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

PURPOSE: Combined modality treatment with chemotherapy followed by consolidation radiation therapy (RT) provides excellent outcomes for patients with early-stage Hodgkin lymphoma. The international standard of care for consolidation RT, involved-site/involved-node radiation therapy (ISRT/INRT), has never been evaluated in a randomized phase 3 trial against the former standard involved-field radiation therapy (IFRT). METHODS AND MATERIALS In the multicenter phase 3 GHSG (German Hodgkin Study Group) HD17 trial, patients with early-stage unfavorable Hodgkin lymphoma were randomized between the standard Combined modality treatment group and a positron-emission tomography (PET)-guided group. In the standard group, patients received 2 cycles of escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (eBEACOPP) and 2 cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) followed by 30 Gy IFRT. In the experimental group, patients received no further therapy if postchemotherapy PET was negative and 30 Gy GHSG INRT, comparable to 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. RESULTS: A total of 1100 patients were randomized, of which 311 had a positive PET after chemotherapy. Kaplan-Meier estimates of 4-year progression-free survival 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. The 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 3/4 toxicities occurred in 8.5% of IFRT patients and 2.6% of ISRT patients (P = .03). CONCLUSIONS: For the first time, consolidation INRT/ISRT was randomly compared with IFRT in a phase 3 trial. Regarding progression-free survival, no advantage of IFRT could be demonstrated. In summary, our data confirm the status of INRT/ISRT as the current standard of care.