Proton Beam Therapy for Pediatric Tumors of the Central Nervous System-Experiences of Clinical Outcome and Feasibility from the KiProReg Study.

As radiotherapy is an important part of the treatment in a variety of pediatric tumors of the central nervous system (CNS), proton beam therapy (PBT) plays an evolving role due to its potential benefits attributable to the unique dose distribution, with the possibility to deliver high doses to the target volume while sparing surrounding tissue. Children receiving PBT for an intracranial tumor between August 2013 and October 2017 were enrolled in the prospective registry study KiProReg. Patient's clinical data including treatment, outcome, and follow-up were analyzed using descriptive statistics, Kaplan-Meier, and Cox regression analysis. Adverse events were scored according to the Common Terminology Criteria for Adverse Events (CTCAE) 4.0 before, during, and after PBT. Written reports of follow-up imaging were screened for newly emerged evidence of imaging changes, according to a list of predefined keywords for the first 14 months after PBT. Two hundred and ninety-four patients were enrolled in this study. The 3-year overall survival of the whole cohort was 82.7%, 3-year progression-free survival was 67.3%, and 3-year local control was 79.5%. Seventeen patients developed grade 3 adverse events of the CNS during long-term follow-up (new adverse event n = 7; deterioration n = 10). Two patients developed vision loss (CTCAE 4°). This analysis demonstrates good general outcomes after PBT.

Proton Beam Therapy for Children With Neuroblastoma: Experiences From the Prospective KiProReg Registry.

OBJECTIVE: Radiotherapy (RT) is an integral part of the interdisciplinary treatment of patients with high-risk neuroblastoma (NB). With the continuous improvements of outcome, the interest in local treatment strategies that reduce treatment-related side effects while achieving optimal oncological results is growing. Proton beam therapy (PBT) represents a promising alternative to conventional photon irradiation with regard to the reduction of treatment burden. METHOD: Retrospective analysis of children with high or intermediate risk NB receiving PBT of the primary tumor site during first-line therapy between 2015 and 2020 was performed. Data from the prospective in-house registry Standard Protonentherapie WPE - Kinder- (KiProReg) with respect to tumor control and treatment toxicity were analyzed. Adverse events were classified according to CTCAE Version 4 (V4.0) before, during, and after PBT. RESULTS: In total, 44 patients (24 male, 20 female) with high (n = 39) or intermediate risk NB (n = 5) were included in the analysis. Median age was 3.4 years (range, 1.4-9.9 years). PBT doses ranged from 21.0 to 39.6 Gray (Gy) (median 36.0 Gy). Five patients received PBT to the MIBG-avid residual at the primary tumor site at time of PBT according to the NB-2004 protocol. In 39 patients radiation was given to the pre-operative tumor bed with or without an additional boost in case of residual tumor. After a median follow-up (FU) of 27.6 months, eight patients developed progression, either local recurrence (n = 1) or distant metastases (n = 7). Four patients died due to tumor progression. At three years, the estimated local control, distant metastatic free survival, progression free survival, and overall survival was 97.7, 84.1, 81.8, and 90.9%, respectively. During radiation, seven patients experienced higher-grade (CTCAE ≥ °3) hematologic toxicity. No other higher grade acute toxicity occurred. After PBT, one patient developed transient myelitis while receiving immunotherapy. No higher grade long-term toxicity was observed up to date. CONCLUSION: PBT was a well tolerated and effective local treatment in children with high and intermediate risk NB. The role of RT in an intensive multidisciplinary treatment regimen remains to be studied in the future in order to better define timing, doses, target volumes, and general need for RT in a particularly sensitive cohort of patients.

Outcome and Patterns of Relapse in Childhood Parameningeal Rhabdomyosarcoma Treated With Proton Beam Therapy.

PURPOSE: The standard of care of childhood parameningeal rhabdomyosarcoma (pRMS) is chemotherapy and local radiation therapy. Protons are increasingly being used to decrease late effects. The aim of the present study is to analyze the pattern of relapse and the correlation with dosimetric factors in pRMS treated with proton therapy. METHODS AND MATERIALS: This retrospective evaluation includes children treated in our institution for pRMS. Information on demographics, treatment, tumor characteristics, and toxicities and outcome was prospectively collected within the in-house registry. For patients presenting with local relapse, a fusion of the dosimetry with magnetic resonance imaging displaying site and geometry of recurrence was performed. RESULTS: Median follow-up time was 2.9 years (0.5-4.7). Forty-six patients were identified in our institution between July 2013 and November 2017. Main characteristics of patients were as follows: 56.5% male, median age 5.1 years (1.3-17.5), 39.1% alveolar histology, 26.1%, 52.2%, 8.7%, and 13% patients with subgroup risk classification D, E/F/G, H, or metastatic, respectively, median total prescribed dose 55.8 Gy (50.4-56.4). Estimated 2-year local control, metastasis-free survival, event-free survival, and overall survival were 83.8%, 87.8%, 76.9%, and 88.9%, respectively. No acute or late local toxicity exceeding grade 3 was observed. Risk-group was identified as prognostic factor for metastasis-free survival in univariate analysis but not in multivariate analysis (trend: P = .09). In this cohort, dosimetric factors did not correlate with outcome. Isolated local failure happened in 5 of the 11 relapses. Local relapses were matched with dosimetry for 6 patients: 4 of them occurred in the high dose volume and 2 in the intermediate or low dose volume. CONCLUSIONS: Proton therapy was effective and well feasible even in a critical cohort. Still, local relapse within the target volume of the radiation therapy remains an important issue in pRMS and new treatment strategies are needed.