Patterns of Relapse From a Phase 3 Study of Response-Based Therapy for Intermediate-Risk Hodgkin Lymphoma (AHOD0031): A Report From the Children's Oncology Group

Abstract

Purpose The study was designed to determine whether response-based therapy improves outcomes in intermediate-risk Hodgkin lymphoma. We examined patterns of first relapse in the study. Methods From 9/02 – 7/10, 1712 patients <22 yrs of age with stage I–IIA with bulk, I–IIAE, I–IIB, and IIIA–IVA with/without bulk were enrolled. Patients were categorized as rapid (RER) or slow early responders (SER) after 2 cycles of doxorubicin, bleomycin, vincristine, etoposide, prednisone, and cyclophosphamide (ABVE-PC). SER patients were randomized to 2 additional ABVE-PC cycles or augmented chemotherapy with 21Gy IFRT. RER patients were stipulated to undergo 2 additional ABVEPC cycles and were then randomized to 21Gy IFRT or no further treatment if complete response (CR) was achieved. RER without CR patients were non-randomly assigned to 21Gy IFRT. Relapses were characterized with respect to site (initial, new or both; and initial bulk or initial non-bulk), and IFRT field (in-field, out-of-field, or both). Patients were grouped by treatment assignment (SER; RER/no CR; RER/CR/IFRT; and RER/CR/no IFRT). Summary statistics were reported. Results At 4-year median follow-up, 244 patients had relapsed, 198 of whom were fully evaluable for review. Those who progressed on treatment (n=30) or lacked relapse imaging (n=16) were excluded. Median time to relapse was 12.8 months. Of the 198 patients, 30% were RER/no CR, 26% were SER, 26% were RER/CR/no IFRT, 16% were RER/CR/IFRT, and 2% remained uncategorized. 74% and 75% relapses involve initially bulky and non-bulky sites, respectively. First relapses rarely occurred at exclusively new or out-of-field sites. In contrast, relapses usually occurred at nodal sites of initial bulky and non-bulky disease. Conclusion While response-based therapy has helped define treatment for select RER patients, it has not improved outcome for SER patients or facilitated refinement of IFRT volumes or doses.

Proton therapy patterns-of-care and early outcomes for Hodgkin lymphoma: results from the Proton Collaborative Group Registry

“…In another study, Wray et al [16] evaluated 17 pediatric patients treated with PT and reported three recurrences, including two among patients with advanced stage IV disease. All three of those recurrences had a component of infield recurrence after 21-25.5 Gy, similar to the pattern of recurrence seen after photon radiation to 21 Gy in pediatric HL [17] and what was seen in the present study. ABVD: doxorubicin (Adriamycin), bleomycin, vinblastine, and dacarbazine; ABVE-PC: doxorubicin (Adriamycin), bleomycin, vincristine, etoposide, prednisone, and cyclophosphamide.…”

Proton Therapy for Pediatric Hodgkin Lymphoma

“…Considering that all the recurrences in our cohort had an in‐field component, our observations are consistent with AHOD0031 and suggest that higher radiation doses similar to the doses used in ECOG 2496 should be considered for slow responders in upcoming trials. Such guidelines are in fact included in AHOD 1331 for patients with Deauville 3 or higher disease on completing chemotherapy …”

Involved site radiation therapy for the treatment of early-stage Hodgkin lymphoma in adolescents and young adults

“…In pediatrics, the Children’s Oncology Group has conducted studies to utilize response-adapted IFRT in intermediate-risk cHL. 13 An analysis of treatment failures confirmed that initially involved sites are most likely to relapse after chemotherapy (but not exclusively). The authors speculated that consolidative ISRT may be a strategy to address such areas at risk while reducing the organ and tissue radiation risks of IFRT.…”