Role of Radiation Therapy in Mortality among Adolescents and Young Adults with Lymphoma: Differences According to Cause of Death

SIMPLE SUMMARY: Despite its efficacy, emerging concerns exist regarding radiation therapy (RT)-associated toxicity in adolescent and young adult (AYA) lymphoma patients. However, the most current research studying the association between RT and outcome is based only on groups of lymphoma patients and is not compared with the general population, which could more accurately reveal the impact of RT on outcomes. This population-based analysis showed that after adjusting for potential confounders, RT administration is associated with a low risk of cause-specific mortality, including death due to the original diagnosis, second malignant neoplasms (SMNs), and noncancer causes, among AYA patients with lymphoma. This analysis may play a guiding role in the design of future lymphoma studies and the formulation of healthcare policies regarding the widespread use of RT, especially for AYA survivors. ABSTRACT: Background: Despite its efficacy, emerging concerns exist regarding radiation therapy (RT)-associated toxicity in adolescent and young adult (AYA) lymphoma patients. Few long-term follow-up studies have examined the association between RT and outcomes. Methods: Lymphoma patients aged 15–39 years were identified in the Surveillance, Epidemiology and End Results (SEER) database from 1992 to 2016. Mortality was assessed by comparing those with and without RT using the Fine–Gray competing risk model. Standardized mortality ratios (SMRs) were used to assess the relative risk of death compared with the general U.S. population. Results: In total, 29,686 patients were included; 10,708 (36.07%) received RT. Cause-specific mortality was compared between patients with and without RT while considering other competing events, including death due to index cancer, second malignant neoplasms (SMNs), and noncancer causes. Patients with RT had a lower probability of death and crude 5-year cumulative incidence of death. Moreover, there were significantly lower SMRs in patients with RT than in patients without RT. Differences between the two groups were greatest for mortality due to hematological malignancies and infections. Additionally, in the RT cohort, the SMR for index-cancer-related death was highest in the first year after diagnosis and gradually decreased. Hematological malignancies and infections were the most common specific SMN and noncancer causes of death, respectively. Conclusions: RT did not increase mortality from index cancer, SMNs, or noncancer causes in AYA patients with lymphoid malignancies. The current analysis may serve as a reference for healthcare providers monitoring RT application for AYA lymphoid malignancy survivors.