This study aimed to investigate the clinicopathological features, treatment strategies and outcomes, failure patterns, and prognostic factors impacting progression-free survival (PFS) and overall survival (OS) in patients with extensive-stage primary small cell esophageal carcinoma (ES-SCEC). This retrospective study included consecutive patients with ES-SCEC diagnosed and treated at Fudan University Shanghai Cancer Center from January 2006 to December 2024. Clinicopathological data related to diagnosis, staging, and follow-up were collected. In patients with available tumor specimens, immunohistochemistry (IHC) was performed to assess the expression of POU2F3 (POU class 2 homeobox 3), standard neuroendocrine markers, thyroid transcription factor-1 and Ki-67. Univariate and multivariate Cox proportional hazards models were used to identify prognostic factors, with statistical significance defined as a two-sided p value < 0.05. Among the 112 patients with ES-SCEC, the median PFS was 5.0 months (95% CI: 4.4-5.6), and the median OS was 9.0 months (95% CI: 7.9-10.1). Liver metastasis was the most common metastatic site at initial diagnosis (58.9%). The use of immune checkpoint inhibitors (ICIs), the number of chemotherapy (CT) cycle and T stage were identified as independent prognostic factors for OS. Independent predictors of PFS included T stage, CT cycle, and thoracic radiotherapy (TRT). The overall response rate (RR) was 52.7%, and the disease control rate (DCR) was 90.2%. Patients receiving CT combined with ICIs (n = 33) achieved significantly longer median OS than those who not treated with ICIs (n = 72) (13.8 months vs. 8.8 months, p = 0.029). Patients treated with TRT (n = 36) demonstrated improved local control and longer median PFS compared with those not receiving TRT (n = 69) (7.9 months vs. 4.1 months, p < 0.001). The combination of CT, ICIs, and TRT was associated with favorable outcomes, with median PFS and OS of 10.1 and 16.9 months, respectively. The addition of ICIs to CT may be associated with improved survival in patients with ES-SCEC. This findings warrant validation in larger cohorts and prospective randomized studies.

Current clinical guidelines mandate routine evaluation of anaplastic lymphoma kinase (ALK) rearrangement in lung adenocarcinoma prior to ALK-targeted therapy initiation. This study aimed to develop and validate a non-invasive predictive model integrating deep learning radiomic (DLR) features from pre-treatment computed tomography (CT) images with clinical data to improve pretherapeutic ALK rearrangement prediction. We retrospectively analyzed 502 patients with histologically confirmed lung adenocarcinoma (153 ALK-positive, 349 ALK-negative), randomly split into training (80%) and validation (20%) cohorts. DLR features were extracted from pre-treatment CT images, and eight machine learning algorithms were compared. The optimal-performing algorithm was used to develop a combined clinical and deep learning radiomics (CDLR) model. Performance was evaluated via receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). Gradient-weighted Class Activation Mapping (Grad-CAM) and Shapley Additive Explanations (SHAP) enhanced model visualization and interpretability. The support vector machine (SVM)-based DLR model yielded the best performance (training area under the curve (AUC): 0.971, 95% confidence interval (CI): 0.9528-0.9888; validation AUC: 0.877, 95% CI: 0.8071-0.9463). The CDLR model exhibited comparable efficacy (training AUC: 0.971, 95% CI: 0.9527-0.9889; validation AUC: 0.887, 95% CI: 0.8203-0.9530), with both significantly outperforming the clinical-only model (training AUC: 0.669, 95% CI: 0.6110-0.7273; validation AUC: 0.660, 95% CI: 0.5443-0.7757). Calibration analysis confirmed good agreement between predicted and observed outcomes. Our CT-based deep learning radiomics model holds promise for non-invasive detection of ALK rearrangements in lung adenocarcinoma, yet remains investigational and necessitates prospective multicenter validation before clinical implementation.

The biological mechanism underlying the association between low body mass index (BMI) and increased risk of esophageal malignancy remains uncertain. We aimed to explore the role of metabolic alterations in the effect of low BMI on esophageal malignancy. We conducted a nested case-control study using a large-scale community-based screening cohort in a high-risk region for esophageal cancer (263 cases and 263 matched controls). Metabolomic profiling was performed based on untargeted ultra-high-performance liquid chromatography-tandem mass spectrometry, using the serum samples collected at enrollment prior to cancer diagnosis. Linear regression and conditional logistic regression were used to identify BMI-related metabolites and metabolites associated with esophageal malignancy, respectively, and the shared metabolites were included in mediation analysis. Low BMI was positively associated with esophageal malignancy (odds ratio (OR) = 1.8 (95% confidence interval: 1.1-2.8)). A total of 160 metabolites were identified to be associated with low BMI, and 107 metabolites were associated with esophageal malignancy. Among the 21 shared metabolites, four metabolites (three lipids and one amino acid) were identified as mediators for the association between low BMI and esophageal malignancy, with the mediation effect (OR) of 1.1 for each mediator. The metabolic signature constructed based on these mediators could explain 46.0% of the effect of low BMI on esophageal malignancy. Lipid-dominated metabolites mediate the association between low BMI and esophageal malignancy, which has provided crucial clues for understanding the etiology of esophageal malignancy and selection of early-warning metabolic biomarkers.

To compare treatment outcomes between first- and second-generation EGFR tyrosine kinase inhibitors (TKIs) in patients with EGFR co-mutated non-small cell lung cancer (NSCLC). EGFR mutation is one of the most common genetic alterations in NSCLC; however, the management of patients harboring EGFR co-mutations has emerged as a major therapeutic challenge in recent years. We conducted a retrospective cohort study (2018-2025) at Vietnam National Lung Hospital analyzing 81 treatment-naïve advanced NSCLC patients with EGFR co-mutations identified by next-generation sequencing. Patients received first- or second-generation EGFR-TKIs, with efficacy evaluated using RECIST v1.1 criteria. Among 81 patients with EGFR co-mutations, dual EGFR mutations were the most common (43%), followed by EGFR combined with PIK3CA (20%), ALK (14%), and KRAS (9%). Multivariate analysis suggested patients with EGFR dual mutations were correlated with higher overall survival (OS) compared with other co-mutation patterns (HR 0.26, 95% CI 0.09-0.76, p = 0.01). No significant differences were observed between first- and second-generation EGFR TKIs in objective response rate (56.5% vs. 73.5%, p = 0.181) or disease control rate, with both achieving a median progression-free survival (PFS) of 9 months. Subgroup analyses showed significantly longer OS with first-generation TKIs in female patients (27.59 vs. 22.72 months, p = 0.003) and brain metastatic groups (27.59 vs. 10.43 months, p = 0.032), whereas PFS remained comparable (9.10 vs. 7.23 months, p = 0.103). First- and second-generation EGFR-TKIs demonstrated comparable overall treatment outcomes in NSCLC patients harboring EGFR co-mutations. However, subgroup analyses suggested potential differences in clinical benefit among female patients and those with brain metastases, warranting further investigation.

This study aimed to investigate the impact of the treatment duration, initiation timing, and inflammatory factors on immunotherapy maintenance in patients with stage III unresectable lung squamous cell carcinoma. A retrospective analysis was conducted on 100 patients with stage III unresectable lung squamous cell carcinoma who received comprehensive treatment consisting of induction chemotherapy followed by concurrent chemoradiotherapy and consolidation immunotherapy (i.e., the "induction + concurrent chemoradiotherapy + consolidation immunotherapy" regimen) between January 2019 and December 2022. The analysis focused on treatment efficacy and prognostic factors. All statistical analyses were performed using SPSS software (version 25.0). Survival analysis was conducted using the Kaplan-Meier method, with between-group comparisons assessed by the Log-rank test (for univariate analysis, significance level α = 0.10). Multivariate analysis was performed using the Cox proportional hazards regression model (significance level α = 0.05). Optimal cutoff values for the neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and platelet-to-lymphocyte ratio (PLR) were determined using SPSS, and their sensitivity and specificity were calculated. Subsequently, based on these optimal cutoff values, patients were stratified into high- and low-value groups, thereby converting these continuous variables into categorical variables for further analysis. Among the 100 patients who received induction chemotherapy followed by concurrent chemoradiotherapy and consolidation immunotherapy, the 1-, 3-, and 5-year overall survival (OS) rates were 88.8%, 61.6%, and 43.6%, respectively. The corresponding 1-, 3-, and 5-year progression-free survival (PFS) rates were 74.6%, 45.3%, and 39.7%. Until the last follow-up, disease recurrence or metastasis occurred in 46 cases, including 15 cases of local recurrence, 16 cases of distant metastasis (8 with intracranial metastasis, 5 with liver metastasis, and 3 with bone metastasis), and 15 cases of regional lymph node metastasis (involving station 2, 4, 7 and supraclavicular lymph nodes).Univariate analysis identified TNM stage (p = 0.002), maintenance immunotherapy duration (p < 0.001), and interval between immunotherapy initiation and the last chemotherapy (p = 0.054) as factors associated with overall survival (OS).Multivariate Cox analysis confirmed that TNM stage (p = 0.03) and maintenance immunotherapy duration (p = 0.005) remained independently associated with OS. For progression-free survival (PFS), univariate analysis showed that the maintenance immunotherapy duration (p = 0.012) and TNM stage (p < 0.001) were significantly associated with PFS. Multivariate Cox analysis further demonstrated that both TNM stage (p = 0.01) and the maintenance immunotherapy duration (p = 0.034) retained independent associations with PFS. For patients with locally advanced lung squamous cell carcinoma, the comprehensive regimen of induction chemotherapy followed by concurrent chemoradiotherapy and consolidation immunotherapy-initiating consolidation immunotherapy two weeks after completing concurrent chemoradiotherapy and continuing for two years-yielded favorable outcomes, with efficacy comparable to that reported in previous studies. In this cohort, more advanced clinical stage, higher neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), and lower lymphocyte-to-monocyte ratio (LMR) were associated with poorer prognosis. The prognostic prediction model constructed based on TNM stage, NLR, PLR, and LMR demonstrated good predictive performance and clinical utility, representing a simple, economical, and effective tool worthy of further exploration for guiding clinical decision-making.

Smoking tobacco is proven to be associated with higher colorectal cancer (CRC) risk. However, the metabolic pathways of smoking and how they relate to CRC risk are unclear. A total of 227,898 participants from the UK Biobank were included. A two-stage strategy with a combination of linear regression and Mendelian randomization analysis was employed to identify smoking-related metabolites. Then the elastic net (EN) regression model was used to construct smoking-related metabolic signature. Multivariable Cox regression, Mediation analysis, and interaction analysis were employed to illustrate the associations of smoking and smoking related metabolic signature on the risk of CRC. Furthermore, the interaction between genetic susceptibility and smoking metabolic signature was estimated based on relative excess risk due to interaction (RERI) and multiplicative-scale interaction. During a follow-up of 12.5years, 3,328 incident CRC patients were observed. We identified 71 smoking-related metabolites and screened 42 of them metabolites by EN model to construct smoking-related metabolic signature. We observed smoking and smoking metabolic signature were both associated with the elevated risk of CRC, with a hazard ratio (HR) value of 1.27 and 1.38, respectively. Mediation analysis revealed metabolic signature can mediate 10.03% in the association between smoking and CRC risk. The additive interaction between genetic susceptibility and metabolic signature was statistically significant (RERI = 0.70, 95% confidence interval [CI] = 0.29-1.10). The detrimental impact of smoking on CRC risk is mediated partially by smoking metabolic signature, which is synergistic with genetic susceptibility.

Ovarian cancer is often diagnosed at an advanced stage, and recurrence after initial platinum-based chemotherapy remains a major challenge. Olaparib, a poly (ADP-ribose) polymerase inhibitor, is an essential maintenance therapy, particularly for patients with homologous recombination deficiency, with proven efficacy. However, hematologic toxicity-especially anemia-is common and frequently leads to dose reductions or treatment interruptions. Japanese patients may be more susceptible to this toxicity because of smaller body size and potentially higher systemic drug exposure. Although dose reduction is recommended for patients with moderate renal impairment in Western guidelines, standardized criteria have not been established in Japan, and real-world evidence on predictors of severe anemia is limited. This study aimed to identify clinical factors associated with grade ≥ 3 anemia during olaparib therapy. We conducted a single-center retrospective cohort study of patients with ovarian cancer who initiated olaparib at Kobe City Medical Center General Hospital between July 2018 and December 2022. Patients who began therapy at external institutions were excluded. Adverse events were assessed using Common Terminology Criteria for Adverse Events version 5.0. Cox proportional hazards models were applied to evaluate predictors of grade ≥ 3 anemia, with statistical significance set at P < 0.05. Among the 75 patients included the median baseline creatinine clearance (Ccr) was 75.7 mL/min. Twenty-five patients (33%) had prior exposure to pegylated liposomal doxorubicin (PLD), and eight (11%) had a baseline Ccr < 50 mL/min. Grade ≥ 3 anemia developed in 33 patients (44%). Multivariate analysis identified prior PLD exposure (hazard ratio [HR] 4.37, 95% confidence interval [CI] 2.30-8.29), baseline Ccr < 50 mL/min (HR 4.03, 95% CI 1.53-10.63), and baseline Grade 2 anemia as independent predictors. Treatment duration was significantly shorter in patients with prior PLD exposure. Prior PLD therapy, impaired renal function, and pre-existing anemia substantially increased the risk of severe anemia during olaparib treatment. These findings highlight the need for risk-adaptive monitoring strategies and proactive management in patients with high risk for severe anemia. Further studies with larger cohorts of patients with renal impairment are recommended to support dose-adjustment strategies and optimize treatment safety.

Pancreatic ductal adenocarcinoma (PDAC) is a major cause of cancer-related deaths in Australia, with a 5-year survival rate of less than 13%. The liver is the most common site of PDAC metastasis, and is observed in over 50% of cases. Standard chemotherapy, including regimens such as FOLFIRINOX or nab-paclitaxel plus gemcitabine, offer limited survival benefits, with median survival rates typically below one year. Selective internal radiation therapy (SIRT) with Yttrium-90 (90Y) microspheres is used to target liver metastases, but the optimal chemotherapy companion for SIRT in metastatic PDAC remains unknown. We conducted a retrospective audit of 32 patients with metastatic PDAC treated with SIRT and chemotherapy, and evaluated the clinical outcomes associated with platinum-based versus non-platinum-based regimens. Patients who received platinum-based chemotherapy alongside SIRT had a median PFS of 10 months, compared to 2 months in those treated with non-platinum-based regimens. Stratified analysis revealed that patients receiving platinum-based chemotherapy in the first-line setting achieved a median post-SIRT survival of 16 months, compared to 4 months for those treated in later lines. For non-platinum-based regimens, median post-SIRT survival was 9 months in the first-line and 6 months in later lines. Median OS from Stage IV diagnosis was 17 months for patients with liver-only metastases and 15 months for those with additional extra-hepatic disease, suggesting that liver disease burden remains a dominant driver of outcomes. These findings describe survival outcomes among patients treated with SIRT and chemotherapy for metastatic PDAC in a real-world setting. Longer observed survival was seen in patients who received platinum-based chemotherapy alongside SIRT, particularly in the first-line setting. Given the descriptive design and small sample size, these findings should be interpreted as hypothesis-generating and may inform future prospective evaluation of SIRT-chemotherapy combinations.