Dose-response relationship of complementary radiotherapy following four cycles of combination chemotherapy in intermediate-stage Hodgkin's disease.

Abstract

PURPOSE To determine the appropriate irradiation dose after four cycles of modern combination chemotherapy in nonbulky involved field (IF/BF) and noninvolved extended-field (EF/IF) sites in patients with intermediate-stage Hodgkin's disease (HD). MATERIALS AND METHODS HD patients in stage I to IIIA with a large mediastinal mass, E stage, or massive spleen involvement were treated with two double cycles of alternating cyclophosphamide, vincristine, procarbazine, and prednisone (COPP) plus doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) followed by EF irradiation in two successive trials (HD1 and HD5). In the HD1 trial (1983 to 1988), 146 patients who responded to chemotherapy were randomized to receive 20 Gy (70 patients) or 40 Gy (76 patients) of EF irradiation in all fields outside bulky disease sites. A cohort of 111 patients who fulfilled the same inclusion criteria in the subsequent trial HD5 (1988 to 1993) were treated with 30 Gy. Bulky disease always received 40 Gy. RESULTS Freedom-from-treatment-failure (FFTF) and survival (SV) curves showed no differences between the 20-, 30-, and 40-Gy groups. However, acute toxicities were more frequent in the 40-Gy arm. Analysis of relapse patterns showed that 18 of 26 relapsing patients either failed to respond in initial bulky sites (n = 5) or had an extranodal relapse (n = 9) or both (n = 4). After 5 years, the cumulative risk for relapse in bulky sites is 10%, despite 40 Gy of radiation. CONCLUSION Our results strongly suggest that there is no relevant radiotherapy dose effect in the range between 20 Gy and 40 Gy in IF/BF and EF/IF after 4 months of modern polychemotherapy in patients with intermediate-stage HD. Relapse patterns indicate that patients destined to relapse need more systemic, rather than local, treatment. Based on our data, we conclude that 20 Gy is sufficient in EF/IF of intermediate-stage HD following four cycles of modern polychemotherapy.

Comparison of initial characteristics and long-term outcome of patients with lymphocyte-predominant Hodgkin lymphoma and classical Hodgkin lymphoma at clinical stages IA and IIA prospectively treated by brief anthracycline-based chemotherapies plus extended high-dose irradiation

“…Decreasing the dose of RT to 25 to 30 Gy in initially involved areas is most likely possible in the 80% of patients having CR after CT without seriously modifying the relapse rate and the resulting HLM rate. [27][28][29] Such a dose decrease would probably decrease the incidence of cardiac complications 19,30 as well as that of second tumors 23 and their resulting mortality. Another possibility is to reduce the extent of RT by suppressing the adjuvant infradiaphragmatic irradiation.…”

Long-term Events in Adult Patients with Clinical Stage IA-IIA Nonbulky Hodgkin's Lymphoma Treated with Four Cycles of Doxorubicin, Bleomycin, Vinblastine, and Dacarbazine and Adjuvant Radiotherapy: A Single-Institution 15-Year Follow-up

“…As to radiotherapy, we used the extendedfield radiotherapy until 1997, and the involved-field radiotherapy thereafter, when data became available on the risk of secondary neoplasia after extensive radiotherapy, with particular emphasis on breast cancer after mantle irradiation in young women (14). We concomitantly reduced the cumulative irradiation dose per field (from 40-44 to 30-36 Gy) when the German Hodgkin's Study Group data indicated that dose could safely be reduced in a combined modality approach (15).…”

Principles of Radiation Therapy for Hodgkin Lymphoma

“…The results of prospective studies testing the concept have been confl icting. A meta-analysis of several randomized studies demonstrated that the addition of radiotherapy to chemotherapy reduces the rate of relapse but did not show survival benefi t for combined modality compared to chemotherapy alone [ 21 ].…”