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Multimodal risk assessment for oral potentially malignant disorders: Integrating patient-centered and specimen-derived data.3 weeks agoOral potentially malignant disorders exhibit heterogeneous malignant transformation risk that clinical approaches fail to adequately predict. Histopathologic dysplasia grading, the reference standard of risk assessment, is associated with poor interobserver reliability and limited prognostic discrimination. It is necessary to define other potential patient- and tissue-associated risk modifiers to improve patient-specific disease prediction.
PubMed was queried for patient- and specimen-derived factors as they relate to oral cancer and oral potentially malignant disorders, with preference for systematic review and meta-analysis articles published within the past 5 years. When not available, guidelines from the American Cancer Society, National Cancer Institute, or other national organizations or the most recent best articles were referenced to support the data presented.
Within patient-associated factors, validated measures of tobacco and alcohol exposure, clinical lesion characteristics, systemic health factors including metabolic syndrome components, comorbidity risk, and dental health indexes were found. Within specimen-derived data, tissue-based analyses encompassing histopathology and advanced molecular profiling (genomic, epigenomic, transcriptomic, spatial approaches), blood-based germline and somatic mutation analysis, and saliva-based microbiome characterization and inflammatory biomarker assessment were addressed.
Malignant transformation reflects intersecting patient and specimen risk pathways that affect each patient differently; no single modality captures this complexity. Realizing precision prognostication in oral precancer will require coordinated expansion and standardization of data collection across research groups. This review is intended to guide covariate selection for prospective study design, improve reproducibility, and ultimately enable the development of validated multimodal risk prediction tools for clinical deployment.CancerAccessCare/ManagementAdvocacyEducation -
Total en bloc resection of a giant cell tumour of the cervical spine involving the vertebral artery.3 weeks agoA woman in her 20s presented with neck pain and was diagnosed with a primary giant cell tumour (GCT) involving the C5 vertebral body and encasing the left vertebral artery (VA). Denosumab therapy was initiated to reduce tumour vascularity and facilitate resection. After preoperative embolisation of the left VA, total en bloc resection of the tumour was performed. Postoperatively, the patient experienced transient left upper extremity weakness, which improved significantly over time. Follow-up imaging showed successful bony fusion and no recurrence. This case highlights the importance of multidisciplinary planning in managing cervical spine GCTs involving critical neurovascular structures. Combined denosumab therapy and VA embolisation can enable safe and complete tumour resection, potentially improving outcomes and reducing recurrence risk, especially in young patients.CancerAccessCare/Management
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Current landscape and emerging trends of PD-1/PD-L1 research in prostate cancer: A data-driven atlas from multidatabase integration.3 weeks agoAlthough programmed cell death protein 1/programmed death ligand 1 (PD-1/PD-L1) blockade has transformed treatment in several malignancies, its role in prostate cancer remains uncertain. Interest in combination therapy, tumor-microenvironment modulation, and biomarker-guided selection highlights the need to clarify research trends. To characterize the knowledge structure, hotspots, thematic evolution, and clinical-trial evidence on PD-1/PD-L1 in prostate cancer. Publications were retrieved from the Web of Science Core Collection and Scopus. CiteSpace, VOSviewer, R, and Python were used to analyze publication trends, collaboration networks, thematic evolution, and knowledge flow. Clinical-trial reports identified in PubMed were screened and summarized. A total of 2,641 publications were included, comprising 1,421 original articles and 1,220 reviews, involving 17,180 authors and 4,658 keywords. Annual publications increased after 2014 and reached a peak in 2022. Among the candidate models, the logistic model performed best (AIC = 116.4), with the fitted trajectory suggesting a possible slowing. The United States and China were the leading contributors, whereas Canada, Germany, and the United Kingdom showed higher proportions of multinational collaboration. Research increasingly emphasized mechanism-driven and precision-oriented strategies, while exploratory and pan-cancer studies remain part of its knowledge base. The 13 included clinical trials covered diverse combination, but evidence was heterogeneous and no standardized treatment paradigm has yet been established. This multidatabase delineates the knowledge structure, evolution, and emerging directions of PD-1/PD-L1 research in prostate cancer. Current evidence indicates limited activity in unselected populations, whereas potential benefit may be concentrated in biomarker-defined subgroups and selected combinations requiring prospective validation.CancerAccessCare/ManagementAdvocacy
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Multimodal Management of Advanced Metastatic Prostate Cancer: Excellent Response Following Resection of Brain Metastasis and 177Lu-PSMA Therapy.3 weeks agoA 68-year-old man with metastatic prostate adenocarcinoma was treated with androgen-deprivation therapy and chemotherapy. Restaging 68Ga-PSMA PET/CT revealed a PSMA-avid lesion in the left temporal lobe, which was treated with brain radiotherapy. Subsequent PSMA PET/CT showed brain lesion progression and skeletal metastases. He underwent brain lesion resection followed by 4 cycles of 177Lu-PSMA-617, achieving near-complete resolution of skeletal metastasis. This case highlights the importance of multimodal treatment, including 177Lu-PSMA, in managing brain metastasis in prostate cancer.CancerAccessCare/Management
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Laryngeal NUT Carcinoma With BRD4::NUTM1 Fusion: A 4-Year Clinical Course Highlighting the Limitations of Current Multimodal Therapy.3 weeks agoNuclear protein in testis (NUT) carcinoma is a rare, aggressive malignancy driven by NUTM1 rearrangement, often misdiagnosed as squamous cell carcinoma, with no established standard therapy. This report describes the clinical course and treatment resistance in primary laryngeal NUT carcinoma and provides insights into potential mechanism-based therapeutic approaches.
A 30-year-old man with a laryngeal tumor was initially treated for poorly differentiated squamous cell carcinoma. Recurrent disease prompted re-evaluation; NUT carcinoma was diagnosed by NUT immunohistochemistry, and the BRD4::NUTM1 fusion was confirmed by molecular analysis. A bromodomain and extra-terminal (BET) inhibitor and alternating vincristine, doxorubicin, and cyclophosphamide (VDC)/ifosfamide and etoposide (IE) chemotherapy induced transient tumor regression, whereas vorinostat, immune checkpoint inhibitors, and other systemic therapies were ineffective. Disease progression was ultimately driven by uncontrolled locoregional recurrence. Autopsy revealed a massive infiltrative tumor with extensive locoregional invasion, whereas distant metastatic disease was limited to minute pulmonary nodules; death resulted from overwhelming infection secondary to uncontrolled locoregional progression rather than systemic metastasis.
Early molecular diagnosis and biologically informed multimodal strategies are essential for managing laryngeal NUT carcinoma and overcoming treatment resistance.CancerChronic respiratory diseaseCare/ManagementAdvocacy -
Robot-assisted brachytherapy targeting the stylomastoid foramen for parotid adenoid cystic carcinoma with facial nerve involvement: a retrospective study.3 weeks agoThe objective was to evaluate the technical feasibility, geometric accuracy, and preliminary short-term safety of using a multimodal, image-guided, robot-assisted iodine-125 seed implantation targeting the stylomastoid foramen and high-risk perilesional regions in selected patients with parotid adenoid cystic carcinoma with facial nerve involvement. A total of 23 consecutive patients treated between January 2020 and January 2023 were reviewed. Preoperative puncture planning was conducted using fused computed tomography (CT)/magnetic resonance imaging datasets. Intraoperative percutaneous needle placement and radioactive seed implantation were performed under robotic navigation. Postoperative CT imaging was obtained within 24 h to quantify implantation accuracy by calculating the spatial deviation between planned and actual seed positions. All patients were followed for up to 3 years, during which neurological function and intracranial tumor progression were systematically evaluated using clinical assessment and imaging. All surgeries were completed successfully without intraoperative incidents or significant perioperative complications. The mean particle placement error was 1.46 ± 0.85 mm (95% confidence interval: 1.09-1.83 mm), with intraoperative blood loss of 2-3 mL. During subsequent follow-up, no further neurological deficits were observed, and serial imaging revealed stable disease in 16 patients, partial response in six, and local progression without intracranial extension in one. The employment of robot-assisted iodine-125 brachytherapy has the potential to offer a safe, accurate, and minimally invasive clinical option for focal neural-pathway irradiation in a selected group of high-risk parotid adenoid cystic carcinoma patients. However, the confirmation of long-term oncological and neurological benefits necessitates the performance of prospective controlled studies.CancerCare/Management
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Camrelizumab plus nimotuzumab as second-line therapy for advanced esophageal squamous cell carcinoma: a multicenter phase II study.3 weeks agoTherapeutic options for advanced esophageal squamous cell carcinoma (ESCC) after first-line failure remain limited, particularly in patients previously exposed to immune checkpoint inhibitors (ICIs). We evaluated the efficacy, safety, and exploratory biomarker correlates of camrelizumab, an ICI, combined with nimotuzumab, an anti-epidermal growth factor receptor (EGFR) monoclonal antibody, as second-line therapy for ESCC.
In this multicenter, single-arm, phase II study, patients with advanced ESCC who progressed after first-line therapy received camrelizumab (200 mg every 2 weeks) plus nimotuzumab (400 mg weekly). The primary endpoint was the objective response rate (ORR).
Between November 2021 and December 2024, 46 patients were enrolled. The confirmed ORR was 32.6% (15/46; 95% CI 19.5 to 48.0) and the disease control rate was 82.6% (38/46; 95% CI 68.6 to 92.2). Median progression-free survival (PFS) was 9.13 months (95% CI 5.95 to 9.76), and median overall survival (OS) was 12.62 months (95% CI 9.40 to 15.01). Clinical activity was observed across subgroups, including immunotherapy-naïve and previously treated patients (ORR 32.0% vs 33.3%). Patients with EGFR amplification demonstrated a higher ORR (47.1% vs 24.0%) and longer median OS (13.17 vs 9.99 months). Among patients with M1 disease (n=39), the ORR was 30.8% (95% CI 17.0 to 47.6), the median PFS was 8.48 months (95% CI 5.95 to 9.59), and the median OS was 12.55 months (95% CI 7.95 to 14.88). Treatment-related adverse events occurred in 80.4% of patients, with grade ≥3 events in 8.7%. Exploratory analyses suggested that MUC16 mutations were associated with lower ORR (8.3% vs 46.4%, p=0.030), NOTCH3 mutations with prolonged survival (median PFS not reached vs 8.21 months, HR 0.20, p=0.015; median OS not reached vs 10.58 months, HR 0.22, p=0.026), and MTAP deletions with shorter PFS (3.71 vs 9.49 months, HR 3.18, p=0.005).
Camrelizumab combined with nimotuzumab demonstrated encouraging antitumor activity and a manageable safety profile as second-line therapy for advanced ESCC.
NCT03766178.CancerCare/Management -
HIF1A+CSF3R+ neutrophils-dominated hypoxic niche induced metabolic reprogramming for neoadjuvant therapy resistance in NSCLC.3 weeks agoNon-small cell lung cancer (NSCLC) is one of the frequently occurring cancers characterized by molecular heterogeneity and multiple immune cell infiltration patterns, which are associated with treatment sensitivity and resistance. However, the specific microenvironmental cells and their mechanisms that lead to treatment resistance in patients need to be explored in greater depth.
On the basis of patients receiving neoadjuvant therapy in our center, a multicenter, multicohort NSCLC spatial transcriptome, single-cell transcriptome, T-cell receptor repertoire sequencing, bulk RNA transcriptome, phosphorylated proteome, genome mutation, and clinical data were included for a comprehensive assessment of the therapeutic and prognostic impact of HIF1A+ CSF3R+ neutrophils in NSCLC. In vitro experiments validated the functional phenotype of HIF1A+ CSF3R+ neutrophils and co-localization interactions with other cellular subpopulations. Gradient boosting machine (GBM) constructed region of interest (ROI) models for evaluation. Computer-aided drug design (CADD) was used to predict targeted small molecule drugs, and in vivo mouse models were constructed to assess the effectiveness of the combination treatment regimen.
Centered on HIF1A+ CSF3R+ neutrophils, recruited exhausted T cells and stromal cells form a hypoxic niche within the tumor region, which was enriched in non-response patients. ROI composed of these specific cellular subpopulations, associated with senescence and glycolysis, accurately predicting NSCLC progression, prognosis, and microenvironment composition. CADD analysis identified that platycodin-D2 specifically targeted CSF3R, reducing HIF1A expression and inhibiting neutrophil activity. Combining navitoclax, platycodin-D2 with anti-programmed cell death protein 1 (PD-1) significantly suppressed tumor proliferation and improved the immunosuppressive microenvironment.
Our study emphasized the role of HIF1A+ CSF3R+ neutrophils in immunotherapeutic resistance of NSCLC, constructed a microenvironmental immune dysregulation network in a hypoxic ecological niche with HIF1A+ CSF3R+ neutrophils as the center. Platycodin-D2 specifically targeted HIF1A+ CSF3R+ neutrophils, enhancing the efficacy of anti-PD-1 therapy in NSCLC.CancerChronic respiratory diseaseCare/Management -
Spectral computed tomography in thoracic pathology: A technological and clinical update.3 weeks agoSpectral computed tomography (CT) is an advanced imaging technique known for its ability to decompose and characterise materials. Understanding the underlying physics can aid radiologists in using the technique effectively, interpreting its imaging signs and identifying potential artifacts or limitations. In the field of thoracic radiology, it provides significant contributions to the diagnosis of vascular diseases such as acute and chronic pulmonary thromboembolism, in the follow-up of malignant pulmonary masses treated with percutaneous ablation, and it plays an emerging role in the characterisation of pulmonary tumours. The aims of this article are, firstly, to review the advantages and limitations of spectral imaging, and secondly, to discuss its applications in thoracic radiology.CancerChronic respiratory diseaseCardiovascular diseasesCare/Management
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Recommendations for the use of gadolinium-based contrast agents in magnetic resonance imaging of the central nervous system.3 weeks agoGadolinium-based contrast agents (GBCAs) are essential for improving the diagnostic accuracy of magnetic resonance imaging (MRI) studies. Although traditionally regarded as highly safe, in recent years the marketing authorisation for certain linear GBCAs has been withdrawn, and the use of macrocyclic GBCAs has become subject to regulatory oversight. Current recommendations advocate the use of the lowest effective dose at all times. Central nervous system (CNS) pathology is the most common indication for MRI with GBCAs. However, clinical recommendations and best practices in this setting often lack a comprehensive approach. This document presents recommendations for the use of GBCAs in the main categories of CNS disease-namely neuro-oncological, inflammatory, infectious and vascular conditions-as well as in CNS angiographic studies. These recommendations have been developed by a nationally convened expert committee. It also highlights the importance of ensuring clinical and environmental safety in the use of these contrast media.CancerCare/Management