Proton beam therapy in pediatric patients with central nervous system tumors: method features, clinical data analysis

Abstract

   Introduction. Central nervous system (CNS) tumors are the most common pediatric solid tumor, that need multimodality treatment approach including surgery, intensive chemotherapy (CT) and radiotherapy (RT). Due to toxicity, mostly late, RT has limited use in children, especially those under 3 years of age. The physical characteristics of proton beam therapy (PBT) minimize the risk and types of toxicity compared to photons, making it the preferred choice for pediatric use.   Aim – to analyze the experience of PBT in patients under 18 years of age with various types of CNS malignancies, the assessment of risk factors for acute and late toxicity and its clinical manifestations. Materials and methods. A retrospective analysis of 63 courses of PBT performed in 58 patients with CNS malignancies for the period from 2018 to 2022 was carried out on Proton Center of the Sergey Beresin Medical Institute. The manifestations of local and systemic toxicity (predominantly acute) were analyzed, with an assessment of the influence of age, the volume of RT, the use of previous and concomitant CT on the severity of adverse events (AE).   Results. In the study cohort, patients with embryonal CNS malignancies predominated (72.3 %). Median age was 5 years 2 months, median follow-up was 15 months. In 36 % of cases, a complete response was achieved by the start of PBT. Patients with craniospinal irradiation (CSI) prevailed (60 %). Among the manifestations of toxicity, AE grade I–II predominated. The most common AE were local reactions (dermatitis (84 %), focal alopecia (96 %)). Among systemic AE, hematological complications (84 %) were the most often occurred. A more pronounced toxicity profile was registered in the group with CSI, while concomitant CT, the patient’s age, previous CT did not significantly affect the severity of most of the assessed AE parameters (p > 0.05). The analysis of late toxic effects was difficult due to the short follow-up period, the cumulative effect of other treatment modalities on the AE’s development. The reported complications included persistent focal alopecia (14 % of cases), endocrinopathies (7 %), neurological manifestations (6 %). One (2 %) child had a severe neurological deficit, secondary epilepsy with psychomotor regression, which can also be associated with the potentiating effect of previous CT and high-dose CT.   Conclusion. The analysis of our data and literature review allows to conclude that PBT has relatively low toxicity profile, which is the determining factor for choosing this method of RT in pediatric patients. The main risk factor of AE’s was CSI. The acceptable acute toxicity of repeat PBT makes it possible to be used in pts with disease progression or relapse in case of absence of alternative therapeutic options.