Frontiers in Oncology最新文献

Background: Pancreatic cancer is notoriously associated with a poor prognosis and limited survival. We aim to develop a simple and accessible model that can accurately predict the prognosis of pancreatic cancer patients.

Methods: This study retrospectively analyzed the blood indicators and overall survival of 500 pancreatic cancer patients. The median value was used as the cutoff for univariate and multivariate analyses. To address the limitations of the median value, receiver operating characteristic analysis was performed, and the optimal cutoff value (the highest Youden index) was determined, followed by univariate and multivariate analyses. Prognostic LASSO coefficient screening was performed to establish a pancreatic cancer prognostic prediction model. Risk factor diagram, Kaplan-Meier curve and prognostic calibration curve were plotted to validate the efficacy of the model.

Results: Multivariate regression analysis showed that neutrophils (hazard ratio (HR) = 1.416, 95% confidence interval (CI) = 1.037-1.932, P = 0.028), lymphocytes (HR = 0.625, 95% CI = 0.462-0.846, P = 0.002), Carcinoembryonic Antigen (CEA) (HR = 1.820, 95% CI = 1.315-2.518, P < 0.001), CA125 (HR = 1.392, 95% CI = 1.001-1.936, P = 0.049), TNM stage (I vs. III: HR = 3.052, 95% CI = 1.900-4.905, P < 0.001; I vs. IV: HR = 4.815, 95% CI = 2.504-9.258, P < 0.001) and Neutrophil-to-Lymphocyte Ratio (NLR) (HR = 1.748, 95% CI = 1.210-2.525, P = 0.003), Lymphocyte-to-Monocyte Ratio (LMR) (HR = 0.597, 95% CI = 0.430-0.829, P = 0.002), Neutrophil-to-Macrophage Ratio (NMR) (HR = 2.065, 95% CI = 1.331-3.206, P = 0.001), and Systemic Immune-Inflammation Index (SII) (HR = 1.751, 95% CI = 1.244-2.466, P = 0.001) were independent risk factors for OS. We have developed a new model incorporating gender, age, treatment, TNM stage, pathological grade, CEA, CA125, and NLR. The model demonstrates good predictive performance, with a C-index of 0.73.

Background: Head and neck squamous cell carcinomas (HNSCC) have high recurrence and poor prognosis, largely due to delayed diagnosis. Identification of somatic mutations and human papillomavirus (HPV) sequences in tumor DNA shed in the oral cavity may provide non-invasive biomarkers for early HNSCC detection.

Objectives: The study aimed to evaluate TERT promoter (TERTp) mutations in tumor DNA extracted from oral rinses as potential biomarkers for head and neck cancers.

Methods: TERTp mutations (C228T and C250T) were examined in DNA extracted from oral rinses of 132 HNSCC patients, of whom 63 had paired tumor tissue available for analysis, and from four head and neck squamous cell carcinoma derived cells lines (CAL27, SCC152, SCC154, FaDu) by using droplet digital PCR (ddPCR). TERT gene expression was analyzed in all cell lines by real time PCR. Associations with tumor site, smoking status, and sex were evaluated, and mutant allele frequencies (MAF) quantified.

Results: TERTp mutations were identified in 25% of oral rinses (33 out of 132, 95%CI 22.7 - 46.3) and in 27% of tumor tissues (17 out of 63, 95%CI 9.9 - 27.2). Mutation rates were highest in oral SCC (OSCC), present in 50% of oral rinses (n=25/50, 95%CI 16.2 - 36.9) and 46% of matched tumor tissues (n=13/28, 95%CI 6.9 - 22.2), with 96% concordance (kappa value 0.86, 95%CI 67-100). MAF were higher in tumor tissues and correlated with levels in corresponding oral fluids. Mutations were uncommon in non-OSCC cases, being detected in 9.7% of oral rinses and 11% of tumor tissues. In OSCC, TERTp mutations were more frequent in males. The CAL27 cell line carried the TERTp C228T mutation and TERT mRNA expression was 11-15 folds higher compared to non-mutated oral carcinoma cell lines.

Conclusions: TERTp C228T and C250T are mutually exclusive and occur at a high frequency in oral rinses and tumor tissues of OSCC patients, showing high concordance between paired samples. These findings support the potential of TERTp mutations as non-invasive biomarkers for OSCC detection. Moreover, their higher prevalence in males suggests possible sex-related differences in OSCC mutation patterns.

Introduction: Understanding factors influencing individual survival outcomes following surgical resection of locally advanced (LARC) rectal cancer remains challenging. Novel biomarkers could show emerging promise in this setting. This study aimed to systematically review the literature on immune prognostic factors in LARC.

Methods: The review protocol was preregistered on the PROSPERO database (CRD42023460541). Included studies were required to report overall survival and at least one immune prognostic factor for at least ten patients with LARC. Final searches of MEDLINE, EMBASE and Central were concluded on 8th September 2023. The risk of bias was assessed using the QUIPS tool.

Results: 22 retrospective cohort studies involving 2,622 LARC patients were included in the review. We did not find any published data on immune prognostic factors in locally recurrent rectal cancer. Due to inconsistency of immune prognostic factor definitions and measurement methods, meta-analysis would not be meaningful. Instead, the results are presented descriptively. Risk of bias was concentrated in the participation, attrition, and confounding domains. Greater cytotoxic cell infiltration was associated with improved overall survival. There was inconsistent evidence of an association of PD-L1 expression and survival. M2 macrophage infiltration and homozygous germline FPR1 loss-of-function were associated with worse survival.

Discussion: These findings support a role for both innate and acquired immune systems in mediating outcomes following surgery for LARC and suggest that further work into immunomodulation may show promise in improving LARC treatment.

Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier [CRD42023460541].

Background: Quantitative evidence on the association between disseminated cancer (DC) and 30-day postoperative mortality after tumor resection craniotomy in adults is limited. This study evaluates the association between them.

Materials and methods: This retrospective analysis utilized propensity score matching (PSM) on cases extracted from the American College of Surgeons National Surgical Quality Improvement Program database (2012-2015). The study examined DC as the independent variable and 30-day postoperative mortality as the dependent outcome. A logistic regression analysis was conducted on the PSM data that were 1:1 matched. The DC-mortality association was assessed using robust statistical estimation methods.

Results: The study cohort comprised 18,642 eligible patients (52.6% male, 47.4% female), including 4,022 (21.57%) with DC. The mortality rate was significantly higher in DC patients (4.97%) compared to the overall cohort undergoing tumor-related craniotomy (2.46%). Multivariate analysis and propensity score-adjusted analysis demonstrated that, compared with non-DC, the postoperative 30-day mortality of patients with DC undergoing craniotomy for brain tumors significantly increased, with associated odds ratios of 1.72 to 2.06.

Conclusion: Given the relatively high risk of mortality within 30 days after craniotomy in patients with DC, both preoperative surgical decision-making and postoperative management strategies should be appropriately modified to reduce mortality.

Background: Neuroblastoma (NB) is the most common extracranial solid tumor in children. The 5-methylcytosine (m5C) modification gene NSUN5 polymorphisms may serve as promising molecular markers for identifying populations susceptible to NB.

Method: TaqMan probes were used to genotype NSUN5 single nucleotide polymorphisms (SNPs) in 402 NB patients and 473 healthy controls. A logistic regression model was applied to calculate the odds ratio (OR) and 95% confidence interval (CI) to evaluate the association between genotype polymorphisms and NB susceptibility. The analysis was further stratified by age, gender, tumor origin site, and clinical stage.

Conclusion: In summary, our study indicates that the selected NSUN5 rs1880948 A>G polymorphisms may not be associated with neuroblastoma susceptibility. However, further studies with larger sample sizes and additional potentially functional polymorphisms are needed to validate these results.

Background and objective: Selecting the optimal treatment for locally advanced non-small cell lung cancer (LA-NSCLC) is complex and typically requires multidisciplinary tumor board (MTB) evaluation. This study investigated whether machine learning (ML) models trained on MTB decisions could support treatment selection by integrating clinicopathological characteristics with radiomic features from both the primary tumor and mediastinal lymph nodes (LN).

Materials and methods: We retrospectively analyzed patients with LA-NSCLC whose treatments had been decided by an expert MTB. Patients were categorized into three pathways: (A) upfront surgery, (B) neoadjuvant systemic treatment followed by surgery, (C) concurrent chemoradiotherapy. Baseline CT scans were segmented to extract radiomic features from primary tumors and mediastinal LNs. Two ML models were developed based on clinicopathological and radiomic data, using MTB decisions as ground truth: (1) A vs. Rest and (2) B vs. C. Performance was assessed in independent training and test cohorts using the area under the receiver operating characteristic curve (AUC) and accuracy.

Results: In the training cohort, the A vs. Rest achieved an AUC of 0.847 and accuracy of 0.795 with 13 features, while the B vs. C model reached an AUC of 0.740 and accuracy of 0.700 with 9 features. In the test cohort, results remained robust, with an AUC of 0.808 (accuracy 0.700) for A vs. Rest and an AUC of 0.754 (accuracy 0.740) for B vs. C.

Conclusions: ML models combining clinicopathological and radiomic features can reproduce MTB treatment recommendations for LA-NSCLC with good accuracy. This approach may provide decision in settings with limited MTB expertise and promote more consistent treatment allocation.

Background: Intussusception in adults is rare and is often associated with an underlying pathology such as tumors. Its coexistence with colorectal cancer (CRC) in young patients presents unique diagnostic challenges as imaging may suggest separate lesions rather than a single malignancy.

Case presentation: A 21-year-old man presented with worsening right upper and central abdominal pain. The contrast-enhanced abdominal CT suggested that the intussusception at the ileocecal region might be caused by a lipoma and revealed a separate mass in the transverse colon. Emergency laparoscopic exploration and subsequent open laparotomy confirmed a 4.0-cm × 5.0-cm cauliflower-like adenocarcinoma originating from the ileocecal region, which had caused the intussusception and mimicked separate pathologies on imaging.

Conclusions: This case highlights the diagnostic complexity of synchronous intestinal lesions in young patients. It underscores the need for a heightened suspicion of an underlying malignancy when encountering intussusception and emphasizes the limitations of imaging in accurately characterizing the complex pathology of the bowel.

Background: Polymerase proofreading-associated polyposis (PPAP) is a rare autosomal dominant cancer predisposition syndrome caused by germline pathogenic variants in POLE or POLD1. While colorectal and endometrial cancers are the most frequent manifestations, the full tumor spectrum of POLD1-related PPAP remains incompletely defined.

Case presentation: We describe two families carrying germline POLD1 variants classified as likely pathogenic. A novel missense variant c.1481T>G p.(Ile494Ser) and a recurrent missense variant c.1204G>A p.(Asp402Asn) were identified within the exonuclease domain. Both variants exhibited features consistent with pathogenicity, including high tumor mutational burden (TMB) and SBS10d mutational signature. Affected carriers developed colorectal and endometrial cancers, but also duodenal adenocarcinomas: this is the first report of this tumor type in germline POLD1 carriers.

Conclusions: Our report expands both the phenotypic and molecular spectrum of POLD1-associated PPAP by documenting the first duodenal adenocarcinomas in germline carriers and describing a novel variant. These findings emphasize the need for systematic upper gastrointestinal surveillance, support the systematic reporting of rare POLD1 variants to refine genotype-phenotype correlations, and underline the potential therapeutic relevance of identifying carriers in the context of immunotherapy.

Background and purpose: To explore the predictive value of a model based on clinical and contrast-enhanced computed tomography (CT) radiomic features for the early prediction of immunotherapy efficacy in patients with advanced non-small cell lung cancer (NSCLC).

Methods: This retrospective study included 144 patients with advanced NSCLC who received immunotherapy at Lanzhou University Second Hospital between January 2023 and December 2024. Clinical data and CT images were collected from each patient. All patients underwent imaging examinations to evaluate the efficacy of immunotherapy after the second treatment cycle. Patients who achieved complete response (CR) or partial response (PR) were considered to be in the reactive group, while those who experienced stable disease (SD) or progressive disease (PD) were considered to be in the non-reactive group. The participants were randomly divided into a training set (n = 115) and a testing set (n = 29) at a ratio of 8:2. Radiomic features were extracted from pre-treatment contrast-enhanced CT venous phase images. Feature reduction was performed using the Spearman rank correlation coefficient and the least absolute shrinkage and selection operator (LASSO) algorithm. The best radiomics signature was built using multiple machine learning algorithms and combined with clinical features to build a nomogram model. The area under the receiver operating characteristic curve (AUC), calibration curve, and decision curve analysis (DCA) were used to evaluate the model's predictive performance, calibration, and clinical net benefit.

Results: Three clinical features (C-reactive protein, baseline tumor size, and programmed death receptor ligand 1) and seven radiomics features (one first-order feature and six texture features) were selected for the model. The radiomic signature performed best based on the Extreme Random Tree algorithm. The radiomic signature and the nomogram model demonstrated superior predictive performance and clinical net benefit compared to the clinical model in both training and testing sets (AUCs: radiomics: 0.926 vs. 0.848; nomogram: 0.953 vs. 0.788; clinical: 0.882 vs. 0.742), with statistically significant differences (P < 0.05).

Conclusion: The integrated clinical-radiomics nomogram establishes a robust framework for early prediction of immunotherapy efficacy in advanced NSCLC, offering valuable support for personalized treatment decisions.

Objective: This study map the 1990-2021 basal-cell carcinoma burden in people ≥55 years worldwide, pinpoint key risk drivers, and offer concise intervention guidance for elder-focused prevention.

Methods: We focused on adults aged ≥55 years because this group shows the highest basal-cell carcinoma (BCC) frequency and matches the Global Burden of Disease (GBD) age strata. Incidence and disability-adjusted life-year (DALY) counts for 1990-2021 were downloaded from the Global Health Data Exchange. After direct age-standardisation, we plotted global, regional and national rates, generated world maps, computed annual percent change (APC) and contrasted 1990 versus 2021 distributions-all with R 4.2.1. A Bayesian hierarchical model then projected the 2050 burden.

Results: 1990-2021, Among adults ≥55 years, global basal-cell carcinoma incidence rose and then plateaued, while DALYs climbed before edging downward. The steepest gains in both age-standardized incidence and DALY rates occurred in high-income North America. Men consistently outpaced women across all metrics. The USA, Brazil and China recorded the largest absolute caseloads, yet the USA always posted the highest incidence rate and Nepal the lowest. Overall, the BCC burden has expanded over the past three decades.

Conclusion: Over the last three decades, both new cases and the overall toll of basal-cell carcinoma among older adults have risen worldwide, fueled by expanding and aging populations, greater ultraviolet exposure, and better case detection. Looking forward, vigorous sun-protection education and unified UV-shielding measures are essential to curb incidence and ease the growing burden.