Secondary Malignancies in Diffuse Large B-cell Lymphoma Survivors With 40 Years of Follow-Up: Influence of Chemotherapy and Radiotherapy

Abstract

Survivors of non-Hodgkin lymphoma (NHL) are more likely to develop secondary malignancies (SM). We quantified this risk in survivors of diffuse large B-cell lymphoma (DLBCL), the most common subtype of NHL, and evaluated differences in risk by treatment modality.Standardized incidence ratios (SIR, observed-to-expected [O/E] ratio), which compare SM risk in patients to the endemic population, and absolute excess risk of SM were assessed in 45,946 patients diagnosed with DLBCL as a first malignancy between 1975 and 2016 in the National Cancer Institute's Surveillance, Epidemiology, and End Results Program. Non-melanoma skin cancers were not counted as SM. We subsequently stratified these risks by treatment modality.In all, 3,214 patients received radiotherapy alone (RT), 26,761 received chemotherapy alone (CT), 10,081 received chemoradiation (CRT), and 6,233 received no RT or CT. In total, 4,247 patients (9%) developed at least one SM, and a total of 4,862 SM developed amongst these patients (O/E 1.23, 95% Confidence Interval [CI] 1.19-1.26 P < .05). This increased risk of SM persisted regardless of treatment modality, including RT alone (O/E 1.15, 95% CI 1.03-1.27 P < .05), CT alone (O/E 1.24, 95% CI 1.2-1.29 P < .05), and CRT (O/E 1.30, 95% CI 1.23-1.38 P < .05). Overall, DLBCL survivors were at increased risk of developing leukemia, Hodgkin lymphoma, Kaposi sarcoma, head and neck, breast, thyroid, renal, bladder, bone, soft tissue, lung, liver/biliary, colon, and anal cancers compared to the endemic population (P < .05). Patients treated with any RT, including RT alone and CRT, had a similar SM risk when compared to those who did not receive any RT [O/E 1.26 (95% CI 1.2-1.33) vs. O/E 1.21 (95% CI 1.17-1.25) respectively P < .05]. Patients treated with RT had a higher risk of developing breast cancer than unirradiated patients [O/E 1.20 (95% CI 1.02-1.39) vs. O/E .86 (95% CI .76-.97) respectively P < .05]. Patients treated with any CT, including CT and CRT, had increased SM rates compared with those who did not receive CT [O/E 1.26 (95% CI 1.22-1.30) vs O/E 1.11 (95% CI 1.04-1.18) respectively P < .05]. Patients treated with CT had a higher risk of developing leukemia than those who did not receive chemotherapy [O/E 2.33 (95% CI 2.03-2.67) vs. O/E 1.4 (95% CI .98-1.93) respectively P < .05].This is the largest study to examine SM risk in patients with DLBCL based on treatment modality. The risk of SM was increased for DLBCL survivors regardless of treatment modality. Different treatment modalities were associated with unique SM risks, however, the magnitude of SM risk was similar with RT and CT. These data may help guide screening protocols for patients following treatment of DLBCL.