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[212Pb]Pb-PSV-359 is a radiopharmaceutical utilizing an alpha particle-emitting radionuclide lead-212 (212Pb) and a fibroblast activation protein (FAPα)-targeted antagonist being assessed as anticancer treatment. Prior nuclear imaging studies have shown that almost all cancer-associated fibroblasts within uterine cervix cancer tumors express the radiopharmaceutical target FAP when assessed by radiotracer uptake criteria. It is unknown whether immunohistopathology supports this claim. Therapeutic response to [212Pb]Pb-PSV-359 likely associates with FAP expression, and thus, it seems sensible to evaluate FAP immunoreactivity as a triage biomarker when intending to use this agent against persistent, recurrent or metastatic uterine cervix cancer. We examined a series of 37 uterine cervix cancer paraffin-embedded tumors to determine whether this tumor type expresses FAP at a sufficient cell proportion and staining intensity for an immunoreactive score (IRS) of six or higher, as [212Pb]Pb-PSV-359 is currently being evaluated in clinical trials only against tumors demonstrating radiotracer uptake criteria rather than also by immunoreactivity criteria. The results show that 28 of 34 (82%) uterine cervix cancer tumors with evaluable desmoplastic stroma had cancer-associated fibroblasts expressing FAP. Twenty (59%) tumors scored at an IRS six or higher. Primary tumors from patients with stage IVB disease at diagnosis (n=11) or metastatic tumors (n=6) had cancer-associated fibroblasts expressing FAP most often (76%). Cancer-associated fibroblast FAP immunoreactivity in this series indicates that [212Pb]Pb-PSV-359 radiopharmaceutical therapy might have usefulness in women with persistent, recurrent or metastatic uterine cervix cancer. A phase I clinical trial inclusive of metastatic uterine cervix cancer patients is underway (NCT06710756).

Prostate cancer development and progression depend on androgen receptor (AR) signaling. Therefore, androgen-deprivation therapy (ADT) and AR signaling inhibitors (ARSIs) are standard therapies for advanced or metastatic disease. Although these treatments are initially effective, prostate cancer inevitably progresses to a lethal stage termed castration-resistant prostate cancer (CRPC). In the majority of patients, CRPC occurs via re-activation of AR signaling (CRPC-AR). However, lineage plasticity is a hallmark of cancer that drives AR-independent CRPC phenotypes in a subset of patients. One subtype of AR-negative CRPC is neuroendocrine prostate cancer (NEPC), which transforms from CRPC-AR by losing the characteristic AR-driven luminal epithelial identity and gaining neuroendocrine identity. Another AR-negative CRPC subtype lacks AR and neuroendocrine features and has therefore been classified as double-negative prostate cancer (DNPC). Chromatin modifications, alterations in three-dimensional (3D) genome structure, and expression of transcriptional regulators are crucial for controlling lineage states and modulating AR-dependent and AR-independent phenotypes in CRPC. Here, we highlight how high-resolution investigations of the 3D genome have revealed interdependence between chromatin architecture and transcriptional regulation, offering novel insights into the mechanisms of CRPC progression and context-specific targets for therapeutic intervention.

Lung cancer is one of the malignant tumors with the highest incidence and mortality rates. Most patients are diagnosed at advanced stages, thus missing the golden period for diagnosis and treatment. Tissue biopsy is the most commonly used method for diagnosing lung cancer, but it is an invasive procedure. Patients with poor physical conditions may be unable to tolerate it, and it may even cause complications such as infection, pneumothorax and hemorrhage. On the other hand, repeated sampling is difficult to perform, which makes dynamic monitoring of tumor changes impossible, thus posing a significant obstacle to the adjustment of subsequent treatment plans. Emerging molecular diagnostic technologies, represented by liquid biopsy, have been developed rapidly. This may become one of the promising approaches for non-invasive monitoring of lung cancer. This review aims to summarize the biological basis, clinical applications, limitations, and future perspectives of ctDNA-based liquid biopsy in lung cancer. Relevant literature was identified through PubMed and a series of major oncology journals. Articles published in English within the past decade were preferentially considered. The selection focused on studies related to circulating tumor DNA (ctDNA)-based liquid biopsy in lung cancer, including its biological basis, clinical applications, and translational potential.Keys Content and Findings: This review describes in detail liquid biopsy centered on ctDNA, summarizes its application advantages in the diagnosis and treatment of lung cancer, and systematically analyzes its clinical translation value. This technology only requires collecting patients' body fluid samples. By utilizing tumor biomarkers such as ctDNA, it enable non-invasive monitoring and guides treatment while avoiding the injuries caused by invasive procedures. Although the clinical value of this technology varies across different application scenarios, and some of its uses are still in the research and exploration stage, it has demonstrated considerable application prospects in clinical practice.

Social media is increasingly used by patients, caregivers, and clinicians to access and share cancer-related information. This study examined how individuals use social media for lung cancer education and their preferences. A cross-sectional survey was conducted on Instagram using interactive story features (polls, open-response questions) over three weeks (August to September 2025). Voluntary participation implied consent. Respondents provided demographic data and responses about social media use, content preferences, trust, and impact. Among 182 respondents, 37% were patients, 31% caregivers, 23% clinicians, and 9% others; most were female (78%), ages 25-44 years (65%) and living in North America (75%). Social media use for lung cancer information was common, particularly on Instagram, with 66% following cancer-related accounts. Respondents preferred content from patients/survivors and practicing clinicians. Short videos/reels, patient stories, and infographics were the most favored formats, with 97% reporting diagrams/animations improved understanding; 93% reported trust in social media content and that posts improved clarity on cancer types and treatments; 70% self-reported that social media influenced a behavior and 67% reported it increased confidence in discussing care. Open response answers highlighted social media as a source of education, hope, peer connection, empowerment, and timely updates, and interest in future content on emerging therapies, conference insights, care navigation, survivorship, and personalized topics. Respondents frequently sought information from clinicians, with concise visual formats, and reported tangible benefits for confidence and health behaviors. Social media may offer a scalable platform for delivering real-time education on lung cancer.

Lung cancer remains one of the leading causes of cancer-related death worldwide. Although low-dose computed tomography (LDCT) has improved early detection, false-positive results, overdiagnosis, and interobserver variability continue to limit screening efficiency and downstream management of pulmonary nodules. This narrative review summarizes recent progress in artificial intelligence (AI)-assisted screening, radiomics-based nodule characterization, and multi-omics integration for the precision diagnosis of lung cancer. A narrative review with thematic analysis was conducted using representative literature on AI-assisted lung cancer screening, quantitative imaging analysis of pulmonary nodules, radiogenomic and multi-omics integration, and clinical translation challenges. Studies were synthesized to highlight technical advances, diagnostic performance, strengths, limitations, and barriers to implementation. AI improves nodule detection, second-reader support, workflow efficiency, and malignancy-risk estimation in LDCT screening. Radiomics converts CT images into quantitative features that can improve discrimination between benign and malignant nodules, especially when combined with clinical variables or deep-learning models. Beyond imaging alone, radiogenomic and other multi-omics approaches link imaging phenotypes with molecular alterations, treatment response, and prognosis, thereby supporting more individualized management. However, current evidence remains limited by dataset heterogeneity, retrospective design, limited interpretability, and insufficient multicenter prospective validation. AI-based imaging and multi-omics integration offer a promising pathway toward earlier detection and more precise diagnosis of lung cancer. Broader clinical adoption will depend on standardized data acquisition, robust external validation, interpretable models, and careful governance of privacy, ethics, and workflow integration.

Pulmonary rehabilitation plays a crucial role in lung cancer patients after surgery. In this context, traditional Chinese exercises (TCEs) are being increasingly utilized. However, the existing studies are characterized by small sample sizes, inconsistent interventions, and diverse outcome measures, which result in high heterogeneity and limited clinical applicability. This meta-analysis systematically assessed the impacts of two common TCEs on postoperative lung cancer patients, aiming to provide a basis for evidence-based rehabilitation strategies. A systematic search of nine electronic databases was conducted for randomized controlled trials (RCTs) from inception to November 3, 2025. After independent screening, data extraction, and risk-of-bias assessment, meta-analysis was performed. Twenty-five RCTs involving 1,834 participants were included. The meta-analysis demonstrated that TCE significantly improved pulmonary function outcomes, including forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), FEV1/FVC ratio, and FEV1% predicted. Additionally, TCE increased the 6-minute walk distance (6MWD) and quality of life (QoL) score. Regarding psychological outcomes, TCE significantly alleviated symptoms of anxiety. TCE showed no statistically significant effect on postoperative fatigue, Borg dyspnea scores and depression in lung cancer patients. Subgroup analyses suggested that timing of intervention initiation and settings may account for the observed heterogeneity in respiratory function outcomes. Furthermore, subgroup showed that Liuzijue was more effective than Baduanjin in improving FEV1/FVC (mean difference: 4.88 vs. 2.71), while Baduanjin was more effective than Liuzijue in alleviating anxiety (mean difference: -7.45 vs. -2.20). TCE appears to be a beneficial intervention for enhancing pulmonary function, QoL, and mental health in postoperative lung cancer patients. However, further-quality studies are warranted to confirm the robustness of these findings due to limitations in certain outcome measures.

The effectiveness and safety of cryoablation therapy in early-stage lung cancer remains unclear now. Therefore, this meta-analysis aimed to further identify the effectiveness and safety of cryoablation therapy among early-stage lung cancer patients. PubMed, Chinese National Knowledge Infrastructure (CNKI) and Web of Science (WOS) databases were searched up to January 10, 2026. Endpoints assessing the effectiveness included the overall survival (OS), cancer-specific survival (CSS), progression-free survival (PFS), local recurrence and metastasis rate. And endpoints evaluating the safety of cryoablation therapy included the risk of hemorrhage, pneumothorax, pneumothorax with chest tube required and 30-day mortality. Additionally, subgroup analysis focusing on patients with stage IA was performed. Seven single-arm pilot studies were included with 353 patients. Most patients were stage IA, with a small proportion of stage IB and two studies reporting a few stage II cases (N0). For effectiveness, pooled results indicated that the 1-, 2-, 3- and 5-year OS was 99% [95% confidence interval (CI): 93-100%], 94% (95% CI: 81-100%), 90% (95% CI: 77-99%) and 67.85%. The overall, 1-, 2- and 3-year PFS was 89.4%, 93% (95% CI: 88-98%), 83% (95% CI: 78-88%) and 68% (95% CI: 54-81%) and 5-year CSS was 56.6%. The local recurrence and metastasis rates were 7% (95% CI: 2-14%) and 4% (95% CI: 0-14%). Regarding safety, the proportions of hemorrhage, pneumothorax, pneumothorax with chest tube required and 30-day mortality were 5% (95% CI: 0-15%), 25% (95% CI: 14-36%), 11% (95% CI: 3-22%) and 0%, respectively. Subgroup analysis for patients with stage IA manifested better effectiveness and safety. For patients with early-stage lung cancer, cryoablation appears to be a feasible minimally invasive treatment option with acceptable short- to mid-term outcomes, particularly in patients with stage IA disease.

Lung cancer associated with cystic airspaces (LCCA) is an uncommon subtype of lung cancer in which cystic lesions are present within or adjacent to the tumor. Despite advances in computed tomography (CT) screening, early diagnosis remains challenging, and radiologic tumor size is often underestimated. This study aimed to evaluate surgical cases of LCCA with radiologic tumor diameter ≤2 cm and to clarify their clinicopathological characteristics and prognostic impact. Among 606 patients who underwent surgical resection for primary lung cancer between 2017 and 2020, 299 had radiologic tumor diameters ≤2 cm. These patients were classified into an LCCA group (n=26) and a non-LCCA group (n=273). Clinicopathological characteristics, radiologic-pathologic tumor size discrepancies, and survival outcomes were compared. Prognostic factors were analyzed using the Cox proportional hazards model, and disease-free survival (DFS) and overall survival (OS) were evaluated using Kaplan-Meier analysis. Preoperative carcinoembryonic antigen (CEA) levels were significantly higher in the LCCA group compared with the non-LCCA group (6.13 vs. 4.71 ng/mL). Univariate analysis identified sex, smoking history, CEA level, and LCCA as prognostic factors, while multivariate analysis demonstrated LCCA as the only independent predictor of poor prognosis. Both DFS and OS were significantly worse in the LCCA group. The mean radiologic tumor diameter in LCCA was 1.5 cm, whereas the mean pathological diameter was 2.53 cm, indicating an approximate 1 cm underestimation on preoperative imaging. In small lung cancers, LCCA is associated with poorer prognosis and substantial radiologic-pathologic size discrepancy. These findings highlight the need for careful surgical decision making, as radiologic measurements may underestimate true tumor extent in LCCA.

Tubulin, the fundamental component of microtubules, remains a critical target in anticancer therapy. The development of small-molecule tubulin polymerization inhibitors continues to drive the discovery of novel chemotherapeutic agents. Through systematic analysis of known tubulin inhibitors and in silico binding pocket models, a focused series of 6-aryl-3-(3,4,5-trimethoxyphenyl)imidazo[1,2-a]pyridine derivatives was rationally designed and synthesized. Compound 8o exhibited superior antiproliferative potency, with IC₅。 values of 0.050-0.078 µM against HeLa, HCT116, and MCF-7 cancer cell lines. Mechanistic investigations confirmed that 8o effectively inhibits tubulin polymerization, disrupts the microtubule cytoskeleton, induces G₂/M phase arrest, and triggers apoptosis. Preliminary physicochemical assessment indicated that 8o adheres to Lipinski's rule of five, supporting favorable drug-likeness. Collectively, these findings identify 8o as a potent, drug-like colchicine-site tubulin inhibitor with compelling anticancer efficacy, meriting further investigation as a promising lead compound.

Esophageal cancer (EC) has high incidence and mortality. Non-cancer deaths, particularly from cardiovascular and cerebrovascular related death (CCD), are increasing. The aim of this study is to investigate the risk factors associated with CCD in patients diagnosed with EC. The data of patients diagnosed with EC was retrospectively extracted from the Surveillance, Epidemiology, and End Results (SEER) database, the cause of death and follow-up information were collected. Mortality was calculated by cumulative incidence function (CIF), and the competing risk regression was utilized for risk factor analysis. In addition, cases of EC with in-hospital death in a Chinese hospital were collected, the cause of death and risk factors of CCD were analyzed. The study included a total of 24,291 patients from SEER cohort and 133 patients from Chinese hospital cohort. During the follow-up period of SEER cohort, 21,272 (87.6%) patients succumbed to mortality, 931 (3.8%) of them were CCD, while 20,341 (83.7%) died from other causes. The median overall survival time was found to be 10 months [interquartile range (IQR), 4-28 months], age, sex, race, surgery, and tumor stage as independent risk factors for CCD. In the Chinese cohort, 133 patients with EC died in hospital, of which 25 (18.8%) were CCD, logistic regression showed that smoking history, history of hypertension, history of heart disease and high total cholesterol were independent risk factors for CCD. CCD is the primary cause among all non-cancer deaths in patients with EC, which seriously affects the expected survival of patients and should be prevented by risk factors.

Enhanced recovery after surgery (ERAS) protocols have revolutionized perioperative care in lung cancer resection, significantly improving postoperative outcomes. However, a comprehensive analysis of the global research trends, intellectual structure, and evolving hotspots in this specific domain over the past 15 years remains lacking. This study aims to bridge this gap by conducting a comprehensive bibliometric and visual analysis of literature from 2010 to 2025. Literature regarding ERAS in lung cancer surgery published from 2010 to 2025 was retrieved from the Web of Science Core Collection (WoSCC). Bibliometric analyses were conducted using VOSviewer, CiteSpace, and R-bibliometrix to visualize spatial distributions, collaboration networks, co-citation structures, and keyword trends. A total of 472 eligible publications were identified, exhibiting an exponential growth trajectory particularly after 2018. China emerged as the leading contributor with 137 documents, followed by the United States with 107 publications, while European nations demonstrated exceptional citation impact. The University of Copenhagen and its affiliated hospitals formed the dominant institutional cluster, and the Journal of Thoracic Disease served as the primary publishing venue. Analysis of citation bursts and keyword evolution revealed a paradigm shift in research focus. The field evolved from initial feasibility studies involving lung resection to protocol standardization and safety. Most recently, the emphasis has shifted towards patient-centered outcomes represented by quality-of-life (QoL) assessments and precision minimally invasive techniques. Research on ERAS for lung cancer is rapidly expanding and has matured from establishing safety to refining comprehensive care. The current trend emphasizes the integration of precision surgery with patient-centered QoL assessments. This study provides a global roadmap for researchers to identify key collaborators and emerging frontiers in thoracic oncology.

Intrinsically disordered regions (IDRs) are pervasive in chromatin regulatory proteins, where their dynamic, multivalent interactions organize nuclear biochemistry, in some cases through biomolecular condensation. Because ∼20% of cancer-driver mutations map to disordered regions - for which traditional structure-function paradigms are often insufficient - there is a need for a mechanistically grounded, predictive framework to interpret their effects. In this Perspective, we first synthesize case-specific studies demonstrating how IDRs coordinate cancer-relevant nuclear functions. Second, we examine the underlying molecular 'grammar' and biophysical behavior of representative IDRs, including amino acid patterning, charge distribution and post-translational modifications. Third, we highlight the emergence of high-content experimental platforms that enable the field to move beyond individual anecdotes toward generalizable principles of IDR function. Finally, we discuss how these mechanistic and systematic perspectives can be integrated into predictive frameworks. By bridging individual functional insights with proteome-scale datasets, a unified approach could improve prediction of how disease-associated variants alter cellular states and help establish a foundation for the therapeutic targeting of the disordered proteome.

The aim of the study is to identify perioperative predictors of positive resection margins in patients with non-small cell lung cancer (NSCLC) undergoing anatomical resections to improve perioperative risk stratification and ultimately, patient care. All patients with primary NSCLC admitted at the Bundeswehrkrankenhaus (Armed Forces Hospital) Ulm for anatomical resections between 01.01.2019 and 31.12.2024 were retrospectively included into the study. Based on resection margins, patients were categorized in two groups: Group 1 (with negative resection margins, R0) and Group 2 (with tumor involvement at the level of resection margins/ positive resection margins at bronchial level, or adjacent structures, R+). A comparative analysis of patients' demographics, topographical, pathological tumor characteristics and surgical approach was performed by Mann-Whitney U test, Chi-squared test, and Fisher test. A logistic regression model was performed to assess the independent predictive value of the selected variables. Of 232 NSCLC patients [median age 69.00 (63.00, 75.00) years, 22% aged >75 years, and 2.2% with an Eastern Cooperative Oncology Group (ECOG) >2] who underwent anatomical resections, 107 (46.1%) female patients were included. While R0 resections were observed in 214 (92.2%) patients, 18 (7.8%) patients had positive resection margins on histopathological evaluation. R+ was more frequently reported in male patients (83.3% vs. 16.7%, P=0.009), large tumors (>50 mm/> pT2, P<0.001), as well as in resection specimens with lymph node metastasis (pN1-2, P<0.001), lymphangiosis (L1, P=0.006), vascular invasion (V1, P=0.008) and squamous histology (P<0.001). No significant differences were observed between groups in terms of lobar distribution, tumor mutational status, regression grade upon neoadjuvant therapy, as well as surgical approach (open/minimally invasive). Multivariable analysis revealed male sex (P=0.042), squamous histology (P=0.02), and pT >2 (P<0.001) as independent predictors for R+. These predictors increased the risk of resection margin positivity by 4.1-, 3.7-, and 8.5-fold, respectively. T stage (pT >2), squamous histology and male sex predict positive resection margins in lung cancer patients undergoing anatomical resections. Consideration of these parameters could help in patients' stratification and care and thus, should be further evaluated in larger patients' cohorts.

Small cell lung cancer (SCLC) accounts for approximately 15% of all lung cancer cases. SCLC is characterized by rapid proliferation, early distant metastasis, high recurrence rate, and poor prognosis, with a 5-year survival rate of less than 7%. Immune checkpoint inhibitor (ICI)-based immunotherapy has been widely applied in SCLC clinical practice, including immunotherapy combined with chemotherapy as first-line therapy, tarlatamab (post-chemo/immunotherapy) and lurbinectedin (post-platinum chemotherapy) as later-line options for extensive-stage SCLC (ES-SCLC), and chemoradiotherapy (CRT) followed by consolidation of immune therapy for limited-stage SCLC (LS-SCLC). However, the efficacy of immune combination therapy in SCLC patients remains limited and studies confirmed that objective response rate (ORR) of first-line immunochemotherapy in advanced SCLC is approximately 60-70%, while the durable response rate remains only 10-20%. The main reason lies in the complex and heterogeneous immune microenvironment of SCLC, where a network of immunosuppressive factors orchestrates an immune-excluded or "cold" phenotype. With the development of genomics application in SCLC research, increasing data have revealed and validated the immune microenvironment features of SCLC. However, there is a lack of systematic reviews in this field. This review focuses on clinical translational research across SCLC stages and subtypes, systematically summarizing the immune microenvironment features of LS-SCLC, ES-SCLC, recurrent/relapse SCLC, and never-smoker SCLC (nsSCLC) by integrating data generated from genomic sequencing, single-cell sequencing, spatial transcriptomics, and other research approaches. We summarize the biological and immune features of SCLC and highlight key biomarkers, with the goal of offering new perspectives to improve immunotherapy outcomes and uncover novel therapeutic vulnerabilities.

Many patients with esophageal cancer experience recurrence after curative-intent multimodality therapy. This study aims to evaluate risk factors, patterns, and outcomes of esophageal cancer recurrence after neoadjuvant chemoradiotherapy and esophagectomy. Single-institution retrospective review of patients who underwent multimodality therapy including esophagectomy for esophageal adenocarcinoma or squamous cell carcinoma (SCC) from 2011 to 2021. Detailed data on recurrence patterns was collected. Factors associated with time to recurrence, overall survival, and survival after recurrence were analyzed. There were 665 patients included of which 627 (94%) had clinical stage &#x2265; II disease. Recurrence after esophagectomy occurred in 241 (36%) patients. Median time to recurrence was 9.9 months (interquartile range, 5.4-18.8 months). Recurrence was distant in 119 (49%) patients, regional in 72 (30%) patients, local in 12 (5%), locoregional in 2 (0.8%), and locoregional + distant in 35 (15%). Factors independently associated with a higher risk of recurrence included male sex, SCC histology, and pN stage. Downstaging after neoadjuvant therapy was associated with a lower risk of recurrence. Recurrence was associated with a higher risk of death (adjusted hazard ratio 5.95, 95% confidence interval: 4.73-7.50, P<0.001). Median overall survival after surgery was 12 months in patients with recurrence and 123 months in patients without recurrence. Recurrences in the pleura and bone were independently associated with decreased post-recurrence survival. The incidence of recurrence, particularly distant, remains high despite neoadjuvant therapy and esophagectomy, consistent with observations from clinical trials. Better perioperative systemic therapies are needed for patients with locally advanced esophageal cancer.

We present a clinical case highlighting total ureteral replacement with a small intestinal graft as a key reconstructive component in the surgical management of recurrent colorectal cancer. A 48-year-old female patient previously underwent low anterior rectal resection with D2 lymph node dissection (pT2N0M0, 2018). Four years later, she presented with clinical signs of obstruction in the middle third of the left ureter. Imaging revealed a mass involving the ureteral wall and left psoas muscle, alongside left adnexal abnormalities. Surgical treatment was staged and included en bloc resection of the recurrent mass with removal of the left ureter, adnexectomy, and segmental colectomy. In the remission phase, ureteral reconstruction was performed using a small intestinal graft, followed by transverse colon mobilization and the creation of a stapled transverse-rectal anastomosis. This case illustrates how timely, organ-preserving reconstruction - integrated into comprehensive oncological surgery - can improve both survival and quality of life in patients with locally advanced recurrent rectal cancer.

The clinical features and prognosis of combined small cell lung cancer (C-SCLC) are not well understood. Given the unique histological heterogeneity of C-SCLC, the 8th tumor-node-metastasis (TNM) staging system has limited prognostic accuracy in this population, necessitating a dedicated prediction model. This study aimed to develop and internally validate dynamic nomograms incorporating combined subtypes and serum tumor markers to predict recurrence and survival in patients with resected C-SCLC. A total of 223 patients with resected C-SCLC were enrolled in this study between 2008 and 2021. Eligibility criteria were as follows: surgically resected and pathologically confirmed C-SCLC with complete clinical data. Due to the limited sample size, no training/validation split was performed; internal validation was conducted using 1,000 bootstrap resamples. All serum tumor markers including neuron-specific enolase (NSE) were measured within one week before surgery. Visceral pleural invasion (VPI) and combined histological components were independently reviewed by two professional pathologists. The independent prognostic factors were identified and integrated to build the nomograms for predicting 3- and 5-year disease-free survival (DFS) and overall survival (OS) based on stepwise Cox regression. The discrimination and predictive accuracy of the models were evaluated using the concordance index (C-index) and calibration curves. Decision curve analyses (DCAs) were performed to verify the clinical utility of the model compared with that of the 8th edition of the International Association for the Study of Lung Cancer (IASLC) TNM staging system. Based on the nomogram scores, the C-SCLC patients were divided into high- and low-risk subgroups. An online webserver was applied to facilitate the convenient use of the model. Ultimately, six independent prognostic factors, including tumor location, combined components, VPI, adjuvant chemotherapy, lymph node metastasis, and serum NSE level, were identified and incorporated into the nomograms. The median follow-up duration was 42.6 months. During follow-up, 101 patients developed recurrence or metastasis, and 121 died. The median age of the cohort was 64 years, with a predominance of male patients (89.7%). Among the patients, 27.8% were classified as stage I, and large cell neuroendocrine carcinoma (LCNEC) was the most common combined component (67.3%). The C-index values of the nomograms for predicting DFS [0.730, 95% confidence interval (CI): 0662-0.720] and OS (0.748, 95% CI: 0.682-0.734) were significantly higher than those of the TNM staging system (0.601, 95% CI: 0.574-0.628 and 0.615, 95% CI: 0.586-0.644 for DFS and OS, respectively; P<0.001). The calibration plots indicated good agreement between the model-predicted and observed survival. The DCA results showed that the developed nomograms demonstrated better predictive performance than the TNM staging system. Our internal validation suggests that the nomograms outperform the TNM staging system; however, these findings should be considered as hypothesis-generating. External validation with multicenter cohorts is essential before clinical implementation. The online tool is primarily intended to facilitate further research.

The risk of distant metastasis (DM) in T1-2 esophageal cancer (EC) is frequently underestimated, and the prognosis for patients who develop metastasis remains poor. Currently, there is a lack of effective tools based on routine clinical data to accurately identify high-risk patients preoperatively or to perform subsequent prognostic stratification for those with metastatic disease. This study aimed to develop an integrated tool to preoperatively identify T1-2 EC patients at high risk of DM and stratify prognosis for metastatic cases, providing evidence-based clinical support. This retrospective study utilized data from the Surveillance, Epidemiology, and End Results (SEER) database, including 12,928 patients. The cohort was split into training and testing sets (7:3). In the training set, univariate and multivariate logistic regression (LR) were first applied to initially identify factors associated with DM. Feature selection was subsequently conducted using the least absolute shrinkage and selection operator (LASSO) regression and the Boruta algorithm. Variables consistently selected by both methods and confirmed as independent predictors were retained for model construction. Next, 12 machine learning algorithms were applied to build prediction models. Model interpretability was achieved using SHapley Additive exPlanations (SHAP). Performance was evaluated using the area under the receiver operating characteristic (ROC) curve (AUC), calibration curves, precision-recall (PR) curves, and decision curve analysis (DCA) curves. For patients who developed DM, a prognostic nomogram was constructed based on factors identified through Cox regression and evaluated using the concordance index (C-index), AUC, calibration curves, and DCA. Among the DM prediction models, the Naive Bayes classifier (NBC) model achieved AUC values of 0.740 and 0.750 in the training and testing sets, respectively, indicating favorable discriminative ability. Additionally, it exhibited the highest sensitivity among all models and was therefore selected as the final prediction model. SHAP analysis identified N stage as the most important predictive factor, with N stage, primary site, and tumor size being confirmed as risk factors for DM, whereas T stage and older age were associated with reduced risk. In the prognostic analysis, race, T stage, chemotherapy, marital status, and median household income were independent prognostic factors for metastatic patients. The resulting overall survival (OS) and cancer-specific survival (CSS) nomograms demonstrated good discrimination, with C-indexes of 0.653 and 0.654 in the testing set, respectively, along with satisfactory calibration and clinical net benefit. We developed a dual-strategy risk assessment tool that predicts DM in T1-2 EC and provides individualized survival estimates for metastatic patients, offering a practical framework for stratified clinical decision making and precision oncology.

Brain metastases from small cell lung cancer (SCLC) are characterized by high malignancy and poor prognosis. Emerging evidence demonstrates that combining brain radiotherapy (BRT) and immunotherapy may improve outcomes; however, the optimal strategy for combining these therapies remains undefined. This study was conducted to evaluate the efficacy and safety of concurrent BRT combined with tislelizumab and chemotherapy in patients with SCLC and brain metastases. Patients with treatment-naive or previously treated SCLC and brain metastases who were admitted to Zhejiang Cancer Hospital (Hangzhou, China) between September 2023 and November 2025 were enrolled. All patients received one cycle of chemotherapy combined with tislelizumab, followed by initiation of BRT within one week. Chemotherapy plus immunotherapy was subsequently continued, followed by maintenance immunotherapy until disease progression. The primary endpoint was intracranial objective response rate (iORR). Secondary endpoints included overall survival (OS), progression-free survival (PFS), disease control rate (DCR), and treatment-related adverse events (TRAEs). Twenty-five patients were included. Among them, the iORR was 76.0%, and intracranial DCR was 100.0%. The systemic ORR and DCR were 56.0% and 80.0%, respectively. The median OS was 11.1 months [95% confidence interval (CI): 7.4-14.8], the median PFS was 5.6 months (95% CI: 3.1-8.1), and the median intracranial PFS was 7.6 months (95% CI: 5.7-9.5). TRAEs of any grade were identified in all patients, while grade &#x2265;3 adverse events were found in 36.0% of patients. Hematological toxicity was most common (88.0%). Concurrent BRT combined with tislelizumab and chemotherapy demonstrated promising intracranial and systemic efficacy with manageable toxicity in SCLC patients with brain metastases and warrants further validation in larger prospective studies.