Abstract

Preventing late toxicity has become the cornerstone in the management of HL as global results greatly improved regarding event-free (EFS) and overall survival (OS) rates. With this aim, the EORTC and GELA groups conducted a trial (H9-F) comparing three radiation doses in patients in complete remission (CR/CRu) after chemotherapy. Adult patients with supradiaphragmatic CS I-II HL and favorable features (age < 50, and CS I-II2–3, and A + ESR < 50 or B + ESR < 30, and MT ratio < 0.35) were eligible. After 6 cycles of EBVP (epirubicin, bleomycin, vinblastine, prednisone), CR/CRu patients were randomized between 36 Gy involved-field radiotherapy (IF-RT), 20 Gy IF-RT and no RT. From September 1998 to May 2004, 783 patients were enrolled in 111 institutions from 10 European countries. Inclusion of patients in the no-RT arm was stopped in May 2002 because stopping rules were met (i.e. > 20% of events). After 6 EBVP response rates were 50% CR, 26% CRu, 18% PR, 3% no change or progression, and 3% unspecified. Of the 591 CR/CRu patients, 13 (2%) were not randomized (6 refusals, 3 protocol violations, 4 causes unspecified). After a median follow-up of 51 months (range 14–81), 130 events (36 progressions, 91 relapses, 1 toxic death, 2 deaths of second cancer) were observed. At July 2005, the 4-year EFS and OS rates are as follows:

TreatmentNo. Pts.Prog. /Rel. /Death4-yr EFS4-yr OS
6 EBVP + IF-RT 36 Gy 239 2 /18 /0 88% 98% 
6 EBVP + IF-RT 20 Gy 209 5 /16 /0 85% 100% 
6 EBVP + no RT 130 1 /35 /1 69% 98% 
P value   < 0.001 0.241 
6 EBVP, no random. 205 28 /22 /2 68% 93% 
TreatmentNo. Pts.Prog. /Rel. /Death4-yr EFS4-yr OS
6 EBVP + IF-RT 36 Gy 239 2 /18 /0 88% 98% 
6 EBVP + IF-RT 20 Gy 209 5 /16 /0 85% 100% 
6 EBVP + no RT 130 1 /35 /1 69% 98% 
P value   < 0.001 0.241 
6 EBVP, no random. 205 28 /22 /2 68% 93% 

Non-randomized patients experienced a significantly worse OS than did complete responders (P=0.0012). Relapses in nodal sites were more frequent in the no RT arm (35 in unirradiated sites) than in RT arms (6 + 10 in irradiated sites). 15 patients have died, 10 of progressive disease, 2 of treatment-related complication, 1 of intercurrent disease and 2 of second cancer (1 AML, 1 NHL). In favorable early stage HL patients who achieve CR(u) after 6 cycles of EBVP, omission of IF-RT leads to an unacceptable failure rate; In contrast, with the current follow-up, IF-RT 20 Gy provides results equivalent to those of IF-RT 36 Gy.

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