fellows from Baylor College of Medicine (BCM) and HO Faculty from BCM, mostly those at the Houston Michael E. DeBakey Veterans Affairs Hospital (VA), were offered the opportunity to participate in the DC sessions. Our VA Cancer Center Chaplain was present for all sessions and helped facilitate the conversation. HO fellows who were invited to a DC and attended were emailed a survey questionnaire after the activity via survey monkey. The sessions and the surveys were not compulsory. Their participation in the session and completion of surveys implied informed consent. After IRB approval, we reviewed responses for the study groups. Sessions were held in person pre-pandemic in 2019 and virtually during the COVID-19 pandemic in 2022.

Results

Five fellows responded to our survey in 2019 and 7 in 2022 for a total of 12 respondents. 100% of respondents had been emotionally affected by a patient’s death. 82% had been emotionally affected by a patient’s death during the preceding 3 months. 90% had previously discussed their emotions relating to patient death with others. 83% would participate in DC again and 92% would recommend DC to a colleague. One 2019 participant commented that they thought attendings needed the session more than fellows, 2 2022 participants commented that they believe the meeting would be better in person. One 2022 participant commented they thought DC “is a good platform to vent emotions, identify self-destructive thoughts and better coping mechanisms.”

Conclusions 

DC provides a framework for HC to share personal and professional experience with mortality from a human perspective and support each other. This approach may be useful for HO departments or fellowships to offer as an opportunity to process end-of-life matters experienced as providers and finite humans.

Introduction

Hematologists and oncologists (HO) face mortality daily. “Death Cafe” (DC) is a safe space set aside for open dialogue about death and dying. Despite origins outside the healthcare setting, DC has been used as a framework to help health care students and workers process death and dying. We aim to assess if DC sessions are perceived to have value by HO trainees and faculty.

Methods

HO fellows from Baylor College of Medicine (BCM) and HO Faculty from BCM, mostly those at the Houston Michael E. DeBakey Veterans Affairs Hospital (VA), were offered the opportunity to participate in the DC sessions. Our VA Cancer Center Chaplain was present for all sessions and helped facilitate the conversation. HO fellows who were invited to a DC and attended were emailed a survey questionnaire after the activity via survey monkey. The sessions and the surveys were not compulsory. Their participation in the session and completion of surveys implied informed consent. After IRB approval, we reviewed responses for the study groups. Sessions were held in person pre-pandemic in 2019 and virtually during the COVID-19 pandemic in 2022.

Results

Five fellows responded to our survey in 2019 and 7 in 2022 for a total of 12 respondents. 100% of respondents had been emotionally affected by a patient’s death. 82% had been emotionally affected by a patient’s death during the preceding 3 months. 90% had previously discussed their emotions relating to patient death with others. 83% would participate in DC again and 92% would recommend DC to a colleague. One 2019 participant commented that they thought attendings needed the session more than fellows, 2 2022 participants commented that they believe the meeting would be better in person. One 2022 participant commented they thought DC “is a good platform to vent emotions, identify self-destructive thoughts and better coping mechanisms.”

Conclusions 

DC provides a framework for HC to share personal and professional experience with mortality from a human perspective and support each other. This approach may be useful for HO departments or fellowships to offer as an opportunity to process end-of-life matters experienced as providers and finite humans.

U.S. veterans of the post-9/11 wars who suffered a traumatic brain injury (TBI) are at increased risk of developing cardiovascular disease (CVD). More severe TBI is associated with higher risk of CVD, new research shows.

Given the relatively young age of post-9/11–era veterans with TBI, there may be an increased burden of heart disease in the future as these veterans age and develop traditional risk factors for CVD, the investigators, led by Ian J. Stewart, MD, with Uniformed Services University, Bethesda, Md., wrote.

The study was published online  in JAMA Neurology.
 

Novel data

Since Sept. 11, 2001, 4.5 million people have served in the U.S. military, with their time in service defined by the long-running wars in Iraq and Afghanistan. Estimates suggest that up to 20% of post-9/11 veterans sustained a TBI.

While some evidence suggests that TBI increases the risk of CVD, prior reports have focused mainly on cerebrovascular outcomes. Until now, the potential association of TBI with CVD has not been comprehensively examined in post-9/11–era veterans.

The retrospective cohort study included 1,559,928 predominantly male post-9/11 veterans, including 301,169 (19.3%) with a history of TBI and 1,258,759 (81%) with no TBI history.

In fully adjusted models, compared with veterans with no TBI history, a history of mild, moderate/severe, or penetrating TBI was associated with increased risk of developing the composite CVD endpoint (coronary artery disease, stroke, peripheral artery disease, and CVD death).

Unrecognized CVD risk factor?

Reached for comment, Shaheen E. Lakhan, MD, PhD, a neurologist and researcher from Boston who wasn’t involved in the study, said the effects of TBI on heart health are “very underreported, and most clinicians would not make the link.”

“When the brain suffers a traumatic injury, it activates a cascade of neuro-inflammation that goes haywire in an attempt to protect further brain damage. Oftentimes, these inflammatory by-products leak into the body, especially in trauma, when the barriers are broken between brain and body, and can cause systemic body inflammation, which is well associated with heart disease,” Dr. Lakhan said.

In addition, Dr. Lakhan said, “TBI itself localized to just the brain can negatively affect good health habits, leading to worsening heart health, too.”

“Research like this brings light where not much exists and underscores the importance of protecting our brains from physical trauma,” he said.

The study was supported by the assistant secretary of defense for health affairs, endorsed by the Department of Defense through the Psychological Health/Traumatic Brain Injury Research Program Long-Term Impact of Military-Relevant Brain Injury Consortium, and by the U.S. Department of Veterans Affairs. Dr. Stewart and Dr. Lakhan have disclosed no relevant financial relationships.

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

U.S. veterans of the post-9/11 wars who suffered a traumatic brain injury (TBI) are at increased risk of developing cardiovascular disease (CVD). More severe TBI is associated with higher risk of CVD, new research shows.

Given the relatively young age of post-9/11–era veterans with TBI, there may be an increased burden of heart disease in the future as these veterans age and develop traditional risk factors for CVD, the investigators, led by Ian J. Stewart, MD, with Uniformed Services University, Bethesda, Md., wrote.

The study was published online  in JAMA Neurology.
 

Novel data

Since Sept. 11, 2001, 4.5 million people have served in the U.S. military, with their time in service defined by the long-running wars in Iraq and Afghanistan. Estimates suggest that up to 20% of post-9/11 veterans sustained a TBI.

While some evidence suggests that TBI increases the risk of CVD, prior reports have focused mainly on cerebrovascular outcomes. Until now, the potential association of TBI with CVD has not been comprehensively examined in post-9/11–era veterans.

The retrospective cohort study included 1,559,928 predominantly male post-9/11 veterans, including 301,169 (19.3%) with a history of TBI and 1,258,759 (81%) with no TBI history.

In fully adjusted models, compared with veterans with no TBI history, a history of mild, moderate/severe, or penetrating TBI was associated with increased risk of developing the composite CVD endpoint (coronary artery disease, stroke, peripheral artery disease, and CVD death).

Unrecognized CVD risk factor?

Reached for comment, Shaheen E. Lakhan, MD, PhD, a neurologist and researcher from Boston who wasn’t involved in the study, said the effects of TBI on heart health are “very underreported, and most clinicians would not make the link.”

“When the brain suffers a traumatic injury, it activates a cascade of neuro-inflammation that goes haywire in an attempt to protect further brain damage. Oftentimes, these inflammatory by-products leak into the body, especially in trauma, when the barriers are broken between brain and body, and can cause systemic body inflammation, which is well associated with heart disease,” Dr. Lakhan said.

In addition, Dr. Lakhan said, “TBI itself localized to just the brain can negatively affect good health habits, leading to worsening heart health, too.”

“Research like this brings light where not much exists and underscores the importance of protecting our brains from physical trauma,” he said.

The study was supported by the assistant secretary of defense for health affairs, endorsed by the Department of Defense through the Psychological Health/Traumatic Brain Injury Research Program Long-Term Impact of Military-Relevant Brain Injury Consortium, and by the U.S. Department of Veterans Affairs. Dr. Stewart and Dr. Lakhan have disclosed no relevant financial relationships.

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

U.S. veterans of the post-9/11 wars who suffered a traumatic brain injury (TBI) are at increased risk of developing cardiovascular disease (CVD). More severe TBI is associated with higher risk of CVD, new research shows.

Given the relatively young age of post-9/11–era veterans with TBI, there may be an increased burden of heart disease in the future as these veterans age and develop traditional risk factors for CVD, the investigators, led by Ian J. Stewart, MD, with Uniformed Services University, Bethesda, Md., wrote.

The study was published online  in JAMA Neurology.
 

Novel data

Since Sept. 11, 2001, 4.5 million people have served in the U.S. military, with their time in service defined by the long-running wars in Iraq and Afghanistan. Estimates suggest that up to 20% of post-9/11 veterans sustained a TBI.

While some evidence suggests that TBI increases the risk of CVD, prior reports have focused mainly on cerebrovascular outcomes. Until now, the potential association of TBI with CVD has not been comprehensively examined in post-9/11–era veterans.

The retrospective cohort study included 1,559,928 predominantly male post-9/11 veterans, including 301,169 (19.3%) with a history of TBI and 1,258,759 (81%) with no TBI history.

In fully adjusted models, compared with veterans with no TBI history, a history of mild, moderate/severe, or penetrating TBI was associated with increased risk of developing the composite CVD endpoint (coronary artery disease, stroke, peripheral artery disease, and CVD death).

Unrecognized CVD risk factor?

Reached for comment, Shaheen E. Lakhan, MD, PhD, a neurologist and researcher from Boston who wasn’t involved in the study, said the effects of TBI on heart health are “very underreported, and most clinicians would not make the link.”

“When the brain suffers a traumatic injury, it activates a cascade of neuro-inflammation that goes haywire in an attempt to protect further brain damage. Oftentimes, these inflammatory by-products leak into the body, especially in trauma, when the barriers are broken between brain and body, and can cause systemic body inflammation, which is well associated with heart disease,” Dr. Lakhan said.

In addition, Dr. Lakhan said, “TBI itself localized to just the brain can negatively affect good health habits, leading to worsening heart health, too.”

“Research like this brings light where not much exists and underscores the importance of protecting our brains from physical trauma,” he said.

The study was supported by the assistant secretary of defense for health affairs, endorsed by the Department of Defense through the Psychological Health/Traumatic Brain Injury Research Program Long-Term Impact of Military-Relevant Brain Injury Consortium, and by the U.S. Department of Veterans Affairs. Dr. Stewart and Dr. Lakhan have disclosed no relevant financial relationships.

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

PARIS – Adding pembrolizumab (Keytruda) to chemoradiotherapy did not significantly improve event-free survival, compared with CRT plus placebo as first-line therapy for patients with locally advanced head and neck squamous cell cancers (HNSCC), reported investigators of the KEYNOTE-412 trial.

Among 804 patients with newly diagnosed, pathologically proven, unresected locally advanced head and neck squamous cell carcinomas who were followed for a median of 47.7 months, the event-free survival (EFS) rate with the pembrolizumab/CRT combination followed by maintenance pembrolizumab was 63.2%, compared with 56.2% for CRT plus placebo. This translated into a nonsignificant hazard ratio of 0.83, said Jean-Pascal Machiels, MD, PhD, at the annual meeting of the European Society for Medical Oncology.

Despite the trial failing to meet its primary endpoint, Dr. Machiels expressed optimism about the results.

“Pembrolizumab with chemoradiation was associated with a favorable trend toward improved event-free survival versus placebo plus chemoradiation in patients with locally advanced head and neck cancer,” he said.

He noted that the 2-year EFS rate was 63% with pembrolizumab, compared with 56% with placebo.

The data also support the hypothesis that programmed death–ligand 1 (PD-L1) expression as measured by a combined positive score (CPS) could be a predictive biomarker for identifying those patients most likely to respond to the immune checkpoint inhibitor, he added.

KEYNOTE-412 details

The rationale for combining the checkpoint inhibitors pembrolizumab with chemoradiotherapy comes from the KEYNOTE-048 trial results of which showed a survival improvement for the use of pembrolizumab plus a platinum-containing regimen as a first-line therapy for recurrent or metastatic HNSCC, as well as pembrolizumab monotherapy for patients with PD-L1 CPS of 1 or greater.

In the current study, Dr. Machiels and colleagues studied whether adding pembrolizumab to CRT could benefit patients with treatment-naive unresected, locally advanced HNSCC.

Eligible patients included those with stage T3 or T4, N0-N3 or any N2a-3 (T1-T4) cancers of the larynx, hypopharynx, or oral cavity, and either p16-negative oropharynx cancers or T4 or N3 p16-positive oropharynx cancer. Patients were required to be eligible for high-dose cisplatin-based CRT.

A total of 804 patients were randomized, 402 in each arm, to receive either pembrolizumab 200 mg intravenously every 3 weeks for 3 cycles plus CRT followed by maintenance pembrolizumab for 14 cycles, or to placebo plus CRT followed by placebo maintenance.

As noted before, there was no significant difference between the study arms for the primary endpoint of EFS. The 24-month EFS rate was 63.2% for the pembrolizumab group, compared with 56.2% for controls. The respective 6-month EFS rates were 57.4% versus 52.1%.­

In a post hoc analysis, both EFS and overall survival were numerically with pembrolizumab among patients with PD-L1 CPS of 20 or greater. The respective 2- and 3-year EFS rates were 71.2% versus 62.6%, and 66.7% versus 57.2%.

The 24-months overall survival rates were 83.3% with pembrolizumab and 79.9% with placebo, and 36-month rates were 79.1% and 73%, respectively.

Neither EFS rates nor OS rates among patients in this subgroup differed significantly; however, there were no new safety signals with the combination, Dr. Machiels said. The incidence of grade 3 or greater adverse events was 92.2% in the pembrolizumab arm versus 88.4% in the placebo arm. Four patients in the pembrolizumab arm and six in the control arm died from treatment-related causes.
 

Benefit still to be proven

In a media briefing held prior to his presentation, Dr. Machiels was asked how he could justify his conclusions about a benefit for adding pembrolizumab given that there was no difference between the treatment groups for the primary endpoint.

He said that when the investigators designed the trial 7 years ago, the CPS score for PD-L1 expression had not yet been developed, and that if it had been they might have designed the trial to explore the effect of the pembrolizumab chemoradiation combination according to CPS subgroups.

He also pointed to the numerically superior 2-year EFS and overall rates.

In the presidential symposium, James Larkin, MD, PhD, an invited discussant from the Royal Marsden Hospital, London, said that chemotherapy and anti–PD-1 therapies are known to offer benefit in advanced cancers despite the trial’s failure.

“There is a signal, particularly as we’ve seen in the high PD-L1 group,” he said, noting that the signal was consistent with that seen in the JAVELIN 100 study, which was also a negative trial. He cautioned against relying too heavily on the comparison, however, as JAVELIN 100 was conducted with avelumab, a PD-L1 inhibitor, whereas pembrolizumab is a PD-1 inhibitor.

“Could there be an issue here with treatment schedule? An example and a comparison might be the PACIFIC study in non–small cell lung cancer, which is a positive trial, where actually the checkpoint inhibit with durvalumab was given immediately after the chemoradiotherapy, leading to benefit, rather than being concurrent,” he said.

Dr. Larkin also questioned whether, as codiscussant Sherene Loi, MD, PhD, from the Peter MacCallum Cancer Center, Melbourne, suggested radiotherapy to lymph nodes might alter the immune response to checkpoint inhibitors.

“Clearly radiotherapy is the central component of treatment in this setting, so it would be quite difficult to scale too much on that, but the question is: ‘Could it be modified?’ For example, just to irradiate the primary tumor and involved lymph nodes and potentially spare noninvolved lymph nodes,” he said.

The KEYNOTE-412 study was funded by Merck Sharp & Dohme. Dr. Machiels reported uncompensated consulting to the company. Dr. Larkin reported consulting for and receiving honoraria from Merck and others. Dr. Loi reported uncompensated advisory board activity for Merck and others.

PARIS – Adding pembrolizumab (Keytruda) to chemoradiotherapy did not significantly improve event-free survival, compared with CRT plus placebo as first-line therapy for patients with locally advanced head and neck squamous cell cancers (HNSCC), reported investigators of the KEYNOTE-412 trial.

Among 804 patients with newly diagnosed, pathologically proven, unresected locally advanced head and neck squamous cell carcinomas who were followed for a median of 47.7 months, the event-free survival (EFS) rate with the pembrolizumab/CRT combination followed by maintenance pembrolizumab was 63.2%, compared with 56.2% for CRT plus placebo. This translated into a nonsignificant hazard ratio of 0.83, said Jean-Pascal Machiels, MD, PhD, at the annual meeting of the European Society for Medical Oncology.

Despite the trial failing to meet its primary endpoint, Dr. Machiels expressed optimism about the results.

“Pembrolizumab with chemoradiation was associated with a favorable trend toward improved event-free survival versus placebo plus chemoradiation in patients with locally advanced head and neck cancer,” he said.

He noted that the 2-year EFS rate was 63% with pembrolizumab, compared with 56% with placebo.

The data also support the hypothesis that programmed death–ligand 1 (PD-L1) expression as measured by a combined positive score (CPS) could be a predictive biomarker for identifying those patients most likely to respond to the immune checkpoint inhibitor, he added.

KEYNOTE-412 details

The rationale for combining the checkpoint inhibitors pembrolizumab with chemoradiotherapy comes from the KEYNOTE-048 trial results of which showed a survival improvement for the use of pembrolizumab plus a platinum-containing regimen as a first-line therapy for recurrent or metastatic HNSCC, as well as pembrolizumab monotherapy for patients with PD-L1 CPS of 1 or greater.

In the current study, Dr. Machiels and colleagues studied whether adding pembrolizumab to CRT could benefit patients with treatment-naive unresected, locally advanced HNSCC.

Eligible patients included those with stage T3 or T4, N0-N3 or any N2a-3 (T1-T4) cancers of the larynx, hypopharynx, or oral cavity, and either p16-negative oropharynx cancers or T4 or N3 p16-positive oropharynx cancer. Patients were required to be eligible for high-dose cisplatin-based CRT.

A total of 804 patients were randomized, 402 in each arm, to receive either pembrolizumab 200 mg intravenously every 3 weeks for 3 cycles plus CRT followed by maintenance pembrolizumab for 14 cycles, or to placebo plus CRT followed by placebo maintenance.

As noted before, there was no significant difference between the study arms for the primary endpoint of EFS. The 24-month EFS rate was 63.2% for the pembrolizumab group, compared with 56.2% for controls. The respective 6-month EFS rates were 57.4% versus 52.1%.­

In a post hoc analysis, both EFS and overall survival were numerically with pembrolizumab among patients with PD-L1 CPS of 20 or greater. The respective 2- and 3-year EFS rates were 71.2% versus 62.6%, and 66.7% versus 57.2%.

The 24-months overall survival rates were 83.3% with pembrolizumab and 79.9% with placebo, and 36-month rates were 79.1% and 73%, respectively.

Neither EFS rates nor OS rates among patients in this subgroup differed significantly; however, there were no new safety signals with the combination, Dr. Machiels said. The incidence of grade 3 or greater adverse events was 92.2% in the pembrolizumab arm versus 88.4% in the placebo arm. Four patients in the pembrolizumab arm and six in the control arm died from treatment-related causes.
 

Benefit still to be proven

In a media briefing held prior to his presentation, Dr. Machiels was asked how he could justify his conclusions about a benefit for adding pembrolizumab given that there was no difference between the treatment groups for the primary endpoint.

He said that when the investigators designed the trial 7 years ago, the CPS score for PD-L1 expression had not yet been developed, and that if it had been they might have designed the trial to explore the effect of the pembrolizumab chemoradiation combination according to CPS subgroups.

He also pointed to the numerically superior 2-year EFS and overall rates.

In the presidential symposium, James Larkin, MD, PhD, an invited discussant from the Royal Marsden Hospital, London, said that chemotherapy and anti–PD-1 therapies are known to offer benefit in advanced cancers despite the trial’s failure.

“There is a signal, particularly as we’ve seen in the high PD-L1 group,” he said, noting that the signal was consistent with that seen in the JAVELIN 100 study, which was also a negative trial. He cautioned against relying too heavily on the comparison, however, as JAVELIN 100 was conducted with avelumab, a PD-L1 inhibitor, whereas pembrolizumab is a PD-1 inhibitor.

“Could there be an issue here with treatment schedule? An example and a comparison might be the PACIFIC study in non–small cell lung cancer, which is a positive trial, where actually the checkpoint inhibit with durvalumab was given immediately after the chemoradiotherapy, leading to benefit, rather than being concurrent,” he said.

Dr. Larkin also questioned whether, as codiscussant Sherene Loi, MD, PhD, from the Peter MacCallum Cancer Center, Melbourne, suggested radiotherapy to lymph nodes might alter the immune response to checkpoint inhibitors.

“Clearly radiotherapy is the central component of treatment in this setting, so it would be quite difficult to scale too much on that, but the question is: ‘Could it be modified?’ For example, just to irradiate the primary tumor and involved lymph nodes and potentially spare noninvolved lymph nodes,” he said.

The KEYNOTE-412 study was funded by Merck Sharp & Dohme. Dr. Machiels reported uncompensated consulting to the company. Dr. Larkin reported consulting for and receiving honoraria from Merck and others. Dr. Loi reported uncompensated advisory board activity for Merck and others.

PARIS – Adding pembrolizumab (Keytruda) to chemoradiotherapy did not significantly improve event-free survival, compared with CRT plus placebo as first-line therapy for patients with locally advanced head and neck squamous cell cancers (HNSCC), reported investigators of the KEYNOTE-412 trial.

Among 804 patients with newly diagnosed, pathologically proven, unresected locally advanced head and neck squamous cell carcinomas who were followed for a median of 47.7 months, the event-free survival (EFS) rate with the pembrolizumab/CRT combination followed by maintenance pembrolizumab was 63.2%, compared with 56.2% for CRT plus placebo. This translated into a nonsignificant hazard ratio of 0.83, said Jean-Pascal Machiels, MD, PhD, at the annual meeting of the European Society for Medical Oncology.

Despite the trial failing to meet its primary endpoint, Dr. Machiels expressed optimism about the results.

“Pembrolizumab with chemoradiation was associated with a favorable trend toward improved event-free survival versus placebo plus chemoradiation in patients with locally advanced head and neck cancer,” he said.

He noted that the 2-year EFS rate was 63% with pembrolizumab, compared with 56% with placebo.

The data also support the hypothesis that programmed death–ligand 1 (PD-L1) expression as measured by a combined positive score (CPS) could be a predictive biomarker for identifying those patients most likely to respond to the immune checkpoint inhibitor, he added.

KEYNOTE-412 details

The rationale for combining the checkpoint inhibitors pembrolizumab with chemoradiotherapy comes from the KEYNOTE-048 trial results of which showed a survival improvement for the use of pembrolizumab plus a platinum-containing regimen as a first-line therapy for recurrent or metastatic HNSCC, as well as pembrolizumab monotherapy for patients with PD-L1 CPS of 1 or greater.

In the current study, Dr. Machiels and colleagues studied whether adding pembrolizumab to CRT could benefit patients with treatment-naive unresected, locally advanced HNSCC.

Eligible patients included those with stage T3 or T4, N0-N3 or any N2a-3 (T1-T4) cancers of the larynx, hypopharynx, or oral cavity, and either p16-negative oropharynx cancers or T4 or N3 p16-positive oropharynx cancer. Patients were required to be eligible for high-dose cisplatin-based CRT.

A total of 804 patients were randomized, 402 in each arm, to receive either pembrolizumab 200 mg intravenously every 3 weeks for 3 cycles plus CRT followed by maintenance pembrolizumab for 14 cycles, or to placebo plus CRT followed by placebo maintenance.

As noted before, there was no significant difference between the study arms for the primary endpoint of EFS. The 24-month EFS rate was 63.2% for the pembrolizumab group, compared with 56.2% for controls. The respective 6-month EFS rates were 57.4% versus 52.1%.­

In a post hoc analysis, both EFS and overall survival were numerically with pembrolizumab among patients with PD-L1 CPS of 20 or greater. The respective 2- and 3-year EFS rates were 71.2% versus 62.6%, and 66.7% versus 57.2%.

The 24-months overall survival rates were 83.3% with pembrolizumab and 79.9% with placebo, and 36-month rates were 79.1% and 73%, respectively.

Neither EFS rates nor OS rates among patients in this subgroup differed significantly; however, there were no new safety signals with the combination, Dr. Machiels said. The incidence of grade 3 or greater adverse events was 92.2% in the pembrolizumab arm versus 88.4% in the placebo arm. Four patients in the pembrolizumab arm and six in the control arm died from treatment-related causes.
 

Benefit still to be proven

In a media briefing held prior to his presentation, Dr. Machiels was asked how he could justify his conclusions about a benefit for adding pembrolizumab given that there was no difference between the treatment groups for the primary endpoint.

He said that when the investigators designed the trial 7 years ago, the CPS score for PD-L1 expression had not yet been developed, and that if it had been they might have designed the trial to explore the effect of the pembrolizumab chemoradiation combination according to CPS subgroups.

He also pointed to the numerically superior 2-year EFS and overall rates.

In the presidential symposium, James Larkin, MD, PhD, an invited discussant from the Royal Marsden Hospital, London, said that chemotherapy and anti–PD-1 therapies are known to offer benefit in advanced cancers despite the trial’s failure.

“There is a signal, particularly as we’ve seen in the high PD-L1 group,” he said, noting that the signal was consistent with that seen in the JAVELIN 100 study, which was also a negative trial. He cautioned against relying too heavily on the comparison, however, as JAVELIN 100 was conducted with avelumab, a PD-L1 inhibitor, whereas pembrolizumab is a PD-1 inhibitor.

“Could there be an issue here with treatment schedule? An example and a comparison might be the PACIFIC study in non–small cell lung cancer, which is a positive trial, where actually the checkpoint inhibit with durvalumab was given immediately after the chemoradiotherapy, leading to benefit, rather than being concurrent,” he said.

Dr. Larkin also questioned whether, as codiscussant Sherene Loi, MD, PhD, from the Peter MacCallum Cancer Center, Melbourne, suggested radiotherapy to lymph nodes might alter the immune response to checkpoint inhibitors.

“Clearly radiotherapy is the central component of treatment in this setting, so it would be quite difficult to scale too much on that, but the question is: ‘Could it be modified?’ For example, just to irradiate the primary tumor and involved lymph nodes and potentially spare noninvolved lymph nodes,” he said.

The KEYNOTE-412 study was funded by Merck Sharp & Dohme. Dr. Machiels reported uncompensated consulting to the company. Dr. Larkin reported consulting for and receiving honoraria from Merck and others. Dr. Loi reported uncompensated advisory board activity for Merck and others.

In non–small cell lung cancer (NSCLC), mutations to the epidermal growth factor receptor (EGFR) gene are generally associated with a poor response to immune checkpoint inhibitor (ICI) therapies. However, there is a range of different EGFR mutations, and different mutation combinations can lead to different tumor characteristics that might in turn affect response to therapy.

A new real-world analysis of 159 NSCLC patients found that a combination of a mutation of the TP53 tumor suppressor gene and the EGFR Ex20 mutation is associated with worse disease outcomes, compared to patients with the EGFR Ex20 mutation alone. But the news wasn’t all bad. The same group of patients also responded better to ICB (immune checkpoint blockade) therapy than did the broader population of EGFR Ex20 patients.

The EGFR Ex20 mutation occurs in about 4% of NSCLC cases, while TP53 is quite common: The new study found a frequency of 43.9%. “We first have to mention that the findings regarding TP53 do not reach statistical significance; however, the trend is very strong, and results might be hampered due to small sample sizes. We think it is [appropriate] to exhaust more treatment options for these patients, especially targeted approaches with newer drugs that specifically target exon 20 insertions, as these drugs were not applied in our cohort,” Anna Kron, Dr. rer. medic., said in an email exchange. Dr. Kron presented the results at a poster session in Paris at the ESMO Congress. She is a researcher at University Hospital of Cologne, Germany.

The ImmunoTarget study, published in 2019, examined over 500 NSCLC patients with a range of driver mutations including EGFR and found that they responded poorly to ICIs in comparison to KRAS mutations.

But Dr. Kron’s group was not convinced. “Ex20 mutations differ clinically from other tyrosine kinase mutations in EGFR. We set out this study to rechallenge the paradigm of impaired benefit from ICI in EGFR-mutated patients, as we consider these mutations not interchangeable with other EGFR mutations,” Dr. Kron said.

“We would postulate that in EGFR Exon 20 mutations, ICI and specific inhibitors should be part of the therapeutic course. In patients with co-occurring TP53 mutations, treatment escalation could be considered,” Dr. Kron said.

The study included 159 patients with advanced NSCLC with the EGFR exon 20 insertion, who were treated between 2014 and 2020 at German hospitals. Among the patients, 37.7% were female; mean age at diagnosis was 65.87 years; 50.3% had a smoking history and 38.4% did not (data were unavailable for the rest); and 9.4% of tumors were stage I, 4.4% stage II, 8.2% stage IIIA, 3.8% stage IIIB, and 74.2% stage IV.

Over a follow-up of 4.1 years, there was a trend toward longer survival among patients with TP53 wild type (OS, 20 versus 12 months; P = .092). Sixty-six patients who received ICI therapy had better OS compared with those who did not (22 versus 10 months; P = .018). Among patients with co-occurring TP53 mutations, receipt of ICI therapy was associated with longer OS (16 versus 8 months; P = .048). There was a trend toward patients with TP53 wild type treated with ICI faring better than those who didn’t receive ICI (27.0 months versus 11.0 months; P = .109).

The researchers are continuing to study patients with EGFR Ex20 to better understand the role of TP53 and ICI therapy in these patients.

The study received no funding. Dr. Kron has no relevant financial disclosures.

In non–small cell lung cancer (NSCLC), mutations to the epidermal growth factor receptor (EGFR) gene are generally associated with a poor response to immune checkpoint inhibitor (ICI) therapies. However, there is a range of different EGFR mutations, and different mutation combinations can lead to different tumor characteristics that might in turn affect response to therapy.

A new real-world analysis of 159 NSCLC patients found that a combination of a mutation of the TP53 tumor suppressor gene and the EGFR Ex20 mutation is associated with worse disease outcomes, compared to patients with the EGFR Ex20 mutation alone. But the news wasn’t all bad. The same group of patients also responded better to ICB (immune checkpoint blockade) therapy than did the broader population of EGFR Ex20 patients.

The EGFR Ex20 mutation occurs in about 4% of NSCLC cases, while TP53 is quite common: The new study found a frequency of 43.9%. “We first have to mention that the findings regarding TP53 do not reach statistical significance; however, the trend is very strong, and results might be hampered due to small sample sizes. We think it is [appropriate] to exhaust more treatment options for these patients, especially targeted approaches with newer drugs that specifically target exon 20 insertions, as these drugs were not applied in our cohort,” Anna Kron, Dr. rer. medic., said in an email exchange. Dr. Kron presented the results at a poster session in Paris at the ESMO Congress. She is a researcher at University Hospital of Cologne, Germany.

The ImmunoTarget study, published in 2019, examined over 500 NSCLC patients with a range of driver mutations including EGFR and found that they responded poorly to ICIs in comparison to KRAS mutations.

But Dr. Kron’s group was not convinced. “Ex20 mutations differ clinically from other tyrosine kinase mutations in EGFR. We set out this study to rechallenge the paradigm of impaired benefit from ICI in EGFR-mutated patients, as we consider these mutations not interchangeable with other EGFR mutations,” Dr. Kron said.

“We would postulate that in EGFR Exon 20 mutations, ICI and specific inhibitors should be part of the therapeutic course. In patients with co-occurring TP53 mutations, treatment escalation could be considered,” Dr. Kron said.

The study included 159 patients with advanced NSCLC with the EGFR exon 20 insertion, who were treated between 2014 and 2020 at German hospitals. Among the patients, 37.7% were female; mean age at diagnosis was 65.87 years; 50.3% had a smoking history and 38.4% did not (data were unavailable for the rest); and 9.4% of tumors were stage I, 4.4% stage II, 8.2% stage IIIA, 3.8% stage IIIB, and 74.2% stage IV.

Over a follow-up of 4.1 years, there was a trend toward longer survival among patients with TP53 wild type (OS, 20 versus 12 months; P = .092). Sixty-six patients who received ICI therapy had better OS compared with those who did not (22 versus 10 months; P = .018). Among patients with co-occurring TP53 mutations, receipt of ICI therapy was associated with longer OS (16 versus 8 months; P = .048). There was a trend toward patients with TP53 wild type treated with ICI faring better than those who didn’t receive ICI (27.0 months versus 11.0 months; P = .109).

The researchers are continuing to study patients with EGFR Ex20 to better understand the role of TP53 and ICI therapy in these patients.

The study received no funding. Dr. Kron has no relevant financial disclosures.

In non–small cell lung cancer (NSCLC), mutations to the epidermal growth factor receptor (EGFR) gene are generally associated with a poor response to immune checkpoint inhibitor (ICI) therapies. However, there is a range of different EGFR mutations, and different mutation combinations can lead to different tumor characteristics that might in turn affect response to therapy.

A new real-world analysis of 159 NSCLC patients found that a combination of a mutation of the TP53 tumor suppressor gene and the EGFR Ex20 mutation is associated with worse disease outcomes, compared to patients with the EGFR Ex20 mutation alone. But the news wasn’t all bad. The same group of patients also responded better to ICB (immune checkpoint blockade) therapy than did the broader population of EGFR Ex20 patients.

The EGFR Ex20 mutation occurs in about 4% of NSCLC cases, while TP53 is quite common: The new study found a frequency of 43.9%. “We first have to mention that the findings regarding TP53 do not reach statistical significance; however, the trend is very strong, and results might be hampered due to small sample sizes. We think it is [appropriate] to exhaust more treatment options for these patients, especially targeted approaches with newer drugs that specifically target exon 20 insertions, as these drugs were not applied in our cohort,” Anna Kron, Dr. rer. medic., said in an email exchange. Dr. Kron presented the results at a poster session in Paris at the ESMO Congress. She is a researcher at University Hospital of Cologne, Germany.

The ImmunoTarget study, published in 2019, examined over 500 NSCLC patients with a range of driver mutations including EGFR and found that they responded poorly to ICIs in comparison to KRAS mutations.

But Dr. Kron’s group was not convinced. “Ex20 mutations differ clinically from other tyrosine kinase mutations in EGFR. We set out this study to rechallenge the paradigm of impaired benefit from ICI in EGFR-mutated patients, as we consider these mutations not interchangeable with other EGFR mutations,” Dr. Kron said.

“We would postulate that in EGFR Exon 20 mutations, ICI and specific inhibitors should be part of the therapeutic course. In patients with co-occurring TP53 mutations, treatment escalation could be considered,” Dr. Kron said.

The study included 159 patients with advanced NSCLC with the EGFR exon 20 insertion, who were treated between 2014 and 2020 at German hospitals. Among the patients, 37.7% were female; mean age at diagnosis was 65.87 years; 50.3% had a smoking history and 38.4% did not (data were unavailable for the rest); and 9.4% of tumors were stage I, 4.4% stage II, 8.2% stage IIIA, 3.8% stage IIIB, and 74.2% stage IV.

Over a follow-up of 4.1 years, there was a trend toward longer survival among patients with TP53 wild type (OS, 20 versus 12 months; P = .092). Sixty-six patients who received ICI therapy had better OS compared with those who did not (22 versus 10 months; P = .018). Among patients with co-occurring TP53 mutations, receipt of ICI therapy was associated with longer OS (16 versus 8 months; P = .048). There was a trend toward patients with TP53 wild type treated with ICI faring better than those who didn’t receive ICI (27.0 months versus 11.0 months; P = .109).

The researchers are continuing to study patients with EGFR Ex20 to better understand the role of TP53 and ICI therapy in these patients.

The study received no funding. Dr. Kron has no relevant financial disclosures.

Cardiometabolic and respiratory comorbidities are associated with worse survival in patients with non–small cell lung cancer (NSCLC), and new research suggests a potential mechanism.

Prior studies had shown mixed results when it came to these comorbidities and survival, according to study coauthor author Geoffrey Liu, MD, who is an epidemiology researcher at the University of Toronto Princess Margaret Cancer Centre. The new work represents data from multiple continents, from various ethnicities and cultures.

“We found that comorbidities had much greater impact on earlier than later stages of lung cancer, consistent with this previous study,” said Dr. Liu in an email. The study was presented by Miguel Garcia-Pardo, who is a researcher at University of Toronto Princess Margaret Cancer Centre, during a poster session at the annual meeting of the European Society for Medical Oncology.

“Deaths from [cardiometabolic] comorbidities were mainly from non–lung cancer competing causes, whereas the deaths from respiratory comorbidities were primarily driven by lung cancer specific survival, i.e., deaths from lung cancer itself. We conclude that it is critical to understand how these patients with different comorbidities died, as it would impact decisions on treatment planning and mitigation strategies,” Dr. Liu said.

Dr. Liu noted that controlling cardiometabolic risk factors like diabetes and hypertension is typically de-emphasized after diagnosis with early-stage lung cancer. The rationale is often that the lung cancer is a more acute concern than longer-term cardiometabolic risks. “The data from our analyses suggest a rethinking of this strategy. We need to pay more attention to controlling cardiovascular risk factors in early-stage lung cancer,” Dr. Liu said.

The findings also suggest that respiratory comorbidities should be managed more aggressively. That would allow more patients to undergo treatments like surgery and stereotactic radiation.

The Clinical Outcome Studies of the International Lung Cancer Consortium drew from two dozen studies conducted across five continents. It examined clinical, epidemiologic, genetic, and genomic factors and their potential influence on NSCLC outcomes. Cardiometabolic comorbidities included coronary artery disease, diabetes, vascular related diseases, and other heart diseases. Respiratory comorbidities included chronic obstructive pulmonary disease and asthma.

The analysis included 16,354 patients. Among patients with stage I NSCLC, there was an association between reduced overall survival (OS) and cardiometabolic comorbidity (adjusted hazard ratio, 1.17; P = .01) and respiratory comorbidity (aHR, 1.36; P < .001). For stage II/III patients, there was no significant association between OS and cardiometabolic comorbidities, but respiratory comorbidity was associated with worse OS (aHR, 1.15; P < .001). In stage 4, worse OS was associated with both cardiometabolic health comorbidity (aHR, 1.11; P = .03), but not respiratory comorbidity.

Among patients with stage IV NSCLC, there were no associations between overall survival or lung cancer–specific survival (LCSS) and respiratory or cardiometabolic risk factors. However, an examination of cause of death found a different pattern in patients with stage IB-IIIA disease: LCSS was worse among patients with respiratory comorbidities (aHR, 1.21; 95% CI, 1.09-1.34). Among those with cardiovascular comorbidities, the risk of non-NSCLC mortality was higher (aHR, 1.36; 95% CI, 1.15-1.63). The presence of respiratory comorbidity was associated with a reduced probability of undergoing surgical resection for both stage I (adjusted odds ratio, 0.45; 95% CI, 0.35-0.59) and stage II/III patients (aOR, 0.66; 95% CI, 0.53-0.80).

There was an association between non-NSCLC mortality and cardiometabolic comorbidities in stage IA (aHR, 1.37; 95% CI, 1.06-1.77) and in stages IB-IIIA (aHR, 1.32; 95% CI, 1.03-1.71) NSCLC. There were also associations between NSCLC mortality and respiratory comorbidity among stage IA (aHR, 1.51; 95% CI, 1.17-1.95) and stages IB-IIIA (aHR, 1.20; 95% CI, 1.06-1.36) NSCLC. There were no associations between respiratory comorbidity and non-NSCLC mortality.

Respiratory comorbidity was associated with a lower chance of undergoing surgical resection in stage IA (aHR, 0.54; 95% CI, 0.35-0.83) and stage IB-IIIA (aHR, 0.57; 95% CI, 0.46-0.70) cancers. Cardiometabolic comorbidity was associated with a lower rate of surgical resection only in stage 1B-3A patients (aHR, 0.73; 95% CI, 0.56-0.96). Among those who underwent resection, stage IA patients were less likely to die of lung cancer (aHR, 0.38; 95% CI, 0.28-0.52) but more likely to die of other causes (aHR, 1.73; 95% CI, 1.07-1.78). Stage IB-IIIA patients who underwent resection were less likely to die of lung cancer (aHR, 0.37; 95%, 0.32-0.42), but there was no significant association with non–lung cancer mortality.

The study was funded by the Lusi Wong Family Fund and the Alan Brown Chair. Dr. Liu has no relevant financial disclosures.

Cardiometabolic and respiratory comorbidities are associated with worse survival in patients with non–small cell lung cancer (NSCLC), and new research suggests a potential mechanism.

Prior studies had shown mixed results when it came to these comorbidities and survival, according to study coauthor author Geoffrey Liu, MD, who is an epidemiology researcher at the University of Toronto Princess Margaret Cancer Centre. The new work represents data from multiple continents, from various ethnicities and cultures.

“We found that comorbidities had much greater impact on earlier than later stages of lung cancer, consistent with this previous study,” said Dr. Liu in an email. The study was presented by Miguel Garcia-Pardo, who is a researcher at University of Toronto Princess Margaret Cancer Centre, during a poster session at the annual meeting of the European Society for Medical Oncology.

“Deaths from [cardiometabolic] comorbidities were mainly from non–lung cancer competing causes, whereas the deaths from respiratory comorbidities were primarily driven by lung cancer specific survival, i.e., deaths from lung cancer itself. We conclude that it is critical to understand how these patients with different comorbidities died, as it would impact decisions on treatment planning and mitigation strategies,” Dr. Liu said.

Dr. Liu noted that controlling cardiometabolic risk factors like diabetes and hypertension is typically de-emphasized after diagnosis with early-stage lung cancer. The rationale is often that the lung cancer is a more acute concern than longer-term cardiometabolic risks. “The data from our analyses suggest a rethinking of this strategy. We need to pay more attention to controlling cardiovascular risk factors in early-stage lung cancer,” Dr. Liu said.

The findings also suggest that respiratory comorbidities should be managed more aggressively. That would allow more patients to undergo treatments like surgery and stereotactic radiation.

The Clinical Outcome Studies of the International Lung Cancer Consortium drew from two dozen studies conducted across five continents. It examined clinical, epidemiologic, genetic, and genomic factors and their potential influence on NSCLC outcomes. Cardiometabolic comorbidities included coronary artery disease, diabetes, vascular related diseases, and other heart diseases. Respiratory comorbidities included chronic obstructive pulmonary disease and asthma.

The analysis included 16,354 patients. Among patients with stage I NSCLC, there was an association between reduced overall survival (OS) and cardiometabolic comorbidity (adjusted hazard ratio, 1.17; P = .01) and respiratory comorbidity (aHR, 1.36; P < .001). For stage II/III patients, there was no significant association between OS and cardiometabolic comorbidities, but respiratory comorbidity was associated with worse OS (aHR, 1.15; P < .001). In stage 4, worse OS was associated with both cardiometabolic health comorbidity (aHR, 1.11; P = .03), but not respiratory comorbidity.

Among patients with stage IV NSCLC, there were no associations between overall survival or lung cancer–specific survival (LCSS) and respiratory or cardiometabolic risk factors. However, an examination of cause of death found a different pattern in patients with stage IB-IIIA disease: LCSS was worse among patients with respiratory comorbidities (aHR, 1.21; 95% CI, 1.09-1.34). Among those with cardiovascular comorbidities, the risk of non-NSCLC mortality was higher (aHR, 1.36; 95% CI, 1.15-1.63). The presence of respiratory comorbidity was associated with a reduced probability of undergoing surgical resection for both stage I (adjusted odds ratio, 0.45; 95% CI, 0.35-0.59) and stage II/III patients (aOR, 0.66; 95% CI, 0.53-0.80).

There was an association between non-NSCLC mortality and cardiometabolic comorbidities in stage IA (aHR, 1.37; 95% CI, 1.06-1.77) and in stages IB-IIIA (aHR, 1.32; 95% CI, 1.03-1.71) NSCLC. There were also associations between NSCLC mortality and respiratory comorbidity among stage IA (aHR, 1.51; 95% CI, 1.17-1.95) and stages IB-IIIA (aHR, 1.20; 95% CI, 1.06-1.36) NSCLC. There were no associations between respiratory comorbidity and non-NSCLC mortality.

Respiratory comorbidity was associated with a lower chance of undergoing surgical resection in stage IA (aHR, 0.54; 95% CI, 0.35-0.83) and stage IB-IIIA (aHR, 0.57; 95% CI, 0.46-0.70) cancers. Cardiometabolic comorbidity was associated with a lower rate of surgical resection only in stage 1B-3A patients (aHR, 0.73; 95% CI, 0.56-0.96). Among those who underwent resection, stage IA patients were less likely to die of lung cancer (aHR, 0.38; 95% CI, 0.28-0.52) but more likely to die of other causes (aHR, 1.73; 95% CI, 1.07-1.78). Stage IB-IIIA patients who underwent resection were less likely to die of lung cancer (aHR, 0.37; 95%, 0.32-0.42), but there was no significant association with non–lung cancer mortality.

The study was funded by the Lusi Wong Family Fund and the Alan Brown Chair. Dr. Liu has no relevant financial disclosures.

Cardiometabolic and respiratory comorbidities are associated with worse survival in patients with non–small cell lung cancer (NSCLC), and new research suggests a potential mechanism.

Prior studies had shown mixed results when it came to these comorbidities and survival, according to study coauthor author Geoffrey Liu, MD, who is an epidemiology researcher at the University of Toronto Princess Margaret Cancer Centre. The new work represents data from multiple continents, from various ethnicities and cultures.

“We found that comorbidities had much greater impact on earlier than later stages of lung cancer, consistent with this previous study,” said Dr. Liu in an email. The study was presented by Miguel Garcia-Pardo, who is a researcher at University of Toronto Princess Margaret Cancer Centre, during a poster session at the annual meeting of the European Society for Medical Oncology.

“Deaths from [cardiometabolic] comorbidities were mainly from non–lung cancer competing causes, whereas the deaths from respiratory comorbidities were primarily driven by lung cancer specific survival, i.e., deaths from lung cancer itself. We conclude that it is critical to understand how these patients with different comorbidities died, as it would impact decisions on treatment planning and mitigation strategies,” Dr. Liu said.

Dr. Liu noted that controlling cardiometabolic risk factors like diabetes and hypertension is typically de-emphasized after diagnosis with early-stage lung cancer. The rationale is often that the lung cancer is a more acute concern than longer-term cardiometabolic risks. “The data from our analyses suggest a rethinking of this strategy. We need to pay more attention to controlling cardiovascular risk factors in early-stage lung cancer,” Dr. Liu said.

The findings also suggest that respiratory comorbidities should be managed more aggressively. That would allow more patients to undergo treatments like surgery and stereotactic radiation.

The Clinical Outcome Studies of the International Lung Cancer Consortium drew from two dozen studies conducted across five continents. It examined clinical, epidemiologic, genetic, and genomic factors and their potential influence on NSCLC outcomes. Cardiometabolic comorbidities included coronary artery disease, diabetes, vascular related diseases, and other heart diseases. Respiratory comorbidities included chronic obstructive pulmonary disease and asthma.

The analysis included 16,354 patients. Among patients with stage I NSCLC, there was an association between reduced overall survival (OS) and cardiometabolic comorbidity (adjusted hazard ratio, 1.17; P = .01) and respiratory comorbidity (aHR, 1.36; P < .001). For stage II/III patients, there was no significant association between OS and cardiometabolic comorbidities, but respiratory comorbidity was associated with worse OS (aHR, 1.15; P < .001). In stage 4, worse OS was associated with both cardiometabolic health comorbidity (aHR, 1.11; P = .03), but not respiratory comorbidity.

Among patients with stage IV NSCLC, there were no associations between overall survival or lung cancer–specific survival (LCSS) and respiratory or cardiometabolic risk factors. However, an examination of cause of death found a different pattern in patients with stage IB-IIIA disease: LCSS was worse among patients with respiratory comorbidities (aHR, 1.21; 95% CI, 1.09-1.34). Among those with cardiovascular comorbidities, the risk of non-NSCLC mortality was higher (aHR, 1.36; 95% CI, 1.15-1.63). The presence of respiratory comorbidity was associated with a reduced probability of undergoing surgical resection for both stage I (adjusted odds ratio, 0.45; 95% CI, 0.35-0.59) and stage II/III patients (aOR, 0.66; 95% CI, 0.53-0.80).

There was an association between non-NSCLC mortality and cardiometabolic comorbidities in stage IA (aHR, 1.37; 95% CI, 1.06-1.77) and in stages IB-IIIA (aHR, 1.32; 95% CI, 1.03-1.71) NSCLC. There were also associations between NSCLC mortality and respiratory comorbidity among stage IA (aHR, 1.51; 95% CI, 1.17-1.95) and stages IB-IIIA (aHR, 1.20; 95% CI, 1.06-1.36) NSCLC. There were no associations between respiratory comorbidity and non-NSCLC mortality.

Respiratory comorbidity was associated with a lower chance of undergoing surgical resection in stage IA (aHR, 0.54; 95% CI, 0.35-0.83) and stage IB-IIIA (aHR, 0.57; 95% CI, 0.46-0.70) cancers. Cardiometabolic comorbidity was associated with a lower rate of surgical resection only in stage 1B-3A patients (aHR, 0.73; 95% CI, 0.56-0.96). Among those who underwent resection, stage IA patients were less likely to die of lung cancer (aHR, 0.38; 95% CI, 0.28-0.52) but more likely to die of other causes (aHR, 1.73; 95% CI, 1.07-1.78). Stage IB-IIIA patients who underwent resection were less likely to die of lung cancer (aHR, 0.37; 95%, 0.32-0.42), but there was no significant association with non–lung cancer mortality.

The study was funded by the Lusi Wong Family Fund and the Alan Brown Chair. Dr. Liu has no relevant financial disclosures.

Lots of things can disrupt your gut health over the years. A high-sugar diet, stress, antibiotics – all are linked to bad changes in the gut microbiome, the microbes that live in your intestinal tract. And this can raise the risk of diseases.

But what if you could erase all that damage, restoring your gut to a time when you were younger and healthier?

It could be possible, scientists say, by having people take a sample of their own stool when they are young to be put back into their colons when they are older.

While the science to back this up isn’t quite there yet, some researchers are saying we shouldn’t wait. They are calling on existing stool banks to let people start banking their stool now, so it’s there for them to use if the science becomes available.

But how would that work?

First, you’d go to a stool bank and provide a fresh sample of your poop, which would be screened for diseases, washed, processed, and deposited into a long-term storage facility.

Then, down the road, if you get a condition such as inflammatory bowel disease, heart disease, or type 2 diabetes – or if you have a procedure that wipes out your microbiome, like a course of antibiotics or chemotherapy – doctors could use your preserved stool to “re-colonize” your gut, restoring it to its earlier, healthier state, said Scott Weiss, MD, professor of medicine at Harvard Medical School, Boston, and a coauthor of a recent paper on the topic. They would do that using fecal microbiota transplantation, or FMT.

Timing is everything. You’d want a sample from when you’re healthy – say, between the ages of 18 and 35, or before a chronic condition is likely, said Dr. Weiss. But if you’re still healthy into your late 30s, 40s, or even 50s, providing a sample then could still benefit you later in life.

If we could pull off a banking system like this, it could have the potential to treat autoimmune disease, inflammatory bowel disease, diabetes, obesity, and heart disease – or even reverse the effects of aging. How can we make this happen?
 

Stool banks of today

While stool banks do exist today, the samples inside are destined not for the original donors but rather for sick patients hoping to treat an illness. Using FMT, doctors transfer the fecal material to the patient’s colon, restoring helpful gut microbiota.

Some research shows FMT may help treat inflammatory bowel diseases, such as Crohn’s or ulcerative colitis. Animal studies suggest it could help treat obesity, lengthen lifespan, and reverse some effects of aging, such as age-related decline in brain function. Other clinical trials are looking into its potential as a cancer treatment, said Dr. Weiss.

But outside the lab, FMT is mainly used for one purpose: to treat Clostridioides difficile infection. It works even better than antibiotics, research shows.

But first you need to find a healthy donor, and that’s harder than you might think.
 

Finding healthy stool samples

Banking our bodily substances is nothing new. Blood banks, for example, are common throughout the United States, and cord blood banking – preserving blood from a baby’s umbilical cord to aid possible future medical needs of the child – is becoming more popular. Sperm donors are highly sought after, and doctors regularly transplant kidneys and bone marrow to patients in need.

So why are we so particular about poop?

Part of the reason may be because feces (like blood, for that matter) can harbor disease – which is why it’s so important to find healthy stool donors. Problem is, this can be surprisingly hard to do.

To donate fecal matter, people must go through a rigorous screening process, said Majdi Osman, MD, chief medical officer for OpenBiome, a nonprofit microbiome research organization.

Until recently, OpenBiome operated a stool donation program, though it has since shifted its focus to research. Potential donors were screened for diseases and mental health conditions, pathogens, and antibiotic resistance. The pass rate was less than 3%.

“We take a very cautious approach because the association between diseases and the microbiome is still being understood,” Dr. Osman said.

FMT also carries risks – though so far, they seem mild. Side effects include mild diarrhea, nausea, belly pain, and fatigue. (The reason? Even the healthiest donor stool may not mix perfectly with your own.)

That’s where the idea of using your own stool comes in, said Yang-Yu Liu, PhD, a Harvard researcher who studies the microbiome and the lead author of the paper mentioned above. It’s not just more appealing but may also be a better “match” for your body.
 

Should you bank your stool?

While the researchers say we have reason to be optimistic about the future, it’s important to remember that many challenges remain. FMT is early in development, and there’s a lot about the microbiome we still don’t know.

There’s no guarantee, for example, that restoring a person’s microbiome to its formerly disease-free state will keep diseases at bay forever, said Dr. Weiss. If your genes raise your odds of having Crohn’s, for instance, it’s possible the disease could come back.

We also don’t know how long stool samples can be preserved, said Dr. Liu. Stool banks currently store fecal matter for 1 or 2 years, not decades. To protect the proteins and DNA structures for that long, samples would likely need to be stashed at the liquid nitrogen storage temperature of –196° C. (Currently, samples are stored at about –80° C.) Even then, testing would be needed to confirm if the fragile microorganisms in the stool can survive.

This raises another question: Who’s going to regulate all this?

The FDA regulates the use of FMT as a drug for the treatment of C. diff, but as Dr. Liu pointed out, many gastroenterologists consider the gut microbiota an organ. In that case, human fecal matter could be regulated the same way blood, bone, or even egg cells are.

Cord blood banking may be a helpful model, Dr. Liu said.

“We don’t have to start from scratch.”

Then there’s the question of cost. Cord blood banks could be a point of reference for that too, the researchers say. They charge about $1,500 to $2,820 for the first collection and processing, plus a yearly storage fee of $185 to $370.

Despite the unknowns, one thing is for sure: The interest in fecal banking is real – and growing. At least one microbiome firm, Cordlife Group Limited, based in Singapore, announced that it has started to allow people to bank their stool for future use.

“More people should talk about it and think about it,” said Dr. Liu.

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

Lots of things can disrupt your gut health over the years. A high-sugar diet, stress, antibiotics – all are linked to bad changes in the gut microbiome, the microbes that live in your intestinal tract. And this can raise the risk of diseases.

But what if you could erase all that damage, restoring your gut to a time when you were younger and healthier?

It could be possible, scientists say, by having people take a sample of their own stool when they are young to be put back into their colons when they are older.

While the science to back this up isn’t quite there yet, some researchers are saying we shouldn’t wait. They are calling on existing stool banks to let people start banking their stool now, so it’s there for them to use if the science becomes available.

But how would that work?

First, you’d go to a stool bank and provide a fresh sample of your poop, which would be screened for diseases, washed, processed, and deposited into a long-term storage facility.

Then, down the road, if you get a condition such as inflammatory bowel disease, heart disease, or type 2 diabetes – or if you have a procedure that wipes out your microbiome, like a course of antibiotics or chemotherapy – doctors could use your preserved stool to “re-colonize” your gut, restoring it to its earlier, healthier state, said Scott Weiss, MD, professor of medicine at Harvard Medical School, Boston, and a coauthor of a recent paper on the topic. They would do that using fecal microbiota transplantation, or FMT.

Timing is everything. You’d want a sample from when you’re healthy – say, between the ages of 18 and 35, or before a chronic condition is likely, said Dr. Weiss. But if you’re still healthy into your late 30s, 40s, or even 50s, providing a sample then could still benefit you later in life.

If we could pull off a banking system like this, it could have the potential to treat autoimmune disease, inflammatory bowel disease, diabetes, obesity, and heart disease – or even reverse the effects of aging. How can we make this happen?
 

Stool banks of today

While stool banks do exist today, the samples inside are destined not for the original donors but rather for sick patients hoping to treat an illness. Using FMT, doctors transfer the fecal material to the patient’s colon, restoring helpful gut microbiota.

Some research shows FMT may help treat inflammatory bowel diseases, such as Crohn’s or ulcerative colitis. Animal studies suggest it could help treat obesity, lengthen lifespan, and reverse some effects of aging, such as age-related decline in brain function. Other clinical trials are looking into its potential as a cancer treatment, said Dr. Weiss.

But outside the lab, FMT is mainly used for one purpose: to treat Clostridioides difficile infection. It works even better than antibiotics, research shows.

But first you need to find a healthy donor, and that’s harder than you might think.
 

Finding healthy stool samples

Banking our bodily substances is nothing new. Blood banks, for example, are common throughout the United States, and cord blood banking – preserving blood from a baby’s umbilical cord to aid possible future medical needs of the child – is becoming more popular. Sperm donors are highly sought after, and doctors regularly transplant kidneys and bone marrow to patients in need.

So why are we so particular about poop?

Part of the reason may be because feces (like blood, for that matter) can harbor disease – which is why it’s so important to find healthy stool donors. Problem is, this can be surprisingly hard to do.

To donate fecal matter, people must go through a rigorous screening process, said Majdi Osman, MD, chief medical officer for OpenBiome, a nonprofit microbiome research organization.

Until recently, OpenBiome operated a stool donation program, though it has since shifted its focus to research. Potential donors were screened for diseases and mental health conditions, pathogens, and antibiotic resistance. The pass rate was less than 3%.

“We take a very cautious approach because the association between diseases and the microbiome is still being understood,” Dr. Osman said.

FMT also carries risks – though so far, they seem mild. Side effects include mild diarrhea, nausea, belly pain, and fatigue. (The reason? Even the healthiest donor stool may not mix perfectly with your own.)

That’s where the idea of using your own stool comes in, said Yang-Yu Liu, PhD, a Harvard researcher who studies the microbiome and the lead author of the paper mentioned above. It’s not just more appealing but may also be a better “match” for your body.
 

Should you bank your stool?

While the researchers say we have reason to be optimistic about the future, it’s important to remember that many challenges remain. FMT is early in development, and there’s a lot about the microbiome we still don’t know.

There’s no guarantee, for example, that restoring a person’s microbiome to its formerly disease-free state will keep diseases at bay forever, said Dr. Weiss. If your genes raise your odds of having Crohn’s, for instance, it’s possible the disease could come back.

We also don’t know how long stool samples can be preserved, said Dr. Liu. Stool banks currently store fecal matter for 1 or 2 years, not decades. To protect the proteins and DNA structures for that long, samples would likely need to be stashed at the liquid nitrogen storage temperature of –196° C. (Currently, samples are stored at about –80° C.) Even then, testing would be needed to confirm if the fragile microorganisms in the stool can survive.

This raises another question: Who’s going to regulate all this?

The FDA regulates the use of FMT as a drug for the treatment of C. diff, but as Dr. Liu pointed out, many gastroenterologists consider the gut microbiota an organ. In that case, human fecal matter could be regulated the same way blood, bone, or even egg cells are.

Cord blood banking may be a helpful model, Dr. Liu said.

“We don’t have to start from scratch.”

Then there’s the question of cost. Cord blood banks could be a point of reference for that too, the researchers say. They charge about $1,500 to $2,820 for the first collection and processing, plus a yearly storage fee of $185 to $370.

Despite the unknowns, one thing is for sure: The interest in fecal banking is real – and growing. At least one microbiome firm, Cordlife Group Limited, based in Singapore, announced that it has started to allow people to bank their stool for future use.

“More people should talk about it and think about it,” said Dr. Liu.

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

Lots of things can disrupt your gut health over the years. A high-sugar diet, stress, antibiotics – all are linked to bad changes in the gut microbiome, the microbes that live in your intestinal tract. And this can raise the risk of diseases.

But what if you could erase all that damage, restoring your gut to a time when you were younger and healthier?

It could be possible, scientists say, by having people take a sample of their own stool when they are young to be put back into their colons when they are older.

While the science to back this up isn’t quite there yet, some researchers are saying we shouldn’t wait. They are calling on existing stool banks to let people start banking their stool now, so it’s there for them to use if the science becomes available.

But how would that work?

First, you’d go to a stool bank and provide a fresh sample of your poop, which would be screened for diseases, washed, processed, and deposited into a long-term storage facility.

Then, down the road, if you get a condition such as inflammatory bowel disease, heart disease, or type 2 diabetes – or if you have a procedure that wipes out your microbiome, like a course of antibiotics or chemotherapy – doctors could use your preserved stool to “re-colonize” your gut, restoring it to its earlier, healthier state, said Scott Weiss, MD, professor of medicine at Harvard Medical School, Boston, and a coauthor of a recent paper on the topic. They would do that using fecal microbiota transplantation, or FMT.

Timing is everything. You’d want a sample from when you’re healthy – say, between the ages of 18 and 35, or before a chronic condition is likely, said Dr. Weiss. But if you’re still healthy into your late 30s, 40s, or even 50s, providing a sample then could still benefit you later in life.

If we could pull off a banking system like this, it could have the potential to treat autoimmune disease, inflammatory bowel disease, diabetes, obesity, and heart disease – or even reverse the effects of aging. How can we make this happen?
 

Stool banks of today

While stool banks do exist today, the samples inside are destined not for the original donors but rather for sick patients hoping to treat an illness. Using FMT, doctors transfer the fecal material to the patient’s colon, restoring helpful gut microbiota.

Some research shows FMT may help treat inflammatory bowel diseases, such as Crohn’s or ulcerative colitis. Animal studies suggest it could help treat obesity, lengthen lifespan, and reverse some effects of aging, such as age-related decline in brain function. Other clinical trials are looking into its potential as a cancer treatment, said Dr. Weiss.

But outside the lab, FMT is mainly used for one purpose: to treat Clostridioides difficile infection. It works even better than antibiotics, research shows.

But first you need to find a healthy donor, and that’s harder than you might think.
 

Finding healthy stool samples

Banking our bodily substances is nothing new. Blood banks, for example, are common throughout the United States, and cord blood banking – preserving blood from a baby’s umbilical cord to aid possible future medical needs of the child – is becoming more popular. Sperm donors are highly sought after, and doctors regularly transplant kidneys and bone marrow to patients in need.

So why are we so particular about poop?

Part of the reason may be because feces (like blood, for that matter) can harbor disease – which is why it’s so important to find healthy stool donors. Problem is, this can be surprisingly hard to do.

To donate fecal matter, people must go through a rigorous screening process, said Majdi Osman, MD, chief medical officer for OpenBiome, a nonprofit microbiome research organization.

Until recently, OpenBiome operated a stool donation program, though it has since shifted its focus to research. Potential donors were screened for diseases and mental health conditions, pathogens, and antibiotic resistance. The pass rate was less than 3%.

“We take a very cautious approach because the association between diseases and the microbiome is still being understood,” Dr. Osman said.

FMT also carries risks – though so far, they seem mild. Side effects include mild diarrhea, nausea, belly pain, and fatigue. (The reason? Even the healthiest donor stool may not mix perfectly with your own.)

That’s where the idea of using your own stool comes in, said Yang-Yu Liu, PhD, a Harvard researcher who studies the microbiome and the lead author of the paper mentioned above. It’s not just more appealing but may also be a better “match” for your body.
 

Should you bank your stool?

While the researchers say we have reason to be optimistic about the future, it’s important to remember that many challenges remain. FMT is early in development, and there’s a lot about the microbiome we still don’t know.

There’s no guarantee, for example, that restoring a person’s microbiome to its formerly disease-free state will keep diseases at bay forever, said Dr. Weiss. If your genes raise your odds of having Crohn’s, for instance, it’s possible the disease could come back.

We also don’t know how long stool samples can be preserved, said Dr. Liu. Stool banks currently store fecal matter for 1 or 2 years, not decades. To protect the proteins and DNA structures for that long, samples would likely need to be stashed at the liquid nitrogen storage temperature of –196° C. (Currently, samples are stored at about –80° C.) Even then, testing would be needed to confirm if the fragile microorganisms in the stool can survive.

This raises another question: Who’s going to regulate all this?

The FDA regulates the use of FMT as a drug for the treatment of C. diff, but as Dr. Liu pointed out, many gastroenterologists consider the gut microbiota an organ. In that case, human fecal matter could be regulated the same way blood, bone, or even egg cells are.

Cord blood banking may be a helpful model, Dr. Liu said.

“We don’t have to start from scratch.”

Then there’s the question of cost. Cord blood banks could be a point of reference for that too, the researchers say. They charge about $1,500 to $2,820 for the first collection and processing, plus a yearly storage fee of $185 to $370.

Despite the unknowns, one thing is for sure: The interest in fecal banking is real – and growing. At least one microbiome firm, Cordlife Group Limited, based in Singapore, announced that it has started to allow people to bank their stool for future use.

“More people should talk about it and think about it,” said Dr. Liu.

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