FEASIBILITY OF PROTON THERAPY WITH AND WITHOUT SIMULTANEOUS CHEMOTHERAPY IN CNS MALIGNANCIES OF CHILDREN AND ADOLESCENTS

Abstract BACKGROUND: Proton therapy (PT) is a valuable alternative to photon radiotherapy in treatment of CNS tumors in children and adolescents. The aim of this study was to investigate the feasibility of recent treatment strategies with a particular focus on the acute toxicity of a simultaneous radiotherapy and chemotherapy (sRCT). PATIENTS AND METHODS: We investigated 199 patients (116 male, 83 female, median age 7.4 years) who received in total 200 cycles of PT (60.5% at new diagnosis, 39.5% at relapse) from September 2013 to February 2017. Entities included ependymomas (34%), medulloblastomas (16%), low grade gliomas (13%), ATRTs (12%), craniopharyngiomas (9%), germ cell tumors (6%), and other entities (10%). SRCT was administered in 52 (26%) treatment cycles. The target tumor was predominantly localized infratentorial (53%), supratentorial (23.5%) and supra-/intrasellar (18%). 38 patients received additional CSI and 8 patients a boost to metastases. Data were collected retrospectively based on patient records. Toxicity was documented according to CTCAE version 4.03. RESULTS: Severe adverse events (SAE ≥ grade 3) occurred in 33.5% of all patients, in particular in form of hematotoxicity (64.1%) and infections (26.8%). In-patient treatment for unexpected SAEs was necessary in 33 patients (16.5%). In the group treated with sRCT 15 out of 52 (28.8%) patients couldn’t receive the recommended dose or time schedule of planned chemotherapy due to SAEs. Comparing the SAE frequency in both groups, the children who have been treated with sRCT had a significantly higher risk of SAEs than the patients who have received proton therapy only (63.5% vs. 23.0%, p=0.001). CONCLUSIONS: PT and concomitant chemotherapy are feasible, but require an interdisciplinary team with continuous out-/inpatient management of patients, as the risk of toxicity is significantly increased. Risk-adapted adjustment of simultaneous chemotherapy is necessary to reduce relevant interruptions of radiotherapy. Funded by the German Childhood Cancer Foundation