IFRT Appears Safe, Effective Standard of Care for Some Pediatric Patients with High-Risk cHL

Response-based consolidation involved-field radiation therapy (IFRT) appears to be a safe and effective standard of care for a cohort of pediatric patients with high-risk classical Hodgkin lymphoma (cHL), with very low rates (2.4%) of failures outside of these modern risk-adapted radiation treatment volumes observed.¹

Additionally, PET2 positivity did not appear to identify the majority of all relapse sites. These findings were presented at the American Society for Radiation Oncology (ASTRO) Annual Meeting and are part of a phase 3 study from the Children’s Oncology Group.

“These results validate that modern combined modality efforts of chemotherapy and radiation therapy for pediatric patients with Hodgkin lymphoma is very effective and leads to excellent outcomes,” lead study investigator Rahul R. Parikh, MD, director of the Laurie Proton Therapy Center at Robert Wood Johnson University Hospital and associate professor of radiation oncology at Rutgers Robert Wood Johnson Medical School, said in a press release.²

From December 2009 to January 2012, 164 evaluable patients 22 years old or younger with stage IIIB (43%) and stage IVB (57%) were eligible for the study. In total, 85 (51.5%) patients presented with a large anterior mediastinal mass, 44 (26.7%) with extra-mediastinal bulk, and 85 (51.5%) with macronodular splenic involvement. Overall, bulk disease was observed in 138 (84%) patients.

Patients were categorized as rapid early responders (RER) or slow early responders (SER) following 2 cycles of doxorubicin, bleomycin, vincristine, etoposide, prednisone, and cyclophosphamide (ABVE-PC). The SER patients were randomized to 2 additional chemotherapy cycles of ifosfamide/vinorelbine and 2 cycles of ABVE-PC, followed by adapted IFRT to areas of bulky disease and/or slow-responding site(s). RER patients underwent 2 additional ABVE-PC cycles and involved-site radiation therapy (ISRT) to sites of initial bulky involvement only.

Ultimately, 125 (76%) patients received radiation therapy (RT). Sixty of the 125 were RER and 65 were SER.

Of note, per protocol specifics, no patients received a boost beyond the prescribed 21 Gy. Relapses were characterized with respect to site (initial, new, or both; and initial bulk or initial non-bulk), and radiation field (in-field, out-of-field, or both).

At a median follow-up of 4.5 years, 27 of 145 (19%) patients relapsed and 23 patients were evaluable. Of those 23 patients, 11 were RER patients and 12 were SER patients. Moreover, within the 23 evaluable patients with relapse (all but 1 received protocol IFRT), there were 105 total sites (median = 4; range, 1-11) of relapse.

Further, 64% of relapses occurred within an initial site of involvement, including 18% that were at an initial site of bulky disease, 32% which occurred in a new site of disease (that would not have been covered by RT), and 2.4% (occurring in 3 RER and 1 SER) which were isolated out-of-field relapses that would have been covered by historical IFRT.

Overall, 94% of relapses occurred in sites that were initially PET2-negative.

References:

1. Parikh RR, Hoppe BS, Hodgson D, et al. Patterns of Relapse from a Phase 3 Study of Response-Based Therapy for High-Risk Hodgkin Lymphoma (AHOD0831): A Report from the Children’s Oncology Group. Presented at the American Society for Radiation Oncology (ASTRO) Annual Meeting. Abstract #: 73.

2. Studying Patterns of Relapse in Pediatric Hodgkin Lymphoma using a Response-Based Therapy Approach [news release]. New Brunswick, NJ. Published October 23, 2020. Accessed November 9, 2020. https://www.newswise.com/articles/studying-patterns-of-relapse-in-pediatric-hodgkin-lymphoma-using-a-response-based-therapy-approach?sc=sphr&xy=10021790