Reversal of Endothelial Cell Anergy by T Cell-Engaging Bispecific Antibodies.

Reduced expression of adhesion molecules in tumor vasculature can limit infiltration of effector T cells. To improve T cell adhesion to tumor endothelial cell (EC) antigens and enhance transendothelial migration, we developed bispecific, T-cell engaging antibodies (bsAb) that activate T cells after cross-linking with EC cell surface antigens. Recombinant T-cell stimulatory anti-VEGFR2-anti-CD3 and costimulatory anti-TIE2-anti-CD28 or anti-PD-L1-anti-CD28 bsAb were engineered and expressed.

Biglycan-driven risk stratification in ZFTA-RELA fusion supratentorial ependymomas through transcriptome profiling.

Recent genomic studies have allowed the subdivision of intracranial ependymomas into molecularly distinct groups with highly specific clinical features and outcomes. The majority of supratentorial ependymomas (ST-EPN) harbor ZFTA-RELA fusions which were designated, in general, as an intermediate risk tumor variant. However, molecular prognosticators within ST-EPN ZFTA-RELA have not been determined yet.

Multi-omics profiling reveals key factors involved in Ewing sarcoma metastasis.

Ewing sarcoma (EWS) is the second most common bone tumor affecting children and young adults, with dismal outcomes for patients with metastasis at diagnosis. Mechanisms leading to metastasis remain poorly understood. To deepen our knowledge on EWS progression, we have profiled tumors and metastases from a spontaneous metastasis mouse model using a multi-omics approach.

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.

Circulating tumor cell plasticity determines breast cancer therapy resistance via neuregulin 1-HER3 signaling.

Circulating tumor cells (CTCs) drive metastasis, the leading cause of death in individuals with breast cancer. Due to their low abundance in the circulation, robust CTC expansion protocols are urgently needed to effectively study disease progression and therapy responses. Here we present the establishment of long-term CTC-derived organoids from female individuals with metastatic breast cancer.

Genomic and phenotypic stability of fusion-driven pediatric sarcoma cell lines.

Human cancer cell lines are the mainstay of cancer research. Recent reports showed that highly mutated adult carcinoma cell lines (mainly HeLa and MCF-7) present striking diversity across laboratories and that long-term continuous culturing results in genomic/transcriptomic heterogeneity with strong phenotypical implications. Here, we hypothesize that oligomutated pediatric sarcoma cell lines mainly driven by a fusion transcription factor, such as Ewing sarcoma (EwS), are genetically and phenotypically more stable than the previously investigated adult carcinoma cell lines.

Targeting molecular pathways to control immune checkpoint inhibitor toxicities.

Immune checkpoint inhibitors (ICIs) have transformed cancer treatment but are frequently associated with immune-related adverse events (irAEs). This article offers a novel synthesis of findings from both preclinical and clinical studies, focusing on the molecular mechanisms driving irAEs across diverse organ systems. It examines key immune cells, such as T cell subsets and myeloid cells, which are instrumental in irAE pathogenesis, alongside an in-depth analysis of cytokine signaling [interleukin (IL)-6, IL-17, IL-4), interferon γ (IFN-γ), IL-1β, tumor necrosis factor α (TNF-α)], integrin-mediated interactions [integrin subunits αITGA)4 and ITGB7], and microbiome-related factors that contribute to irAE pathology.

Evaluation of Pelvic MRI-to-CT Deformable Registration for Adaptive MR-Guided Particle Therapy.

Purpose: We aim to assess the magnetic resonance imaging (MRI)-to-CT deformable image registration (DIR) quality of our treatment planning system in the pelvic region as the first step of an online MRI-guided particle therapy clinical workflow.

Materials And Methods: Using 2 different DIR algorithms, ANAtomically CONstrained Deformation Algorithm (ANACONDA), the DIR algorithm incorporated in RayStation, and Elastix, an open-source registration software, we retrospectively assessed the quality of the deformed CT (dCT) generation in the pelvic region for 5 patients. T1- and T2-weighted daily control MRI acquired prior to treatment delivery were used for the DIR.

The immune checkpoint LAG-3 is expressed by melanoma cells and correlates with clinical progression of the melanoma.

Immune checkpoint blockers have substantially improved prognosis of melanoma patients, nevertheless, resistance remains a significant problem. Here, intrinsic and extrinsic factors in the tumor microenvironment are discussed, including the expression of alternative immune checkpoints such as lymphocyte activation gene 3 (LAG-3) and T-cell immunoglobulin and mucin domain-containing protein 3 (TIM-3). While most studies focus on immune cell expression of these proteins, we investigated their melanoma cell intrinsic expression by immunohistochemistry in melanoma metastases of 60 patients treated with anti-programmed cell death protein 1 (PD-1) and/or anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) therapy, and correlated it with the expression of potential ligands, RNA sequencing data and clinical outcome.

Detection of an internal density change in an anthropomorphic head phantom via tracking of charged nuclear fragments in carbon-ion radiotherapy.

Background: Carbon-ion radiotherapy provides steep dose gradients that allow the simultaneous application of high tumor doses as well as the sparing of healthy tissue and radio-sensitive organs. However, even small anatomical changes may have a severe impact on the dose distribution because of the finite range of ion beams.

Purpose: An in-vivo monitoring method based on secondary-ion emission could potentially provide feedback about the patient anatomy and thus the treatment quality.

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.

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.

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).

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).

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.

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.

Mixed- and multi-relative biological effectiveness model simultaneous optimization in carbon ion radiotherapy: A proof-of-concept.

Background And Purpose: In carbon ion radiotherapy (CIRT), different relative biological effectiveness (RBE) models have been used for calculating RBE-weighted dose (D). Conversion between current RBE predictions and introduction of novel approaches remains a challenging task. Our aim is to introduce a framework considering multiple RBE models simultaneously during CIRT plan optimization, easing the translation between D prescriptions.

Hematologic Toxicity Profiles and the Impact of Hemoglobin Nadir and Transfusion on Oncologic Outcome in Definitive Radiochemotherapy for Cervical Cancer.

: Definitive radiochemotherapy with concomitant cisplatin 40 mg/m weekly represents the standard of care for locally advanced cervical cancer. Current studies (KEYNOTE-A18 and INTERLACE) are intensifying this regimen at the cost of increased hematologic toxicity. We aimed to evaluate influencing factors on hematotoxicity to ensure the safe application of radiochemotherapy.

The prognostic influence of hospital type, method of first histological confirmation and time to chemotherapy in patients with advanced primary ovarian cancer.

Purpose: Ovarian cancer is the fifth most common cancer in women and the leading cause of death of all gynecological malignancies. Prognosis is determined by optimal surgical outcome (macroscopic complete resection) most commonly achieved in tertiary hospitals. We investigated whether tertiary versus non-tertiary hospital as the location of an initial diagnostic intervention for histological confirmation before cytoreductive surgery versus immediate primary debulking surgery impacts outcome in patients with advanced ovarian cancer.

Second Comment on 'Modeling for predicting survival fraction of cells after ultra-high dose rate irradiation'.

We comment on the reply by Shiraishito our comments regarding their recently published study 'Modeling for Predicting Survival Fraction of Cells after Ultra-High Dose Rate Irradiation'. While we appreciate the effort of the authors to consider our comments, we see ourselves compelled to add another short comment as we believe that some of our suggestions have been misrepresented. This may have resulted in a misguiding re-evaluation of the model.

Variability in resistance training trajectories of breast cancer patients undergoing therapy.

Purpose: In resistance training (RT), the change in volume-load from training sessions (TS) to TS is an indicator of training progress. Resulting growth trajectories are likely to differ between individuals. Understanding this variation is important for exercise planning in general, but even more for clinical populations.