Comparison of Three Radiation Dose Levels after EBVP Regimen in Favorable Supradiaphragmatic Clinical Stages (CS) I-II Hodgkin’s Lymphoma (HL): Preliminary Results of the EORTC-GELA H9-F Trial.

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: Treatment No. Pts. Prog. /Rel. /Death 4-yr EFS 4-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.

Involved Nodal Radiotherapy vs. Involved Field Radiotherapy after Chemotherapy in the Treatment of Early Stage Hodgkin’s Lymphoma

“…In the EORTC-GELA H9-F study for early favorable Hodgkin's lymphoma investigating reduction or omission of IFRT following complete remission to EBVP (epirubicin, bleomycin, vinblastine, and prednisone), no differences were seen between 20 and 36 Gy radiation on interim analysis [21]. However, the no-RT arm was closed due to excess relapse [21].…”

Chemotherapy only for localized Hodgkin lymphoma

“…Preliminary results of the EORTC‐GELA H9‐F trial were reported in abstract form [29]. This trial randomized early‐stage patients with HL and favourable features to chemotherapy alone with epirubicin, bleomycin vinblastine and prednisone (EBVP), EBVP and 20 Gy involved field radiation therapy (IF RT) or EBVP and 36 Gy IF RT.…”

The Case for Chemotherapy Only for Localized Hodgkin Lymphoma

“…Preliminary results of the EORTC-Groupe d'Etude des Lymphomes de l'Adulte H9-F trial were recently reported [24]. That trial, conducted after 1999 and recently closed, randomized early-stage HL patients with favorable features to chemotherapy alone with EBVP, EBVP plus 20 Gy IFRT, or EBVP plus 36 Gy IFRT.…”