Thymus Composition, Disease Control, and Toxicity in Locally Advanced Lung Cancer Thymic involution, characterized by adipose replacement of functional thymic tissue, is a broadly recognized feature of age-related immunosenescence. Currently, no established, non-invasive method measures residual thymus in adults, its relationship with host immunity, or its influence on tumor immunosurveillance, cancer outcomes, and treatment-related toxicities. In a multi-institutional cohort of patients with locally advanced non-small cell lung cancer (NSCLC), we created… medRxiv Oncology November 7, 2025 Original source
The ENGAGE Study: A Randomized Trial Optimizing Uptake of Germline Cancer Genetic Services in Childhood Cancer Survivors BackgroundIdentifying childhood cancer survivors who are already at high risk of subsequent neoplasms and may also have an inherited genetic susceptibility is essential for effective surveillance and prevention. This trial evaluated the effectiveness of remote, centralized telehealth genetic services in increasing service uptake. MethodsChildhood Cancer Survivor Study (CCSS) participants at the St. Jude Research Hospital, who were >18 years old… medRxiv Oncology November 7, 2025 Original source
Multimodal Activity-Affinity Assay of ADAM-10 Extracellular Vesicles in Untreated Plasma Reveals Metastatic Stage of Colorectal Cancer Metalloproteinases (MPs) such as a-disintegrin and metalloproteinase-10 (ADAM-10) are key drivers of extracellular matrix remodeling during tumor progression, yet MP-based liquid biopsy tests have not reached clinical utility. Here, we show that active ADAM-10 is selectively enriched on the surface of circulating extracellular vesicles (EVs) in the plasma of colorectal cancer patients. Our findings further suggest ADAM-10+ EVs are locally… medRxiv Oncology November 7, 2025 Original source
Distinct molecular profiles characterize the spontaneous growth rate of IDHmt low-grade astrocytoma and oligodendroglioma, WHO grade 2 BackgroundThe life expectancy of patients with diffuse IDH-mutant low-grade gliomas (IDHmt LGG) WHO grade 2 ranges from 5 to over 20 years. Tumor behavior, including spontaneous growth rate, varies even within homogeneously classified subtypes of oligodendroglioma and astrocytoma. Risk-adjusted treatment strategies are needed to avoid therapy-related toxicities, without compromising outcome. The spontaneous tumor volume growth rate (TVGR) serves as a… medRxiv Oncology November 7, 2025 Original source
From Genes to Personalized Cancer Care: A Systematic Review of Toxicity-Associated Genetic Variants in Solid Tumor Treatments BackgroundPharmacogenomics has emerged as a crucial tool in precision medicine, offering the potential to personalise cancer treatments by predicting and managing therapy-induced toxicities. This systematic review examined the genetic basis of toxicities associated with radiotherapy, chemotherapy, and immunotherapy in solid tumours. MethodsA comprehensive literature search was conducted across PubMed, Google Scholar, and PharmKB databases, covering the period from December 2019… medRxiv Oncology November 7, 2025 Original source
Cell-free DNA Whole Genome Sequencing for Non-Invasive Minimal Residual Disease Detection in Multiple Myeloma Minimal residual disease (MRD) monitoring in multiple myeloma (MM) relies on invasive bone marrow (BM) biopsies, which often yield insufficient tumor material. We performed whole genome sequencing of cell-free DNA from 163 plasma samples from 51 patients to develop a non-invasive MRD classifier. BM WGS identified a median of 2,502 clonal mutations, enabling cfDNA tracking at levels comparable to BM-based… medRxiv Oncology November 7, 2025 Original source
Detection of p53 and SV40 Immunostaining in Archived Tumor Nephrectomy Blocks of Children with Nephroblastoma in Kano, Nigeria. BackgroundImmunohistochemical expression of p53 protein in tumor nephrectomy specimens of patients with nephroblastoma has been associated with an adverse clinical outcome. SV40 is a known tumorigenic virus associated with inflammatory kidney diseases. This study aimed to evaluate the role in clinical outcome of p53 and SV40 immunopositivity in formalin-fixed paraffin-embedded (FFPE) tissue blocks of children with nephroblastoma. Materials and methodsThis… medRxiv Oncology November 7, 2025 Original source
Thymus Composition Predicts Pneumonitis Risk in Lung Cancer Therapy BackgroundDurvalumab consolidation after concurrent chemoradiotherapy (cCRT) is the standard-of-care for unresectable stage III non-small cell lung cancer (NSCLC) without actionable driver mutations. However, pneumonitis remains a dose-limiting toxicity that often precludes or interrupts immunotherapy. Conventional predictors based on lung dosimetry alone exhibit limited individual-level discrimination. We investigated whether the thymus, long considered vestigial in adults, influences post-treatment immune recovery and… medRxiv Oncology November 7, 2025 Original source
Robust CD4+ CAR T cell Expansion Is Associated with Non-ICANS Neurotoxicities Following Ciltacabtagene Autoleucel Non-ICANS neurotoxicities (NINTs) are serious, atypical toxicities associated with ciltacabtagene autoleucel, a commercial chimeric antigen receptor (CAR) T cell therapy approved for relapsed/refractory multiple myeloma. Risk factors contributing to the development of NINTs are poorly understood. In a cohort of 109 patients, we identify predisposing risk factors and propose strategies to mitigate NINTs. We show that high peak absolute lymphocyte… medRxiv Oncology November 7, 2025 Original source
Biogeneric native and polyethylene glycol-conjugated E. coli asparaginases for treating children with acute lymphoblastic leukaemia Escherichia coli asparaginases (EcASNase) available for the treatment of children with acute lymphoblastic leukaemia (ALL) are largely of suboptimal quality in low-middle income countries (LMIC) and contribute to inferior outcomes. The pharmacokinetics, activity, and immunogenicity of a native (EcASNase) and a PEGylated ASNase (PEG-EcASNase) were analysed. Biogeneric EcASNase 10,000 IU/m2 was administered intramuscularly every 72 hours (Cohort 1, 76 patients)… medRxiv Oncology November 7, 2025 Original source
Second-line therapy following osimertinib in metastatic EGFR-mutated non-small cell lung cancer at an academic medical center PurposeFLAURA2 demonstrated that adding chemotherapy to osimertinib improved overall survival compared with osimertinib monotherapy in metastatic epidermal growth factor receptor-mutated (EGFR-mut) non-small cell lung cancer (NSCLC). Notably, only 60% of patients in the osimertinib monotherapy arm received second-line therapy after discontinuing first-line osimertinib, raising the concern that FLAURA2 did not accurately reflect real-world practices at academic medical centers. We hypothesized… medRxiv Oncology November 7, 2025 Original source
The impact of preoperative imaging strategies in EGFR-mutant non-small cell lung cancer: a multicenter retrospective review BackgroundThe ADAURA trial demonstrated an overall survival benefit with adjuvant osimertinib in epidermal growth factor receptor-mutant (EGFR-mut) non-small cell lung cancer (NSCLC). As only 50% of patients underwent a preoperative brain MRI scan and PET-CT rates were not reported, concerns were raised that suboptimal staging could have led to the inclusion of patients with metastatic disease. There is, however, limited… medRxiv Oncology November 7, 2025 Original source
Characterization of Liver Metastasis Risk and Timing in Pancreatic Cancer Patients Using Electronic Health Records Liver metastasis is a frequent and serious complication of pancreatic cancer, contributing to its high mortality rate. Identifying risk factors and understanding the timing of liver metastasis may improve early detection and support more effective treatment planning. A cohort of 12,955 incident pancreatic cancer patients was assembled from the Truveta platform. A subgroup of cases and controls that met the… medRxiv Oncology November 7, 2025 Original source
Impact of Targeted Therapy on Progression-Free Survival in Breast Cancer: A Decade of Evidence from Randomized and Clinical Trials BackgroundTargeted therapies have transformed breast cancer management by focusing on molecular drivers such as HER2 amplification, hormone receptor signaling, and CDK4/6 pathways. They aim to increase disease control while reducing systemic toxicity compared to conventional chemotherapy. ObjectiveThis review assessed the effectiveness and safety of targeted therapies in advanced and metastatic breast cancer, with progression-free survival (PFS) as the primary outcome… medRxiv Oncology November 7, 2025 Original source
Efficacy and safety of integrated Chinese and western medicine for cancer therapy-induced thrombocytopenia: A meta-analysis ObjectiveTo evaluate the efficacy and safety of Traditional Chinese medicine (TC M) combined with Western medicine (WM) for cancer therapy-induced thrombocytopenia (CTIT). MethodsA comprehensive literature search was performed across multiple databases, including PubMed, Embase, Cochrane Library, China biology medicine, China national knowledge infrastructure, Wanfang, and VIP, from inception to August 2025. Randomized controlled trials (RCTs) examining the effects of integrated… medRxiv Oncology November 7, 2025 Original source
A multimodal cross-attention pathotranscriptome integration for enhanced survival prediction of oral squamous cell carcinoma Oral squamous cell carcinoma (OSCC) accounts for a major part of cancer mortality, with survival outcomes highly dependent on early diagnosis. While many approaches have been proposed for OSCC survival prediction, they often rely on unimodal data, which may be suboptimal. In this study, we introduced a unified cross-attention-based deep learning framework that integrates whole-slide histopathology images (WSIs) and transcriptomic… medRxiv Oncology November 7, 2025 Original source
Re-evaluating the effect of SARS-CoV-2 mRNA vaccination on clinical outcomes in patients treated with immune checkpoint inhibitors SARS-CoV-2 mRNA vaccination (COVID-19 vaccination) within 100 days of immune checkpoint inhibitor (ICI) treatment was reported to improve survival and prevent disease progression in patients with non-small cell lung cancer (NSCLC) and metastatic melanoma (Grippin et al., Nature, 2025). However, the clinical evidence, derived from real-world observational data, suffers from methodological limitations. Specifically, the vaccinated and unvaccinated groups differed in… medRxiv Oncology November 7, 2025 Original source
Distinct Sarcoma Microenvironments Predict Benefit from Addition of Pembrolizumab to Preoperative Radiotherapy and Surgery in SU2C-SARC032 The addition of pembrolizumab to preoperative radiotherapy (RT) improved disease-free survival (DFS) for patients with stage III undifferentiated pleomorphic sarcoma (UPS) and dedifferentiated/pleomorphic liposarcoma (LPS) in the randomized SU2C-SARC032 trial. To precisely identify patients who benefit from pembrolizumab and RT, we performed comprehensive multi-omics profiling of pre- and post-treatment tumor and blood samples, including bulk RNA-seq, flow cytometry, and cytometry… medRxiv Oncology November 7, 2025 Original source
Comparison of treatment planning techniques at the linear accelerator for left-sided breast carcinoma considering the treatment volume and organs at risk Breast cancer is the most common type of cancer in women. Nowadays, postoperative radiation therapy is one of the standard treatment procedures. However, the radiation used may not only lead to a positive therapeutic outcome, but also has a negative impact on the surrounding organs at risk. Organs, such as the heart, can also have damaged and serious late effects… medRxiv Oncology November 7, 2025 Original source
Melanoma to rhabdomyosarcoma plasticity in the setting of immunotherapy Acquired resistance to immune checkpoint inhibitors (ICIs) remains a significant challenge in the treatment of metastatic melanoma. Phenotypic plasticity, such as dedifferentiation and transdifferentiation, is an increasingly recognized mechanism for treatment resistance. We present a case of a man in his 70s with metastatic melanoma who experienced progression through sequential treatments including pembrolizumab in combination with the HDAC inhibitor entinostat,… medRxiv Oncology November 7, 2025 Original source