Treatment Approaches and Outcomes for Patients with Pineoblastomas (PBs) and other Supratentorial Embryonal Tumors (STETs) Treated with Radiation Therapy (RT): A Study from the Pediatric Proton/Photon Consortium Registry (PPCR)

Abstract

<h3>Purpose/Objective(s)</h3> STETs are rare, aggressive pediatric brain tumors and include PBs of the pineal gland. They have traditionally been treated with surgery, 36 Gy craniospinal irradiation (CSI) with a boost to the primary tumor bed, and chemotherapy (CT). Some advocate deescalating CSI dose to 23.4 Gy for patients with M0 and minimal residual disease (< 1.5 cm²). Here we describe treatment approaches and report event-free survival (EFS) and overall survival (OS) in patients with STETs enrolled in the PPCR. <h3>Materials/Methods</h3> Patients with STETs and PBs were identified from the PPCR, a multi-institutional registry of pediatric patients treated with RT. We estimated time-to-event outcomes using the Kaplan-Meier method and log-rank test. All tests were two-sided with an alpha value of 0.05. <h3>Results</h3> 73 patients with STETs were identified in the PPCR, and 46 patients had at least 1 year of follow up required for inclusion. There were 28 (61%) PBs and 18 (39%) non-PB STETs. Median follow-up was 42.4 months; median age at RT was 7.1 years (range, 2.1-21.1); 33% of patients were female; 80% received CSI; 91% received CT. At diagnosis, 10 (36%) PB and 2 (11%) non-PB STET patients had M+ disease, and 11/24 (46%) PBs and 13/14 (93%) non-PB STETs had a GTR/NTR. 3-year EFS and OS was 71% and 81% for all STET patients, and 67% and 79% for PBs compared to 77% and 85% for non-PB STETs (p=0.74, p=0.26). Median time from surgery to RT was 5.4 weeks (range, 2.3-39.0). Median CSI dose was 36 Gy (range, 18-36); 23% received ≤23.4 Gy CSI. Among the 20 patients who received > 23.4 Gy CSI, 18 (90%) received 36 Gy. Median total tumor bed dose was 54.1 Gy (range, 50.4-59.4) for non-PB STETs and 54.0 Gy (range, 50.4-55.8) for PBs (p=0.02). There were no statistically significant correlations between either EFS or OS with M0 disease, CSI use, CSI dose, CT use, high-dose CT, or extent of resection in the entire cohort or PB/non-PB STET subgroups. However, there were trends favoring better 3-year EFS with M0 disease (77% v 57%, p=0.20), GTR/NTR (78% v 58%, p=0.34), use of CSI (73% v 61%, p=0.63), and CSI dose >23.4 Gy (75% v 62%, p=0.33). The trend toward improved 3-year EFS with CSI dose >23.4 Gy remained among patients with M0 disease (85% v 67%, p=0.27). <h3>Conclusion</h3> Most STET patients in the PPCR were treated with surgery, RT inclusive of CSI, and CT. There was no difference in EFS or OS between the PB and non-PB STET cohorts though this may be limited by small sample size. While numbers remain small, there may be trends to improved outcomes with GTR/NTR, CSI use, and higher dose CSI, including among M0 patients treated with higher dose CSI. More detailed study is warranted.