Outcomes and Acute Toxicities of Proton Therapy for Pediatric Atypical Teratoid/Rhabdoid Tumor of the Central Nervous System

Abstract

Purpose Atypical teratoid/rhabdoid tumor (AT/RT) of the central nervous system is a rare cancer primarily affecting children younger than age five. Because patients are young and receive intensive chemotherapy, there is concern regarding late radiation toxicity, particularly as survival rates improve. Therefore, there is interest in using proton therapy to treat these tumors. This study was undertaken to investigate outcomes and acute toxicities associated with proton therapy for AT/RT. Materials and Methods The records of 31 patients with AT/RT treated with proton radiation from October 2008 to August 2013 were reviewed. Demographics, treatment characteristics and outcomes were recorded and analyzed. Results Median age at diagnosis was 19 months (range, 4 – 55 months), with median age at radiation start of 24 months (range, 6 – 62 months). Seventeen received local radiation with median dose of 50.4 GyRBE (range, 9 – 54). Fourteen received craniospinal radiation; half received 24 GyRBE or less and half received 30.6 GyRBE or higher. For patients receiving craniospinal radiation, the median tumor dose was 54 GyRBE (range, 43.2 – 55.8). Twenty-seven (87%) completed the planned radiation. With median follow-up of 24 months for all patients (range, 3 – 53 months), median progression-free survival was 20.8 months and median overall survival was 34.3 months. Five patients (16%) developed clinical findings and imaging changes in the brainstem one to four months after radiation consistent with radiation reaction; all resolved with steroids or bevacizumab. Conclusions This is the largest report of children with AT/RT treated with proton therapy. Preliminary survival outcomes in this young pediatric population are encouraging compared to historic results, but further study is warranted.

A systematic review of the cost and cost‐effectiveness studies of proton radiotherapy

“…Emerging data suggest dosimetric superiority and/or reduced toxicities with PBT for several pediatric tumors, including retinoblastoma, brain tumors and craniopharyngiomas, rhabdomyosarcoma, ependymoma, and esthesioneuroblastoma . However, to date, CE analyses for these tumors have not been performed.…”

Trimodality therapy for atypical teratoid/rhabdoid tumor is associated with improved overall survival: A surveillance, epidemiology, and end results analysis

“…Although the use of RT in patients < 3 years old remains controversial, a risk‐adapted approach that emphasizes focal RT in the infant population may strike a balance in toxicity. In addition, referral of these patients to centers with access to proton therapy could further mitigate late toxicity …”

“…This is largely due to the observation of heightened late CNS toxicity as a function of dose and younger age at the time of irradiation; specifically, intellectual impairment, endocrine dysfunction, growth disturbances, and increased secondary malignancy have been reported. [15][16][17] Nevertheless, the clinical benefit of RT in the management of AT/RT has been published in a number of series [2][3][4][18][19][20][21][22][23][24] ; but, in one of the largest series, <40% of patients received RT as part of their management. 25 The purpose of the current investigation is to robustly analyze the impact of RT among pediatric AT/RT patients who underwent definitive surgical resection followed by receiving chemotherapy using the Surveillance, Epidemiology, and…”

Clinical outcomes following proton therapy for children with central nervous system tumors referred overseas

“…Nevertheless, the utility of proton therapy in pediatric brain tumors is now documented in a growing number of dosimetric and clinical studies. [7][8][9][10][11][12][13][14][15][16][17][18][19][20] In 2016, a study was published describing 24 pediatric cancer patients transferred from Denmark to the United States for proton therapy. 21 Most of these children had brain tumors.…”