The Impact of Radiation Therapy on the Incidence of Second Malignant Neoplasm among Adolescent and Young Adult Cancer Survivors

Abstract

<h3>Purpose/Objective(s)</h3> The risks of second malignancy, including radiation-associated malignancies, are well described in adult populations as well as among pediatric patients. Adolescents and young adults (AYA) are a vulnerable population in which the risks of late effects may be increased relative to older adult patients but are not fully characterized. We sought to investigate the incidence second malignant neoplasm among AYA patients and hypothesize that receiving radiation therapy is associated with increased risk of secondary cancers in this population. <h3>Materials/Methods</h3> The Surveillance, Epidemiology, and End Results (SEER) Research Plus database was queried for patients age 15-39 who survived at least 5 years after diagnosis of a solid-tumor primary malignancy between 1975-2017. Descriptive statistics were obtained and univariate comparisons were performed using ANOVA and chi-square test. The 15-year cumulative incidence of second malignant neoplasm (SMN) was calculated among AYA patients overall, among those who did vs did not receive radiation therapy, and across other significant variables. A multivariable model was created to assess the effect of receiving radiation therapy on the risk of SMN when adjusting for age, sex, decade of diagnosis, and disease. <h3>Results</h3> A total of 159,829 AYA patients with ≥5-year survival were included, 31.1% of whom received radiation therapy. Median follow up among the entire cohort was 17 years (range, 5-43 years). The cumulative incidence of SMN among all AYA patients at 15 years was 5.6%. The cumulative incidence of SMN at 15 years was significantly increased among AYA patients who received radiation therapy as part of their definitive treatment (6.6% with radiation therapy versus 5.1% without, p<0.001). Cumulative incidence of SMN was also affected by sex, age, decade of initial diagnosis, and AYA primary cancer diagnosis (see Table 1). On multivariable analysis, patients who received radiation therapy remained more likely to develop a second malignancy than those who did not (HR 1.4, p<0.001). <h3>Conclusion</h3> This study uses national data to report the incidence of second malignancy among adolescents and young adults diagnosed with cancer. Receiving radiation therapy was associated with an increase in SMN at 15 years, with an absolute increase of 1.5% and HR of 1.4 compared to those who did not receive radiation. These results provide an important reference for counseling patients regarding risks of treatment and should guide further efforts to improve treatment delivery and outcomes among this vulnerable population.