A prospective trial of involved field radiation (IFRT) + chemotherapy compared to extended field (EFRT) radiation for favorable Hodgkin disease: Survival differences and implications of mature follow-up for current combined modality therapy

Abstract

8014 Background: We conducted a prospective randomized trial from 1980–88 comparing IFRT plus VBM (vinblastine, bleomycin, methotrexate) chemotherapy to extended field radiation (EFRT) in patients with favorable stage I-IIIA disease to limit radiation exposure and define an effective treatment regimen that preserved fertility and did not increase the risk of leukemia. Methods: Patients (pt) with favorable, laparotomy-staged disease were defined as those with no bulky mediastinal disease, no or minimal abdominal disease (<5 cm), no or minimal splenic disease, and <1 extranodal site. VBM was given for 6 cycles after 44 Gy IFRT. EFRT was subtotal lymphoid for stage I-IIA and total lymphoid irradiation for I-IIB, IIIA pt. We previously reported (J Clin Oncol 6:1822, 1988) no survival differences in this study. Follow-up was similar for both arms and was further supplemented by an approved SSA Epidemiologic Vital Status Data Record application. Results: 72 pt were randomized, 34 to IFRT + VBM and 38 to EFRT. Median follow-up is 20.8 yr (10.3–25.1) and just 8 pt were censored at <15 yr. Twenty-one yr freedom from progression is 96% for IFRT + VBM vs 74% for EFRT (p= 0.035). A single death at 18 yr was recorded in IFRT + VBM pt (3%) whereas 11 deaths occurred among EFRT pt (29%). Overall survival (OS) at 21 yr is 95% for IFRT + VBM vs 68% for EFRT (p=0.003). As previously reported, fertility was informally assessed, but premature menopause was not observed and both men and women conceived after IFRT + VBM. Conclusion: The reduction of radiation to IFRT, combined with a less toxic chemotherapy in our study, resulted in excellent long-term OS that was significantly superior to EFRT. The survival data with IFRT + VBM also compare favorably with our historical EFRT experience. Moreover, these results have implications for current combined modality therapy where much lower doses of RT, more limited fields and brief chemotherapy should lead to even less late morbidity and mortality. No significant financial relationships to disclose.