In the Journals

Younger cancer survivors face higher mortality from noncancer causes

Adolescents and young adults who are cancer survivors have a significantly higher rate of mortality from noncancer causes compared with the general population, according to results of a study published in Cancer.

The data show that this is especially true when it comes to long-term mortality related to infectious diseases.

“Despite the unique characteristics associated with cancers in this age group, few studies have examined long-term health outcomes among patients diagnosed as [adolescents and young adults],” Chelsea Anderson, MPH, doctoral student at The University of North Carolina’s Gillings School of Public Global Health, and colleagues wrote. “In our analyses, mortality from all noncancer causes among [adolescent and young adult] cancer survivors was approximately 1.8 times that of the general population, with the highest [standardized mortality ratios] noted among those with hematologic malignancies and [central nervous system] tumors, cancers that are more predominant among patients diagnosed as adolescents.”

In this study, Anderson and colleagues used SEER data to analyze mortality from noncancer causes among adolescent and young adult (aged 15-39 years) cancer survivors compared with the general U.S. population.

The analysis included 235,641 adolescent and young adult cancer survivors (60% female, 65% aged 30-39 years at diagnosis), among whom 12,948 noncancer-related deaths occurred during about 3.1 million person-years of follow-up.

The study included patients first diagnosed with cancer between the ages of 15 and 39 years from 1973 to 2015. Researchers excluded patients with unknown race or cause of death and those lacking a death certificate, as well as patients diagnosed with Kaposi sarcoma because of its relationship with HIV infection.

The study results showed that adolescents and young adult cancer survivors were nearly twice as likely to die of noncancer-related causes compared with the general population (standardized mortality ratio [SMR] = 1.84; 95% CI, 1.8-1.87). This ratio was pointedly higher when evaluating deaths related to infectious disease (SMR = 5.13; 95% CI, 4.95-5.32).

Increased mortality risk among adolescent and young adult cancer survivors remained elevated when evaluated for cardiovascular (SMR = 1.55; 95% CI, 1.5-1.6) and renal (SMR = 2.4; 95% CI, 2.12-2.71) diseases.

Several cancer types showed increased risk for mortality from noncancer causes, including leukemias (SMR = 5.26; 95% CI, 4.87-5.66), Hodgkin lymphoma (SMR = 3.12; 95% CI, 2.96-3.28)), non-Hodgkin lymphoma (SMR = 6.33; 95% CI, 6.07-6.6), CNS tumors (SMR = 3.38; 95% CI, 3.11-3.66), head and neck cancers (SMR = 2.09; 95% CI, 1.91-2.29) and cervical/uterine cancers (SMR = 2.03; 95% CI, 1.91-2.15)).

“Notably, SMRs remained significantly elevated at 20 [or more] years postdiagnosis for [adolescents and young adults] with breast, cervical/uterine, and head and neck cancers, highlighting priority groups for long-term cardiovascular surveillance and disease management in addition to those identified in previous childhood cancer studies,” Anderson and colleagues wrote.

The researchers wrote that some deaths evaluated in the study could be misclassified because of errors in the coding of death certificates. In addition, the analysis was unable to distinguish between HIV-related deaths and those of other infectious diseases because of patient confidentiality policies that group them as a single code in SEER data.

Further, SEER data lack detailed information on the type of cancer treatment a patient received. This prevented Anderson and colleagues from analyzing the long-term impact of certain cancer therapies on noncancer mortality in the study population.

“The results of the current study suggest that [adolescents and young adults] with cancer face an elevated burden of mortality from noncancer causes relative to the general population that persists many years after cancer diagnosis, thereby suggesting the importance of comprehensive, coordinated follow-up care throughout survivorship,” Anderson and colleagues wrote. “Examining long-term patterns of noncancer health outcomes according to receipt of specific cancer therapies is an area for future research among [adolescent and young adult] cancer survivors.”

The population evaluated in the study by Anderson and colleagues has historically low clinical trial participation rates, yet cancer incidence in this group is increasing over time, Robert J. Hayashi, MD, professor of pediatrics in the division of pediatric hematology/oncology at Washington University School of Medicine in St. Louis, wrote in an accompanying editorial.

Hayashi observed that most studies on the long-term side effects of cancer treatments have focused on pediatric populations, the results of which may not be applicable to the study group evaluated by Anderson and colleagues. Adolescents and young adults have benefited “in a passive fashion” from cancer treatment advances across other age groups; therefore, this survivor population will continue to expand and should be the focus of further research on long-term outcomes, he added.

“[Adolescent and young adult] cancer survivorship represents a new frontier of discovery for investigators who study the long-term consequences of cancer therapy,” he wrote. “[T]he observations in this report highlight the important point that advances in cancer therapy, while curing patients, will invariably lead to the development of long-term toxicities that may increase the risk [for] late mortality, thus tempering the successes achieved from cancer eradication.” – by Drew Amorosi

Disclosures: Anderson received funding support from The University of North Carolina Lineberger Cancer Control Education Program. One study author reports funding from St. Baldrick’s Foundation, and another author reports research funding from Genentech and Pfizer. Hayashi reports no relevant financial disclosures.

Adolescents and young adults who are cancer survivors have a significantly higher rate of mortality from noncancer causes compared with the general population, according to results of a study published in Cancer.

The data show that this is especially true when it comes to long-term mortality related to infectious diseases.

“Despite the unique characteristics associated with cancers in this age group, few studies have examined long-term health outcomes among patients diagnosed as [adolescents and young adults],” Chelsea Anderson, MPH, doctoral student at The University of North Carolina’s Gillings School of Public Global Health, and colleagues wrote. “In our analyses, mortality from all noncancer causes among [adolescent and young adult] cancer survivors was approximately 1.8 times that of the general population, with the highest [standardized mortality ratios] noted among those with hematologic malignancies and [central nervous system] tumors, cancers that are more predominant among patients diagnosed as adolescents.”

In this study, Anderson and colleagues used SEER data to analyze mortality from noncancer causes among adolescent and young adult (aged 15-39 years) cancer survivors compared with the general U.S. population.

The analysis included 235,641 adolescent and young adult cancer survivors (60% female, 65% aged 30-39 years at diagnosis), among whom 12,948 noncancer-related deaths occurred during about 3.1 million person-years of follow-up.

The study included patients first diagnosed with cancer between the ages of 15 and 39 years from 1973 to 2015. Researchers excluded patients with unknown race or cause of death and those lacking a death certificate, as well as patients diagnosed with Kaposi sarcoma because of its relationship with HIV infection.

The study results showed that adolescents and young adult cancer survivors were nearly twice as likely to die of noncancer-related causes compared with the general population (standardized mortality ratio [SMR] = 1.84; 95% CI, 1.8-1.87). This ratio was pointedly higher when evaluating deaths related to infectious disease (SMR = 5.13; 95% CI, 4.95-5.32).

Increased mortality risk among adolescent and young adult cancer survivors remained elevated when evaluated for cardiovascular (SMR = 1.55; 95% CI, 1.5-1.6) and renal (SMR = 2.4; 95% CI, 2.12-2.71) diseases.

Several cancer types showed increased risk for mortality from noncancer causes, including leukemias (SMR = 5.26; 95% CI, 4.87-5.66), Hodgkin lymphoma (SMR = 3.12; 95% CI, 2.96-3.28)), non-Hodgkin lymphoma (SMR = 6.33; 95% CI, 6.07-6.6), CNS tumors (SMR = 3.38; 95% CI, 3.11-3.66), head and neck cancers (SMR = 2.09; 95% CI, 1.91-2.29) and cervical/uterine cancers (SMR = 2.03; 95% CI, 1.91-2.15)).

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“Notably, SMRs remained significantly elevated at 20 [or more] years postdiagnosis for [adolescents and young adults] with breast, cervical/uterine, and head and neck cancers, highlighting priority groups for long-term cardiovascular surveillance and disease management in addition to those identified in previous childhood cancer studies,” Anderson and colleagues wrote.

The researchers wrote that some deaths evaluated in the study could be misclassified because of errors in the coding of death certificates. In addition, the analysis was unable to distinguish between HIV-related deaths and those of other infectious diseases because of patient confidentiality policies that group them as a single code in SEER data.

Further, SEER data lack detailed information on the type of cancer treatment a patient received. This prevented Anderson and colleagues from analyzing the long-term impact of certain cancer therapies on noncancer mortality in the study population.

“The results of the current study suggest that [adolescents and young adults] with cancer face an elevated burden of mortality from noncancer causes relative to the general population that persists many years after cancer diagnosis, thereby suggesting the importance of comprehensive, coordinated follow-up care throughout survivorship,” Anderson and colleagues wrote. “Examining long-term patterns of noncancer health outcomes according to receipt of specific cancer therapies is an area for future research among [adolescent and young adult] cancer survivors.”

The population evaluated in the study by Anderson and colleagues has historically low clinical trial participation rates, yet cancer incidence in this group is increasing over time, Robert J. Hayashi, MD, professor of pediatrics in the division of pediatric hematology/oncology at Washington University School of Medicine in St. Louis, wrote in an accompanying editorial.

Hayashi observed that most studies on the long-term side effects of cancer treatments have focused on pediatric populations, the results of which may not be applicable to the study group evaluated by Anderson and colleagues. Adolescents and young adults have benefited “in a passive fashion” from cancer treatment advances across other age groups; therefore, this survivor population will continue to expand and should be the focus of further research on long-term outcomes, he added.

“[Adolescent and young adult] cancer survivorship represents a new frontier of discovery for investigators who study the long-term consequences of cancer therapy,” he wrote. “[T]he observations in this report highlight the important point that advances in cancer therapy, while curing patients, will invariably lead to the development of long-term toxicities that may increase the risk [for] late mortality, thus tempering the successes achieved from cancer eradication.” – by Drew Amorosi

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Disclosures: Anderson received funding support from The University of North Carolina Lineberger Cancer Control Education Program. One study author reports funding from St. Baldrick’s Foundation, and another author reports research funding from Genentech and Pfizer. Hayashi reports no relevant financial disclosures.