Long-Term Outcomes in Patients with Intermediate-Risk Hodgkin′s Disease Treated with ≤3 Cycles of Chemotherapy followed by Subtotal Nodal Irradiation

Abstract

Purpose/Objective: To assess long-term outcomes including disease control, late treatment effects, and quality of life in a cohort of patients treated with ≤3 cycles of chemotherapy (CT) followed by subtotal nodal irradiation (STNI). Materials/Methods: Among a consecutive series of 415 Hodgkin′s patients, 37 who were identified with “intermediate risk Hodgkin′s disease” (large mediastinal masses with MMT >0.33 (74%), B symptoms (19%), and/or >4 involved nodal regions) were treated with ≤3 cycles of CT followed by STNI. Disease stages were I (3), II (24), and III (10). Alkylating agent-based chemotherapy was employed in 36 of 37 patients. STNI consisted of mantle, para-aortic, and splenic or splenic pedicle fields. Minimum potential follow-up was 5 years and observed follow-up ranged from 3.3 to 32 years (median of 13.6 y). Absolute (AS), cause-specific (CS) and event-free survival (EFS), and freedom from relapse (FFR) rates were calculated using the Kaplan-Meier product limit method. Quality of life was assessed in all living patients using the Functional Assessment of Cancer Therapy (FACT) questionnaire. Results: The 15 and 20 rates of FFR were 97% and 97%; AS, 89% and 77%; CSS, 94% and 94%; and EFS, 74% and 58%. Hypothyroidism developed in 46%, herpes zoster in 24%, infertility in 11%, and transient radiation pneumonitis in 8%. One patient died from Hodgkin′s, one from treatment related leukemia, and three from intercurrent disease. Three developed second malignancies at 9 to 15 years and two developed benign tumors at 18 years. None have had any evidence of disease after treatment. All living patients completed FACT surveys and self-reported excellent quality of life with median overall physical well-being scores of 0 (on a scale of 0 to 4, with 0 being complete physical well-being) and median functional well-being scores of 4 (on a scale of 4 to 0, with 4 being complete functional well-being). Conclusions: High disease control rates can be achieved in Hodgkin′s patients with a variety of approaches, but increasing importance in treatment selection is ascribed to long-term outcomes including not only disease control but also treatment-related toxicity. This report documents excellent long-term outcomes achieved in intermediate risk Hodgkin′s disease with ≤3 cycles of chemotherapy followed by subtotal nodal irradiation, including not only disease control, toxicity profiles, cause specific and event free survival, but also self-reported physical and functional well-being.