Open Access

Simple Summary Radiation therapy is an important cornerstone of the treatment of many different types of brain tumors occurring in childhood. Proton beam therapy offers the opportunity to reduce doses outside of the target volume due to its physical characteristics. By sparing a large volume of the brain from radiation doses, proton beam therapy aims at reducing long-term side effects and preserving cognitive function. Our study aims at better understanding side effects and therefore contributing to better treatment decisions in this vulnerable group of patients. Therefore, the study analyses outcome and side effects including imaging changes in a large cohort of children with brain tumors from a prospective registry. Abstract 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.

The international precision oncology program INFORM enrolls relapsed/refractory pediatric cancer patients for comprehensive molecular analysis. We report a two-year pilot study implementing ex vivo drug sensitivity profiling (DSP) using a library of 75–78 clinically relevant drugs. We included 132 viable tumor samples from 35 pediatric oncology centers in seven countries. DSP was conducted on multicellular fresh tumor tissue spheroid cultures in 384-well plates with an overall mean processing time of three weeks. In 89 cases (67%), sufficient viable tissue was received; 69 (78%) passed internal quality controls. The DSP results matched the identified molecular targets, including BRAF, ALK, MET, and TP53 status. Drug vulnerabilities were identified in 80% of cases lacking actionable (very) high-evidence molecular events, adding value to the molecular data. Striking parallels between clinical courses and the DSP results were observed in selected patients. Overall, DSP in clinical real-time is feasible in international multicenter precision oncology programs.

Background: Malignant rhabdoid tumors occasionally develop along cranial nerves, but clinical, histopathological, and molecular features have not been examined in larger series. Procedure: We retrospectively interrogated data from the European Rhabdoid Registry, EU-RHAB, to identify malignant rhabdoid tumors affecting cranial nerves. We retrieved clinical information and reviewed magnetic resonance imaging (MRI) data. Furthermore, histopathological review and molecular profiling were performed. Results: Among 425 patients, we identified a total of 14 harboring malignant rhabdoid tumors with cranial nerve involvement. Median age at diagnosis was 28 months (range: 0–13 years). Various cranial nerves were affected, the trigeminal nerve (n = 4) and the facial and/or vestibulocochlear nerve (n = 5) being most frequently involved. In most cases, the initial clinical and neuroradiological suspicion was schwannoma. Neuroradiology review of magnetic resonance imaging studies confirmed a tumor