VGLL-fusions define a new class of intraparenchymal CNS schwannoma.

Background: Intracerebral schwannomas are rare tumors resembling their peripheral nerve sheath counterparts but localized in the CNS. They are not classified as a separate tumor type in the 2021 WHO classification. This study aimed to compile and characterize these rare neoplasms morphologically and molecularly.

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.

Armoring chimeric antigen receptor (CAR) T cells as micropharmacies for cancer therapy.

Chimeric antigen receptor (CAR)-T-cell therapy has emerged as a powerful weapon in the fight against cancer. However, its efficacy is often hindered by challenges such as limited tumor penetration, antigen escape, and immune suppression within the tumor microenvironment. This review explores the potential of armored CAR-T cells, or 'micropharmacies', in overcoming these obstacles and enhancing the therapeutic outcomes of adoptive T-cell (ATC) therapy.

Prognostic value of metabolic tumor volume on [F]FDG PET/CT in addition to the TNM classification system of locally advanced non-small cell lung cancer.

Purpose: Staging of non-small cell lung cancer (NSCLC) is commonly based on [F]FDG PET/CT, in particular to exclude distant metastases and guide local therapy approaches like resection and radiotherapy. Although it is hoped that PET/CT will increase the value of primary staging compared to conventional imaging, it is generally limited to the characterization of TNM. The first aim of this study was to evaluate the PET parameter metabolic tumor volume (MTV) above liver background uptake as a prognostic marker in lung cancer.

Single-cell RNA seq-derived signatures define response patterns to atezolizumab + bevacizumab in advanced hepatocellular carcinoma.

Background & Aims: The combination of atezolizumab and bevacizumab (atezo+bev) is the current standard of care for advanced hepatocellular carcinoma (HCC), providing a median overall survival (OS) of 19.2 months. Here, we aim to uncover the underlying cellular processes driving clinical benefit versus resistance to atezo+bev.

Antigen presentation by MHC-II is shaped by competitive and cooperative allosteric mechanisms of peptide exchange.

Major histocompatibility complex class II (MHC-II) presents antigens to T helper cells. The spectrum of presented peptides is regulated by the exchange catalyst human leukocyte antigen DM (HLA-DM), which dissociates peptide-MHC-II complexes in the endosome. How susceptible a peptide is to HLA-DM is mechanistically not understood.

Metastasis-directed stereotactic radiotherapy in patients with breast cancer: results of an international multicenter cohort study.

Metastasis-directed therapy (MDT) for oligometastatic breast cancer (≤ 5 metastases) has shown little effect in specific scenarios of randomized trials. Therefore, we aimed to assess outcomes after metastasis-directed stereotactic radiotherapy (SRT) in various clinical scenarios. We conducted an international retrospective cohort study in thirteen centers including breast cancer patients receiving SRT to any metastatic site.

Prognostic Biomarkers in Evolving Melanoma Immunotherapy.

Melanoma, a highly aggressive form of skin cancer, has seen significant advancements in treatment through the introduction of immunotherapy. However, the variability in patient responses underscores the need for reliable biomarkers to guide treatment decisions. This article reviews key biomarkers in melanoma immunotherapy, such as PD-L1 expression, tumor mutational burden (TMB), and gene expression profiles (GEPs).

Pitfalls in interpreting calibration in comparative evaluations of risk models for precision lung cancer screening.

Lung cancer screening by low-dose computed tomography reduces lung cancer mortality, but reliable risk-based selection of participants is crucial to maximize benefits and minimize harms. Multiple risk models have been developed for this purpose, and their discrimination and calibration performance is commonly evaluated based on large-scale cohort studies. Using a recent comparative evaluation of 10 risk models as an example, we illustrate the merits, limitations and pitfalls of such evaluations.

Evaluation of S100A8/A9 and neutrophils as prognostic markers in metastatic melanoma patients under immune-checkpoint inhibition.

Immune-checkpoint inhibitors (ICIs) have revolutionized melanoma treatment, yet approximately half of patients do not respond to these therapies. Identifying prognostic biomarkers is crucial for treatment decisions. Our retrospective study assessed liquid biopsies and tumor tissue analyses for two potential biomarkers: danger-associated molecular pattern (DAMP) S100A8/A9 and its source, neutrophils.

Epstein-Barr virus lytic replication and cancer.

Epidemiological studies have provided strong evidence that Epstein-Barr virus (EBV) lytic replication is linked to cancer development. Evidence of abortive lytic replication in some tumors and infections with recombinant viruses incapable of lytic replication in animal models have reinforced this view. Furthermore, multiple lytic proteins have been shown to induce genetic instability, a well-characterized precancerous state.

Radiographic and visual response to the type II RAF inhibitor tovorafenib in children with relapsed/refractory optic pathway glioma in the FIREFLY-1 trial.

Background: Due to their anatomical locations, optic pathway gliomas (OPGs) can rarely be cured by resection. Given the importance of preserving visual function, we analyzed radiological and visual acuity (VA) outcomes for the type II RAF inhibitor tovorafenib in the OPG subgroup of the phase 2 FIREFLY-1 trial.

Methods: FIREFLY-1 investigated the efficacy (arm 1, n=77), safety, and tolerability (arms 1/2) of tovorafenib (420 mg/m2 once weekly; 600 mg maximum) in patients with BRAF-altered relapsed/refractory pediatric low-grade glioma (pLGG).

Personalized deep learning auto-segmentation models for adaptive fractionated magnetic resonance-guided radiation therapy of the abdomen.

Background: Manual contour corrections during fractionated magnetic resonance (MR)-guided radiotherapy (MRgRT) are time-consuming. Conventional population models for deep learning auto-segmentation might be suboptimal for MRgRT at MR-Linacs since they do not incorporate manual segmentation from treatment planning and previous fractions.

Purpose: In this work, we investigate patient-specific (PS) auto-segmentation methods leveraging expert-segmented planning and prior fraction MR images (MRIs) to improve auto-segmentation on consecutive treatment days.

Pushing the boundaries of radiotherapy-immunotherapy combinations: highlights from the 7 immunorad conference.

Over the last decade, the annual Immunorad Conference, held under the joint auspicies of Gustave Roussy (Villejuif, France) and the Weill Cornell Medical College (New-York, USA) has aimed at exploring the latest advancements in the fields of tumor immunology and radiotherapy-immunotherapy combinations for the treatment of cancer. Gathering medical oncologists, radiation oncologists, physicians and researchers with esteemed expertise in these fields, the Immunorad Conference bridges the gap between preclinical outcomes and clinical opportunities. Thus, it paves a promising way toward optimizing radiotherapy-immunotherapy combinations and, from a broader perspective, improving therapeutic strategies for patients with cancer.

HIPSD&R-seq enables scalable genomic copy number and transcriptome profiling.

Single-cell DNA sequencing (scDNA-seq) enables decoding somatic cancer variation. Existing methods are hampered by low throughput or cannot be combined with transcriptome sequencing in the same cell. We propose HIPSD&R-seq (HIgh-throughPut Single-cell Dna and Rna-seq), a scalable yet simple and accessible assay to profile low-coverage DNA and RNA in thousands of cells in parallel.

Metastatic breast cancer patients' preferences for exercise programs: a latent class analysis using data from a survey in five European countries.

Purpose: We aimed to identify metastatic breast cancer (MBC) patients' preferences for exercise programs and identify patients' characteristics associated with these preferences, to facilitate implementation of exercise programs for MBC patients.

Methods: We used data from a multinational cross-sectional survey conducted among MBC patients. Patients reported their preferred exercise frequency, intensity, type, session duration, and supervision mode.

Amide proton transfer weighted MRI measurements yield consistent and repeatable results in patients with gliomas: a prospective test-retest study.

Objectives: Chemical exchange saturation transfer (CEST) imaging has emerged as a promising imaging biomarker, but its reliability for clinical practice remains uncertain. This study aimed to investigate the robustness of CEST parameters in healthy volunteers and patients with brain tumours.

Methods: A total of n = 52 healthy volunteers and n = 52 patients with histologically confirmed glioma underwent two consecutive 3-T MRI scans separated by a 1-min break.

Global Distribution of Colorectal Cancer Staging at Diagnosis: An Evidence Synthesis.

Background And Aims: Stage at diagnosis is a key prognostic factor for colorectal cancer (CRC) survival. We aimed to assess the global distribution of CRC staging at diagnosis using population-based or hospital-based registry data.

Methods: We systematically searched in MEDLINE and Embase from their inception until 6 December 2023.

The Progression-Free-Survival Ratio in Molecularly Aided Tumor Trials: A Critical Examination of Current Practice and Suggestions for Alternative Methods.

The progression-free-survival ratio is a popular endpoint in oncology trials, which is frequently applied to evaluate the efficacy of molecularly targeted treatments in late-stage patients. Using elementary calculations and simulations, numerous shortcomings of the current methodology are pointed out. As a remedy to these shortcomings, an alternative methodology is proposed, using a marginal Cox model or a marginal accelerated failure time model for clustered time-to-event data.

Metastasis Detection Using True and Artificial T1-Weighted Postcontrast Images in Brain MRI.

Objectives: Small lesions are the limiting factor for reducing gadolinium-based contrast agents in brain magnetic resonance imaging (MRI). The purpose of this study was to compare the sensitivity and precision in metastasis detection on true contrast-enhanced T1-weighted (T1w) images and artificial images synthesized by a deep learning method using low-dose images.

Materials And Methods: In this prospective, multicenter study (5 centers, 12 scanners), 917 participants underwent brain MRI between October 2021 and March 2023 including T1w low-dose (0.