A Prospective Trial of Radiation Alone vs Combination Chemotherapy Alone for Early-Stage Hodgkin’s Disease: Implications of 25-Year Follow-Up to Current Combined Modality Therapy.

We conducted a prospective randomized trial comparing radiation therapy to MOPP chemotherapy in patients with stages IA through IIIA Hodgkin’s disease (HD). Patients with peripheral stage IA disease received radiation therapy without randomization. Median follow-up is now 25 years. Among the 30 patients with peripheral stage IA disease, all achieved complete response, 4 relapsed (13%), 8 died [27%; 2 from HD, 1 suicide, 1 myocardial infarction (MI), and 4 from second malignancies). Among the 51 patients randomized to receive radiation, 49 (96%) achieved complete response, 19 relapsed (39%), 18 died (35%; 10 from HD, 1 AIDS, 1 anorexia nervosa, 1 pulmonary fibrosis, 3 congestive heart failure, and 2 from second malignancies). In addition, 7 other second cancers have been observed in 6 patients treated with radiation who are alive and significant treatment toxicities affect the lives of 5 others. Among the 54 patients randomized to receive MOPP chemotherapy, 52 (96%) achieved complete response, 7 relapsed (13%), 10 died [18%; 5 from HD, 2 MI (1 in cycle 1), 1 from Pneumocystis pneumonia during treatment, and 2 from second malignancies]. Two other patients are alive with a second cancer and one has AIDS. Disease-free survival is 87% for MOPP and 61% for radiation in the randomized arms at 25 years (p=0.0034). Overall survival is 81% for MOPP and 63% for radiation in the randomized arms at 25 years (p=0.048). When the peripheral IA patients are added to the randomized radiation-treated patients, disease-free survival is 70% (p=0.36 vs MOPP) and overall survival is 67% (p=0.07 vs MOPP). The design of the study permits an analysis of the late effects associated with the administration of radiation alone or MOPP alone as a substantial fraction of patients achieved complete response and remained in their initial remission. Among all patients treated with radiation, 11 died in first remission (5 from a second cancer, 2 from CHF, 1 MI, 1 pulmonary fibrosis, 1 AIDS, 1 suicide). Among all patients treated with MOPP, 3 died in first remission (2 from a second cancer, 1 MI). The difference in survival after achieving initial CR (93% for MOPP, 78% for radiation) is significant (p=0.054). The current standard practice of using combined modality therapy might be expected to incur the toxicities associated with both chemotherapy and radiation therapy. Furthermore, synergistic toxicities associated with the combination have been described. Thus, efforts should be made to define the substantial fraction of patients whose disease can be controlled with a single modality and reserve combined modality therapy for the subset that requires it for disease control.