Clinical Context

The increasing population of long-term cancer survivors remains at high risk for premature death, despite reduced treatment intensity, mostly from subsequent cancers and cardiac and pulmonary causes. Modifiable cardiovascular and other risk factors suggest potential interventions to reduce late mortality.

Behavioral and lifestyle factors, including physical activity and tobacco use, may also affect late mortality. Childhood cancer survivors commonly experience individual-level disadvantages, including lower educational attainment, unemployment, inadequate insurance, and lower income, which may all lower health care access and survival.

Study Synopsis and Perspective

Modifiable chronic health conditions and socioeconomic factors may raise the risk for death in adult survivors of childhood cancer, according to new data from the St Jude Lifetime Cohort.

Survivors with a greater number and severity of modifiable chronic health conditions, as well as those living in the most vs least resource-deprived areas, had a significantly higher risk for all-cause and health-related late death.

Finding ways to mitigate these factors “will be important to improving health outcomes and developing risk-stratification strategies to optimize care delivery to survivors at varying risk of adverse health events,” the researchers write.

The study indicates that treating chronic health conditions alone may not be enough to increase a cancer survivor’s lifespan; improving local environments matters too.

“It is important for clinicians to ask patients about their specific situation,” first author Matthew J. Ehrhardt, MD, Department of Oncology, St Jude Children’s Research Hospital, Memphis, Tennessee, said in a news release. “It’s easy to prescribe medications or to tell people to exercise. It takes more time and more thoughtfulness to sit and understand environments in which they are residing.”

“As clinicians, we may have limited ability to modify some of those factors. But we can work closely with the rest of the healthcare team, such as social workers, for example, to help survivors to identify and access local resources,” Dr Ehrhardt added.

The study was published online February 10 in JAMA Network Open.^[1]

A growing population of childhood cancer survivors faces an increased risk for premature death in the years after their diagnosis. However, associations among social determinants of health, modifiable health conditions, and late mortality in childhood cancer survivors remain unclear.

To assess late mortality, the study team analyzed data on 9440 participants (median age at assessment, 27.5 years; range, 5.3 to 71.9 years) who lived at least 5 years after being diagnosed with a childhood cancer between 1962 and 2012.

During a median follow-up of about 18 years, childhood cancer survivors had an increased rate for both all-cause and health-related late mortality (standardized mortality rate [SMR], 7.6 for both). Among specific health-related causes of death, SMRs were 16.0 for subsequent neoplasms, 9.0 for pulmonary causes, 4.2 for cardiac causes, and 4.3 for other health-related causes.

To evaluate ties among modifiable chronic health conditions, social determinants, and late mortality, the researchers restricted their analysis to 3407 adult study participants for whom relevant data were available. Modifiable chronic health conditions included dyslipidemia, hypertension, diabetes, underweight or obesity, bone mineral deficiency, and hypothyroidism.

After adjusting for individual factors, including age at diagnosis and treatment, as well as neighborhood-level factors, the researchers observed a significantly increased risk for death among survivors with 1 or more modifiable chronic health conditions of grade 2 or higher (relative risk [RR], 2.2), 2 chronic health conditions of grade 2 or higher (RR, 2.6) or 3 chronic health conditions of grade 2 or higher (RR, 3.6).

These findings suggest that “increased late mortality experienced by childhood cancer survivors in adulthood may not be predetermined by treatment-related risk factors alone,” the researchers say.

In addition, survivors living in the most disadvantaged areas, as measured by the area deprivation index (ADI), had a 5- to 8-fold increased risk for late death from any cause compared with those living in the least disadvantaged areas, even after adjusting for modifiable chronic health conditions, cancer treatment, demographics, and individual socioeconomic factors.

The findings have important public health implications, Ehrhardt and colleagues said. The results can, for instance, help identify and stratify cancer survivors at higher lifetime risk for specific chronic conditions and late death. 

This risk-stratified approach to care, however, is “relatively static” and does not account for risk factors acquired after cancer diagnosis and treatment, such as social determinants of health.

That is why also focusing on socioeconomic factors is important, and transitional care services after cancer treatment should consider that survivors in disadvantaged neighborhoods may lack supportive resources to address health issues, potentially leading to increased risk for death, the researchers said.

The knowledge that living in a resource-poor neighborhood may raise the risk for late death in childhood cancer survivors “strengthens support for public health policies that will direct resources to such regions and facilitate a multipronged approach to risk mitigation,” the authors conclude.

This study was supported by grants from the National Institutes of Health (NIH) and the American Lebanese Syrian Associated Charities. The authors have disclosed no relevant financial relationships.

JAMA Netw Open. Published online February 10, 2023.

Clinical Implications

• Childhood cancer survivors had 7-fold significantly increased adjusted risk for all-cause and health-related death.
• Treatment-related risk factors alone may not predetermine increased late mortality.
• Implications for the Health Care Team: Clinicians should ask patients about their CHCs and specific socioeconomic situation and collaborate with social workers and other healthcare team members to help survivors identify and access local resources.

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