Reduced versus full doses of irradiation after 3 cycles of combined doxorubicin, bleomycin, vinblastine, and dacarbazine in early stage Hodgkin lymphomas: results of a randomized trial

BACKGROUND: The combination of 3 cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) and a tailored, extended irradiation schedule has been used to treat patients with early Hodgkin lymphoma (HL) in the authors' group since 1981. The randomized H97-E trial (1997-2004) was designed to assess the impact of a slightly reduced irradiation dose on the freedom from treatment failure (FFTF) rate.

METHODS: Patients with supradiaphragmatic HL at clinical stages I and II who had </=2 affected lymph node areas and a mediastinal mass ratio <0.33 were randomized into an experimental arm (EA) and a control arm (CA). Patients in the EA received 3 cycles of ABVD followed by irradiation at 36 grays (Gy) to initially involved sites and 24 Gy to adjacent sites, the upper infradiaphragmatic area, and the spleen. Patients in the CA received the same chemotherapy regimen and the same irradiation given at doses of 40 Gy and 30 Gy, respectively. Two hundred two patients who had received the CA treatment in 2 previous trials served as a historic control group (HCG).

RESULTS: The 10-year FFTF and overall survival rates were similar for the 89 patients in the EA (88.6% and 97.8%, respectively), for the 99 patients in the CA (92.6% and 95%, respectively), and for the 202 patients in the HCG (91.9% and 92.9%, respectively). Surprisingly, the 10-year incidence of severe or fatal complications was nil in the EA but reached 15.5% in the CA (P < .003) and 11.1% in the HCG.

CONCLUSIONS: Slightly lowering the radiation dose did not have an impact on the excellent cure rate among patients with early HL but significantly reduced the rate of long-term, radiation-induced complications.