Comparison of 36 Gy, 20 Gy or No Radiotherapy After Six Cycles of EBVP Chemotherapy and Complete Remission in Early Stage Hodgkin Lymphoma Without Risk Factors : Results of the EORTC–GELA H9-F Intergroup Randomized Trial
Mené sur 578 patients atteints d'un lymphome hodgkinien de stade précoce et ayant reçu 6 cycles de chimiothérapie de type "EBVP", cet essai évalue, du point de vue de la survie sans récidive à 5 ans et de la toxicité, la possibilité de ne pas ajouter de radiothérapie au traitement ou de réduire la dose de rayonnements à administrer
Purpose : While patients with early-stage Hodgkin lymphoma (HL) have an excellent outcome with combined treatment, radiotherapy dose and treatment with chemotherapy alone remain questionable. The noninferiority trial evaluates the feasibility of reducing the dose or omitting radiotherapy after chemotherapy. Patients and Methods : Patients with untreated supra-diaphragmatic HL without risk factors (age≥50 years, 4-5 nodal areas involved, mediastinum/thoracic ratio≥0.35, erythrocyte sedimentation rate (ESR)≥50 mm/1st hour without B-symptoms or ESR≥30 mm/1st hour with B-symptoms) were eligible for the trial. Patients in complete remission after chemotherapy were randomized to no radiotherapy (noRT), low dose RT (20Gy/10 fractions) or standard dose involved-field radiotherapy (IFRT; 36Gy/18 fractions). The limit of noninferiority was 10% for the difference between 5-year relapse-free survival (RFS) estimates. From September 1998 to May 2004, 783 patients received six cycles of epirubicin, bleomycin, vinblastine, and prednisone (EBVP); 592 achieved a CR or unconfirmed CR of whom 578 were randomized to receive 36Gy (n=239), 20Gy of IFRT (n=209) or noRT (n=130). Results : Randomization to the noRT arm was prematurely stopped (≥20% of inacceptable events: toxicity, treatment modification, early relapse or death). Results in the 20Gy arm (5-year RFS, 84.2%) were not inferior to those of the 36Gy arm (5-year RFS, 88.6%) (Difference=4.4%; 90% CI, -1.2% to 9.9%). A difference of 16.5% (90% CI, 8.0% to 25.0%) in 5-year RFS estimates was observed between the noRT arm (69.8%) and the 36Gy arm (86.3%); hazard ratio was 2.55 (95% CI, 1.44 to 4.53; P<.001). The 5-year overall survival estimates ranged from 97% to 99%. Conclusions : In adult patients with early stage HL without risk factors in complete remission after EBVP chemotherapy, radiotherapy dose may be limited to 20 Gy without compromising disease control. Omitting radiotherapy in these patients may jeopardize treatment outcome.