Proton Therapy for Management of Pediatric Hodgkin Lymphoma Involving the Mediastinum: Evaluation of Toxicity and Evolution of Therapy Over 7 Years of Experience

Abstract

Clinical trial design in pediatric Hodgkin lymphoma has prioritized identification of patients who respond rapidly and completely to systemic therapy and can safely forego radiation therapy. However, this comprises a small number of patients overall and many require consolidative radiation therapy to provide durable disease control. Given the excellent projected long-term survival in this patient population, proton therapy is an appealing approach to minimize long-term and late toxicity. Here, we present our 7-year experience with proton therapy. Patients with Hodgkin lymphoma receiving mediastinal radiation between 2011-2017 were evaluated. Demographics, treatment details, and therapy-related toxicity were collected. Survival was recorded as time from diagnosis to last contact or death, using Kaplan-Meier estimates for progression free (PFS) and overall survival (OS). Patients with 3 or more years of follow up were reviewed for late toxicities. Sixty-six patients were evaluated, with median age of 16 (range 7-20) and slight female predominance (55%). The majority of patients had stage II disease (63%), with 25% presenting with B symptoms, and 50% with bulky disease. All patients had disease involving the mediastinum, with additional neck involvement in 61%, disease below the diaphragm in 27%, and bone in 6% of patients. Patients were treated with mixed proton-photon plans through 2013, using double scattered protons over the mediastinum with matched 3DCRT or IMRT photons for treatment of the neck. Full pencil beam scanning plans were standard by 2015. This variation was the result of differences in technology available at our center based on treatment era. Common acute side effects were fatigue (50% of patients) and radiation dermatitis (39%), however the majority were grade 1 and mild. There were no grade 3 toxicities. Acute toxicity frequency did not change as proton planning methods evolved. Relapses occurred in 14 patients (21%) with in-field recurrence in 10 of the cases (15%). Median follow up time was 3.5 years. Three and 5 year PFS were 79 and 71%, respectively, and OS was 98% at both intervals with only one death in a patient with refractory disease. Thirty-six patients (55%) had 3 or more years of follow up. Echocardiography and pulmonary function tests were available in 42 and 67% of those patients, respectively, with no documented changes other than pulmonary changes following bleomycin. There were no other reported late toxicities. Hodgkin lymphoma involving the mediastinum can be consolidated with proton therapy, achieving control rates similar to historical measures. The greatest benefit of proton therapy will likely be a decrease in late toxicities by reducing the amount of normal tissue exposed to radiation; this clinical sparing is suggested by these early data, and longer follow up with this cohort is planned.