Involved-Field Radiation Therapy Prevents Recurrences in the Early Stages of Hodgkin Lymphoma in PET-Negative Patients After ABVD Chemotherapy: Relapse Analysis of GHSG Phase 3 HD16 Trial.

Abstract

The HD16 trial of the German Hodgkin Study Group (NCT00736320) demonstrated that radiation therapy in early-stage Hodgkin lymphoma without risk factors cannot be safely omitted, and therefore combined modality therapy (CMT) remains the standard treatment. To demonstrate the local effect of consolidating involved-field radiation therapy (IF-RT), we performed an analysis of the recurrence pattern of positron emission tomography (PET)-negative HD16 patients. Between 2009 and 2015, 1150 patients with early-stage Hodgkin lymphoma without risk factors were randomly assigned to PET guided to 20 Gy IF-RT after 2 cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine chemotherapy in the HD16 study of the German Hodgkin Study Group. The study was designed as a prospective randomized controlled trial. We correlated the localization of recurrence with the panel-based IF-RT plan, which was drawn up for all patients prospectively, blinded to treatment allocation. Accordingly, we were able to identify recurrences that occurred at least in part inside or outside of the (potential) radiation field (in-field and out-field, respectively). There were 328 and 300 PET-negative patients assigned to CMT and PET-guided treatment (ie, chemotherapy alone), respectively. Within a median 47-month follow-up, disease progression or recurrence was documented for 15 and 29 patients treated with and without IF-RT, respectively. Relapse localization was unknown in 1 CMT patient. Without IF-RT, 5-year incidence of in-field relapses was 10.5% (95% confidence interval, 6.5-14.6) compared with 2.4% (0.5-4.3) with CMT (P = .0008). There were no relevant differences in out-field recurrences (5-year incidence 4.1% [1.7-6.6] vs 6.6% [3.0-10.3], P = .54). There was no grade 4 toxicity observed during IF-RT, and incidence of second primary malignancies was similar in both groups. PET-negative patients of the HD16 study showed no significant toxicity after 20 Gy IF-RT, and we demonstrated that omission of IF-RT resulted in more, particularly local, recurrences. Therefore, consolidation IF-RT should still be considered as standard therapy in this setting.