BMC Cancer最新文献

Background: Oropharyngeal squamous cell carcinoma (OPSCC) is increasing worldwide, with a well-established link to human papillomavirus (HPV). However, evidence on how lifestyle risk factors-particularly smoking, alcohol consumption, and betel-quid chewing-modify the prognostic impact of HPV-associated disease remains limited, especially in regions with high exposure burden such as Taiwan. Understanding the interplay between viral and lifestyle determinants is essential for accurate prognostication and treatment planning.

Methods: We conducted a retrospective cohort study of 5,671 OPSCC patients using data from the Taiwan Cancer Registry between 2018 and 2021. p16 status was used as a surrogate marker for HPV infection. Overall survival and cancer-specific survival were compared across p16 status, age, sex, tumor location, cancer stage, lifestyle risk factors and treatment pattern using Kaplan-Meier method and multiple Cox models. Treatment-stratified analyses were additionally performed to evaluate whether lifestyle risk factors modified prognosis within p16-positive disease.

Results: Overall, 23.2% of OPSCC cases were p16-positive, with substantially higher p16 positivity among females (52.5%) and in tonsillar subsites. p16-positive patients had significantly better 5-year overall survival (69.0%; 95% CI, 66.0%-71.8%) than p16-negative patients (37.9%; 36.1%-39.6%). However, among p16-positive individuals, the presence of multiple lifestyle risk factors markedly attenuated the survival advantage, reducing 5-year overall survival from 78.6% (74.0%-82.5%) in those without lifestyle exposures to 57.6% (52.6%-62.4%) in those with smoking plus other risks. These gradients persisted after multivariable adjustment and across treatment modalities. In contrast, lifestyle risk factors were not independently associated with survival in p16-negative OPSCC, where prognosis was primarily driven by tumor stage, subsite, and treatment.

Conclusions: This nationwide study provides novel evidence that the prognostic benefit associated with p16 positivity is substantially attenuated by multiple lifestyle risk factors. These findings highlight the importance of integrating viral and behavioral determinants into prognostic assessment and treatment planning. They also underscore the need to pair HPV-associated prevention strategies with efforts to reduce tobacco, alcohol, and betel-quid use in regions with high burdens of these exposures.

Background: The prognostic significance of high mobility group box 1 (HMGB1) expression in the non-small cell lung cancer (NSCLC) population remains controversial. This study endeavors to systematically evaluate the relation of HMGB1 expression levels to NSCLC prognosis via a comprehensive meta-analysis.

Methods: Embase, the Cochrane Library, Web of Science, as well as PubMed were retrieved for eligible studies until September 18, 2025. Two reviewers independently extracted relevant data and appraised the study quality. The study quality was examined via the Newcastle-Ottawa Scale (NOS). Hazard Ratio (HR) with corresponding confidence intervals (CIs) for survival outcomes were calculated and summarized respectively. Subgroup analysis, regression analysis, sensitivity analysis and publication bias were conducted to investigate the findings further.

Results: 11 studies on 4,527 NSCLC patients were encompassed. All eligible studies had high methodological quality. The pooled HR of OS was 1.08 (95% CI: 0.91-1.29, P = 0.356), suggesting no significant association of HMGB1 expression levels with NSCLC prognosis. Subgroup analysis of studies with sample sizes < 100 revealed a significant relation of high HMGB1 expression to poorer OS (HR: 1.51, 95% CI: 1.22-1.87). Conversely, when HMGB1 expression level was detected before chemotherapy, high HMGB1 expression was linked to improved OS (HR: 0.96, 95% CI: 0.93-0.99).

Conclusion: This meta-analysis demonstrated that HMGB1 expression was not significantly associated with OS in the overall NSCLC population, but may have context-dependent prognostic value warranting further investigation.

Background: Tumor deposits (TD) have been identified as adverse prognostic indicators in gastric cancer (GC); however, their incorporation into the TNM staging system remains controversial. This study aimed to determine the most effective approach for integrating TD into the TNM staging system to improve prognostic accuracy.

Methods: A retrospective analysis was performed on clinicopathological and follow-up data from patients who underwent radical surgery for gastric cancer (GC) at Yijishan Hospital, affiliated with Wannan Medical College, between January 2012 and December 2021. Patients were classified into TD-negative and TD-positive groups according to the presence or absence of TD in postoperative pathological reports.

Results: A total of 4,972 patients were analyzed, of whom 575 (11.56%) had TD. These patients were matched in a 1:1 ratio with 523 TD-negative patients. Several clinicopathological factors, including tumor size, T stage, N stage, neural invasion, and vascular invasion, were significantly associated with the presence of TD. Survival analysis revealed that patients with TD had significantly lower 5-year overall survival (OS) rates than those without TD across all TNM stage subgroups (I-II, IIIa, IIIb, and IIIc) (P < 0.05). The 5-year OS rates of patients with TD in stages I-II, IIIa, IIIb, and IIIc were comparable to those of TD-negative patients in stages IIIa, IIIc, IIIc, and IV, respectively (P > 0.05). The proposed staging system incorporating TD demonstrated the highest χ² value (181.658), the highest C-index (0.634), and the lowest - 2 log-likelihood (8427.456), indicating improved prognostic stratification.

Conclusion: TD represent independent prognostic factors in GC, distinct from the T, N, and M categories, and should be incorporated into the TNM staging system.

Background: Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) colorectal cancer, offering durable clinical benefits to a subset of patients. However, long-term survival is heterogeneous, and effective risk-stratification biomarkers for this subgroup are needed. This study investigated the prognostic significance of baseline serum uric acid (UA) levels in patients with dMMR/MSI-H colorectal cancer undergoing ICI therapy.

Patients and methods: This retrospective study enrolled 171 patients with advanced dMMR/MSI-H colorectal cancer receiving ICIs (monotherapy or combined with chemotherapy/targeted agents). Serum UA was measured within three days pre-treatment. An optimal UA cut-off was determined by receiver operating characteristic (ROC) curve analysis. Kaplan-Meier estimates and Cox proportional hazards models assessed the UA-overall survival (OS) association.

Results: Median follow-up was 21.1 months (range: 1.2-48.0). ROC analysis identified an optimal serum UA threshold of 274 µmol/L (Area Under Curve (AUC) = 0.82; sensitivity = 70.0%; specificity = 70.8%). Patients with UA ≥ 274 µmol/L exhibited significantly shorter OS compared to those with lower UA (Hazard Ratio (HR) = 2.31; 95% CI: 1.04-6.12; p = 0.001). Multivariate analysis confirmed elevated UA as an independent predictor of poorer OS (HR = 2.73; 95% CI: 1.37-6.16; p = 0.015), alongside stage IV disease, concurrent use of multiple ICI agents and the use of immunotherapy in the ≥ 3rd-line setting.

Conclusion: Elevated baseline serum UA is associated with poorer long-term survival in patients with dMMR/MSI-H advanced colorectal cancer receiving immunotherapy. As an accessible and cost-effective biomarker, UA shows potential for early risk-stratification and guiding individualized treatment strategies within this immunotherapy-sensitive population.

Background: Lung cancer, particularly adenocarcinoma and squamous cell carcinoma, remains a leading cause of cancer-related deaths globally. The diagnosis of multiple primary lung cancers (MPLCs) has become more frequent due to advanced chest CT technology and improved health surveillance. However, differentiating MPLCs from intrapulmonary metastases (IPMs) and multiple benign pulmonary lesions (MBPLs) remains challenging.

Objectives: Distinguishing multiple primary lung cancers from metastases and benign lesions on CT remains challenging yet critical for treatment planning. Current approaches rely on subjective interpretation and invasive procedures. This study aims to develop and validate an automated deep learning classification system to provide rapid, objective diagnoses for optimizing patient management.

Materials and methods: We studied 260 patients (MPLC = 83, IPM = 81, MBPL = 96; 881 axial CT slices). Six pretrained architectures (DenseNet-121, EfficientNet-B1, MambaOut-Kobe, ResNet-50, SwinV2-CR-Tiny-224, ViT-Tiny-Patch16-224) were compared in a five-seed ablation (seeds 42, 789, 1011, 2025, 2048). Pairwise one-vs-rest DeLong tests were aggregated across seeds to compare AUCs. Clinical utility was assessed using decision curve analysis (DCA). The final model (MambaOut-Kobe) underwent stratified five-fold cross-validation.

Results: Considering efficiency, MambaOut-Kobe combined competitive accuracy with the lowest memory (~ 100 ± 14 MB) and low latency (~ 0.0093 ± 0.0017 s/image). Aggregated DeLong testing found no significant AUC differences among these models after multiplicity control. On five-fold cross-validation, MambaOut-Kobe achieved a macro-AUC of 0.946 ± 0.004 (95% CI 0.942-0.950), and an accuracy 0.829 ± 0.029 (95% CI 0.800-0.858). DCA demonstrated a positive net benefit across clinically relevant threshold probabilities compared with treat-all and treat-none strategies. Grad-CAM visualizations highlighted diagnostically relevant regions in CT images, providing interpretable decision-making support.

Conclusions: The MambaOut Kobe model demonstrates outstanding potential for clinical application in classifying MPLC, IPM, and MBPL. Its combination of high accuracy and computational efficiency makes it a promising tool for lung cancer diagnosis and treatment planning. This automated approach could reduce diagnostic uncertainty, minimize unnecessary invasive procedures, and facilitate timely, personalized treatment decisions for patients with multiple lung lesions. Future studies should focus on validating the model on larger, multicenter datasets and enhancing its discriminatory capacity between MPLC and IPM.

Background: Patients with a tumor regression grade of 0 or 1 (CAP), are classified as well-responders after neoadjuvant chemoradiotherapy (NCRT). Although well-responders are expected to have superior prognosis, occurrences of recurrence and metastasis still exist.

Methods: Clinical data of patients from January 2017 to 2022 were analyzed.

Inclusion criteria: adenocarcinoma, cT3-4N0 or cTanyN+, receiving NCRT and surgery, CAP 0 ~ 1. The primary endpoint was three-year disease-free survival (3y-DFS). According to occurrence of DFS events, patients were divided into DFS (470, 91.8%) and non-DFS group (42, 8.2%). Cox regression analysis was applied to identify risk factors affecting prognosis of well-responders.

Results: A total of 512 well-responders were included, with mean age of 59.1 ± 10.6 years. Compared to DFS group, patients in non-DFS group had advanced mrT4 stage (33.3% vs. 18.1%, P = 0.017), higher positive rates of mesorectal fascia (52.4% vs. 35.1%, P = 0.026) and extramural vascular invasion (59.5% vs. 36.6%, P = 0.003), advanced ypT4 stage (56.2% vs. 23.8%, P < 0.001), ypN+ (23.8% vs. 9.4%, P = 0.014), and tumor deposits (14.3% vs. 3.6%, P = 0.005). The follow-up was end up to May 2024, with a duration of 36 (18 to 53) months. The tumor recurrence and metastasis rates were 0.8% (4) and 7.0% (36). The estimated 3y-DFS and overall survival in well-responders were 90.1% and 97.4%. Cox analysis identified ypT3 ~ 4 stage as independent risk factor resulting inferior DFS.

Conclusion: Well-responders are expected to have superior prognosis. Special attention should be given to patients with advanced stages or those exhibiting positive mesorectal fascia or extramural vascular invasion, or adverse pathological features.