Long-Term Outcomes of Pediatric Patients with Chordomas Treated with Proton Beam Radiation Therapy

Abstract

<h3>Purpose/Objective(s)</h3> Chordomas are rare tumors that arise from embryonic remnants of the notochord and can arise anywhere along the spine or the base of skull. This condition is even more uncommon within the pediatric population, and standard of care treatment includes maximal safe resection with subsequent radiation. The use of proton radiation allows for a conformal delivery of radiation dose that potentially minimizes the exposure of sensitive nearby structures to harmful treatment effects. The purpose of this study is to evaluate the long-term survival and toxicity of pediatric patients with base of skull or cervical spine chordomas treated at this institution with proton-based radiation therapy. <h3>Materials/Methods</h3> This IRB-approved single-institution study examines a cohort of 36 pediatric patients (≤ 18 years old) with 39 lesions treated with proton radiation between 1994 and 2016. Patients were included if they were treated with definitive intent and had at least five years of time since completing radiation treatment. Median age at treatment of patients was 10.9 years old. 79% of lesions received subtotal resection, while 21% received gross total resection. 10 patients received chemotherapy. The vast majority of tumors was treated to 72-77.4Gy in 40-43 fractions. Two patients were treated to 66.6Gy in 37 fractions. <h3>Results</h3> Median follow-up time was 100 months. The 5-year overall survival for the entire cohort was 26/36 (72%), further stratified by gender to reveal 68% in the female cohort and 75% in the male cohort. Seven patients (19%) developed distant metastases and subsequent passed away from their disease. GTV over size of 25cc and poorly differentiated histology were associated with decreased overall survival and local control. Of the 30 patients with base of skull lesions, at most recent follow-up, 15 patients (50%) had ototoxicity with 12 of those cases related to adjuvant treatment. 17 patients had confirmed pituitary dysfunction or required pituitary hormone replacement at some timepoint after treatment, 7 patients had no dysfunction, 5 patients died without evidence of pituitary dysfunction, 1 patient did not have pituitary function tests available. No instances of brain or brainstem necrosis were seen. Of the 21 survivors, 20 were either in school or employed with no cognitive or learning disabilities present. <h3>Conclusion</h3> This single-institution experience shows the efficacy and safety of proton radiation in pediatric patients with chordomas. Limitations include small number of patients and retrospective nature of the study. Future directions include analysis at 10-year follow-up and further evaluation of long-term toxicity.