Involved-site radiotherapy is equally effective and less toxic than Involved-field radiotherapy in patients receiving combined modality treatment for early-stage unfavorable Hodgkin lymphoma - an analysis of the randomized phase III HD17 trial of the German Hodgkin Study Group.

Combined modality treatment (CMT) with chemotherapy followed by consolidation radiotherapy (RT), provides excellent outcomes for patients with early-stage Hodgkin lymphoma (HL). The international standard of care for consolidation RT, involved-site/involved-node radiotherapy (ISRT/INRT), has never been evaluated in a randomized phase III trial against the former standard involved-field radiotherapy (IFRT). In the multicenter phase III AnonymizedStudyGroupXXX AnonymizedStudyYYY trial, patients with early stage unfavorable HL were randomized between the standard CMT group and a positron-emission tomography (PET) -guided group. In the standard group, patients received two cycles of escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (eBEACOPP) and two cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) followed by 30 Gray (Gy) IFRT. In the experimental group patients received no further therapy if post-chemotherapy PET was negative, and 30 Gy AnonymizedStudyGroupXXX -INRT, comparable and therefore termed here ISRT, if PET was positive. Here, we analyze the interim PET positive patients in a post hoc analysis, and therefore the randomized comparison of IFRT versus INRT/ISRT. 1,100 patients were randomized, of which 311 had a positive PET after chemotherapy. Kaplan-Meier estimates of 4-year progression-free survival (PFS) were 96.8 % (95% CI: 91.6% - 98.8%) in the IFRT group and 95.4% (95% CI: 89.9% - 97.9%; HR: 1.40, 95% CI: 0.44 - 4.42) in the ISRT group. Pattern of recurrence analyses indicated that none of the cases of disease progression or recurrence in the ISRT group would have been prevented by the use of IFRT. Acute grade III/IV toxicities occurred in 8.5% of IFRT patients and 2.6% of ISRT patients (p=0.03). For the first time, consolidation INRT/ISRT was randomly compared to IFRT in a phase III trial. Regarding PFS, no advantage for IFRT could be demonstrated. In summary, our data confirm the place of INRT/ISRT as the current standard of care.

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Déclaration de conflit d'intérêts

Declaration of interests MO and HE report support from the German Cancer Aid for quality assurance for RT in GHSG HD 16/17 (70112331). HE is member of the ILROG-steering committee and speaker of working group “radiation therapy” of the German lymphoma alliance. DAE received honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Takeda and Sanfoi-Genzyme. PJB received contracts/grants of BeiGene, BMS, MSD and Takeda, received consulting fees from BeiGene and Takeda, received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from BeiGene, BMS, MSD, Stemline and Takeda and received support for attending meetings and/or travel from Celgene.. BvT is an advisor or consultant for Allogene, BMS/Celgene, Cerus, Incyte, IQVIA, Gilead Kite, Lilly, Miltenyi, Novartis, Noscendo, Pentixapharm, Roche, Amgen, Pfizer, Takeda, Merck Sharp & Dohme, and Gilead Kite; has received honoraria from AstraZeneca, BMS, Incyte, Lilly, Novartis, Roche Pharma AG, Takeda, and Merck Sharp & Dohme; reports research funding from Novartis (Inst), Merck Sharp & Dohme (Inst), and Takeda (Inst); and reports travel support from AbbVie, AstraZeneca, Gilead Kite, Lilly, Merck Sharp & Dohme, Pierre Fabre, Roche, Takeda, and Novartis. MF received payment or honoraria for lectures/presentations from Takeda, Janssen, Celgene, Lukon, BMS and Affimed. All other authors declare no competing interests.