Response-Adapted Omission of Radiotherapy in Pediatric Patients with Intermediate- and High-Risk Hodgkin Lymphoma Treated per EuroNet-PHL-C1: A Single Institution Analysis of Outcomes and Patterns of Failure

Abstract

EuroNet-PHL-C1 demonstrated that 40% of intermediate- and high-risk pediatric Hodgkin lymphoma (HL) patients treated with OEPA-COPDAC chemotherapy achieved adequate response (AR) at early response assessment (ERA), and thus were able to omit radiotherapy (RT). However, patterns of failure with this treatment paradigm, and specifically, whether or not all initial sites of disease require RT for those with inadequate response (IR) at ERA is unknown. The purpose of our study is to examine outcomes and patterns of failure for those treated per EuroNet-PHL-C1 at our institution. Our hypothesis is that limiting RT to only sites of IR at ERA does not result in increased failures. An IRB-approved retrospective review of all intermediate- and high-risk classical HL pediatric patients treated at our institution per EuroNet-PHL-C1 between 2015 and 2021 was performed. Patients were treated per protocol with radiation omitted for those with AR (Deauville 1-2 and >75% tumor shrinkage) at ERA (PET/CDT after 2 cycles of chemo). For those with IR who required RT, only sites of IR (Deauville 3-5) at ERA were treated using involved site radiation treatment (ISRT), instead of all initial sites of disease as on EuroNet-PHL-C1. Outcomes including overall survival (OS) and progression free survival (PFS) were calculated using Kaplan-Meier curves and patterns of failure were classified as either initial site only, new site only, or initial and new sites. A total of 35 patients were identified, of which 33 had evaluable follow up with median follow up of 33 months. The median age at diagnosis was 14 (range, 4-18) and 48% were female. Of the 33, 7 (21%) had IR at ERA and thus required RT, while 26 (79%) were spared RT. In the group who received RT, 4/7 (57%) had initial B-symptoms and 4/7 (57%) had initial bulky disease, compared to 9/26 (35%) and 20/26 (77%), respectively, in those who did not receive RT. For our entire cohort, 2-year PFS and OS were 91% and 100%, respectively. For those who had RT, 2-year PFS was 83% compared to 92% in those who did not need RT. There was a total of 3 relapses (9%) at last follow up with 1/7 (14%) in those who had RT vs. 2/26 (8%) in those without RT. For the patient who relapsed after RT, relapse occurred both at initial and new sites. For the 2 who relapsed who did not receive RT, 1 was both in initial and new sites, while the other was initial site only. At our institution, the majority of patients treated per EuroNet-PHL-C1 avoided RT with excellent outcomes. For those requiring RT, limiting RT to only sites of IR at ERA does not appear to adversely affect outcomes, though analysis is limited by the low number of failures.