Involved-site Radiation Therapy is Equally Effective and Less Toxic Than Involved-field Radiation Therapy in Patients Receiving Combined Modality Treatment for Early-stage Unfavorable Hodgkin Lymphoma—An Analysis of the Randomized Phase 3 HD17 Trial of the German Hodgkin Study Group

Abstract

PurposeCombined 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). Methods and materialsIn 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. Results1,100 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). ConclusionsFor 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.