crossing96/oncoscreening huggingface dataset:
Prognostic value of serum inflammatory markers in patients with esophageal squamous cell carcinoma undergoing surgery: a two-center retrospective cohort study.	BACKGROUND AND PURPOSE: The combined assessment of the neutrophil-platelet score and prognostic nutritional index is yet to be applied in evaluating the prognosis of patients following an operation for esophageal cancer. This study aimed to identify independent prognostic factors for patients undergoing operation for esophageal cancer and to construct a nomogram model for predicting median overall survival (mOS). METHODS: A cohort of 660 patients with esophageal cancer from two clinical centers in China was recruited, comprising a training cohort (n = 511) and a validation cohort (n = 149). Survival rates were compared using Kaplan-Meier curves and the log-rank test. The Cox regression model was used to identify independent prognostic factors. RESULTS: The Multi-variable Cox regression analysis revealed that tumor, node, metastasis stage, smoking status, neutrophil-platelet score, and prognostic nutritional index were independent postoperative prognostic factors for patients with esophageal cancer (P < 0.05). The mOS (129.0 months, 95% confidence interval (CI) not reached) was significantly higher in patients with a low neutrophil-platelet score than those with a high score (43.0 months, 28.1-57.9; P < 0.05). Conversely, the mOS (42.0 months, 95% CI 6.7-55.2) was lower in the low prognostic nutritional index score group than the high score group (125.0 months, 95% CI 96.4-153.6; P < 0.05). Evaluation metrics, including the concordance index (0.69 in the training group and 0.70 in the validation group), receiver operator characteristic curve analysis (In the training cohort, the AUCs for predicting 1-, 3-, 5- and 10-year overall survival rates using the nomogram were 76.19%, 69.07%, 70.12% and 68.17%, respectively; in the validation cohort, the corresponding predicted values were 76.66%, 77.18%, 75.04% and 79.57%, respectively), calibration curve, and decision curve analysis, demonstrated the clinical utility of the constructed prediction model. CONCLUSIONS: Serving as systemic inflammatory biomarkers, the neutrophil-platelet score and prognostic nutritional index offer valuable prognostic insights for patients with esophageal cancer, augmenting predictive capabilities.	esophagus
Optimal timing for initiating first-line palliative systemic therapy in asymptomatic metastatic esophagogastric cancer: Insights from a European Delphi study.	BACKGROUND: The enhanced application of imaging techniques is resulting in the diagnosis of more patients with asymptomatic metastatic esophagogastric cancer (mEGC). We conducted a Delphi study to gather insights from European experts on the optimal timing for initiating palliative systemic therapy for these patients. METHODS: An online survey featured 14 scenarios where physicians chose their preferred timing for initiating systemic therapy: immediate(<3 weeks) or deferred. The standard scenario was a 65-year-old male, WHO/ECOG 0 with asymptomatic mEGC, 2 metastases in each lung, HER2 -, PDL1-CPS 2. In every subsequent case, one characteristic was modified. To investigate the fortitude of the physicians' preference for an immediate start, scenarios also included a patient who was motivated to start but preferred to defer if the physician deemed it judicious. Consensus was defined as ≥ 75 % agreement; scenarios without consensus were re-evaluated in Delphi round 2. RESULTS: Thirty-nine physicians participated in the first round, and 33 in the second round. Consensus to start treatment immediately was reached in 12 (86 %) scenarios. When patients preferred to defer, the consensus was to still advise to start palliative systemic treatment immediately in half (n = 7) of the scenarios. Only 2 scenarios (pre-existent WHO/ECOG 2 or 78 years old) reached the consensus that treatment could be deferred. CONCLUSIONS: In asymptomatic mEGC, immediate start of treatment is preferred by European experts. Consensus was established that treatment can be deferred for patients who prefer deferral and either have a pre-existent WHO/ECOG performance status of 2 or are of advanced age.	esophagus
(177)Lu-Labeled Anticlaudin 6 Monoclonal Antibody for Targeted Therapy in Esophageal Cancer.	Advanced or metastatic esophageal cancer (EC) is associated with poor prognosis, necessitating new and effective treatment methods. We assess whether claudin 6 (CLDN6) is a useful target for the imaging and radiopharmaceutical therapy of EC using a novel pair of radioactive nuclides, (89)Zr and (177)Lu. Methods: CLDN6 messenger RNA expression was evaluated in 2 EC datasets (n = 436) and through a retrospective analysis of 109 patients with EC. We then used an anti-CLDN6 monoclonal antibody (IMAB027) labeled with (89)Zr and (177)Lu ([(89)Zr]Zr-DFO-IMAB027 and [(177)Lu]Lu-DOTA-IMAB027) for PET imaging and therapy, respectively. Imaging and biodistribution analyses were performed using the TE-1-CLDN6 xenograft model. Finally, the therapeutic potential of [(177)Lu]Lu-DOTA-IMAB027 was evaluated in both the TE-1-CLDN6 and the CLDN6-PDX (patient-derived xenograft) models. Results: CLDN6 messenger RNA expression was elevated in EC compared with healthy esophageal tissues. The CLDN6 expression rate was 0 in healthy esophageal tissue but was 79.8% in EC tissue. The [(89)Zr]Zr-DFO-IMAB027 showed the ability to effectively image EC xenografts with high CLDN6 expression. In the TE-1-CLDN6 model, there was a significant difference in tumor volume between the 11.1-MBq [(177)Lu]Lu-DOTA-IMAB027 treatment group and the control group (P < 0.001). The tumor growth inhibition rate in the 11.1-MBq [(177)Lu]Lu-DOTA-IMAB027 group was 101.74%. In the PDX model, significant differences in tumor volume were observed among all [(177)Lu]Lu-DOTA-IMAB027 treatment groups and the control group (P < 0.05). Specifically, the tumor growth inhibition rate of the 11.1-MBq [(177)Lu]Lu-DOTA-IMAB027 group was 79.04%, whereas that of the 3.7-MBq group was 77.20%. However, the difference in efficacy between the high-dose and low-dose groups was not statistically significant (P > 0.05). Conclusion: The differential expression of CLDN6 between tumors and the normal esophagus shows its potential as a diagnostic and therapeutic target for EC. The radiotracer [(89)Zr]Zr-DFO-IMAB027 showed high contrast when visualizing CLDN6-expressing xenografts for PET imaging, and [(177)Lu]Lu-DOTA-IMAB027 induced rapid tumor regression in both the TE-1-CLDN6 and the CLDN6-PDX models. This research has implications for improving the radioligand diagnosis and treatment of EC.	esophagus
Comparison and validation of the Japanese classification 12th edition and American joint committee on cancer 8th edition on intrathoracic esophageal squamous cell carcinoma.	BACKGROUND: The American Joint Committee on Cancer (AJCC) 8th edition and Japanese classification 12th edition can be applied for esophageal cancer staging. This retrospective study aimed to compare these two staging systems in patients with surgically treated esophageal squamous cell carcinoma (ESCC). METHODS: We retrospectively reviewed 2,853 patients who underwent esophagectomy and lymphadenectomy from 1994 to 2020. Patients were divided into the upfront (n = 2156) and neoadjuvant (n = 697) groups. RESULTS: The mean age of the patients was 63.5 ± 8.2 years with a median follow-up of 7.6 years. Comparing both staging systems showed that patients were more likely to be staged lower by the Japanese classification. Survival curves for overall survival (OS) and disease-free survival in the upfront group were well separated in the two staging systems (p < 0.01), and the HR for survival significantly increased as the stage increased. In the neoadjuvant group, there were crossovers of survival curves between stages II and III in the AJCC, and crossovers between stages I and II, and stages III and IV in the Japanese classification. The HR for OS demonstrated less statistical differences in the neoadjuvant group. CONCLUSION: The AJCC 8th edition and Japanese classification 12th edition predicted survival well for patients received the upfront surgery, whereas both showed crossovers of survival curves for patients undergoing neoadjuvant therapy. More accurate staging systems for patients with ESCC who received neoadjuvant therapy and surgery are needed.	esophagus
Efficacy and safety of camrelizumab combined with chemotherapy as second-line treatment for locally advanced, recurrent, or metastatic esophageal squamous cell carcinoma.	BACKGROUND: This study aims to evaluate the efficacy and safety of camrelizumab in combination with chemotherapy as a second-line treatment for patients with locally advanced, recurrent, or metastatic esophageal squamous cell carcinoma (ESCC). METHODS: In this retrospective, single-center observational study, we collected medical records of patients with locally advanced, recurrent, or metastatic ESCC who received either camrelizumab combined with chemotherapy or chemotherapy alone as second-line treatment between July 1, 2019, and May 31, 2023. We evaluated short-term efficacy, including overall response rate (ORR) and disease control rate (DCR), as well as survival outcomes, including progression-free survival (PFS) and overall survival (OS). Safety was also assessed. Additionally, factors influencing OS in ESCC patients were analyzed. RESULTS: A total of 60 patients with locally advanced, recurrent, or metastatic ESCC were included, with 30 receiving camrelizumab combined with chemotherapy and 30 receiving chemotherapy alone as second-line treatment. There were no statistically significant differences in ORR (33.33% vs. 13.33%) and DCR (73.33% vs. 56.67%) between the combination therapy and chemotherapy-alone groups (P > 0.05). However, the median PFS was significantly longer in the combination therapy group compared to the chemotherapy group (4.7 months vs. 3.4 months, P = 0.048). Additionally, the median OS was significantly improved in the combination therapy group compared to the chemotherapy group (11.7 months vs. 6.5 months, P = 0.003). Age and history of radical surgery were significantly associated with OS in patients receiving camrelizumab combined with chemotherapy as second-line treatment (P < 0.05). CONCLUSION: Second-line treatment with camrelizumab combined with chemotherapy is well-tolerated and associated with favorable oncological outcomes in patients with locally advanced, recurrent, or metastatic ESCC. Furthermore, younger patients and those who have undergone radical surgery may derive greater benefit from camrelizumab combined with chemotherapy as a second-line treatment.	esophagus
Deciphering the generation of heterogeneity in esophageal squamous cell carcinoma metastasis via single-cell multiomics analysis.	BACKGROUND: Chromatin accessibility plays a crucial role in mediating transcriptional dysregulation and heterogeneity in Esophageal Squamous Cell Carcinoma (ESCC). Examining the chromatin accessibility of ESCC at single-cell level is imperative to understand how it activates oncogenes and contributes to the onset and metastasis of ESCC. METHODS: We performed single-cell assay for transposase-accessible chromatin sequencing (scATAC-seq) on cancerous and adjacent noncancerous tissues from four ESCC patients who were pathological staged as T1a, T2b, T3b, or T4a, to investigate whether regulatory elements are pivotal in instigating cellular heterogeneity during ESCC metastasis. In conjunction, we integrated these data with 55 scRNA-seq datasets, ChIP-seq or CUT&Tag sequencing data, Hi-C sequencing data, bulk RNA-seq data, and bulk ATAC-seq data from ESCC cell lines to dissect the mechanisms underlying the heterogeneity of ESCC and tumor microenvironment (TME). RESULTS: Our study identified enhancer-specific activation within epithelial cells orchestrated by the three-dimensional structure of chromatin that regulates SERPINH1 transcription, and promotes the epithelial-mesenchymal transition (EMT) and metastasis of ESCC. Additionally, chromatin element activation facilitated the expression of TNFSF4 in CD8 + exhausted T cells, thereby activating Tregs. Furthermore, we observed that chromatin accessibility promoted the differentiation of tumor-associated macrophages (TAMs) and cancer associated fibroblasts (CAFs). CONCLUSIONS: In summary, utilizing multiomics analyses, we have revealed chromatin accessibility maps and illuminated the intricate molecular mechanisms that underlie cellular heterogeneity during ESCC metastasis, offering valuable insights to further advance research on tumor progression and deterioration.	esophagus
Cardiac CT reveals high prevalence of coronary artery disease in esophageal cancer eligible for radiotherapy.	BACKGROUND: Assessment of cardiac disease before cancer therapy is crucial, as advancements in cancer treatment have led to prolonged survival and an increase in cardiovascular complications. Specifically, esophageal cancer and heart disease share common risk factors, such as smoking and obesity. Radiation therapy (RT) for esophageal cancer is associated with elevated cardiac radiation exposure. This study aimed to assess the prevalence of coronary artery disease (CAD) in patients with esophageal cancer who were eligible for RT. METHODS: We examined the prevalence of coronary artery stenosis, abnormal myocardial perfusion, and late enhancement using pre-RT cardiac computed tomography (CT) data of 41 patients with thoracic esophageal cancer who were referred for RT between January 2017 and June 2023 and had no history of ischemic heart disease. RESULTS: The median age of the 41 patients was 71 years, with 40 patients being male. Cardiac CT identified significant coronary stenosis (≥50% luminal narrowing) in 18 patients (44%), among whom 9 (50%) had severe stenosis, multivessel disease, or myocardial ischemia. Significant stenosis was most frequently observed in the left anterior descending artery (16/18). Late enhancement, indicating myocardial infarction, was observed in seven patients (17%). INTERPRETATION: Patients with esophageal cancer without a history of ischemic heart disease had a high prevalence (44%) of CAD, with half of them having severe stenosis, multivessel disease, or myocardial ischemia. Given the high prevalence of coronary stenosis, pre-treatment cardiac evaluation is crucial for patients with esophageal cancer. Incorporating cardiac CT findings into radiotherapy planning is recommended to optimize patient care.	esophagus
IgG4-mediated M2 macrophage polarization in tertiary lymphoid structures of esophageal cancer: implications for immunosuppression.	BACKGROUND: Our previous research highlighted the potential role of immunoglobulin G4 (IgG4) in mediating immunosuppression within the tumor microenvironment (TME). Tertiary lymphoid structures (TLS) in the TME have important immune-related functions. This study aims to analyze the distribution characteristics of IgG4-expressing cells, regulatory T cells (Tregs), and M2-type macrophages as well as to elucidate the relationship between IgG4 and the polarization of M2 macrophages within TLS in esophageal cancer. OBJECT: To elucidate the distribution of IgG4, Treg cells, and M2 macrophages in TLS and to assess the impact of IgG4 on macrophage polarization. METHODS: Esophageal cancer tissue were analyzed with multiplex immunofluorescence to determine the spatial distribution and density of B cells, T cells, and their subtypes. The relationship between IgG4 and CD8+ T cells in TLS, along with interleukin-10 (IL-10) expression and Treg presence, was studied. Serum IgG4 and IL-10 levels were compared between patients and healthy controls. In vitro, the impact of IgG4 on monocyte differentiation into M2 macrophages was observed. RESULTS: IgG4 density was inversely related with CD8+ T cells in mature TLS indicating a potential immunosuppressive role (P<0.05,*). Serum analysis revealed that both IgG4 (P<0.01, **) and IL-10 (P<0.0001, ****) were significantly elevated and positively correlated in tumor patients compared to controls (P<0.01, **). In vitro experiments confirmed that IgG4 monocyte differentiation into M2 macrophages, potentially enhancing the immunosuppressive phenotype in TLS. CONCLUSION: IgG4 and IL-10 may contribute to immunosuppression in esophageal cancer by promoting the polarization of M2 macrophages within TLS, which could be a therapeutic target.	esophagus
Nuclear ANLN regulates transcription initiation related Pol II clustering and target gene expression.	Anillin (ANLN), a mitotic protein that regulates contractile ring assembly, has been reported as an oncoprotein. However, the function of ANLN in cancer cells, especially in the nucleus, has not been fully understood. Here, we report a role of nuclear ANLN in gene transcriptional regulation. We find that nuclear ANLN directly interacts with the RNA polymerase II (Pol II) large subunit to form transcriptional condensates. ANLN enhances initiated Pol II clustering and promotes Pol II CTD phase separation. Short-term depletion of ANLN alters the chromatin binding and enhancer-mediated transcriptional activity of Pol II. The target genes of ANLN-Pol II axis are involved in oxidoreductase activity, Wnt signaling and cell differentiation. THZ1, a super-enhancer inhibitor, specifically inhibits ANLN-Pol II clustering, target gene expression and esophageal squamous cell carcinoma (ESCC) cell proliferation. Our results reveal the function of nuclear ANLN in transcriptional regulation, providing a theoretical basis for ESCC treatment.	esophagus
Optimizing AI models to predict esophageal squamous cell carcinoma risk by incorporating small datasets of soft palate images.	There is a currently an unmet need for non-invasive methods to predict the risk of esophageal squamous cell carcinoma (ESCC). Previously, we found that specific soft palate morphologies are strongly associated with increased ESCC risk. However, there is currently no artificial intelligence (AI) system that utilizes oral images for ESCC risk assessment. Here, we evaluated three AI models and three fine-tuning approaches with regard to their ESCC predictive power. Our dataset contained 539 cases, which were subdivided into 221 high-risk cases (2491 images) and 318 non-high-risk cases (2524 images). We used 480 cases (4295 images) for the training dataset, and the rest for validation. The Bilinear convolutional neural network (CNN) model (especially when pre-trained on fractal images) demonstrated diagnostic precision that was comparable to or better than other models for distinguishing between high-risk and non-high-risk groups. In addition, when tested with a small number of images containing soft palate data, the model showed high precision: the best AUC model had 0.91 (sensitivity 0.86, specificity 0.79). This study presents a significant advance in the development of an AI-based non-invasive screening tool for the identification of high-risk ESCC patients. The approach may be particularly suitable for institutes with limited medical imaging resources.	esophagus
SUMO modified ETV1 promotes M2-polarized tumor-associated macrophage infiltration and cancer progression by facilitating CCL2 transcription in esophageal squamous cell carcinoma cells.	OBJECTIVE: Esophageal squamous cell carcinoma (ESCC) is one of the most common malignant tumors with a high metastasis rate and a poor prognosis. ETS variant transcription factor 1 (ETV1) plays an important role in multiple malignancies. However, its function in ESCC progression and tumor microenvironment (TME) remains to be explored. In this study, we characterized the role of ETV1 in ESCC process and TME. METHODS: Gene expression and immune infiltration in ESCC samples from the Cancer Genome Atlas (TCGA) were analyzed. The expression of ETV1 in clinical samples was detected by real-time PCR, western blot and immunohistochemistry staining. Cell growth was detected by CCK-8 and colony formation assays. Macrophage phenotypes were determined using flow cytometry. Immunofluorescence double staining was used to detect the tumor-associated macrophage (TAM) infiltration. The tumor volume was recorded and weighed. Transcriptional activity was measured using dual-luciferase assay, chromatin immunoprecipitation (ChIP) assay and DNA pull-down assay. RESULTS: In this study, through analysis of ESCC samples from TCGA database and the clinic, we noticed that ETV1 was highly expressed in ESCC tumor tissues and was associated with TAM infiltration. Overexpression of ETV1 promoted ESCC cell proliferation in vitro and xenograft tumor growth in nude mice, while ETV1 knockdown elicited the opposite effects. Furthermore, ETV1 upregulation in tumor tissues was found to drive M2 macrophage infiltration both in vitro (transwell assays) and in vivo (xenograft tumor models). C-C motif chemokine ligand 2 (CCL2), a key factor inducing M2 macrophage polarization, was also found to be elevated in ESCC tumor tissues. Mechanism study demonstrated that ETV1 facilitated M2 macrophage infiltration via the transcriptional modulation of CCL2. In addition, the cause of the changes in ETV1 activity and expression was investigated. The E2 small ubiquitin-like modifier (SUMO) binding enzyme UBC9 increased ETV1 activity and expression, indicating the presence of SUMO modification in ETV1. CONCLUSIONS: Our data deciphered the mechanism of ETV1-mediated M2 macrophage infiltration in the TME of ESCC, which has important implications for the development of novel prognostic and therapeutic targets to optimize current therapies against ESCC.	esophagus
Achieving textbook outcomes with robotic-assisted Ivor Lewis esophagectomy: a single-center experience with 150 consecutive patients.	BACKGROUND: With published randomized data, minimally invasive esophagectomy (MIE) has become increasingly popular. However, substantial variability in techniques and outcomes still exists. METHODS: This was a retrospective analysis of 150 consecutive robotic-assisted MIEs (RAMIEs) from a prospectively maintained database from 2020 to 2024 at a single comprehensive cancer center. This study aimed to evaluate the textbook outcome rates after RAMIE. RESULTS: A total of 150 consecutive patients underwent RAMIE from 2020 to 2024. Tumor location included the esophagus in 18 patients, type 1 gastroesophageal junction (GEJ) in 52 patients, type 2 GEJ in 71 patients, and type 3 GEJ in 9 patients. Most patients had clinical stage T3 tumors. Neoadjuvant therapy was used in 85% of the patients. A complete pathologic response was observed in 27% of patients. The median number of lymph nodes retrieved was 21. Anastomotic leak occurred in 2 patients, none of whom required reoperation. The median hospital stay duration was 7 days. The 30- and 90-day mortality rates were 0.7% and 1.3%, respectively. In addition, the 90-day stricture rate after endoscopic dilation was 0.7%. Of note, 90% of patients had a textbook outcome. CONCLUSION: This single-center experience highlights that the combination of a robotic platform and a side-to-side stapled anastomotic technique helps achieve exceptional postoperative outcomes for MIE, with a textbook outcome rate of 90%. With the increasing worldwide adoption of MIE, this seems to be an appropriate time to standardize operative techniques to optimize postoperative outcomes.	esophagus