First Report On the H10 EORTC/GELA/IIL Randomized Intergroup Trial On Early FDG-PET Scan Guided Treatment Adaptation Versus Standard Combined Modality Treatment in Patients with Supra-Diaphragmatic Stage I/II Hodgkin's Lymphoma, for the Groupe d'Etude Des Lymphomes De l'Adulte (GELA), European Organisation for the Research and Treatment of Cancer (EORTC) Lymphoma Group and the Intergruppo Italiano Linfomi (IIL).

Early stage classical Hodgkin lymphoma (cHL) is highly curable with a combination of chemotherapy and radiotherapy. However, long term toxicities due to radiotherapy, mainly secondary tumors and cardiovascular events, are altering the outcome. FDG-PET has emerged as a potential new tool to early select good prognosis patients after a few cycles of chemotherapy. We use it as an experimental tool to adapt therapy in the current trial.

All patients with a stage I or II supra-diaphragmatic cHL, between 15 and 70 years-old, are eligible for the study and stratified according to GELA/EORTC criteria. Unfavorable (U) prognostic factors included patients with: CSII ≥ 4 nodal areas or age ≥ 50 yrs or MT ratio ≥ 0.35 or ESR ' 50 (without B-symptoms) or ESR ≥ 30 (with B-symptoms). All others are considered favorable (F). In the F group, the standard treatment is ABVDx3 and 30Gy involved-node radiotherapy (IN-RT); the interim FDG-PET scan after 2 cycles is made solely for sake of comparison with the experimental arm but will not affect treatment. The experimental arm consist of ABVDx2 followed by an FDG-PET: if the FDG-PET is negative, patients receive 2 additional cycles of ABVD and no radiotherapy. If the FDG-PET is positive, patients receive BEACOPPesc x2 and 30 Gy IN-RT. In the U group, the same principles are used, the standard treatment is ABVDx4 and 30Gy IN-RT; an FDG-PET is performed for all patients after cycle 2 with no modification of treatment. The experimental arm is ABVDx2 followed by an FDG-PET: if the FDG-PET is negative, patients receive 4 additional cycles of ABVD and no radiotherapy. If the FDG-PET is positive, patients receive BEACOPPesc x2 and 30 Gy IN-RT.

The trial started in December 2006 and at the end of July 2009, 1097 patients were included. A total of 530 patients have been entered during the last year. The main patients characteristics are as follows: median age 31 years-old (range 15-70), stage I: 16%, stage II: 84%. Thirty-nine % of the patients are in the F group and 61% in the U group. A baseline FDG-PET is not mandatory in the trial but highly recommended; it is available for 93% of patients entered with an improvement over time (from 88% during the first year of accrual to 96% during the last year). A central FDG-PET review is performed after cycle 2 by a panel of 6 nuclear medicine experts according to Juweid's criteria (J Clin Oncol 2007;25,571).The agreement between experts is good with a k=0.63 (95% CI 0.58-0.64) and 85% agreement (95% CI 83-87%), p=0.0008 (J Clin Oncol 2009;27;2739). On the first 485 cases centrally reviewed, a difference of interpretation between the local site reader and the central review panel is observed in 8% of the cases, in 58% of which PET after 2 cycles result was altered from “negative” to “positive”. Results of FDG-PET are available for the first 894 included patients. In the F group (355 patients), 14% are positive and 86% are negative. In the U group (539 patients), 24% are positive and 76% negative.

FDG-PET treatment adaptation is feasible in a large intergroup randomized trial and a baseline FDG-PET was shown to be available for most and recently all included patients. A centralized FDG-PET is feasible within 72 hours with an excellent agreement between involved experts and a low level of discrepancy with local nuclear physician

No relevant conflicts of interest to declare.