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).
Authors: André Marc PE , Reman Oumédaly , Fédérico Massimo , Brice Pauline , Brusamolino Ercole , Girinski Théodore , Ferme Christophe , Maazen Richard vander , Bellei Monica , Sebban Catherine , Morschhauser Franck , Lugtenburg Elly , Stamatoullas Aspasia , Baila Liliana , Fortpied Catherine , Meignan Michel , Raemaekers John M. 
Published: October 2019

Abstract
Abstract 97

Introduction
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.

Patients and methods
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.

Results
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.

Conclusion
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

Disclosures:
No relevant conflicts of interest to declare.