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COVID is especially dangerous for mesothelioma
according to Susana Cedres, MD, PhD, a thoracic medical oncologist at Vall d’Hebron University Hospital, Barcelona.
At the annual World Conference on Lung Cancer, she reported on her institution’s experience during the first year of the pandemic before widespread vaccine rollouts.
Among 38 malignant pleural mesothelioma (MPM) patients, seven (18%) patients were diagnosed with COVID-19 and of these, three patients were asymptomatic, four (57%) died of complications including bilateral pneumonia within a median of less than half a month after diagnosis, and a fifth patient died from MPM progression.
The findings confirm the particular risk of COVID in MPM. According to researchers reporting in Scientific Reports, mesothelioma was the only cancer linked to significantly worse outcomes. Other risks included tuberculosis, drug use, hepatitis, HIV/AIDS, cardiomyopathy, and diabetes.
However, the Barcelona report only has seven patients, and it’s one of only a few to address the specifics of COVID in MPM.
“There really is a need for more inclusion of MPM patients in international [COVID] registries” to better characterize the course of infection and improve outcomes, said study discussant Francoise Galateau-Salle, MD, PhD, a mesothelioma expert at the Cancer Center Leon Berard in Lyon, France.
Among the seven positive cases in Barcelona, almost all had comorbidities, with the most common being cardiovascular disease in four patients (57%). Only two patients (29%) were on oncologic treatment at the time they were diagnosed, and the median age at diagnosis was 62 years. Four cases were in men, three in women. MPM stage was not reported.
WCLC 2021 was organized by the International Association for the Study of Lung Cancer.
No funding source was reported. Dr. Cedres is an adviser and/or reported travel expenses from a number of companies, including Merck, Pfizer, and Bristol-Myers Squibb. Dr. Galateau-Salle had no disclosures.
according to Susana Cedres, MD, PhD, a thoracic medical oncologist at Vall d’Hebron University Hospital, Barcelona.
At the annual World Conference on Lung Cancer, she reported on her institution’s experience during the first year of the pandemic before widespread vaccine rollouts.
Among 38 malignant pleural mesothelioma (MPM) patients, seven (18%) patients were diagnosed with COVID-19 and of these, three patients were asymptomatic, four (57%) died of complications including bilateral pneumonia within a median of less than half a month after diagnosis, and a fifth patient died from MPM progression.
The findings confirm the particular risk of COVID in MPM. According to researchers reporting in Scientific Reports, mesothelioma was the only cancer linked to significantly worse outcomes. Other risks included tuberculosis, drug use, hepatitis, HIV/AIDS, cardiomyopathy, and diabetes.
However, the Barcelona report only has seven patients, and it’s one of only a few to address the specifics of COVID in MPM.
“There really is a need for more inclusion of MPM patients in international [COVID] registries” to better characterize the course of infection and improve outcomes, said study discussant Francoise Galateau-Salle, MD, PhD, a mesothelioma expert at the Cancer Center Leon Berard in Lyon, France.
Among the seven positive cases in Barcelona, almost all had comorbidities, with the most common being cardiovascular disease in four patients (57%). Only two patients (29%) were on oncologic treatment at the time they were diagnosed, and the median age at diagnosis was 62 years. Four cases were in men, three in women. MPM stage was not reported.
WCLC 2021 was organized by the International Association for the Study of Lung Cancer.
No funding source was reported. Dr. Cedres is an adviser and/or reported travel expenses from a number of companies, including Merck, Pfizer, and Bristol-Myers Squibb. Dr. Galateau-Salle had no disclosures.
according to Susana Cedres, MD, PhD, a thoracic medical oncologist at Vall d’Hebron University Hospital, Barcelona.
At the annual World Conference on Lung Cancer, she reported on her institution’s experience during the first year of the pandemic before widespread vaccine rollouts.
Among 38 malignant pleural mesothelioma (MPM) patients, seven (18%) patients were diagnosed with COVID-19 and of these, three patients were asymptomatic, four (57%) died of complications including bilateral pneumonia within a median of less than half a month after diagnosis, and a fifth patient died from MPM progression.
The findings confirm the particular risk of COVID in MPM. According to researchers reporting in Scientific Reports, mesothelioma was the only cancer linked to significantly worse outcomes. Other risks included tuberculosis, drug use, hepatitis, HIV/AIDS, cardiomyopathy, and diabetes.
However, the Barcelona report only has seven patients, and it’s one of only a few to address the specifics of COVID in MPM.
“There really is a need for more inclusion of MPM patients in international [COVID] registries” to better characterize the course of infection and improve outcomes, said study discussant Francoise Galateau-Salle, MD, PhD, a mesothelioma expert at the Cancer Center Leon Berard in Lyon, France.
Among the seven positive cases in Barcelona, almost all had comorbidities, with the most common being cardiovascular disease in four patients (57%). Only two patients (29%) were on oncologic treatment at the time they were diagnosed, and the median age at diagnosis was 62 years. Four cases were in men, three in women. MPM stage was not reported.
WCLC 2021 was organized by the International Association for the Study of Lung Cancer.
No funding source was reported. Dr. Cedres is an adviser and/or reported travel expenses from a number of companies, including Merck, Pfizer, and Bristol-Myers Squibb. Dr. Galateau-Salle had no disclosures.
FROM WCLC 2021
Pandemic strategies to boost trial enrollment should stay
Although enrollment into lung cancer clinical trials fell during the early months of the COVID-19 pandemic, it increased after a number of mitigation strategies were introduced.
These strategies should now be maintained, say experts, in order to improve enrollment and access to trials and to ensure that trials are more pragmatic and streamlined.
These were the findings from a survey sent to 173 sites of clinical trials in 45 countries around the world. The findings were presented recently at the World Conference on Lung Cancer (WCLC) 2021. The meeting and the survey were organized by the International Association for the Study of Lung Cancer (IASLC).
Responses to the survey revealed that enrollment into lung cancer trials fell by 43% during the early months of the pandemic. Patients stopped attending clinics, and some trials were suspended.
Patients were less willing to visit clinical trial sites, and lockdown restrictions made travel difficult.
Organizers of clinical trials responded by implementing mitigation strategies, such as changing monitoring requirements, increasing use of telehealth, and using local non-study facilities for laboratory and radiology services.
These measures led to an increase in trial enrollment toward the end of 2020, the survey results show.
“The COVID-19 pandemic created many challenges [that led to] reductions in lung cancer clinical trial enrollment,” commented study presenter Matthew P. Smeltzer, PhD, from the Division of Epidemiology, Biostatistics, and Environmental Health, University of Memphis.
The employment of mitigation strategies allowed the removal of “barriers,” and although the pandemic “worsened, trial enrollment began to improve due in part to these strategies,” Dr. Smeltzer said.
Many of these measures were successful and should be maintained, he suggested. Strategies include allowing telehealth visits, performing testing at local laboratories, using local radiology services, mailing experimental agents “where possible,” and allowing flexibility in trial schedules.
This is a “very important” study, commented Marina Garassino, MD, professor of medicine, hematology, and oncology, the University of Chicago Medicine, in her discussion of the abstract.
Irrespective of the pandemic, the regulation and the bureaucracy of clinical trials hinder participation by patients and physicians, she said.
Many of the mitigation strategies highlighted by the survey were similar to recommendations on the conduct of clinical trials published by the American Society of Clinical Oncology during the pandemic. Those recommendations emphasize the use of telehealth and offsite strategies to help with patient monitoring, she noted.
The findings from the survey show that it is possible to conduct more “streamlined and pragmatic trials,” she said.
“More flexible approaches should be approved by the sponsors of clinical trials and global regulatory bodies,” she added.
However, she expressed concern that “with the telehealth visits, we can create some disparities.”
“We have to remember that lung cancer patients are sometimes a very old population, and they are not digitally evolved,” she commented.
Commenting on Twitter, Jennifer C. King, PhD, chief scientific officer at the GO2 Foundation for Lung Cancer, in Washington, D.C., agreed that many of the mitigation strategies identified in the study “are good for patients all of the time, not just during a pandemic.”
Impact on lung cancer clinical trials
The survey, which included 64 questions, was intended to assess the impact of the COVID pandemic on lung cancer clinical trials.
Most of the survey responses came from sites in Europe (37.6%); 21.4% came from Asia, 13.3% came from the United States, and 7.5% came from Canada.
The team found that enrollment into lung cancer trials declined by 43% in 2020 compared to 2019, at an incidence rate ratio of 0.57 (P = .0115).
The largest decreases in enrollment were between April and August 2020, Dr. Smeltzer noted. However, in the last quarter of 2020 (October to December), the differences in enrollment were significantly smaller (P = .0160), despite a marked increase in global COVID-19 cases per month, he added.
The most common challenges faced by clinical trial sites during the pandemic were the following: There were fewer eligible patients (cited by 67% of respondents); compliance protocol was worse (61%); trials were suspended (60%); there was a lack of research staff (48%); and there were institutional closures (39%).
Regarding patient-related challenges, 67% of sites cited less willingness to visit the site. Other challenges included less ability to travel (cited by 60%), reduced access to the trial site (52%), quarantining because of exposure to COVID-19 (40%), and SARS-CoV-2 infection (26%).
Concerns of patients included the following: Fear of SARS-CoV-2 infection, which was cited by 83%; travel restrictions (47%); securing transportation (38%); and access to the laboratory/radiology services (14%).
“Patient willingness to visit the site was a consistent barrier reported across Europe, the U.S., and Canada,” said Dr. Smeltzer, although the effect was smaller in North America, he added.
Regarding mitigation strategies that were employed during the pandemic to combat the challenges and concerns, the team found that the most common measure was the modification of monitoring requirements, used by 44% of sites.
This was followed by the use of telehealth visits (43% sites), the use of laboratories at non-study facilities ( 27%), and alterations to the number of required visits (25%).
Other mitigation strategies included use of mail-order medications, (24%), using radiology services at a non-study site (20%), and altering the trial schedules (19%).
The most effective mitigation strategies were felt to be those that allowed flexibility with respect to location. These measures included use of remote monitoring, remote diagnostics, telehealth visits, and modified symptom monitoring.
Effective strategies that increased flexibility in time were delayed visits, delayed assessments, and changes to the Institutional Review Board.
The study was funded by the IASLC, which received industry support to conduct the project. Dr. Smeltzer reported no relevant financial relationships. Dr. Garassino has relationships with AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Daiichi Sankyo, Eli Lilly, Ignyta, Incyte, MedImmune, Mirati, MSD International, Novartis, Pfizer, Regeneron, Roche, Takeda, and Seattle Genetics.
A version of this article first appeared on Medscape.com.
Although enrollment into lung cancer clinical trials fell during the early months of the COVID-19 pandemic, it increased after a number of mitigation strategies were introduced.
These strategies should now be maintained, say experts, in order to improve enrollment and access to trials and to ensure that trials are more pragmatic and streamlined.
These were the findings from a survey sent to 173 sites of clinical trials in 45 countries around the world. The findings were presented recently at the World Conference on Lung Cancer (WCLC) 2021. The meeting and the survey were organized by the International Association for the Study of Lung Cancer (IASLC).
Responses to the survey revealed that enrollment into lung cancer trials fell by 43% during the early months of the pandemic. Patients stopped attending clinics, and some trials were suspended.
Patients were less willing to visit clinical trial sites, and lockdown restrictions made travel difficult.
Organizers of clinical trials responded by implementing mitigation strategies, such as changing monitoring requirements, increasing use of telehealth, and using local non-study facilities for laboratory and radiology services.
These measures led to an increase in trial enrollment toward the end of 2020, the survey results show.
“The COVID-19 pandemic created many challenges [that led to] reductions in lung cancer clinical trial enrollment,” commented study presenter Matthew P. Smeltzer, PhD, from the Division of Epidemiology, Biostatistics, and Environmental Health, University of Memphis.
The employment of mitigation strategies allowed the removal of “barriers,” and although the pandemic “worsened, trial enrollment began to improve due in part to these strategies,” Dr. Smeltzer said.
Many of these measures were successful and should be maintained, he suggested. Strategies include allowing telehealth visits, performing testing at local laboratories, using local radiology services, mailing experimental agents “where possible,” and allowing flexibility in trial schedules.
This is a “very important” study, commented Marina Garassino, MD, professor of medicine, hematology, and oncology, the University of Chicago Medicine, in her discussion of the abstract.
Irrespective of the pandemic, the regulation and the bureaucracy of clinical trials hinder participation by patients and physicians, she said.
Many of the mitigation strategies highlighted by the survey were similar to recommendations on the conduct of clinical trials published by the American Society of Clinical Oncology during the pandemic. Those recommendations emphasize the use of telehealth and offsite strategies to help with patient monitoring, she noted.
The findings from the survey show that it is possible to conduct more “streamlined and pragmatic trials,” she said.
“More flexible approaches should be approved by the sponsors of clinical trials and global regulatory bodies,” she added.
However, she expressed concern that “with the telehealth visits, we can create some disparities.”
“We have to remember that lung cancer patients are sometimes a very old population, and they are not digitally evolved,” she commented.
Commenting on Twitter, Jennifer C. King, PhD, chief scientific officer at the GO2 Foundation for Lung Cancer, in Washington, D.C., agreed that many of the mitigation strategies identified in the study “are good for patients all of the time, not just during a pandemic.”
Impact on lung cancer clinical trials
The survey, which included 64 questions, was intended to assess the impact of the COVID pandemic on lung cancer clinical trials.
Most of the survey responses came from sites in Europe (37.6%); 21.4% came from Asia, 13.3% came from the United States, and 7.5% came from Canada.
The team found that enrollment into lung cancer trials declined by 43% in 2020 compared to 2019, at an incidence rate ratio of 0.57 (P = .0115).
The largest decreases in enrollment were between April and August 2020, Dr. Smeltzer noted. However, in the last quarter of 2020 (October to December), the differences in enrollment were significantly smaller (P = .0160), despite a marked increase in global COVID-19 cases per month, he added.
The most common challenges faced by clinical trial sites during the pandemic were the following: There were fewer eligible patients (cited by 67% of respondents); compliance protocol was worse (61%); trials were suspended (60%); there was a lack of research staff (48%); and there were institutional closures (39%).
Regarding patient-related challenges, 67% of sites cited less willingness to visit the site. Other challenges included less ability to travel (cited by 60%), reduced access to the trial site (52%), quarantining because of exposure to COVID-19 (40%), and SARS-CoV-2 infection (26%).
Concerns of patients included the following: Fear of SARS-CoV-2 infection, which was cited by 83%; travel restrictions (47%); securing transportation (38%); and access to the laboratory/radiology services (14%).
“Patient willingness to visit the site was a consistent barrier reported across Europe, the U.S., and Canada,” said Dr. Smeltzer, although the effect was smaller in North America, he added.
Regarding mitigation strategies that were employed during the pandemic to combat the challenges and concerns, the team found that the most common measure was the modification of monitoring requirements, used by 44% of sites.
This was followed by the use of telehealth visits (43% sites), the use of laboratories at non-study facilities ( 27%), and alterations to the number of required visits (25%).
Other mitigation strategies included use of mail-order medications, (24%), using radiology services at a non-study site (20%), and altering the trial schedules (19%).
The most effective mitigation strategies were felt to be those that allowed flexibility with respect to location. These measures included use of remote monitoring, remote diagnostics, telehealth visits, and modified symptom monitoring.
Effective strategies that increased flexibility in time were delayed visits, delayed assessments, and changes to the Institutional Review Board.
The study was funded by the IASLC, which received industry support to conduct the project. Dr. Smeltzer reported no relevant financial relationships. Dr. Garassino has relationships with AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Daiichi Sankyo, Eli Lilly, Ignyta, Incyte, MedImmune, Mirati, MSD International, Novartis, Pfizer, Regeneron, Roche, Takeda, and Seattle Genetics.
A version of this article first appeared on Medscape.com.
Although enrollment into lung cancer clinical trials fell during the early months of the COVID-19 pandemic, it increased after a number of mitigation strategies were introduced.
These strategies should now be maintained, say experts, in order to improve enrollment and access to trials and to ensure that trials are more pragmatic and streamlined.
These were the findings from a survey sent to 173 sites of clinical trials in 45 countries around the world. The findings were presented recently at the World Conference on Lung Cancer (WCLC) 2021. The meeting and the survey were organized by the International Association for the Study of Lung Cancer (IASLC).
Responses to the survey revealed that enrollment into lung cancer trials fell by 43% during the early months of the pandemic. Patients stopped attending clinics, and some trials were suspended.
Patients were less willing to visit clinical trial sites, and lockdown restrictions made travel difficult.
Organizers of clinical trials responded by implementing mitigation strategies, such as changing monitoring requirements, increasing use of telehealth, and using local non-study facilities for laboratory and radiology services.
These measures led to an increase in trial enrollment toward the end of 2020, the survey results show.
“The COVID-19 pandemic created many challenges [that led to] reductions in lung cancer clinical trial enrollment,” commented study presenter Matthew P. Smeltzer, PhD, from the Division of Epidemiology, Biostatistics, and Environmental Health, University of Memphis.
The employment of mitigation strategies allowed the removal of “barriers,” and although the pandemic “worsened, trial enrollment began to improve due in part to these strategies,” Dr. Smeltzer said.
Many of these measures were successful and should be maintained, he suggested. Strategies include allowing telehealth visits, performing testing at local laboratories, using local radiology services, mailing experimental agents “where possible,” and allowing flexibility in trial schedules.
This is a “very important” study, commented Marina Garassino, MD, professor of medicine, hematology, and oncology, the University of Chicago Medicine, in her discussion of the abstract.
Irrespective of the pandemic, the regulation and the bureaucracy of clinical trials hinder participation by patients and physicians, she said.
Many of the mitigation strategies highlighted by the survey were similar to recommendations on the conduct of clinical trials published by the American Society of Clinical Oncology during the pandemic. Those recommendations emphasize the use of telehealth and offsite strategies to help with patient monitoring, she noted.
The findings from the survey show that it is possible to conduct more “streamlined and pragmatic trials,” she said.
“More flexible approaches should be approved by the sponsors of clinical trials and global regulatory bodies,” she added.
However, she expressed concern that “with the telehealth visits, we can create some disparities.”
“We have to remember that lung cancer patients are sometimes a very old population, and they are not digitally evolved,” she commented.
Commenting on Twitter, Jennifer C. King, PhD, chief scientific officer at the GO2 Foundation for Lung Cancer, in Washington, D.C., agreed that many of the mitigation strategies identified in the study “are good for patients all of the time, not just during a pandemic.”
Impact on lung cancer clinical trials
The survey, which included 64 questions, was intended to assess the impact of the COVID pandemic on lung cancer clinical trials.
Most of the survey responses came from sites in Europe (37.6%); 21.4% came from Asia, 13.3% came from the United States, and 7.5% came from Canada.
The team found that enrollment into lung cancer trials declined by 43% in 2020 compared to 2019, at an incidence rate ratio of 0.57 (P = .0115).
The largest decreases in enrollment were between April and August 2020, Dr. Smeltzer noted. However, in the last quarter of 2020 (October to December), the differences in enrollment were significantly smaller (P = .0160), despite a marked increase in global COVID-19 cases per month, he added.
The most common challenges faced by clinical trial sites during the pandemic were the following: There were fewer eligible patients (cited by 67% of respondents); compliance protocol was worse (61%); trials were suspended (60%); there was a lack of research staff (48%); and there were institutional closures (39%).
Regarding patient-related challenges, 67% of sites cited less willingness to visit the site. Other challenges included less ability to travel (cited by 60%), reduced access to the trial site (52%), quarantining because of exposure to COVID-19 (40%), and SARS-CoV-2 infection (26%).
Concerns of patients included the following: Fear of SARS-CoV-2 infection, which was cited by 83%; travel restrictions (47%); securing transportation (38%); and access to the laboratory/radiology services (14%).
“Patient willingness to visit the site was a consistent barrier reported across Europe, the U.S., and Canada,” said Dr. Smeltzer, although the effect was smaller in North America, he added.
Regarding mitigation strategies that were employed during the pandemic to combat the challenges and concerns, the team found that the most common measure was the modification of monitoring requirements, used by 44% of sites.
This was followed by the use of telehealth visits (43% sites), the use of laboratories at non-study facilities ( 27%), and alterations to the number of required visits (25%).
Other mitigation strategies included use of mail-order medications, (24%), using radiology services at a non-study site (20%), and altering the trial schedules (19%).
The most effective mitigation strategies were felt to be those that allowed flexibility with respect to location. These measures included use of remote monitoring, remote diagnostics, telehealth visits, and modified symptom monitoring.
Effective strategies that increased flexibility in time were delayed visits, delayed assessments, and changes to the Institutional Review Board.
The study was funded by the IASLC, which received industry support to conduct the project. Dr. Smeltzer reported no relevant financial relationships. Dr. Garassino has relationships with AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Daiichi Sankyo, Eli Lilly, Ignyta, Incyte, MedImmune, Mirati, MSD International, Novartis, Pfizer, Regeneron, Roche, Takeda, and Seattle Genetics.
A version of this article first appeared on Medscape.com.
Air pollution – second leading cause of lung cancer
The new data show that the rate of lung cancer deaths attributable to air pollution varies widely between countries. Serbia, Poland, China, Mongolia, and Turkey are among the worst affected. The analysis shows an association between deaths from lung cancer and the proportion of national energy that is produced from coal.
“Both smoking and air pollution are important causes of lung cancer,” said study presenter Christine D. Berg, MD, former codirector of the National Lung Screening Trial, and “both need to be eliminated to help prevent lung cancer and save lives.
“As lung cancer professionals, we can mitigate the effects of air pollution on causing lung cancer by speaking out for clean energy standards,” she said.
Dr. Berg presented the new analysis on Sept. 9 at the 2021 World Conference on Lung Cancer, which was organized by the International Association for the Study of Lung Cancer.
She welcomed the recent statement issued by the IASLC in support of the International Day of Clean Air for Blue Skies, which took place on Sept. 7. It was a call for action that emphasized the need for further efforts to improve air quality to protect human health.
The findings from the new analysis are “depressing,” commented Joachim G. J. V. Aerts, MD. PhD, department of pulmonary diseases, Erasmus University Medical Center, Rotterdam, the Netherlands.
It is now clear that air pollution has an impact not only on the incidence of lung cancer but also on its outcome, he added.
Indeed, previous research showed that each 10 mcg/m3 increase in particular matter of 2.5 mcg in size was associated with a 15%-27% increase in lung cancer mortality. There was no difference in rates between women and men.
A key question, Dr. Aerts said, is whether reducing air pollution would be beneficial.
Efforts to reduce air pollution over recent decades in the United Kingdom have not led to a reduction in lung cancer deaths. This is because of the increase in life expectancy – individuals have been exposed to pollution for longer, albeit at lower levels, he pointed out.
Because of lockdowns during the COVID pandemic, travel has been greatly reduced. This has resulted in a dramatic reduction in air pollution, “and this led to a decrease in the number of children born with low birth weight,” said Dr. Aerts.
Hopefully, that benefit will also be seen regarding other diseases, he added.
The call to action to reduce air pollution is of the “utmost importance,” he said. He noted that the focus should be on global, national, local, and personal preventive measures.
“It is time to join forces,” he added, “to ‘clean the air.’ ”
Dr. Berg’s presentation was warmly received on social media.
It was “fabulous,” commented Eric H. Bernicker, MD, director of medical thoracic oncology at Houston Methodist Cancer Center.
“Thoracic oncologists need to add air pollution to things they advocate about; we have an important voice here,” he added.
It is “so important to understand that air pollution is a human carcinogen,” commented Ivy Elkins, a lung cancer survivor and advocate and cofounder of the EGFR Resisters Lung Cancer Patient Group. “All you need are lungs to get lung cancer!”
Contribution of air pollution to lung cancer
In her presentation, Dr. Berg emphasized that lung cancer is the leading cause of cancer death worldwide, although the distribution between countries “depends on historical and current smoking patterns and the demographics of the population.”
Overall, data from GLOBOCAN 2018 indicate that annually there are approximately 2.1 million incident cases of lung cancer and almost 1.8 million lung cancer deaths around the globe.
A recent study estimated that, worldwide, 14.1% of all lung cancer deaths, including in never-smokers, are directly linked to air pollution.
Dr. Berg said that this makes it the “second-leading cause of lung cancer” behind smoking.
The figure is somewhat lower for the United States, where around 4.7% of lung cancer deaths each year are directly attributable to pollution. However, with “the wildfires out West, we’re going to be seeing more of a toll from air pollution,” she predicted.
She pointed out that the International Agency for Research on Cancer classifies outdoor air pollution, especially particulate matter, as a human carcinogen on the basis of evidence of an association with lung cancer.
It is thought that direct deposits and local effects of particulate matter lead to oxidative damage and low-grade chronic inflammation. These in turn result in molecular changes that affect DNA and gene transcription and inhibit apoptosis, all of which lead to the development of cancerous lesions, she explained.
Synthesizing various estimates on global burden of disease, Dr. Berg and colleagues calculated that in 2019 the rate of lung cancer deaths attributable to particular matter in people aged 50-69 years was highest in Serbia, at 36.88 attributable deaths per 100,000.
Next was Poland, with a rate of 27.97 per 100,000, followed by China at 24.63 per 100,000, Mongolia at 19.71 per 100,000, and Turkey at 19.2 per 100,000.
The major sources of air pollution in the most affected countries were transportation, indoor cooking, and energy sources, she said.
In Serbia, 70% of energy production was from coal. It was 74% in Poland, 65% in China, 80% in Mongolia, 35% in Turkey, and 19% in the United States.
At the time of the analysis, only 17.3% of U.S. adults were smokers, and the air concentration of particular matter of 2.5 mcm was 9.6% mcg/m3. Both of these rates are far below those seen in more severely affected countries.
“But 40% of our energy now comes from natural gas,” noted Dr. Berg, “which is still a pollutant and a source of methane. It’s a very potent greenhouse gas.”
No funding for the study has been reported. Dr. Berg has relationships with GRAIL and Mercy BioAnalytics. Dr. Aerts has relationships with Amphera, AstraZeneca, Bayer, BIOCAD, Bristol-Myers Squibb, Eli Lilly, and Roche.
A version of this article first appeared on Medscape.com.
The new data show that the rate of lung cancer deaths attributable to air pollution varies widely between countries. Serbia, Poland, China, Mongolia, and Turkey are among the worst affected. The analysis shows an association between deaths from lung cancer and the proportion of national energy that is produced from coal.
“Both smoking and air pollution are important causes of lung cancer,” said study presenter Christine D. Berg, MD, former codirector of the National Lung Screening Trial, and “both need to be eliminated to help prevent lung cancer and save lives.
“As lung cancer professionals, we can mitigate the effects of air pollution on causing lung cancer by speaking out for clean energy standards,” she said.
Dr. Berg presented the new analysis on Sept. 9 at the 2021 World Conference on Lung Cancer, which was organized by the International Association for the Study of Lung Cancer.
She welcomed the recent statement issued by the IASLC in support of the International Day of Clean Air for Blue Skies, which took place on Sept. 7. It was a call for action that emphasized the need for further efforts to improve air quality to protect human health.
The findings from the new analysis are “depressing,” commented Joachim G. J. V. Aerts, MD. PhD, department of pulmonary diseases, Erasmus University Medical Center, Rotterdam, the Netherlands.
It is now clear that air pollution has an impact not only on the incidence of lung cancer but also on its outcome, he added.
Indeed, previous research showed that each 10 mcg/m3 increase in particular matter of 2.5 mcg in size was associated with a 15%-27% increase in lung cancer mortality. There was no difference in rates between women and men.
A key question, Dr. Aerts said, is whether reducing air pollution would be beneficial.
Efforts to reduce air pollution over recent decades in the United Kingdom have not led to a reduction in lung cancer deaths. This is because of the increase in life expectancy – individuals have been exposed to pollution for longer, albeit at lower levels, he pointed out.
Because of lockdowns during the COVID pandemic, travel has been greatly reduced. This has resulted in a dramatic reduction in air pollution, “and this led to a decrease in the number of children born with low birth weight,” said Dr. Aerts.
Hopefully, that benefit will also be seen regarding other diseases, he added.
The call to action to reduce air pollution is of the “utmost importance,” he said. He noted that the focus should be on global, national, local, and personal preventive measures.
“It is time to join forces,” he added, “to ‘clean the air.’ ”
Dr. Berg’s presentation was warmly received on social media.
It was “fabulous,” commented Eric H. Bernicker, MD, director of medical thoracic oncology at Houston Methodist Cancer Center.
“Thoracic oncologists need to add air pollution to things they advocate about; we have an important voice here,” he added.
It is “so important to understand that air pollution is a human carcinogen,” commented Ivy Elkins, a lung cancer survivor and advocate and cofounder of the EGFR Resisters Lung Cancer Patient Group. “All you need are lungs to get lung cancer!”
Contribution of air pollution to lung cancer
In her presentation, Dr. Berg emphasized that lung cancer is the leading cause of cancer death worldwide, although the distribution between countries “depends on historical and current smoking patterns and the demographics of the population.”
Overall, data from GLOBOCAN 2018 indicate that annually there are approximately 2.1 million incident cases of lung cancer and almost 1.8 million lung cancer deaths around the globe.
A recent study estimated that, worldwide, 14.1% of all lung cancer deaths, including in never-smokers, are directly linked to air pollution.
Dr. Berg said that this makes it the “second-leading cause of lung cancer” behind smoking.
The figure is somewhat lower for the United States, where around 4.7% of lung cancer deaths each year are directly attributable to pollution. However, with “the wildfires out West, we’re going to be seeing more of a toll from air pollution,” she predicted.
She pointed out that the International Agency for Research on Cancer classifies outdoor air pollution, especially particulate matter, as a human carcinogen on the basis of evidence of an association with lung cancer.
It is thought that direct deposits and local effects of particulate matter lead to oxidative damage and low-grade chronic inflammation. These in turn result in molecular changes that affect DNA and gene transcription and inhibit apoptosis, all of which lead to the development of cancerous lesions, she explained.
Synthesizing various estimates on global burden of disease, Dr. Berg and colleagues calculated that in 2019 the rate of lung cancer deaths attributable to particular matter in people aged 50-69 years was highest in Serbia, at 36.88 attributable deaths per 100,000.
Next was Poland, with a rate of 27.97 per 100,000, followed by China at 24.63 per 100,000, Mongolia at 19.71 per 100,000, and Turkey at 19.2 per 100,000.
The major sources of air pollution in the most affected countries were transportation, indoor cooking, and energy sources, she said.
In Serbia, 70% of energy production was from coal. It was 74% in Poland, 65% in China, 80% in Mongolia, 35% in Turkey, and 19% in the United States.
At the time of the analysis, only 17.3% of U.S. adults were smokers, and the air concentration of particular matter of 2.5 mcm was 9.6% mcg/m3. Both of these rates are far below those seen in more severely affected countries.
“But 40% of our energy now comes from natural gas,” noted Dr. Berg, “which is still a pollutant and a source of methane. It’s a very potent greenhouse gas.”
No funding for the study has been reported. Dr. Berg has relationships with GRAIL and Mercy BioAnalytics. Dr. Aerts has relationships with Amphera, AstraZeneca, Bayer, BIOCAD, Bristol-Myers Squibb, Eli Lilly, and Roche.
A version of this article first appeared on Medscape.com.
The new data show that the rate of lung cancer deaths attributable to air pollution varies widely between countries. Serbia, Poland, China, Mongolia, and Turkey are among the worst affected. The analysis shows an association between deaths from lung cancer and the proportion of national energy that is produced from coal.
“Both smoking and air pollution are important causes of lung cancer,” said study presenter Christine D. Berg, MD, former codirector of the National Lung Screening Trial, and “both need to be eliminated to help prevent lung cancer and save lives.
“As lung cancer professionals, we can mitigate the effects of air pollution on causing lung cancer by speaking out for clean energy standards,” she said.
Dr. Berg presented the new analysis on Sept. 9 at the 2021 World Conference on Lung Cancer, which was organized by the International Association for the Study of Lung Cancer.
She welcomed the recent statement issued by the IASLC in support of the International Day of Clean Air for Blue Skies, which took place on Sept. 7. It was a call for action that emphasized the need for further efforts to improve air quality to protect human health.
The findings from the new analysis are “depressing,” commented Joachim G. J. V. Aerts, MD. PhD, department of pulmonary diseases, Erasmus University Medical Center, Rotterdam, the Netherlands.
It is now clear that air pollution has an impact not only on the incidence of lung cancer but also on its outcome, he added.
Indeed, previous research showed that each 10 mcg/m3 increase in particular matter of 2.5 mcg in size was associated with a 15%-27% increase in lung cancer mortality. There was no difference in rates between women and men.
A key question, Dr. Aerts said, is whether reducing air pollution would be beneficial.
Efforts to reduce air pollution over recent decades in the United Kingdom have not led to a reduction in lung cancer deaths. This is because of the increase in life expectancy – individuals have been exposed to pollution for longer, albeit at lower levels, he pointed out.
Because of lockdowns during the COVID pandemic, travel has been greatly reduced. This has resulted in a dramatic reduction in air pollution, “and this led to a decrease in the number of children born with low birth weight,” said Dr. Aerts.
Hopefully, that benefit will also be seen regarding other diseases, he added.
The call to action to reduce air pollution is of the “utmost importance,” he said. He noted that the focus should be on global, national, local, and personal preventive measures.
“It is time to join forces,” he added, “to ‘clean the air.’ ”
Dr. Berg’s presentation was warmly received on social media.
It was “fabulous,” commented Eric H. Bernicker, MD, director of medical thoracic oncology at Houston Methodist Cancer Center.
“Thoracic oncologists need to add air pollution to things they advocate about; we have an important voice here,” he added.
It is “so important to understand that air pollution is a human carcinogen,” commented Ivy Elkins, a lung cancer survivor and advocate and cofounder of the EGFR Resisters Lung Cancer Patient Group. “All you need are lungs to get lung cancer!”
Contribution of air pollution to lung cancer
In her presentation, Dr. Berg emphasized that lung cancer is the leading cause of cancer death worldwide, although the distribution between countries “depends on historical and current smoking patterns and the demographics of the population.”
Overall, data from GLOBOCAN 2018 indicate that annually there are approximately 2.1 million incident cases of lung cancer and almost 1.8 million lung cancer deaths around the globe.
A recent study estimated that, worldwide, 14.1% of all lung cancer deaths, including in never-smokers, are directly linked to air pollution.
Dr. Berg said that this makes it the “second-leading cause of lung cancer” behind smoking.
The figure is somewhat lower for the United States, where around 4.7% of lung cancer deaths each year are directly attributable to pollution. However, with “the wildfires out West, we’re going to be seeing more of a toll from air pollution,” she predicted.
She pointed out that the International Agency for Research on Cancer classifies outdoor air pollution, especially particulate matter, as a human carcinogen on the basis of evidence of an association with lung cancer.
It is thought that direct deposits and local effects of particulate matter lead to oxidative damage and low-grade chronic inflammation. These in turn result in molecular changes that affect DNA and gene transcription and inhibit apoptosis, all of which lead to the development of cancerous lesions, she explained.
Synthesizing various estimates on global burden of disease, Dr. Berg and colleagues calculated that in 2019 the rate of lung cancer deaths attributable to particular matter in people aged 50-69 years was highest in Serbia, at 36.88 attributable deaths per 100,000.
Next was Poland, with a rate of 27.97 per 100,000, followed by China at 24.63 per 100,000, Mongolia at 19.71 per 100,000, and Turkey at 19.2 per 100,000.
The major sources of air pollution in the most affected countries were transportation, indoor cooking, and energy sources, she said.
In Serbia, 70% of energy production was from coal. It was 74% in Poland, 65% in China, 80% in Mongolia, 35% in Turkey, and 19% in the United States.
At the time of the analysis, only 17.3% of U.S. adults were smokers, and the air concentration of particular matter of 2.5 mcm was 9.6% mcg/m3. Both of these rates are far below those seen in more severely affected countries.
“But 40% of our energy now comes from natural gas,” noted Dr. Berg, “which is still a pollutant and a source of methane. It’s a very potent greenhouse gas.”
No funding for the study has been reported. Dr. Berg has relationships with GRAIL and Mercy BioAnalytics. Dr. Aerts has relationships with Amphera, AstraZeneca, Bayer, BIOCAD, Bristol-Myers Squibb, Eli Lilly, and Roche.
A version of this article first appeared on Medscape.com.
Unequal resource distribution underlies lung cancer disparities
Lung cancer disparities are reversible, but it will take changes at the social policy and organizational levels to do it, according to Ray Osarogiagbon, MBBS, a medical oncologist in the thoracic oncology program at Baptist Cancer Center, Memphis.
Much of the issue comes down to unequal distribution of services across the country, with less high-end care available in areas hardest hit by lung cancer, which are often areas with higher percentages of Black people, Dr. Osarogiagbon said. He addressed the issues – which he conceptualizes as “avoidable differences” – in a plenary presentation at the virtual 2021 World Conference on Lung Cancer.
He said that much of disparity research has focused on patient-level issues, but it has the least potential to effect change and also has “the unpleasant side effect of stigmatizing the victims of disparate health care delivery.”
Better to look at the big picture. “We have to focus on the areas where we are most likely to be successful, the social policy level, next the organizational level, and then providers,” he said.
Kentucky, followed by Mississippi, Arkansas, Tennessee, West Virginia, and Alabama, has the highest lung cancer burden in the United States. While lung cancer has been on the decline for decades nationwide, some counties in those states in particular continue to struggle with rising lung cancer mortality.
Dr. Osarogiagbon’s own health care system, which serves western Tennessee as well as eastern Arkansas and northern Mississippi, sees about 1,300 lung cancer cases annually, more than many states in the United States.
Regional disparities in lung cancer care span the entirety of available services, from unequal access to tobacco cessation and other preventive measures straight through to access to leading-edge systemic therapies. Disparities are particularly acute with more recent advances such as immunotherapy and low-dose CT screening.
One recent study, for instance, found that several southern states with high lung cancer burdens had screening rates below 4%, while several New England states had rates ranging to over 15%.
“There is a mismatch between the places were lung cancer kills and the places where we have invested in low-dose CT scan facilities,” Dr. Osarogiagbon said. As a side effect, White patients have better access,
It’s not, he said, that Black people are more likely to refuse such services, as least as far as clinical trials go.
Black patients are significantly underrepresented in pharmaceutical industry trials. Part of the issues is that areas hardest hit by lung cancer are often also ones less likely to have the infrastructure to support trials.
But on an equal playing field, Black patients are at least as eager as White patients to sign up for a trial. Dr. Osarogiagbon and colleagues found that, if offered the chance, almost 60% of Black patients said they would participate in a trial versus 53.4% of White patients. If access were equal, there would be “no race-based disparities” in trial participation, he said.
It’s also emerging that Black patients might benefit more from innovations such as immune checkpoint inhibitors treatment and low-dose CT screening, which means that, if they were included in more trials, companies would likely have stronger study results.
It’s something they should pay attention to, if for no other reason than it would help their bottom line, Dr. Osarogiagbon said.
Curative surgery for early-stage lung tumors is another issue. At the county level in the United States, he and his team found that it’s offered to anywhere from 13% to 92% of patients who qualify.
“Counties in the lowest quartile for receipt of surgery were those with a high proportion of non-Hispanic Black subjects, high poverty and uninsured rates, low surgeon-to-population ratio, and nonmetropolitan status,” they found.
Dr. Osarogiagbon is a consultant for and/or has stock in a number of companies, including AstraZeneca, Eli Lilly, and Genentech.
Lung cancer disparities are reversible, but it will take changes at the social policy and organizational levels to do it, according to Ray Osarogiagbon, MBBS, a medical oncologist in the thoracic oncology program at Baptist Cancer Center, Memphis.
Much of the issue comes down to unequal distribution of services across the country, with less high-end care available in areas hardest hit by lung cancer, which are often areas with higher percentages of Black people, Dr. Osarogiagbon said. He addressed the issues – which he conceptualizes as “avoidable differences” – in a plenary presentation at the virtual 2021 World Conference on Lung Cancer.
He said that much of disparity research has focused on patient-level issues, but it has the least potential to effect change and also has “the unpleasant side effect of stigmatizing the victims of disparate health care delivery.”
Better to look at the big picture. “We have to focus on the areas where we are most likely to be successful, the social policy level, next the organizational level, and then providers,” he said.
Kentucky, followed by Mississippi, Arkansas, Tennessee, West Virginia, and Alabama, has the highest lung cancer burden in the United States. While lung cancer has been on the decline for decades nationwide, some counties in those states in particular continue to struggle with rising lung cancer mortality.
Dr. Osarogiagbon’s own health care system, which serves western Tennessee as well as eastern Arkansas and northern Mississippi, sees about 1,300 lung cancer cases annually, more than many states in the United States.
Regional disparities in lung cancer care span the entirety of available services, from unequal access to tobacco cessation and other preventive measures straight through to access to leading-edge systemic therapies. Disparities are particularly acute with more recent advances such as immunotherapy and low-dose CT screening.
One recent study, for instance, found that several southern states with high lung cancer burdens had screening rates below 4%, while several New England states had rates ranging to over 15%.
“There is a mismatch between the places were lung cancer kills and the places where we have invested in low-dose CT scan facilities,” Dr. Osarogiagbon said. As a side effect, White patients have better access,
It’s not, he said, that Black people are more likely to refuse such services, as least as far as clinical trials go.
Black patients are significantly underrepresented in pharmaceutical industry trials. Part of the issues is that areas hardest hit by lung cancer are often also ones less likely to have the infrastructure to support trials.
But on an equal playing field, Black patients are at least as eager as White patients to sign up for a trial. Dr. Osarogiagbon and colleagues found that, if offered the chance, almost 60% of Black patients said they would participate in a trial versus 53.4% of White patients. If access were equal, there would be “no race-based disparities” in trial participation, he said.
It’s also emerging that Black patients might benefit more from innovations such as immune checkpoint inhibitors treatment and low-dose CT screening, which means that, if they were included in more trials, companies would likely have stronger study results.
It’s something they should pay attention to, if for no other reason than it would help their bottom line, Dr. Osarogiagbon said.
Curative surgery for early-stage lung tumors is another issue. At the county level in the United States, he and his team found that it’s offered to anywhere from 13% to 92% of patients who qualify.
“Counties in the lowest quartile for receipt of surgery were those with a high proportion of non-Hispanic Black subjects, high poverty and uninsured rates, low surgeon-to-population ratio, and nonmetropolitan status,” they found.
Dr. Osarogiagbon is a consultant for and/or has stock in a number of companies, including AstraZeneca, Eli Lilly, and Genentech.
Lung cancer disparities are reversible, but it will take changes at the social policy and organizational levels to do it, according to Ray Osarogiagbon, MBBS, a medical oncologist in the thoracic oncology program at Baptist Cancer Center, Memphis.
Much of the issue comes down to unequal distribution of services across the country, with less high-end care available in areas hardest hit by lung cancer, which are often areas with higher percentages of Black people, Dr. Osarogiagbon said. He addressed the issues – which he conceptualizes as “avoidable differences” – in a plenary presentation at the virtual 2021 World Conference on Lung Cancer.
He said that much of disparity research has focused on patient-level issues, but it has the least potential to effect change and also has “the unpleasant side effect of stigmatizing the victims of disparate health care delivery.”
Better to look at the big picture. “We have to focus on the areas where we are most likely to be successful, the social policy level, next the organizational level, and then providers,” he said.
Kentucky, followed by Mississippi, Arkansas, Tennessee, West Virginia, and Alabama, has the highest lung cancer burden in the United States. While lung cancer has been on the decline for decades nationwide, some counties in those states in particular continue to struggle with rising lung cancer mortality.
Dr. Osarogiagbon’s own health care system, which serves western Tennessee as well as eastern Arkansas and northern Mississippi, sees about 1,300 lung cancer cases annually, more than many states in the United States.
Regional disparities in lung cancer care span the entirety of available services, from unequal access to tobacco cessation and other preventive measures straight through to access to leading-edge systemic therapies. Disparities are particularly acute with more recent advances such as immunotherapy and low-dose CT screening.
One recent study, for instance, found that several southern states with high lung cancer burdens had screening rates below 4%, while several New England states had rates ranging to over 15%.
“There is a mismatch between the places were lung cancer kills and the places where we have invested in low-dose CT scan facilities,” Dr. Osarogiagbon said. As a side effect, White patients have better access,
It’s not, he said, that Black people are more likely to refuse such services, as least as far as clinical trials go.
Black patients are significantly underrepresented in pharmaceutical industry trials. Part of the issues is that areas hardest hit by lung cancer are often also ones less likely to have the infrastructure to support trials.
But on an equal playing field, Black patients are at least as eager as White patients to sign up for a trial. Dr. Osarogiagbon and colleagues found that, if offered the chance, almost 60% of Black patients said they would participate in a trial versus 53.4% of White patients. If access were equal, there would be “no race-based disparities” in trial participation, he said.
It’s also emerging that Black patients might benefit more from innovations such as immune checkpoint inhibitors treatment and low-dose CT screening, which means that, if they were included in more trials, companies would likely have stronger study results.
It’s something they should pay attention to, if for no other reason than it would help their bottom line, Dr. Osarogiagbon said.
Curative surgery for early-stage lung tumors is another issue. At the county level in the United States, he and his team found that it’s offered to anywhere from 13% to 92% of patients who qualify.
“Counties in the lowest quartile for receipt of surgery were those with a high proportion of non-Hispanic Black subjects, high poverty and uninsured rates, low surgeon-to-population ratio, and nonmetropolitan status,” they found.
Dr. Osarogiagbon is a consultant for and/or has stock in a number of companies, including AstraZeneca, Eli Lilly, and Genentech.
FROM WCLC 2021
Finding the most bang for the buck with adjuvant atezolizumab for NSCLC
Investigators are zeroing in on the stage II-IIIa non–small cell lung cancer patients most likely to benefit from adjuvant atezolizumab (Tecentriq) following resection and chemotherapy.
It seems that PD-L1 positive patients, those who undergo lobectomy, those who have nodal involvement, and those treated with all common platinum doublets, with the possible exception of cisplatin-gemcitabine, are most likely to benefit from adjuvant treatment, according to a report at the virtual 2021 World Congress on Lung Cancer.
Results come for an analysis of IMpower010, which randomized 1,005 patients equally to either best supportive care or atezolizumab every 21 days for 16 cycles following resection and chemotherapy.
The topline results, reported recently, found a 34% improvement in disease-free survival (DFS) in stage II-IIIa patients expressing PD-L1 and a 21% improvement across all patients regardless of PD-L1 expression.
It was the first positive phase 3 trial for adjuvant immunotherapy in NSCLC. Maker Hoffman-La Roche subsequently applied to the U.S. Food and Drug Administration for an indication for adjuvant treatment following surgery and platinum-based chemotherapy for NSCLC with PD-L1 expression of at least 1%.
At the WCLC meeting, investigators took a closer look at IMpower010 to gauge the impact of different surgery and chemotherapy types on outcomes.
“Improved DFS was observed with adjuvant atezolizumab” for II-IIIa disease across most stages in patients “with nodal involvement, and across most surgery resection types and chemotherapy regimens,” said lead investigator Nasser Altorki, MD, director of the division of thoracic surgery at New York Presbyterian-Weill Cornell Medical Center in New York.
Study discussant Ichiro Yoshino, MD, PhD, a thoracic surgeon at Chiba University, in Japan, expanded on the “most” part of the assertion.
“Patients who underwent lobectomy [78%] had more evident benefit. … Patients who had a pneumonectomy [16%] did not benefit from atezolizumab,” he said (DFS hazard ratio, 0.91, 95% confidence interval, 0.56-1.47).
The reasons are unclear. It could be because patients who have pneumonectomies are less tolerant of adjuvant chemotherapy, so might have not gotten complete courses, but whatever the cause, Dr. Yoshino said it’s an important finding that needs further investigation.
Also, there was no DFS benefit in the 16% of patients who received cisplatin-gemcitabine for chemotherapy instead of other platinum doublets (HR, 0.94, 95% CI, 0.56-1.57).
It might have to do with the fact that under 80% of cisplatin-gemcitabine patients completed all four cycles of chemotherapy versus completion rates of up to more than 90% with other platinum doublets. It might also, however, have something to do with the way gemcitabine works or its interaction with atezolizumab.
The issue is another one that needs “to be examined,” Dr. Yoshino said.
The trial was funded by Hoffman-La Roche. Dr. Altorki is an advisor and/or researcher for AstraZeneca, Merck, and Johnson & Johnson. Among various company ties, Dr. Yoshino is an advisor and speaker for AstraZeneca and Johnson & Johnson and a researcher for Pfizer.
Investigators are zeroing in on the stage II-IIIa non–small cell lung cancer patients most likely to benefit from adjuvant atezolizumab (Tecentriq) following resection and chemotherapy.
It seems that PD-L1 positive patients, those who undergo lobectomy, those who have nodal involvement, and those treated with all common platinum doublets, with the possible exception of cisplatin-gemcitabine, are most likely to benefit from adjuvant treatment, according to a report at the virtual 2021 World Congress on Lung Cancer.
Results come for an analysis of IMpower010, which randomized 1,005 patients equally to either best supportive care or atezolizumab every 21 days for 16 cycles following resection and chemotherapy.
The topline results, reported recently, found a 34% improvement in disease-free survival (DFS) in stage II-IIIa patients expressing PD-L1 and a 21% improvement across all patients regardless of PD-L1 expression.
It was the first positive phase 3 trial for adjuvant immunotherapy in NSCLC. Maker Hoffman-La Roche subsequently applied to the U.S. Food and Drug Administration for an indication for adjuvant treatment following surgery and platinum-based chemotherapy for NSCLC with PD-L1 expression of at least 1%.
At the WCLC meeting, investigators took a closer look at IMpower010 to gauge the impact of different surgery and chemotherapy types on outcomes.
“Improved DFS was observed with adjuvant atezolizumab” for II-IIIa disease across most stages in patients “with nodal involvement, and across most surgery resection types and chemotherapy regimens,” said lead investigator Nasser Altorki, MD, director of the division of thoracic surgery at New York Presbyterian-Weill Cornell Medical Center in New York.
Study discussant Ichiro Yoshino, MD, PhD, a thoracic surgeon at Chiba University, in Japan, expanded on the “most” part of the assertion.
“Patients who underwent lobectomy [78%] had more evident benefit. … Patients who had a pneumonectomy [16%] did not benefit from atezolizumab,” he said (DFS hazard ratio, 0.91, 95% confidence interval, 0.56-1.47).
The reasons are unclear. It could be because patients who have pneumonectomies are less tolerant of adjuvant chemotherapy, so might have not gotten complete courses, but whatever the cause, Dr. Yoshino said it’s an important finding that needs further investigation.
Also, there was no DFS benefit in the 16% of patients who received cisplatin-gemcitabine for chemotherapy instead of other platinum doublets (HR, 0.94, 95% CI, 0.56-1.57).
It might have to do with the fact that under 80% of cisplatin-gemcitabine patients completed all four cycles of chemotherapy versus completion rates of up to more than 90% with other platinum doublets. It might also, however, have something to do with the way gemcitabine works or its interaction with atezolizumab.
The issue is another one that needs “to be examined,” Dr. Yoshino said.
The trial was funded by Hoffman-La Roche. Dr. Altorki is an advisor and/or researcher for AstraZeneca, Merck, and Johnson & Johnson. Among various company ties, Dr. Yoshino is an advisor and speaker for AstraZeneca and Johnson & Johnson and a researcher for Pfizer.
Investigators are zeroing in on the stage II-IIIa non–small cell lung cancer patients most likely to benefit from adjuvant atezolizumab (Tecentriq) following resection and chemotherapy.
It seems that PD-L1 positive patients, those who undergo lobectomy, those who have nodal involvement, and those treated with all common platinum doublets, with the possible exception of cisplatin-gemcitabine, are most likely to benefit from adjuvant treatment, according to a report at the virtual 2021 World Congress on Lung Cancer.
Results come for an analysis of IMpower010, which randomized 1,005 patients equally to either best supportive care or atezolizumab every 21 days for 16 cycles following resection and chemotherapy.
The topline results, reported recently, found a 34% improvement in disease-free survival (DFS) in stage II-IIIa patients expressing PD-L1 and a 21% improvement across all patients regardless of PD-L1 expression.
It was the first positive phase 3 trial for adjuvant immunotherapy in NSCLC. Maker Hoffman-La Roche subsequently applied to the U.S. Food and Drug Administration for an indication for adjuvant treatment following surgery and platinum-based chemotherapy for NSCLC with PD-L1 expression of at least 1%.
At the WCLC meeting, investigators took a closer look at IMpower010 to gauge the impact of different surgery and chemotherapy types on outcomes.
“Improved DFS was observed with adjuvant atezolizumab” for II-IIIa disease across most stages in patients “with nodal involvement, and across most surgery resection types and chemotherapy regimens,” said lead investigator Nasser Altorki, MD, director of the division of thoracic surgery at New York Presbyterian-Weill Cornell Medical Center in New York.
Study discussant Ichiro Yoshino, MD, PhD, a thoracic surgeon at Chiba University, in Japan, expanded on the “most” part of the assertion.
“Patients who underwent lobectomy [78%] had more evident benefit. … Patients who had a pneumonectomy [16%] did not benefit from atezolizumab,” he said (DFS hazard ratio, 0.91, 95% confidence interval, 0.56-1.47).
The reasons are unclear. It could be because patients who have pneumonectomies are less tolerant of adjuvant chemotherapy, so might have not gotten complete courses, but whatever the cause, Dr. Yoshino said it’s an important finding that needs further investigation.
Also, there was no DFS benefit in the 16% of patients who received cisplatin-gemcitabine for chemotherapy instead of other platinum doublets (HR, 0.94, 95% CI, 0.56-1.57).
It might have to do with the fact that under 80% of cisplatin-gemcitabine patients completed all four cycles of chemotherapy versus completion rates of up to more than 90% with other platinum doublets. It might also, however, have something to do with the way gemcitabine works or its interaction with atezolizumab.
The issue is another one that needs “to be examined,” Dr. Yoshino said.
The trial was funded by Hoffman-La Roche. Dr. Altorki is an advisor and/or researcher for AstraZeneca, Merck, and Johnson & Johnson. Among various company ties, Dr. Yoshino is an advisor and speaker for AstraZeneca and Johnson & Johnson and a researcher for Pfizer.
FROM WCLC 2021
Microwave ablation an alternative therapy in lung malignancy
Lung cancer patients with relatively small nodules who cannot or will not undergo surgery or radiotherapy can be successfully treated with targeted transbronchial microwave ablation, indicate results from a U.K.-led preliminary trial.
The NAVABLATE study included 30 patients from the U.K. and Hong Kong who had malignant lung nodules no more than 30 mm in diameter, who underwent transbronchial microwave ablation and were followed up one month later.
On the day, the technique was performed successfully in all 30 patients, while follow-up imaging at one month suggested that the ablation had been satisfactory in every case, with no repeat procedures necessary.
It was also associated with a “low rate of device-related adverse events and no serious adverse events,” said lead author Kevin Lau, Barts Thorax Centre, St. Bartholomew’s Hospital, Barts Health NHS Trust, London.
Consequently, transbronchial microwave ablation can be considered “an alternative treatment modality for patients with primary and metastatic malignant lung nodules … who decline or are ineligible” for surgery and radiotherapy.
The research was presented at the European Respiratory Society International Congress (ERS) 2021 on September 5.
‘Encouraging’ results
Professor Stefano Elia, head of the European Respiratory Society’s Assembly on Thoracic Surgery and Transplantation, told this news organization that the results “are encouraging.”
However, the patient numbers are “very low, so it is difficult to draw value conclusions,” and he would like to have seen more detailed characterization of the patients’ tumors.
Prof. Elia, from the University of Rome Tor Vergata, added that transbronchial microwave ablation should, in line with the study’s inclusion criteria, “probably be reserved” for lung cancer patients “who are unfit for or refuse surgery or alternative treatment strategies.”
He added that “prospective, randomized trials are warranted to see if the technique is feasible, safe and indicated” in these patients, and the potential cost of performing it needs to be specified.
Study details
Presenting the study, Mr. Lau explained that NAVABLATE was a prospective, multicenter study that enrolled patients with a confirmed malignant lung nodule ≤30 mm that did not abut the pleura, fissure, or critical structures.
In addition, the patients had declined or were not eligible for both surgery and stereotactic body radiotherapy.
They underwent transbronchial microwave ablation with the Emprint ablation catheter (Medtronic) in a hybrid theatre while undergoing cone-beam computed tomography. Only one nodule was ablated if the patients had more than one.
The team recruited 30 patients at two centres in the U.K. and Hong Kong, who had a mean age of 68.4 years and of whom 40% were female. The majority (66.7%) were prior or current tobacco users.
Primary lung cancer was the diagnosis in 20 patients, while 10 had oligometastatic disease, and the median nodule size was 12.5 mm. Thirty percent of patients had previously undergone lobectomy and 16.7% wedge resection.
Thirty-nine ablations were performed in the 30 patients, with 22 having a single ablation. Two ablations were performed in seven patients, while one had three ablations.
The most common ablation times were 10 minutes, in 21 procedures, and 7 minutes, in eight procedures, and the average total bronchoscopy time was 127 minutes.
Technical success
The procedure was deemed a technical success, defined as the nodule being reached and ablated according to the study protocol, in all patients.
The average ablation margin was 9.9 mm, and 1-month follow-up imaging was performed in all patients. This revealed a satisfactory ablation in 100% of cases. No patients required retreatment.
One patient had an adverse event relating to the ablation itself over the one-month follow-up, consisting of grade 1 mild haemoptysis on day 5, which self-resolved.
Adverse events relating to any aspect of the bronchoscopy were seen in 70% of patients, while 13.3% had grade ≥3 events, These included post-procedure pleuritic chest pain in two patients, pleural effusion in two patients, post-ablation syndrome in one patient, and ablation site infection in one patient, all grade 3.
The researchers found that the patients reported only mild pain immediately post-procedure, at an average score of 1.5 on a 10-point scale, falling to 1.4 one week later. At one month, the average pain score was 0.5.
Quality of life, as measured on the EQ-5D-3L was unaffected by the procedure, with scores rising slightly from 74.6 at baseline to 77.4 at the one-month follow-up.
The study was sponsored and funded by Medtronic.
Mr. Lau declares relationships with Medtronic, Philips, and Johnson & Johnson.
A version of this article first appeared on Medscape.com.
Lung cancer patients with relatively small nodules who cannot or will not undergo surgery or radiotherapy can be successfully treated with targeted transbronchial microwave ablation, indicate results from a U.K.-led preliminary trial.
The NAVABLATE study included 30 patients from the U.K. and Hong Kong who had malignant lung nodules no more than 30 mm in diameter, who underwent transbronchial microwave ablation and were followed up one month later.
On the day, the technique was performed successfully in all 30 patients, while follow-up imaging at one month suggested that the ablation had been satisfactory in every case, with no repeat procedures necessary.
It was also associated with a “low rate of device-related adverse events and no serious adverse events,” said lead author Kevin Lau, Barts Thorax Centre, St. Bartholomew’s Hospital, Barts Health NHS Trust, London.
Consequently, transbronchial microwave ablation can be considered “an alternative treatment modality for patients with primary and metastatic malignant lung nodules … who decline or are ineligible” for surgery and radiotherapy.
The research was presented at the European Respiratory Society International Congress (ERS) 2021 on September 5.
‘Encouraging’ results
Professor Stefano Elia, head of the European Respiratory Society’s Assembly on Thoracic Surgery and Transplantation, told this news organization that the results “are encouraging.”
However, the patient numbers are “very low, so it is difficult to draw value conclusions,” and he would like to have seen more detailed characterization of the patients’ tumors.
Prof. Elia, from the University of Rome Tor Vergata, added that transbronchial microwave ablation should, in line with the study’s inclusion criteria, “probably be reserved” for lung cancer patients “who are unfit for or refuse surgery or alternative treatment strategies.”
He added that “prospective, randomized trials are warranted to see if the technique is feasible, safe and indicated” in these patients, and the potential cost of performing it needs to be specified.
Study details
Presenting the study, Mr. Lau explained that NAVABLATE was a prospective, multicenter study that enrolled patients with a confirmed malignant lung nodule ≤30 mm that did not abut the pleura, fissure, or critical structures.
In addition, the patients had declined or were not eligible for both surgery and stereotactic body radiotherapy.
They underwent transbronchial microwave ablation with the Emprint ablation catheter (Medtronic) in a hybrid theatre while undergoing cone-beam computed tomography. Only one nodule was ablated if the patients had more than one.
The team recruited 30 patients at two centres in the U.K. and Hong Kong, who had a mean age of 68.4 years and of whom 40% were female. The majority (66.7%) were prior or current tobacco users.
Primary lung cancer was the diagnosis in 20 patients, while 10 had oligometastatic disease, and the median nodule size was 12.5 mm. Thirty percent of patients had previously undergone lobectomy and 16.7% wedge resection.
Thirty-nine ablations were performed in the 30 patients, with 22 having a single ablation. Two ablations were performed in seven patients, while one had three ablations.
The most common ablation times were 10 minutes, in 21 procedures, and 7 minutes, in eight procedures, and the average total bronchoscopy time was 127 minutes.
Technical success
The procedure was deemed a technical success, defined as the nodule being reached and ablated according to the study protocol, in all patients.
The average ablation margin was 9.9 mm, and 1-month follow-up imaging was performed in all patients. This revealed a satisfactory ablation in 100% of cases. No patients required retreatment.
One patient had an adverse event relating to the ablation itself over the one-month follow-up, consisting of grade 1 mild haemoptysis on day 5, which self-resolved.
Adverse events relating to any aspect of the bronchoscopy were seen in 70% of patients, while 13.3% had grade ≥3 events, These included post-procedure pleuritic chest pain in two patients, pleural effusion in two patients, post-ablation syndrome in one patient, and ablation site infection in one patient, all grade 3.
The researchers found that the patients reported only mild pain immediately post-procedure, at an average score of 1.5 on a 10-point scale, falling to 1.4 one week later. At one month, the average pain score was 0.5.
Quality of life, as measured on the EQ-5D-3L was unaffected by the procedure, with scores rising slightly from 74.6 at baseline to 77.4 at the one-month follow-up.
The study was sponsored and funded by Medtronic.
Mr. Lau declares relationships with Medtronic, Philips, and Johnson & Johnson.
A version of this article first appeared on Medscape.com.
Lung cancer patients with relatively small nodules who cannot or will not undergo surgery or radiotherapy can be successfully treated with targeted transbronchial microwave ablation, indicate results from a U.K.-led preliminary trial.
The NAVABLATE study included 30 patients from the U.K. and Hong Kong who had malignant lung nodules no more than 30 mm in diameter, who underwent transbronchial microwave ablation and were followed up one month later.
On the day, the technique was performed successfully in all 30 patients, while follow-up imaging at one month suggested that the ablation had been satisfactory in every case, with no repeat procedures necessary.
It was also associated with a “low rate of device-related adverse events and no serious adverse events,” said lead author Kevin Lau, Barts Thorax Centre, St. Bartholomew’s Hospital, Barts Health NHS Trust, London.
Consequently, transbronchial microwave ablation can be considered “an alternative treatment modality for patients with primary and metastatic malignant lung nodules … who decline or are ineligible” for surgery and radiotherapy.
The research was presented at the European Respiratory Society International Congress (ERS) 2021 on September 5.
‘Encouraging’ results
Professor Stefano Elia, head of the European Respiratory Society’s Assembly on Thoracic Surgery and Transplantation, told this news organization that the results “are encouraging.”
However, the patient numbers are “very low, so it is difficult to draw value conclusions,” and he would like to have seen more detailed characterization of the patients’ tumors.
Prof. Elia, from the University of Rome Tor Vergata, added that transbronchial microwave ablation should, in line with the study’s inclusion criteria, “probably be reserved” for lung cancer patients “who are unfit for or refuse surgery or alternative treatment strategies.”
He added that “prospective, randomized trials are warranted to see if the technique is feasible, safe and indicated” in these patients, and the potential cost of performing it needs to be specified.
Study details
Presenting the study, Mr. Lau explained that NAVABLATE was a prospective, multicenter study that enrolled patients with a confirmed malignant lung nodule ≤30 mm that did not abut the pleura, fissure, or critical structures.
In addition, the patients had declined or were not eligible for both surgery and stereotactic body radiotherapy.
They underwent transbronchial microwave ablation with the Emprint ablation catheter (Medtronic) in a hybrid theatre while undergoing cone-beam computed tomography. Only one nodule was ablated if the patients had more than one.
The team recruited 30 patients at two centres in the U.K. and Hong Kong, who had a mean age of 68.4 years and of whom 40% were female. The majority (66.7%) were prior or current tobacco users.
Primary lung cancer was the diagnosis in 20 patients, while 10 had oligometastatic disease, and the median nodule size was 12.5 mm. Thirty percent of patients had previously undergone lobectomy and 16.7% wedge resection.
Thirty-nine ablations were performed in the 30 patients, with 22 having a single ablation. Two ablations were performed in seven patients, while one had three ablations.
The most common ablation times were 10 minutes, in 21 procedures, and 7 minutes, in eight procedures, and the average total bronchoscopy time was 127 minutes.
Technical success
The procedure was deemed a technical success, defined as the nodule being reached and ablated according to the study protocol, in all patients.
The average ablation margin was 9.9 mm, and 1-month follow-up imaging was performed in all patients. This revealed a satisfactory ablation in 100% of cases. No patients required retreatment.
One patient had an adverse event relating to the ablation itself over the one-month follow-up, consisting of grade 1 mild haemoptysis on day 5, which self-resolved.
Adverse events relating to any aspect of the bronchoscopy were seen in 70% of patients, while 13.3% had grade ≥3 events, These included post-procedure pleuritic chest pain in two patients, pleural effusion in two patients, post-ablation syndrome in one patient, and ablation site infection in one patient, all grade 3.
The researchers found that the patients reported only mild pain immediately post-procedure, at an average score of 1.5 on a 10-point scale, falling to 1.4 one week later. At one month, the average pain score was 0.5.
Quality of life, as measured on the EQ-5D-3L was unaffected by the procedure, with scores rising slightly from 74.6 at baseline to 77.4 at the one-month follow-up.
The study was sponsored and funded by Medtronic.
Mr. Lau declares relationships with Medtronic, Philips, and Johnson & Johnson.
A version of this article first appeared on Medscape.com.
Racial Disparities in Treatment and Survival for Early-Stage Non-Small Cell Lung Cancer: Is Equal Access Health Care System the Answer?
Background
Survival for early-stage non-small cell lung cancer (NSCLC) has dramatically improved with advancement in surgical and radiation techniques over last two decades but there exists a disparity for African Americans (AA) having worse overall survival (OS) in recent studies on the general US population. We studied this racial disparity in Veteran population.
Methods
Data for 2589 AA and 14184 Caucasian Veterans diagnosed with early-stage (I, II) NSCLC between 2011-2017 was obtained from the Cancer Cube Registry (VACCR). IRB approval was obtained.
Results
The distribution of newly diagnosed cases of Stage I (73.92% AA vs 74.71% Caucasians) and Stage II (26.07% vs 25.29%) between the two races was comparable (p = .41). More Caucasians were diagnosed above the age of 60 compared to AA (92.22% vs 84.51%, p < .05). More AA were diagnosed with adenocarcinoma at diagnosis (56.01% vs 45.88% Caucasians, p < .05) for both Stage I and II disease. For the limited number of Veterans with reported performance status (PS), similar proportion of patients had a good PS defined as ECOG 0-2 among the two races (93.70% AA vs 93.97% Caucasians, p = .73). There was no statistically significant difference between 5-year OS for AA and Caucasians (69.81% vs 70.78%, p = .33) for both Stage I and II NSCLC. Both groups had similar rate of receipt of surgery as first line treatment or in combination with other treatments (58.90% AA vs 59.07% Caucasians, p = .90). Similarly, the rate of receiving radiation therapy was comparable between AA and Caucasians (42.4% vs 42.3%, p = .96). Although both races showed improved 5-year OS after surgery, there was no statistical difference in survival benefit between AA and Caucasians (69.8% vs 70.8%, p = .33).
Conclusion
In contrast to the studies assessing general US population trends, there was no racial disparity for 5-year OS in early-stage NSCLC for the Veteran population. This points to the inequities in access to treatment and preventive healthcare services as a possible contributing cause to the increased mortality in AA in general US population and a more equitable healthcare delivery within the VHA system.
Background
Survival for early-stage non-small cell lung cancer (NSCLC) has dramatically improved with advancement in surgical and radiation techniques over last two decades but there exists a disparity for African Americans (AA) having worse overall survival (OS) in recent studies on the general US population. We studied this racial disparity in Veteran population.
Methods
Data for 2589 AA and 14184 Caucasian Veterans diagnosed with early-stage (I, II) NSCLC between 2011-2017 was obtained from the Cancer Cube Registry (VACCR). IRB approval was obtained.
Results
The distribution of newly diagnosed cases of Stage I (73.92% AA vs 74.71% Caucasians) and Stage II (26.07% vs 25.29%) between the two races was comparable (p = .41). More Caucasians were diagnosed above the age of 60 compared to AA (92.22% vs 84.51%, p < .05). More AA were diagnosed with adenocarcinoma at diagnosis (56.01% vs 45.88% Caucasians, p < .05) for both Stage I and II disease. For the limited number of Veterans with reported performance status (PS), similar proportion of patients had a good PS defined as ECOG 0-2 among the two races (93.70% AA vs 93.97% Caucasians, p = .73). There was no statistically significant difference between 5-year OS for AA and Caucasians (69.81% vs 70.78%, p = .33) for both Stage I and II NSCLC. Both groups had similar rate of receipt of surgery as first line treatment or in combination with other treatments (58.90% AA vs 59.07% Caucasians, p = .90). Similarly, the rate of receiving radiation therapy was comparable between AA and Caucasians (42.4% vs 42.3%, p = .96). Although both races showed improved 5-year OS after surgery, there was no statistical difference in survival benefit between AA and Caucasians (69.8% vs 70.8%, p = .33).
Conclusion
In contrast to the studies assessing general US population trends, there was no racial disparity for 5-year OS in early-stage NSCLC for the Veteran population. This points to the inequities in access to treatment and preventive healthcare services as a possible contributing cause to the increased mortality in AA in general US population and a more equitable healthcare delivery within the VHA system.
Background
Survival for early-stage non-small cell lung cancer (NSCLC) has dramatically improved with advancement in surgical and radiation techniques over last two decades but there exists a disparity for African Americans (AA) having worse overall survival (OS) in recent studies on the general US population. We studied this racial disparity in Veteran population.
Methods
Data for 2589 AA and 14184 Caucasian Veterans diagnosed with early-stage (I, II) NSCLC between 2011-2017 was obtained from the Cancer Cube Registry (VACCR). IRB approval was obtained.
Results
The distribution of newly diagnosed cases of Stage I (73.92% AA vs 74.71% Caucasians) and Stage II (26.07% vs 25.29%) between the two races was comparable (p = .41). More Caucasians were diagnosed above the age of 60 compared to AA (92.22% vs 84.51%, p < .05). More AA were diagnosed with adenocarcinoma at diagnosis (56.01% vs 45.88% Caucasians, p < .05) for both Stage I and II disease. For the limited number of Veterans with reported performance status (PS), similar proportion of patients had a good PS defined as ECOG 0-2 among the two races (93.70% AA vs 93.97% Caucasians, p = .73). There was no statistically significant difference between 5-year OS for AA and Caucasians (69.81% vs 70.78%, p = .33) for both Stage I and II NSCLC. Both groups had similar rate of receipt of surgery as first line treatment or in combination with other treatments (58.90% AA vs 59.07% Caucasians, p = .90). Similarly, the rate of receiving radiation therapy was comparable between AA and Caucasians (42.4% vs 42.3%, p = .96). Although both races showed improved 5-year OS after surgery, there was no statistical difference in survival benefit between AA and Caucasians (69.8% vs 70.8%, p = .33).
Conclusion
In contrast to the studies assessing general US population trends, there was no racial disparity for 5-year OS in early-stage NSCLC for the Veteran population. This points to the inequities in access to treatment and preventive healthcare services as a possible contributing cause to the increased mortality in AA in general US population and a more equitable healthcare delivery within the VHA system.
Survival Analysis of Untreated Early-Stage Non-Small Cell Lung Cancer (NSCLC) in a Veteran Population
Introduction
Veterans with early-stage NSCLC who do not receive any form of treatment have been shown to have a worse overall survival compared to those who receive treatment. Factors that may influence the decision to administer treatment including age, performance status (PS), comorbidities, and racial disparity have not been assessed on a national level in recent years.
Methods
Data for 31,966 veterans diagnosed with early-stage (0, I) NSCLC between 2003-2017 was obtained from the Cancer cube registry (VACCR). IRB approval was obtained.
Results
Patients were divided into treatment (26,833/31,966, 83.16%) and no-treatment group (3096/31966, 9.68%). Of the no-treatment group, 3004 patients were stage I and 92 were stage 0 whereas in the treatment group, the distribution was 26,584 and 249 respectively. Gender, race, and histology distribution were comparable between the two. Patients with poor PS (defined as ECOG III and IV) received less treatment with any modality compared to those with good PS (ECOG I and II) (15.07% in no treatment group vs 4.03% in treatment group, p<0.05). The treatment group had a better 5-year overall survival (OS) as compared to no-treatment group (43.1% vs 14.7%, p<0.05). Regardless of treatment, patients above the age of 60 (41% vs 13.4%, p<0.05) and those with poor PS (19.6% vs 5.8%, p<0.05) had worse 5-year survival, with the effect being greater in the treatment group. Adenocarcinoma had a better 5-year survival compared to squamous cell carcinoma (SCC) in both groups (49.56% vs 39.1% p<0.05). There was no clinically significant OS difference in terms of race (Caucasian or African American) or tumor location (upper, middle, or lower lobe) in between the two groups. Our study was limited by lack of patient- level data including smoking status or reason why no treatment was given.
Conclusion
Patients with early-stage NSCLC who receive no treatment based on poor PS have a worse overall survival compared to the patients that receive treatment. Further investigation is required to assess what other criteria are used to decide treatment eligibility and whether these patients would be candidates for immunotherapy or targeted therapy in the future.
Introduction
Veterans with early-stage NSCLC who do not receive any form of treatment have been shown to have a worse overall survival compared to those who receive treatment. Factors that may influence the decision to administer treatment including age, performance status (PS), comorbidities, and racial disparity have not been assessed on a national level in recent years.
Methods
Data for 31,966 veterans diagnosed with early-stage (0, I) NSCLC between 2003-2017 was obtained from the Cancer cube registry (VACCR). IRB approval was obtained.
Results
Patients were divided into treatment (26,833/31,966, 83.16%) and no-treatment group (3096/31966, 9.68%). Of the no-treatment group, 3004 patients were stage I and 92 were stage 0 whereas in the treatment group, the distribution was 26,584 and 249 respectively. Gender, race, and histology distribution were comparable between the two. Patients with poor PS (defined as ECOG III and IV) received less treatment with any modality compared to those with good PS (ECOG I and II) (15.07% in no treatment group vs 4.03% in treatment group, p<0.05). The treatment group had a better 5-year overall survival (OS) as compared to no-treatment group (43.1% vs 14.7%, p<0.05). Regardless of treatment, patients above the age of 60 (41% vs 13.4%, p<0.05) and those with poor PS (19.6% vs 5.8%, p<0.05) had worse 5-year survival, with the effect being greater in the treatment group. Adenocarcinoma had a better 5-year survival compared to squamous cell carcinoma (SCC) in both groups (49.56% vs 39.1% p<0.05). There was no clinically significant OS difference in terms of race (Caucasian or African American) or tumor location (upper, middle, or lower lobe) in between the two groups. Our study was limited by lack of patient- level data including smoking status or reason why no treatment was given.
Conclusion
Patients with early-stage NSCLC who receive no treatment based on poor PS have a worse overall survival compared to the patients that receive treatment. Further investigation is required to assess what other criteria are used to decide treatment eligibility and whether these patients would be candidates for immunotherapy or targeted therapy in the future.
Introduction
Veterans with early-stage NSCLC who do not receive any form of treatment have been shown to have a worse overall survival compared to those who receive treatment. Factors that may influence the decision to administer treatment including age, performance status (PS), comorbidities, and racial disparity have not been assessed on a national level in recent years.
Methods
Data for 31,966 veterans diagnosed with early-stage (0, I) NSCLC between 2003-2017 was obtained from the Cancer cube registry (VACCR). IRB approval was obtained.
Results
Patients were divided into treatment (26,833/31,966, 83.16%) and no-treatment group (3096/31966, 9.68%). Of the no-treatment group, 3004 patients were stage I and 92 were stage 0 whereas in the treatment group, the distribution was 26,584 and 249 respectively. Gender, race, and histology distribution were comparable between the two. Patients with poor PS (defined as ECOG III and IV) received less treatment with any modality compared to those with good PS (ECOG I and II) (15.07% in no treatment group vs 4.03% in treatment group, p<0.05). The treatment group had a better 5-year overall survival (OS) as compared to no-treatment group (43.1% vs 14.7%, p<0.05). Regardless of treatment, patients above the age of 60 (41% vs 13.4%, p<0.05) and those with poor PS (19.6% vs 5.8%, p<0.05) had worse 5-year survival, with the effect being greater in the treatment group. Adenocarcinoma had a better 5-year survival compared to squamous cell carcinoma (SCC) in both groups (49.56% vs 39.1% p<0.05). There was no clinically significant OS difference in terms of race (Caucasian or African American) or tumor location (upper, middle, or lower lobe) in between the two groups. Our study was limited by lack of patient- level data including smoking status or reason why no treatment was given.
Conclusion
Patients with early-stage NSCLC who receive no treatment based on poor PS have a worse overall survival compared to the patients that receive treatment. Further investigation is required to assess what other criteria are used to decide treatment eligibility and whether these patients would be candidates for immunotherapy or targeted therapy in the future.
Metformin disappoints in two phase 2 lung cancer trials
Although well tolerated, metformin does not improve survival when given alongside chemoradiotherapy to patients with locally advanced non–small cell lung cancer (NSCLC), and may even make survival worse, suggest results from two recent phase 2 trials.
Epidemiologic studies have suggested that metformin is associated with a reduced incidence of cancer, while retrospective case studies have indicated that patients taking the drug have improved outcomes.
Moreover, preclinical data indicated that metformin has antineoplastic effects, with the drug showing both cytostatic and cytotoxic effects.
The current results cast doubt, however, over whether these benefits can be replicated in randomized controlled trials and thence brought to the clinic.
Despite this, “I don’t think metformin is dead,” commented Heath D. Skinner, MD, PhD, first author on one of the trials, published in JAMA Oncology.
He said in an interview there are “a few key areas where I think metformin could be of benefit” in lung cancer, such as in combination with tyrosine kinase inhibitors, or with immunotherapy.
Dr. Skinner also highlighted the unexpectedly good performance of standard chemoradiation, showing the “progress” that has been made in recent years in treatment delivery and quality.
No survival benefit
In the first trial, which was an open-label phase 2 study, NRG-LU001, patients with unresectable stage 3 NSCLC who did not have diabetes were randomized to carboplatin and paclitaxel-based chemoradiation either alone or with metformin.
Among the 167 patients eligible for analysis, 1-year progression-free survival (PFS) was 60.4% in the control group and 51.3% in the metformin group (P = .24) after a median follow-up of 27.7 months.
The only clinical factor associated with progression-free survival on multivariate analysis was clinical stage, at a hazard ratio of 1.79 (P = .05), reports Dr. Skinner, from the University of Pittsburgh Hillman Cancer Center, and colleagues.
With 1-year overall survival at 80.2% in the control group and 80.8% in the metformin arm, and no significant differences in rates of locoregional recurrence or distant metastasis, the team concluded that adding metformin to chemoradiation may have been “well tolerated but did not improve survival.”
Not recommended
The second randomized controlled trial, OCOG-ALMERA, involved patients with locally advanced NSCLC stratified into stages 3A and 3B, again without diabetes.
They were treated with platinum-based chemoradiotherapy, with chest radiotherapy with or without consolidation chemotherapy. They were randomized to metformin or no additional treatment for up to 12 months.
The trial had to be stopped early because of slow accrual, with only 54 patients randomized between 2014 and 2019, wrote the authors who were led by Theodoros Tsakiridis, MD, PhD, Juravinski Cancer Center, McMaster University, Hamilton, Ont.
The results revealed that treatment failure at 1 year was seen in 69.2% of metformin patients and 42.9% of those in the control arm.
The 1-year progression survival was markedly worse with metformin, at 34.8% versus 63.0% in the control arm and an HR for progression of 2.42, while overall survival was 47.4% versus 85.2% and an HR for death of 3.80.
With more than twice as many metformin than control patients reporting at least one grade 3 or higher adverse event, the researchers conclude the drug is “not recommended in patients with locally advanced non–small cell lung cancer who are candidates for chemoradiotherapy.”
Future research directions
Do these results sound the death knell for metformin in the treatment of lung cancer, or could lessons be learned from both studies that leave the door open for future research?
Chukwuka Eze, MD, of the University Hospital LMU Munich (Germany), thinks there may well be.
In an editorial accompanying the two studies, he and colleagues wrote: “Despite the negative results of both studies, invaluable information for the subsequent design of future trials could be extracted.”
For example, “there might yet be a role for metformin in selected patients with non–small cell lung cancer patients,” they continued, such as those with KRAS/LKB1-mutated tumors, or with tumors that have elevated fluorodeoxyglucose metabolism.
They also suggested that future studies should include continuous assessment of metabolic parameters and “comprehensive” analysis of responses on imaging, as well as biomarker analysis.
Moreover, in the era of immuno-oncology, “special attention to the immunomodulatory effects of metformin in the host and tumor are pertinent.”
Better-than-expected outcomes
Beyond that, both studies were hampered by limitations that make drawing conclusions difficult.
In the OCOG-ALMERA trial, the lack of double-blinding or placebo control, and limited accrual are identified by the authors as “weaknesses.”
The “much slower than anticipated” accrual may have been caused not only by exclusion of patients with diabetes, but also bias against the trial among physicians, who may have looked instead to immunotherapy trials for their patients.
On the other hand, the issue for NRG-LU001 was the “better-than-expected” performance of control arm, the researchers noted.
They make the comparison with the PACIFIC trial, which showed that giving durvalumab (Imfinzi, AstraZeneca) after platinum-based doublet chemotherapy and concurrent radiotherapy was associated with a doubling of progression-free survival over chemoradiation alone.
However, Dr. Skinner and colleagues pointed out that the 1-year progression-free survival achieved in PACIFIC with durvalumab after chemoradiotherapy was, at 55.9%, lower than that seen in the control arm of NRG-LU001.
“The PFS in NRG-LU001 remains striking, particularly as PACIFIC trial patients were randomized only when progression was not detected after concurrent chemoradiation,” the researchers wrote.
Dr. Skinner said in an interview they expected the control arm in their study “to do far worse than it actually did.”
He continued that they did not follow up chemoradiation with adjuvant immunotherapy, as would be the case nowadays, because it was “not the standard when we started the trial,” and did not become so “until the very end of accrual.”
Dr. Skinner warned that there are “many caveats” to comparing two different trials, but looking at the current results alongside those from PACIFIC, he said that, “for me, it seems like we have been making progress in the delivery of concurrent chemoradiation. I think that good quality concurrent chemoradiation and improvement in delivery really is one of the take-homes from this trial.”
NRG-LU001 was supported by grants from NRG Oncology and the National Cancer Institute. OCOG-ALMERA was funded by a grant from the Canadian Institutes of Health Research to Dr Tsakiridis. The Ontario Clinical Oncology Group assumed the role of the sponsor of this trial. Dr. Skinner reported receiving research funding from the National Cancer Institute and National Institute of Dental and Craniofacial Research outside the submitted work and has previously received a grant from the National Cancer Institute for a separate metformin-related clinical trial. Dr. Tsakiridis reported receiving a grant from Sanofi Canada for prostate cancer research outside the submitted work. Dr. Eze declares no relevant relationships.
Although well tolerated, metformin does not improve survival when given alongside chemoradiotherapy to patients with locally advanced non–small cell lung cancer (NSCLC), and may even make survival worse, suggest results from two recent phase 2 trials.
Epidemiologic studies have suggested that metformin is associated with a reduced incidence of cancer, while retrospective case studies have indicated that patients taking the drug have improved outcomes.
Moreover, preclinical data indicated that metformin has antineoplastic effects, with the drug showing both cytostatic and cytotoxic effects.
The current results cast doubt, however, over whether these benefits can be replicated in randomized controlled trials and thence brought to the clinic.
Despite this, “I don’t think metformin is dead,” commented Heath D. Skinner, MD, PhD, first author on one of the trials, published in JAMA Oncology.
He said in an interview there are “a few key areas where I think metformin could be of benefit” in lung cancer, such as in combination with tyrosine kinase inhibitors, or with immunotherapy.
Dr. Skinner also highlighted the unexpectedly good performance of standard chemoradiation, showing the “progress” that has been made in recent years in treatment delivery and quality.
No survival benefit
In the first trial, which was an open-label phase 2 study, NRG-LU001, patients with unresectable stage 3 NSCLC who did not have diabetes were randomized to carboplatin and paclitaxel-based chemoradiation either alone or with metformin.
Among the 167 patients eligible for analysis, 1-year progression-free survival (PFS) was 60.4% in the control group and 51.3% in the metformin group (P = .24) after a median follow-up of 27.7 months.
The only clinical factor associated with progression-free survival on multivariate analysis was clinical stage, at a hazard ratio of 1.79 (P = .05), reports Dr. Skinner, from the University of Pittsburgh Hillman Cancer Center, and colleagues.
With 1-year overall survival at 80.2% in the control group and 80.8% in the metformin arm, and no significant differences in rates of locoregional recurrence or distant metastasis, the team concluded that adding metformin to chemoradiation may have been “well tolerated but did not improve survival.”
Not recommended
The second randomized controlled trial, OCOG-ALMERA, involved patients with locally advanced NSCLC stratified into stages 3A and 3B, again without diabetes.
They were treated with platinum-based chemoradiotherapy, with chest radiotherapy with or without consolidation chemotherapy. They were randomized to metformin or no additional treatment for up to 12 months.
The trial had to be stopped early because of slow accrual, with only 54 patients randomized between 2014 and 2019, wrote the authors who were led by Theodoros Tsakiridis, MD, PhD, Juravinski Cancer Center, McMaster University, Hamilton, Ont.
The results revealed that treatment failure at 1 year was seen in 69.2% of metformin patients and 42.9% of those in the control arm.
The 1-year progression survival was markedly worse with metformin, at 34.8% versus 63.0% in the control arm and an HR for progression of 2.42, while overall survival was 47.4% versus 85.2% and an HR for death of 3.80.
With more than twice as many metformin than control patients reporting at least one grade 3 or higher adverse event, the researchers conclude the drug is “not recommended in patients with locally advanced non–small cell lung cancer who are candidates for chemoradiotherapy.”
Future research directions
Do these results sound the death knell for metformin in the treatment of lung cancer, or could lessons be learned from both studies that leave the door open for future research?
Chukwuka Eze, MD, of the University Hospital LMU Munich (Germany), thinks there may well be.
In an editorial accompanying the two studies, he and colleagues wrote: “Despite the negative results of both studies, invaluable information for the subsequent design of future trials could be extracted.”
For example, “there might yet be a role for metformin in selected patients with non–small cell lung cancer patients,” they continued, such as those with KRAS/LKB1-mutated tumors, or with tumors that have elevated fluorodeoxyglucose metabolism.
They also suggested that future studies should include continuous assessment of metabolic parameters and “comprehensive” analysis of responses on imaging, as well as biomarker analysis.
Moreover, in the era of immuno-oncology, “special attention to the immunomodulatory effects of metformin in the host and tumor are pertinent.”
Better-than-expected outcomes
Beyond that, both studies were hampered by limitations that make drawing conclusions difficult.
In the OCOG-ALMERA trial, the lack of double-blinding or placebo control, and limited accrual are identified by the authors as “weaknesses.”
The “much slower than anticipated” accrual may have been caused not only by exclusion of patients with diabetes, but also bias against the trial among physicians, who may have looked instead to immunotherapy trials for their patients.
On the other hand, the issue for NRG-LU001 was the “better-than-expected” performance of control arm, the researchers noted.
They make the comparison with the PACIFIC trial, which showed that giving durvalumab (Imfinzi, AstraZeneca) after platinum-based doublet chemotherapy and concurrent radiotherapy was associated with a doubling of progression-free survival over chemoradiation alone.
However, Dr. Skinner and colleagues pointed out that the 1-year progression-free survival achieved in PACIFIC with durvalumab after chemoradiotherapy was, at 55.9%, lower than that seen in the control arm of NRG-LU001.
“The PFS in NRG-LU001 remains striking, particularly as PACIFIC trial patients were randomized only when progression was not detected after concurrent chemoradiation,” the researchers wrote.
Dr. Skinner said in an interview they expected the control arm in their study “to do far worse than it actually did.”
He continued that they did not follow up chemoradiation with adjuvant immunotherapy, as would be the case nowadays, because it was “not the standard when we started the trial,” and did not become so “until the very end of accrual.”
Dr. Skinner warned that there are “many caveats” to comparing two different trials, but looking at the current results alongside those from PACIFIC, he said that, “for me, it seems like we have been making progress in the delivery of concurrent chemoradiation. I think that good quality concurrent chemoradiation and improvement in delivery really is one of the take-homes from this trial.”
NRG-LU001 was supported by grants from NRG Oncology and the National Cancer Institute. OCOG-ALMERA was funded by a grant from the Canadian Institutes of Health Research to Dr Tsakiridis. The Ontario Clinical Oncology Group assumed the role of the sponsor of this trial. Dr. Skinner reported receiving research funding from the National Cancer Institute and National Institute of Dental and Craniofacial Research outside the submitted work and has previously received a grant from the National Cancer Institute for a separate metformin-related clinical trial. Dr. Tsakiridis reported receiving a grant from Sanofi Canada for prostate cancer research outside the submitted work. Dr. Eze declares no relevant relationships.
Although well tolerated, metformin does not improve survival when given alongside chemoradiotherapy to patients with locally advanced non–small cell lung cancer (NSCLC), and may even make survival worse, suggest results from two recent phase 2 trials.
Epidemiologic studies have suggested that metformin is associated with a reduced incidence of cancer, while retrospective case studies have indicated that patients taking the drug have improved outcomes.
Moreover, preclinical data indicated that metformin has antineoplastic effects, with the drug showing both cytostatic and cytotoxic effects.
The current results cast doubt, however, over whether these benefits can be replicated in randomized controlled trials and thence brought to the clinic.
Despite this, “I don’t think metformin is dead,” commented Heath D. Skinner, MD, PhD, first author on one of the trials, published in JAMA Oncology.
He said in an interview there are “a few key areas where I think metformin could be of benefit” in lung cancer, such as in combination with tyrosine kinase inhibitors, or with immunotherapy.
Dr. Skinner also highlighted the unexpectedly good performance of standard chemoradiation, showing the “progress” that has been made in recent years in treatment delivery and quality.
No survival benefit
In the first trial, which was an open-label phase 2 study, NRG-LU001, patients with unresectable stage 3 NSCLC who did not have diabetes were randomized to carboplatin and paclitaxel-based chemoradiation either alone or with metformin.
Among the 167 patients eligible for analysis, 1-year progression-free survival (PFS) was 60.4% in the control group and 51.3% in the metformin group (P = .24) after a median follow-up of 27.7 months.
The only clinical factor associated with progression-free survival on multivariate analysis was clinical stage, at a hazard ratio of 1.79 (P = .05), reports Dr. Skinner, from the University of Pittsburgh Hillman Cancer Center, and colleagues.
With 1-year overall survival at 80.2% in the control group and 80.8% in the metformin arm, and no significant differences in rates of locoregional recurrence or distant metastasis, the team concluded that adding metformin to chemoradiation may have been “well tolerated but did not improve survival.”
Not recommended
The second randomized controlled trial, OCOG-ALMERA, involved patients with locally advanced NSCLC stratified into stages 3A and 3B, again without diabetes.
They were treated with platinum-based chemoradiotherapy, with chest radiotherapy with or without consolidation chemotherapy. They were randomized to metformin or no additional treatment for up to 12 months.
The trial had to be stopped early because of slow accrual, with only 54 patients randomized between 2014 and 2019, wrote the authors who were led by Theodoros Tsakiridis, MD, PhD, Juravinski Cancer Center, McMaster University, Hamilton, Ont.
The results revealed that treatment failure at 1 year was seen in 69.2% of metformin patients and 42.9% of those in the control arm.
The 1-year progression survival was markedly worse with metformin, at 34.8% versus 63.0% in the control arm and an HR for progression of 2.42, while overall survival was 47.4% versus 85.2% and an HR for death of 3.80.
With more than twice as many metformin than control patients reporting at least one grade 3 or higher adverse event, the researchers conclude the drug is “not recommended in patients with locally advanced non–small cell lung cancer who are candidates for chemoradiotherapy.”
Future research directions
Do these results sound the death knell for metformin in the treatment of lung cancer, or could lessons be learned from both studies that leave the door open for future research?
Chukwuka Eze, MD, of the University Hospital LMU Munich (Germany), thinks there may well be.
In an editorial accompanying the two studies, he and colleagues wrote: “Despite the negative results of both studies, invaluable information for the subsequent design of future trials could be extracted.”
For example, “there might yet be a role for metformin in selected patients with non–small cell lung cancer patients,” they continued, such as those with KRAS/LKB1-mutated tumors, or with tumors that have elevated fluorodeoxyglucose metabolism.
They also suggested that future studies should include continuous assessment of metabolic parameters and “comprehensive” analysis of responses on imaging, as well as biomarker analysis.
Moreover, in the era of immuno-oncology, “special attention to the immunomodulatory effects of metformin in the host and tumor are pertinent.”
Better-than-expected outcomes
Beyond that, both studies were hampered by limitations that make drawing conclusions difficult.
In the OCOG-ALMERA trial, the lack of double-blinding or placebo control, and limited accrual are identified by the authors as “weaknesses.”
The “much slower than anticipated” accrual may have been caused not only by exclusion of patients with diabetes, but also bias against the trial among physicians, who may have looked instead to immunotherapy trials for their patients.
On the other hand, the issue for NRG-LU001 was the “better-than-expected” performance of control arm, the researchers noted.
They make the comparison with the PACIFIC trial, which showed that giving durvalumab (Imfinzi, AstraZeneca) after platinum-based doublet chemotherapy and concurrent radiotherapy was associated with a doubling of progression-free survival over chemoradiation alone.
However, Dr. Skinner and colleagues pointed out that the 1-year progression-free survival achieved in PACIFIC with durvalumab after chemoradiotherapy was, at 55.9%, lower than that seen in the control arm of NRG-LU001.
“The PFS in NRG-LU001 remains striking, particularly as PACIFIC trial patients were randomized only when progression was not detected after concurrent chemoradiation,” the researchers wrote.
Dr. Skinner said in an interview they expected the control arm in their study “to do far worse than it actually did.”
He continued that they did not follow up chemoradiation with adjuvant immunotherapy, as would be the case nowadays, because it was “not the standard when we started the trial,” and did not become so “until the very end of accrual.”
Dr. Skinner warned that there are “many caveats” to comparing two different trials, but looking at the current results alongside those from PACIFIC, he said that, “for me, it seems like we have been making progress in the delivery of concurrent chemoradiation. I think that good quality concurrent chemoradiation and improvement in delivery really is one of the take-homes from this trial.”
NRG-LU001 was supported by grants from NRG Oncology and the National Cancer Institute. OCOG-ALMERA was funded by a grant from the Canadian Institutes of Health Research to Dr Tsakiridis. The Ontario Clinical Oncology Group assumed the role of the sponsor of this trial. Dr. Skinner reported receiving research funding from the National Cancer Institute and National Institute of Dental and Craniofacial Research outside the submitted work and has previously received a grant from the National Cancer Institute for a separate metformin-related clinical trial. Dr. Tsakiridis reported receiving a grant from Sanofi Canada for prostate cancer research outside the submitted work. Dr. Eze declares no relevant relationships.
FROM JAMA ONCOLOGY
A case is building for personalized, genome-based radiation dosing
A team of researchers from the Cleveland Clinic, the Moffitt Cancer Center in Tampa, and Case Western Reserve University in Cleveland is zeroing in on a way to personalize radiation therapy for cancer patients based on genomic profile, much as genomics is used to tailor oncologic drug therapy.
It’s called “genomic-adjusted radiation dose” (GARD), a dose tailored to a person’s radiosensitivity as determined by the expression of 10 genes, known as the radiosensitivity index (RSI), combined with a linear quadratic model to yield GARD, a prediction of risk and benefit at various radiation doses for a particular patient.
A recent report in The Lancet Oncology validated GARD in 1,615 patients with seven cancer types from 11 study cohorts. If it holds up in clinical trials set to start later this year, GARD should “allow us to predict the benefit of radiation for an individual patient and adjust their treatment strategy,” wrote the authors of an editorial that accompanied the study. “The efforts need to be applauded worldwide, because radiotherapy is considerably lagging, compared with the enormous progress done in the field of personalized medicine,” Orit Kaidar-Person, MD, a radiation oncologist at Sheba Medical Center in Ramat Gan, Israel, and colleagues wrote.
GARD was associated with time to first recurrence and overall survival for patients receiving radiotherapy and predicted radiotherapy benefit, while physical dose did not. The team found a relative 2% reduction in risk of first recurrence for each unit increase of GARD (P = .0017) and a relative 3% increase in overall survival for each unit increase in GARD (P = .0007), among those who got radiotherapy. Values of GARD run from 0 to over 100, with higher scores meaning more radiation benefit.
The radiosensitivity index, which was derived from genomic studies of cancer cell lines exposed to radiation, was previously validated by the team and other groups across several tumor types.
Currently, radiation dosing is generally uniform for a given disease site and stage, based on the assumption that a given dose of radiation results in the same clinical effect across patients. In fact, the biological effect of a given dose varies widely between individual patients. “Patients we treat uniformly do not have a uniform response” which is why a more personalized approach would help, said lead investigator and Cleveland Clinic radiation oncologist Jacob Scott, MD, DPhil.
One patient with a given tumor might benefit from 2 extra fractions, while the next might need an extra 15 for the same benefit. “You need to know about [a patient’s] tumor genomics to know how hard you have to work,” he said.
Dr. Scott and colleagues are working with a genomics company to commercialize the approach. The vision for now is that physicians would ship in biopsy samples to be analyzed; RSI and GARD would be calculated, and then a decision support report would be sent back to the treatment team outlining the risks and benefits of various doses for the patient.
Dr. Scott, who holds proprietary rights on the approach, is bullish. When asked if he anticipates GARD dosing to be standard of care in 10 years, he said that “I can’t imagine another world. Everything else in cancer is personalized. Why aren’t we? It just makes sense. I know there’s a better way” to prescribe radiation, “and I’m excited for the future when I can use it.”
When asked for comment, Brian Marples, PhD, a radiation oncology professor at the University of Rochester (N.Y.), said the data so far for GARD “seem very solid. I’m very excited by the concept.”
It’s been “the holy grail” of radiation researchers to find a biologic marker that predicts what dosages patients need and what can be given safely. “This strategy is a good way of doing that. Other groups are proposing similar strategies, but I think this group is ahead. I can see [GARD] being readily applied to the clinic because patients are [already] getting their tumors genomically characterized as part of care,” Dr. Marples said.
But many questions remain. For instance, the editorial writers questioned how GARD is “affected by tumor heterogeneity, response to systemic therapy, and changes in the tumor microenvironment.” Also, the approach is based on conventional 2 Gy fractions, but other fractionation regimens are becoming more common.
For Dr. Marples, the big caveat is that most cancer patients are treated with both radiation and chemotherapy. He said he would like to see GARD validated in patients who receive both.
They seven tumor types in the study included breast cancer, head and neck cancer, non–small cell lung cancer, pancreatic cancer, endometrial cancer, melanoma, and glioma. The majority of the subjects were treated with radiation, and each had the genomic data needed to calculate GARD.
Dr. Scott, senior author and Moffitt Center radiation oncologist Javier Torres-Roca, MD, and a third author hold intellectual property rights on RSI, GARD, and prescription dose base on RSI, plus equity in Cvergenx, a company that seeks to commercialize the approach. Dr. Torres-Roca and another author are cofounders. The editorial writers and Dr. Marples did not have any relevant disclosures.
A team of researchers from the Cleveland Clinic, the Moffitt Cancer Center in Tampa, and Case Western Reserve University in Cleveland is zeroing in on a way to personalize radiation therapy for cancer patients based on genomic profile, much as genomics is used to tailor oncologic drug therapy.
It’s called “genomic-adjusted radiation dose” (GARD), a dose tailored to a person’s radiosensitivity as determined by the expression of 10 genes, known as the radiosensitivity index (RSI), combined with a linear quadratic model to yield GARD, a prediction of risk and benefit at various radiation doses for a particular patient.
A recent report in The Lancet Oncology validated GARD in 1,615 patients with seven cancer types from 11 study cohorts. If it holds up in clinical trials set to start later this year, GARD should “allow us to predict the benefit of radiation for an individual patient and adjust their treatment strategy,” wrote the authors of an editorial that accompanied the study. “The efforts need to be applauded worldwide, because radiotherapy is considerably lagging, compared with the enormous progress done in the field of personalized medicine,” Orit Kaidar-Person, MD, a radiation oncologist at Sheba Medical Center in Ramat Gan, Israel, and colleagues wrote.
GARD was associated with time to first recurrence and overall survival for patients receiving radiotherapy and predicted radiotherapy benefit, while physical dose did not. The team found a relative 2% reduction in risk of first recurrence for each unit increase of GARD (P = .0017) and a relative 3% increase in overall survival for each unit increase in GARD (P = .0007), among those who got radiotherapy. Values of GARD run from 0 to over 100, with higher scores meaning more radiation benefit.
The radiosensitivity index, which was derived from genomic studies of cancer cell lines exposed to radiation, was previously validated by the team and other groups across several tumor types.
Currently, radiation dosing is generally uniform for a given disease site and stage, based on the assumption that a given dose of radiation results in the same clinical effect across patients. In fact, the biological effect of a given dose varies widely between individual patients. “Patients we treat uniformly do not have a uniform response” which is why a more personalized approach would help, said lead investigator and Cleveland Clinic radiation oncologist Jacob Scott, MD, DPhil.
One patient with a given tumor might benefit from 2 extra fractions, while the next might need an extra 15 for the same benefit. “You need to know about [a patient’s] tumor genomics to know how hard you have to work,” he said.
Dr. Scott and colleagues are working with a genomics company to commercialize the approach. The vision for now is that physicians would ship in biopsy samples to be analyzed; RSI and GARD would be calculated, and then a decision support report would be sent back to the treatment team outlining the risks and benefits of various doses for the patient.
Dr. Scott, who holds proprietary rights on the approach, is bullish. When asked if he anticipates GARD dosing to be standard of care in 10 years, he said that “I can’t imagine another world. Everything else in cancer is personalized. Why aren’t we? It just makes sense. I know there’s a better way” to prescribe radiation, “and I’m excited for the future when I can use it.”
When asked for comment, Brian Marples, PhD, a radiation oncology professor at the University of Rochester (N.Y.), said the data so far for GARD “seem very solid. I’m very excited by the concept.”
It’s been “the holy grail” of radiation researchers to find a biologic marker that predicts what dosages patients need and what can be given safely. “This strategy is a good way of doing that. Other groups are proposing similar strategies, but I think this group is ahead. I can see [GARD] being readily applied to the clinic because patients are [already] getting their tumors genomically characterized as part of care,” Dr. Marples said.
But many questions remain. For instance, the editorial writers questioned how GARD is “affected by tumor heterogeneity, response to systemic therapy, and changes in the tumor microenvironment.” Also, the approach is based on conventional 2 Gy fractions, but other fractionation regimens are becoming more common.
For Dr. Marples, the big caveat is that most cancer patients are treated with both radiation and chemotherapy. He said he would like to see GARD validated in patients who receive both.
They seven tumor types in the study included breast cancer, head and neck cancer, non–small cell lung cancer, pancreatic cancer, endometrial cancer, melanoma, and glioma. The majority of the subjects were treated with radiation, and each had the genomic data needed to calculate GARD.
Dr. Scott, senior author and Moffitt Center radiation oncologist Javier Torres-Roca, MD, and a third author hold intellectual property rights on RSI, GARD, and prescription dose base on RSI, plus equity in Cvergenx, a company that seeks to commercialize the approach. Dr. Torres-Roca and another author are cofounders. The editorial writers and Dr. Marples did not have any relevant disclosures.
A team of researchers from the Cleveland Clinic, the Moffitt Cancer Center in Tampa, and Case Western Reserve University in Cleveland is zeroing in on a way to personalize radiation therapy for cancer patients based on genomic profile, much as genomics is used to tailor oncologic drug therapy.
It’s called “genomic-adjusted radiation dose” (GARD), a dose tailored to a person’s radiosensitivity as determined by the expression of 10 genes, known as the radiosensitivity index (RSI), combined with a linear quadratic model to yield GARD, a prediction of risk and benefit at various radiation doses for a particular patient.
A recent report in The Lancet Oncology validated GARD in 1,615 patients with seven cancer types from 11 study cohorts. If it holds up in clinical trials set to start later this year, GARD should “allow us to predict the benefit of radiation for an individual patient and adjust their treatment strategy,” wrote the authors of an editorial that accompanied the study. “The efforts need to be applauded worldwide, because radiotherapy is considerably lagging, compared with the enormous progress done in the field of personalized medicine,” Orit Kaidar-Person, MD, a radiation oncologist at Sheba Medical Center in Ramat Gan, Israel, and colleagues wrote.
GARD was associated with time to first recurrence and overall survival for patients receiving radiotherapy and predicted radiotherapy benefit, while physical dose did not. The team found a relative 2% reduction in risk of first recurrence for each unit increase of GARD (P = .0017) and a relative 3% increase in overall survival for each unit increase in GARD (P = .0007), among those who got radiotherapy. Values of GARD run from 0 to over 100, with higher scores meaning more radiation benefit.
The radiosensitivity index, which was derived from genomic studies of cancer cell lines exposed to radiation, was previously validated by the team and other groups across several tumor types.
Currently, radiation dosing is generally uniform for a given disease site and stage, based on the assumption that a given dose of radiation results in the same clinical effect across patients. In fact, the biological effect of a given dose varies widely between individual patients. “Patients we treat uniformly do not have a uniform response” which is why a more personalized approach would help, said lead investigator and Cleveland Clinic radiation oncologist Jacob Scott, MD, DPhil.
One patient with a given tumor might benefit from 2 extra fractions, while the next might need an extra 15 for the same benefit. “You need to know about [a patient’s] tumor genomics to know how hard you have to work,” he said.
Dr. Scott and colleagues are working with a genomics company to commercialize the approach. The vision for now is that physicians would ship in biopsy samples to be analyzed; RSI and GARD would be calculated, and then a decision support report would be sent back to the treatment team outlining the risks and benefits of various doses for the patient.
Dr. Scott, who holds proprietary rights on the approach, is bullish. When asked if he anticipates GARD dosing to be standard of care in 10 years, he said that “I can’t imagine another world. Everything else in cancer is personalized. Why aren’t we? It just makes sense. I know there’s a better way” to prescribe radiation, “and I’m excited for the future when I can use it.”
When asked for comment, Brian Marples, PhD, a radiation oncology professor at the University of Rochester (N.Y.), said the data so far for GARD “seem very solid. I’m very excited by the concept.”
It’s been “the holy grail” of radiation researchers to find a biologic marker that predicts what dosages patients need and what can be given safely. “This strategy is a good way of doing that. Other groups are proposing similar strategies, but I think this group is ahead. I can see [GARD] being readily applied to the clinic because patients are [already] getting their tumors genomically characterized as part of care,” Dr. Marples said.
But many questions remain. For instance, the editorial writers questioned how GARD is “affected by tumor heterogeneity, response to systemic therapy, and changes in the tumor microenvironment.” Also, the approach is based on conventional 2 Gy fractions, but other fractionation regimens are becoming more common.
For Dr. Marples, the big caveat is that most cancer patients are treated with both radiation and chemotherapy. He said he would like to see GARD validated in patients who receive both.
They seven tumor types in the study included breast cancer, head and neck cancer, non–small cell lung cancer, pancreatic cancer, endometrial cancer, melanoma, and glioma. The majority of the subjects were treated with radiation, and each had the genomic data needed to calculate GARD.
Dr. Scott, senior author and Moffitt Center radiation oncologist Javier Torres-Roca, MD, and a third author hold intellectual property rights on RSI, GARD, and prescription dose base on RSI, plus equity in Cvergenx, a company that seeks to commercialize the approach. Dr. Torres-Roca and another author are cofounders. The editorial writers and Dr. Marples did not have any relevant disclosures.
FROM LANCET ONCOLOGY