In the Journals

Prevalence of secondary cancers underscores need for trial inclusion

A quarter of older adults newly diagnosed with cancer from 2009 to 2013 had a prior cancer history, according to an observational study published in JAMA Oncology.

Additionally, 11% of patients aged younger than 65 years diagnosed during that period also had a prior cancer history, researchers reported.

“Patients with prior cancer diagnoses are frequently excluded from cancer clinical trials,” Sandi L. Pruitt, PhD, MPH, assistant professor of epidemiology in the department of clinical sciences at University of Texas Southwestern Medical Center, told HemOnc Today. “To our knowledge, the prevalence of prior cancer has not previously been described among a large, representative sample of patients in the United States with multiple types of cancer. Thus, this study was necessary so that we know the potential number of patients who may be impacted by these clinical trial exclusion policies.”

Largely driven by an aging population, the number of cancer survivors in the United States is expected to climb from 15.5 million to an estimated 26.1 million by 2040. Nearly half of all cancer survivors have lived 10 years after their initial diagnosis and two-thirds have survived beyond 5 years.

However, survivors have complex needs — including surveillance for recurrence, monitoring treatment-related toxicities, and managing chronic conditions or new primary cancers — which frequently preclude them from clinical trials. More than 80% of NCI-affiliated lung cancer trials exclude patients with a prior cancer, which may prevent as many as 25% of patients newly diagnosed with lung cancer from participating in clinical trials.

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From left: Caitlin C. Murphy, PhD, MPH, David E. Gerber, MD, MSCS, and Sandi L. Pruitt, PhD, MPH.
Photo courtesy of University of Texas Southwestern Medical Center.

Pruitt and co-authors Caitlin C. Murphy, PhD, MPH, and David E. Gerber, MD, MSCS, also with University of Texas Southwestern Medical Center, used the SEER database to identify 740,990 persons newly diagnosed with 765,843 incident cancers between 2009 and 2013. Researchers estimated prevalence of a cancer history by age — 65 years or older, and younger than 65 years — and incident cancer type. They also categorized incident cancers as first or primary; second order or higher primary in the same cancer site; and second order or higher primary in a different cancer site.

Results showed 18.4% (n = 141,021) of incident cancers represented a second order or higher primary cancer. This represented 25.2% of incident cancers among those aged 65 years or older, and 11% among those aged 20 to 64 years.

For patients aged 65 years or older, the most common incidences of secondary cancers included melanoma (36.9%), myeloid and monocytic leukemia (36.9%), cancer of the bone and joints (34%), and urinary bladder and other urinary organ cancers (32.5%). Most prior cancers among the older age group occurred in a different site.

For patients aged 20 to 64 years, prior cancer appeared most prevalent among those diagnosed with incident myeloid and monocytic leukemia (24.8%); anus, anal canal and rectum cancers (18,2%); cervix, vagina and vulva cancers (15%); and lung and other respiratory cancers (14.6%). Prior cancers in the younger age group generally occurred in a different site, although second order breast, cervical and other female genital, male genital and testicular cancers were more often in the same site.

Researchers noted an inability to determine order of multiple cancers diagnosed in the same year as a limitation, adding it was unlikely it impacted their conclusions.

“We feel that this study represents a key first step in understanding this large, important and often overlooked patient population,” Pruitt said. “As evidenced by our results, prior cancer diagnoses can be quite common among individuals with cancer. To know whether these patients should be included routinely in clinical trials, further work is needed.

“If it is shown that prior cancer diagnoses do not adversely impact clinical outcomes for the cancer types in the present study — as we previously demonstrated for individuals with lung cancer — then it seems reasonable and appropriate to open up clinical trials to these patients,” Pruitt added.

Excluding patients with a prior cancer from clinical trials likely arises from a long-held belief that a prior cancer diagnosis may interfere with study conduct and/or outcomes, according to the researchers. This is particularly concerning for older adults with uncommon cancers, where trial accrual is critical, standard therapies may be suboptimal and prior cancer is prevalent.

“Clinical trials can provide important options for patients with cancer,” Pruitt said. “For some patients, cancer clinical trials may provide their best treatment option. Also, by participating, patients help to advance new discovery about cancer treatments.”

Further, results of trials that excluded patients with prior cancers may not be generalizable or relevant to them.

“Unless it is known that patients with prior cancer would alter study results or be at greater risk for harm, we feel that patients with prior cancer deserve the opportunity to participate in trials,” Pruitt said.

The study reinforces the “common knowledge” that diagnosis of a first cancer is frequently associated with diagnosis of a second cancer because of shared underlying risk factors like tobacco use, obesity or HPV exposure, according to an accompanying editorial by Nancy E. Davidson, MD, senior vice president and director of the clinical research division at Fred Hutchinson Cancer Research Center, and president and executive director of Seattle Cancer Care Alliance.

“A first cancer affirms the need to develop and apply evidence-based prevention and screening strategies for survivors of cancer because they are a particularly high-risk population,” Davidson wrote. “These findings also confirm that individuals with a first cancer are especially well suited to participate in research studies to identify biomarkers of risk for subsequent cancers and prevention strategies, areas where we know far less than we wish.”

Current guidelines greatly limit older patients from participating in clinical trials, underserving the population that could benefit most by new treatments, Davidson noted.

“[Inclusion of older cancer survivors] will require not only a consensus among trialists but also agreement by regulatory agencies like the FDA and pharmaceutical firms that thoughtful inclusion of previous cancer survivors in cancer clinical trials is both safe and ethical,” Davidson wrote. – by Chuck Gormley

 

For more information:

Sandi L. Pruitt, PhD, MPH , can be reached at sandi.pruitt@utsouthwestern.edu.

 

Disclosures: The NCI funded this study. The authors and Davidson report no relevant financial disclosures.

A quarter of older adults newly diagnosed with cancer from 2009 to 2013 had a prior cancer history, according to an observational study published in JAMA Oncology.

Additionally, 11% of patients aged younger than 65 years diagnosed during that period also had a prior cancer history, researchers reported.

“Patients with prior cancer diagnoses are frequently excluded from cancer clinical trials,” Sandi L. Pruitt, PhD, MPH, assistant professor of epidemiology in the department of clinical sciences at University of Texas Southwestern Medical Center, told HemOnc Today. “To our knowledge, the prevalence of prior cancer has not previously been described among a large, representative sample of patients in the United States with multiple types of cancer. Thus, this study was necessary so that we know the potential number of patients who may be impacted by these clinical trial exclusion policies.”

Largely driven by an aging population, the number of cancer survivors in the United States is expected to climb from 15.5 million to an estimated 26.1 million by 2040. Nearly half of all cancer survivors have lived 10 years after their initial diagnosis and two-thirds have survived beyond 5 years.

However, survivors have complex needs — including surveillance for recurrence, monitoring treatment-related toxicities, and managing chronic conditions or new primary cancers — which frequently preclude them from clinical trials. More than 80% of NCI-affiliated lung cancer trials exclude patients with a prior cancer, which may prevent as many as 25% of patients newly diagnosed with lung cancer from participating in clinical trials.

#
From left: Caitlin C. Murphy, PhD, MPH, David E. Gerber, MD, MSCS, and Sandi L. Pruitt, PhD, MPH.
Photo courtesy of University of Texas Southwestern Medical Center.

Pruitt and co-authors Caitlin C. Murphy, PhD, MPH, and David E. Gerber, MD, MSCS, also with University of Texas Southwestern Medical Center, used the SEER database to identify 740,990 persons newly diagnosed with 765,843 incident cancers between 2009 and 2013. Researchers estimated prevalence of a cancer history by age — 65 years or older, and younger than 65 years — and incident cancer type. They also categorized incident cancers as first or primary; second order or higher primary in the same cancer site; and second order or higher primary in a different cancer site.

Results showed 18.4% (n = 141,021) of incident cancers represented a second order or higher primary cancer. This represented 25.2% of incident cancers among those aged 65 years or older, and 11% among those aged 20 to 64 years.

For patients aged 65 years or older, the most common incidences of secondary cancers included melanoma (36.9%), myeloid and monocytic leukemia (36.9%), cancer of the bone and joints (34%), and urinary bladder and other urinary organ cancers (32.5%). Most prior cancers among the older age group occurred in a different site.

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For patients aged 20 to 64 years, prior cancer appeared most prevalent among those diagnosed with incident myeloid and monocytic leukemia (24.8%); anus, anal canal and rectum cancers (18,2%); cervix, vagina and vulva cancers (15%); and lung and other respiratory cancers (14.6%). Prior cancers in the younger age group generally occurred in a different site, although second order breast, cervical and other female genital, male genital and testicular cancers were more often in the same site.

Researchers noted an inability to determine order of multiple cancers diagnosed in the same year as a limitation, adding it was unlikely it impacted their conclusions.

“We feel that this study represents a key first step in understanding this large, important and often overlooked patient population,” Pruitt said. “As evidenced by our results, prior cancer diagnoses can be quite common among individuals with cancer. To know whether these patients should be included routinely in clinical trials, further work is needed.

“If it is shown that prior cancer diagnoses do not adversely impact clinical outcomes for the cancer types in the present study — as we previously demonstrated for individuals with lung cancer — then it seems reasonable and appropriate to open up clinical trials to these patients,” Pruitt added.

Excluding patients with a prior cancer from clinical trials likely arises from a long-held belief that a prior cancer diagnosis may interfere with study conduct and/or outcomes, according to the researchers. This is particularly concerning for older adults with uncommon cancers, where trial accrual is critical, standard therapies may be suboptimal and prior cancer is prevalent.

“Clinical trials can provide important options for patients with cancer,” Pruitt said. “For some patients, cancer clinical trials may provide their best treatment option. Also, by participating, patients help to advance new discovery about cancer treatments.”

Further, results of trials that excluded patients with prior cancers may not be generalizable or relevant to them.

“Unless it is known that patients with prior cancer would alter study results or be at greater risk for harm, we feel that patients with prior cancer deserve the opportunity to participate in trials,” Pruitt said.

The study reinforces the “common knowledge” that diagnosis of a first cancer is frequently associated with diagnosis of a second cancer because of shared underlying risk factors like tobacco use, obesity or HPV exposure, according to an accompanying editorial by Nancy E. Davidson, MD, senior vice president and director of the clinical research division at Fred Hutchinson Cancer Research Center, and president and executive director of Seattle Cancer Care Alliance.

PAGE BREAK

“A first cancer affirms the need to develop and apply evidence-based prevention and screening strategies for survivors of cancer because they are a particularly high-risk population,” Davidson wrote. “These findings also confirm that individuals with a first cancer are especially well suited to participate in research studies to identify biomarkers of risk for subsequent cancers and prevention strategies, areas where we know far less than we wish.”

Current guidelines greatly limit older patients from participating in clinical trials, underserving the population that could benefit most by new treatments, Davidson noted.

“[Inclusion of older cancer survivors] will require not only a consensus among trialists but also agreement by regulatory agencies like the FDA and pharmaceutical firms that thoughtful inclusion of previous cancer survivors in cancer clinical trials is both safe and ethical,” Davidson wrote. – by Chuck Gormley

 

For more information:

Sandi L. Pruitt, PhD, MPH , can be reached at sandi.pruitt@utsouthwestern.edu.

 

Disclosures: The NCI funded this study. The authors and Davidson report no relevant financial disclosures.