Cardiac mortality in patients with stage I and II diffuse large B-cell lymphoma treated with and without radiation: a surveillance, epidemiology, and end-results analysis

Purpose: Standard therapy for stage I and II diffuse large B-cell lymphoma consists of combined modality therapy with anthracycline-based chemotherapy, anti-CD20 antibody, and radiation therapy (RT). Curative approaches without RT typically utilize more intensive and/or protracted chemotherapy schedules. Anthracycline-based chemotherapy regimens are associated with a dose-dependent risk of left ventricular systolic dysfunction. We hypothesize that patients treated without RT, i.e., those who are treated with greater total chemotherapy cycles and hence cumulative anthracycline exposure, are at increased risk of cardiac mortality.

Methods and materials: The rate of cardiac-specific mortality (CSM) was analyzed in patients with stage I and II diffuse large B-cell lymphoma diagnosed between 1988 and 2004 by querying the National Cancer Institute Surveillance, Epidemiology, and End-Results database. Analyzable data included gender, age, race, stage, presence of extranodal disease, and RT administration.

Results: A total of 15,454 patients met selection criteria; 6,021 (39%) patients received RT. The median follow-up was 36 months (range, 6-180 months). The median age was 64 years. The actuarial incidence rates of CSM at 5, 10, and 15 years were 4.3%, 9.0%, and 13.8%, respectively, in patients treated with RT vs. 5.9%, 10.8% and 16.1%, respectively, in patients treated without RT (p < 0.0001; hazard ratio, 1.35; 95% confidence interval [CI]: 1.16-1.56). The increase in cardiac deaths for patients treated without RT persisted throughout the follow-up period. On multivariate analysis, treatment without RT remained independently associated with an increased risk of CSM (Cox hazard ratio, 1.32; 95% CI: 1.13-1.54; p = 0.0005).

Conclusions: Increased anthracycline exposure in patients treated only with chemotherapy regimens may result in an increase in cardiac deaths, detectable only through analysis of large sample sizes. Confirmatory evaluation through meta-analysis of randomized data and design of large prospective trials is warranted.