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Clinical factors and treatment tied to COVID-19 mortality in cancer patients
according to two presentations at the European Society for Medical Oncology Virtual Congress 2020.
Two analyses of data from the COVID-19 and Cancer Consortium (CCC19) were presented at the meeting.
The data suggest that older age, male sex, more comorbidities, poor performance status, progressive cancer or multiple cancers, hematologic malignancy, and recent cancer therapy are all associated with higher mortality among patients with cancer and COVID-19. Anti-CD20 therapy is associated with an especially high mortality rate, according to an investigator.
Among hospitalized patients, increased absolute neutrophil count as well as abnormal D-dimer, high-sensitivity troponin, and C-reactive protein are associated with a higher risk of mortality.
Prior analyses of CCC19 data pointed to several factors associated with higher COVID-19 death rates, according to Petros Grivas, MD, PhD, of University of Washington, Seattle, who presented some CCC19 data at the meeting. However, the prior analyses were limited by weak statistical power and low event rates, Dr. Grivas said.
Clinical and laboratory factors: Abstract LBA72
The aim of Dr. Grivas’s analysis was to validate a priori identified demographic and clinicopathologic factors associated with 30-day all-cause mortality in patients with COVID-19 and cancer. Dr. Grivas and colleagues also explored the potential association between laboratory parameters and 30-day all-cause mortality.
The analysis included 3,899 patients with cancer and COVID-19 from 124 centers. Most centers are in the United States, but 4% are in Canada, and 2% are in Spain. About two-thirds of patients were 60 years of age or younger at baseline, half were men, 79% had solid tumors, and 21% had hematologic malignancies.
Cancer-specific factors associated with an increased risk of 30-day all-cause mortality were having progressive cancer (adjusted odds ratio, 2.9), receiving cancer therapy within 3 months (aOR, 1.2), having a hematologic versus solid tumor (aOR, 1.7), and having multiple malignancies (aOR, 1.5).
Clinical factors associated with an increased risk of 30-day all-cause mortality were Black versus White race (aOR, 1.5), older age (aOR, 1.7 per 10 years), three or more actively treated comorbidities (versus none; aOR, 2.1), and Eastern Cooperative Oncology Group performance status of 2 or more (versus 0; aOR, 4.6).
In hospitalized patients, several laboratory variables were associated with an increased risk of 30-day all-cause mortality. Having an absolute neutrophil count above the upper limit of normal doubled the risk (aOR, 2.0), while abnormal D-dimer, high-sensitivity troponin, and C-reactive protein all more than doubled the risk of mortality (aORs of 2.5, 2.5, and 2.4, respectively).
Further risk modeling with multivariable analysis will be performed after longer follow-up, Dr. Grivas noted.
Treatment-related outcomes: Abstract LBA71
An additional analysis of CCC19 data encompassed 3,654 patients. In this analysis, researchers investigated the correlation between timing of cancer treatment and COVID-19–related complications and 30-day mortality.
Mortality was highest among cancer patients treated 1-3 months prior to COVID-19 diagnosis, with all-cause mortality at 28%, said Trisha M. Wise-Draper, MD, PhD, of University of Cincinnati, when presenting the data at the meeting.
Rates for other complications (hospitalization, oxygen required, ICU admission, and mechanical ventilation) were similar regardless of treatment timing.
The unadjusted 30-day mortality rate was highest for patients treated most recently with chemoimmunotherapy (30%), followed by chemotherapy (18%), chemoradiotherapy (18%), and targeted therapy (17%).
The mortality rate was “particularly high,” at 50%, in patients receiving anti-CD20 therapy 1-3 months prior to COVID-19 diagnosis – the time period for which significant B-cell depletion develops, Dr. Wise-Draper observed.
An analysis of disease status among 1,449 patients treated within 3 months of COVID-19 diagnosis showed mortality risk increasing from 6% among patients in remission or with newly emergent disease, to 22% in patients with any active cancer, to 34% in those with progressing disease, Dr. Wise-Draper said.
Discussant Benjamin Solomon, MD, PhD, of Peter MacCallum Cancer Centre in Melbourne, made note of the high 30-day mortality rate seen in patients receiving anti-CD20 therapy as well as the elevated standardized mortality ratios with recent chemoimmunotherapy and targeted therapy.
“Although there are some limitations of this analysis, it provides the best data we have to date about the effects of treatment on early mortality in patients with COVID-19 and cancer. It points to a modest but heterogeneous effect of treatment on outcome, one which is likely to become clearer with larger cohorts and additional analysis,” Dr. Solomon said.
This research was funded by the American Cancer Society, Hope Foundation for Cancer Research, Jim and Carol O’Hare Fund, National Cancer Institute, National Human Genome Research Institute, Vanderbilt Institute for Clinical and Translational Research, and Fonds de Recherche du Quebec-Sante. Dr. Grivas disclosed relationships with many companies, but none are related to this work. Dr. Wise-Draper disclosed relationships with Merck, Bristol-Myers Squibb, Tesaro, GlaxoSmithKline, AstraZeneca, Shattuck Labs, and Rakuten. Dr. Solomon disclosed relationships with Amgen, AstraZeneca, Merck, Bristol-Myers Squibb, Novartis, Pfizer, and Roche-Genentech.
SOURCES: Grivas P et al. ESMO 2020, Abstract LBA72; Wise-Draper TM et al. ESMO 2020, Abstract LBA71.
according to two presentations at the European Society for Medical Oncology Virtual Congress 2020.
Two analyses of data from the COVID-19 and Cancer Consortium (CCC19) were presented at the meeting.
The data suggest that older age, male sex, more comorbidities, poor performance status, progressive cancer or multiple cancers, hematologic malignancy, and recent cancer therapy are all associated with higher mortality among patients with cancer and COVID-19. Anti-CD20 therapy is associated with an especially high mortality rate, according to an investigator.
Among hospitalized patients, increased absolute neutrophil count as well as abnormal D-dimer, high-sensitivity troponin, and C-reactive protein are associated with a higher risk of mortality.
Prior analyses of CCC19 data pointed to several factors associated with higher COVID-19 death rates, according to Petros Grivas, MD, PhD, of University of Washington, Seattle, who presented some CCC19 data at the meeting. However, the prior analyses were limited by weak statistical power and low event rates, Dr. Grivas said.
Clinical and laboratory factors: Abstract LBA72
The aim of Dr. Grivas’s analysis was to validate a priori identified demographic and clinicopathologic factors associated with 30-day all-cause mortality in patients with COVID-19 and cancer. Dr. Grivas and colleagues also explored the potential association between laboratory parameters and 30-day all-cause mortality.
The analysis included 3,899 patients with cancer and COVID-19 from 124 centers. Most centers are in the United States, but 4% are in Canada, and 2% are in Spain. About two-thirds of patients were 60 years of age or younger at baseline, half were men, 79% had solid tumors, and 21% had hematologic malignancies.
Cancer-specific factors associated with an increased risk of 30-day all-cause mortality were having progressive cancer (adjusted odds ratio, 2.9), receiving cancer therapy within 3 months (aOR, 1.2), having a hematologic versus solid tumor (aOR, 1.7), and having multiple malignancies (aOR, 1.5).
Clinical factors associated with an increased risk of 30-day all-cause mortality were Black versus White race (aOR, 1.5), older age (aOR, 1.7 per 10 years), three or more actively treated comorbidities (versus none; aOR, 2.1), and Eastern Cooperative Oncology Group performance status of 2 or more (versus 0; aOR, 4.6).
In hospitalized patients, several laboratory variables were associated with an increased risk of 30-day all-cause mortality. Having an absolute neutrophil count above the upper limit of normal doubled the risk (aOR, 2.0), while abnormal D-dimer, high-sensitivity troponin, and C-reactive protein all more than doubled the risk of mortality (aORs of 2.5, 2.5, and 2.4, respectively).
Further risk modeling with multivariable analysis will be performed after longer follow-up, Dr. Grivas noted.
Treatment-related outcomes: Abstract LBA71
An additional analysis of CCC19 data encompassed 3,654 patients. In this analysis, researchers investigated the correlation between timing of cancer treatment and COVID-19–related complications and 30-day mortality.
Mortality was highest among cancer patients treated 1-3 months prior to COVID-19 diagnosis, with all-cause mortality at 28%, said Trisha M. Wise-Draper, MD, PhD, of University of Cincinnati, when presenting the data at the meeting.
Rates for other complications (hospitalization, oxygen required, ICU admission, and mechanical ventilation) were similar regardless of treatment timing.
The unadjusted 30-day mortality rate was highest for patients treated most recently with chemoimmunotherapy (30%), followed by chemotherapy (18%), chemoradiotherapy (18%), and targeted therapy (17%).
The mortality rate was “particularly high,” at 50%, in patients receiving anti-CD20 therapy 1-3 months prior to COVID-19 diagnosis – the time period for which significant B-cell depletion develops, Dr. Wise-Draper observed.
An analysis of disease status among 1,449 patients treated within 3 months of COVID-19 diagnosis showed mortality risk increasing from 6% among patients in remission or with newly emergent disease, to 22% in patients with any active cancer, to 34% in those with progressing disease, Dr. Wise-Draper said.
Discussant Benjamin Solomon, MD, PhD, of Peter MacCallum Cancer Centre in Melbourne, made note of the high 30-day mortality rate seen in patients receiving anti-CD20 therapy as well as the elevated standardized mortality ratios with recent chemoimmunotherapy and targeted therapy.
“Although there are some limitations of this analysis, it provides the best data we have to date about the effects of treatment on early mortality in patients with COVID-19 and cancer. It points to a modest but heterogeneous effect of treatment on outcome, one which is likely to become clearer with larger cohorts and additional analysis,” Dr. Solomon said.
This research was funded by the American Cancer Society, Hope Foundation for Cancer Research, Jim and Carol O’Hare Fund, National Cancer Institute, National Human Genome Research Institute, Vanderbilt Institute for Clinical and Translational Research, and Fonds de Recherche du Quebec-Sante. Dr. Grivas disclosed relationships with many companies, but none are related to this work. Dr. Wise-Draper disclosed relationships with Merck, Bristol-Myers Squibb, Tesaro, GlaxoSmithKline, AstraZeneca, Shattuck Labs, and Rakuten. Dr. Solomon disclosed relationships with Amgen, AstraZeneca, Merck, Bristol-Myers Squibb, Novartis, Pfizer, and Roche-Genentech.
SOURCES: Grivas P et al. ESMO 2020, Abstract LBA72; Wise-Draper TM et al. ESMO 2020, Abstract LBA71.
according to two presentations at the European Society for Medical Oncology Virtual Congress 2020.
Two analyses of data from the COVID-19 and Cancer Consortium (CCC19) were presented at the meeting.
The data suggest that older age, male sex, more comorbidities, poor performance status, progressive cancer or multiple cancers, hematologic malignancy, and recent cancer therapy are all associated with higher mortality among patients with cancer and COVID-19. Anti-CD20 therapy is associated with an especially high mortality rate, according to an investigator.
Among hospitalized patients, increased absolute neutrophil count as well as abnormal D-dimer, high-sensitivity troponin, and C-reactive protein are associated with a higher risk of mortality.
Prior analyses of CCC19 data pointed to several factors associated with higher COVID-19 death rates, according to Petros Grivas, MD, PhD, of University of Washington, Seattle, who presented some CCC19 data at the meeting. However, the prior analyses were limited by weak statistical power and low event rates, Dr. Grivas said.
Clinical and laboratory factors: Abstract LBA72
The aim of Dr. Grivas’s analysis was to validate a priori identified demographic and clinicopathologic factors associated with 30-day all-cause mortality in patients with COVID-19 and cancer. Dr. Grivas and colleagues also explored the potential association between laboratory parameters and 30-day all-cause mortality.
The analysis included 3,899 patients with cancer and COVID-19 from 124 centers. Most centers are in the United States, but 4% are in Canada, and 2% are in Spain. About two-thirds of patients were 60 years of age or younger at baseline, half were men, 79% had solid tumors, and 21% had hematologic malignancies.
Cancer-specific factors associated with an increased risk of 30-day all-cause mortality were having progressive cancer (adjusted odds ratio, 2.9), receiving cancer therapy within 3 months (aOR, 1.2), having a hematologic versus solid tumor (aOR, 1.7), and having multiple malignancies (aOR, 1.5).
Clinical factors associated with an increased risk of 30-day all-cause mortality were Black versus White race (aOR, 1.5), older age (aOR, 1.7 per 10 years), three or more actively treated comorbidities (versus none; aOR, 2.1), and Eastern Cooperative Oncology Group performance status of 2 or more (versus 0; aOR, 4.6).
In hospitalized patients, several laboratory variables were associated with an increased risk of 30-day all-cause mortality. Having an absolute neutrophil count above the upper limit of normal doubled the risk (aOR, 2.0), while abnormal D-dimer, high-sensitivity troponin, and C-reactive protein all more than doubled the risk of mortality (aORs of 2.5, 2.5, and 2.4, respectively).
Further risk modeling with multivariable analysis will be performed after longer follow-up, Dr. Grivas noted.
Treatment-related outcomes: Abstract LBA71
An additional analysis of CCC19 data encompassed 3,654 patients. In this analysis, researchers investigated the correlation between timing of cancer treatment and COVID-19–related complications and 30-day mortality.
Mortality was highest among cancer patients treated 1-3 months prior to COVID-19 diagnosis, with all-cause mortality at 28%, said Trisha M. Wise-Draper, MD, PhD, of University of Cincinnati, when presenting the data at the meeting.
Rates for other complications (hospitalization, oxygen required, ICU admission, and mechanical ventilation) were similar regardless of treatment timing.
The unadjusted 30-day mortality rate was highest for patients treated most recently with chemoimmunotherapy (30%), followed by chemotherapy (18%), chemoradiotherapy (18%), and targeted therapy (17%).
The mortality rate was “particularly high,” at 50%, in patients receiving anti-CD20 therapy 1-3 months prior to COVID-19 diagnosis – the time period for which significant B-cell depletion develops, Dr. Wise-Draper observed.
An analysis of disease status among 1,449 patients treated within 3 months of COVID-19 diagnosis showed mortality risk increasing from 6% among patients in remission or with newly emergent disease, to 22% in patients with any active cancer, to 34% in those with progressing disease, Dr. Wise-Draper said.
Discussant Benjamin Solomon, MD, PhD, of Peter MacCallum Cancer Centre in Melbourne, made note of the high 30-day mortality rate seen in patients receiving anti-CD20 therapy as well as the elevated standardized mortality ratios with recent chemoimmunotherapy and targeted therapy.
“Although there are some limitations of this analysis, it provides the best data we have to date about the effects of treatment on early mortality in patients with COVID-19 and cancer. It points to a modest but heterogeneous effect of treatment on outcome, one which is likely to become clearer with larger cohorts and additional analysis,” Dr. Solomon said.
This research was funded by the American Cancer Society, Hope Foundation for Cancer Research, Jim and Carol O’Hare Fund, National Cancer Institute, National Human Genome Research Institute, Vanderbilt Institute for Clinical and Translational Research, and Fonds de Recherche du Quebec-Sante. Dr. Grivas disclosed relationships with many companies, but none are related to this work. Dr. Wise-Draper disclosed relationships with Merck, Bristol-Myers Squibb, Tesaro, GlaxoSmithKline, AstraZeneca, Shattuck Labs, and Rakuten. Dr. Solomon disclosed relationships with Amgen, AstraZeneca, Merck, Bristol-Myers Squibb, Novartis, Pfizer, and Roche-Genentech.
SOURCES: Grivas P et al. ESMO 2020, Abstract LBA72; Wise-Draper TM et al. ESMO 2020, Abstract LBA71.
FROM ESMO 2020
The scope of under- and overtreatment in older adults with cancer
Because of physiological changes with aging and differences in cancer biology, caring for older adults (OAs) with cancer requires careful assessment and planning.
Clark Dumontier, MD, of Brigham and Women’s Hospital in Boston, and colleagues sought to define the meaning of the terms “undertreatment” and “overtreatment” for OAs with cancer in a scoping literature review published in the Journal of Clinical Oncology.
Though OAs are typically defined as adults aged 65 years and older, in this review, the authors defined OAs as patients aged 60 years and older.
The authors theorized that a scoping review of papers about this patient population could provide clues about limitations in the oncology literature and guidance about patient management and future research. Despite comprising the majority of cancer patients, OAs are underrepresented in clinical trials.
About scoping reviews
Scoping reviews are used to identify existing evidence in a field, clarify concepts or definitions in the literature, survey how research on a topic is conducted, and identify knowledge gaps. In addition, scoping reviews summarize available evidence without answering a discrete research question.
Industry standards for scoping reviews have been established by the Johanna Briggs Institute and Preferred Reporting Items for Systematic Reviews and Meta-analyses extension for scoping reviews. According to these standards, scoping reviews should:
- Establish eligibility criteria with a rationale for each criterion clearly explained
- Search multiple databases in multiple languages
- Include “gray literature,” defined as studies that are unpublished or difficult to locate
- Have several independent reviewers screen titles and abstracts
- Ask multiple independent reviewers to review full text articles
- Present results with charts or diagrams that align with the review’s objective
- Graphically depict the decision process for including/excluding sources
- Identify implications for further research.
In their review, Dr. DuMontier and colleagues fulfilled many of the aforementioned criteria. The team searched three English-language databases for titles and abstracts that included the terms undertreatment and/or overtreatment, and were related to OAs with cancer, inclusive of all types of articles, cancer types, and treatments.
Definitions of undertreatment and overtreatment were extracted, and categories underlying these definitions were derived. Within a random subset of articles, two coauthors independently determined final categories of definitions and independently assigned those categories.
Findings and implications
To define OA, Dr. DuMontier and colleagues used a cutoff of 60 years or older. Articles mentioning undertreatment (n = 236), overtreatment (n = 71), or both (n = 51) met criteria for inclusion (n = 256), but only 14 articles (5.5%) explicitly provided formal definitions.
For most of the reviewed articles, the authors judged definitions from the surrounding context. In a random subset of 50 articles, there was a high level of agreement (87.1%; κ = 0.81) between two coauthors in independently assigning categories of definitions.
Undertreatment was applied to therapy that was less than recommended (148 articles; 62.7%) or less than recommended with worse outcomes (88 articles; 37.3%).
Overtreatment most commonly denoted intensive treatment of an OA in whom harms outweighed the benefits of treatment (38 articles; 53.5%) or intensive treatment of a cancer not expected to affect the OA during the patient’s remaining life (33 articles; 46.5%).
Overall, the authors found that undertreatment and overtreatment of OAs with cancer are imprecisely defined concepts. Formal geriatric assessment was recommended in just over half of articles, and only 26.2% recommended formal assessments of age-related vulnerabilities for management. The authors proposed definitions that accounted for both oncologic factors and geriatric domains.
Care of individual patients and clinical research
National Comprehensive Cancer Network (NCCN) guidelines for OAs with cancer recommend initial consideration of overall life expectancy. If a patient is a candidate for cancer treatment on that basis, the next recommended assessment is that of the patient’s capacity to understand the relevant information, appreciate the underlying values and overall medical situation, reason through decisions, and communicate a choice that is consistent with the patient’s articulated goals.
In the pretreatment evaluation of OAs in whom there are no concerns about tolerance to antineoplastic therapy, NCCN guidelines suggest geriatric screening with standardized tools and, if abnormal, comprehensive geriatric screening. The guidelines recommend considering alternative treatment options if nonmodifiable abnormalities are identified.
Referral to a geriatric clinical specialist, use of the Cancer and Aging Research Group’s Chemo Toxicity Calculator, and calculation of Chemotherapy Risk Assessment Scale for High-Age Patients score are specifically suggested if high-risk procedures (such as chemotherapy, radiation, or complex surgery, which most oncologists would consider to be “another day in the office”) are contemplated.
The American Society of Clinical Oncology (ASCO) guidelines for geriatric oncology are similarly detailed and endorse similar evaluations and management.
Employing disease-centric and geriatric domains
Dr. DuMontier and colleagues noted that, for OAs with comorbidity or psychosocial challenges, surrogate survival endpoints are unrelated to quality of life (QOL) outcomes. Nonetheless, QOL is valued by OAs at least as much as survival improvement.
Through no fault of their own, the authors’ conclusion that undertreatment and overtreatment are imperfectly defined concepts has a certain neutrality to it. However, the terms undertreatment and overtreatment are commonly used to signify that inappropriate treatment decisions were made. Therefore, the terms are inherently negative and pejorative.
As with most emotionally charged issues in oncology, it is ideal for professionals in our field to take charge when deficiencies exist. ASCO, NCCN, and the authors of this scoping review have provided a conceptual basis for doing so.
An integrated oncologist-geriatrician approach was shown to be effective in the randomized INTEGERATE trial, showing improved QOL, reduced hospital admissions, and reduced early treatment discontinuation from adverse events (ASCO 2020, Abstract 12011).
Therefore, those clinicians who have not formally, systematically, and routinely supplemented the traditional disease-centric endpoints with patient-centered criteria need to do so.
Similarly, a retrospective study published in JAMA Network Open demonstrated that geriatric and surgical comanagement of OAs with cancer was associated with significantly lower 90-day postoperative mortality and receipt of more supportive care services (physical therapy, occupational therapy, speech and swallow rehabilitation, and nutrition services), in comparison with management from the surgical service only.
These clinical and administrative changes will not only enhance patient management but also facilitate the clinical trials required to clarify optimal treatment intensity. As that occurs, we will be able to apply as much precision to the care of OAs with cancer as we do in other areas of cancer treatment.
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: Dumontier C et al. J Clin Oncol. 2020 Aug 1;38(22):2558-2569.
Because of physiological changes with aging and differences in cancer biology, caring for older adults (OAs) with cancer requires careful assessment and planning.
Clark Dumontier, MD, of Brigham and Women’s Hospital in Boston, and colleagues sought to define the meaning of the terms “undertreatment” and “overtreatment” for OAs with cancer in a scoping literature review published in the Journal of Clinical Oncology.
Though OAs are typically defined as adults aged 65 years and older, in this review, the authors defined OAs as patients aged 60 years and older.
The authors theorized that a scoping review of papers about this patient population could provide clues about limitations in the oncology literature and guidance about patient management and future research. Despite comprising the majority of cancer patients, OAs are underrepresented in clinical trials.
About scoping reviews
Scoping reviews are used to identify existing evidence in a field, clarify concepts or definitions in the literature, survey how research on a topic is conducted, and identify knowledge gaps. In addition, scoping reviews summarize available evidence without answering a discrete research question.
Industry standards for scoping reviews have been established by the Johanna Briggs Institute and Preferred Reporting Items for Systematic Reviews and Meta-analyses extension for scoping reviews. According to these standards, scoping reviews should:
- Establish eligibility criteria with a rationale for each criterion clearly explained
- Search multiple databases in multiple languages
- Include “gray literature,” defined as studies that are unpublished or difficult to locate
- Have several independent reviewers screen titles and abstracts
- Ask multiple independent reviewers to review full text articles
- Present results with charts or diagrams that align with the review’s objective
- Graphically depict the decision process for including/excluding sources
- Identify implications for further research.
In their review, Dr. DuMontier and colleagues fulfilled many of the aforementioned criteria. The team searched three English-language databases for titles and abstracts that included the terms undertreatment and/or overtreatment, and were related to OAs with cancer, inclusive of all types of articles, cancer types, and treatments.
Definitions of undertreatment and overtreatment were extracted, and categories underlying these definitions were derived. Within a random subset of articles, two coauthors independently determined final categories of definitions and independently assigned those categories.
Findings and implications
To define OA, Dr. DuMontier and colleagues used a cutoff of 60 years or older. Articles mentioning undertreatment (n = 236), overtreatment (n = 71), or both (n = 51) met criteria for inclusion (n = 256), but only 14 articles (5.5%) explicitly provided formal definitions.
For most of the reviewed articles, the authors judged definitions from the surrounding context. In a random subset of 50 articles, there was a high level of agreement (87.1%; κ = 0.81) between two coauthors in independently assigning categories of definitions.
Undertreatment was applied to therapy that was less than recommended (148 articles; 62.7%) or less than recommended with worse outcomes (88 articles; 37.3%).
Overtreatment most commonly denoted intensive treatment of an OA in whom harms outweighed the benefits of treatment (38 articles; 53.5%) or intensive treatment of a cancer not expected to affect the OA during the patient’s remaining life (33 articles; 46.5%).
Overall, the authors found that undertreatment and overtreatment of OAs with cancer are imprecisely defined concepts. Formal geriatric assessment was recommended in just over half of articles, and only 26.2% recommended formal assessments of age-related vulnerabilities for management. The authors proposed definitions that accounted for both oncologic factors and geriatric domains.
Care of individual patients and clinical research
National Comprehensive Cancer Network (NCCN) guidelines for OAs with cancer recommend initial consideration of overall life expectancy. If a patient is a candidate for cancer treatment on that basis, the next recommended assessment is that of the patient’s capacity to understand the relevant information, appreciate the underlying values and overall medical situation, reason through decisions, and communicate a choice that is consistent with the patient’s articulated goals.
In the pretreatment evaluation of OAs in whom there are no concerns about tolerance to antineoplastic therapy, NCCN guidelines suggest geriatric screening with standardized tools and, if abnormal, comprehensive geriatric screening. The guidelines recommend considering alternative treatment options if nonmodifiable abnormalities are identified.
Referral to a geriatric clinical specialist, use of the Cancer and Aging Research Group’s Chemo Toxicity Calculator, and calculation of Chemotherapy Risk Assessment Scale for High-Age Patients score are specifically suggested if high-risk procedures (such as chemotherapy, radiation, or complex surgery, which most oncologists would consider to be “another day in the office”) are contemplated.
The American Society of Clinical Oncology (ASCO) guidelines for geriatric oncology are similarly detailed and endorse similar evaluations and management.
Employing disease-centric and geriatric domains
Dr. DuMontier and colleagues noted that, for OAs with comorbidity or psychosocial challenges, surrogate survival endpoints are unrelated to quality of life (QOL) outcomes. Nonetheless, QOL is valued by OAs at least as much as survival improvement.
Through no fault of their own, the authors’ conclusion that undertreatment and overtreatment are imperfectly defined concepts has a certain neutrality to it. However, the terms undertreatment and overtreatment are commonly used to signify that inappropriate treatment decisions were made. Therefore, the terms are inherently negative and pejorative.
As with most emotionally charged issues in oncology, it is ideal for professionals in our field to take charge when deficiencies exist. ASCO, NCCN, and the authors of this scoping review have provided a conceptual basis for doing so.
An integrated oncologist-geriatrician approach was shown to be effective in the randomized INTEGERATE trial, showing improved QOL, reduced hospital admissions, and reduced early treatment discontinuation from adverse events (ASCO 2020, Abstract 12011).
Therefore, those clinicians who have not formally, systematically, and routinely supplemented the traditional disease-centric endpoints with patient-centered criteria need to do so.
Similarly, a retrospective study published in JAMA Network Open demonstrated that geriatric and surgical comanagement of OAs with cancer was associated with significantly lower 90-day postoperative mortality and receipt of more supportive care services (physical therapy, occupational therapy, speech and swallow rehabilitation, and nutrition services), in comparison with management from the surgical service only.
These clinical and administrative changes will not only enhance patient management but also facilitate the clinical trials required to clarify optimal treatment intensity. As that occurs, we will be able to apply as much precision to the care of OAs with cancer as we do in other areas of cancer treatment.
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: Dumontier C et al. J Clin Oncol. 2020 Aug 1;38(22):2558-2569.
Because of physiological changes with aging and differences in cancer biology, caring for older adults (OAs) with cancer requires careful assessment and planning.
Clark Dumontier, MD, of Brigham and Women’s Hospital in Boston, and colleagues sought to define the meaning of the terms “undertreatment” and “overtreatment” for OAs with cancer in a scoping literature review published in the Journal of Clinical Oncology.
Though OAs are typically defined as adults aged 65 years and older, in this review, the authors defined OAs as patients aged 60 years and older.
The authors theorized that a scoping review of papers about this patient population could provide clues about limitations in the oncology literature and guidance about patient management and future research. Despite comprising the majority of cancer patients, OAs are underrepresented in clinical trials.
About scoping reviews
Scoping reviews are used to identify existing evidence in a field, clarify concepts or definitions in the literature, survey how research on a topic is conducted, and identify knowledge gaps. In addition, scoping reviews summarize available evidence without answering a discrete research question.
Industry standards for scoping reviews have been established by the Johanna Briggs Institute and Preferred Reporting Items for Systematic Reviews and Meta-analyses extension for scoping reviews. According to these standards, scoping reviews should:
- Establish eligibility criteria with a rationale for each criterion clearly explained
- Search multiple databases in multiple languages
- Include “gray literature,” defined as studies that are unpublished or difficult to locate
- Have several independent reviewers screen titles and abstracts
- Ask multiple independent reviewers to review full text articles
- Present results with charts or diagrams that align with the review’s objective
- Graphically depict the decision process for including/excluding sources
- Identify implications for further research.
In their review, Dr. DuMontier and colleagues fulfilled many of the aforementioned criteria. The team searched three English-language databases for titles and abstracts that included the terms undertreatment and/or overtreatment, and were related to OAs with cancer, inclusive of all types of articles, cancer types, and treatments.
Definitions of undertreatment and overtreatment were extracted, and categories underlying these definitions were derived. Within a random subset of articles, two coauthors independently determined final categories of definitions and independently assigned those categories.
Findings and implications
To define OA, Dr. DuMontier and colleagues used a cutoff of 60 years or older. Articles mentioning undertreatment (n = 236), overtreatment (n = 71), or both (n = 51) met criteria for inclusion (n = 256), but only 14 articles (5.5%) explicitly provided formal definitions.
For most of the reviewed articles, the authors judged definitions from the surrounding context. In a random subset of 50 articles, there was a high level of agreement (87.1%; κ = 0.81) between two coauthors in independently assigning categories of definitions.
Undertreatment was applied to therapy that was less than recommended (148 articles; 62.7%) or less than recommended with worse outcomes (88 articles; 37.3%).
Overtreatment most commonly denoted intensive treatment of an OA in whom harms outweighed the benefits of treatment (38 articles; 53.5%) or intensive treatment of a cancer not expected to affect the OA during the patient’s remaining life (33 articles; 46.5%).
Overall, the authors found that undertreatment and overtreatment of OAs with cancer are imprecisely defined concepts. Formal geriatric assessment was recommended in just over half of articles, and only 26.2% recommended formal assessments of age-related vulnerabilities for management. The authors proposed definitions that accounted for both oncologic factors and geriatric domains.
Care of individual patients and clinical research
National Comprehensive Cancer Network (NCCN) guidelines for OAs with cancer recommend initial consideration of overall life expectancy. If a patient is a candidate for cancer treatment on that basis, the next recommended assessment is that of the patient’s capacity to understand the relevant information, appreciate the underlying values and overall medical situation, reason through decisions, and communicate a choice that is consistent with the patient’s articulated goals.
In the pretreatment evaluation of OAs in whom there are no concerns about tolerance to antineoplastic therapy, NCCN guidelines suggest geriatric screening with standardized tools and, if abnormal, comprehensive geriatric screening. The guidelines recommend considering alternative treatment options if nonmodifiable abnormalities are identified.
Referral to a geriatric clinical specialist, use of the Cancer and Aging Research Group’s Chemo Toxicity Calculator, and calculation of Chemotherapy Risk Assessment Scale for High-Age Patients score are specifically suggested if high-risk procedures (such as chemotherapy, radiation, or complex surgery, which most oncologists would consider to be “another day in the office”) are contemplated.
The American Society of Clinical Oncology (ASCO) guidelines for geriatric oncology are similarly detailed and endorse similar evaluations and management.
Employing disease-centric and geriatric domains
Dr. DuMontier and colleagues noted that, for OAs with comorbidity or psychosocial challenges, surrogate survival endpoints are unrelated to quality of life (QOL) outcomes. Nonetheless, QOL is valued by OAs at least as much as survival improvement.
Through no fault of their own, the authors’ conclusion that undertreatment and overtreatment are imperfectly defined concepts has a certain neutrality to it. However, the terms undertreatment and overtreatment are commonly used to signify that inappropriate treatment decisions were made. Therefore, the terms are inherently negative and pejorative.
As with most emotionally charged issues in oncology, it is ideal for professionals in our field to take charge when deficiencies exist. ASCO, NCCN, and the authors of this scoping review have provided a conceptual basis for doing so.
An integrated oncologist-geriatrician approach was shown to be effective in the randomized INTEGERATE trial, showing improved QOL, reduced hospital admissions, and reduced early treatment discontinuation from adverse events (ASCO 2020, Abstract 12011).
Therefore, those clinicians who have not formally, systematically, and routinely supplemented the traditional disease-centric endpoints with patient-centered criteria need to do so.
Similarly, a retrospective study published in JAMA Network Open demonstrated that geriatric and surgical comanagement of OAs with cancer was associated with significantly lower 90-day postoperative mortality and receipt of more supportive care services (physical therapy, occupational therapy, speech and swallow rehabilitation, and nutrition services), in comparison with management from the surgical service only.
These clinical and administrative changes will not only enhance patient management but also facilitate the clinical trials required to clarify optimal treatment intensity. As that occurs, we will be able to apply as much precision to the care of OAs with cancer as we do in other areas of cancer treatment.
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: Dumontier C et al. J Clin Oncol. 2020 Aug 1;38(22):2558-2569.
Cancer disparities: One of the most pressing public health issues
“The burden of cancer is not shouldered equally by all segments of the U.S. population,” the AACR adds. “The adverse differences in cancer burden that exist among certain population groups are one of the most pressing public health challenges that we face in the United States.”
AACR president Antoni Ribas, MD, PhD, gave some examples of these disparities at a September 16 Congressional briefing that focused on the inaugural AACR Cancer Disparities Progress Report 2020.
He noted that:
- Black men have more than double the rate of death from prostate cancer compared with men of other racial and ethnic groups.
- Hispanic children are 24% more likely to develop leukemia than non-Hispanic children.
- Non-Hispanic Black children and adolescents with cancer are more than 50% more likely to die from the cancer than non-Hispanic white children and adolescents with cancer.
- Women of low socioeconomic status with early stage ovarian cancer are 50% less likely to receive recommended care than are women of high socioeconomic status.
- In addition to racial and ethnic minority groups, other populations that bear a disproportionate burden when it comes to cancer include individuals lacking adequate health insurance coverage, immigrants, those with disabilities, residents in rural areas, and members of the lesbian, gay, bisexual, and transgender communities.
“It is absolutely unacceptable that advances in cancer care and treatment are not benefiting everyone equally,” Ribas commented.
Making progress against cancer
Progress being made against cancer was highlighted in another publication, the annual AACR Cancer Progress Report 2020.
U.S. cancer deaths declined by 29% between 1991 and 2017, translating to nearly 3 million cancer deaths avoided, the report notes. In addition, 5-year survival rates for all cancers combined increased from 49% in the mid-1970s to 70% for patients diagnosed from 2010-2016.
Between August 2019 and July 31 of this year, the U.S. Food and Drug Administration approved 20 new anticancer drugs for various cancer types and 15 new indications for previously approved cancer drugs, marking the highest number of approvals in one 12-month period since AACR started producing these reports 10 years ago.
A continuing reduction in the cigarette smoking rate among US adults, which is now below 14%, is contributing greatly to declines in lung cancer rates, which have largely driven the improvements in cancer survival, the AACR noted.
This report also notes that progress has been made toward reducing cancer disparities. Overall disparities in cancer death rates among racial and ethnic groups are less pronounced now than they have been in the past two decades. For example, the overall cancer death rate for African American patients was 33% higher than for White patients in 1990 but just 14% higher in 2016.
However, both reports agree that more must be done to reduce cancer disparities even further.
They highlight initiatives that are underway, including:
- The draft guidance issued by the FDA to promote diversification of clinical trial populations.
- The National Institutes of Health’s (NIH’s) Continuing Umbrella of Research Experiences (CURE) program supporting underrepresented students and scientists along their academic and research career pathway.
- The Centers for Disease Control and Prevention’s Racial and Ethnic Approaches to Community Health (REACH) program, a grant-making program focused on encouraging preventive behaviors in underserved communities.
- The NIH’s All of Us program, which is gathering information from the genomes of 1 million healthy individuals with a focus on recruitment from historically underrepresented populations.
Ribas also announced that AACR has established a task force to focus on racial inequalities in cancer research.
Eliminating disparities would save money, argued John D. Carpten, PhD, from the University of Southern California, Los Angeles, who chaired the steering committee that developed the AACR Cancer Disparities Progress Report.
Carpten noted research showing that eliminating disparities for racial and ethnic minorities between 2003 and 2006 would have reduced health care costs by more than $1 trillion in the United States. This underscores the potentially far-reaching impact of efforts to eliminate disparities, he said.
“Without a doubt, socioeconomics and inequities in access to quality care represent major factors influencing cancer health disparities, and these disparities will persist until we address these issues” he said.
Both progress reports culminate in a call to action, largely focused on the need for “unwavering, bipartisan support from Congress, in the form of robust and sustained annual increases in funding for the NIH, NCI [National Cancer Institute], and FDA,” which is vital for accelerating the pace of progress.
The challenge is now compounded by the ongoing COVID-19 pandemic: Both progress reports note that racial and ethnic minorities, including African Americans, are not only affected disproportionately by cancer, but also by COVID-19, further highlighting the “stark inequities in health care.”
Ribas further called for action from national leadership and the scientific community.
“During this unprecedented time in our nation’s history, there is also a need for our nation’s leaders to take on a much bigger role in confronting and combating the structural and systemic racism that contributes to health disparities,” he said. The “pervasive racism and social injustices” that have contributed to disparities in both COVID-19 and cancer underscore the need for “the scientific community to step up and partner with Congress to assess and address this issue within the research community.”
This article first appeared on Medscape.com.
“The burden of cancer is not shouldered equally by all segments of the U.S. population,” the AACR adds. “The adverse differences in cancer burden that exist among certain population groups are one of the most pressing public health challenges that we face in the United States.”
AACR president Antoni Ribas, MD, PhD, gave some examples of these disparities at a September 16 Congressional briefing that focused on the inaugural AACR Cancer Disparities Progress Report 2020.
He noted that:
- Black men have more than double the rate of death from prostate cancer compared with men of other racial and ethnic groups.
- Hispanic children are 24% more likely to develop leukemia than non-Hispanic children.
- Non-Hispanic Black children and adolescents with cancer are more than 50% more likely to die from the cancer than non-Hispanic white children and adolescents with cancer.
- Women of low socioeconomic status with early stage ovarian cancer are 50% less likely to receive recommended care than are women of high socioeconomic status.
- In addition to racial and ethnic minority groups, other populations that bear a disproportionate burden when it comes to cancer include individuals lacking adequate health insurance coverage, immigrants, those with disabilities, residents in rural areas, and members of the lesbian, gay, bisexual, and transgender communities.
“It is absolutely unacceptable that advances in cancer care and treatment are not benefiting everyone equally,” Ribas commented.
Making progress against cancer
Progress being made against cancer was highlighted in another publication, the annual AACR Cancer Progress Report 2020.
U.S. cancer deaths declined by 29% between 1991 and 2017, translating to nearly 3 million cancer deaths avoided, the report notes. In addition, 5-year survival rates for all cancers combined increased from 49% in the mid-1970s to 70% for patients diagnosed from 2010-2016.
Between August 2019 and July 31 of this year, the U.S. Food and Drug Administration approved 20 new anticancer drugs for various cancer types and 15 new indications for previously approved cancer drugs, marking the highest number of approvals in one 12-month period since AACR started producing these reports 10 years ago.
A continuing reduction in the cigarette smoking rate among US adults, which is now below 14%, is contributing greatly to declines in lung cancer rates, which have largely driven the improvements in cancer survival, the AACR noted.
This report also notes that progress has been made toward reducing cancer disparities. Overall disparities in cancer death rates among racial and ethnic groups are less pronounced now than they have been in the past two decades. For example, the overall cancer death rate for African American patients was 33% higher than for White patients in 1990 but just 14% higher in 2016.
However, both reports agree that more must be done to reduce cancer disparities even further.
They highlight initiatives that are underway, including:
- The draft guidance issued by the FDA to promote diversification of clinical trial populations.
- The National Institutes of Health’s (NIH’s) Continuing Umbrella of Research Experiences (CURE) program supporting underrepresented students and scientists along their academic and research career pathway.
- The Centers for Disease Control and Prevention’s Racial and Ethnic Approaches to Community Health (REACH) program, a grant-making program focused on encouraging preventive behaviors in underserved communities.
- The NIH’s All of Us program, which is gathering information from the genomes of 1 million healthy individuals with a focus on recruitment from historically underrepresented populations.
Ribas also announced that AACR has established a task force to focus on racial inequalities in cancer research.
Eliminating disparities would save money, argued John D. Carpten, PhD, from the University of Southern California, Los Angeles, who chaired the steering committee that developed the AACR Cancer Disparities Progress Report.
Carpten noted research showing that eliminating disparities for racial and ethnic minorities between 2003 and 2006 would have reduced health care costs by more than $1 trillion in the United States. This underscores the potentially far-reaching impact of efforts to eliminate disparities, he said.
“Without a doubt, socioeconomics and inequities in access to quality care represent major factors influencing cancer health disparities, and these disparities will persist until we address these issues” he said.
Both progress reports culminate in a call to action, largely focused on the need for “unwavering, bipartisan support from Congress, in the form of robust and sustained annual increases in funding for the NIH, NCI [National Cancer Institute], and FDA,” which is vital for accelerating the pace of progress.
The challenge is now compounded by the ongoing COVID-19 pandemic: Both progress reports note that racial and ethnic minorities, including African Americans, are not only affected disproportionately by cancer, but also by COVID-19, further highlighting the “stark inequities in health care.”
Ribas further called for action from national leadership and the scientific community.
“During this unprecedented time in our nation’s history, there is also a need for our nation’s leaders to take on a much bigger role in confronting and combating the structural and systemic racism that contributes to health disparities,” he said. The “pervasive racism and social injustices” that have contributed to disparities in both COVID-19 and cancer underscore the need for “the scientific community to step up and partner with Congress to assess and address this issue within the research community.”
This article first appeared on Medscape.com.
“The burden of cancer is not shouldered equally by all segments of the U.S. population,” the AACR adds. “The adverse differences in cancer burden that exist among certain population groups are one of the most pressing public health challenges that we face in the United States.”
AACR president Antoni Ribas, MD, PhD, gave some examples of these disparities at a September 16 Congressional briefing that focused on the inaugural AACR Cancer Disparities Progress Report 2020.
He noted that:
- Black men have more than double the rate of death from prostate cancer compared with men of other racial and ethnic groups.
- Hispanic children are 24% more likely to develop leukemia than non-Hispanic children.
- Non-Hispanic Black children and adolescents with cancer are more than 50% more likely to die from the cancer than non-Hispanic white children and adolescents with cancer.
- Women of low socioeconomic status with early stage ovarian cancer are 50% less likely to receive recommended care than are women of high socioeconomic status.
- In addition to racial and ethnic minority groups, other populations that bear a disproportionate burden when it comes to cancer include individuals lacking adequate health insurance coverage, immigrants, those with disabilities, residents in rural areas, and members of the lesbian, gay, bisexual, and transgender communities.
“It is absolutely unacceptable that advances in cancer care and treatment are not benefiting everyone equally,” Ribas commented.
Making progress against cancer
Progress being made against cancer was highlighted in another publication, the annual AACR Cancer Progress Report 2020.
U.S. cancer deaths declined by 29% between 1991 and 2017, translating to nearly 3 million cancer deaths avoided, the report notes. In addition, 5-year survival rates for all cancers combined increased from 49% in the mid-1970s to 70% for patients diagnosed from 2010-2016.
Between August 2019 and July 31 of this year, the U.S. Food and Drug Administration approved 20 new anticancer drugs for various cancer types and 15 new indications for previously approved cancer drugs, marking the highest number of approvals in one 12-month period since AACR started producing these reports 10 years ago.
A continuing reduction in the cigarette smoking rate among US adults, which is now below 14%, is contributing greatly to declines in lung cancer rates, which have largely driven the improvements in cancer survival, the AACR noted.
This report also notes that progress has been made toward reducing cancer disparities. Overall disparities in cancer death rates among racial and ethnic groups are less pronounced now than they have been in the past two decades. For example, the overall cancer death rate for African American patients was 33% higher than for White patients in 1990 but just 14% higher in 2016.
However, both reports agree that more must be done to reduce cancer disparities even further.
They highlight initiatives that are underway, including:
- The draft guidance issued by the FDA to promote diversification of clinical trial populations.
- The National Institutes of Health’s (NIH’s) Continuing Umbrella of Research Experiences (CURE) program supporting underrepresented students and scientists along their academic and research career pathway.
- The Centers for Disease Control and Prevention’s Racial and Ethnic Approaches to Community Health (REACH) program, a grant-making program focused on encouraging preventive behaviors in underserved communities.
- The NIH’s All of Us program, which is gathering information from the genomes of 1 million healthy individuals with a focus on recruitment from historically underrepresented populations.
Ribas also announced that AACR has established a task force to focus on racial inequalities in cancer research.
Eliminating disparities would save money, argued John D. Carpten, PhD, from the University of Southern California, Los Angeles, who chaired the steering committee that developed the AACR Cancer Disparities Progress Report.
Carpten noted research showing that eliminating disparities for racial and ethnic minorities between 2003 and 2006 would have reduced health care costs by more than $1 trillion in the United States. This underscores the potentially far-reaching impact of efforts to eliminate disparities, he said.
“Without a doubt, socioeconomics and inequities in access to quality care represent major factors influencing cancer health disparities, and these disparities will persist until we address these issues” he said.
Both progress reports culminate in a call to action, largely focused on the need for “unwavering, bipartisan support from Congress, in the form of robust and sustained annual increases in funding for the NIH, NCI [National Cancer Institute], and FDA,” which is vital for accelerating the pace of progress.
The challenge is now compounded by the ongoing COVID-19 pandemic: Both progress reports note that racial and ethnic minorities, including African Americans, are not only affected disproportionately by cancer, but also by COVID-19, further highlighting the “stark inequities in health care.”
Ribas further called for action from national leadership and the scientific community.
“During this unprecedented time in our nation’s history, there is also a need for our nation’s leaders to take on a much bigger role in confronting and combating the structural and systemic racism that contributes to health disparities,” he said. The “pervasive racism and social injustices” that have contributed to disparities in both COVID-19 and cancer underscore the need for “the scientific community to step up and partner with Congress to assess and address this issue within the research community.”
This article first appeared on Medscape.com.
Survey quantifies COVID-19’s impact on oncology
An international survey provides new insights into how COVID-19 has affected, and may continue to affect, the field of oncology.
The survey showed that “COVID-19 has had a major impact on the organization of patient care, on the well-being of caregivers, on continued medical education, and on clinical trial activities in oncology,” stated Guy Jerusalem, MD, PhD, of Centre Hospitalier Universitaire de Liège (Belgium).
Dr. Jerusalem presented these findings at the European Society for Medical Oncology Virtual Congress 2020.
The survey was distributed by 20 oncologists from 10 of the countries most affected by COVID-19. Responses were obtained from 109 oncologists representing centers in 18 countries. The responses were recorded between June 17 and July 14, 2020.
The survey consisted of 95 items intended to evaluate the impact of COVID-19 on the organization of oncologic care. Questions encompassed the capacity and service offered at each center, the magnitude of COVID-19–based care interruptions and the reasons for them, the ensuing challenges faced, interventions implemented, and the estimated harms to patients during the pandemic.
The 109 oncologists surveyed had a median of 20 years of oncology experience. A majority of respondents were men (61.5%), and the median age was 48.5 years.
The respondents had worked predominantly (62.4%) at academic hospitals, with 29.6% at community hospitals. Most respondents worked at general hospitals with an oncology unit (66.1%) rather than a specialized separate cancer center (32.1%).
The most common specialty was breast cancer (60.6%), followed by gastrointestinal cancer (10.1%), urogenital cancer (9.2%), and lung cancer (8.3%).
Impact on treatment
The treatment modalities affected by the pandemic – through cancellations or delays in more than 10% of patients – included surgery (in 34% of centers), chemotherapy (22%), radiotherapy (13.7%), checkpoint inhibitor therapy (9.1%), monoclonal antibodies (9%), and oral targeted therapy (3.7%).
Among oncologists treating breast cancer, cancellations/delays in more than 10% of patients were reported for everolimus (18%), CDK4/6 inhibitors (8.9%), and endocrine therapy (2.2%).
Overall, 34.8% of respondents reported increased use of granulocyte colony–stimulating factor, and 6.4% reported increased use of erythropoietin.
On the other hand, 11.1% of respondents reported a decrease in the use of double immunotherapy, and 21.9% reported decreased use of corticosteroids.
Not only can the immunosuppressive effects of steroid use increase infection risks, Dr. Jerusalem noted, fever suppression can lead to a delayed diagnosis of COVID-19.
“To circumvent potential higher infection risks or greater disease severity, we use lower doses of steroids, but this is not based on studies,” he said.
“Previous exposure to steroids or being on steroids at the time of COVID-19 infection is a detrimental factor for complications and mortality,” commented ESMO President Solange Peters, MD, PhD, of Centre Hospitalier Universitaire Vaudois in Lausanne, Switzerland.
Dr. Peters noted that the observation was based on lung cancer registry findings. Furthermore, because data from smaller outbreaks of other coronavirus infections suggested worse prognosis and increased mortality, steroid use was already feared in the very early days of the COVID-19 pandemic.
Lastly, earlier cessation of palliative treatment was observed in 32.1% of centers, and 64.2% of respondents agreed that undertreatment because of COVID-19 is a major concern.
Dr. Jerusalem noted that the survey data do not explain the early cessation of palliative treatment. “I suspect that many patients died at home rather than alone in institutions because it was the only way they could die with their families around them.”
Telehealth, meetings, and trials
The survey also revealed rationales for the use of teleconsultation, including follow-up (94.5%), oral therapy (92.7%), immunotherapy (57.8%), and chemotherapy (55%).
Most respondents reported more frequent use of virtual meetings for continuing medical education (94%), oncologic team meetings (92%), and tumor boards (82%).
While about 82% of respondents said they were likely to continue the use of telemedicine, 45% said virtual conferences are not an acceptable alternative to live international conferences such as ESMO, Dr. Jerusalem said.
Finally, nearly three-quarters of respondents (72.5%) said all clinical trial activities are or will soon be activated, or never stopped, at their centers. On the other hand, 27.5% of respondents reported that their centers had major protocol violations or deviations, and 37% of respondents said they expect significant reductions in clinical trial activities this year.
Dr. Jerusalem concluded that COVID-19 is having a major, long-term impact on the organization of patient care, caregivers, continued medical education, and clinical trial activities in oncology.
He cautioned that “the risk of a delayed diagnosis of new cancers and economic consequences of COVID-19 on access to health care and cancer treatments have to be carefully evaluated.”
This research was funded by Fondation Léon Fredericq. Dr. Jerusalem disclosed relationships with Novartis, Roche, Lilly, Pfizer, Amgen, Bristol-Myers Squibb, AstraZeneca, Daiichi Sankyo, AbbVie, MedImmune, and Merck. Dr. Peters disclosed relationships with AbbVie, Amgen, AstraZeneca, and many other companies.
SOURCE: Jerusalem G et al. ESMO 2020, Abstract LBA76.
An international survey provides new insights into how COVID-19 has affected, and may continue to affect, the field of oncology.
The survey showed that “COVID-19 has had a major impact on the organization of patient care, on the well-being of caregivers, on continued medical education, and on clinical trial activities in oncology,” stated Guy Jerusalem, MD, PhD, of Centre Hospitalier Universitaire de Liège (Belgium).
Dr. Jerusalem presented these findings at the European Society for Medical Oncology Virtual Congress 2020.
The survey was distributed by 20 oncologists from 10 of the countries most affected by COVID-19. Responses were obtained from 109 oncologists representing centers in 18 countries. The responses were recorded between June 17 and July 14, 2020.
The survey consisted of 95 items intended to evaluate the impact of COVID-19 on the organization of oncologic care. Questions encompassed the capacity and service offered at each center, the magnitude of COVID-19–based care interruptions and the reasons for them, the ensuing challenges faced, interventions implemented, and the estimated harms to patients during the pandemic.
The 109 oncologists surveyed had a median of 20 years of oncology experience. A majority of respondents were men (61.5%), and the median age was 48.5 years.
The respondents had worked predominantly (62.4%) at academic hospitals, with 29.6% at community hospitals. Most respondents worked at general hospitals with an oncology unit (66.1%) rather than a specialized separate cancer center (32.1%).
The most common specialty was breast cancer (60.6%), followed by gastrointestinal cancer (10.1%), urogenital cancer (9.2%), and lung cancer (8.3%).
Impact on treatment
The treatment modalities affected by the pandemic – through cancellations or delays in more than 10% of patients – included surgery (in 34% of centers), chemotherapy (22%), radiotherapy (13.7%), checkpoint inhibitor therapy (9.1%), monoclonal antibodies (9%), and oral targeted therapy (3.7%).
Among oncologists treating breast cancer, cancellations/delays in more than 10% of patients were reported for everolimus (18%), CDK4/6 inhibitors (8.9%), and endocrine therapy (2.2%).
Overall, 34.8% of respondents reported increased use of granulocyte colony–stimulating factor, and 6.4% reported increased use of erythropoietin.
On the other hand, 11.1% of respondents reported a decrease in the use of double immunotherapy, and 21.9% reported decreased use of corticosteroids.
Not only can the immunosuppressive effects of steroid use increase infection risks, Dr. Jerusalem noted, fever suppression can lead to a delayed diagnosis of COVID-19.
“To circumvent potential higher infection risks or greater disease severity, we use lower doses of steroids, but this is not based on studies,” he said.
“Previous exposure to steroids or being on steroids at the time of COVID-19 infection is a detrimental factor for complications and mortality,” commented ESMO President Solange Peters, MD, PhD, of Centre Hospitalier Universitaire Vaudois in Lausanne, Switzerland.
Dr. Peters noted that the observation was based on lung cancer registry findings. Furthermore, because data from smaller outbreaks of other coronavirus infections suggested worse prognosis and increased mortality, steroid use was already feared in the very early days of the COVID-19 pandemic.
Lastly, earlier cessation of palliative treatment was observed in 32.1% of centers, and 64.2% of respondents agreed that undertreatment because of COVID-19 is a major concern.
Dr. Jerusalem noted that the survey data do not explain the early cessation of palliative treatment. “I suspect that many patients died at home rather than alone in institutions because it was the only way they could die with their families around them.”
Telehealth, meetings, and trials
The survey also revealed rationales for the use of teleconsultation, including follow-up (94.5%), oral therapy (92.7%), immunotherapy (57.8%), and chemotherapy (55%).
Most respondents reported more frequent use of virtual meetings for continuing medical education (94%), oncologic team meetings (92%), and tumor boards (82%).
While about 82% of respondents said they were likely to continue the use of telemedicine, 45% said virtual conferences are not an acceptable alternative to live international conferences such as ESMO, Dr. Jerusalem said.
Finally, nearly three-quarters of respondents (72.5%) said all clinical trial activities are or will soon be activated, or never stopped, at their centers. On the other hand, 27.5% of respondents reported that their centers had major protocol violations or deviations, and 37% of respondents said they expect significant reductions in clinical trial activities this year.
Dr. Jerusalem concluded that COVID-19 is having a major, long-term impact on the organization of patient care, caregivers, continued medical education, and clinical trial activities in oncology.
He cautioned that “the risk of a delayed diagnosis of new cancers and economic consequences of COVID-19 on access to health care and cancer treatments have to be carefully evaluated.”
This research was funded by Fondation Léon Fredericq. Dr. Jerusalem disclosed relationships with Novartis, Roche, Lilly, Pfizer, Amgen, Bristol-Myers Squibb, AstraZeneca, Daiichi Sankyo, AbbVie, MedImmune, and Merck. Dr. Peters disclosed relationships with AbbVie, Amgen, AstraZeneca, and many other companies.
SOURCE: Jerusalem G et al. ESMO 2020, Abstract LBA76.
An international survey provides new insights into how COVID-19 has affected, and may continue to affect, the field of oncology.
The survey showed that “COVID-19 has had a major impact on the organization of patient care, on the well-being of caregivers, on continued medical education, and on clinical trial activities in oncology,” stated Guy Jerusalem, MD, PhD, of Centre Hospitalier Universitaire de Liège (Belgium).
Dr. Jerusalem presented these findings at the European Society for Medical Oncology Virtual Congress 2020.
The survey was distributed by 20 oncologists from 10 of the countries most affected by COVID-19. Responses were obtained from 109 oncologists representing centers in 18 countries. The responses were recorded between June 17 and July 14, 2020.
The survey consisted of 95 items intended to evaluate the impact of COVID-19 on the organization of oncologic care. Questions encompassed the capacity and service offered at each center, the magnitude of COVID-19–based care interruptions and the reasons for them, the ensuing challenges faced, interventions implemented, and the estimated harms to patients during the pandemic.
The 109 oncologists surveyed had a median of 20 years of oncology experience. A majority of respondents were men (61.5%), and the median age was 48.5 years.
The respondents had worked predominantly (62.4%) at academic hospitals, with 29.6% at community hospitals. Most respondents worked at general hospitals with an oncology unit (66.1%) rather than a specialized separate cancer center (32.1%).
The most common specialty was breast cancer (60.6%), followed by gastrointestinal cancer (10.1%), urogenital cancer (9.2%), and lung cancer (8.3%).
Impact on treatment
The treatment modalities affected by the pandemic – through cancellations or delays in more than 10% of patients – included surgery (in 34% of centers), chemotherapy (22%), radiotherapy (13.7%), checkpoint inhibitor therapy (9.1%), monoclonal antibodies (9%), and oral targeted therapy (3.7%).
Among oncologists treating breast cancer, cancellations/delays in more than 10% of patients were reported for everolimus (18%), CDK4/6 inhibitors (8.9%), and endocrine therapy (2.2%).
Overall, 34.8% of respondents reported increased use of granulocyte colony–stimulating factor, and 6.4% reported increased use of erythropoietin.
On the other hand, 11.1% of respondents reported a decrease in the use of double immunotherapy, and 21.9% reported decreased use of corticosteroids.
Not only can the immunosuppressive effects of steroid use increase infection risks, Dr. Jerusalem noted, fever suppression can lead to a delayed diagnosis of COVID-19.
“To circumvent potential higher infection risks or greater disease severity, we use lower doses of steroids, but this is not based on studies,” he said.
“Previous exposure to steroids or being on steroids at the time of COVID-19 infection is a detrimental factor for complications and mortality,” commented ESMO President Solange Peters, MD, PhD, of Centre Hospitalier Universitaire Vaudois in Lausanne, Switzerland.
Dr. Peters noted that the observation was based on lung cancer registry findings. Furthermore, because data from smaller outbreaks of other coronavirus infections suggested worse prognosis and increased mortality, steroid use was already feared in the very early days of the COVID-19 pandemic.
Lastly, earlier cessation of palliative treatment was observed in 32.1% of centers, and 64.2% of respondents agreed that undertreatment because of COVID-19 is a major concern.
Dr. Jerusalem noted that the survey data do not explain the early cessation of palliative treatment. “I suspect that many patients died at home rather than alone in institutions because it was the only way they could die with their families around them.”
Telehealth, meetings, and trials
The survey also revealed rationales for the use of teleconsultation, including follow-up (94.5%), oral therapy (92.7%), immunotherapy (57.8%), and chemotherapy (55%).
Most respondents reported more frequent use of virtual meetings for continuing medical education (94%), oncologic team meetings (92%), and tumor boards (82%).
While about 82% of respondents said they were likely to continue the use of telemedicine, 45% said virtual conferences are not an acceptable alternative to live international conferences such as ESMO, Dr. Jerusalem said.
Finally, nearly three-quarters of respondents (72.5%) said all clinical trial activities are or will soon be activated, or never stopped, at their centers. On the other hand, 27.5% of respondents reported that their centers had major protocol violations or deviations, and 37% of respondents said they expect significant reductions in clinical trial activities this year.
Dr. Jerusalem concluded that COVID-19 is having a major, long-term impact on the organization of patient care, caregivers, continued medical education, and clinical trial activities in oncology.
He cautioned that “the risk of a delayed diagnosis of new cancers and economic consequences of COVID-19 on access to health care and cancer treatments have to be carefully evaluated.”
This research was funded by Fondation Léon Fredericq. Dr. Jerusalem disclosed relationships with Novartis, Roche, Lilly, Pfizer, Amgen, Bristol-Myers Squibb, AstraZeneca, Daiichi Sankyo, AbbVie, MedImmune, and Merck. Dr. Peters disclosed relationships with AbbVie, Amgen, AstraZeneca, and many other companies.
SOURCE: Jerusalem G et al. ESMO 2020, Abstract LBA76.
FROM ESMO 2020
New radiomic model may improve prognostication in meningioma
, according to a study published in the European Journal of Radiology.
The model – which combines conventional magnetic resonance imaging (cMRI), apparent diffusion coefficient (ADC) maps, and susceptibility weighted imaging (SWI) – was the best performer of all models tested.
Recent studies have shown that radiomic features from cMRI or ADC maps could build “a robust model to predict the grade of meningioma by using machine learning algorithms,” wrote study author Jianping Hu, MD, PhD, of Fujian Medical University in Fujian, China, and colleagues.
With that in mind, the researchers evaluated the role of radiomic models based on cMRI, ADC maps, and/or SWI in predicting meningioma grade.
Patients and models
The team retrospectively analyzed 514 patients with meningioma who underwent preoperative MRI assessment over a 10-year period. There were 316 patients included in the final analysis, 229 with low-grade (grade I) and 87 with high-grade (grade II-III) meningioma.
Radiomic features from cMRI, ADC maps, and SWI were extracted based on total tumor volume.
Using a nested leave-one-out cross-validation method, the researchers evaluated the prediction performance of various radiomic models, including cMRI, ADC, SWI, ADC plus SWI, cMRI plus ADC, cMRI plus SWI, and cMRI plus ADC plus SWI.
To establish the final prediction model, the researchers used least absolute shrinkage and selection operator feature selection and implemented a random forest classifier that was trained with and without subsampling. The area under the receiver operating characteristic curve (AUC) was used to evaluate the prediction performance of each model.
Results
The model combining cMRI, ADC, and SWI had the best performance in predicting meningioma grade. The AUC of this model was 0.81 with subsampling and 0.84 without subsampling. The other models had an AUC range of 0.71-0.79 with subsampling and 0.75-0.80 without subsampling.
“Our results indicated that [the] multiparametric radiomic model based on cMRI, ADC map, and SWI [tended] to be the best model for the prediction of meningioma grade,” Dr. Hu and colleagues wrote.
Other recent studies have demonstrated that radiomic features from various imaging parameters, such as diffusion weighted imaging and cMRI, can establish robust prediction models for the prediction of meningioma grade, in which AUCs have ranged from 0.63 to 0.91.
While these findings are encouraging, the researchers acknowledged that these data should be interpreted with discretion as the cystic or necrotic areas of tumor were included in the analysis. In addition, the retrospective nature of the study could have introduced selection bias.
No funding sources were reported. The authors reported having no conflicts of interest.
SOURCE: Hu J et al. Eur J Radiol. 2020 Aug 28. doi: 10.1016/j.ejrad.2020.109251.
, according to a study published in the European Journal of Radiology.
The model – which combines conventional magnetic resonance imaging (cMRI), apparent diffusion coefficient (ADC) maps, and susceptibility weighted imaging (SWI) – was the best performer of all models tested.
Recent studies have shown that radiomic features from cMRI or ADC maps could build “a robust model to predict the grade of meningioma by using machine learning algorithms,” wrote study author Jianping Hu, MD, PhD, of Fujian Medical University in Fujian, China, and colleagues.
With that in mind, the researchers evaluated the role of radiomic models based on cMRI, ADC maps, and/or SWI in predicting meningioma grade.
Patients and models
The team retrospectively analyzed 514 patients with meningioma who underwent preoperative MRI assessment over a 10-year period. There were 316 patients included in the final analysis, 229 with low-grade (grade I) and 87 with high-grade (grade II-III) meningioma.
Radiomic features from cMRI, ADC maps, and SWI were extracted based on total tumor volume.
Using a nested leave-one-out cross-validation method, the researchers evaluated the prediction performance of various radiomic models, including cMRI, ADC, SWI, ADC plus SWI, cMRI plus ADC, cMRI plus SWI, and cMRI plus ADC plus SWI.
To establish the final prediction model, the researchers used least absolute shrinkage and selection operator feature selection and implemented a random forest classifier that was trained with and without subsampling. The area under the receiver operating characteristic curve (AUC) was used to evaluate the prediction performance of each model.
Results
The model combining cMRI, ADC, and SWI had the best performance in predicting meningioma grade. The AUC of this model was 0.81 with subsampling and 0.84 without subsampling. The other models had an AUC range of 0.71-0.79 with subsampling and 0.75-0.80 without subsampling.
“Our results indicated that [the] multiparametric radiomic model based on cMRI, ADC map, and SWI [tended] to be the best model for the prediction of meningioma grade,” Dr. Hu and colleagues wrote.
Other recent studies have demonstrated that radiomic features from various imaging parameters, such as diffusion weighted imaging and cMRI, can establish robust prediction models for the prediction of meningioma grade, in which AUCs have ranged from 0.63 to 0.91.
While these findings are encouraging, the researchers acknowledged that these data should be interpreted with discretion as the cystic or necrotic areas of tumor were included in the analysis. In addition, the retrospective nature of the study could have introduced selection bias.
No funding sources were reported. The authors reported having no conflicts of interest.
SOURCE: Hu J et al. Eur J Radiol. 2020 Aug 28. doi: 10.1016/j.ejrad.2020.109251.
, according to a study published in the European Journal of Radiology.
The model – which combines conventional magnetic resonance imaging (cMRI), apparent diffusion coefficient (ADC) maps, and susceptibility weighted imaging (SWI) – was the best performer of all models tested.
Recent studies have shown that radiomic features from cMRI or ADC maps could build “a robust model to predict the grade of meningioma by using machine learning algorithms,” wrote study author Jianping Hu, MD, PhD, of Fujian Medical University in Fujian, China, and colleagues.
With that in mind, the researchers evaluated the role of radiomic models based on cMRI, ADC maps, and/or SWI in predicting meningioma grade.
Patients and models
The team retrospectively analyzed 514 patients with meningioma who underwent preoperative MRI assessment over a 10-year period. There were 316 patients included in the final analysis, 229 with low-grade (grade I) and 87 with high-grade (grade II-III) meningioma.
Radiomic features from cMRI, ADC maps, and SWI were extracted based on total tumor volume.
Using a nested leave-one-out cross-validation method, the researchers evaluated the prediction performance of various radiomic models, including cMRI, ADC, SWI, ADC plus SWI, cMRI plus ADC, cMRI plus SWI, and cMRI plus ADC plus SWI.
To establish the final prediction model, the researchers used least absolute shrinkage and selection operator feature selection and implemented a random forest classifier that was trained with and without subsampling. The area under the receiver operating characteristic curve (AUC) was used to evaluate the prediction performance of each model.
Results
The model combining cMRI, ADC, and SWI had the best performance in predicting meningioma grade. The AUC of this model was 0.81 with subsampling and 0.84 without subsampling. The other models had an AUC range of 0.71-0.79 with subsampling and 0.75-0.80 without subsampling.
“Our results indicated that [the] multiparametric radiomic model based on cMRI, ADC map, and SWI [tended] to be the best model for the prediction of meningioma grade,” Dr. Hu and colleagues wrote.
Other recent studies have demonstrated that radiomic features from various imaging parameters, such as diffusion weighted imaging and cMRI, can establish robust prediction models for the prediction of meningioma grade, in which AUCs have ranged from 0.63 to 0.91.
While these findings are encouraging, the researchers acknowledged that these data should be interpreted with discretion as the cystic or necrotic areas of tumor were included in the analysis. In addition, the retrospective nature of the study could have introduced selection bias.
No funding sources were reported. The authors reported having no conflicts of interest.
SOURCE: Hu J et al. Eur J Radiol. 2020 Aug 28. doi: 10.1016/j.ejrad.2020.109251.
FROM EUROPEAN JOURNAL OF RADIOLOGY
COVID-19 prompts ‘democratization’ of cancer trials
The pandemic has taught researchers how to decentralize trials, which should not only improve patient satisfaction but increase trial accrual by providing access to typically underserved populations, Patricia M. LoRusso, DO, of Yale University, New Haven, Conn., said at the meeting.
Dr. LoRusso was one of six panelists who participated in a forum about changes to cancer trials that were prompted by the pandemic. The forum was moderated by Keith T. Flaherty, MD, of Massachusetts General Hospital in Boston.
Dr. Flaherty asked the panelists to explain adjustments their organizations have made in response to the pandemic, discuss accomplishments, and speculate on future challenges and priorities.
Trial, administrative, and patient-care modifications
COVID-19 put some cancer trials on hold. For others, the pandemic forced sponsors and study chairs to reduce trial complexity and identify nonessential aspects of the studies, according to panelist José Baselga, MD, PhD, of AstraZeneca.
Specifically, exploratory objectives were subjugated to patient safety and a focus on the primary endpoints of each trial.
Once the critical data were identified, study chairs were asked to determine whether data could be obtained through technologies that could substitute for face-to-face contact between patients and staff – for example, patient-reported outcome tools and at-home digital monitoring.
Modifications prompted by the pandemic include the following:
- On-site auditing was suspended.
- Oral investigational agents were shipped directly to patients.
- “Remote” informed consent (telephone or video consenting) was permitted.
- Local providers could perform study-related services, with oversight by the research site.
- Minor deviations from the written protocols were allowed, provided the deviations did not affect patient care or data integrity.
“Obviously, the pandemic has been horrible, but what it has allowed us to do, as investigators in the clinical research landscape, … is to change our focus somewhat and realize, first and foremost, the patient is at the center of this,” Dr. LoRusso said.
Operational accomplishments and benefits
The pandemic caused a 40% decline in accrual to studies supported by the National Cancer Institute’s (NCI) Clinical Trials Network (NCTN) from mid-March to early April, according to James H. Doroshow, MD, of NCI.
However, after modifications to administrative and regulatory procedures, accrual to NCTN trials recovered to approximately 80% of prepandemic levels, Dr. Doroshow said.
The pandemic prompted investigators to leverage tools and technology they had not previously used frequently or at all, the panelists pointed out.
Investigators discovered perforce that telehealth could be used for almost all trial-related assessments. In lieu of physical examination, patients could send pictures of rashes and use electronic devices to monitor blood sugar values and vital signs.
Digital radiographic studies were performed at sites that were most convenient for patients, downloaded, and reinterpreted at the study institution. Visiting nurses and neighborhood laboratories enabled less-frequent in-person visits for assessments.
These adjustments have been particularly important for geographically and/or socioeconomically disadvantaged patients, the panelists said.
Overall, there was agreement among the panelists that shared values and trust among regulatory authorities, sponsors, investigators, and clinicians were impressive in their urgency, sincerity, and patient centricity.
“This pandemic … has forced us to think differently and be nimble and creative to our approach to maintaining our overriding goals while at the same time bringing these innovative therapies forward for patients with cancer and other serious and life-threatening diseases as quickly as possible,” said panelist Kristen M. Hege, MD, of Bristol-Myers Squibb.
In fact, Dr. Hege noted, some cancer-related therapies (e.g., BTK inhibitors, JAK inhibitors, and immunomodulatory agents) were “repurposed” rapidly and tested against COVID-related complications.
Streamlining trial regulatory processes
In addition to changing ongoing trials, the pandemic has affected how new research projects are launched.
One new study that came together quickly in response to the pandemic is the NCI COVID-19 in Cancer Patients Study (NCCAPS). NCCAPS is a natural history study with biospecimens and an imaging library. It was approved in just 5 weeks and is active in 650 sites, with “gangbusters” accrual, Dr. Doroshow said.
The rapidness of NCCAPS’ design and implementation should prompt the revision of previously accepted timelines for trial activation and lead to streamlined future processes.
Another project that was launched quickly in response to the pandemic is the COVID-19 evidence accelerator, according to Paul G. Kluetz, MD, of the Food and Drug Administration.
The COVID-19 evidence accelerator integrates real-world evidence into a database to provide investigators and health systems with the ability to gather information, design rapid turnaround queries, and share results. The evidence accelerator can provide study chairs with information that may have relevance to the safety of participants in clinical trials.
Future directions and challenges
The panelists agreed that pandemic-related modifications in processes will not only accelerate trial approval and activation but should facilitate higher study accrual, increase the diversity of protocol participants, and decrease the costs associated with clinical trial conduct.
With that in mind, the NCI is planning randomized clinical trials in which “process A” is compared with “process B,” Dr. Doroshow said. The goal is to determine which modifications are most likely to make trials available to patients without compromising data integrity or patient safety.
“How much less data do you need to have an outcome that will be similar?” Dr. Doroshow asked. “How many fewer visits, how many fewer tests, how much can you save? Physicians, clinical trialists, all of us respond to data, and if you get the same outcome at a third of the cost, then everybody benefits.”
Nonetheless, we will need to be vigilant for unintended vulnerabilities from well-intended efforts, according to Dr. Kluetz. Study chairs, sponsors, and regulatory agencies will need to be attentive to whether there are important differences in scan quality or interpretation, missing data that influence trial outcomes, and so on.
Dr. Hege pointed out that differences among data sources may be less important when treatments generate large effects but may be vitally important when the relative differences among treatments are small.
On a practical level, decentralizing clinical research may negatively impact the finances of tertiary care centers, which could threaten the required infrastructure for clinical trials, a few panelists noted.
The relative balance of NCI-, industry-, and investigator-initiated trials may require adjustment so that research income is adequate to maintain the costs associated with cancer clinical trials.
Shared goals and democratization
The pandemic has required all stakeholders in clinical research to rely on relationships of trust and shared goals, said Caroline Robert, MD, PhD, of Institut Gustave Roussy in Villejuif, France.
Dr. Kluetz summarized those goals as improving trial efficiencies, decreasing patient burden, decentralizing trials, and maintaining trial integrity.
A decentralized clinical trials operational model could lead to better generalizability of study outcomes, normalization of life for patients on studies, and lower costs of trial conduct. As such, decentralization would promote democratization.
Coupled with ongoing efforts to reduce eligibility criteria in cancer trials, the pandemic has brought operational solutions that should be perpetuated and has reminded us of the interlocking and mutually supportive relationships on which clinical research success depends.
Dr. Doroshow and Dr. Kluetz disclosed no conflicts of interest. All other panelists disclosed financial relationships, including employment, with a range of companies.
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: Flaherty KT et al. AACR: COVID-19 and Cancer, Regulatory and Operational Implications of Cancer Clinical Trial Changes During COVID-19.
The pandemic has taught researchers how to decentralize trials, which should not only improve patient satisfaction but increase trial accrual by providing access to typically underserved populations, Patricia M. LoRusso, DO, of Yale University, New Haven, Conn., said at the meeting.
Dr. LoRusso was one of six panelists who participated in a forum about changes to cancer trials that were prompted by the pandemic. The forum was moderated by Keith T. Flaherty, MD, of Massachusetts General Hospital in Boston.
Dr. Flaherty asked the panelists to explain adjustments their organizations have made in response to the pandemic, discuss accomplishments, and speculate on future challenges and priorities.
Trial, administrative, and patient-care modifications
COVID-19 put some cancer trials on hold. For others, the pandemic forced sponsors and study chairs to reduce trial complexity and identify nonessential aspects of the studies, according to panelist José Baselga, MD, PhD, of AstraZeneca.
Specifically, exploratory objectives were subjugated to patient safety and a focus on the primary endpoints of each trial.
Once the critical data were identified, study chairs were asked to determine whether data could be obtained through technologies that could substitute for face-to-face contact between patients and staff – for example, patient-reported outcome tools and at-home digital monitoring.
Modifications prompted by the pandemic include the following:
- On-site auditing was suspended.
- Oral investigational agents were shipped directly to patients.
- “Remote” informed consent (telephone or video consenting) was permitted.
- Local providers could perform study-related services, with oversight by the research site.
- Minor deviations from the written protocols were allowed, provided the deviations did not affect patient care or data integrity.
“Obviously, the pandemic has been horrible, but what it has allowed us to do, as investigators in the clinical research landscape, … is to change our focus somewhat and realize, first and foremost, the patient is at the center of this,” Dr. LoRusso said.
Operational accomplishments and benefits
The pandemic caused a 40% decline in accrual to studies supported by the National Cancer Institute’s (NCI) Clinical Trials Network (NCTN) from mid-March to early April, according to James H. Doroshow, MD, of NCI.
However, after modifications to administrative and regulatory procedures, accrual to NCTN trials recovered to approximately 80% of prepandemic levels, Dr. Doroshow said.
The pandemic prompted investigators to leverage tools and technology they had not previously used frequently or at all, the panelists pointed out.
Investigators discovered perforce that telehealth could be used for almost all trial-related assessments. In lieu of physical examination, patients could send pictures of rashes and use electronic devices to monitor blood sugar values and vital signs.
Digital radiographic studies were performed at sites that were most convenient for patients, downloaded, and reinterpreted at the study institution. Visiting nurses and neighborhood laboratories enabled less-frequent in-person visits for assessments.
These adjustments have been particularly important for geographically and/or socioeconomically disadvantaged patients, the panelists said.
Overall, there was agreement among the panelists that shared values and trust among regulatory authorities, sponsors, investigators, and clinicians were impressive in their urgency, sincerity, and patient centricity.
“This pandemic … has forced us to think differently and be nimble and creative to our approach to maintaining our overriding goals while at the same time bringing these innovative therapies forward for patients with cancer and other serious and life-threatening diseases as quickly as possible,” said panelist Kristen M. Hege, MD, of Bristol-Myers Squibb.
In fact, Dr. Hege noted, some cancer-related therapies (e.g., BTK inhibitors, JAK inhibitors, and immunomodulatory agents) were “repurposed” rapidly and tested against COVID-related complications.
Streamlining trial regulatory processes
In addition to changing ongoing trials, the pandemic has affected how new research projects are launched.
One new study that came together quickly in response to the pandemic is the NCI COVID-19 in Cancer Patients Study (NCCAPS). NCCAPS is a natural history study with biospecimens and an imaging library. It was approved in just 5 weeks and is active in 650 sites, with “gangbusters” accrual, Dr. Doroshow said.
The rapidness of NCCAPS’ design and implementation should prompt the revision of previously accepted timelines for trial activation and lead to streamlined future processes.
Another project that was launched quickly in response to the pandemic is the COVID-19 evidence accelerator, according to Paul G. Kluetz, MD, of the Food and Drug Administration.
The COVID-19 evidence accelerator integrates real-world evidence into a database to provide investigators and health systems with the ability to gather information, design rapid turnaround queries, and share results. The evidence accelerator can provide study chairs with information that may have relevance to the safety of participants in clinical trials.
Future directions and challenges
The panelists agreed that pandemic-related modifications in processes will not only accelerate trial approval and activation but should facilitate higher study accrual, increase the diversity of protocol participants, and decrease the costs associated with clinical trial conduct.
With that in mind, the NCI is planning randomized clinical trials in which “process A” is compared with “process B,” Dr. Doroshow said. The goal is to determine which modifications are most likely to make trials available to patients without compromising data integrity or patient safety.
“How much less data do you need to have an outcome that will be similar?” Dr. Doroshow asked. “How many fewer visits, how many fewer tests, how much can you save? Physicians, clinical trialists, all of us respond to data, and if you get the same outcome at a third of the cost, then everybody benefits.”
Nonetheless, we will need to be vigilant for unintended vulnerabilities from well-intended efforts, according to Dr. Kluetz. Study chairs, sponsors, and regulatory agencies will need to be attentive to whether there are important differences in scan quality or interpretation, missing data that influence trial outcomes, and so on.
Dr. Hege pointed out that differences among data sources may be less important when treatments generate large effects but may be vitally important when the relative differences among treatments are small.
On a practical level, decentralizing clinical research may negatively impact the finances of tertiary care centers, which could threaten the required infrastructure for clinical trials, a few panelists noted.
The relative balance of NCI-, industry-, and investigator-initiated trials may require adjustment so that research income is adequate to maintain the costs associated with cancer clinical trials.
Shared goals and democratization
The pandemic has required all stakeholders in clinical research to rely on relationships of trust and shared goals, said Caroline Robert, MD, PhD, of Institut Gustave Roussy in Villejuif, France.
Dr. Kluetz summarized those goals as improving trial efficiencies, decreasing patient burden, decentralizing trials, and maintaining trial integrity.
A decentralized clinical trials operational model could lead to better generalizability of study outcomes, normalization of life for patients on studies, and lower costs of trial conduct. As such, decentralization would promote democratization.
Coupled with ongoing efforts to reduce eligibility criteria in cancer trials, the pandemic has brought operational solutions that should be perpetuated and has reminded us of the interlocking and mutually supportive relationships on which clinical research success depends.
Dr. Doroshow and Dr. Kluetz disclosed no conflicts of interest. All other panelists disclosed financial relationships, including employment, with a range of companies.
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: Flaherty KT et al. AACR: COVID-19 and Cancer, Regulatory and Operational Implications of Cancer Clinical Trial Changes During COVID-19.
The pandemic has taught researchers how to decentralize trials, which should not only improve patient satisfaction but increase trial accrual by providing access to typically underserved populations, Patricia M. LoRusso, DO, of Yale University, New Haven, Conn., said at the meeting.
Dr. LoRusso was one of six panelists who participated in a forum about changes to cancer trials that were prompted by the pandemic. The forum was moderated by Keith T. Flaherty, MD, of Massachusetts General Hospital in Boston.
Dr. Flaherty asked the panelists to explain adjustments their organizations have made in response to the pandemic, discuss accomplishments, and speculate on future challenges and priorities.
Trial, administrative, and patient-care modifications
COVID-19 put some cancer trials on hold. For others, the pandemic forced sponsors and study chairs to reduce trial complexity and identify nonessential aspects of the studies, according to panelist José Baselga, MD, PhD, of AstraZeneca.
Specifically, exploratory objectives were subjugated to patient safety and a focus on the primary endpoints of each trial.
Once the critical data were identified, study chairs were asked to determine whether data could be obtained through technologies that could substitute for face-to-face contact between patients and staff – for example, patient-reported outcome tools and at-home digital monitoring.
Modifications prompted by the pandemic include the following:
- On-site auditing was suspended.
- Oral investigational agents were shipped directly to patients.
- “Remote” informed consent (telephone or video consenting) was permitted.
- Local providers could perform study-related services, with oversight by the research site.
- Minor deviations from the written protocols were allowed, provided the deviations did not affect patient care or data integrity.
“Obviously, the pandemic has been horrible, but what it has allowed us to do, as investigators in the clinical research landscape, … is to change our focus somewhat and realize, first and foremost, the patient is at the center of this,” Dr. LoRusso said.
Operational accomplishments and benefits
The pandemic caused a 40% decline in accrual to studies supported by the National Cancer Institute’s (NCI) Clinical Trials Network (NCTN) from mid-March to early April, according to James H. Doroshow, MD, of NCI.
However, after modifications to administrative and regulatory procedures, accrual to NCTN trials recovered to approximately 80% of prepandemic levels, Dr. Doroshow said.
The pandemic prompted investigators to leverage tools and technology they had not previously used frequently or at all, the panelists pointed out.
Investigators discovered perforce that telehealth could be used for almost all trial-related assessments. In lieu of physical examination, patients could send pictures of rashes and use electronic devices to monitor blood sugar values and vital signs.
Digital radiographic studies were performed at sites that were most convenient for patients, downloaded, and reinterpreted at the study institution. Visiting nurses and neighborhood laboratories enabled less-frequent in-person visits for assessments.
These adjustments have been particularly important for geographically and/or socioeconomically disadvantaged patients, the panelists said.
Overall, there was agreement among the panelists that shared values and trust among regulatory authorities, sponsors, investigators, and clinicians were impressive in their urgency, sincerity, and patient centricity.
“This pandemic … has forced us to think differently and be nimble and creative to our approach to maintaining our overriding goals while at the same time bringing these innovative therapies forward for patients with cancer and other serious and life-threatening diseases as quickly as possible,” said panelist Kristen M. Hege, MD, of Bristol-Myers Squibb.
In fact, Dr. Hege noted, some cancer-related therapies (e.g., BTK inhibitors, JAK inhibitors, and immunomodulatory agents) were “repurposed” rapidly and tested against COVID-related complications.
Streamlining trial regulatory processes
In addition to changing ongoing trials, the pandemic has affected how new research projects are launched.
One new study that came together quickly in response to the pandemic is the NCI COVID-19 in Cancer Patients Study (NCCAPS). NCCAPS is a natural history study with biospecimens and an imaging library. It was approved in just 5 weeks and is active in 650 sites, with “gangbusters” accrual, Dr. Doroshow said.
The rapidness of NCCAPS’ design and implementation should prompt the revision of previously accepted timelines for trial activation and lead to streamlined future processes.
Another project that was launched quickly in response to the pandemic is the COVID-19 evidence accelerator, according to Paul G. Kluetz, MD, of the Food and Drug Administration.
The COVID-19 evidence accelerator integrates real-world evidence into a database to provide investigators and health systems with the ability to gather information, design rapid turnaround queries, and share results. The evidence accelerator can provide study chairs with information that may have relevance to the safety of participants in clinical trials.
Future directions and challenges
The panelists agreed that pandemic-related modifications in processes will not only accelerate trial approval and activation but should facilitate higher study accrual, increase the diversity of protocol participants, and decrease the costs associated with clinical trial conduct.
With that in mind, the NCI is planning randomized clinical trials in which “process A” is compared with “process B,” Dr. Doroshow said. The goal is to determine which modifications are most likely to make trials available to patients without compromising data integrity or patient safety.
“How much less data do you need to have an outcome that will be similar?” Dr. Doroshow asked. “How many fewer visits, how many fewer tests, how much can you save? Physicians, clinical trialists, all of us respond to data, and if you get the same outcome at a third of the cost, then everybody benefits.”
Nonetheless, we will need to be vigilant for unintended vulnerabilities from well-intended efforts, according to Dr. Kluetz. Study chairs, sponsors, and regulatory agencies will need to be attentive to whether there are important differences in scan quality or interpretation, missing data that influence trial outcomes, and so on.
Dr. Hege pointed out that differences among data sources may be less important when treatments generate large effects but may be vitally important when the relative differences among treatments are small.
On a practical level, decentralizing clinical research may negatively impact the finances of tertiary care centers, which could threaten the required infrastructure for clinical trials, a few panelists noted.
The relative balance of NCI-, industry-, and investigator-initiated trials may require adjustment so that research income is adequate to maintain the costs associated with cancer clinical trials.
Shared goals and democratization
The pandemic has required all stakeholders in clinical research to rely on relationships of trust and shared goals, said Caroline Robert, MD, PhD, of Institut Gustave Roussy in Villejuif, France.
Dr. Kluetz summarized those goals as improving trial efficiencies, decreasing patient burden, decentralizing trials, and maintaining trial integrity.
A decentralized clinical trials operational model could lead to better generalizability of study outcomes, normalization of life for patients on studies, and lower costs of trial conduct. As such, decentralization would promote democratization.
Coupled with ongoing efforts to reduce eligibility criteria in cancer trials, the pandemic has brought operational solutions that should be perpetuated and has reminded us of the interlocking and mutually supportive relationships on which clinical research success depends.
Dr. Doroshow and Dr. Kluetz disclosed no conflicts of interest. All other panelists disclosed financial relationships, including employment, with a range of companies.
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: Flaherty KT et al. AACR: COVID-19 and Cancer, Regulatory and Operational Implications of Cancer Clinical Trial Changes During COVID-19.
FROM AACR: COVID-19 and Cancer
Hair dye and cancer study ‘offers some reassurance’
Findings limited to White women in United States
The largest study of its kind has found no positive association between personal use of permanent hair dye and the risk for most cancers and cancer mortality.
The findings come from the Nurses’ Health Study, an ongoing prospective cohort study of more than 117,000 women who have been followed for 36 years and who did not have cancer at baseline.
The findings were published online on September 2 in the BMJ.
The results “offer some reassurance against concerns that personal use of permanent hair dyes might be associated with increased cancer risk or mortality,” write the investigators, with first author Yin Zhang, PhD, of Harvard Medical School, Boston.
The findings, which are limited to White women in the United States, indicate correlation, not causation, the authors emphasize.
Nevertheless, the researchers found an increased risk for some cancers among hair dye users, especially with greater cumulative dose (200 or more uses during the study period). The risk was increased for basal cell carcinoma, breast cancer (specifically, estrogen receptor negative [ER–], progesterone receptor negative [PR–], and hormone receptor negative [ER–, PR–]), and ovarian cancer.
A British expert not involved in the study dismissed these findings. “The reported associations are very weak, and, given the number of associations reported in this manuscript, they are very likely to be chance findings,” commented Paul Pharoah, PhD, professor of cancer epidemiology at the University of Cambridge (England).
“For the cancers where an increase in risk is reported, the results are not compelling. Even if they were real findings, the associations may not be cause-and-effect, and, even if they were causal associations, the magnitude of the effects are so small that any risk would be trivial.
“In short, none of the findings reported in this manuscript suggest that women who use hair dye are putting themselves at increased risk of cancer,” he stated.
A U.S. researcher who has previously coauthored a study suggesting an association between hair dye and breast cancer agreed that the increases in risk reported in this current study are “small.” But they are “of interest,” especially for breast and ovarian cancer, said Alexandra White, PhD, of the National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, N.C.
Hair dyes include compounds that “are not just potential carcinogens but also act as endocrine disruptors,” she said in an interview.
“In both breast and ovarian cancer, we know that hormones play an important part in the etiology ... so it’s biologically plausible that you would see [these associations in the current study],” added Dr. White, who was approached for comment.
However, she added that, even with the “modest” 20%-28% increase in the relative risk for certain breast cancers linked to a heavy cumulative dose of dyes in the current study, “there doesn’t seem to be any strong association with any cancer type.”
But she also pointed out that the most outstanding risk association was among ER–/PR– breast cancers, which are the “most aggressive and difficult to treat,” and thus the new findings are “important.”
Dr. White is the lead author of a 2019 study that received a lot of media attention because it rang an alarm bell about hair dyes and breast cancer risk.
That study concluded that ever using permanent hair dye or hair straighteners was associated with a higher risk for breast cancer than never using them and that this higher risk was especially associated with Black women. However, the study participants were from the prospective Sister Study. The participants in that study had no history of breast cancer, but they each had at least one sister who did. This family history of breast cancer may represent selection bias.
With changes in the 1980s, even safer now?
The study of hair dyes and cancer has “major public health implications” because the use of hair dye is widespread, Dr. Zhang and colleagues write in their article. They estimate that 50% to 80% of women and 10% of men aged 40 years and older in the United States and Europe use hair dye.
Permanent hair dyes “pose the greatest potential concern,” they stated, adding that these account for approximately 80% of hair dyes used in the United States and Europe and an even higher percentage in Asia.
The International Agency for Research on Cancer classifies occupational exposure to hair dyes as probably carcinogenic, but the carcinogenicity resulting from personal use of hair dyes is not classifiable – thus, there is no warning about at-home usage.
Notably, there was “a huge and very important” change in hair dye ingredients in the 1980s after the Food and Drug Administration warned about some chemicals in permanent hair dyes and the cosmetic industry altered their formulas, lead author Dr. Zhang said.
However, the researchers could not analyze use before and after the changes because not enough women reported first use of permanent hair dye after 1980 (only 1890 of 117,200 participants).
“We could expect that the current ingredients should make it safer,” Dr. Zhang said.
Study details
The researchers report that ever-users of permanent hair dyes had no significant increases in risk for solid cancers (n = 20,805; hazard ratio, 0.98, 95% confidence interval, 0.96-1.01) or hematopoietic cancers overall (n = 1,807; HR, 1.00; 95% CI, 0.91-1.10) compared with nonusers.
Additionally, ever-users did not have an increased risk for most specific cancers or cancer-related death (n = 4,860; HR, 0.96; 95% CI, 0.91-1.02).
As noted above, there were some exceptions.
Basal cell carcinoma risk was slightly increased for ever-users (n = 22,560; HR, 1.05; 95% CI, 1.02-1.08). Cumulative dose (a calculation of duration and frequency) was positively associated with risk for ER– breast cancer, PR– breast cancer, ER–/PR– breast cancer, and ovarian cancer, with risk rising in accordance with the total amount of dye.
Notably, at a cumulative dose of ≥200 uses, there was a 20% increase in the relative risk for ER- breast cancer (n = 1521; HR, 1.20; 95% CI, 1.02-1.41; P value for trend, .03). At the same cumulative dose, there was a 28% increase in the relative risk for ER-/PR- breast cancer (n = 1287; HR, 1.28, 95% CI, 1.08-1.52; P value for trend, .006).
In addition, an increased risk for Hodgkin lymphoma was observed, but only for women with naturally dark hair (the calculation was based on 70 women, 24 of whom had dark hair).
In a press statement, senior author Eva Schernhammer, PhD, of Harvard and the Medical University of Vienna, said the results “justify further prospective validation.”
She also explained that there are many variables to consider in this research, including different populations and countries, different susceptibility genotypes, different exposure settings (personal use vs. occupational exposure), and different colors of the permanent hair dyes used (dark dyes vs. light dyes).
Geographic location is a particularly important variable, suggested the study authors.
They pointed out that Europe, but not the United States, banned some individual hair dye ingredients that were considered carcinogenic during both the 1980s and 2000s. One country has even tighter oversight: “The most restrictive regulation of hair dyes exists in Japan, where cosmetic products are considered equivalent to drugs.”
The study was funded by the Centers for Disease Control and Prevention and the National Institute for Occupational Safety and Health. The study authors and Dr. White have disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
Findings limited to White women in United States
Findings limited to White women in United States
The largest study of its kind has found no positive association between personal use of permanent hair dye and the risk for most cancers and cancer mortality.
The findings come from the Nurses’ Health Study, an ongoing prospective cohort study of more than 117,000 women who have been followed for 36 years and who did not have cancer at baseline.
The findings were published online on September 2 in the BMJ.
The results “offer some reassurance against concerns that personal use of permanent hair dyes might be associated with increased cancer risk or mortality,” write the investigators, with first author Yin Zhang, PhD, of Harvard Medical School, Boston.
The findings, which are limited to White women in the United States, indicate correlation, not causation, the authors emphasize.
Nevertheless, the researchers found an increased risk for some cancers among hair dye users, especially with greater cumulative dose (200 or more uses during the study period). The risk was increased for basal cell carcinoma, breast cancer (specifically, estrogen receptor negative [ER–], progesterone receptor negative [PR–], and hormone receptor negative [ER–, PR–]), and ovarian cancer.
A British expert not involved in the study dismissed these findings. “The reported associations are very weak, and, given the number of associations reported in this manuscript, they are very likely to be chance findings,” commented Paul Pharoah, PhD, professor of cancer epidemiology at the University of Cambridge (England).
“For the cancers where an increase in risk is reported, the results are not compelling. Even if they were real findings, the associations may not be cause-and-effect, and, even if they were causal associations, the magnitude of the effects are so small that any risk would be trivial.
“In short, none of the findings reported in this manuscript suggest that women who use hair dye are putting themselves at increased risk of cancer,” he stated.
A U.S. researcher who has previously coauthored a study suggesting an association between hair dye and breast cancer agreed that the increases in risk reported in this current study are “small.” But they are “of interest,” especially for breast and ovarian cancer, said Alexandra White, PhD, of the National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, N.C.
Hair dyes include compounds that “are not just potential carcinogens but also act as endocrine disruptors,” she said in an interview.
“In both breast and ovarian cancer, we know that hormones play an important part in the etiology ... so it’s biologically plausible that you would see [these associations in the current study],” added Dr. White, who was approached for comment.
However, she added that, even with the “modest” 20%-28% increase in the relative risk for certain breast cancers linked to a heavy cumulative dose of dyes in the current study, “there doesn’t seem to be any strong association with any cancer type.”
But she also pointed out that the most outstanding risk association was among ER–/PR– breast cancers, which are the “most aggressive and difficult to treat,” and thus the new findings are “important.”
Dr. White is the lead author of a 2019 study that received a lot of media attention because it rang an alarm bell about hair dyes and breast cancer risk.
That study concluded that ever using permanent hair dye or hair straighteners was associated with a higher risk for breast cancer than never using them and that this higher risk was especially associated with Black women. However, the study participants were from the prospective Sister Study. The participants in that study had no history of breast cancer, but they each had at least one sister who did. This family history of breast cancer may represent selection bias.
With changes in the 1980s, even safer now?
The study of hair dyes and cancer has “major public health implications” because the use of hair dye is widespread, Dr. Zhang and colleagues write in their article. They estimate that 50% to 80% of women and 10% of men aged 40 years and older in the United States and Europe use hair dye.
Permanent hair dyes “pose the greatest potential concern,” they stated, adding that these account for approximately 80% of hair dyes used in the United States and Europe and an even higher percentage in Asia.
The International Agency for Research on Cancer classifies occupational exposure to hair dyes as probably carcinogenic, but the carcinogenicity resulting from personal use of hair dyes is not classifiable – thus, there is no warning about at-home usage.
Notably, there was “a huge and very important” change in hair dye ingredients in the 1980s after the Food and Drug Administration warned about some chemicals in permanent hair dyes and the cosmetic industry altered their formulas, lead author Dr. Zhang said.
However, the researchers could not analyze use before and after the changes because not enough women reported first use of permanent hair dye after 1980 (only 1890 of 117,200 participants).
“We could expect that the current ingredients should make it safer,” Dr. Zhang said.
Study details
The researchers report that ever-users of permanent hair dyes had no significant increases in risk for solid cancers (n = 20,805; hazard ratio, 0.98, 95% confidence interval, 0.96-1.01) or hematopoietic cancers overall (n = 1,807; HR, 1.00; 95% CI, 0.91-1.10) compared with nonusers.
Additionally, ever-users did not have an increased risk for most specific cancers or cancer-related death (n = 4,860; HR, 0.96; 95% CI, 0.91-1.02).
As noted above, there were some exceptions.
Basal cell carcinoma risk was slightly increased for ever-users (n = 22,560; HR, 1.05; 95% CI, 1.02-1.08). Cumulative dose (a calculation of duration and frequency) was positively associated with risk for ER– breast cancer, PR– breast cancer, ER–/PR– breast cancer, and ovarian cancer, with risk rising in accordance with the total amount of dye.
Notably, at a cumulative dose of ≥200 uses, there was a 20% increase in the relative risk for ER- breast cancer (n = 1521; HR, 1.20; 95% CI, 1.02-1.41; P value for trend, .03). At the same cumulative dose, there was a 28% increase in the relative risk for ER-/PR- breast cancer (n = 1287; HR, 1.28, 95% CI, 1.08-1.52; P value for trend, .006).
In addition, an increased risk for Hodgkin lymphoma was observed, but only for women with naturally dark hair (the calculation was based on 70 women, 24 of whom had dark hair).
In a press statement, senior author Eva Schernhammer, PhD, of Harvard and the Medical University of Vienna, said the results “justify further prospective validation.”
She also explained that there are many variables to consider in this research, including different populations and countries, different susceptibility genotypes, different exposure settings (personal use vs. occupational exposure), and different colors of the permanent hair dyes used (dark dyes vs. light dyes).
Geographic location is a particularly important variable, suggested the study authors.
They pointed out that Europe, but not the United States, banned some individual hair dye ingredients that were considered carcinogenic during both the 1980s and 2000s. One country has even tighter oversight: “The most restrictive regulation of hair dyes exists in Japan, where cosmetic products are considered equivalent to drugs.”
The study was funded by the Centers for Disease Control and Prevention and the National Institute for Occupational Safety and Health. The study authors and Dr. White have disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
The largest study of its kind has found no positive association between personal use of permanent hair dye and the risk for most cancers and cancer mortality.
The findings come from the Nurses’ Health Study, an ongoing prospective cohort study of more than 117,000 women who have been followed for 36 years and who did not have cancer at baseline.
The findings were published online on September 2 in the BMJ.
The results “offer some reassurance against concerns that personal use of permanent hair dyes might be associated with increased cancer risk or mortality,” write the investigators, with first author Yin Zhang, PhD, of Harvard Medical School, Boston.
The findings, which are limited to White women in the United States, indicate correlation, not causation, the authors emphasize.
Nevertheless, the researchers found an increased risk for some cancers among hair dye users, especially with greater cumulative dose (200 or more uses during the study period). The risk was increased for basal cell carcinoma, breast cancer (specifically, estrogen receptor negative [ER–], progesterone receptor negative [PR–], and hormone receptor negative [ER–, PR–]), and ovarian cancer.
A British expert not involved in the study dismissed these findings. “The reported associations are very weak, and, given the number of associations reported in this manuscript, they are very likely to be chance findings,” commented Paul Pharoah, PhD, professor of cancer epidemiology at the University of Cambridge (England).
“For the cancers where an increase in risk is reported, the results are not compelling. Even if they were real findings, the associations may not be cause-and-effect, and, even if they were causal associations, the magnitude of the effects are so small that any risk would be trivial.
“In short, none of the findings reported in this manuscript suggest that women who use hair dye are putting themselves at increased risk of cancer,” he stated.
A U.S. researcher who has previously coauthored a study suggesting an association between hair dye and breast cancer agreed that the increases in risk reported in this current study are “small.” But they are “of interest,” especially for breast and ovarian cancer, said Alexandra White, PhD, of the National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, N.C.
Hair dyes include compounds that “are not just potential carcinogens but also act as endocrine disruptors,” she said in an interview.
“In both breast and ovarian cancer, we know that hormones play an important part in the etiology ... so it’s biologically plausible that you would see [these associations in the current study],” added Dr. White, who was approached for comment.
However, she added that, even with the “modest” 20%-28% increase in the relative risk for certain breast cancers linked to a heavy cumulative dose of dyes in the current study, “there doesn’t seem to be any strong association with any cancer type.”
But she also pointed out that the most outstanding risk association was among ER–/PR– breast cancers, which are the “most aggressive and difficult to treat,” and thus the new findings are “important.”
Dr. White is the lead author of a 2019 study that received a lot of media attention because it rang an alarm bell about hair dyes and breast cancer risk.
That study concluded that ever using permanent hair dye or hair straighteners was associated with a higher risk for breast cancer than never using them and that this higher risk was especially associated with Black women. However, the study participants were from the prospective Sister Study. The participants in that study had no history of breast cancer, but they each had at least one sister who did. This family history of breast cancer may represent selection bias.
With changes in the 1980s, even safer now?
The study of hair dyes and cancer has “major public health implications” because the use of hair dye is widespread, Dr. Zhang and colleagues write in their article. They estimate that 50% to 80% of women and 10% of men aged 40 years and older in the United States and Europe use hair dye.
Permanent hair dyes “pose the greatest potential concern,” they stated, adding that these account for approximately 80% of hair dyes used in the United States and Europe and an even higher percentage in Asia.
The International Agency for Research on Cancer classifies occupational exposure to hair dyes as probably carcinogenic, but the carcinogenicity resulting from personal use of hair dyes is not classifiable – thus, there is no warning about at-home usage.
Notably, there was “a huge and very important” change in hair dye ingredients in the 1980s after the Food and Drug Administration warned about some chemicals in permanent hair dyes and the cosmetic industry altered their formulas, lead author Dr. Zhang said.
However, the researchers could not analyze use before and after the changes because not enough women reported first use of permanent hair dye after 1980 (only 1890 of 117,200 participants).
“We could expect that the current ingredients should make it safer,” Dr. Zhang said.
Study details
The researchers report that ever-users of permanent hair dyes had no significant increases in risk for solid cancers (n = 20,805; hazard ratio, 0.98, 95% confidence interval, 0.96-1.01) or hematopoietic cancers overall (n = 1,807; HR, 1.00; 95% CI, 0.91-1.10) compared with nonusers.
Additionally, ever-users did not have an increased risk for most specific cancers or cancer-related death (n = 4,860; HR, 0.96; 95% CI, 0.91-1.02).
As noted above, there were some exceptions.
Basal cell carcinoma risk was slightly increased for ever-users (n = 22,560; HR, 1.05; 95% CI, 1.02-1.08). Cumulative dose (a calculation of duration and frequency) was positively associated with risk for ER– breast cancer, PR– breast cancer, ER–/PR– breast cancer, and ovarian cancer, with risk rising in accordance with the total amount of dye.
Notably, at a cumulative dose of ≥200 uses, there was a 20% increase in the relative risk for ER- breast cancer (n = 1521; HR, 1.20; 95% CI, 1.02-1.41; P value for trend, .03). At the same cumulative dose, there was a 28% increase in the relative risk for ER-/PR- breast cancer (n = 1287; HR, 1.28, 95% CI, 1.08-1.52; P value for trend, .006).
In addition, an increased risk for Hodgkin lymphoma was observed, but only for women with naturally dark hair (the calculation was based on 70 women, 24 of whom had dark hair).
In a press statement, senior author Eva Schernhammer, PhD, of Harvard and the Medical University of Vienna, said the results “justify further prospective validation.”
She also explained that there are many variables to consider in this research, including different populations and countries, different susceptibility genotypes, different exposure settings (personal use vs. occupational exposure), and different colors of the permanent hair dyes used (dark dyes vs. light dyes).
Geographic location is a particularly important variable, suggested the study authors.
They pointed out that Europe, but not the United States, banned some individual hair dye ingredients that were considered carcinogenic during both the 1980s and 2000s. One country has even tighter oversight: “The most restrictive regulation of hair dyes exists in Japan, where cosmetic products are considered equivalent to drugs.”
The study was funded by the Centers for Disease Control and Prevention and the National Institute for Occupational Safety and Health. The study authors and Dr. White have disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
VTE, sepsis risk increased among COVID-19 patients with cancer
, according to data from a registry study.
Researchers analyzed data on 5,556 patients with COVID-19 who had an inpatient or emergency encounter at Mount Sinai Health System (MSHS) in New York between March 1 and May 27, 2020. Patients were included in an anonymous MSHS COVID-19 registry.
There were 421 patients who had cancer: 96 with a hematologic malignancy and 325 with solid tumors.
After adjustment for age, gender, and number of comorbidities, the odds ratios for acute VTE and sepsis for patients with cancer (versus those without cancer) were 1.77 and 1.34, respectively. The adjusted odds ratio for mortality in cancer patients was 1.02.
The results remained “relatively consistent” after stratification by solid and nonsolid cancer types, with no significant difference in outcomes between those two groups, and results remained consistent in a propensity-matched model, according to Naomi Alpert, a biostatistician at Icahn School of Medicine at Mount Sinai, New York.
Ms. Alpert reported these findings at the AACR virtual meeting: COVID-19 and Cancer.
She noted that the cancer patients were older than the noncancer patients (mean age, 69.2 years vs. 63.8 years), and cancer patients were more likely to have two or more comorbid conditions (48.2% vs. 30.4%). Cancer patients also had significantly lower hemoglobin levels and red blood cell, platelet, and white blood cell counts (P < .01 for all).
“Low white blood cell count may be one of the reasons for higher risk of sepsis in cancer patients, as it may lead to a higher risk of infection,” Ms. Alpert said. “However, it’s not clear what role cancer therapies play in the risks of COVID-19 morbidity and mortality, so there is still quite a bit to learn.”
In fact, the findings are limited by a lack of information about cancer treatment, as the registry was not designed for that purpose, she noted.
Another study limitation is the short follow-up of a month or less in most patients, due, in part, to the novelty of COVID-19, but also to the lack of information on patients after they left the hospital.
“However, we had a very large sample size, with more than 400 cancer patients included, and, to our knowledge, this is the largest analysis of its kind to be done so far,” Ms. Alpert said. “In the future, it’s going to be very important to assess the effect of cancer therapies on COVID-19 complications and to see if prior therapies had any effect on outcomes.”
Longer follow-up would also be helpful for assessing the chronic effects of COVID-19 on cancer patients over time, she said. “It would be important to see whether some of these elevated risks of venous thromboembolism and sepsis are associated with longer-term mortality risks than what we were able to measure here,” she added.
Asked about the discrepancy between mortality in this study and those of larger registries, such as the COVID-19 and Cancer Consortium (CCC19) and TERAVOLT, Ms. Alpert noted that the current study included only patients who required hospitalization or emergency care.
“Our mortality rate was actually a bit higher than what was reported in some of the other studies,” she said. “We had about a 30% mortality rate in the cancer patients and about 25% for the noncancer patients, so ... we’re sort of looking at a subset of patients who we know are the sickest of the sick, which may explain some of the higher mortality that we’re seeing.”
Ms. Alpert reported having no disclosures.
SOURCE: Alpert N et al. AACR COVID-19 and Cancer, Abstract S12-02.
, according to data from a registry study.
Researchers analyzed data on 5,556 patients with COVID-19 who had an inpatient or emergency encounter at Mount Sinai Health System (MSHS) in New York between March 1 and May 27, 2020. Patients were included in an anonymous MSHS COVID-19 registry.
There were 421 patients who had cancer: 96 with a hematologic malignancy and 325 with solid tumors.
After adjustment for age, gender, and number of comorbidities, the odds ratios for acute VTE and sepsis for patients with cancer (versus those without cancer) were 1.77 and 1.34, respectively. The adjusted odds ratio for mortality in cancer patients was 1.02.
The results remained “relatively consistent” after stratification by solid and nonsolid cancer types, with no significant difference in outcomes between those two groups, and results remained consistent in a propensity-matched model, according to Naomi Alpert, a biostatistician at Icahn School of Medicine at Mount Sinai, New York.
Ms. Alpert reported these findings at the AACR virtual meeting: COVID-19 and Cancer.
She noted that the cancer patients were older than the noncancer patients (mean age, 69.2 years vs. 63.8 years), and cancer patients were more likely to have two or more comorbid conditions (48.2% vs. 30.4%). Cancer patients also had significantly lower hemoglobin levels and red blood cell, platelet, and white blood cell counts (P < .01 for all).
“Low white blood cell count may be one of the reasons for higher risk of sepsis in cancer patients, as it may lead to a higher risk of infection,” Ms. Alpert said. “However, it’s not clear what role cancer therapies play in the risks of COVID-19 morbidity and mortality, so there is still quite a bit to learn.”
In fact, the findings are limited by a lack of information about cancer treatment, as the registry was not designed for that purpose, she noted.
Another study limitation is the short follow-up of a month or less in most patients, due, in part, to the novelty of COVID-19, but also to the lack of information on patients after they left the hospital.
“However, we had a very large sample size, with more than 400 cancer patients included, and, to our knowledge, this is the largest analysis of its kind to be done so far,” Ms. Alpert said. “In the future, it’s going to be very important to assess the effect of cancer therapies on COVID-19 complications and to see if prior therapies had any effect on outcomes.”
Longer follow-up would also be helpful for assessing the chronic effects of COVID-19 on cancer patients over time, she said. “It would be important to see whether some of these elevated risks of venous thromboembolism and sepsis are associated with longer-term mortality risks than what we were able to measure here,” she added.
Asked about the discrepancy between mortality in this study and those of larger registries, such as the COVID-19 and Cancer Consortium (CCC19) and TERAVOLT, Ms. Alpert noted that the current study included only patients who required hospitalization or emergency care.
“Our mortality rate was actually a bit higher than what was reported in some of the other studies,” she said. “We had about a 30% mortality rate in the cancer patients and about 25% for the noncancer patients, so ... we’re sort of looking at a subset of patients who we know are the sickest of the sick, which may explain some of the higher mortality that we’re seeing.”
Ms. Alpert reported having no disclosures.
SOURCE: Alpert N et al. AACR COVID-19 and Cancer, Abstract S12-02.
, according to data from a registry study.
Researchers analyzed data on 5,556 patients with COVID-19 who had an inpatient or emergency encounter at Mount Sinai Health System (MSHS) in New York between March 1 and May 27, 2020. Patients were included in an anonymous MSHS COVID-19 registry.
There were 421 patients who had cancer: 96 with a hematologic malignancy and 325 with solid tumors.
After adjustment for age, gender, and number of comorbidities, the odds ratios for acute VTE and sepsis for patients with cancer (versus those without cancer) were 1.77 and 1.34, respectively. The adjusted odds ratio for mortality in cancer patients was 1.02.
The results remained “relatively consistent” after stratification by solid and nonsolid cancer types, with no significant difference in outcomes between those two groups, and results remained consistent in a propensity-matched model, according to Naomi Alpert, a biostatistician at Icahn School of Medicine at Mount Sinai, New York.
Ms. Alpert reported these findings at the AACR virtual meeting: COVID-19 and Cancer.
She noted that the cancer patients were older than the noncancer patients (mean age, 69.2 years vs. 63.8 years), and cancer patients were more likely to have two or more comorbid conditions (48.2% vs. 30.4%). Cancer patients also had significantly lower hemoglobin levels and red blood cell, platelet, and white blood cell counts (P < .01 for all).
“Low white blood cell count may be one of the reasons for higher risk of sepsis in cancer patients, as it may lead to a higher risk of infection,” Ms. Alpert said. “However, it’s not clear what role cancer therapies play in the risks of COVID-19 morbidity and mortality, so there is still quite a bit to learn.”
In fact, the findings are limited by a lack of information about cancer treatment, as the registry was not designed for that purpose, she noted.
Another study limitation is the short follow-up of a month or less in most patients, due, in part, to the novelty of COVID-19, but also to the lack of information on patients after they left the hospital.
“However, we had a very large sample size, with more than 400 cancer patients included, and, to our knowledge, this is the largest analysis of its kind to be done so far,” Ms. Alpert said. “In the future, it’s going to be very important to assess the effect of cancer therapies on COVID-19 complications and to see if prior therapies had any effect on outcomes.”
Longer follow-up would also be helpful for assessing the chronic effects of COVID-19 on cancer patients over time, she said. “It would be important to see whether some of these elevated risks of venous thromboembolism and sepsis are associated with longer-term mortality risks than what we were able to measure here,” she added.
Asked about the discrepancy between mortality in this study and those of larger registries, such as the COVID-19 and Cancer Consortium (CCC19) and TERAVOLT, Ms. Alpert noted that the current study included only patients who required hospitalization or emergency care.
“Our mortality rate was actually a bit higher than what was reported in some of the other studies,” she said. “We had about a 30% mortality rate in the cancer patients and about 25% for the noncancer patients, so ... we’re sort of looking at a subset of patients who we know are the sickest of the sick, which may explain some of the higher mortality that we’re seeing.”
Ms. Alpert reported having no disclosures.
SOURCE: Alpert N et al. AACR COVID-19 and Cancer, Abstract S12-02.
FROM AACR: COVID-19 AND CANCER
Aspirin may accelerate cancer progression in older adults
Aspirin may accelerate the progression of advanced cancers and lead to an earlier death as a result, new data from the ASPREE study suggest.
The results showed that patients 65 years and older who started taking daily low-dose aspirin had a 19% higher chance of being diagnosed with metastatic cancer, a 22% higher chance of being diagnosed with a stage 4 tumor, and a 31% increased risk of death from stage 4 cancer, when compared with patients who took a placebo.
John J. McNeil, MBBS, PhD, of Monash University in Melbourne, Australia, and colleagues detailed these findings in the Journal of the National Cancer Institute.
“If confirmed, the clinical implications of these findings could be important for the use of aspirin in an older population,” the authors wrote.
When results of the ASPREE study were first reported in 2018, they “raised important concerns,” Ernest Hawk, MD, and Karen Colbert Maresso wrote in an editorial related to the current publication.
“Unlike ARRIVE, ASCEND, and nearly all prior primary prevention CVD [cardiovascular disease] trials of aspirin, ASPREE surprisingly demonstrated increased all-cause mortality in the aspirin group, which appeared to be driven largely by an increase in cancer-related deaths,” wrote the editorialists, who are both from the University of Texas MD Anderson Cancer Center in Houston.
Even though the ASPREE investigators have now taken a deeper dive into their data, the findings “neither explain nor alleviate the concerns raised by the initial ASPREE report,” the editorialists noted.
ASPREE design and results
ASPREE is a multicenter, double-blind trial of 19,114 older adults living in Australia (n = 16,703) or the United States (n = 2,411). Most patients were 70 years or older at baseline. However, the U.S. group also included patients 65 years and older who were racial/ethnic minorities (n = 564).
Patients were randomized to receive 100 mg of enteric-coated aspirin daily (n = 9,525) or matching placebo (n = 9,589) from March 2010 through December 2014.
At inclusion, all participants were free from cardiovascular disease, dementia, or physical disability. A previous history of cancer was not used to exclude participants, and 19.1% of patients had cancer at randomization. Most patients (89%) had not used aspirin regularly before entering the trial.
At a median follow-up of 4.7 years, there were 981 incident cancer events in the aspirin-treated group and 952 in the placebo-treated group, with an overall incident cancer rate of 10.1%.
Of the 1,933 patients with newly diagnosed cancer, 65.7% had a localized cancer, 18.8% had a new metastatic cancer, 5.8% had metastatic disease from an existing cancer, and 9.7% had a new hematologic or lymphatic cancer.
A quarter of cancer patients (n = 495) died as a result of their malignancy, with 52 dying from a cancer they already had at randomization.
Aspirin was not associated with the risk of first incident cancer diagnosis or incident localized cancer diagnosis. The hazard ratios were 1.04 for all incident cancers (95% confidence interval, 0.95-1.14) and 0.99 for incident localized cancers (95% CI, 0.89-1.11).
However, aspirin was associated with an increased risk of metastatic cancer and cancer presenting at stage 4. The HR for metastatic cancer was 1.19 (95% CI, 1.00-1.43), and the HR for newly diagnosed stage 4 cancer was 1.22 (95% CI, 1.02-1.45).
Furthermore, “an increased progression to death was observed amongst those randomized to aspirin, regardless of whether the initial cancer presentation had been localized or metastatic,” the investigators wrote.
The HRs for death were 1.35 for all cancers (95% CI, 1.13-1.61), 1.47 for localized cancers (95% CI, 1.07-2.02), and 1.30 for metastatic cancers (95% CI, 1.03-1.63).
“Deaths were particularly high among those on aspirin who were diagnosed with advanced solid cancers,” study author Andrew Chan, MD, of Massachusetts General Hospital in Boston, said in a press statement.
Indeed, HRs for death in patients with solid tumors presenting at stage 3 and 4 were a respective 2.11 (95% CI, 1.03-4.33) and 1.31 (95% CI, 1.04-1.64). This suggests a possible adverse effect of aspirin on the growth of cancers once they have already developed in older adults, Dr. Chan said.
Where does that leave aspirin for cancer prevention?
“Although these results suggest that we should be cautious about starting aspirin therapy in otherwise healthy older adults, this does not mean that individuals who are already taking aspirin – particularly if they began taking it at a younger age – should stop their aspirin regimen,” Dr. Chan said.
There are decades of data supporting the use of daily aspirin to prevent multiple cancer types, particularly colorectal cancer, in individuals under the age of 70 years. In a recent meta-analysis, for example, regular aspirin use was linked to a 27% reduced risk for colorectal cancer, a 33% reduced risk for squamous cell esophageal cancer, a 39% decreased risk for adenocarcinoma of the esophagus and gastric cardia, a 36% decreased risk for stomach cancer, a 38% decreased risk for hepatobiliary tract cancer, and a 22% decreased risk for pancreatic cancer.
While these figures are mostly based on observational and case-control studies, it “reaffirms the fact that, overall, when you look at all of the ages, that there is still a benefit of aspirin for cancer,” John Cuzick, PhD, of Queen Mary University of London (England), said in an interview.
In fact, the meta-analysis goes as far as suggesting that perhaps the dose of aspirin being used is too low, with the authors noting that there was a 35% risk reduction in colorectal cancer with a dose of 325 mg daily. That’s a new finding, Dr. Cuzick said.
He noted that the ASPREE study largely consists of patients 70 years of age or older, and the authors “draw some conclusions which we can’t ignore about potential safety.”
One of the safety concerns is the increased risk for gastrointestinal bleeding, which is why Dr. Cuzick and colleagues previously recommended caution in the use of aspirin to prevent cancer in elderly patients. The group published a study in 2015 that suggested a benefit of taking aspirin daily for 5-10 years in patients aged 50-65 years, but the risk/benefit ratio was unclear for patients 70 years and older.
The ASPREE data now add to those uncertainties and suggest “there may be some side effects that we do not understand,” Dr. Cuzick said.
“I’m still optimistic that aspirin is going to be important for cancer prevention, but probably focusing on ages 50-70,” he added. “[The ASPREE data] reinforce the caution that we have to take in terms of trying to understand what the side effects are and what’s going on at these older ages.”
Dr. Cuzick is currently leading the AsCaP Project, an international effort to better understand why aspirin might work in preventing some cancer types but not others. AsCaP is supported by Cancer Research UK and also includes Dr. Chan among the researchers attempting to find out which patients may benefit the most from aspirin and which may be at greater risk of adverse effects.
The ASPREE trial was funded by grants from the National Institute on Aging, the National Cancer Institute, the National Health and Medical Research Council of Australia, Monash University, and the Victorian Cancer Agency. Several ASPREE investigators disclosed financial relationships with Bayer Pharma. The editorialists had no conflicts of interest. Dr. Cuzick has been an advisory board member for Bayer in the past.
SOURCE: McNeil J et al. J Natl Cancer Inst. 2020 Aug 11. doi: 10.1093/jnci/djaa114.
Aspirin may accelerate the progression of advanced cancers and lead to an earlier death as a result, new data from the ASPREE study suggest.
The results showed that patients 65 years and older who started taking daily low-dose aspirin had a 19% higher chance of being diagnosed with metastatic cancer, a 22% higher chance of being diagnosed with a stage 4 tumor, and a 31% increased risk of death from stage 4 cancer, when compared with patients who took a placebo.
John J. McNeil, MBBS, PhD, of Monash University in Melbourne, Australia, and colleagues detailed these findings in the Journal of the National Cancer Institute.
“If confirmed, the clinical implications of these findings could be important for the use of aspirin in an older population,” the authors wrote.
When results of the ASPREE study were first reported in 2018, they “raised important concerns,” Ernest Hawk, MD, and Karen Colbert Maresso wrote in an editorial related to the current publication.
“Unlike ARRIVE, ASCEND, and nearly all prior primary prevention CVD [cardiovascular disease] trials of aspirin, ASPREE surprisingly demonstrated increased all-cause mortality in the aspirin group, which appeared to be driven largely by an increase in cancer-related deaths,” wrote the editorialists, who are both from the University of Texas MD Anderson Cancer Center in Houston.
Even though the ASPREE investigators have now taken a deeper dive into their data, the findings “neither explain nor alleviate the concerns raised by the initial ASPREE report,” the editorialists noted.
ASPREE design and results
ASPREE is a multicenter, double-blind trial of 19,114 older adults living in Australia (n = 16,703) or the United States (n = 2,411). Most patients were 70 years or older at baseline. However, the U.S. group also included patients 65 years and older who were racial/ethnic minorities (n = 564).
Patients were randomized to receive 100 mg of enteric-coated aspirin daily (n = 9,525) or matching placebo (n = 9,589) from March 2010 through December 2014.
At inclusion, all participants were free from cardiovascular disease, dementia, or physical disability. A previous history of cancer was not used to exclude participants, and 19.1% of patients had cancer at randomization. Most patients (89%) had not used aspirin regularly before entering the trial.
At a median follow-up of 4.7 years, there were 981 incident cancer events in the aspirin-treated group and 952 in the placebo-treated group, with an overall incident cancer rate of 10.1%.
Of the 1,933 patients with newly diagnosed cancer, 65.7% had a localized cancer, 18.8% had a new metastatic cancer, 5.8% had metastatic disease from an existing cancer, and 9.7% had a new hematologic or lymphatic cancer.
A quarter of cancer patients (n = 495) died as a result of their malignancy, with 52 dying from a cancer they already had at randomization.
Aspirin was not associated with the risk of first incident cancer diagnosis or incident localized cancer diagnosis. The hazard ratios were 1.04 for all incident cancers (95% confidence interval, 0.95-1.14) and 0.99 for incident localized cancers (95% CI, 0.89-1.11).
However, aspirin was associated with an increased risk of metastatic cancer and cancer presenting at stage 4. The HR for metastatic cancer was 1.19 (95% CI, 1.00-1.43), and the HR for newly diagnosed stage 4 cancer was 1.22 (95% CI, 1.02-1.45).
Furthermore, “an increased progression to death was observed amongst those randomized to aspirin, regardless of whether the initial cancer presentation had been localized or metastatic,” the investigators wrote.
The HRs for death were 1.35 for all cancers (95% CI, 1.13-1.61), 1.47 for localized cancers (95% CI, 1.07-2.02), and 1.30 for metastatic cancers (95% CI, 1.03-1.63).
“Deaths were particularly high among those on aspirin who were diagnosed with advanced solid cancers,” study author Andrew Chan, MD, of Massachusetts General Hospital in Boston, said in a press statement.
Indeed, HRs for death in patients with solid tumors presenting at stage 3 and 4 were a respective 2.11 (95% CI, 1.03-4.33) and 1.31 (95% CI, 1.04-1.64). This suggests a possible adverse effect of aspirin on the growth of cancers once they have already developed in older adults, Dr. Chan said.
Where does that leave aspirin for cancer prevention?
“Although these results suggest that we should be cautious about starting aspirin therapy in otherwise healthy older adults, this does not mean that individuals who are already taking aspirin – particularly if they began taking it at a younger age – should stop their aspirin regimen,” Dr. Chan said.
There are decades of data supporting the use of daily aspirin to prevent multiple cancer types, particularly colorectal cancer, in individuals under the age of 70 years. In a recent meta-analysis, for example, regular aspirin use was linked to a 27% reduced risk for colorectal cancer, a 33% reduced risk for squamous cell esophageal cancer, a 39% decreased risk for adenocarcinoma of the esophagus and gastric cardia, a 36% decreased risk for stomach cancer, a 38% decreased risk for hepatobiliary tract cancer, and a 22% decreased risk for pancreatic cancer.
While these figures are mostly based on observational and case-control studies, it “reaffirms the fact that, overall, when you look at all of the ages, that there is still a benefit of aspirin for cancer,” John Cuzick, PhD, of Queen Mary University of London (England), said in an interview.
In fact, the meta-analysis goes as far as suggesting that perhaps the dose of aspirin being used is too low, with the authors noting that there was a 35% risk reduction in colorectal cancer with a dose of 325 mg daily. That’s a new finding, Dr. Cuzick said.
He noted that the ASPREE study largely consists of patients 70 years of age or older, and the authors “draw some conclusions which we can’t ignore about potential safety.”
One of the safety concerns is the increased risk for gastrointestinal bleeding, which is why Dr. Cuzick and colleagues previously recommended caution in the use of aspirin to prevent cancer in elderly patients. The group published a study in 2015 that suggested a benefit of taking aspirin daily for 5-10 years in patients aged 50-65 years, but the risk/benefit ratio was unclear for patients 70 years and older.
The ASPREE data now add to those uncertainties and suggest “there may be some side effects that we do not understand,” Dr. Cuzick said.
“I’m still optimistic that aspirin is going to be important for cancer prevention, but probably focusing on ages 50-70,” he added. “[The ASPREE data] reinforce the caution that we have to take in terms of trying to understand what the side effects are and what’s going on at these older ages.”
Dr. Cuzick is currently leading the AsCaP Project, an international effort to better understand why aspirin might work in preventing some cancer types but not others. AsCaP is supported by Cancer Research UK and also includes Dr. Chan among the researchers attempting to find out which patients may benefit the most from aspirin and which may be at greater risk of adverse effects.
The ASPREE trial was funded by grants from the National Institute on Aging, the National Cancer Institute, the National Health and Medical Research Council of Australia, Monash University, and the Victorian Cancer Agency. Several ASPREE investigators disclosed financial relationships with Bayer Pharma. The editorialists had no conflicts of interest. Dr. Cuzick has been an advisory board member for Bayer in the past.
SOURCE: McNeil J et al. J Natl Cancer Inst. 2020 Aug 11. doi: 10.1093/jnci/djaa114.
Aspirin may accelerate the progression of advanced cancers and lead to an earlier death as a result, new data from the ASPREE study suggest.
The results showed that patients 65 years and older who started taking daily low-dose aspirin had a 19% higher chance of being diagnosed with metastatic cancer, a 22% higher chance of being diagnosed with a stage 4 tumor, and a 31% increased risk of death from stage 4 cancer, when compared with patients who took a placebo.
John J. McNeil, MBBS, PhD, of Monash University in Melbourne, Australia, and colleagues detailed these findings in the Journal of the National Cancer Institute.
“If confirmed, the clinical implications of these findings could be important for the use of aspirin in an older population,” the authors wrote.
When results of the ASPREE study were first reported in 2018, they “raised important concerns,” Ernest Hawk, MD, and Karen Colbert Maresso wrote in an editorial related to the current publication.
“Unlike ARRIVE, ASCEND, and nearly all prior primary prevention CVD [cardiovascular disease] trials of aspirin, ASPREE surprisingly demonstrated increased all-cause mortality in the aspirin group, which appeared to be driven largely by an increase in cancer-related deaths,” wrote the editorialists, who are both from the University of Texas MD Anderson Cancer Center in Houston.
Even though the ASPREE investigators have now taken a deeper dive into their data, the findings “neither explain nor alleviate the concerns raised by the initial ASPREE report,” the editorialists noted.
ASPREE design and results
ASPREE is a multicenter, double-blind trial of 19,114 older adults living in Australia (n = 16,703) or the United States (n = 2,411). Most patients were 70 years or older at baseline. However, the U.S. group also included patients 65 years and older who were racial/ethnic minorities (n = 564).
Patients were randomized to receive 100 mg of enteric-coated aspirin daily (n = 9,525) or matching placebo (n = 9,589) from March 2010 through December 2014.
At inclusion, all participants were free from cardiovascular disease, dementia, or physical disability. A previous history of cancer was not used to exclude participants, and 19.1% of patients had cancer at randomization. Most patients (89%) had not used aspirin regularly before entering the trial.
At a median follow-up of 4.7 years, there were 981 incident cancer events in the aspirin-treated group and 952 in the placebo-treated group, with an overall incident cancer rate of 10.1%.
Of the 1,933 patients with newly diagnosed cancer, 65.7% had a localized cancer, 18.8% had a new metastatic cancer, 5.8% had metastatic disease from an existing cancer, and 9.7% had a new hematologic or lymphatic cancer.
A quarter of cancer patients (n = 495) died as a result of their malignancy, with 52 dying from a cancer they already had at randomization.
Aspirin was not associated with the risk of first incident cancer diagnosis or incident localized cancer diagnosis. The hazard ratios were 1.04 for all incident cancers (95% confidence interval, 0.95-1.14) and 0.99 for incident localized cancers (95% CI, 0.89-1.11).
However, aspirin was associated with an increased risk of metastatic cancer and cancer presenting at stage 4. The HR for metastatic cancer was 1.19 (95% CI, 1.00-1.43), and the HR for newly diagnosed stage 4 cancer was 1.22 (95% CI, 1.02-1.45).
Furthermore, “an increased progression to death was observed amongst those randomized to aspirin, regardless of whether the initial cancer presentation had been localized or metastatic,” the investigators wrote.
The HRs for death were 1.35 for all cancers (95% CI, 1.13-1.61), 1.47 for localized cancers (95% CI, 1.07-2.02), and 1.30 for metastatic cancers (95% CI, 1.03-1.63).
“Deaths were particularly high among those on aspirin who were diagnosed with advanced solid cancers,” study author Andrew Chan, MD, of Massachusetts General Hospital in Boston, said in a press statement.
Indeed, HRs for death in patients with solid tumors presenting at stage 3 and 4 were a respective 2.11 (95% CI, 1.03-4.33) and 1.31 (95% CI, 1.04-1.64). This suggests a possible adverse effect of aspirin on the growth of cancers once they have already developed in older adults, Dr. Chan said.
Where does that leave aspirin for cancer prevention?
“Although these results suggest that we should be cautious about starting aspirin therapy in otherwise healthy older adults, this does not mean that individuals who are already taking aspirin – particularly if they began taking it at a younger age – should stop their aspirin regimen,” Dr. Chan said.
There are decades of data supporting the use of daily aspirin to prevent multiple cancer types, particularly colorectal cancer, in individuals under the age of 70 years. In a recent meta-analysis, for example, regular aspirin use was linked to a 27% reduced risk for colorectal cancer, a 33% reduced risk for squamous cell esophageal cancer, a 39% decreased risk for adenocarcinoma of the esophagus and gastric cardia, a 36% decreased risk for stomach cancer, a 38% decreased risk for hepatobiliary tract cancer, and a 22% decreased risk for pancreatic cancer.
While these figures are mostly based on observational and case-control studies, it “reaffirms the fact that, overall, when you look at all of the ages, that there is still a benefit of aspirin for cancer,” John Cuzick, PhD, of Queen Mary University of London (England), said in an interview.
In fact, the meta-analysis goes as far as suggesting that perhaps the dose of aspirin being used is too low, with the authors noting that there was a 35% risk reduction in colorectal cancer with a dose of 325 mg daily. That’s a new finding, Dr. Cuzick said.
He noted that the ASPREE study largely consists of patients 70 years of age or older, and the authors “draw some conclusions which we can’t ignore about potential safety.”
One of the safety concerns is the increased risk for gastrointestinal bleeding, which is why Dr. Cuzick and colleagues previously recommended caution in the use of aspirin to prevent cancer in elderly patients. The group published a study in 2015 that suggested a benefit of taking aspirin daily for 5-10 years in patients aged 50-65 years, but the risk/benefit ratio was unclear for patients 70 years and older.
The ASPREE data now add to those uncertainties and suggest “there may be some side effects that we do not understand,” Dr. Cuzick said.
“I’m still optimistic that aspirin is going to be important for cancer prevention, but probably focusing on ages 50-70,” he added. “[The ASPREE data] reinforce the caution that we have to take in terms of trying to understand what the side effects are and what’s going on at these older ages.”
Dr. Cuzick is currently leading the AsCaP Project, an international effort to better understand why aspirin might work in preventing some cancer types but not others. AsCaP is supported by Cancer Research UK and also includes Dr. Chan among the researchers attempting to find out which patients may benefit the most from aspirin and which may be at greater risk of adverse effects.
The ASPREE trial was funded by grants from the National Institute on Aging, the National Cancer Institute, the National Health and Medical Research Council of Australia, Monash University, and the Victorian Cancer Agency. Several ASPREE investigators disclosed financial relationships with Bayer Pharma. The editorialists had no conflicts of interest. Dr. Cuzick has been an advisory board member for Bayer in the past.
SOURCE: McNeil J et al. J Natl Cancer Inst. 2020 Aug 11. doi: 10.1093/jnci/djaa114.
FROM JOURNAL OF THE NATIONAL CANCER INSTITUTE
Subgroups predict adjuvant chemoradiotherapy benefits in low-grade glioma
Adjuvant chemoradiotherapy beat radiotherapy alone for treatment of certain patients with World Health Organization (WHO)–defined low-grade glioma (LGG), according to researchers.
Prior results from this trial, NRG Oncology/RTOG 9802 (NCT00003375), demonstrated an increase in progression-free survival (PFS) and overall survival (OS) when procarbazine, lomustine, and vincristine (PCV) chemotherapy was added to radiation in patients with high-risk LGG.
The current results, published in the Journal of Clinical Oncology, displayed highly variable survival outcomes depending on molecular subgroup.
The initial report included only IDH1 R132H immunohistochemistry data because of limited tissue availability. However, retrospective retrieval of additional tissues subsequently enabled rigorous examination of the prognostic and predictive significance of these genetic biomarkers.
Prognostic and predictive
The trial included 251 patients with LGG (grade 2). Among the 106 eligible patients with WHO-defined molecular groups successfully profiled, 26 (24%) were IDH wild-type, 43 (41%) were IDH-mutant/non-codeleted, and 37 (35%) were IDH-mutant/codeleted.
After adjustment for clinical variables and treatment, multivariate analysis confirmed WHO-defined subgroup was a significant predictor of survival. All predictive analyses, however, were considered exploratory because of small sample sizes for patients with specific biomarker features in most cases.
In prognostic multivariable analyses, significantly favorable molecular subgroup associations were observed for OS in the IDH-mutant subgroups versus that in the wild type group (IDH-mutant/codeleted group HR, 0.18; P < .0001; IDH mutant/non-codeleleted group HR, 0.56; P = .048). Individually, the statistical significance was maintained for favorable OS for IDH1/2 mutations and 1p/19q codeletions.
In the predictive analyses, OS was longer for patients harboring IDH mutant/codeleted tumors receiving radiotherapy plus PCV than for those receiving radiotherapy alone (HR, 0.21; P = .029). The median OS was 13.9 years for radiotherapy and was not reached for PCV and radiotherapy.
PFS in the IDH-mutant/codeleted subgroup also was longer for patients receiving PCV (HR, 0.13; P < .001). The median PFS was 5.8 years for radiotherapy alone and was not reached for added PCV.
In the IDH-mutant/non-codeleted subgroup, OS was longer with PCV (HR, 0.38; P = .013). The median OS was 4.3 years for radiotherapy alone and 11.4 years when PCV was added.
PFS was also longer in the IDH-mutant/non-codeleted subgroup (HR, 0.32; P = .003). The median PFS was 3.3 years for radiotherapy and 10.4 years with PCV added.
IDH–wild type patients displayed no significant clinical benefit from the addition of PCV.
“Historically, many have thought that primarily patients with codeletions received benefit from PCV,” study author Erica H. Bell, PhD, of The Ohio State University in Columbus, said in an interview. “But we showed here that there is benefit in both IDH-mutant groups.”
Primary predictor
“Our evidence suggests that IDH mutation status could serve as the primary predictor of response to PCV in addition to radiotherapy in high-risk, low-grade gliomas and is a more accurate predictor of response than historical histopathological classifications,” Dr. Bell and colleagues wrote. “Consideration should be given for adjuvant PCV in the setting of high-risk, low-grade glioma patients harboring IDH mutations.”
High-risk was defined as being 40 years or older or having a subtotal resection biopsy.
“While both IDH mutant subgroups received benefit from the addition of PCV for both overall survival and PFS, the patients in the wild-type subgroup did not do well," Dr. Bell said. "We need to treat them more aggressively. We need to determine exactly what therapy modality they should receive. This is an active question in our field.”
“Another conclusion from the study,” she added, “is that upfront tissue collection and molecular subtyping are absolutely necessary for moving our field forward.”
Finding novel biomarkers and novel therapeutic targets remain as a further goal.
Dr. Bell commented that results of the CODEL trial of temozolomide in newly diagnosed 1p/19q-codeleted anaplastic glioma are widely anticipated.
“PCV is a very toxic treatment," she said. "If another agent that is less toxic, but just as efficacious, becomes available, we would rather use that. At this point, though, there are no head-to-head trials comparing temozolomide with PCV in codeleted populations.”
The current study was sponsored by the National Cancer Institute and The Ohio State University. The authors disclosed patents, royalties, and other intellectual property.
SOURCE: Bell EH et al. J Clin Oncol. 2020. doi: 10.1200/JCO.19.02983.
Adjuvant chemoradiotherapy beat radiotherapy alone for treatment of certain patients with World Health Organization (WHO)–defined low-grade glioma (LGG), according to researchers.
Prior results from this trial, NRG Oncology/RTOG 9802 (NCT00003375), demonstrated an increase in progression-free survival (PFS) and overall survival (OS) when procarbazine, lomustine, and vincristine (PCV) chemotherapy was added to radiation in patients with high-risk LGG.
The current results, published in the Journal of Clinical Oncology, displayed highly variable survival outcomes depending on molecular subgroup.
The initial report included only IDH1 R132H immunohistochemistry data because of limited tissue availability. However, retrospective retrieval of additional tissues subsequently enabled rigorous examination of the prognostic and predictive significance of these genetic biomarkers.
Prognostic and predictive
The trial included 251 patients with LGG (grade 2). Among the 106 eligible patients with WHO-defined molecular groups successfully profiled, 26 (24%) were IDH wild-type, 43 (41%) were IDH-mutant/non-codeleted, and 37 (35%) were IDH-mutant/codeleted.
After adjustment for clinical variables and treatment, multivariate analysis confirmed WHO-defined subgroup was a significant predictor of survival. All predictive analyses, however, were considered exploratory because of small sample sizes for patients with specific biomarker features in most cases.
In prognostic multivariable analyses, significantly favorable molecular subgroup associations were observed for OS in the IDH-mutant subgroups versus that in the wild type group (IDH-mutant/codeleted group HR, 0.18; P < .0001; IDH mutant/non-codeleleted group HR, 0.56; P = .048). Individually, the statistical significance was maintained for favorable OS for IDH1/2 mutations and 1p/19q codeletions.
In the predictive analyses, OS was longer for patients harboring IDH mutant/codeleted tumors receiving radiotherapy plus PCV than for those receiving radiotherapy alone (HR, 0.21; P = .029). The median OS was 13.9 years for radiotherapy and was not reached for PCV and radiotherapy.
PFS in the IDH-mutant/codeleted subgroup also was longer for patients receiving PCV (HR, 0.13; P < .001). The median PFS was 5.8 years for radiotherapy alone and was not reached for added PCV.
In the IDH-mutant/non-codeleted subgroup, OS was longer with PCV (HR, 0.38; P = .013). The median OS was 4.3 years for radiotherapy alone and 11.4 years when PCV was added.
PFS was also longer in the IDH-mutant/non-codeleted subgroup (HR, 0.32; P = .003). The median PFS was 3.3 years for radiotherapy and 10.4 years with PCV added.
IDH–wild type patients displayed no significant clinical benefit from the addition of PCV.
“Historically, many have thought that primarily patients with codeletions received benefit from PCV,” study author Erica H. Bell, PhD, of The Ohio State University in Columbus, said in an interview. “But we showed here that there is benefit in both IDH-mutant groups.”
Primary predictor
“Our evidence suggests that IDH mutation status could serve as the primary predictor of response to PCV in addition to radiotherapy in high-risk, low-grade gliomas and is a more accurate predictor of response than historical histopathological classifications,” Dr. Bell and colleagues wrote. “Consideration should be given for adjuvant PCV in the setting of high-risk, low-grade glioma patients harboring IDH mutations.”
High-risk was defined as being 40 years or older or having a subtotal resection biopsy.
“While both IDH mutant subgroups received benefit from the addition of PCV for both overall survival and PFS, the patients in the wild-type subgroup did not do well," Dr. Bell said. "We need to treat them more aggressively. We need to determine exactly what therapy modality they should receive. This is an active question in our field.”
“Another conclusion from the study,” she added, “is that upfront tissue collection and molecular subtyping are absolutely necessary for moving our field forward.”
Finding novel biomarkers and novel therapeutic targets remain as a further goal.
Dr. Bell commented that results of the CODEL trial of temozolomide in newly diagnosed 1p/19q-codeleted anaplastic glioma are widely anticipated.
“PCV is a very toxic treatment," she said. "If another agent that is less toxic, but just as efficacious, becomes available, we would rather use that. At this point, though, there are no head-to-head trials comparing temozolomide with PCV in codeleted populations.”
The current study was sponsored by the National Cancer Institute and The Ohio State University. The authors disclosed patents, royalties, and other intellectual property.
SOURCE: Bell EH et al. J Clin Oncol. 2020. doi: 10.1200/JCO.19.02983.
Adjuvant chemoradiotherapy beat radiotherapy alone for treatment of certain patients with World Health Organization (WHO)–defined low-grade glioma (LGG), according to researchers.
Prior results from this trial, NRG Oncology/RTOG 9802 (NCT00003375), demonstrated an increase in progression-free survival (PFS) and overall survival (OS) when procarbazine, lomustine, and vincristine (PCV) chemotherapy was added to radiation in patients with high-risk LGG.
The current results, published in the Journal of Clinical Oncology, displayed highly variable survival outcomes depending on molecular subgroup.
The initial report included only IDH1 R132H immunohistochemistry data because of limited tissue availability. However, retrospective retrieval of additional tissues subsequently enabled rigorous examination of the prognostic and predictive significance of these genetic biomarkers.
Prognostic and predictive
The trial included 251 patients with LGG (grade 2). Among the 106 eligible patients with WHO-defined molecular groups successfully profiled, 26 (24%) were IDH wild-type, 43 (41%) were IDH-mutant/non-codeleted, and 37 (35%) were IDH-mutant/codeleted.
After adjustment for clinical variables and treatment, multivariate analysis confirmed WHO-defined subgroup was a significant predictor of survival. All predictive analyses, however, were considered exploratory because of small sample sizes for patients with specific biomarker features in most cases.
In prognostic multivariable analyses, significantly favorable molecular subgroup associations were observed for OS in the IDH-mutant subgroups versus that in the wild type group (IDH-mutant/codeleted group HR, 0.18; P < .0001; IDH mutant/non-codeleleted group HR, 0.56; P = .048). Individually, the statistical significance was maintained for favorable OS for IDH1/2 mutations and 1p/19q codeletions.
In the predictive analyses, OS was longer for patients harboring IDH mutant/codeleted tumors receiving radiotherapy plus PCV than for those receiving radiotherapy alone (HR, 0.21; P = .029). The median OS was 13.9 years for radiotherapy and was not reached for PCV and radiotherapy.
PFS in the IDH-mutant/codeleted subgroup also was longer for patients receiving PCV (HR, 0.13; P < .001). The median PFS was 5.8 years for radiotherapy alone and was not reached for added PCV.
In the IDH-mutant/non-codeleted subgroup, OS was longer with PCV (HR, 0.38; P = .013). The median OS was 4.3 years for radiotherapy alone and 11.4 years when PCV was added.
PFS was also longer in the IDH-mutant/non-codeleted subgroup (HR, 0.32; P = .003). The median PFS was 3.3 years for radiotherapy and 10.4 years with PCV added.
IDH–wild type patients displayed no significant clinical benefit from the addition of PCV.
“Historically, many have thought that primarily patients with codeletions received benefit from PCV,” study author Erica H. Bell, PhD, of The Ohio State University in Columbus, said in an interview. “But we showed here that there is benefit in both IDH-mutant groups.”
Primary predictor
“Our evidence suggests that IDH mutation status could serve as the primary predictor of response to PCV in addition to radiotherapy in high-risk, low-grade gliomas and is a more accurate predictor of response than historical histopathological classifications,” Dr. Bell and colleagues wrote. “Consideration should be given for adjuvant PCV in the setting of high-risk, low-grade glioma patients harboring IDH mutations.”
High-risk was defined as being 40 years or older or having a subtotal resection biopsy.
“While both IDH mutant subgroups received benefit from the addition of PCV for both overall survival and PFS, the patients in the wild-type subgroup did not do well," Dr. Bell said. "We need to treat them more aggressively. We need to determine exactly what therapy modality they should receive. This is an active question in our field.”
“Another conclusion from the study,” she added, “is that upfront tissue collection and molecular subtyping are absolutely necessary for moving our field forward.”
Finding novel biomarkers and novel therapeutic targets remain as a further goal.
Dr. Bell commented that results of the CODEL trial of temozolomide in newly diagnosed 1p/19q-codeleted anaplastic glioma are widely anticipated.
“PCV is a very toxic treatment," she said. "If another agent that is less toxic, but just as efficacious, becomes available, we would rather use that. At this point, though, there are no head-to-head trials comparing temozolomide with PCV in codeleted populations.”
The current study was sponsored by the National Cancer Institute and The Ohio State University. The authors disclosed patents, royalties, and other intellectual property.
SOURCE: Bell EH et al. J Clin Oncol. 2020. doi: 10.1200/JCO.19.02983.
FROM THE JOURNAL OF CLINICAL ONCOLOGY