Primary Mediastinal Ewing's Sarcoma: Post Hoc Analysis from Two International Multicenter Prospective Randomized Trials.

Objective: Ewing sarcoma (EWS) of the mediastinum is extremely rare, with only a few cases reported in the literature. We aimed to gain a better understanding of primary mediastinal EWS, describing patients treated within two international, multicenter, prospective, randomized EWS trials.

Methods: Data from patients with primary mediastinal EWS were retrieved from the database of the EURO-E.

The sarcoma ring trial: a case-based analysis of inter-center agreement across 21 German-speaking sarcoma centers.

Purpose: The management of soft tissue sarcoma (STS) at reference centers with specialized multidisciplinary tumor boards (MTB) improves patient survival. The German Cancer Society (DKG) certifies sarcoma centers in German-speaking countries, promoting high standards of care. This study investigated the variability in treatment recommendations for localized STS across different German-speaking tertiary sarcoma centers.

Impact of molecular classification on prognosis in children and adolescents with spinal ependymoma: Results from the HIT-MED database.

Background: Ependymomas of the spinal cord are rare among children and adolescents, and the individual risk of disease progression is difficult to predict. This study aims to evaluate the prognostic impact of molecular typing on pediatric spinal cord ependymomas.

Methods: Eighty-three patients with spinal ependymomas ≤22 years registered in the HIT-MED database (German brain tumor registry for children, adolescents, and adults with medulloblastoma, ependymoma, pineoblastoma, and CNS-primitive neuroectodermal tumors) between 1992 and 2022 were included.

Treatment of Pediatric, Adolescent, and Young Adult Patients With Fusion-Positive Alveolar Rhabdomyosarcoma Infiltrating Regional Lymph Nodes in the European CWS-2002P and RMS 2005 Studies and the Soft Tissue Sarcoma Registry.

Background: Patients with alveolar rhabdomyosarcoma (ARMS) with regional lymph node involvement (N1) are defined as "very-high-risk rhabdomyosarcoma" in Europe. Different chemotherapy regimens were used in European study protocols.

Methods: Patients with FOXO1 fusion-positive N1 ARMS registered in the CWS-2002P study, the EpSSG RMS 2005 study, and SoTiSaR were retrospectively investigated.

Dose distributions of proton therapy plans are robust against lowering the resolution of CTs combined with increasing noise.

Background: Treatment planning in radiation therapy (RT) is performed on image sets acquired with commercial x-ray computed tomography (CT) scanners. Considering an increased frequency of verification scans for adaptive RT and the advent of alternatives to x-ray CTs, there is a need to review the requirements for image sets used in RT planning.

Purpose: This study aims to derive the required image quality (IQ) for the computation of the dose distribution in proton therapy (PT) regarding spatial resolution and the combination of spatial resolution and noise.

Proof-of-principle of 3D-printed track-end detectors for dosimetry in proton therapy.

Background: Dosimetric equipment in particle therapy (PT) is associated with high costs. There is a lack of versatile, tissue-equivalent detectors suitable for in-vivo dosimetry. Faraday-cup (FC) type detectors are sensitive to stopped protons, that is, to track-ends (TEs).

ESTRO-EANO guideline on target delineation and radiotherapy for IDH-mutant WHO CNS grade 2 and 3 diffuse glioma.

Purpose: This guideline will discuss radiotherapeutic management of IDH-mutant grade 2 and grade 3 diffuse glioma, using the latest 2021 WHO (5th) classification of brain tumours focusing on: imaging modalities, tumour volume delineation, irradiation dose and fractionation.

Methods: The ESTRO Guidelines Committee, CNS subgroup, nominated 15 European experts who identified questions for this guideline. Four working groups were established addressing specific questions concerning imaging, target volume delineation, radiation techniques and fractionation.

Mesenchymal Osr1+ cells regulate embryonic lymphatic vessel formation.

The lymphatic system is formed during embryonic development by the commitment of specialized lymphatic endothelial cells (LECs) and their subsequent assembly in primary lymphatic vessels. Although lymphatic cells are in continuous contact with mesenchymal cells during development and in adult tissues, the role of mesenchymal cells in lymphatic vasculature development remains poorly characterized. Here, we show that a subpopulation of mesenchymal cells expressing the transcription factor Osr1 are in close association with migrating LECs and established lymphatic vessels in mice.

Distinct relapse pattern across molecular ependymoma types.

Background: Ependymoma (EPN) is not a uniform disease but represents different disease types with biological and clinical heterogeneity. However, the pattern of when and where different types of EPN relapse is not yet comprehensively described.

Methods: We assembled 269 relapsed intracranial EPN from pediatric (n=233) and adult (n=36) patients from European and Northern American cohorts and correlated DNA methylation patterns and copy-number alterations with clinical information.

Linear energy transfer dependent variation in viability and proliferation along the Bragg peak curve in sarcoma and normal tissue cells.

The energy deposition of photons and protons differs. It depends on the position in the proton Bragg peak (BP) and the linear energy transfer (LET) leading to a variable relative biological effectiveness (RBE). Here, we investigate LET dependent alterations on metabolic viability and proliferation of sarcoma and endothelium cell lines following proton irradiation in comparison to photon exposure.

A deep-learning-based surrogate model for Monte-Carlo simulations of the linear energy transfer in primary brain tumor patients treated with proton-beam radiotherapy.

This study explores the use of neural networks (NNs) as surrogate models for Monte-Carlo (MC) simulations in predicting the dose-averaged linear energy transfer (LET) of protons in proton-beam therapy based on the planned dose distribution and patient anatomy in the form of computed tomography (CT) images. As LETis associated with variability in the relative biological effectiveness (RBE) of protons, we also evaluate the implications of using NN predictions for normal tissue complication probability (NTCP) models within a variable-RBE context.The predictive performance of three-dimensional NN architectures was evaluated using five-fold cross-validation on a cohort of brain tumor patients (= 151).

Clinical practice in European centres treating paediatric posterior fossa tumours with pencil beam scanning proton therapy.

Background And Purpose: As no guidelines for pencil beam scanning (PBS) proton therapy (PT) of paediatric posterior fossa (PF) tumours exist to date, this study investigated planning techniques across European PT centres, with special considerations for brainstem and spinal cord sparing.

Materials And Methods: A survey and a treatment planning comparison were initiated across nineteen European PBS-PT centres treating paediatric patients. The survey assessed all aspects of the treatment chain, including but not limited to delineations, dose constraints and treatment planning.

Radiotherapy for Recurrent Medulloblastoma in Children and Adolescents: Survival after Re-Irradiation and First-Time Irradiation.

Background: Radiotherapy (RT) involving craniospinal irradiation (CSI) is important in the initial treatment of medulloblastoma. At recurrence, the re-irradiation options are limited and associated with severe side-effects.

Methods: For pre-irradiated patients, patients with re-irradiation (RT2) were matched by sex, histology, time to recurrence, disease status and treatment at recurrence to patients without RT2.

Depletion of TBC1D4 Improves the Metabolic Exercise Response by Overcoming Genetically Induced Peripheral Insulin Resistance.

The Rab-GTPase-activating protein (RabGAP) TBC1D4 (AS160) represents a key component in the regulation of glucose transport into skeletal muscle and white adipose tissue (WAT) and is therefore crucial during the development of insulin resistance and type 2 diabetes. Increased daily activity has been shown to be associated with improved postprandial hyperglycemia in allele carriers of a loss-of-function variant in the human TBC1D4 gene. Using conventional Tbc1d4-deficient mice (D4KO) fed a high-fat diet, we show that moderate endurance exercise training leads to substantially improved glucose and insulin tolerance and enhanced expression levels of markers for mitochondrial activity and browning in WAT from D4KO animals.

Ependymoma from Benign to Highly Aggressive Diseases: A Review.

Ependymomas comprise biologically distinct tumor types with respect to age distribution, (epi)genetics, localization, and prognosis. Multimodal risk-stratification, including histopathological and molecular features, is essential in these biologically defined tumor types. Gross total resection (GTR), achieved with intraoperative monitoring and neuronavigation, and if necessary, second-look surgery, is the most effective treatment.

Outcome After Modern Proton Beam Therapy in Childhood Craniopharyngioma: Results of the Prospective Registry Study KiProReg.

Purpose: Craniopharyngiomas (CPs) are rare tumors of the sellar region often leading to significant comorbidities due to their close proximity to critical structures. The aim of this study was to analyze survival outcome and late toxicities after surgery and proton beam therapy (PBT) in childhood CPs.

Methods And Materials: Within the prospective registry study "KiProReg" (DRKS0000536), data of 74 childhood patients with CP, receiving PBT between August 2013 to June 2022 were eligible.

ESTRO-SIOPE guideline: Clinical management of radiotherapy in atypical teratoid/rhabdoid tumors (AT/RTs).

Background And Purpose: Treatment of patients with atypical teratoid/rhabdoid (AT/RT) is challenging, especially when very young (below the age of three years). Radiotherapy (RT) is part of a complex trimodality therapy. The purpose of this guideline is to provide appropriate recommendations for RT in the clinical management of patients not enrolled in clinical trials.

Proteomic and transcriptomic profiling of brainstem, cerebellum and olfactory tissues in early- and late-phase COVID-19.

Neurological symptoms, including cognitive impairment and fatigue, can occur in both the acute infection phase of coronavirus disease 2019 (COVID-19) and at later stages, yet the mechanisms that contribute to this remain unclear. Here we profiled single-nucleus transcriptomes and proteomes of brainstem tissue from deceased individuals at various stages of COVID-19. We detected an inflammatory type I interferon response in acute COVID-19 cases, which resolves in the late disease phase.

Neurofibromin 1 controls metabolic balance and Notch-dependent quiescence of murine juvenile myogenic progenitors.

Patients affected by neurofibromatosis type 1 (NF1) frequently show muscle weakness with unknown etiology. Here we show that, in mice, Neurofibromin 1 (Nf1) is not required in muscle fibers, but specifically in early postnatal myogenic progenitors (MPs), where Nf1 loss led to cell cycle exit and differentiation blockade, depleting the MP pool resulting in reduced myonuclear accretion as well as reduced muscle stem cell numbers. This was caused by precocious induction of stem cell quiescence coupled to metabolic reprogramming of MPs impinging on glycolytic shutdown, which was conserved in muscle fibers.

Survivors of infant atypical teratoid/rhabdoid tumors present with severely impaired cognitive functions especially for fluid intelligence and visual processing: data from the German brain tumor studies.

Background: The contribution of tumor type, multimodal treatment, and other patient-related factors upon long-term cognitive sequelae in infant brain tumor survivors remains undefined. We add our retrospective analysis of neuropsychological and quality of survival (QoS) outcome data of survivors of atypical teratoid/rhabdoid tumors (ATRT) and extracranial malignant rhabdoid tumors of the soft tissues (eMRT) and kidneys (RTK) treated within the same framework. Neuropsychological data from children with ATRT were compared to data from children with non-irradiated low-grade glioma (LGG).

Brain and Brain Stem Necrosis After Reirradiation for Recurrent Childhood Primary Central Nervous System Tumors: A PENTEC Comprehensive Review.

Purpose: Reirradiation is increasingly used in children and adolescents/young adults (AYA) with recurrent primary central nervous system tumors. The Pediatric Normal Tissue Effects in the Clinic (PENTEC) reirradiation task force aimed to quantify risks of brain and brain stem necrosis after reirradiation.

Methods And Materials: A systematic literature search using the PubMed and Cochrane databases for peer-reviewed articles from 1975 to 2021 identified 92 studies on reirradiation for recurrent tumors in children/AYA.

Radiation Therapy Plays an Important Role in the Treatment of Atypical Teratoid/Rhabdoid Tumors: Analysis of the EU-RHAB Cohorts and Their Precursors.

Purpose: Atypical teratoid/rhabdoid tumor (AT/RT) is a rare malignancy of the central nervous system in young children with a dismal prognosis. Prognostic markers have been extensively investigated but have not been validated. The role of radiation therapy (RT) remains controversial.

Combination of nivolumab with standard induction chemotherapy in children and adults with EBV-positive nasopharyngeal carcinoma : Protocol of a prospective multicenter phase 2 trial.

Background: Treatment of Epstein-Barr virus(EBV)-positive nasopharyngeal carcinoma (NPC) with cisplatin/5-fluorouracil (5-FU) induction chemotherapy, followed by radiochemotherapy and subsequent interferon‑β, has yielded high survival rates in children, adolescents, and young adults. A previous study has shown that reduction of radiation dose from 59.4 to 54.