Long-term complications such as radiation-induced second malignancies occur in a subset of patients following radiation-therapy, particularly relevant in pediatric patients due to the long follow-up period in case of survival. Radiation-induced gliomas (RIGs) have been reported in patients after treatment with cranial irradiation for various primary malignancies such as acute lymphoblastic leukemia (ALL) and medulloblastoma (MB). We perform comprehensive (epi-) genetic and expression profiling of RIGs arising after cranial irradiation for MB (n = 23) and ALL (n = 9). Our study reveals a unifying molecular signature for the majority of RIGs, with recurrentPDGFRAamplification and loss ofCDKN2A/Band an absence of somatic hotspot mutations in genes encoding histone 3 variants orIDH1/2, uncovering diagnostic markers and potentially actionable targets.

Background: Novel radiotherapeutic modalities using carbon ions provide an increased relative biological effectiveness (RBE) compared to photons, delivering a higher biological dose while reducing radiation exposure for adjacent organs. This prospective phase 2 trial investigated bimodal radiotherapy using photons with carbon-ion (C12)-boost in patients with WHO grade 2 meningiomas following subtotal resection (Simpson grade 4 or 5). Methods: A total of 33 patients were enrolled from July 2012 until July 2020. The study treatment comprised a C12-boost (18 Gy [RBE] in 6 fractions) applied to the macroscopic tumor in combination with photon radiotherapy (50 Gy in 25 fractions). The primary endpoint was the 3-year progression-free survival (PFS), and the secondary endpoints included overall survival, safety and treatment toxicities. Results: With a median follow-up of 42 months, the 3-year estimates of PFS, local PFS and overall survival were 80.3%, 86.7%, and 89.8%, respectively. Radiation-induced contrast enhancement (RICE) was encountered in 45%, particularly in patients with periventricularly located meningiomas. Patients exhibiting RICE were mostly either asymptomatic (40%) or presented immediate neurological and radiological improvement (47%) after the administration of corticosteroids or bevacizumab in case of radiation necrosis (3/33). Treatment-associated complications occurred in 1 patient with radiation necrosis who died due to postoperative complications after resection of radiation necrosis. The study was prematurely terminated after recruiting 33 of the planned 40 patients. Conclusions: Our study demonstrates a bimodal approach utilizing photons with C12-boost may achieve a superior local PFS to conventional photon RT, but must be balanced against the potential risks of toxicities.

Ependymomas are the third most-frequent pediatric brain tumors. To prevent local recurrence, the resection site should be irradiated. Compared to photon radiation treatment, proton therapy often achieves even better results regarding target coverage and organ-sparing. Due to their physical properties, helium ions could further reduce side effects, providing better protection of healthy tissue despite similar target coverage. In our in silico study, 15 pediatric ependymoma patients were considered. All patients underwent adjuvant radiotherapeutic treatment with active-scanned protons at Heidelberg Ion Beam Therapy Center (HIT). Both helium ion and highly conformal IMRT plans were calculated to evaluate the potential dosimetric advantage of ion beam therapy compared to the current state-of-the-art photon-based treatments. To estimate the potential clinical benefit of helium ions, normal tissue complication probabilities (NTCP) were calculated. Target coverage was comparable in all three modalities. As expected, the integral dose absorbed by healthy brain tissue could be significantly reduced with protons by up to −48% vs. IMRT. Even compared to actively scanned protons, relative dose reductions for critical neuronal structures of up to another −39% were achieved when using helium ions. The dose distribution of helium ions is significantly superior when compared to proton therapy and IMRT due to the improved sparing of OAR. In fact, previous studies could clearly demonstrate that the dosimetric advantage of protons translates into a measurable clinical benefit for pediatric patients with brain tumors. Given the dose–response relationship of critical organs at risk combined with NTCP calculation, the results of our study provide a strong rationale that the use of helium ions has the potential to even further reduce the risk for treatment related sequelae.

BACKGROUND AND PURPOSE: Diffuse glioneuronal tumor with oligodendroglioma-like features and nuclear clusters (DGONC) is a new, molecularly defined glioneuronal CNS tumor type. The objective of the present study was to describe MR imaging and clinical characteristics of patients with DGONC. MATERIALS AND METHODS: Preoperative MR images of 9 patients with DGONC (median age at diagnosis, 9.9 years; range, 4.2–21.8 years) were reviewed. RESULTS: All tumors were located superficially in the frontal/temporal lobes and sharply delineated, displaying little mass effect. Near the circle of Willis, the tumors encompassed the arteries. All except one demonstrated characteristics of low-to-intermediate aggressiveness with high-to-intermediate T2WI and ADC signals and bone remodeling. Most tumors (n = 7) showed a homogeneous ground-glass aspect on T2-weighted and FLAIR images. On the basis of the original histopathologic diagnosis, 6 patients received postsurgical chemo-/radiotherapy, 2 were irradiated after surgery, and 1 patient underwent tumor resection only. At a median follow-up of 61 months (range, 10–154 months), 6 patients were alive in a first complete remission and 2 with stable disease 10 and 21 months after diagnosis. The only patient with progressive disease was lost to follow-up. Five-year overall and event-free survival was 100% and 86±13%, respectively. CONCLUSIONS: This case series presents radiomorphologic characteristics highly predictive of DGONC that contrast with the typical aspects of the original histopathologic diagnoses. This presentation underlines the definition of DGONC as a separate entity, from a clinical perspective. Complete resection may be favorable for long-term disease control in patients with DGONC. The efficacy of nonsurgical treatment modalities should be evaluated in larger series.

Purpose: To provide the first report on proton radiotherapy (PRT) in the management of advanced nasopharyngeal angiofibroma (JNA) and evaluate potential benefits compared to conformal photon therapy (XRT). Methods: We retrospectively reviewed 10 consecutive patients undergoing PRT for advanced JNA in a definitive or postoperative setting with a relative biological effectiveness weighted dose of 45 Gy in 25 fractions between 2012 and 2022 at the Heidelberg Ion Beam Therapy Center. Furthermore, dosimetric comparisons and risk estimations for short- and long-term radiation-induced complications between PRT plans and helical XRT plans were conducted. Results: PRT was well tolerated, with only low-grade acute toxicities (CTCAE I–II) being reported. The local control rate was 100% after a median follow-up of 27.0 (interquartile range 13.3–58.0) months. PRT resulted in considerable tumor shrinkage, leading to complete remission in five patients and bearing the potential to provide partial or complete symptom relief. Favorable dosimetric outcomes in critical brain substructures by the use of PRT translated into reduced estimated risks for neurocognitive impairment and radiation-induced CNS malignancies compared to XRT. Conclusions: PRT is an effective treatment option for advanced JNA with minimal acute morbidity and the potential for reduced radiation-induced long-term complications.