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Incidence, Relative Risk and Risk Factors for Chronic Comorbidities in Long-Term Survivors of AYA Cancer

In an article published on 16 July 2020 in the Journal of Clinical Oncology, the researchers of the Kaiser Permanente Southern California in Pasadena, CA, USA described the incidence and relative risk of development of chronic comorbidities among survivors of adolescent and young adult (AYA) cancer compared with controls without a history of cancer. They found that the risk of nearly all comorbidities was significantly elevated in survivors of cancer, with magnitudes of incidence rate ratio (IRR) ranging from 1.3 for dyslipidaemia to 8.3 for avascular necrosis. Moreover, 2 in 5 survivors had multiple comorbidities just 10 years after the index date. Among survivors of AYA cancer, the study team observed significant associations between treatment exposures and certain comorbidities such as cardiomyopathy, hearing loss, stroke, thyroid disorders, and diabetes. The data highlight the burden of adverse long-term health outcomes of cancer and its treatment in survivors of AYA cancer and will facilitate the identification of high-risk survivors who may benefit from tailored surveillance and prevention strategies.

To describe the incidence, relative risk, and risk factors for chronic comorbidities in survivors of AYA cancer, this retrospective cohort study included 2-year survivors of AYA cancer diagnosed between age 15 and 39 years at Kaiser Permanente Southern California from 2000 to 2012. A comparison cohort without cancer was individually matched (13:1) to survivors of cancer on age, sex, and calendar year.

By using electronic medical records, all participants were followed through 31 December 2014 for chronic comorbidity diagnoses. Poisson regression was used to evaluate the association between cancer survivor status and risk of developing each comorbidity. The associations between cumulative exposure to chemotherapy and radiation therapy and selected comorbidities were examined for AYA survivors of cancer.

The cohort included 6,778 survivors of AYA cancer and 87,737 persons without a history of cancer. Among survivors of AYA cancer, median age at initial cancer diagnosis was 31 years (8% of age 15-19 years; 25% of age 20-29 years; and 67% of age 30-39 years). Approximately 65% of survivors were female, and 42% were non-Hispanic White.

The most common cancer diagnoses were breast cancer (16%) and thyroid cancer (16%), followed by lymphoma (11%) and melanoma (10%). Approximately a quarter of survivors of AYA cancer (23%) received external-beam radiation therapy. Exposure to selected chemotherapy agents ranged from 3% in case of epipodophyllotoxins to 24% for anthracyclines. The median follow-up time after cancer diagnosis was 5.1 years.

The IRR for survivors of cancer was significantly increased for nearly all comorbidities examined. The IRR ranged from 1.3 (95% confidence interval [CI], 1.2 to 1.4) for dyslipidaemia to 8.3 (95% CI, 4.6 to 14.9) for avascular necrosis.

Survivors of AYA cancer had a 2- to 3-fold increased risk for cardiomyopathy, stroke, premature ovarian failure, chronic liver disease, and renal failure.

Among survivors of cancer, significant associations between chemotherapy and radiation therapy exposures and late effects of cardiomyopathy, hearing loss, stroke, thyroid disorders, and diabetes were observed from the multivariable analyses.

The authors reported that 40% of survivors of AYA cancer had multiple (≥2) comorbidities at 10 years after index date, compared with 20% of those without cancer.

The authors concluded that findings from their study provide a comprehensive overview of the incidence and relative risk of chronic comorbidities in long-term survivors of AYA cancer compared with matched individuals without a history of cancer. They showed that the risk of developing chronic comorbidities was increased across nearly all outcomes examined and highlighted important treatment-related modifiers of risk in survivors of AYA cancer. These data may help provide much-needed information for the development of personalised survivorship care plans for survivors of AYA cancer, taking into consideration the unique phenotypes of comorbidities over time. Furthermore, it may set the stage for prevention, early diagnosis, or intervention strategies to mitigate long-term comorbidity burden in this growing population of long-term survivors.

The study was supported by grant from the American Cancer Society.


Chao C, Bhatia S, Xu L, et al. Chronic Comorbidities Among Survivors of Adolescent and Young Adult Cancer. JCO; Published online 16 July 2020. DOI10.1200/JCO.20.00722.



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