AVAHO

There was no evidence of an abscopal effect with the addition of limited radiation therapy to nivolumab in patients with metastatic head and neck squamous cell carcinoma, according to new results from a randomized trial. 

The phase 2, single-center study was conducted in 62 patients with head and neck cancer and at least two metastatic lesions. They were randomly assigned to receive nivolumab with or without additional radiation, delivered as stereotactic body radiation therapy (SBRT), but directed at only one of the metastatic lesions.

The results showed a similar rate of tumor shrinkage and disappearance in both groups (34.5% for nivolumab vs. 29.0% for the combination; P = .86) reported Sean McBride, MD, MPH, Memorial Sloan Kettering Cancer Center, New York, and colleagues in a paper published online in the Journal of Clinical Oncology.

The finding indicates that there was no abscopal effect, the team concluded.

The abscopal (from the Latin ab “away from” and scopus “target”) effect, first described in the 1950s, is a hypothetical result of radiation, whereby tumors situated outside the radiation field are reduced or eliminated by an assumed reaction mediated by the immune system.

This study is only the second randomized controlled trial to look at this effect. A previous trial in lung cancer (JAMA Oncol. 2019;5:1276) also failed to show a significant difference in objective response rate, the primary outcome.

In both studies, there was also no improvement in progression-free survival (PFS) or overall survival (OS) with the addition of radiation.

“There are still die-hard proponents of the existence of an abscopal response, but it is clear from our data – there is no abscopal response,” lead study author Nancy Lee, MD, said in an interview.

Dr. Lee, also from Memorial Sloan Kettering, was referring to this trial in head and neck cancer specifically. But previous nonrandomized studies have also reported response rates for the combination of SBRT and immunotherapy that are similar to monotherapy, the authors point out. Overall, the collective data in oncology suggest that the abscopal response is “relatively rare,” the team comments.

A more emphatic statement comes from a pair of oncologists in an accompanying editorial.

The new study “provides the clearest evidence so far that the abscopal effect, contrary to widely held perception in the field, remains exceedingly rare,” wrote Tanguy Seiwert, MD, medical oncologist, and Ana Kiess, MD, PhD, radiation oncologist, both at Johns Hopkins University, Baltimore.

This is a “well-executed study that has broader implications beyond head and neck cancer and speaks to larger issues of combination therapies in the era of cancer immunotherapy,” they also wrote.

The practice of using limited SBRT on any tumor type – along with anti–PD-1/PD-L1 therapy – “should not be pursued for the sole purpose of induction of an abscopal effect until we have better data to support any benefit,” the editorialists added.

It’s time to put the abscopal effect to rest, suggested Dr. Lee.

“Instead of focusing on whether an abscopal response exists or not, as it clearly did not in our phase 2 study, our focus should shift to the broader picture. What is the optimal timing of PD-1 or PD-L1 therapy in relation to radiotherapy?” she said.

The answer appears to be sequentially – and not concurrently, which is how radiation has been used to induce the would-be abscopal effect, she explained. “I personally feel that immunotherapy should not be given concurrently with radiation therapy.”

Damning data for the concurrent approach come from the phase 3 Javelin Head and Neck 100 trial, she said. In March, trial sponsors announced that the trial was terminated as it was unlikely to meet its primary endpoint. Specifically, adding an anti–PD-L1 therapy to chemoradiotherapy was not superior to chemoradiotherapy alone.

On the other hand, in the phase 3 lung cancer study known as PACIFIC, chemoradiotherapy followed by sequential anti–PD-L1 therapy showed “dramatic” improvements in PFS and OS, the editorialists pointed out.
 

Radiation and immunotherapy combinations

Despite the failure of this trial, radiation has “significant potential for combination with immunotherapy,” observed Dr. Seiwert and Dr. Kiess.

There are at least three potential roles of radiation therapy in combination with anti–PD-1/PD-L1 therapy, they wrote.

They explained that the first is single-site palliative radiation therapy/SBRT, which can control local symptoms. The second is “consolidation” of all tumor sites with radiation therapy/SBRT, which may decrease tumor burden and heterogeneity. And the third potential role is definitive locoregional radiation therapy to achieve long-term locoregional tumor control.

Thus, the editorialists, like Dr. Lee, believed the question of concurrent versus sequential immunotherapy is “important.” But the field of oncology has an abundance of treatments that can now be aimed at a cancer, in a variety of potential combinations, they observed.

The editorialists concluded their commentary with a long list of needed work: “We should take this study to guide us to explore promising approaches in rigorous clinical trials, with a focus on sequential approaches such as definitive RT followed by immunotherapy, consolidative SBRT of all tumor sites in combination with immunotherapy, and trials that incorporate surrogate immunotherapy-relevant biomarkers to assess earlier and more efficiently the impact of an intervention.”

The study was partly supported by a grant from the National Cancer Institute. Bristol-Myers Squibb provided the study drug and funded tumor staining.

Multiple study authors have financial ties to industry, including two with ties to Bristol-Myers Squibb. Both editorialists have ties to industry, including Dr. Seiwert’s ties to Bristol-Myers Squibb.

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

There was no evidence of an abscopal effect with the addition of limited radiation therapy to nivolumab in patients with metastatic head and neck squamous cell carcinoma, according to new results from a randomized trial. 

The phase 2, single-center study was conducted in 62 patients with head and neck cancer and at least two metastatic lesions. They were randomly assigned to receive nivolumab with or without additional radiation, delivered as stereotactic body radiation therapy (SBRT), but directed at only one of the metastatic lesions.

The results showed a similar rate of tumor shrinkage and disappearance in both groups (34.5% for nivolumab vs. 29.0% for the combination; P = .86) reported Sean McBride, MD, MPH, Memorial Sloan Kettering Cancer Center, New York, and colleagues in a paper published online in the Journal of Clinical Oncology.

The finding indicates that there was no abscopal effect, the team concluded.

The abscopal (from the Latin ab “away from” and scopus “target”) effect, first described in the 1950s, is a hypothetical result of radiation, whereby tumors situated outside the radiation field are reduced or eliminated by an assumed reaction mediated by the immune system.

This study is only the second randomized controlled trial to look at this effect. A previous trial in lung cancer (JAMA Oncol. 2019;5:1276) also failed to show a significant difference in objective response rate, the primary outcome.

In both studies, there was also no improvement in progression-free survival (PFS) or overall survival (OS) with the addition of radiation.

“There are still die-hard proponents of the existence of an abscopal response, but it is clear from our data – there is no abscopal response,” lead study author Nancy Lee, MD, said in an interview.

Dr. Lee, also from Memorial Sloan Kettering, was referring to this trial in head and neck cancer specifically. But previous nonrandomized studies have also reported response rates for the combination of SBRT and immunotherapy that are similar to monotherapy, the authors point out. Overall, the collective data in oncology suggest that the abscopal response is “relatively rare,” the team comments.

A more emphatic statement comes from a pair of oncologists in an accompanying editorial.

The new study “provides the clearest evidence so far that the abscopal effect, contrary to widely held perception in the field, remains exceedingly rare,” wrote Tanguy Seiwert, MD, medical oncologist, and Ana Kiess, MD, PhD, radiation oncologist, both at Johns Hopkins University, Baltimore.

This is a “well-executed study that has broader implications beyond head and neck cancer and speaks to larger issues of combination therapies in the era of cancer immunotherapy,” they also wrote.

The practice of using limited SBRT on any tumor type – along with anti–PD-1/PD-L1 therapy – “should not be pursued for the sole purpose of induction of an abscopal effect until we have better data to support any benefit,” the editorialists added.

It’s time to put the abscopal effect to rest, suggested Dr. Lee.

“Instead of focusing on whether an abscopal response exists or not, as it clearly did not in our phase 2 study, our focus should shift to the broader picture. What is the optimal timing of PD-1 or PD-L1 therapy in relation to radiotherapy?” she said.

The answer appears to be sequentially – and not concurrently, which is how radiation has been used to induce the would-be abscopal effect, she explained. “I personally feel that immunotherapy should not be given concurrently with radiation therapy.”

Damning data for the concurrent approach come from the phase 3 Javelin Head and Neck 100 trial, she said. In March, trial sponsors announced that the trial was terminated as it was unlikely to meet its primary endpoint. Specifically, adding an anti–PD-L1 therapy to chemoradiotherapy was not superior to chemoradiotherapy alone.

On the other hand, in the phase 3 lung cancer study known as PACIFIC, chemoradiotherapy followed by sequential anti–PD-L1 therapy showed “dramatic” improvements in PFS and OS, the editorialists pointed out.
 

Radiation and immunotherapy combinations

Despite the failure of this trial, radiation has “significant potential for combination with immunotherapy,” observed Dr. Seiwert and Dr. Kiess.

There are at least three potential roles of radiation therapy in combination with anti–PD-1/PD-L1 therapy, they wrote.

They explained that the first is single-site palliative radiation therapy/SBRT, which can control local symptoms. The second is “consolidation” of all tumor sites with radiation therapy/SBRT, which may decrease tumor burden and heterogeneity. And the third potential role is definitive locoregional radiation therapy to achieve long-term locoregional tumor control.

Thus, the editorialists, like Dr. Lee, believed the question of concurrent versus sequential immunotherapy is “important.” But the field of oncology has an abundance of treatments that can now be aimed at a cancer, in a variety of potential combinations, they observed.

The editorialists concluded their commentary with a long list of needed work: “We should take this study to guide us to explore promising approaches in rigorous clinical trials, with a focus on sequential approaches such as definitive RT followed by immunotherapy, consolidative SBRT of all tumor sites in combination with immunotherapy, and trials that incorporate surrogate immunotherapy-relevant biomarkers to assess earlier and more efficiently the impact of an intervention.”

The study was partly supported by a grant from the National Cancer Institute. Bristol-Myers Squibb provided the study drug and funded tumor staining.

Multiple study authors have financial ties to industry, including two with ties to Bristol-Myers Squibb. Both editorialists have ties to industry, including Dr. Seiwert’s ties to Bristol-Myers Squibb.

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

There was no evidence of an abscopal effect with the addition of limited radiation therapy to nivolumab in patients with metastatic head and neck squamous cell carcinoma, according to new results from a randomized trial. 

The phase 2, single-center study was conducted in 62 patients with head and neck cancer and at least two metastatic lesions. They were randomly assigned to receive nivolumab with or without additional radiation, delivered as stereotactic body radiation therapy (SBRT), but directed at only one of the metastatic lesions.

The results showed a similar rate of tumor shrinkage and disappearance in both groups (34.5% for nivolumab vs. 29.0% for the combination; P = .86) reported Sean McBride, MD, MPH, Memorial Sloan Kettering Cancer Center, New York, and colleagues in a paper published online in the Journal of Clinical Oncology.

The finding indicates that there was no abscopal effect, the team concluded.

The abscopal (from the Latin ab “away from” and scopus “target”) effect, first described in the 1950s, is a hypothetical result of radiation, whereby tumors situated outside the radiation field are reduced or eliminated by an assumed reaction mediated by the immune system.

This study is only the second randomized controlled trial to look at this effect. A previous trial in lung cancer (JAMA Oncol. 2019;5:1276) also failed to show a significant difference in objective response rate, the primary outcome.

In both studies, there was also no improvement in progression-free survival (PFS) or overall survival (OS) with the addition of radiation.

“There are still die-hard proponents of the existence of an abscopal response, but it is clear from our data – there is no abscopal response,” lead study author Nancy Lee, MD, said in an interview.

Dr. Lee, also from Memorial Sloan Kettering, was referring to this trial in head and neck cancer specifically. But previous nonrandomized studies have also reported response rates for the combination of SBRT and immunotherapy that are similar to monotherapy, the authors point out. Overall, the collective data in oncology suggest that the abscopal response is “relatively rare,” the team comments.

A more emphatic statement comes from a pair of oncologists in an accompanying editorial.

The new study “provides the clearest evidence so far that the abscopal effect, contrary to widely held perception in the field, remains exceedingly rare,” wrote Tanguy Seiwert, MD, medical oncologist, and Ana Kiess, MD, PhD, radiation oncologist, both at Johns Hopkins University, Baltimore.

This is a “well-executed study that has broader implications beyond head and neck cancer and speaks to larger issues of combination therapies in the era of cancer immunotherapy,” they also wrote.

The practice of using limited SBRT on any tumor type – along with anti–PD-1/PD-L1 therapy – “should not be pursued for the sole purpose of induction of an abscopal effect until we have better data to support any benefit,” the editorialists added.

It’s time to put the abscopal effect to rest, suggested Dr. Lee.

“Instead of focusing on whether an abscopal response exists or not, as it clearly did not in our phase 2 study, our focus should shift to the broader picture. What is the optimal timing of PD-1 or PD-L1 therapy in relation to radiotherapy?” she said.

The answer appears to be sequentially – and not concurrently, which is how radiation has been used to induce the would-be abscopal effect, she explained. “I personally feel that immunotherapy should not be given concurrently with radiation therapy.”

Damning data for the concurrent approach come from the phase 3 Javelin Head and Neck 100 trial, she said. In March, trial sponsors announced that the trial was terminated as it was unlikely to meet its primary endpoint. Specifically, adding an anti–PD-L1 therapy to chemoradiotherapy was not superior to chemoradiotherapy alone.

On the other hand, in the phase 3 lung cancer study known as PACIFIC, chemoradiotherapy followed by sequential anti–PD-L1 therapy showed “dramatic” improvements in PFS and OS, the editorialists pointed out.
 

Radiation and immunotherapy combinations

Despite the failure of this trial, radiation has “significant potential for combination with immunotherapy,” observed Dr. Seiwert and Dr. Kiess.

There are at least three potential roles of radiation therapy in combination with anti–PD-1/PD-L1 therapy, they wrote.

They explained that the first is single-site palliative radiation therapy/SBRT, which can control local symptoms. The second is “consolidation” of all tumor sites with radiation therapy/SBRT, which may decrease tumor burden and heterogeneity. And the third potential role is definitive locoregional radiation therapy to achieve long-term locoregional tumor control.

Thus, the editorialists, like Dr. Lee, believed the question of concurrent versus sequential immunotherapy is “important.” But the field of oncology has an abundance of treatments that can now be aimed at a cancer, in a variety of potential combinations, they observed.

The editorialists concluded their commentary with a long list of needed work: “We should take this study to guide us to explore promising approaches in rigorous clinical trials, with a focus on sequential approaches such as definitive RT followed by immunotherapy, consolidative SBRT of all tumor sites in combination with immunotherapy, and trials that incorporate surrogate immunotherapy-relevant biomarkers to assess earlier and more efficiently the impact of an intervention.”

The study was partly supported by a grant from the National Cancer Institute. Bristol-Myers Squibb provided the study drug and funded tumor staining.

Multiple study authors have financial ties to industry, including two with ties to Bristol-Myers Squibb. Both editorialists have ties to industry, including Dr. Seiwert’s ties to Bristol-Myers Squibb.

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

The incidence of esophageal adenocarcinoma in adults aged younger than 50 years increased threefold between 1975 and 2015, based on data from more than 34,000 cases.

Esophageal carcinoma rates overall have risen in the United States over the past 4 decades, but the average patient is in their 60s, wrote Don C. Codipilly, MD, of the Mayo Clinic, Rochester, Minn., and colleagues. Therefore, “data on the incidence, stage distribution, and outcomes of this segment of patients [younger than 50 years] with esophageal adenocarcinoma are relatively limited.”

In a study published in Cancer Epidemiology, Biomarkers & Prevention, the researchers identified 34,443 cases of esophageal adenocarcinoma using the Surveillance, Epidemiology, and End Results (SEER) database for the periods of 1975-1989, 1990-1999, and 2000-2015. The cases were limited to histologically confirmed cases and were stratified according to age at diagnosis: younger than 50 years, 50-69 years, and 70 years and older

Overall, the annual incidence of esophageal adenocarcinoma among individuals younger than 50 years increased from 0.08 per 100,000 persons in 1975 to 0.27 per 100,000 persons in 2015.
 

Younger patients show more advanced illness

Although the incidence rose across all three age groups during the study period, the largest increase was seen in those aged 70 years and older. However, the younger group was significantly more likely to present at more-advanced stages, the researchers pointed out: Between 2000 and 2015, localized disease represented only 15.1% of cases in those younger than 50 years, compared with 22.4% in patients aged 50-69 years and 32.2% in those 70 years and older. The incidence of regional/distant disease among younger patients has increased over time, with 81.8% in 1975-1989, 75.5% in 1990-1999, and 84.9% in 2000-2015 (P < .01), and this increase has been faster than among older groups, the researches noted. For comparison, during 2000-2015 only 77.6% of patients aged 50-69 years and 67.8% of patients 70 years and older had regional/distant disease.

In addition, the majority of cases of young-onset esophageal adenocarcinoma occurred in men in a trend that persisted across the study periods; 90% of patients younger than 50 years were male in 1975, and 86% of the younger patients in 2015 were male.

“There is no clear explanation for the higher proportion of advanced disease in younger patients, and further study is required to identify biologic, genetic, and environmental factors that may underlie this observation,” the researchers wrote. “A potential hypothesis is that ‘young-onset esophageal adenocarcinoma’ may involve rapid transition from intestinal metaplasia to esophageal adenocarcinoma, driven by an increase in signaling molecules that are active in the intestine,” they suggested.

The study findings were limited by several factors including the inability to review individual case records to confirm disease stage and to compare outcomes across ethnicities, and the lack of data on comorbidities in the SEER database, the researchers noted.

However, the results were strengthened by overall quality of the SEER database and use of multivariate analysis, they added. The evidence of increased incidence and increased odds of advanced disease in younger adults suggest that “reevaluation of our diagnostic and treatment strategies in this age group might need to be considered.”
 

Reasons for increase remain unclear

“While esophageal adenocarcinoma is uncommon overall in younger patients, this study importantly highlights that not only has the incidence of esophageal adenocarcinoma increased more than threefold in patients under the age of 50 over the last 4 decades, but that younger patients are presenting with more advanced disease and have overall poorer survival, compared to older patients,” Rahul A. Shimpi, MD, of Duke University, Durham, N.C., said in an interview.

“The reasons for these findings are unclear, but the authors propose a number of potential factors that could explain them. These include differences in tumor biology, rising rates of obesity and [gastroesophageal reflux disease] in younger patients, decreased endoscopic screening for and surveillance of Barrett’s esophagus in this age group, and differing therapeutic approaches to management,” Dr. Shimpi said.

“The findings from this study underscore that, while uncommon, clinicians need to be aware of the rising incidence of esophageal cancer in younger patients. It is important that even younger patients presenting with esophageal symptoms, such as dysphagia, undergo investigation,” he emphasized.

“I would like to see further study into the potential factors driving the findings in this study, including whether trends in differential treatment modalities account for some of the survival differences found in different age groups,” Dr. Shimpi added. “Finally, further research will ideally clarify optimal Barrett’s screening and surveillance approaches in patients younger than age 50 in order to determine whether new strategies might impact esophageal adenocarcinoma incidence and outcomes in this group.”

The study was funded in part by the National Cancer Institute and the National Center for Advancing Translational Sciences. Two authors disclosed relationships outside the submitted work, but Dr. Codipilly and the remaining authors had no financial conflicts to disclose. Dr. Shimpi had no financial conflicts to disclose.

SOURCE: Codipilly DC et al. Cancer Epidemiol Biomarkers Prev. 2020 Dec 11. doi: 10.1158/1055-9965.EPI-20-0944.

The incidence of esophageal adenocarcinoma in adults aged younger than 50 years increased threefold between 1975 and 2015, based on data from more than 34,000 cases.

Esophageal carcinoma rates overall have risen in the United States over the past 4 decades, but the average patient is in their 60s, wrote Don C. Codipilly, MD, of the Mayo Clinic, Rochester, Minn., and colleagues. Therefore, “data on the incidence, stage distribution, and outcomes of this segment of patients [younger than 50 years] with esophageal adenocarcinoma are relatively limited.”

In a study published in Cancer Epidemiology, Biomarkers & Prevention, the researchers identified 34,443 cases of esophageal adenocarcinoma using the Surveillance, Epidemiology, and End Results (SEER) database for the periods of 1975-1989, 1990-1999, and 2000-2015. The cases were limited to histologically confirmed cases and were stratified according to age at diagnosis: younger than 50 years, 50-69 years, and 70 years and older

Overall, the annual incidence of esophageal adenocarcinoma among individuals younger than 50 years increased from 0.08 per 100,000 persons in 1975 to 0.27 per 100,000 persons in 2015.
 

Younger patients show more advanced illness

Although the incidence rose across all three age groups during the study period, the largest increase was seen in those aged 70 years and older. However, the younger group was significantly more likely to present at more-advanced stages, the researchers pointed out: Between 2000 and 2015, localized disease represented only 15.1% of cases in those younger than 50 years, compared with 22.4% in patients aged 50-69 years and 32.2% in those 70 years and older. The incidence of regional/distant disease among younger patients has increased over time, with 81.8% in 1975-1989, 75.5% in 1990-1999, and 84.9% in 2000-2015 (P < .01), and this increase has been faster than among older groups, the researches noted. For comparison, during 2000-2015 only 77.6% of patients aged 50-69 years and 67.8% of patients 70 years and older had regional/distant disease.

In addition, the majority of cases of young-onset esophageal adenocarcinoma occurred in men in a trend that persisted across the study periods; 90% of patients younger than 50 years were male in 1975, and 86% of the younger patients in 2015 were male.

“There is no clear explanation for the higher proportion of advanced disease in younger patients, and further study is required to identify biologic, genetic, and environmental factors that may underlie this observation,” the researchers wrote. “A potential hypothesis is that ‘young-onset esophageal adenocarcinoma’ may involve rapid transition from intestinal metaplasia to esophageal adenocarcinoma, driven by an increase in signaling molecules that are active in the intestine,” they suggested.

The study findings were limited by several factors including the inability to review individual case records to confirm disease stage and to compare outcomes across ethnicities, and the lack of data on comorbidities in the SEER database, the researchers noted.

However, the results were strengthened by overall quality of the SEER database and use of multivariate analysis, they added. The evidence of increased incidence and increased odds of advanced disease in younger adults suggest that “reevaluation of our diagnostic and treatment strategies in this age group might need to be considered.”
 

Reasons for increase remain unclear

“While esophageal adenocarcinoma is uncommon overall in younger patients, this study importantly highlights that not only has the incidence of esophageal adenocarcinoma increased more than threefold in patients under the age of 50 over the last 4 decades, but that younger patients are presenting with more advanced disease and have overall poorer survival, compared to older patients,” Rahul A. Shimpi, MD, of Duke University, Durham, N.C., said in an interview.

“The reasons for these findings are unclear, but the authors propose a number of potential factors that could explain them. These include differences in tumor biology, rising rates of obesity and [gastroesophageal reflux disease] in younger patients, decreased endoscopic screening for and surveillance of Barrett’s esophagus in this age group, and differing therapeutic approaches to management,” Dr. Shimpi said.

“The findings from this study underscore that, while uncommon, clinicians need to be aware of the rising incidence of esophageal cancer in younger patients. It is important that even younger patients presenting with esophageal symptoms, such as dysphagia, undergo investigation,” he emphasized.

“I would like to see further study into the potential factors driving the findings in this study, including whether trends in differential treatment modalities account for some of the survival differences found in different age groups,” Dr. Shimpi added. “Finally, further research will ideally clarify optimal Barrett’s screening and surveillance approaches in patients younger than age 50 in order to determine whether new strategies might impact esophageal adenocarcinoma incidence and outcomes in this group.”

The study was funded in part by the National Cancer Institute and the National Center for Advancing Translational Sciences. Two authors disclosed relationships outside the submitted work, but Dr. Codipilly and the remaining authors had no financial conflicts to disclose. Dr. Shimpi had no financial conflicts to disclose.

SOURCE: Codipilly DC et al. Cancer Epidemiol Biomarkers Prev. 2020 Dec 11. doi: 10.1158/1055-9965.EPI-20-0944.

The incidence of esophageal adenocarcinoma in adults aged younger than 50 years increased threefold between 1975 and 2015, based on data from more than 34,000 cases.

Esophageal carcinoma rates overall have risen in the United States over the past 4 decades, but the average patient is in their 60s, wrote Don C. Codipilly, MD, of the Mayo Clinic, Rochester, Minn., and colleagues. Therefore, “data on the incidence, stage distribution, and outcomes of this segment of patients [younger than 50 years] with esophageal adenocarcinoma are relatively limited.”

In a study published in Cancer Epidemiology, Biomarkers & Prevention, the researchers identified 34,443 cases of esophageal adenocarcinoma using the Surveillance, Epidemiology, and End Results (SEER) database for the periods of 1975-1989, 1990-1999, and 2000-2015. The cases were limited to histologically confirmed cases and were stratified according to age at diagnosis: younger than 50 years, 50-69 years, and 70 years and older

Overall, the annual incidence of esophageal adenocarcinoma among individuals younger than 50 years increased from 0.08 per 100,000 persons in 1975 to 0.27 per 100,000 persons in 2015.
 

Younger patients show more advanced illness

Although the incidence rose across all three age groups during the study period, the largest increase was seen in those aged 70 years and older. However, the younger group was significantly more likely to present at more-advanced stages, the researchers pointed out: Between 2000 and 2015, localized disease represented only 15.1% of cases in those younger than 50 years, compared with 22.4% in patients aged 50-69 years and 32.2% in those 70 years and older. The incidence of regional/distant disease among younger patients has increased over time, with 81.8% in 1975-1989, 75.5% in 1990-1999, and 84.9% in 2000-2015 (P < .01), and this increase has been faster than among older groups, the researches noted. For comparison, during 2000-2015 only 77.6% of patients aged 50-69 years and 67.8% of patients 70 years and older had regional/distant disease.

In addition, the majority of cases of young-onset esophageal adenocarcinoma occurred in men in a trend that persisted across the study periods; 90% of patients younger than 50 years were male in 1975, and 86% of the younger patients in 2015 were male.

“There is no clear explanation for the higher proportion of advanced disease in younger patients, and further study is required to identify biologic, genetic, and environmental factors that may underlie this observation,” the researchers wrote. “A potential hypothesis is that ‘young-onset esophageal adenocarcinoma’ may involve rapid transition from intestinal metaplasia to esophageal adenocarcinoma, driven by an increase in signaling molecules that are active in the intestine,” they suggested.

The study findings were limited by several factors including the inability to review individual case records to confirm disease stage and to compare outcomes across ethnicities, and the lack of data on comorbidities in the SEER database, the researchers noted.

However, the results were strengthened by overall quality of the SEER database and use of multivariate analysis, they added. The evidence of increased incidence and increased odds of advanced disease in younger adults suggest that “reevaluation of our diagnostic and treatment strategies in this age group might need to be considered.”
 

Reasons for increase remain unclear

“While esophageal adenocarcinoma is uncommon overall in younger patients, this study importantly highlights that not only has the incidence of esophageal adenocarcinoma increased more than threefold in patients under the age of 50 over the last 4 decades, but that younger patients are presenting with more advanced disease and have overall poorer survival, compared to older patients,” Rahul A. Shimpi, MD, of Duke University, Durham, N.C., said in an interview.

“The reasons for these findings are unclear, but the authors propose a number of potential factors that could explain them. These include differences in tumor biology, rising rates of obesity and [gastroesophageal reflux disease] in younger patients, decreased endoscopic screening for and surveillance of Barrett’s esophagus in this age group, and differing therapeutic approaches to management,” Dr. Shimpi said.

“The findings from this study underscore that, while uncommon, clinicians need to be aware of the rising incidence of esophageal cancer in younger patients. It is important that even younger patients presenting with esophageal symptoms, such as dysphagia, undergo investigation,” he emphasized.

“I would like to see further study into the potential factors driving the findings in this study, including whether trends in differential treatment modalities account for some of the survival differences found in different age groups,” Dr. Shimpi added. “Finally, further research will ideally clarify optimal Barrett’s screening and surveillance approaches in patients younger than age 50 in order to determine whether new strategies might impact esophageal adenocarcinoma incidence and outcomes in this group.”

The study was funded in part by the National Cancer Institute and the National Center for Advancing Translational Sciences. Two authors disclosed relationships outside the submitted work, but Dr. Codipilly and the remaining authors had no financial conflicts to disclose. Dr. Shimpi had no financial conflicts to disclose.

SOURCE: Codipilly DC et al. Cancer Epidemiol Biomarkers Prev. 2020 Dec 11. doi: 10.1158/1055-9965.EPI-20-0944.

Now that COVID-19 vaccines are being distributed, the American Association for Cancer Research has called for people with cancer to be considered as a high-priority group.

“The available evidence supports the conclusion that patients with cancer, in particular with hematologic malignancies, should be considered among the high-risk groups for priority COVID-19 vaccination,” according to the AACR’s COVID-19 and Cancer Task Force.

A review of literature suggested that COVID-19 fatality rates for patients with cancer were double that of individuals without cancer, the team noted. The higher mortality rates still trended upward, even after adjusting for confounders including age, sex, and comorbidities, indicating that there is a greater risk for severe disease and COVID-19–related mortality.

The new AACR position paper was published online Dec. 19 in Cancer Discovery.

“We conclude that patients with an active cancer should be considered for priority access to COVID-19 vaccination, along other particularly vulnerable populations with risk factors for adverse outcomes with COVID-19,” the team wrote.

However, the authors noted that “it is unclear whether this recommendation should be applicable to patients with a past diagnosis of cancer, as cancer survivors can be considered having the same risk as other persons with matched age and other risk factors. 

“Given that there are nearly 17 million people living with a history of cancer in the United States alone, it is critical to understand whether these individuals are at a higher risk to contract SARS-COV-2 and to experience severe outcomes from COVID-19,” they added.
 

Allocation of initial doses

There has already been much discussion on the allocation of the initial doses of COVID-19 vaccines that have become available in the United States. The Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention recommended that the first wave of vaccinations, described as phase 1a, should be administered to health care workers (about 21 million people) and residents of long-term care facilities (about 3 million).

The next priority group, phase 1b, should consist of frontline essential workers, a group of about 30 million, and adults aged 75 years or older, a group of about 21 million. When overlap between the groups is taken into account, phase 1b covers about 49 million people, according to the CDC.

Finally, phase 1c, the third priority group, would include adults aged 65-74 years (a group of about 32 million), adults aged 16-64 years with high-risk medical conditions (a group of about 110 million), and essential workers who did not qualify for inclusion in phase 1b (a group of about 57 million). With the overlap, Phase 1c would cover about 129 million people.

The AACR task force, led by Antoni Ribas, MD, PhD, of the Jonsson Comprehensive Cancer Center at the University of California, Los Angeles, noted in their position paper that their recommendation is consistent with ACIP’s guidelines. Those guidelines concluded that patients with cancer are at a higher risk for severe COVID-19, and should be one of the groups considered for early COVID-19 vaccination.
 

Questions remain

Approached for independent comment, Cardinale Smith, MD, PhD, chief quality officer for cancer services for the Mount Sinai Health System in New York, agreed with the AACR task force. “I share that they should be high priority,” she said, “But we don’t know that the efficacy will the same.”

Dr. Smith noted that the impact of cancer therapy on patient immune systems is more related to the type of treatment they’re receiving, and B- and T-cell responses. “But regardless, they should be getting the vaccine, and we just need to follow the guidelines.”

The AACR task force noted that information thus far is quite limited as to the effects of COVID-19 vaccination in patients with cancer. In the Pfizer-BioNTech BNT162b2 COVID vaccine trial, of 43,540 participants, only 3.7% were reported to have cancer. Other large COVID-19 vaccine trials will provide further follow-up information on the effectiveness of the vaccines in patients receiving different cancer treatments, they wrote, but for now, there is “currently not enough data to evaluate the interactions between active oncologic therapy with the ability to induce protective immunity” to COVID-19 with vaccination.

In a recent interview, Nora Disis, MD, a medical oncologist and director of both the Institute of Translational Health Sciences and the Cancer Vaccine Institute, University of Washington, Seattle, also discussed vaccinating cancer patients.

She pointed out that even though there are data suggesting that cancer patients are at higher risk, “they are a bit murky, in part because cancer patients are a heterogeneous group.”

“For example, there are data suggesting that lung and blood cancer patients fare worse,” said Dr. Disis, who is also editor in chief of JAMA Oncology. “There is also a suggestion that, like in the general population, COVID risk in cancer patients remains driven by comorbidities.”

She also pointed out the likelihood that individualized risk factors, including the type of cancer therapy, site of disease, and comorbidities, “will shape individual choices about vaccination among cancer patients.”

It is also reasonable to expect that patients with cancer will respond to the vaccines, even though historically some believed that they would be unable to mount an immune response. “Data on other viral vaccines have shown otherwise,” said Dr. Disis. “For example, there has been a long history of studies of flu vaccination in cancer patients, and in general, those vaccines confer protection.”

Several of the authors of the AACR position paper, including Dr. Ribas, reported relationships with industry as detailed in the paper. Dr. Smith has disclosed no relevant financial relationships.

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

Now that COVID-19 vaccines are being distributed, the American Association for Cancer Research has called for people with cancer to be considered as a high-priority group.

“The available evidence supports the conclusion that patients with cancer, in particular with hematologic malignancies, should be considered among the high-risk groups for priority COVID-19 vaccination,” according to the AACR’s COVID-19 and Cancer Task Force.

A review of literature suggested that COVID-19 fatality rates for patients with cancer were double that of individuals without cancer, the team noted. The higher mortality rates still trended upward, even after adjusting for confounders including age, sex, and comorbidities, indicating that there is a greater risk for severe disease and COVID-19–related mortality.

The new AACR position paper was published online Dec. 19 in Cancer Discovery.

“We conclude that patients with an active cancer should be considered for priority access to COVID-19 vaccination, along other particularly vulnerable populations with risk factors for adverse outcomes with COVID-19,” the team wrote.

However, the authors noted that “it is unclear whether this recommendation should be applicable to patients with a past diagnosis of cancer, as cancer survivors can be considered having the same risk as other persons with matched age and other risk factors. 

“Given that there are nearly 17 million people living with a history of cancer in the United States alone, it is critical to understand whether these individuals are at a higher risk to contract SARS-COV-2 and to experience severe outcomes from COVID-19,” they added.
 

Allocation of initial doses

There has already been much discussion on the allocation of the initial doses of COVID-19 vaccines that have become available in the United States. The Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention recommended that the first wave of vaccinations, described as phase 1a, should be administered to health care workers (about 21 million people) and residents of long-term care facilities (about 3 million).

The next priority group, phase 1b, should consist of frontline essential workers, a group of about 30 million, and adults aged 75 years or older, a group of about 21 million. When overlap between the groups is taken into account, phase 1b covers about 49 million people, according to the CDC.

Finally, phase 1c, the third priority group, would include adults aged 65-74 years (a group of about 32 million), adults aged 16-64 years with high-risk medical conditions (a group of about 110 million), and essential workers who did not qualify for inclusion in phase 1b (a group of about 57 million). With the overlap, Phase 1c would cover about 129 million people.

The AACR task force, led by Antoni Ribas, MD, PhD, of the Jonsson Comprehensive Cancer Center at the University of California, Los Angeles, noted in their position paper that their recommendation is consistent with ACIP’s guidelines. Those guidelines concluded that patients with cancer are at a higher risk for severe COVID-19, and should be one of the groups considered for early COVID-19 vaccination.
 

Questions remain

Approached for independent comment, Cardinale Smith, MD, PhD, chief quality officer for cancer services for the Mount Sinai Health System in New York, agreed with the AACR task force. “I share that they should be high priority,” she said, “But we don’t know that the efficacy will the same.”

Dr. Smith noted that the impact of cancer therapy on patient immune systems is more related to the type of treatment they’re receiving, and B- and T-cell responses. “But regardless, they should be getting the vaccine, and we just need to follow the guidelines.”

The AACR task force noted that information thus far is quite limited as to the effects of COVID-19 vaccination in patients with cancer. In the Pfizer-BioNTech BNT162b2 COVID vaccine trial, of 43,540 participants, only 3.7% were reported to have cancer. Other large COVID-19 vaccine trials will provide further follow-up information on the effectiveness of the vaccines in patients receiving different cancer treatments, they wrote, but for now, there is “currently not enough data to evaluate the interactions between active oncologic therapy with the ability to induce protective immunity” to COVID-19 with vaccination.

In a recent interview, Nora Disis, MD, a medical oncologist and director of both the Institute of Translational Health Sciences and the Cancer Vaccine Institute, University of Washington, Seattle, also discussed vaccinating cancer patients.

She pointed out that even though there are data suggesting that cancer patients are at higher risk, “they are a bit murky, in part because cancer patients are a heterogeneous group.”

“For example, there are data suggesting that lung and blood cancer patients fare worse,” said Dr. Disis, who is also editor in chief of JAMA Oncology. “There is also a suggestion that, like in the general population, COVID risk in cancer patients remains driven by comorbidities.”

She also pointed out the likelihood that individualized risk factors, including the type of cancer therapy, site of disease, and comorbidities, “will shape individual choices about vaccination among cancer patients.”

It is also reasonable to expect that patients with cancer will respond to the vaccines, even though historically some believed that they would be unable to mount an immune response. “Data on other viral vaccines have shown otherwise,” said Dr. Disis. “For example, there has been a long history of studies of flu vaccination in cancer patients, and in general, those vaccines confer protection.”

Several of the authors of the AACR position paper, including Dr. Ribas, reported relationships with industry as detailed in the paper. Dr. Smith has disclosed no relevant financial relationships.

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

Now that COVID-19 vaccines are being distributed, the American Association for Cancer Research has called for people with cancer to be considered as a high-priority group.

“The available evidence supports the conclusion that patients with cancer, in particular with hematologic malignancies, should be considered among the high-risk groups for priority COVID-19 vaccination,” according to the AACR’s COVID-19 and Cancer Task Force.

A review of literature suggested that COVID-19 fatality rates for patients with cancer were double that of individuals without cancer, the team noted. The higher mortality rates still trended upward, even after adjusting for confounders including age, sex, and comorbidities, indicating that there is a greater risk for severe disease and COVID-19–related mortality.

The new AACR position paper was published online Dec. 19 in Cancer Discovery.

“We conclude that patients with an active cancer should be considered for priority access to COVID-19 vaccination, along other particularly vulnerable populations with risk factors for adverse outcomes with COVID-19,” the team wrote.

However, the authors noted that “it is unclear whether this recommendation should be applicable to patients with a past diagnosis of cancer, as cancer survivors can be considered having the same risk as other persons with matched age and other risk factors. 

“Given that there are nearly 17 million people living with a history of cancer in the United States alone, it is critical to understand whether these individuals are at a higher risk to contract SARS-COV-2 and to experience severe outcomes from COVID-19,” they added.
 

Allocation of initial doses

There has already been much discussion on the allocation of the initial doses of COVID-19 vaccines that have become available in the United States. The Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention recommended that the first wave of vaccinations, described as phase 1a, should be administered to health care workers (about 21 million people) and residents of long-term care facilities (about 3 million).

The next priority group, phase 1b, should consist of frontline essential workers, a group of about 30 million, and adults aged 75 years or older, a group of about 21 million. When overlap between the groups is taken into account, phase 1b covers about 49 million people, according to the CDC.

Finally, phase 1c, the third priority group, would include adults aged 65-74 years (a group of about 32 million), adults aged 16-64 years with high-risk medical conditions (a group of about 110 million), and essential workers who did not qualify for inclusion in phase 1b (a group of about 57 million). With the overlap, Phase 1c would cover about 129 million people.

The AACR task force, led by Antoni Ribas, MD, PhD, of the Jonsson Comprehensive Cancer Center at the University of California, Los Angeles, noted in their position paper that their recommendation is consistent with ACIP’s guidelines. Those guidelines concluded that patients with cancer are at a higher risk for severe COVID-19, and should be one of the groups considered for early COVID-19 vaccination.
 

Questions remain

Approached for independent comment, Cardinale Smith, MD, PhD, chief quality officer for cancer services for the Mount Sinai Health System in New York, agreed with the AACR task force. “I share that they should be high priority,” she said, “But we don’t know that the efficacy will the same.”

Dr. Smith noted that the impact of cancer therapy on patient immune systems is more related to the type of treatment they’re receiving, and B- and T-cell responses. “But regardless, they should be getting the vaccine, and we just need to follow the guidelines.”

The AACR task force noted that information thus far is quite limited as to the effects of COVID-19 vaccination in patients with cancer. In the Pfizer-BioNTech BNT162b2 COVID vaccine trial, of 43,540 participants, only 3.7% were reported to have cancer. Other large COVID-19 vaccine trials will provide further follow-up information on the effectiveness of the vaccines in patients receiving different cancer treatments, they wrote, but for now, there is “currently not enough data to evaluate the interactions between active oncologic therapy with the ability to induce protective immunity” to COVID-19 with vaccination.

In a recent interview, Nora Disis, MD, a medical oncologist and director of both the Institute of Translational Health Sciences and the Cancer Vaccine Institute, University of Washington, Seattle, also discussed vaccinating cancer patients.

She pointed out that even though there are data suggesting that cancer patients are at higher risk, “they are a bit murky, in part because cancer patients are a heterogeneous group.”

“For example, there are data suggesting that lung and blood cancer patients fare worse,” said Dr. Disis, who is also editor in chief of JAMA Oncology. “There is also a suggestion that, like in the general population, COVID risk in cancer patients remains driven by comorbidities.”

She also pointed out the likelihood that individualized risk factors, including the type of cancer therapy, site of disease, and comorbidities, “will shape individual choices about vaccination among cancer patients.”

It is also reasonable to expect that patients with cancer will respond to the vaccines, even though historically some believed that they would be unable to mount an immune response. “Data on other viral vaccines have shown otherwise,” said Dr. Disis. “For example, there has been a long history of studies of flu vaccination in cancer patients, and in general, those vaccines confer protection.”

Several of the authors of the AACR position paper, including Dr. Ribas, reported relationships with industry as detailed in the paper. Dr. Smith has disclosed no relevant financial relationships.

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

The European PET-Boost trial finds that both of two strategies for delivering a radiation boost to locally advanced non–small cell lung cancer (NSCLC) tumors improve local control relative to that seen historically. Results were reported at the European Society for Radiology and Oncology 2020 Online Congress. 

“From previous studies, we know that local recurrences have an important negative impact on survival,” said presenting author Saskia A. Cooke, an MD, PhD candidate in the department of Radiation Oncology Research, the Netherlands Cancer Institute, Amsterdam.

In addition, research shows that, despite advances in drug therapy, the most common site of progression in this population is intrathoracic.

“These results further underline the need to develop treatment strategies which effectively prevent intrathoracic and local recurrences,” Ms. Cooke said.

PET-Boost is a multicenter, randomized trial that enrolled patients with inoperable stage II or III NSCLC and a primary tumor measuring 4 cm or greater.

“The study was a phase 2 ‘pick the winner’ trial, which, by design, does not compare the two arms to one another but to a historic rate of outcome,” Ms. Cooke explained.

The patients were randomized evenly to receive the standard 66 Gy of radiotherapy given in 24 fractions of 2.75 Gy with one of two dose-escalation strategies: a boost to the whole primary tumor or a boost to only the tumor area having high metabolic activity, with a maximum standard uptake value (SUVmax) of at least 50% on the pretreatment FDG-PET scan.

For each patient, both plans were created before randomization, with the dose escalated as high as possible up to an organ-at-risk constraint, Ms. Cooke noted.

“A key element is that the two plans were made isotoxic by equaling the mean lung dose, and in both arms, the dose was delivered integrated into the 24 fractions, so without prolongation of the overall treatment time,” she said.

The trial’s goal was to improve the 1-year rate of freedom from local failure from the 70% seen historically with conventional chemoradiotherapy to 85%.

The trial was stopped early because of slow accrual, after enrollment of 107 patients, Ms. Cooke reported. The large majority received concurrent or sequential chemotherapy with their radiotherapy.

With a median follow-up of 12.6 months for the endpoint, the 1-year rate of freedom from local failure as determined on centrally reviewed CT scans was 97% with the whole-tumor boost and 91% with the PET-directed boost. The 2-year rates were 89% and 82%, respectively.

With a median follow-up of 61 months for the endpoint, the 1-year rate of overall survival was 77% with the whole-tumor boost and 62% with the PET-directed boost. The 2-year rates were 46% and 43%, respectively.

The two boost strategies increased acute and late toxicity over that seen historically, but not to unacceptable levels, as reported previously (Radiother Oncol. 2019;131:166-73).

“In this PET-Boost trial, using hypofractionated personalized dose escalation led to a very good local control rate, which, in both arms, was more than 90% at 1 year,” Ms. Cooke summarized.

In fact, values compare favorably with those seen in the phase 3 RTOG 0617 trial using conventional chemoradiotherapy and dose escalation, even though patients in that trial had smaller tumors.

“Survival, especially in the group treated with the homogeneous boost, was actually similar to the RTOG 0617 high-dose arm and also quite similar to the 1-year survival in the placebo arm of the PACIFIC trial,” she added. The somewhat poorer survival at 2 years in PET-Boost was likely related, in part, to the large tumor volumes and the mediastinal radiation dose, she speculated.

The investigators are now evaluating specific sites of failure and extrathoracic recurrences, as well as assessing associations of toxicity with organ-at-risk doses and quality of life.

“While further results of the trial are awaited, so far, we do believe that in selected patients with locally advanced NSCLC, hypofractionated dose escalation to the tumor is a very important subject for future research,” Ms. Cooke said.

The investigators plan to carry the whole-tumor boost strategy forward because it yields similar efficacy but is easier to plan.

Not ready for prime time

“Overall, this study conceptually is well designed as it is forward thinking and uses imaging to personalize radiation treatment, going to higher doses to active areas of disease based on FDG-PET imaging,” Arya Amini, MD, assistant clinical professor in the department of radiation oncology, City of Hope Comprehensive Cancer Center, Duarte, Calif., said in an interview.

SOURCE: Lalezari F et al. ESTRO 2020. Abstract OC-0609.

The European PET-Boost trial finds that both of two strategies for delivering a radiation boost to locally advanced non–small cell lung cancer (NSCLC) tumors improve local control relative to that seen historically. Results were reported at the European Society for Radiology and Oncology 2020 Online Congress. 

“From previous studies, we know that local recurrences have an important negative impact on survival,” said presenting author Saskia A. Cooke, an MD, PhD candidate in the department of Radiation Oncology Research, the Netherlands Cancer Institute, Amsterdam.

In addition, research shows that, despite advances in drug therapy, the most common site of progression in this population is intrathoracic.

“These results further underline the need to develop treatment strategies which effectively prevent intrathoracic and local recurrences,” Ms. Cooke said.

PET-Boost is a multicenter, randomized trial that enrolled patients with inoperable stage II or III NSCLC and a primary tumor measuring 4 cm or greater.

“The study was a phase 2 ‘pick the winner’ trial, which, by design, does not compare the two arms to one another but to a historic rate of outcome,” Ms. Cooke explained.

The patients were randomized evenly to receive the standard 66 Gy of radiotherapy given in 24 fractions of 2.75 Gy with one of two dose-escalation strategies: a boost to the whole primary tumor or a boost to only the tumor area having high metabolic activity, with a maximum standard uptake value (SUVmax) of at least 50% on the pretreatment FDG-PET scan.

For each patient, both plans were created before randomization, with the dose escalated as high as possible up to an organ-at-risk constraint, Ms. Cooke noted.

“A key element is that the two plans were made isotoxic by equaling the mean lung dose, and in both arms, the dose was delivered integrated into the 24 fractions, so without prolongation of the overall treatment time,” she said.

The trial’s goal was to improve the 1-year rate of freedom from local failure from the 70% seen historically with conventional chemoradiotherapy to 85%.

The trial was stopped early because of slow accrual, after enrollment of 107 patients, Ms. Cooke reported. The large majority received concurrent or sequential chemotherapy with their radiotherapy.

With a median follow-up of 12.6 months for the endpoint, the 1-year rate of freedom from local failure as determined on centrally reviewed CT scans was 97% with the whole-tumor boost and 91% with the PET-directed boost. The 2-year rates were 89% and 82%, respectively.

With a median follow-up of 61 months for the endpoint, the 1-year rate of overall survival was 77% with the whole-tumor boost and 62% with the PET-directed boost. The 2-year rates were 46% and 43%, respectively.

The two boost strategies increased acute and late toxicity over that seen historically, but not to unacceptable levels, as reported previously (Radiother Oncol. 2019;131:166-73).

“In this PET-Boost trial, using hypofractionated personalized dose escalation led to a very good local control rate, which, in both arms, was more than 90% at 1 year,” Ms. Cooke summarized.

In fact, values compare favorably with those seen in the phase 3 RTOG 0617 trial using conventional chemoradiotherapy and dose escalation, even though patients in that trial had smaller tumors.

“Survival, especially in the group treated with the homogeneous boost, was actually similar to the RTOG 0617 high-dose arm and also quite similar to the 1-year survival in the placebo arm of the PACIFIC trial,” she added. The somewhat poorer survival at 2 years in PET-Boost was likely related, in part, to the large tumor volumes and the mediastinal radiation dose, she speculated.

The investigators are now evaluating specific sites of failure and extrathoracic recurrences, as well as assessing associations of toxicity with organ-at-risk doses and quality of life.

“While further results of the trial are awaited, so far, we do believe that in selected patients with locally advanced NSCLC, hypofractionated dose escalation to the tumor is a very important subject for future research,” Ms. Cooke said.

The investigators plan to carry the whole-tumor boost strategy forward because it yields similar efficacy but is easier to plan.

Not ready for prime time

“Overall, this study conceptually is well designed as it is forward thinking and uses imaging to personalize radiation treatment, going to higher doses to active areas of disease based on FDG-PET imaging,” Arya Amini, MD, assistant clinical professor in the department of radiation oncology, City of Hope Comprehensive Cancer Center, Duarte, Calif., said in an interview.

SOURCE: Lalezari F et al. ESTRO 2020. Abstract OC-0609.

The European PET-Boost trial finds that both of two strategies for delivering a radiation boost to locally advanced non–small cell lung cancer (NSCLC) tumors improve local control relative to that seen historically. Results were reported at the European Society for Radiology and Oncology 2020 Online Congress. 

“From previous studies, we know that local recurrences have an important negative impact on survival,” said presenting author Saskia A. Cooke, an MD, PhD candidate in the department of Radiation Oncology Research, the Netherlands Cancer Institute, Amsterdam.

In addition, research shows that, despite advances in drug therapy, the most common site of progression in this population is intrathoracic.

“These results further underline the need to develop treatment strategies which effectively prevent intrathoracic and local recurrences,” Ms. Cooke said.

PET-Boost is a multicenter, randomized trial that enrolled patients with inoperable stage II or III NSCLC and a primary tumor measuring 4 cm or greater.

“The study was a phase 2 ‘pick the winner’ trial, which, by design, does not compare the two arms to one another but to a historic rate of outcome,” Ms. Cooke explained.

The patients were randomized evenly to receive the standard 66 Gy of radiotherapy given in 24 fractions of 2.75 Gy with one of two dose-escalation strategies: a boost to the whole primary tumor or a boost to only the tumor area having high metabolic activity, with a maximum standard uptake value (SUVmax) of at least 50% on the pretreatment FDG-PET scan.

For each patient, both plans were created before randomization, with the dose escalated as high as possible up to an organ-at-risk constraint, Ms. Cooke noted.

“A key element is that the two plans were made isotoxic by equaling the mean lung dose, and in both arms, the dose was delivered integrated into the 24 fractions, so without prolongation of the overall treatment time,” she said.

The trial’s goal was to improve the 1-year rate of freedom from local failure from the 70% seen historically with conventional chemoradiotherapy to 85%.

The trial was stopped early because of slow accrual, after enrollment of 107 patients, Ms. Cooke reported. The large majority received concurrent or sequential chemotherapy with their radiotherapy.

With a median follow-up of 12.6 months for the endpoint, the 1-year rate of freedom from local failure as determined on centrally reviewed CT scans was 97% with the whole-tumor boost and 91% with the PET-directed boost. The 2-year rates were 89% and 82%, respectively.

With a median follow-up of 61 months for the endpoint, the 1-year rate of overall survival was 77% with the whole-tumor boost and 62% with the PET-directed boost. The 2-year rates were 46% and 43%, respectively.

The two boost strategies increased acute and late toxicity over that seen historically, but not to unacceptable levels, as reported previously (Radiother Oncol. 2019;131:166-73).

“In this PET-Boost trial, using hypofractionated personalized dose escalation led to a very good local control rate, which, in both arms, was more than 90% at 1 year,” Ms. Cooke summarized.

In fact, values compare favorably with those seen in the phase 3 RTOG 0617 trial using conventional chemoradiotherapy and dose escalation, even though patients in that trial had smaller tumors.

“Survival, especially in the group treated with the homogeneous boost, was actually similar to the RTOG 0617 high-dose arm and also quite similar to the 1-year survival in the placebo arm of the PACIFIC trial,” she added. The somewhat poorer survival at 2 years in PET-Boost was likely related, in part, to the large tumor volumes and the mediastinal radiation dose, she speculated.

The investigators are now evaluating specific sites of failure and extrathoracic recurrences, as well as assessing associations of toxicity with organ-at-risk doses and quality of life.

“While further results of the trial are awaited, so far, we do believe that in selected patients with locally advanced NSCLC, hypofractionated dose escalation to the tumor is a very important subject for future research,” Ms. Cooke said.

The investigators plan to carry the whole-tumor boost strategy forward because it yields similar efficacy but is easier to plan.

Not ready for prime time

“Overall, this study conceptually is well designed as it is forward thinking and uses imaging to personalize radiation treatment, going to higher doses to active areas of disease based on FDG-PET imaging,” Arya Amini, MD, assistant clinical professor in the department of radiation oncology, City of Hope Comprehensive Cancer Center, Duarte, Calif., said in an interview.

SOURCE: Lalezari F et al. ESTRO 2020. Abstract OC-0609.

Rare cancers comprise about 20% of all cancers in the United States and Europe, according to recent estimates, but patients with rare cancers are vastly underrepresented in clinical trials.

Recently, there has been a focus on immune checkpoint blockade (ICB) in common cancer types. Since several rare tumor types share similar biologic features with the more common tumors, there is a need to test ICB in rare tumors, particularly because remissions with ICB can be durable.

Enter the DART trial, a phase 2, single-arm study of combinatorial ICB with ipilimumab plus nivolumab in patients with unresectable or metastatic rare cancers.

Results from DART were recently presented at the Society for Immunotherapy of Cancer’s 35th Anniversary Annual Meeting. Michael J. Wagner, MD, of the University of Washington, Seattle, reported results in patients with advanced or unresectable angiosarcoma, one of the rare tumor types included in DART.
 

About angiosarcomas

Angiosarcomas account for less than 3% of all adult soft-tissue sarcomas, according to a review published in The Lancet Oncology. Angiosarcomas may arise in any part of the body, especially the head and neck (27%), breast (19.7%), and extremities (15.3%). These cancers can be primary or secondary (i.e., associated with prior radiation therapy or chronic lymphedema).

Angiosarcomas are aggressive, difficult to treat, and confer high mortality. The tumors are responsive to chemotherapy, but responses are brief. The estimated 5-year survival rate for all patients with angiosarcoma, including those who present with localized disease, is 30%-40%.

According to Dr. Wagner, a subset of angiosarcomas are characterized by high tumor mutational burden (TMB) and COSMIC signature 7, a DNA mutational signature that is consistent with other cancers caused by ultraviolet light exposure.

The high TMB subset of angiosarcomas is comparable with other cancer types that are responsive to ICB. Indeed, patients with angiosarcoma treated with ICB have shown responses, according to research published in the Journal for Immunotherapy of Cancer. However, no prospective studies of ICB in angiosarcoma have been published.
 

About DART

The DART trial includes more than 50 cohorts of rare cancer subtypes. Patients receive IV ipilimumab at 1 mg/kg every 6 weeks and IV nivolumab at 240 mg every 2 weeks.

The primary endpoint is objective response rate, as assessed by RECIST v1.1. Secondary endpoints include progression-free survival, overall survival, stable disease at 6 months, and toxicity.

The trial has a two-stage design. Six patients are enrolled in the first stage, and, if at least one patient responds to treatment, an additional 10 patients are enrolled in the second stage.

If at least two responses are seen among the 16 patients enrolled, further study of ICB is considered warranted.
 

Results in angiosarcoma

Dr. Wagner reported on the 16 angiosarcoma patients enrolled in DART. Nine patients had cutaneous primary tumors, seven had noncutaneous primary tumors, and three patients had radiation-associated angiosarcoma of the breast or chest wall.

Patients had received a median of two (range, zero to five) prior lines of therapy.

Adverse events (AEs) were consistent with prior safety results of the ipilimumab-nivolumab combination. Three-quarters of patients experienced an AE of any grade. The most common AEs were transaminase elevation, anemia, diarrhea, fatigue, hypothyroidism, pneumonitis, pruritus, and rash.

A quarter of patients had a grade 3-4 AE, and 12.5% of AEs led to premature treatment discontinuation. There were no fatal AEs.

The ORR was 25%. Responses occurred in 4 of the 16 patients, including 3 of 5 patients with primary cutaneous tumors of the scalp or face and 1 of 3 patients with radiation-associated breast angiosarcoma.

Two of the four responses and one case of stable disease have persisted for almost a year, and these patients remain on treatment. To put these results into perspective, Dr. Wagner noted that responses to cytotoxic chemotherapy rarely last 6 months.

The 6-month progression-free survival rate was 38%. The median overall survival has not yet been reached.

Dr. Wagner concluded that the combinatorial ICB regimen employed in DART was well tolerated and had an ORR of 25% in angiosarcoma regardless of primary site. Per the criteria of the DART trial, further investigation of ICB in angiosarcoma is warranted.
 

Molecular insights

Although correlative analyses of tumor tissue and peripheral blood are embedded in the DART trial, those analyses have not yet been performed. Eight of the 16 angiosarcoma patients had diagnostic molecular studies performed at their parent institutions, utilizing a variety of commercial platforms.

All eight patients for whom molecular data were available had at least two deleterious genomic alterations detected, but each had a distinct molecular profile.

Seven patients had TMB analyzed, including two partial responders to ICB. One of the seven patients had a high TMB, and this patient was one of the two responders. The other responder had an intermediate TMB.

Three patients had programmed death–ligand 1 staining on their tumors. Two of the three had high expression of PD-L1, including the responder with an intermediate TMB.
 

The real impact of DART

The DART trial is a “basket trial,” employing a similar treatment regimen for multiple tumor types. It provides a uniform framework for studying tumors that have been neglected in clinical trials heretofore.

Although the cohort of angiosarcoma patients is small, central pathology review was not required, and the treatment regimen was not compared directly with other potential therapies, the reported results of the ipilimumab-nivolumab regimen justify further study.

The biospecimens collected in DART will provide a rich source of data to identify common themes among responders and nonresponders, among patients who experience durable remissions and those who do not.

Angiosarcoma is not the only rare cancer for which combinatorial ICB has been valuable under the auspices of the DART trial. In Clinical Cancer Research, investigators reported an ORR of 44% among patients with high-grade neuroendocrine cancers, independent of primary site of origin. Progression-free survival at 6 months was 31%.

The DART trial is available at more than 800 sites, providing access to potentially promising treatment in a rigorous, scientifically valuable study for geographically underserved populations, including patients who live in rural areas.

The key message for practicing oncologists and clinical investigators is that clinical trials in rare tumors are feasible and can yield hope for patients who might lack it otherwise.

DART is funded by the National Cancer Institute and Bristol-Myers Squibb. Dr. Wagner disclosed relationships with Deciphera, Adaptimmune, GlaxoSmithKline, Athenex, and Incyte.

Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.

SOURCE: Wagner M et al. SITC 2020, Abstract 795.

Rare cancers comprise about 20% of all cancers in the United States and Europe, according to recent estimates, but patients with rare cancers are vastly underrepresented in clinical trials.

Recently, there has been a focus on immune checkpoint blockade (ICB) in common cancer types. Since several rare tumor types share similar biologic features with the more common tumors, there is a need to test ICB in rare tumors, particularly because remissions with ICB can be durable.

Enter the DART trial, a phase 2, single-arm study of combinatorial ICB with ipilimumab plus nivolumab in patients with unresectable or metastatic rare cancers.

Results from DART were recently presented at the Society for Immunotherapy of Cancer’s 35th Anniversary Annual Meeting. Michael J. Wagner, MD, of the University of Washington, Seattle, reported results in patients with advanced or unresectable angiosarcoma, one of the rare tumor types included in DART.
 

About angiosarcomas

Angiosarcomas account for less than 3% of all adult soft-tissue sarcomas, according to a review published in The Lancet Oncology. Angiosarcomas may arise in any part of the body, especially the head and neck (27%), breast (19.7%), and extremities (15.3%). These cancers can be primary or secondary (i.e., associated with prior radiation therapy or chronic lymphedema).

Angiosarcomas are aggressive, difficult to treat, and confer high mortality. The tumors are responsive to chemotherapy, but responses are brief. The estimated 5-year survival rate for all patients with angiosarcoma, including those who present with localized disease, is 30%-40%.

According to Dr. Wagner, a subset of angiosarcomas are characterized by high tumor mutational burden (TMB) and COSMIC signature 7, a DNA mutational signature that is consistent with other cancers caused by ultraviolet light exposure.

The high TMB subset of angiosarcomas is comparable with other cancer types that are responsive to ICB. Indeed, patients with angiosarcoma treated with ICB have shown responses, according to research published in the Journal for Immunotherapy of Cancer. However, no prospective studies of ICB in angiosarcoma have been published.
 

About DART

The DART trial includes more than 50 cohorts of rare cancer subtypes. Patients receive IV ipilimumab at 1 mg/kg every 6 weeks and IV nivolumab at 240 mg every 2 weeks.

The primary endpoint is objective response rate, as assessed by RECIST v1.1. Secondary endpoints include progression-free survival, overall survival, stable disease at 6 months, and toxicity.

The trial has a two-stage design. Six patients are enrolled in the first stage, and, if at least one patient responds to treatment, an additional 10 patients are enrolled in the second stage.

If at least two responses are seen among the 16 patients enrolled, further study of ICB is considered warranted.
 

Results in angiosarcoma

Dr. Wagner reported on the 16 angiosarcoma patients enrolled in DART. Nine patients had cutaneous primary tumors, seven had noncutaneous primary tumors, and three patients had radiation-associated angiosarcoma of the breast or chest wall.

Patients had received a median of two (range, zero to five) prior lines of therapy.

Adverse events (AEs) were consistent with prior safety results of the ipilimumab-nivolumab combination. Three-quarters of patients experienced an AE of any grade. The most common AEs were transaminase elevation, anemia, diarrhea, fatigue, hypothyroidism, pneumonitis, pruritus, and rash.

A quarter of patients had a grade 3-4 AE, and 12.5% of AEs led to premature treatment discontinuation. There were no fatal AEs.

The ORR was 25%. Responses occurred in 4 of the 16 patients, including 3 of 5 patients with primary cutaneous tumors of the scalp or face and 1 of 3 patients with radiation-associated breast angiosarcoma.

Two of the four responses and one case of stable disease have persisted for almost a year, and these patients remain on treatment. To put these results into perspective, Dr. Wagner noted that responses to cytotoxic chemotherapy rarely last 6 months.

The 6-month progression-free survival rate was 38%. The median overall survival has not yet been reached.

Dr. Wagner concluded that the combinatorial ICB regimen employed in DART was well tolerated and had an ORR of 25% in angiosarcoma regardless of primary site. Per the criteria of the DART trial, further investigation of ICB in angiosarcoma is warranted.
 

Molecular insights

Although correlative analyses of tumor tissue and peripheral blood are embedded in the DART trial, those analyses have not yet been performed. Eight of the 16 angiosarcoma patients had diagnostic molecular studies performed at their parent institutions, utilizing a variety of commercial platforms.

All eight patients for whom molecular data were available had at least two deleterious genomic alterations detected, but each had a distinct molecular profile.

Seven patients had TMB analyzed, including two partial responders to ICB. One of the seven patients had a high TMB, and this patient was one of the two responders. The other responder had an intermediate TMB.

Three patients had programmed death–ligand 1 staining on their tumors. Two of the three had high expression of PD-L1, including the responder with an intermediate TMB.
 

The real impact of DART

The DART trial is a “basket trial,” employing a similar treatment regimen for multiple tumor types. It provides a uniform framework for studying tumors that have been neglected in clinical trials heretofore.

Although the cohort of angiosarcoma patients is small, central pathology review was not required, and the treatment regimen was not compared directly with other potential therapies, the reported results of the ipilimumab-nivolumab regimen justify further study.

The biospecimens collected in DART will provide a rich source of data to identify common themes among responders and nonresponders, among patients who experience durable remissions and those who do not.

Angiosarcoma is not the only rare cancer for which combinatorial ICB has been valuable under the auspices of the DART trial. In Clinical Cancer Research, investigators reported an ORR of 44% among patients with high-grade neuroendocrine cancers, independent of primary site of origin. Progression-free survival at 6 months was 31%.

The DART trial is available at more than 800 sites, providing access to potentially promising treatment in a rigorous, scientifically valuable study for geographically underserved populations, including patients who live in rural areas.

The key message for practicing oncologists and clinical investigators is that clinical trials in rare tumors are feasible and can yield hope for patients who might lack it otherwise.

DART is funded by the National Cancer Institute and Bristol-Myers Squibb. Dr. Wagner disclosed relationships with Deciphera, Adaptimmune, GlaxoSmithKline, Athenex, and Incyte.

Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.

SOURCE: Wagner M et al. SITC 2020, Abstract 795.

Rare cancers comprise about 20% of all cancers in the United States and Europe, according to recent estimates, but patients with rare cancers are vastly underrepresented in clinical trials.

Recently, there has been a focus on immune checkpoint blockade (ICB) in common cancer types. Since several rare tumor types share similar biologic features with the more common tumors, there is a need to test ICB in rare tumors, particularly because remissions with ICB can be durable.

Enter the DART trial, a phase 2, single-arm study of combinatorial ICB with ipilimumab plus nivolumab in patients with unresectable or metastatic rare cancers.

Results from DART were recently presented at the Society for Immunotherapy of Cancer’s 35th Anniversary Annual Meeting. Michael J. Wagner, MD, of the University of Washington, Seattle, reported results in patients with advanced or unresectable angiosarcoma, one of the rare tumor types included in DART.
 

About angiosarcomas

Angiosarcomas account for less than 3% of all adult soft-tissue sarcomas, according to a review published in The Lancet Oncology. Angiosarcomas may arise in any part of the body, especially the head and neck (27%), breast (19.7%), and extremities (15.3%). These cancers can be primary or secondary (i.e., associated with prior radiation therapy or chronic lymphedema).

Angiosarcomas are aggressive, difficult to treat, and confer high mortality. The tumors are responsive to chemotherapy, but responses are brief. The estimated 5-year survival rate for all patients with angiosarcoma, including those who present with localized disease, is 30%-40%.

According to Dr. Wagner, a subset of angiosarcomas are characterized by high tumor mutational burden (TMB) and COSMIC signature 7, a DNA mutational signature that is consistent with other cancers caused by ultraviolet light exposure.

The high TMB subset of angiosarcomas is comparable with other cancer types that are responsive to ICB. Indeed, patients with angiosarcoma treated with ICB have shown responses, according to research published in the Journal for Immunotherapy of Cancer. However, no prospective studies of ICB in angiosarcoma have been published.
 

About DART

The DART trial includes more than 50 cohorts of rare cancer subtypes. Patients receive IV ipilimumab at 1 mg/kg every 6 weeks and IV nivolumab at 240 mg every 2 weeks.

The primary endpoint is objective response rate, as assessed by RECIST v1.1. Secondary endpoints include progression-free survival, overall survival, stable disease at 6 months, and toxicity.

The trial has a two-stage design. Six patients are enrolled in the first stage, and, if at least one patient responds to treatment, an additional 10 patients are enrolled in the second stage.

If at least two responses are seen among the 16 patients enrolled, further study of ICB is considered warranted.
 

Results in angiosarcoma

Dr. Wagner reported on the 16 angiosarcoma patients enrolled in DART. Nine patients had cutaneous primary tumors, seven had noncutaneous primary tumors, and three patients had radiation-associated angiosarcoma of the breast or chest wall.

Patients had received a median of two (range, zero to five) prior lines of therapy.

Adverse events (AEs) were consistent with prior safety results of the ipilimumab-nivolumab combination. Three-quarters of patients experienced an AE of any grade. The most common AEs were transaminase elevation, anemia, diarrhea, fatigue, hypothyroidism, pneumonitis, pruritus, and rash.

A quarter of patients had a grade 3-4 AE, and 12.5% of AEs led to premature treatment discontinuation. There were no fatal AEs.

The ORR was 25%. Responses occurred in 4 of the 16 patients, including 3 of 5 patients with primary cutaneous tumors of the scalp or face and 1 of 3 patients with radiation-associated breast angiosarcoma.

Two of the four responses and one case of stable disease have persisted for almost a year, and these patients remain on treatment. To put these results into perspective, Dr. Wagner noted that responses to cytotoxic chemotherapy rarely last 6 months.

The 6-month progression-free survival rate was 38%. The median overall survival has not yet been reached.

Dr. Wagner concluded that the combinatorial ICB regimen employed in DART was well tolerated and had an ORR of 25% in angiosarcoma regardless of primary site. Per the criteria of the DART trial, further investigation of ICB in angiosarcoma is warranted.
 

Molecular insights

Although correlative analyses of tumor tissue and peripheral blood are embedded in the DART trial, those analyses have not yet been performed. Eight of the 16 angiosarcoma patients had diagnostic molecular studies performed at their parent institutions, utilizing a variety of commercial platforms.

All eight patients for whom molecular data were available had at least two deleterious genomic alterations detected, but each had a distinct molecular profile.

Seven patients had TMB analyzed, including two partial responders to ICB. One of the seven patients had a high TMB, and this patient was one of the two responders. The other responder had an intermediate TMB.

Three patients had programmed death–ligand 1 staining on their tumors. Two of the three had high expression of PD-L1, including the responder with an intermediate TMB.
 

The real impact of DART

The DART trial is a “basket trial,” employing a similar treatment regimen for multiple tumor types. It provides a uniform framework for studying tumors that have been neglected in clinical trials heretofore.

Although the cohort of angiosarcoma patients is small, central pathology review was not required, and the treatment regimen was not compared directly with other potential therapies, the reported results of the ipilimumab-nivolumab regimen justify further study.

The biospecimens collected in DART will provide a rich source of data to identify common themes among responders and nonresponders, among patients who experience durable remissions and those who do not.

Angiosarcoma is not the only rare cancer for which combinatorial ICB has been valuable under the auspices of the DART trial. In Clinical Cancer Research, investigators reported an ORR of 44% among patients with high-grade neuroendocrine cancers, independent of primary site of origin. Progression-free survival at 6 months was 31%.

The DART trial is available at more than 800 sites, providing access to potentially promising treatment in a rigorous, scientifically valuable study for geographically underserved populations, including patients who live in rural areas.

The key message for practicing oncologists and clinical investigators is that clinical trials in rare tumors are feasible and can yield hope for patients who might lack it otherwise.

DART is funded by the National Cancer Institute and Bristol-Myers Squibb. Dr. Wagner disclosed relationships with Deciphera, Adaptimmune, GlaxoSmithKline, Athenex, and Incyte.

Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.

SOURCE: Wagner M et al. SITC 2020, Abstract 795.

COVID-19 has thrown a wrench in standard treatment protocols for patients with chronic lymphocytic leukemia (CLL). These patients already face a greater risk of dying from infections, and recent research suggests they tend to have risk factors that increase their likelihood of complications and death from COVID-19.

In August, a group of oncologists from the United States and Europe published a literature-informed expert opinion to help their colleagues navigate this new CLL treatment landscape. It offers a roadmap for balancing patients’ therapeutic needs against their risk for viral infection and outlines the safest course of action for patients who test positive for COVID-19.

Mazyar Shadman, MD, MPH, an associate professor in the Clinical Research Division of the Fred Hutchinson Cancer Research Center and the Division of Medical Oncology at the University of Washington School of Medicine, in Seattle, Washington, was contacted for comment to break down what clinicians need to know about treating CLL during the pandemic. This interview has been edited for length and clarity.
 

Question: What prompted you and colleagues from the United States and Europe to write these recommendations?

Dr. Shadman: When we began the collaboration earlier this year, our colleagues in Italy and the rest of Europe had more experience with COVID-19, so they led the effort. We wanted to help oncologists manage their patients with CLL during the pandemic based on the evidence we had at the time and the unknowns we faced.
 

What’s an example of how the available evidence informed your recommendations?

At the time, we didn’t know whether patients with CLL were more likely to get COVID-19, compared to the general population, but we did have evidence already that cancer increases patients’ risk of bad outcomes and death from COVID-19. CLL, for example, can increase risk factors for infection, including hypogammaglobulinemia, innate immune dysfunction, and neutropenia, which may be exacerbated by anticancer treatments. Patients’ existing immune suppression might prevent or delay their ability to react to or cope with the virus. And many patients with CLL have other conditions that increase their risk of a severe response to COVID-19, including older age (70% of CLL patients are older than 65 years), hypertension (21%), and diabetes (26%).

These factors informed our recommendations to limit patients’ exposure to COVID-19 by reducing or postponing the number of in-person visits and routine in-hospital follow-ups, especially if they could be substituted with virtual check-ins.
 

The expert opinion recommendations are divided into three main categories: patients who are newly diagnosed with CLL but have not begun receiving therapy, those already receiving therapy but are free of COVID-19, and those who test positive for COVID-19. Let’s start with the first category. What do the recommendations say about waiting versus proceeding for newly diagnosed patients?

Our priority was balancing the negative impacts of getting COVID-19 with the negative impacts of postponing cancer treatment. We suggested taking each new CLL case on a patient-by-patient basis to determine who needed treatment tomorrow and who could wait a few weeks or months. Fortunately, CLL rarely requires immediate therapy, so the preference was to postpone treatment a few weeks, depending on the local COVID-19 outbreak situation.

In my practice, for instance, we tried to postpone visits as much as we could. Before the pandemic, patients with CLL in the watch-and-wait phase – those diagnosed but who don’t require treatment immediately – would come in for bloodwork and exams every 3-6 months. But when the pandemic hit, we skipped 3-month visits for patients with stable lab results and switched to telehealth visits instead. For those who needed blood draws, we used local labs closer to the patient’s home to minimize their exposure and transportation requirements.

When treatment cannot be deferred, we’ve recommended starting patients on therapies that require fewer in-person visits and are less immune suppressive. We recommended oncologists consider Bruton tyrosine kinase (BTK) inhibitors, such as ibrutinib and acalabrutinib, as well as venetoclax. Some research suggests these inhibitors may be protective against COVID-19 by blunting a patient’s hyperinflammatory response to the virus. These drugs also require minimal routine treatment and lab visits, which helps limit patients’ potential exposure to COVID-19.

But there are risks to waiting. Even during the peak of the pandemic here in Seattle, if patients needed treatment immediately, we did not delay. Patients with significant drops in their platelet or neutrophil count or those with bulky disease, for instance, do require therapy.

It’s important to mention that we did have bad experiences with patients who needed immediate treatment and their treating physicians decided to wait because of COVID-19 risks. These patients who came in with aggressive CLL and experienced delays in care had much more complicated CLL treatment than if they had started treatment earlier.

When organ function became abnormal, for example, some patients could no longer receive certain therapies. If someone’s kidney function becomes abnormal, I wouldn’t recommend giving a drug like venetoclax. Although rare, some patients on venetoclax develop tumor lysis syndrome, which can lead to kidney failure.

Bottom line: Don’t just assume it’s a low-grade disease and that you can wait.



What about patients already receiving treatment for CLL who are free of COVID-19?

For patients on active treatment, we suggested stopping or holding treatment with monoclonal antibodies, such as rituximab and obinutuzumab, and chemotherapy regimens, such as idelalisib plus rituximab and duvelisib, when possible. We recommended oncologists consider continuing treatment for patients on BTK inhibitors.



What happens if a patient with CLL tests positive for COVID-19?

If a patient tests positive for COVID-19 but is not yet on CLL treatment, we recommend postponing CLL care until they’ve recovered from the infection. If a patient is already receiving treatment, the recommendations are similar to those above for COVID-19–negative patients: Delay care for those on chemotherapy and monoclonal antibodies, but consider continuing treatment for patients on BTK inhibitors.
 

The expert opinion was submitted in May and ultimately published in August. How has our understanding of treating CLL during the pandemic changed since then? Would you change any recommendations?

When we published this paper, it was still early on in the pandemic, and we didn’t know as much about COVID-19 and CLL as we do now. Since we published the recommendations, we have received confirmation from several studies that patients with cancer have a more complicated course of COVID-19 and have worse outcomes. But I believe the recommendations we devised early in the pandemic still hold now. Decisions about delivering treatment should be influenced by the local COVID-19 numbers and hospital resources as well as the patient’s specific situation – whether they have more stable disease and can delay or postpone care or whether they need more immediate attention.

With a further surge in cases predicted as we move even deeper into flu season, what would you recommend for initiating treatment in newly diagnosed patients?

The pandemic has created a very fluid situation for treating CLL. What’s happening now in Seattle may not be the same story in New York, California, or elsewhere. In early November [when Dr. Shadman was first contacted], in Seattle, we were not postponing care because our COVID-19 numbers were fairly good. But, as of mid December, that is starting to change as the COVID-19 numbers fluctuate.
 

If we do experience a second peak of COVID-19 cases, we would need to modify our practice as we did during the initial surge earlier this year. That would mean avoiding treatment with monoclonal antibodies and chemotherapy, as well as minimizing blood draws and drugs that require frequent in-person visits.
 

How important is it for patients to be vaccinated against COVID-19?

There are two key things to consider about a vaccine. Is the vaccine safe from the general safety standpoint that everyone is worried about? And if the vaccine is not harmful, will it work in patients will CLL?

Because we don’t yet know the complete side-effect profile of a COVID-19 vaccine, we would need to assess each patient’s condition to limit adverse reactions and to see whether the vaccine alters a patient’s immune response to the CLL drug they’re taking.

At the University of Washington, Seattle, we have a plan to start studying the effectiveness of the Pfizer and Moderna vaccines in patients with CLL – carefully assessing patients’ response to the vaccine in terms of antibody response. We already know, based on small studies, that the antibody response to the flu vaccine, for instance, is not as strong in patients with CLL, compared to those without. But, overall, as long as the vaccine won’t cause harm, I would recommend my patients get it.

Dr. Shadman has disclosed no relevant financial relationships.

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

COVID-19 has thrown a wrench in standard treatment protocols for patients with chronic lymphocytic leukemia (CLL). These patients already face a greater risk of dying from infections, and recent research suggests they tend to have risk factors that increase their likelihood of complications and death from COVID-19.

In August, a group of oncologists from the United States and Europe published a literature-informed expert opinion to help their colleagues navigate this new CLL treatment landscape. It offers a roadmap for balancing patients’ therapeutic needs against their risk for viral infection and outlines the safest course of action for patients who test positive for COVID-19.

Mazyar Shadman, MD, MPH, an associate professor in the Clinical Research Division of the Fred Hutchinson Cancer Research Center and the Division of Medical Oncology at the University of Washington School of Medicine, in Seattle, Washington, was contacted for comment to break down what clinicians need to know about treating CLL during the pandemic. This interview has been edited for length and clarity.
 

Question: What prompted you and colleagues from the United States and Europe to write these recommendations?

Dr. Shadman: When we began the collaboration earlier this year, our colleagues in Italy and the rest of Europe had more experience with COVID-19, so they led the effort. We wanted to help oncologists manage their patients with CLL during the pandemic based on the evidence we had at the time and the unknowns we faced.
 

What’s an example of how the available evidence informed your recommendations?

At the time, we didn’t know whether patients with CLL were more likely to get COVID-19, compared to the general population, but we did have evidence already that cancer increases patients’ risk of bad outcomes and death from COVID-19. CLL, for example, can increase risk factors for infection, including hypogammaglobulinemia, innate immune dysfunction, and neutropenia, which may be exacerbated by anticancer treatments. Patients’ existing immune suppression might prevent or delay their ability to react to or cope with the virus. And many patients with CLL have other conditions that increase their risk of a severe response to COVID-19, including older age (70% of CLL patients are older than 65 years), hypertension (21%), and diabetes (26%).

These factors informed our recommendations to limit patients’ exposure to COVID-19 by reducing or postponing the number of in-person visits and routine in-hospital follow-ups, especially if they could be substituted with virtual check-ins.
 

The expert opinion recommendations are divided into three main categories: patients who are newly diagnosed with CLL but have not begun receiving therapy, those already receiving therapy but are free of COVID-19, and those who test positive for COVID-19. Let’s start with the first category. What do the recommendations say about waiting versus proceeding for newly diagnosed patients?

Our priority was balancing the negative impacts of getting COVID-19 with the negative impacts of postponing cancer treatment. We suggested taking each new CLL case on a patient-by-patient basis to determine who needed treatment tomorrow and who could wait a few weeks or months. Fortunately, CLL rarely requires immediate therapy, so the preference was to postpone treatment a few weeks, depending on the local COVID-19 outbreak situation.

In my practice, for instance, we tried to postpone visits as much as we could. Before the pandemic, patients with CLL in the watch-and-wait phase – those diagnosed but who don’t require treatment immediately – would come in for bloodwork and exams every 3-6 months. But when the pandemic hit, we skipped 3-month visits for patients with stable lab results and switched to telehealth visits instead. For those who needed blood draws, we used local labs closer to the patient’s home to minimize their exposure and transportation requirements.

When treatment cannot be deferred, we’ve recommended starting patients on therapies that require fewer in-person visits and are less immune suppressive. We recommended oncologists consider Bruton tyrosine kinase (BTK) inhibitors, such as ibrutinib and acalabrutinib, as well as venetoclax. Some research suggests these inhibitors may be protective against COVID-19 by blunting a patient’s hyperinflammatory response to the virus. These drugs also require minimal routine treatment and lab visits, which helps limit patients’ potential exposure to COVID-19.

But there are risks to waiting. Even during the peak of the pandemic here in Seattle, if patients needed treatment immediately, we did not delay. Patients with significant drops in their platelet or neutrophil count or those with bulky disease, for instance, do require therapy.

It’s important to mention that we did have bad experiences with patients who needed immediate treatment and their treating physicians decided to wait because of COVID-19 risks. These patients who came in with aggressive CLL and experienced delays in care had much more complicated CLL treatment than if they had started treatment earlier.

When organ function became abnormal, for example, some patients could no longer receive certain therapies. If someone’s kidney function becomes abnormal, I wouldn’t recommend giving a drug like venetoclax. Although rare, some patients on venetoclax develop tumor lysis syndrome, which can lead to kidney failure.

Bottom line: Don’t just assume it’s a low-grade disease and that you can wait.



What about patients already receiving treatment for CLL who are free of COVID-19?

For patients on active treatment, we suggested stopping or holding treatment with monoclonal antibodies, such as rituximab and obinutuzumab, and chemotherapy regimens, such as idelalisib plus rituximab and duvelisib, when possible. We recommended oncologists consider continuing treatment for patients on BTK inhibitors.



What happens if a patient with CLL tests positive for COVID-19?

If a patient tests positive for COVID-19 but is not yet on CLL treatment, we recommend postponing CLL care until they’ve recovered from the infection. If a patient is already receiving treatment, the recommendations are similar to those above for COVID-19–negative patients: Delay care for those on chemotherapy and monoclonal antibodies, but consider continuing treatment for patients on BTK inhibitors.
 

The expert opinion was submitted in May and ultimately published in August. How has our understanding of treating CLL during the pandemic changed since then? Would you change any recommendations?

When we published this paper, it was still early on in the pandemic, and we didn’t know as much about COVID-19 and CLL as we do now. Since we published the recommendations, we have received confirmation from several studies that patients with cancer have a more complicated course of COVID-19 and have worse outcomes. But I believe the recommendations we devised early in the pandemic still hold now. Decisions about delivering treatment should be influenced by the local COVID-19 numbers and hospital resources as well as the patient’s specific situation – whether they have more stable disease and can delay or postpone care or whether they need more immediate attention.

With a further surge in cases predicted as we move even deeper into flu season, what would you recommend for initiating treatment in newly diagnosed patients?

The pandemic has created a very fluid situation for treating CLL. What’s happening now in Seattle may not be the same story in New York, California, or elsewhere. In early November [when Dr. Shadman was first contacted], in Seattle, we were not postponing care because our COVID-19 numbers were fairly good. But, as of mid December, that is starting to change as the COVID-19 numbers fluctuate.
 

If we do experience a second peak of COVID-19 cases, we would need to modify our practice as we did during the initial surge earlier this year. That would mean avoiding treatment with monoclonal antibodies and chemotherapy, as well as minimizing blood draws and drugs that require frequent in-person visits.
 

How important is it for patients to be vaccinated against COVID-19?

There are two key things to consider about a vaccine. Is the vaccine safe from the general safety standpoint that everyone is worried about? And if the vaccine is not harmful, will it work in patients will CLL?

Because we don’t yet know the complete side-effect profile of a COVID-19 vaccine, we would need to assess each patient’s condition to limit adverse reactions and to see whether the vaccine alters a patient’s immune response to the CLL drug they’re taking.

At the University of Washington, Seattle, we have a plan to start studying the effectiveness of the Pfizer and Moderna vaccines in patients with CLL – carefully assessing patients’ response to the vaccine in terms of antibody response. We already know, based on small studies, that the antibody response to the flu vaccine, for instance, is not as strong in patients with CLL, compared to those without. But, overall, as long as the vaccine won’t cause harm, I would recommend my patients get it.

Dr. Shadman has disclosed no relevant financial relationships.

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

COVID-19 has thrown a wrench in standard treatment protocols for patients with chronic lymphocytic leukemia (CLL). These patients already face a greater risk of dying from infections, and recent research suggests they tend to have risk factors that increase their likelihood of complications and death from COVID-19.

In August, a group of oncologists from the United States and Europe published a literature-informed expert opinion to help their colleagues navigate this new CLL treatment landscape. It offers a roadmap for balancing patients’ therapeutic needs against their risk for viral infection and outlines the safest course of action for patients who test positive for COVID-19.

Mazyar Shadman, MD, MPH, an associate professor in the Clinical Research Division of the Fred Hutchinson Cancer Research Center and the Division of Medical Oncology at the University of Washington School of Medicine, in Seattle, Washington, was contacted for comment to break down what clinicians need to know about treating CLL during the pandemic. This interview has been edited for length and clarity.
 

Question: What prompted you and colleagues from the United States and Europe to write these recommendations?

Dr. Shadman: When we began the collaboration earlier this year, our colleagues in Italy and the rest of Europe had more experience with COVID-19, so they led the effort. We wanted to help oncologists manage their patients with CLL during the pandemic based on the evidence we had at the time and the unknowns we faced.
 

What’s an example of how the available evidence informed your recommendations?

At the time, we didn’t know whether patients with CLL were more likely to get COVID-19, compared to the general population, but we did have evidence already that cancer increases patients’ risk of bad outcomes and death from COVID-19. CLL, for example, can increase risk factors for infection, including hypogammaglobulinemia, innate immune dysfunction, and neutropenia, which may be exacerbated by anticancer treatments. Patients’ existing immune suppression might prevent or delay their ability to react to or cope with the virus. And many patients with CLL have other conditions that increase their risk of a severe response to COVID-19, including older age (70% of CLL patients are older than 65 years), hypertension (21%), and diabetes (26%).

These factors informed our recommendations to limit patients’ exposure to COVID-19 by reducing or postponing the number of in-person visits and routine in-hospital follow-ups, especially if they could be substituted with virtual check-ins.
 

The expert opinion recommendations are divided into three main categories: patients who are newly diagnosed with CLL but have not begun receiving therapy, those already receiving therapy but are free of COVID-19, and those who test positive for COVID-19. Let’s start with the first category. What do the recommendations say about waiting versus proceeding for newly diagnosed patients?

Our priority was balancing the negative impacts of getting COVID-19 with the negative impacts of postponing cancer treatment. We suggested taking each new CLL case on a patient-by-patient basis to determine who needed treatment tomorrow and who could wait a few weeks or months. Fortunately, CLL rarely requires immediate therapy, so the preference was to postpone treatment a few weeks, depending on the local COVID-19 outbreak situation.

In my practice, for instance, we tried to postpone visits as much as we could. Before the pandemic, patients with CLL in the watch-and-wait phase – those diagnosed but who don’t require treatment immediately – would come in for bloodwork and exams every 3-6 months. But when the pandemic hit, we skipped 3-month visits for patients with stable lab results and switched to telehealth visits instead. For those who needed blood draws, we used local labs closer to the patient’s home to minimize their exposure and transportation requirements.

When treatment cannot be deferred, we’ve recommended starting patients on therapies that require fewer in-person visits and are less immune suppressive. We recommended oncologists consider Bruton tyrosine kinase (BTK) inhibitors, such as ibrutinib and acalabrutinib, as well as venetoclax. Some research suggests these inhibitors may be protective against COVID-19 by blunting a patient’s hyperinflammatory response to the virus. These drugs also require minimal routine treatment and lab visits, which helps limit patients’ potential exposure to COVID-19.

But there are risks to waiting. Even during the peak of the pandemic here in Seattle, if patients needed treatment immediately, we did not delay. Patients with significant drops in their platelet or neutrophil count or those with bulky disease, for instance, do require therapy.

It’s important to mention that we did have bad experiences with patients who needed immediate treatment and their treating physicians decided to wait because of COVID-19 risks. These patients who came in with aggressive CLL and experienced delays in care had much more complicated CLL treatment than if they had started treatment earlier.

When organ function became abnormal, for example, some patients could no longer receive certain therapies. If someone’s kidney function becomes abnormal, I wouldn’t recommend giving a drug like venetoclax. Although rare, some patients on venetoclax develop tumor lysis syndrome, which can lead to kidney failure.

Bottom line: Don’t just assume it’s a low-grade disease and that you can wait.



What about patients already receiving treatment for CLL who are free of COVID-19?

For patients on active treatment, we suggested stopping or holding treatment with monoclonal antibodies, such as rituximab and obinutuzumab, and chemotherapy regimens, such as idelalisib plus rituximab and duvelisib, when possible. We recommended oncologists consider continuing treatment for patients on BTK inhibitors.



What happens if a patient with CLL tests positive for COVID-19?

If a patient tests positive for COVID-19 but is not yet on CLL treatment, we recommend postponing CLL care until they’ve recovered from the infection. If a patient is already receiving treatment, the recommendations are similar to those above for COVID-19–negative patients: Delay care for those on chemotherapy and monoclonal antibodies, but consider continuing treatment for patients on BTK inhibitors.
 

The expert opinion was submitted in May and ultimately published in August. How has our understanding of treating CLL during the pandemic changed since then? Would you change any recommendations?

When we published this paper, it was still early on in the pandemic, and we didn’t know as much about COVID-19 and CLL as we do now. Since we published the recommendations, we have received confirmation from several studies that patients with cancer have a more complicated course of COVID-19 and have worse outcomes. But I believe the recommendations we devised early in the pandemic still hold now. Decisions about delivering treatment should be influenced by the local COVID-19 numbers and hospital resources as well as the patient’s specific situation – whether they have more stable disease and can delay or postpone care or whether they need more immediate attention.

With a further surge in cases predicted as we move even deeper into flu season, what would you recommend for initiating treatment in newly diagnosed patients?

The pandemic has created a very fluid situation for treating CLL. What’s happening now in Seattle may not be the same story in New York, California, or elsewhere. In early November [when Dr. Shadman was first contacted], in Seattle, we were not postponing care because our COVID-19 numbers were fairly good. But, as of mid December, that is starting to change as the COVID-19 numbers fluctuate.
 

If we do experience a second peak of COVID-19 cases, we would need to modify our practice as we did during the initial surge earlier this year. That would mean avoiding treatment with monoclonal antibodies and chemotherapy, as well as minimizing blood draws and drugs that require frequent in-person visits.
 

How important is it for patients to be vaccinated against COVID-19?

There are two key things to consider about a vaccine. Is the vaccine safe from the general safety standpoint that everyone is worried about? And if the vaccine is not harmful, will it work in patients will CLL?

Because we don’t yet know the complete side-effect profile of a COVID-19 vaccine, we would need to assess each patient’s condition to limit adverse reactions and to see whether the vaccine alters a patient’s immune response to the CLL drug they’re taking.

At the University of Washington, Seattle, we have a plan to start studying the effectiveness of the Pfizer and Moderna vaccines in patients with CLL – carefully assessing patients’ response to the vaccine in terms of antibody response. We already know, based on small studies, that the antibody response to the flu vaccine, for instance, is not as strong in patients with CLL, compared to those without. But, overall, as long as the vaccine won’t cause harm, I would recommend my patients get it.

Dr. Shadman has disclosed no relevant financial relationships.

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

Dexamethasone can have a detrimental effect on survival in patients with glioblastoma who are receiving immunotherapy, according to a study published in Clinical Cancer Research.

Investigators found that baseline dexamethasone use was associated with poor overall survival (OS) in glioblastoma patients receiving anti–PD-1 or anti–PD-L1 therapy. In fact, in a multivariable analysis, baseline dexamethasone use was the strongest predictor of poor survival.

These results “support accumulating concerns that corticosteroids can be detrimental to immunotherapy for oncology patients,” wrote senior study author David Reardon, MD, of Dana-Farber Cancer Institute in Boston and colleagues.

The concerns are particularly relevant for glioblastoma patients because dexamethasone is a cornerstone of glioblastoma therapy, being used to reduce tumor-associated edema. Patients often receive dexamethasone early on and in significant doses for a protracted period of time to stay ahead of evolving symptoms.

However, the current study suggests dexamethasone and other corticosteroids may be contraindicated in glioblastoma patients on immunotherapy. Therefore, Dr. Reardon and colleagues recommended “careful evaluation of dexamethasone use” in these patients.

“If a glioblastoma patient requires corticosteroids, and they often do for debilitating symptoms, only use these drugs if the patient really needs them,” Dr. Reardon advised. “Start at a low dose and use the shortest treatment interval possible.”
 

Preclinical and clinical results

Dr. Reardon and colleagues initially evaluated the effects of dexamethasone when administered with PD-1 blockade and/or radiotherapy in an immunocompetent syngeneic mouse model.

Most mice that received anti–PD-1 monotherapy were cured, but the benefit of anti–PD-1 therapy was significantly diminished, in a dose-dependent manner, when dexamethasone was added.

At 100 days, the OS rate was about 76% in the anti–PD-1 monotherapy group, 47% when dexamethasone was given at 1 mg/kg, 31% with dexamethasone at 2.5 mg/kg, and 27% with dexamethasone at 10 mg/kg.

A mechanistic study, including analysis of immune cells in the spleen, showed that dexamethasone decreased intratumoral T cells and systemic levels of T cells, natural killer cells, and myeloid cells, while qualitatively impairing lymphocyte function. The mechanism of T-cell depletion included induction of apoptosis, which was noted as soon as 1 hour after the dexamethasone dose, Dr. Reardon said.

The researchers also evaluated 181 consecutive glioblastoma patients treated with PD-1– or PD-L1–targeted therapy. The study included a multivariable statistical analysis that accounted for age, performance status, extent of resection, size of tumor, bulk tumor burden, and MGMT promoter methylation status.

In an initial unadjusted analysis, baseline dexamethasone decreased the median OS to 8.1 months when it was given at less than 2 mg daily and 6.3 months when given at 2 mg or more daily. The median OS was 13.1 months for patients who did not receive dexamethasone.

After multivariable adjustment, baseline dexamethasone eliminated the survival benefit of immunotherapy, the researchers said. The hazard ratio was 2.16 (P = .003) when dexamethasone was given at less than 2 mg daily and 1.97 (P = .005) with dexamethasone at 2 mg or more daily, compared with no baseline dexamethasone.

In fact, the strongest negative risk factor for OS was the use of dexamethasone at initiation of checkpoint inhibitor therapy.
 

Implications: Use corticosteroids ‘very judiciously’

The results of this research suggest “corticosteroids can be detrimental when used along with checkpoint inhibitors,” Dr. Reardon said. He added that this effect could extend to other immunotherapies, such as vaccines, cellular therapies, and oncolytic viruses.

“We need to understand what is driving the inflammatory response,” Dr. Reardon said. “Other targets in the downstream pathway may be regulated to avoid the detrimental effect of corticosteroids.”

Ongoing prospective clinical trials need to build in whether concurrent use of corticosteroids leads to poorer outcomes, according to Dr. Reardon.

“We are validating this prospectively in ongoing clinical trials to evaluate differences in outcome in glioblastoma patients and exploring different types of immunotherapies,” he said.

Though questions remain, Dr. Reardon advises judicious use of corticosteroids or even substituting corticosteroids with bevacizumab in glioblastoma patients.

“If a glioblastoma patient develops debilitating symptoms due to swelling in the brain and is a candidate for immunotherapy, then consider using bevacizumab to avoid using corticosteroids,” Dr. Reardon said, adding that this is being tested prospectively in a clinical trial as well.

“We know corticosteroids have a host of side effects. An additional side effect may be limiting immune function in brain cancer patients and jeopardizing the potential benefits of immunotherapy going forward. I implore practicing oncologists to use corticosteroids very judiciously and as little as possible for as little time as possible,” Dr. Reardon said.

This research was funded by grants from the National Institutes of Health and support from various foundations and institutions. The researchers disclosed relationships with many pharmaceutical companies.

SOURCE: Iorgulescu JB et al. Clin Cancer Res. 2020 Nov 25. doi: 10.1158/1078-0432.CCR-20-2291.

Dexamethasone can have a detrimental effect on survival in patients with glioblastoma who are receiving immunotherapy, according to a study published in Clinical Cancer Research.

Investigators found that baseline dexamethasone use was associated with poor overall survival (OS) in glioblastoma patients receiving anti–PD-1 or anti–PD-L1 therapy. In fact, in a multivariable analysis, baseline dexamethasone use was the strongest predictor of poor survival.

These results “support accumulating concerns that corticosteroids can be detrimental to immunotherapy for oncology patients,” wrote senior study author David Reardon, MD, of Dana-Farber Cancer Institute in Boston and colleagues.

The concerns are particularly relevant for glioblastoma patients because dexamethasone is a cornerstone of glioblastoma therapy, being used to reduce tumor-associated edema. Patients often receive dexamethasone early on and in significant doses for a protracted period of time to stay ahead of evolving symptoms.

However, the current study suggests dexamethasone and other corticosteroids may be contraindicated in glioblastoma patients on immunotherapy. Therefore, Dr. Reardon and colleagues recommended “careful evaluation of dexamethasone use” in these patients.

“If a glioblastoma patient requires corticosteroids, and they often do for debilitating symptoms, only use these drugs if the patient really needs them,” Dr. Reardon advised. “Start at a low dose and use the shortest treatment interval possible.”
 

Preclinical and clinical results

Dr. Reardon and colleagues initially evaluated the effects of dexamethasone when administered with PD-1 blockade and/or radiotherapy in an immunocompetent syngeneic mouse model.

Most mice that received anti–PD-1 monotherapy were cured, but the benefit of anti–PD-1 therapy was significantly diminished, in a dose-dependent manner, when dexamethasone was added.

At 100 days, the OS rate was about 76% in the anti–PD-1 monotherapy group, 47% when dexamethasone was given at 1 mg/kg, 31% with dexamethasone at 2.5 mg/kg, and 27% with dexamethasone at 10 mg/kg.

A mechanistic study, including analysis of immune cells in the spleen, showed that dexamethasone decreased intratumoral T cells and systemic levels of T cells, natural killer cells, and myeloid cells, while qualitatively impairing lymphocyte function. The mechanism of T-cell depletion included induction of apoptosis, which was noted as soon as 1 hour after the dexamethasone dose, Dr. Reardon said.

The researchers also evaluated 181 consecutive glioblastoma patients treated with PD-1– or PD-L1–targeted therapy. The study included a multivariable statistical analysis that accounted for age, performance status, extent of resection, size of tumor, bulk tumor burden, and MGMT promoter methylation status.

In an initial unadjusted analysis, baseline dexamethasone decreased the median OS to 8.1 months when it was given at less than 2 mg daily and 6.3 months when given at 2 mg or more daily. The median OS was 13.1 months for patients who did not receive dexamethasone.

After multivariable adjustment, baseline dexamethasone eliminated the survival benefit of immunotherapy, the researchers said. The hazard ratio was 2.16 (P = .003) when dexamethasone was given at less than 2 mg daily and 1.97 (P = .005) with dexamethasone at 2 mg or more daily, compared with no baseline dexamethasone.

In fact, the strongest negative risk factor for OS was the use of dexamethasone at initiation of checkpoint inhibitor therapy.
 

Implications: Use corticosteroids ‘very judiciously’

The results of this research suggest “corticosteroids can be detrimental when used along with checkpoint inhibitors,” Dr. Reardon said. He added that this effect could extend to other immunotherapies, such as vaccines, cellular therapies, and oncolytic viruses.

“We need to understand what is driving the inflammatory response,” Dr. Reardon said. “Other targets in the downstream pathway may be regulated to avoid the detrimental effect of corticosteroids.”

Ongoing prospective clinical trials need to build in whether concurrent use of corticosteroids leads to poorer outcomes, according to Dr. Reardon.

“We are validating this prospectively in ongoing clinical trials to evaluate differences in outcome in glioblastoma patients and exploring different types of immunotherapies,” he said.

Though questions remain, Dr. Reardon advises judicious use of corticosteroids or even substituting corticosteroids with bevacizumab in glioblastoma patients.

“If a glioblastoma patient develops debilitating symptoms due to swelling in the brain and is a candidate for immunotherapy, then consider using bevacizumab to avoid using corticosteroids,” Dr. Reardon said, adding that this is being tested prospectively in a clinical trial as well.

“We know corticosteroids have a host of side effects. An additional side effect may be limiting immune function in brain cancer patients and jeopardizing the potential benefits of immunotherapy going forward. I implore practicing oncologists to use corticosteroids very judiciously and as little as possible for as little time as possible,” Dr. Reardon said.

This research was funded by grants from the National Institutes of Health and support from various foundations and institutions. The researchers disclosed relationships with many pharmaceutical companies.

SOURCE: Iorgulescu JB et al. Clin Cancer Res. 2020 Nov 25. doi: 10.1158/1078-0432.CCR-20-2291.

Dexamethasone can have a detrimental effect on survival in patients with glioblastoma who are receiving immunotherapy, according to a study published in Clinical Cancer Research.

Investigators found that baseline dexamethasone use was associated with poor overall survival (OS) in glioblastoma patients receiving anti–PD-1 or anti–PD-L1 therapy. In fact, in a multivariable analysis, baseline dexamethasone use was the strongest predictor of poor survival.

These results “support accumulating concerns that corticosteroids can be detrimental to immunotherapy for oncology patients,” wrote senior study author David Reardon, MD, of Dana-Farber Cancer Institute in Boston and colleagues.

The concerns are particularly relevant for glioblastoma patients because dexamethasone is a cornerstone of glioblastoma therapy, being used to reduce tumor-associated edema. Patients often receive dexamethasone early on and in significant doses for a protracted period of time to stay ahead of evolving symptoms.

However, the current study suggests dexamethasone and other corticosteroids may be contraindicated in glioblastoma patients on immunotherapy. Therefore, Dr. Reardon and colleagues recommended “careful evaluation of dexamethasone use” in these patients.

“If a glioblastoma patient requires corticosteroids, and they often do for debilitating symptoms, only use these drugs if the patient really needs them,” Dr. Reardon advised. “Start at a low dose and use the shortest treatment interval possible.”
 

Preclinical and clinical results

Dr. Reardon and colleagues initially evaluated the effects of dexamethasone when administered with PD-1 blockade and/or radiotherapy in an immunocompetent syngeneic mouse model.

Most mice that received anti–PD-1 monotherapy were cured, but the benefit of anti–PD-1 therapy was significantly diminished, in a dose-dependent manner, when dexamethasone was added.

At 100 days, the OS rate was about 76% in the anti–PD-1 monotherapy group, 47% when dexamethasone was given at 1 mg/kg, 31% with dexamethasone at 2.5 mg/kg, and 27% with dexamethasone at 10 mg/kg.

A mechanistic study, including analysis of immune cells in the spleen, showed that dexamethasone decreased intratumoral T cells and systemic levels of T cells, natural killer cells, and myeloid cells, while qualitatively impairing lymphocyte function. The mechanism of T-cell depletion included induction of apoptosis, which was noted as soon as 1 hour after the dexamethasone dose, Dr. Reardon said.

The researchers also evaluated 181 consecutive glioblastoma patients treated with PD-1– or PD-L1–targeted therapy. The study included a multivariable statistical analysis that accounted for age, performance status, extent of resection, size of tumor, bulk tumor burden, and MGMT promoter methylation status.

In an initial unadjusted analysis, baseline dexamethasone decreased the median OS to 8.1 months when it was given at less than 2 mg daily and 6.3 months when given at 2 mg or more daily. The median OS was 13.1 months for patients who did not receive dexamethasone.

After multivariable adjustment, baseline dexamethasone eliminated the survival benefit of immunotherapy, the researchers said. The hazard ratio was 2.16 (P = .003) when dexamethasone was given at less than 2 mg daily and 1.97 (P = .005) with dexamethasone at 2 mg or more daily, compared with no baseline dexamethasone.

In fact, the strongest negative risk factor for OS was the use of dexamethasone at initiation of checkpoint inhibitor therapy.
 

Implications: Use corticosteroids ‘very judiciously’

The results of this research suggest “corticosteroids can be detrimental when used along with checkpoint inhibitors,” Dr. Reardon said. He added that this effect could extend to other immunotherapies, such as vaccines, cellular therapies, and oncolytic viruses.

“We need to understand what is driving the inflammatory response,” Dr. Reardon said. “Other targets in the downstream pathway may be regulated to avoid the detrimental effect of corticosteroids.”

Ongoing prospective clinical trials need to build in whether concurrent use of corticosteroids leads to poorer outcomes, according to Dr. Reardon.

“We are validating this prospectively in ongoing clinical trials to evaluate differences in outcome in glioblastoma patients and exploring different types of immunotherapies,” he said.

Though questions remain, Dr. Reardon advises judicious use of corticosteroids or even substituting corticosteroids with bevacizumab in glioblastoma patients.

“If a glioblastoma patient develops debilitating symptoms due to swelling in the brain and is a candidate for immunotherapy, then consider using bevacizumab to avoid using corticosteroids,” Dr. Reardon said, adding that this is being tested prospectively in a clinical trial as well.

“We know corticosteroids have a host of side effects. An additional side effect may be limiting immune function in brain cancer patients and jeopardizing the potential benefits of immunotherapy going forward. I implore practicing oncologists to use corticosteroids very judiciously and as little as possible for as little time as possible,” Dr. Reardon said.

This research was funded by grants from the National Institutes of Health and support from various foundations and institutions. The researchers disclosed relationships with many pharmaceutical companies.

SOURCE: Iorgulescu JB et al. Clin Cancer Res. 2020 Nov 25. doi: 10.1158/1078-0432.CCR-20-2291.

The US Food and Drug Administration (FDA) has approved osimertinib (Tagrisso) as the first adjuvant treatment for adults with early-stage non–small cell lung cancer (NSCLC) bearing EGFR exon 19 deletions or exon 21 L858R mutations.

Osimertinib was first approved in the US in 2018 for the first-line treatment of patients with metastatic EGFR-mutated NSCLC.

With this new indication, “patients may be treated with this targeted therapy in an earlier and potentially more curative stage of non-small cell lung cancer,” Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research, said in a news release.

The expanded indication is based on results of the ADAURA clinical trial, which compared osimertinib with placebo following complete resection of localized or locally advanced NSCLC with negative margins. 

In the trial, adjuvant osimertinib reduced the relative risk of disease recurrence or death by 83% in patients with stage II and IIIA disease (hazard ratio [HR], 0.17; 95% CI, 0.12 - 0.23; P < .0001).

Disease-free survival (DFS) in the overall trial population of patients with stage IB-IIIA disease showed osimertinib reduced the risk of disease recurrence or death by 80% (HR, 0.20; 95% CI, 0.15 - 0.27; P < .0001).

At 2 years, 89% of patients treated with the targeted agent remained alive and disease free vs 52% on placebo after surgery. The safety and tolerability of osimertinib in the adjuvant setting was consistent with previous trials in the metastatic setting.

The trial of 682 patients was unblinded early and halted on the recommendation of the independent data-monitoring committee, because of the efficacy of osimertinib.

“If I were on the committee, I would have done the same thing. These are extraordinary results,” study investigator Roy S. Herbst, MD, PhD, chief of medical oncology at the Yale Cancer Center, New Haven, Connecticut, said at a press briefing prior to the study presentation at the American Society of Clinical Oncology’s (ASCO) virtual scientific program last spring.

In a Medscape commentary, Mark Kris, MD, of Memorial Sloan Kettering Cancer Center in New York City, said the data with osimertinib in the adjuvant setting are “important and practice-changing.”

“The potential for this drug to improve outcomes has been there for a long time. This phase 3 randomized trial presented at the plenary session of ASCO showed a more than doubling of disease-free survival at 2 years. It shows that we can use therapies in the earlier stages of disease,” Kris noted.

“This approval dispels the notion that treatment is over after surgery and chemotherapy, as the ADAURA results show that Tagrisso can dramatically change the course of this disease,” Dave Fredrickson, executive vice president, AstraZeneca oncology business unit, said in a news release.

Osimertinib had orphan drug status and breakthrough therapy designation for treatment of EGFR mutation-positive NSCLC.

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

The US Food and Drug Administration (FDA) has approved osimertinib (Tagrisso) as the first adjuvant treatment for adults with early-stage non–small cell lung cancer (NSCLC) bearing EGFR exon 19 deletions or exon 21 L858R mutations.

Osimertinib was first approved in the US in 2018 for the first-line treatment of patients with metastatic EGFR-mutated NSCLC.

With this new indication, “patients may be treated with this targeted therapy in an earlier and potentially more curative stage of non-small cell lung cancer,” Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research, said in a news release.

The expanded indication is based on results of the ADAURA clinical trial, which compared osimertinib with placebo following complete resection of localized or locally advanced NSCLC with negative margins. 

In the trial, adjuvant osimertinib reduced the relative risk of disease recurrence or death by 83% in patients with stage II and IIIA disease (hazard ratio [HR], 0.17; 95% CI, 0.12 - 0.23; P < .0001).

Disease-free survival (DFS) in the overall trial population of patients with stage IB-IIIA disease showed osimertinib reduced the risk of disease recurrence or death by 80% (HR, 0.20; 95% CI, 0.15 - 0.27; P < .0001).

At 2 years, 89% of patients treated with the targeted agent remained alive and disease free vs 52% on placebo after surgery. The safety and tolerability of osimertinib in the adjuvant setting was consistent with previous trials in the metastatic setting.

The trial of 682 patients was unblinded early and halted on the recommendation of the independent data-monitoring committee, because of the efficacy of osimertinib.

“If I were on the committee, I would have done the same thing. These are extraordinary results,” study investigator Roy S. Herbst, MD, PhD, chief of medical oncology at the Yale Cancer Center, New Haven, Connecticut, said at a press briefing prior to the study presentation at the American Society of Clinical Oncology’s (ASCO) virtual scientific program last spring.

In a Medscape commentary, Mark Kris, MD, of Memorial Sloan Kettering Cancer Center in New York City, said the data with osimertinib in the adjuvant setting are “important and practice-changing.”

“The potential for this drug to improve outcomes has been there for a long time. This phase 3 randomized trial presented at the plenary session of ASCO showed a more than doubling of disease-free survival at 2 years. It shows that we can use therapies in the earlier stages of disease,” Kris noted.

“This approval dispels the notion that treatment is over after surgery and chemotherapy, as the ADAURA results show that Tagrisso can dramatically change the course of this disease,” Dave Fredrickson, executive vice president, AstraZeneca oncology business unit, said in a news release.

Osimertinib had orphan drug status and breakthrough therapy designation for treatment of EGFR mutation-positive NSCLC.

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

The US Food and Drug Administration (FDA) has approved osimertinib (Tagrisso) as the first adjuvant treatment for adults with early-stage non–small cell lung cancer (NSCLC) bearing EGFR exon 19 deletions or exon 21 L858R mutations.

Osimertinib was first approved in the US in 2018 for the first-line treatment of patients with metastatic EGFR-mutated NSCLC.

With this new indication, “patients may be treated with this targeted therapy in an earlier and potentially more curative stage of non-small cell lung cancer,” Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research, said in a news release.

The expanded indication is based on results of the ADAURA clinical trial, which compared osimertinib with placebo following complete resection of localized or locally advanced NSCLC with negative margins. 

In the trial, adjuvant osimertinib reduced the relative risk of disease recurrence or death by 83% in patients with stage II and IIIA disease (hazard ratio [HR], 0.17; 95% CI, 0.12 - 0.23; P < .0001).

Disease-free survival (DFS) in the overall trial population of patients with stage IB-IIIA disease showed osimertinib reduced the risk of disease recurrence or death by 80% (HR, 0.20; 95% CI, 0.15 - 0.27; P < .0001).

At 2 years, 89% of patients treated with the targeted agent remained alive and disease free vs 52% on placebo after surgery. The safety and tolerability of osimertinib in the adjuvant setting was consistent with previous trials in the metastatic setting.

The trial of 682 patients was unblinded early and halted on the recommendation of the independent data-monitoring committee, because of the efficacy of osimertinib.

“If I were on the committee, I would have done the same thing. These are extraordinary results,” study investigator Roy S. Herbst, MD, PhD, chief of medical oncology at the Yale Cancer Center, New Haven, Connecticut, said at a press briefing prior to the study presentation at the American Society of Clinical Oncology’s (ASCO) virtual scientific program last spring.

In a Medscape commentary, Mark Kris, MD, of Memorial Sloan Kettering Cancer Center in New York City, said the data with osimertinib in the adjuvant setting are “important and practice-changing.”

“The potential for this drug to improve outcomes has been there for a long time. This phase 3 randomized trial presented at the plenary session of ASCO showed a more than doubling of disease-free survival at 2 years. It shows that we can use therapies in the earlier stages of disease,” Kris noted.

“This approval dispels the notion that treatment is over after surgery and chemotherapy, as the ADAURA results show that Tagrisso can dramatically change the course of this disease,” Dave Fredrickson, executive vice president, AstraZeneca oncology business unit, said in a news release.

Osimertinib had orphan drug status and breakthrough therapy designation for treatment of EGFR mutation-positive NSCLC.

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

Tending to patients who opt for outpatient autologous stem cell transplants is well tolerated by caregivers, so long as they have the resources and support necessary, according to a recent Italian report.

Investigators surveyed the primary caregivers – most often the spouse – of 25 multiple myeloma patients who, in consultation with their caregiver, opted for an outpatient procedure and 71 others who chose standard inpatient treatment, and compared the results. Outpatients were discharged a day after transplant with twice-weekly clinic visits until sustained hematologic recovery as reported in Clinical Lymphoma, Myeloma and Leukemia.

The teams used portions of the Caregiver Reaction Assessment survey that focused on self-reported sense of family support plus affect on daily activities and general health. Surveys were taken a week before transplant and 3 months afterwards.

Results did not differ significantly between outpatient and inpatient caregivers at either point, and there was no meaningful change in responses over time.

“The outpatient model neither improves nor impairs global caregivers’ burden, compared with” inpatient transplant. Outpatient caregivers “do not show that they suffer from a greater burden of responsibility as compared to those belonging to the inpatient’s arm,” said investigators led by Massimo Martino, MD, director of stem cell transplants at the Great Metropolitan Hospital in Reggio Calabria, Italy, where the patients were treated.

The relatively short-lasting neutropenia and the limited nonhematologic toxicity of high-dose melphalan make multiple myeloma good candidates for outpatient programs. Indeed, the incidence rate of mucositis, fever, chemotherapy-induced nausea and vomiting, and other adverse events did not differ between in and outpatients, which is in keeping with previous reports supporting the feasibility and safety of outpatient programs.

However, the burden on loved ones is considerable. At least during the aplastic phase, outpatient caregivers are on call around the clock and spend most of their time with the patient. Homes have to be kept meticulously clean, vital signs checked, medications administered, and ins and outs monitored, among other duties normally handled by inpatient staff.

The main limit of the study was that outpatients were a self-selected group. They and their caregivers may simply have had the resources and support needed for successful outpatient transplants, while other patients did not. As the investigators put it, “we cannot exclude the problem of residual confounding due to unmeasured variables” such as “factors underlying patients’ preference, which could potentially impact the study results.”

Administering the follow-up survey 3 months after transplant might also have missed the acute impact on outpatient caregivers. It’s been “reported that the quality of life of patients undergoing an” outpatient procedure decreases immediately post treatment but bounces back by 6 months. “The same result can probably be observed in caregivers,” the team said.

The outpatient and inpatient groups were comparable, with a majority of men and a mean age of about 60 years in both. The number of infused stem cells, engraftment kinetics, and hematopoietic cell transplantation–comorbidity index scores did not differ significantly between the two groups.

There was no funding for the work, and the investigators reported that they didn’t have any conflicts of interest.

[email protected]

SOURCE: Martino M et al. Clin Lymphoma Myeloma Leuk. 2020 Nov 19. doi: 10.1016/j.clml.2020.11.011.

Tending to patients who opt for outpatient autologous stem cell transplants is well tolerated by caregivers, so long as they have the resources and support necessary, according to a recent Italian report.

Investigators surveyed the primary caregivers – most often the spouse – of 25 multiple myeloma patients who, in consultation with their caregiver, opted for an outpatient procedure and 71 others who chose standard inpatient treatment, and compared the results. Outpatients were discharged a day after transplant with twice-weekly clinic visits until sustained hematologic recovery as reported in Clinical Lymphoma, Myeloma and Leukemia.

The teams used portions of the Caregiver Reaction Assessment survey that focused on self-reported sense of family support plus affect on daily activities and general health. Surveys were taken a week before transplant and 3 months afterwards.

Results did not differ significantly between outpatient and inpatient caregivers at either point, and there was no meaningful change in responses over time.

“The outpatient model neither improves nor impairs global caregivers’ burden, compared with” inpatient transplant. Outpatient caregivers “do not show that they suffer from a greater burden of responsibility as compared to those belonging to the inpatient’s arm,” said investigators led by Massimo Martino, MD, director of stem cell transplants at the Great Metropolitan Hospital in Reggio Calabria, Italy, where the patients were treated.

The relatively short-lasting neutropenia and the limited nonhematologic toxicity of high-dose melphalan make multiple myeloma good candidates for outpatient programs. Indeed, the incidence rate of mucositis, fever, chemotherapy-induced nausea and vomiting, and other adverse events did not differ between in and outpatients, which is in keeping with previous reports supporting the feasibility and safety of outpatient programs.

However, the burden on loved ones is considerable. At least during the aplastic phase, outpatient caregivers are on call around the clock and spend most of their time with the patient. Homes have to be kept meticulously clean, vital signs checked, medications administered, and ins and outs monitored, among other duties normally handled by inpatient staff.

The main limit of the study was that outpatients were a self-selected group. They and their caregivers may simply have had the resources and support needed for successful outpatient transplants, while other patients did not. As the investigators put it, “we cannot exclude the problem of residual confounding due to unmeasured variables” such as “factors underlying patients’ preference, which could potentially impact the study results.”

Administering the follow-up survey 3 months after transplant might also have missed the acute impact on outpatient caregivers. It’s been “reported that the quality of life of patients undergoing an” outpatient procedure decreases immediately post treatment but bounces back by 6 months. “The same result can probably be observed in caregivers,” the team said.

The outpatient and inpatient groups were comparable, with a majority of men and a mean age of about 60 years in both. The number of infused stem cells, engraftment kinetics, and hematopoietic cell transplantation–comorbidity index scores did not differ significantly between the two groups.

There was no funding for the work, and the investigators reported that they didn’t have any conflicts of interest.

[email protected]

SOURCE: Martino M et al. Clin Lymphoma Myeloma Leuk. 2020 Nov 19. doi: 10.1016/j.clml.2020.11.011.

Tending to patients who opt for outpatient autologous stem cell transplants is well tolerated by caregivers, so long as they have the resources and support necessary, according to a recent Italian report.

Investigators surveyed the primary caregivers – most often the spouse – of 25 multiple myeloma patients who, in consultation with their caregiver, opted for an outpatient procedure and 71 others who chose standard inpatient treatment, and compared the results. Outpatients were discharged a day after transplant with twice-weekly clinic visits until sustained hematologic recovery as reported in Clinical Lymphoma, Myeloma and Leukemia.

The teams used portions of the Caregiver Reaction Assessment survey that focused on self-reported sense of family support plus affect on daily activities and general health. Surveys were taken a week before transplant and 3 months afterwards.

Results did not differ significantly between outpatient and inpatient caregivers at either point, and there was no meaningful change in responses over time.

“The outpatient model neither improves nor impairs global caregivers’ burden, compared with” inpatient transplant. Outpatient caregivers “do not show that they suffer from a greater burden of responsibility as compared to those belonging to the inpatient’s arm,” said investigators led by Massimo Martino, MD, director of stem cell transplants at the Great Metropolitan Hospital in Reggio Calabria, Italy, where the patients were treated.

The relatively short-lasting neutropenia and the limited nonhematologic toxicity of high-dose melphalan make multiple myeloma good candidates for outpatient programs. Indeed, the incidence rate of mucositis, fever, chemotherapy-induced nausea and vomiting, and other adverse events did not differ between in and outpatients, which is in keeping with previous reports supporting the feasibility and safety of outpatient programs.

However, the burden on loved ones is considerable. At least during the aplastic phase, outpatient caregivers are on call around the clock and spend most of their time with the patient. Homes have to be kept meticulously clean, vital signs checked, medications administered, and ins and outs monitored, among other duties normally handled by inpatient staff.

The main limit of the study was that outpatients were a self-selected group. They and their caregivers may simply have had the resources and support needed for successful outpatient transplants, while other patients did not. As the investigators put it, “we cannot exclude the problem of residual confounding due to unmeasured variables” such as “factors underlying patients’ preference, which could potentially impact the study results.”

Administering the follow-up survey 3 months after transplant might also have missed the acute impact on outpatient caregivers. It’s been “reported that the quality of life of patients undergoing an” outpatient procedure decreases immediately post treatment but bounces back by 6 months. “The same result can probably be observed in caregivers,” the team said.

The outpatient and inpatient groups were comparable, with a majority of men and a mean age of about 60 years in both. The number of infused stem cells, engraftment kinetics, and hematopoietic cell transplantation–comorbidity index scores did not differ significantly between the two groups.

There was no funding for the work, and the investigators reported that they didn’t have any conflicts of interest.

[email protected]

SOURCE: Martino M et al. Clin Lymphoma Myeloma Leuk. 2020 Nov 19. doi: 10.1016/j.clml.2020.11.011.

The issue of race and survival in patients with clear cell renal cell carcinoma (ccRCC) has been debated in the literature.

Some studies have shown worse survival for Black patients, while others have suggested that Black race is instead a stand-in for social determinants, including access to care.

New research suggests that Black race is not correlated with increased mortality from ccRCC. These results were published in Urology.

“Despite well documented racial biases and race-specific outcomes in the health care landscape, our study found race was not associated with 5-year cause-specific survival from ccRCC,” wrote investigator Dhaval Jivanji, a medical student at Florida International University, Miami, and colleagues.

In their retrospective study, the investigators examined 5-year survival in ccRCC patients, comparing results across races. The team used data from the Surveillance Epidemiology, and End Results (SEER) database, which collects cancer data from 13 states using population-based cancer registries. They extracted data on demographics, prevalence, and mortality, in relation to ccRCC.

A total of 8,421 subjects with ccRCC were included in the analysis, which covered the years 2007-2015. The primary outcome was 5-year survival, defined as cause-specific mortality up to the first 60 months from time of cancer diagnosis.

In addition to race, variables included in the statistical model were age (18-50, 51-60, 61-70,71-80, >80), sex (male/female), SEER Summary tumor staging (localized, regionalized, distant), insurance status (uninsured, insured, insured not specific, Medicaid), and marital status (single, married/partner, separated/divorced/widowed).
 

Demographic determinism

In the adjusted analysis, the researchers found no association between race and 5-year cause-specific survival in patients with ccRCC.

The hazard ratios for death were 0.96 for Black patients, 1.01 for American Indian/Alaska Native patients, and 0.99 for Asian/Pacific Islander patients, with White patients as the comparator.

In terms of the other covariates studied, the researchers found that older age (>50 years) and the presence of regional or distant tumors were associated with an increased hazard of death, while female sex and having insurance were associated with a decreased hazard of death.

“Our study found that age, tumor stage, and insurance status are significantly associated with 5-year cause-specific survival. Future studies will benefit from complete assessment of other demographic factors, including income, medical comorbidities, and access to care. These are negative predictors, and [their] potential impact on overall survival should be considered by the clinician in treatment and management plans for RCC patients,” the researchers concluded.

In an editorial commentary published within the main article, Paul Russo, MD, of Weill Cornell Medicine, New York, stated: “Investigations such as this utilizing the SEER registries provide a 30,000-foot demographic view of some disease elements but lack important granularity, such as tumor size and grade, family income, critical medical comorbidities, and patient access to hospitals with surgical and medical oncologic expertise.”

Dr. Russo said it is well known that disparate access to diagnosis, surgical intervention, and expert treatment have an impact on survival.

He went on to ask: “Could African Americans have had superior outcomes if the data was controlled for these important variables? As urologic surgeons, we must join the greater medical community in understanding the root causes leading to structural racial and economic disparities, inequities in access to care, and the profound negative impact these disparities have on health outcomes in general and cancer outcomes specifically.”

The authors did not disclose funding or conflicts of interest.

[email protected]

SOURCE: Jivanji D et al. Urology. 2020. doi: 10.1016/j.urology.2020.10.055.

The issue of race and survival in patients with clear cell renal cell carcinoma (ccRCC) has been debated in the literature.

Some studies have shown worse survival for Black patients, while others have suggested that Black race is instead a stand-in for social determinants, including access to care.

New research suggests that Black race is not correlated with increased mortality from ccRCC. These results were published in Urology.

“Despite well documented racial biases and race-specific outcomes in the health care landscape, our study found race was not associated with 5-year cause-specific survival from ccRCC,” wrote investigator Dhaval Jivanji, a medical student at Florida International University, Miami, and colleagues.

In their retrospective study, the investigators examined 5-year survival in ccRCC patients, comparing results across races. The team used data from the Surveillance Epidemiology, and End Results (SEER) database, which collects cancer data from 13 states using population-based cancer registries. They extracted data on demographics, prevalence, and mortality, in relation to ccRCC.

A total of 8,421 subjects with ccRCC were included in the analysis, which covered the years 2007-2015. The primary outcome was 5-year survival, defined as cause-specific mortality up to the first 60 months from time of cancer diagnosis.

In addition to race, variables included in the statistical model were age (18-50, 51-60, 61-70,71-80, >80), sex (male/female), SEER Summary tumor staging (localized, regionalized, distant), insurance status (uninsured, insured, insured not specific, Medicaid), and marital status (single, married/partner, separated/divorced/widowed).
 

Demographic determinism

In the adjusted analysis, the researchers found no association between race and 5-year cause-specific survival in patients with ccRCC.

The hazard ratios for death were 0.96 for Black patients, 1.01 for American Indian/Alaska Native patients, and 0.99 for Asian/Pacific Islander patients, with White patients as the comparator.

In terms of the other covariates studied, the researchers found that older age (>50 years) and the presence of regional or distant tumors were associated with an increased hazard of death, while female sex and having insurance were associated with a decreased hazard of death.

“Our study found that age, tumor stage, and insurance status are significantly associated with 5-year cause-specific survival. Future studies will benefit from complete assessment of other demographic factors, including income, medical comorbidities, and access to care. These are negative predictors, and [their] potential impact on overall survival should be considered by the clinician in treatment and management plans for RCC patients,” the researchers concluded.

In an editorial commentary published within the main article, Paul Russo, MD, of Weill Cornell Medicine, New York, stated: “Investigations such as this utilizing the SEER registries provide a 30,000-foot demographic view of some disease elements but lack important granularity, such as tumor size and grade, family income, critical medical comorbidities, and patient access to hospitals with surgical and medical oncologic expertise.”

Dr. Russo said it is well known that disparate access to diagnosis, surgical intervention, and expert treatment have an impact on survival.

He went on to ask: “Could African Americans have had superior outcomes if the data was controlled for these important variables? As urologic surgeons, we must join the greater medical community in understanding the root causes leading to structural racial and economic disparities, inequities in access to care, and the profound negative impact these disparities have on health outcomes in general and cancer outcomes specifically.”

The authors did not disclose funding or conflicts of interest.

[email protected]

SOURCE: Jivanji D et al. Urology. 2020. doi: 10.1016/j.urology.2020.10.055.

The issue of race and survival in patients with clear cell renal cell carcinoma (ccRCC) has been debated in the literature.

Some studies have shown worse survival for Black patients, while others have suggested that Black race is instead a stand-in for social determinants, including access to care.

New research suggests that Black race is not correlated with increased mortality from ccRCC. These results were published in Urology.

“Despite well documented racial biases and race-specific outcomes in the health care landscape, our study found race was not associated with 5-year cause-specific survival from ccRCC,” wrote investigator Dhaval Jivanji, a medical student at Florida International University, Miami, and colleagues.

In their retrospective study, the investigators examined 5-year survival in ccRCC patients, comparing results across races. The team used data from the Surveillance Epidemiology, and End Results (SEER) database, which collects cancer data from 13 states using population-based cancer registries. They extracted data on demographics, prevalence, and mortality, in relation to ccRCC.

A total of 8,421 subjects with ccRCC were included in the analysis, which covered the years 2007-2015. The primary outcome was 5-year survival, defined as cause-specific mortality up to the first 60 months from time of cancer diagnosis.

In addition to race, variables included in the statistical model were age (18-50, 51-60, 61-70,71-80, >80), sex (male/female), SEER Summary tumor staging (localized, regionalized, distant), insurance status (uninsured, insured, insured not specific, Medicaid), and marital status (single, married/partner, separated/divorced/widowed).
 

Demographic determinism

In the adjusted analysis, the researchers found no association between race and 5-year cause-specific survival in patients with ccRCC.

The hazard ratios for death were 0.96 for Black patients, 1.01 for American Indian/Alaska Native patients, and 0.99 for Asian/Pacific Islander patients, with White patients as the comparator.

In terms of the other covariates studied, the researchers found that older age (>50 years) and the presence of regional or distant tumors were associated with an increased hazard of death, while female sex and having insurance were associated with a decreased hazard of death.

“Our study found that age, tumor stage, and insurance status are significantly associated with 5-year cause-specific survival. Future studies will benefit from complete assessment of other demographic factors, including income, medical comorbidities, and access to care. These are negative predictors, and [their] potential impact on overall survival should be considered by the clinician in treatment and management plans for RCC patients,” the researchers concluded.

In an editorial commentary published within the main article, Paul Russo, MD, of Weill Cornell Medicine, New York, stated: “Investigations such as this utilizing the SEER registries provide a 30,000-foot demographic view of some disease elements but lack important granularity, such as tumor size and grade, family income, critical medical comorbidities, and patient access to hospitals with surgical and medical oncologic expertise.”

Dr. Russo said it is well known that disparate access to diagnosis, surgical intervention, and expert treatment have an impact on survival.

He went on to ask: “Could African Americans have had superior outcomes if the data was controlled for these important variables? As urologic surgeons, we must join the greater medical community in understanding the root causes leading to structural racial and economic disparities, inequities in access to care, and the profound negative impact these disparities have on health outcomes in general and cancer outcomes specifically.”

The authors did not disclose funding or conflicts of interest.

[email protected]

SOURCE: Jivanji D et al. Urology. 2020. doi: 10.1016/j.urology.2020.10.055.