The risk of developing chronic comorbidities was 2- to 3-fold higher in adolescents and young adults (AYAs) who were successfully treated for cancer, as compared with the general population across nearly all outcomes examined in a large retrospective study appearing in the September 2020 edition of the Journal of Clinical Oncology.
Lead author Chun Chao, PhD, research scientist at the Kaiser Permanente Southern California and Assistant Professor, Department of Epidemiology, UCLA in Los Angeles, USA and colleagues underscored two key components of AYA cancer survivors: There is now a population of approximately 633,000 AYA cancer survivors in the United States that will continue to grow, and data regarding the risk of chronic comorbidities among AYAs are sparse compared to that compiled for survivors of childhood cancer.
Importantly, the study described the incidence, and relative risk for developing chronic comorbidities in survivors to facilitate development of personalised survivorship care plans for AYA cancer survivors.
The cohorts were well-balanced as to racial, ethnic, and socioeconomic factors
The large retrospective study identified 6,778 survivors of AYA cancer and 87,737 persons with no history of cancer recorded in the Kaiser Permanente Southern California database. This institution provides comprehensive health services to 4.4 million racially, ethnically, and socioeconomically diverse individuals who are representative of the general population.
The AYA cancer cohort comprised individuals diagnosed with invasive cancer between the ages of 15 to 39 years from 2000 to 2012 who survived ≥2 years after cancer diagnosis. The reference cohort included individuals with no cancer history who were matched 13:1 per age, sex and calendar year. Both cohorts were followed for the diagnosis of chronic comorbidity using electronic medical records through 31st December 2014.
The median age of survivors at cancer diagnosis was 31 years; 8% (15 to 19), 25% (20 to 29), and 67% (30 to 39). Approximately 65% of survivors were female, and 42% were non-Hispanic White. The most common cancer diagnoses included breast cancer (16%), thyroid cancer (16%), lymphoma (11%), and melanoma (10%).
Twenty-three percent of survivors were treated with external-beam radiation therapy. Exposure to selected chemotherapy agents ranged from 3% with epipodophyllotoxins to 24% with anthracyclines.
AYA cancer survivors had a 2- to 3-fold increased risk compared to the general population for cardiomyopathy, stroke, premature ovarian failure, chronic liver disease, and renal failure
With median follow-up post cancer diagnosis of 5.1 years, 1,443 (17%) survivors developed ≥1 comorbidity. By Poisson regression the researchers found a significantly higher incidence rate ratio (IRR) for survivors for nearly all comorbidities investigated. The adjusted IRR of developing any comorbidity among survivors of compared with the reference cohort was 1.47 (95% confidence interval [CI] 1.39-1.55).
The IRR was highest for avascular necrosis (IRR 8.25), followed by osteoporosis (IRR 5.75), joint replacement (IRR 3.89), stroke (IRR 3.19), premature ovarian failure (IRR 2.87), and cardiomyopathy or heart failure (IRR 2.64).
The adjusted IRR of developing ≥2 incident comorbidities was 1.63 (95% CI 1.48-1.78). At 10 years after the index date the prevalence of multiple comorbidities in survivors approached 49% versus 20% in the reference population (p < 0.001).
The most common co-morbidities among AYA survivors included dyslipidemia hypertension, diabetes, thyroid disorders, and severe depression or anxiety.
Chemotherapy and radiation therapy significantly associated with specific co-morbidities
Significant associations by multivariable analyses were found between exposure to cancer treatments versus no exposure and the development of co-morbidities. Cardiomyopathy associated with alkylating agent treatment at >2,500 mg/m2 (IRR 2.8), anthracycline at >240 mg/m2 (IRR 3.3), and trastuzumab at >4,000 mg/m2 (IRR 8.1) as well as chest radiation ≥30 Gy (IRR 2.6). Pulmonary fibrosis was significantly associated with bleomycin >120 mg/m2 therapy (IRR 4.7).
Avascular necrosis associated with any dose level of methotrexate (IRR 21.6) or corticosteroids (IRR 5.4), and any dose of corticosteroids significantly associated with osteoporosis (IRR 2.3).
Premature ovarian failure associated with the use of alkylating agents at >2,500 mg/m2 (IRR 4.5) or platinum agents >450 mg/m2 (IRR 9.0).
Hearing loss significantly associated with combined exposure to platinum at >450 mg/m2 and radiation ≥30 Gy to the head (IRR 14.9). Radiation therapy ≥30 Gy to the head and/or neck also was associated with the risk of stroke (IRR 3.5), thyroid disorders (IRR 3.1), and diabetes (IRR 1.9).
This study highlights the increased risk of developing comorbidities in AYA survivors of cancer compared with the general population and correlates the exposure to cancer treatment with the risk of developing specific comorbidities. The data have important implications for survivorship care planning. The findings facilitate the identification of high-risk survivors who may benefit from tailored surveillance and prevention strategies.
These findings underscore the need for age-appropriate survivorship guidelines for survivors of AYA cancer and set the stage for prevention, early diagnosis, and intervention strategies to mitigate the long-term comorbidity burden in the growing population of long-term survivors.
No external funding was disclosed.
Chao C, Bhatia S, Xu L, et al. Chronic Comorbidities Among Survivors of Adolescent and Young Adult Cancer. Journal of Clinical Oncology 2020;38(27):3161-3174. DOI: 10.1200/JCO.20.00722.