Journal of Clinical Oncology, Vol 15, 2275-2287, Copyright © 1997 by American Society of Clinical Oncology
Dose-response relationship of complementary radiotherapy following four cycles of combination chemotherapy in intermediate-stage Hodgkin's disease
M Loeffler, V Diehl, M Pfreundschuh, U Ruhl, D Hasenclever, H Nisters-Backes, M Sieber, H Tesch, J Franklin, W Geilen, H Bartels, C Cartoni, G Dolken, J Enzian, R Fuchs, W Gassmann, H Gerhartz, U Hagen-Aukamp, E Hiller, H Hinkelbein, W Hinterberger, H Kirchner, P Koch, B Kruger and EW Schwarze
German Hodgkin Lymphoma Study Group, Cologne. loeffler@imisc.uni_leipzig.de
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.
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