Incidence of Secondary Malignancy and Other Late Effects after Proton Radiotherapy for Retinoblastoma

Abstract

<h3>Purpose/Objective(s)</h3> Radiotherapy is an important treatment modality for retinoblastoma (RB), an often-inherited pediatric cancer. Proton radiotherapy (PRT) is an infrequently used treatment modality for RB, and the late effects, particularly secondary malignancies, after PRT remain not well described. <h3>Materials/Methods</h3> We conducted an Institutional Review Board-approved retrospective cohort analysis of RB patients who received PRT from 1987-2011 at a major tertiary center. We recorded clinical and treatment characteristics, outcomes, and toxicities, including secondary malignancies. Follow-up time was calculated from the end of RT. Survival outcomes were analyzed using Kaplan-Meier method. <h3>Results</h3> We identified 60 patients who received PRT for RB, with 107 eyes diagnosed and 75 eyes receiving PRT. Median age was 0 years (range: 0.02-11) at diagnosis and 1 year (range: 0.2-12) at time of RT. International Classification for Intraocular Retinoblastoma (ICIR) Staging has 44.1% of patients in stages A-C, 37.3% of patients in stage D, and 18.6% of patients in stage E. Median follow-up time was 11.5 years (range: 0.02 - 34.4). No patients had follow-up beyond age 40. 10-year overall survival was 100%. 42 patients kept 50 irradiated eyes (67% of PRT-treated eyes) throughout follow-up. 3 (5%) patients were found to have secondary malignancies outside of the RT field: bladder cancer, localized melanoma on the left shoulder, and osteosarcoma in the left femur; none were found within the RT field. The patient with secondary osteosarcoma had a history of familial Rb1 mutation and ultimately passed due to her osteosarcoma after 14 years. Ocular changes were the most common side effects observed in follow-up. 13 patients developed cataracts (21%); 13 patients (21%) experienced considerable vision loss unrelated to cataracts. 5 patients (8.3%) were noted to have radiation retinopathy. 2 patients (3.2%) noted hearing decrease after completing treatment; notably both received carboplatin. No other non-ocular neurological sequelae were noted. <h3>Conclusion</h3> With a median follow-up of 11.4 years, we found no patients with secondary malignancies in the PRT field. Our findings suggest that PRT is effective and reasonably safe and that other factors, such as systemic chemotherapy and genetic Rb mutation, likely continue to contribute to secondary cancer risk. Patients remain at risk for development of cataracts and vision loss after PRT, though other components of treatment may also play a role. Prospective comparisons with photon cohorts with long-term follow-up are needed to determine the risks and benefits of PRT.