Accurately estimating physiological fitness and life expectancy is challenging in older patients with early-stage non-small cell lung cancer (NSCLC) considered for stereotactic body radiotherapy (SBRT). Noninvasive biological age metrics may improve assessment beyond chronological age.

Real-world evidence (RWE) is increasingly used in health technology assessment (HTA) to address uncertainties surrounding the generalizability of randomized clinical trial (RCT) data. Pembrolizumab plus platinum-based chemotherapy improves survival in metastatic, non-small cell cancer (mNSCLC); however, existing economic evaluations primarily rely on RCT inputs. This study aimed to provide a within-model comparison of cost-effectiveness estimates derived from RCT and population-based RWE for pembrolizumab plus platinum therapy versus platinum therapy alone.

Androgen deprivation therapy (ADT) remains the standard treatment for advanced prostate cancer (PCa); however, most patients ultimately progress to lethal castration-resistant PCa (CRPC). Emerging evidence implicates RNA N⁶-methyladenosine (m⁶A) modification as a key regulator of cancer biology, yet its role in CRPC remains poorly understood. As a critical adaptor in the m⁶A methyltransferase complex, RNA-binding motif protein 15 (RBM15) directs m⁶A deposition to specific mRNA targets. Here, we identified RBM15 as the key methyltransferase member significantly upregulated in CRPC tissues and strongly correlated with poor patient survival. Functionally, RBM15 overexpression reduces PCa cell sensitivity to enzalutamide, whereas its knockdown suppresses tumor growth and invasion. Mechanistically, RBM15 is an androgen-responsive protein whose expression increases upon chronic androgen deprivation. It catalyzes m⁶A methylation at position A1384 of damaged DNA binding protein 1 (DDB1) mRNA, leading to YTHDF2-dependent transcript decay and reduced DDB1 protein levels. Lower DDB1 impairs K48-linked polyubiquitination of the androgen receptor (AR), thereby stabilizing AR and amplifying AR signaling. Importantly, AR transcriptionally activates RBM15, forming a feed-forward loop that drives CRPC progression. Collectively, our findings establish RBM15 as a central epitranscriptomic driver of CRPC and identify the RBM15-DDB1-AR axis as a promising therapeutic target. Dual inhibition of RBM15 and AR may offer a novel strategy to overcome treatment resistance in advanced PCa.

Real-world evidence on the treatment of early triple-negative breast cancer (TNBC) remains limited. This study provides an overview of neoadjuvant chemotherapy (NACT) regimens used in the 2010s of the 21st century, analyzing patient outcomes and treatment patterns based on real-world data from a large population-based cancer registry.

IntroductionThe prognosis differences of gastrointestinal stromal tumors (GISTs) between the jejunum and ileum have rarely been studied. This study aimed to evaluate the long-term survival outcomes in patients with jejunal and ileal GISTs.MethodsThis population-based retrospective cohort study utilized data from the Surveillance, Epidemiology, and End Results (SEER) database from 2000 to 2019. Kaplan-Meier analyses and Cox proportional hazards models were employed to assess overall survival (OS) and cancer-specific survival (CSS). A 1:1 propensity score matching (PSM) approach was implemented to address confounding factors, and subgroup analyses were performed for various variables.ResultsA total of 1237 patients were analyzed, with 848 in the jejunum and 389 in the ileum. Ileal GISTs patients were older, exhibited higher T stages, larger tumor sizes, elevated mitotic rates, and were more susceptible to distant metastasis (P<0.05). After PSM, the jejunal GISTs group and the ileal GISTs group demonstrated comparable OS (hazard ratio [HR]: 1.25, 95% confidence interval [CI]: 0.97-1.60, P=0.082) and CSS (HR: 1.13, 95% CI: 0.81-1.59, P=0.461). Additionally, jejunal GISTs and ileal GISTs exhibited similar OS and CSS across various subgroups. Multivariate Cox regression analysis revealed age, TNM stage, and mitotic rate as independent risk factors influencing OS, whereas race, N stage, and M stage were identified as independent risk factors affecting CSS.ConclusionsJejunal GISTs and ileal GISTs have comparable OS and CSS, with the occurrence of lymph node metastasis and distant metastasis being important factors affecting their prognosis.

Osteosarcoma is the most common primary malignant bone tumor in children and adolescents, yet its genetic etiology remains poorly understood. In this study, we described a family from the Shanghai General Hospital Osteosarcoma (SGH-OS) cohort in which two siblings developed osteosarcoma as their first primary malignancy, and we investigated the germline and somatic genetic basis underlying this familial presentation.

Diabetes mellitus and cancer are growing global health concerns with a rising prevalence and substantial associated mortality. The study aims to find impact of diabetes mellitus in cancer. A narrative review was conducted by analysing evidence from various sources, including meta-analyses, systematic reviews, retrospective studies, database analyses, and cohort studies. The review explored the complex interplay between Diabetes Mellitus and cancer, like cancer incidence, oncology outcome i.e., acute and late toxicities, treatment compliance, overall survival (OS), and quality of life (QoL). Diabetes mellitus increases the risk of developing cancer by 10%. Diabetic patients had higher infection rates [2.6%-52%, odds ratio (OR) 1.38-1.57], increased haematologic toxicity (13%-65.7%, P=0.004), and greater hospital admissions (17.2%-74.5%, OR 2.1, P< 0.001). They received significantly lower cisplatin doses (18%-33% reduction), experienced more surgical delays [adjusted OR 1.16, 95% confidence interval (CI) 1.05-1.27], higher risk of flap failure (RR=1.83, 95% CI 1.18-2.85, P=0.007) and were less likely to undergo breast reconstruction (adjusted OR 0.48-0.54, 95% CI 0.24-1.00). Diabetes mellitus decreases local control by 10-20%, increases mortality by 27-98%, and decreases OS by 18-50% across various cancers. It increases late toxicity and negatively impacts QOL with a 1.3-2.7 times higher risk of grade ≥2 genitourinary and gastrointestinal toxicity in prostate cancer, a twofold increase in grade ≥3 radiation pneumonitis in lung cancer, and a 50% higher incidence of severe peripheral neuropathy in breast cancer, leading to delayed recovery and long-term morbidity. In patients receiving cancer directed therapy, diabetes mellitus increases acute and late toxicities, decreased local control and overall survival, and have poor quality of life.

Background and objectives The relationship between sarcopenia and prognosis in patients undergoing chemotherapy for testicular germ cell tumours remains underexplored. We aimed to evaluate the impact of sarcopenia on disease progression and overall survival in these patients. Methods This retrospective multicentre study included patients who received chemotherapy for testicular germ cell tumours between January 2010 and December 2023. The psoas muscle index was calculated by measuring the cross-sectional area of the psoas muscle at the third lumbar vertebral level and was divided by the square of the height. Patients were divided into two groups based on changes in PMI (before and after chemotherapy): Group 1 (<10% change) and Group 2 (≥10% change). Results A total of 159 patients were analysed. Of these, 113 (71.1%) were in Group 1 and 46 (28.9%) in Group 2. Group 2 showed higher rates of disease progression (26.1% vs. 10.6%) and mortality (8.7% vs. 1.8%) (P=0.023 and P=0.038, respectively). In multivariable analysis, ≥10 % decrease in psoas muscle index [Hazard Ratio (HR)=6.499, P<0.001], rete testis invasion (HR=3.459, P=0.007), and non-seminomatous/mixed histology (HR=5.777, P=0.020) were identified as independent predictors of disease progression. For mortality, only a ≥10 % decrease in psoas muscle index was found to be a significant predictor (HR=5.994, P=0.049). Interpretation and conclusions A reduction in PMI is an independent prognostic factor for both disease progression and mortality in patients undergoing systemic chemotherapy for testicular germ cell tumours.

Telomerase is active in the majority of high-risk neuroblastomas, a pediatric tumor associated with poor patient outcomes. In other cancer types, resistance to immune checkpoint blockade was overcome by induction of telomere dysfunction using the telomerase substrate precursor 6-thio-2'-deoxyguanosine (6-thio-dG). Here, we explored whether induction of telomere dysfunction improves the anti-tumor efficacy of immune checkpoint inhibition in neuroblastoma. 6-thio-dG treatment induced the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway and programmed cell death ligand-1 (PD-L1) expression in murine neuroblastoma cells in vitro. In a MYCN;ALKF1174L-driven transgenic neuroblastoma mouse model, 6-thio-dG treatment delayed tumor growth and prolonged survival. Treatment with anti-PD-L1 also led to growth delay and improved survival, which occurred; however, only after an initial lag phase. Combination with anti-PD-L1 improved the anti-tumor effects of 6-thio-dG and overcame the initial lag phase of anti-PD-L1 treatment. Mechanistically, 6-thio-dG combined with anti-PD-L1 treatment induced cGAS and PD-L1 expression and promoted immune cell infiltration in the tumors. Our findings suggest that 6-thio-dG treatment activates the cGAS-STING pathway in neuroblastoma and that induction of telomere dysfunction in combination with immune checkpoint blockade boosts intratumoral immune cell infiltration and improves survival in a high-risk neuroblastoma mouse model.

Cancer therapy imposes sustained mechanical and biochemical stress on lymphatic tissues, reshaping the signaling environments in which endothelial and contractile programs operate via molecular signals, cell-cell interactions, and mechanical forces. We propose that cancer-associated lymphedema arises from destabilized receptor crosstalk within integrated lymphatic signaling units rather than solely from anatomical insufficiency. Lymphatic vessels function as multicellular signal-processing systems in which receptor activity is context dependent and continuously modulated by ligand availability, tissue stiffness, inflammatory tone, and metabolic state. Under therapeutic stress, receptor systems that are secondary under homeostatic conditions, including mechanosensitive ion channels, purinergic receptors, and stress-responsive G protein-coupled receptors, can exert disproportionate influence over endothelial transcription, barrier function, contractile coordination, and immune-vascular feedback loops. Sustained activation of these networks may reinforce inflammatory and remodeling programs, providing a mechanistic explanation for delayed onset, nonlinear progression, and interindividual variability. This signaling-centered framework positions lymphatic failure after cancer therapy as a disorder of network integration and identifies stress-responsive receptor systems as tractable points for early intervention.

Supernumerary centrosomes are a hallmark of cancer. To maintain viability, cancer cells cluster these centrosomes during mitosis, enabling bipolar division similar to that of normal cells. Disruption of this centrosome clustering leads to multipolar anaphase and apoptosis (anaphase catastrophe), which selectively eliminates cancer cells harboring supernumerary centrosomes. In this context, because the motor protein KIFC1 contributes to centrosome clustering, we investigated whether targeting of this mechanism through KIFC1 inhibition could be exploited in small-cell lung cancer (SCLC), an aggressive malignancy with limited treatment options and poor prognosis. Through in silico and in vitro analyses, as well as IHC of clinical samples, we found that KIFC1 is overexpressed and that centrosome amplification occurs more frequently in SCLC compared with normal tissues and other cancer types. Pharmacological and genetic inhibition of KIFC1 disrupted the clustering of supernumerary centrosomes, triggered multipolar mitosis, and exerted antineoplastic effects in SCLC cells, with minimal effects on noncancerous cells. These findings were validated and extended in vivo using SCLC xenograft models. Finally, cotargeting KIFC1 and the centrosome duplication regulator PLK4 further enhanced growth suppression in SCLC cells. Together, these results suggest that disrupting centrosome clustering and triggering anaphase catastrophe via KIFC1 inhibition may represent a promising therapeutic strategy for SCLC.

Cancer is a leading cause of mortality worldwide, yet access to specialized pathology services remains limited in many low- and middle-income countries, including Tanzania. Telepathology offers a practical means to expand diagnostic capacity and improve timely cancer care. Through a partnership with the American Society for Clinical Pathology (ASCP) and Duke University, Kilimanjaro Christian Medical Centre (KCMC) implemented a telepathology consultation platform to provide expert review for diagnostically challenging cases.

The bone marrow workshop (session 3), held at the 22nd Meeting of the European Association for Hematopathology/Society of Hematopathology in Dubrovnik, was dedicated to myeloid/lymphoid precursor cell neoplasms and mixed-phenotype acute leukemias (MPALs). We hereby report the clinicopathologic, immunophenotypic, and genetic features of the submitted cases.

Neuropilin-1 (NRP1) is overexpressed in various malignant solid tumors, modulating the tumor microenvironment (TME) via multiple mechanisms to promote immune suppression, angiogenesis, and epithelial-mesenchymal transition (EMT), ultimately resulting in poor patient survival. Autophagy, a highly conserved cellular self-degradation process, plays a stage-dependent, bidirectional role in cancer. At early stages it suppresses tumorigenesis by clearing damaged cellular components, whereas at advanced stages it supports tumor survival under stress and thereby enhances proliferation, invasiveness, and therapy resistance. The interplay between NRP1 and autophagy in the TME is characterized by reciprocal regulation: NRP1 activates certain pathways to regulate autophagy, whereas autophagy induction promotes NRP1 degradation. This bidirectional interplay directly governs tumor progression and therapy resistance. Although prior studies have provided some clues about their interaction, the regulatory network and the precise mechanisms linking NRP1 and autophagy in the TME remain incompletely characterized. Precision therapies targeting the NRP1-autophagy axis still face multiple obstacles. This review synthesizes data from the atlas cancer genome (TCGA), the genotype-tissue expression (GTEx) database, and the human autophagy database (HADb) to explore associations between NRP1 and autophagy-related gene (ATG) in expression and prognosis, elucidate NRP1-autophagy interaction mechanisms and therapeutic opportunities and challenges in targeting the NRP1-autophagy axis. Pan-cancer analysis showed significant upregulation of NRP1 in 10 solid tumor types and revealed co-expression relationships between NRP1 and 340 ATGs. Among these, co-expression patterns involving genes such as CXCR4 and HSPA5 had significant prognostic value in gastric cancer and glioblastoma. This review systematically explores the panoramic regulatory framework of the NRP1-autophagy axis in the tumor immune microenvironment through bidirectional regulation of activating immunity and inhibitory immunity at the pan-cancer level. It fills the gap in the systematic summary of the NRP1-autophagy axis in regulating the dynamics of the tumor immune microenvironment, and provides a theoretical basis for the clinical translation of combination chemotherapy and immunotherapy targeting the NRP1-autophagy axis.

Exosomes can promote tumor development and regulate tumor immune responses, making them of significant value in Lung Adenocarcinoma (LUAD) management. In-depth exploration of exosome-related genes in LUAD is of great significance for expanding LUAD clinical treatment options.

Therapeutic resistance remains the principal cause of mortality in breast cancer. While the tumor microenvironment (TME) is a key contributor, therapies targeting isolated TME components, whether immune, metabolic, or spatial, have largely failed due to compensatory adaptations and ecological resilience. This review synthesizes recent advances to propose a tripartite "Immune-Metabolic-Spatial" axis as the fundamental organizer of a robust resistance niche. We elucidate how immunosuppressive cells, such as TAMs and Tregs, are metabolically sustained by altered nutrient availability like lactate and hypoxia, while spatial constraints, including CAF-deposited ECM and DDR1-mediated collagen alignment, physically impede drug delivery and immune infiltration. Critically, we highlight reciprocal crosstalk where metabolic reprogramming dictates immune cell function, in turn influencing stromal remodeling to create a self-reinforcing resistance loop. Beyond mechanism, we evaluate emerging strategies that concurrently target multiple axes, such as combining immune checkpoint blockade with metabolic inhibitors or stromal disruptors. Finally, we discuss clinical translation through biomarker development and innovative trial designs, framing the tripartite axis as an actionable framework for overcoming therapeutic resistance.

Bladder cancer is the tenth most common cancer worldwide and the sixth most common among men. However, research into representative tumor models for bladder cancer remains underdeveloped, limiting insights into tumor biology and drug development.

Unintentional weight loss (UWL) is the primary diagnostic parameter for cancer cachexia in the clinic. Prompt identification of UWL can lead to earlier diagnoses and interventions for cancer. This study investigates the frequency and timing of UWL documentation and diagnoses in a cohort of cancer patients with measured UWL and sought to understand how recognition of UWL is related to stage of disease at cancer diagnosis.

Epithelioid angiosarcoma (EA) is a malignant tumor of endothelium origin that most commonly arises in the deep soft tissues of extremities but may occasionally be primary in skin, adrenal gland, and bone. A 72-year-old male presented with a painless enlargement of his thyroid for more than 10 days before hospitalization. A walnut-sized mass in the right thyroid was found simultaneously by palpation and Color Doppler Ultrasound. After a total thyroidectomy was performed, a mass with a size of 4.5 cm × 3.5 cm was found at the lower pole of the right thyroid gland. Histologically, the tumor was diffusely distributed in a sheet-like pattern, with tumor cells being epithelioid. There was extensive coagulative necrosis while no components of papillary carcinoma, follicular carcinoma and insular poorly differentiated carcinoma were noticed. CD31 and vimentin were positive for immunostaining. The diagnosis of primary epithelioid angiosarcoma of right thyroid was then given to the patient. Eleven months after the operation, the patient died from brain metastasis. It is suggested that primary epithelioid angiosarcoma of thyroid, as an extremely rare tumor, have no characteristic clinical manifestations, laboratory and imaging examinations, and the diagnosis mainly depend on its unique clinical pathological features. Although extensive surgical resection is the preferred treatment, the prognosis is still very poor.

Combined large cell neuroendocrine carcinoma (LCNEC) of the endometrium is rare and carries a poor prognosis. A 61-year-old woman with suspected endometrial serous carcinoma was referred to our hospital. Imaging studies staged the disease as stage IIIC1. We performed a total hysterectomy, bilateral salpingo-oophorectomy, omentectomy, and retroperitoneal lymph node dissection. Histopathological examination revealed a combination of LCNEC, endometrioid carcinoma, and multiple lymph node metastases. Postoperative computed tomography showed multiple pulmonary metastases not detected preoperatively. Given the advanced and recurrent nature of the disease, treatment with paclitaxel, carboplatin, and durvalumab was initiated. After the first cycle, the pulmonary metastases disappeared. Maintenance therapy with durvalumab and olaparib was continued because of proficient mismatch repair status. This case demonstrates that durvalumab may be a viable treatment option for endometrial LCNEC, as it is also approved for small cell lung cancer, which shares similarities with neuroendocrine carcinoma.