crossing96/oncoscreening huggingface dataset:
Current status and clinical usefulness of genomic panel testing using PleSSision-160 in resectable esophageal squamous cell carcinoma.	INTRODUCTION: The clinical importance of treatment approaches based on genomic sequencing has increased in esophageal cancer. This study aimed to clarify the current status and clinical usefulness of genomic panel testing using PleSSision-160 for resectable esophageal squamous cell carcinoma (ESCC). MATERIALS AND METHODS: Sixty-six tumor tissue samples from 61 patients with ESCC, including prospectively collected 46 surgical samples and retrospectively collected 20 biopsy samples before neoadjuvant chemotherapy, were tested using the PleSSision-160 panel. The associations of mutation profiles with long-term survival and chemotherapy resistance were investigated. RESULTS: The top five mutations identified in surgical samples using PleSSision-160 were TP53 (80.4 %), KMT2D (13.0 %), NOTCH1 (13.0 %), EP300 (8.7 %), and AMER1 (8.7 %). Although individual mutations did not show significant associations with long-term survival, patients with high copy number alteration (CNA) status (≥30 counts) had poorer 5-year overall survival (OS) and recurrence-free survival (RFS) compared to those with low CNA status (p = 0.019 and 0.077 for OS and RFS, respectively). Multivariate analyses identified minimally invasive surgery, pStage ≥ III, and high CNA status as independent factors associated with both 5-year OS and RFS. CONCLUSION: This study is the first to investigate postoperative survival and chemotherapy resistance based on genomic panel testing using PleSSision-160 for resectable ESCC. The findings suggested that high CNA status was a risk factor for long-term survival. Compared to previous genomic sequencing studies in ESCC, further investigation using PleSSision-160 appears to be a promising approach.	esophagus
Identification of novel variants with predicted pathogenicity as key targets in esophageal cancer.	Esophageal cancer (EC) remains a major global health challenge due to its aggressive nature and poor prognosis. Genetic alterations play a crucial role in tumor progression; however, a deeper understanding of the genetic landscape of EC is essential for identifying novel and potent therapeutic targets. This study aims to identify key genes and their variants with potential pathogenicity driving EC progression. Whole-exome sequencing (WES) was performed on EC samples to identify missense variants. A comprehensive in-silico analysis was conducted using SIFT, FATHMM, PROVEAN, MutationTaster, and LRT to classify high-risk variants. Gene expression, mutation frequency, and prognostic relevance were analyzed using GEPIA and cBioPortal platforms. Protein stability was assessed with MuPro and I-Mutant to evaluate the impact of the identified variant, while protein-protein interaction (PPI) analysis via STRING and enrichment analysis through Metascape were performed to explore associated biological pathways. A total of 331 novel high-risk missense variants were identified across 274 genes and systematically refined, narrowing down to 23 prognostically significant variants in 11 genes (PSMC1, SCN8A, HNRNPA3, RPL23, COL5A2, TBL1XR1, TCP1, HNRNPD, CALM2, ABCC2, and HNRNPA1), which were also among the most differentially expressed in EC. Variants in these genes were predicted to destabilize their corresponding proteins, contributing to EC progression. In-silico survival analysis further indicated significantly worse outcomes for patients harboring alterations in these genes, including others. Protein stability analysis confirmed their destabilizing effects, while functional enrichment highlighted their involvement in key pathways driving tumorigenesis. This study identified 11 key DEGs harboring potentially pathogenic novel missense variants, highlighting vulnerabilities for precision-targeted therapies in EC.	esophagus
Cost-effectiveness of sugemalimab plus chemotherapy as first-line therapy in advanced gastric cancer and gastroesophageal junction cancer.	BACKGROUND: The GEMSTONE-303 trial demonstrated that sugemalimab combined with capecitabine and oxaliplatin (CAPOX) improved survival benefit in patients with advanced gastric/gastroesophageal junction cancer (GC/GEJC) and a programmed death-ligand 1 (PD-L1) combined positive score (CPS) ≥5. However, its cost-effectiveness in China remains unassessed. METHODS: A partitioned survival model was developed from the Chinese healthcare payer perspective using data from the GEMSTONE-303 trial. Costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs) were evaluated over a 10-year horizon. Sensitivity analyses assessed model uncertainty, while subgroup and scenario analyses examined the impact of PD-L1 expression, drug pricing, and patient assistance programs (PAPs). RESULTS: In the PD-L1 CPS ≥ 5 group, sugemalimab plus CAPOX yielded an incremental cost of $44,455.46 and 0.22 additional QALYs compared to chemotherapy, resulting in an ICER of $206,024.50/QALY. For patients with CPS ≥10, the ICER dropped to $173,182.90/QALY, but still exceeded the willingness-to-pay (WTP) threshold. One-way sensitivity analysis revealed sugemalimab price as the most influential parameter, requiring a 75.6% price reduction to achieve cost-effectiveness. A PAP reduced ICERs to $44,926.00/QALY and $39,513.96/QALY in the CPS ≥5 and CPS ≥10 subgroups, respectively. CONCLUSION: At current prices, sugemalimab plus CAPOX is not cost-effective as a first-line treatment for advanced GC/GEJC in China. It is essential to adopt a combination of targeted patient selection, price negotiation, and broader PAP access to bring the ICER below the WTP threshold. These findings inform reimbursement negotiations and highlight the need for stratified pricing strategies to optimize accessibility in economically diverse populations.	esophagus
Short-Term Outcomes of Minimally-Invasive Esophagectomy Compared to Thoracotomy and Transhiatal Approaches in Total Esophagectomy With Pharyngolaryngectomy.	BACKGROUND: Esophageal squamous cell carcinoma (ESCC) and squamous cell carcinoma of the head and neck (HN) often occur simultaneously. Total esophagectomy with pharyngolaryngectomy (TE-TPL) is a highly invasive surgery associated with significant mortality. In thoracic esophagectomy, minimally invasive esophagectomy (MIE) has gained widespread acceptance. This study evaluates the efficacy of MIE in TE-TPL. METHODS: We retrospectively analyzed patients who underwent TE-TPL between January 2007 and December 2022 at the National Cancer Center Hospital in Tokyo, Japan. A total of 33 patients were enrolled, with 19 undergoing minimally invasive esophagectomy (MIE group) and 14 undergoing conventional esophagectomy (Open group). RESULTS: MIE was associated with a significantly shorter operative time (532 min vs. 687 min, p = 0.028), less intraoperative bleeding (371 mL vs. 840 mL, p < 0.01), shorter hospital stays (21 days vs. 34 days, p < 0.01), and a lower reoperation rate (11% vs. 29%, p = 0.036) compared to the Open group. The 3-year overall survival (OS) and progression-free survival (PFS) rates were not significantly different between the two groups (OS: 47.4% vs. 50.0%, p = 0.72; PFS: 34.0% vs. 47.1%, p = 0.41). CONCLUSION: MIE may be a more feasible and efficient option than the conventional approach for TE-TPL.	esophagus
Risk factors of postoperative complications and prognostic factors in patients undergoing esophagectomy reconstructed with colonic interposition.	Colonic interposition following esophageal resection remains challenging. Few studies have investigated the risk factors for postoperative complications and the prognostic factors in patients who underwent this type of surgery. We evaluated 83 patients who underwent esophagectomy with colonic interposition for esophageal and esophagogastric junction cancers. We analyzed factors associated with postoperative complications using logistic regression analysis and prognostic factors using Cox regression analysis. Postoperative complications occurred in 53.0% of patients, including anastomotic leakage in 22.9%, pneumonia in 19.3%, superficial surgical site infection in 7.2%, and deep surgical site infection in 7.2%. Preoperative malnutrition (odds ratio 5.31, 95% confidence interval 1.64-20.1, P = 0.005), synchronous gastrectomy (odds ratio 7.46, 95% confidence interval 2.15-31.5, P = .001), and upper (odds ratio 4.79, 95% confidence interval 1.05-25.1, P = .044) and middle (odds ratio 2.96, 95% confidence interval 1.01-9.33, P = .049) tumor locations were significantly associated with a higher incidence of postoperative complications. In addition, postoperative complications were independently associated with poor overall survival (hazard ratio 2.17, 95% confidence interval 1.13-4.17, P = .021) and cancer-specific survival (hazard ratio 2.52, 95% confidence interval 1.05-6.04, P = .039). Preoperative malnutrition, synchronous gastrectomy, and upper and middle tumor locations were independent risk factors for postoperative complications. Reducing the incidence of postoperative complications may contribute to improved long-term outcomes.	esophagus
Feasibility of antibiotic-assisted fecal microbiota transplantation with immunotherapy for esophageal and gastric cancer.	AIMS: Immune checkpoint inhibitors (ICIs) have improved outcomes in several malignancies, but survival remains poor for patients with unresectable advanced or recurrent esophageal or gastric cancer. Recent evidence suggests that modulation of the intestinal microbiota may influence the therapeutic response to ICIs. This study aims to evaluate the safety and preliminary efficacy of fecal microbiota transplantation following antibiotic pretreatment (A-FMT) in patients scheduled to receive ICI-containing regimens. METHODS: This phase I - II, single-institution clinical trial enrolls patients with unresectable advanced or recurrent esophageal or gastric cancer. Participants receive a 1-week course of oral antibiotics (amoxicillin, fosfomycin, and metronidazole) prior to transplantation. A single dose of donor-derived intestinal microbiota solution is administered via colonoscopy, followed by initiation of ICI-based therapy on the next day. The primary endpoint is the incidence of dose-limiting toxicity. Secondary endpoints include response rate, disease control rate, progression-free survival, overall survival, and adverse events. Comprehensive translational research is conducted using stool, blood, and tissue samples to characterize immune responses and identify biomarkers associated with A-FMT and ICI efficacy.Trial registration: jRCTs031240170.The study is ongoing, and patients are currently being enrolled. Enrollment started in June 2024. A total of 7 patients have been enrolled as of August 2025. This protocol is version 3.2.	esophagus
Navigating Diagnostic Challenges in Pseudoachalasia: A Case Study of Esophagogastric Junction Adenocarcinoma.	BACKGROUND Pseudoachalasia is a rare condition, with up to 4% of cases presenting with achalasia-like symptoms. The early diagnosis of pseudoachalasia can be challenging due to nonspecific manifestations and the limited diagnostic yield of imaging modalities. This report presents the case of a 62-year-old man with a delayed presentation of pseudoachalasia with negative results of various diagnostic methods. CASE REPORT A 62-year-old man with long-term tobacco use and gastroesophageal reflux disease presented with a 2-year history of dysphagia, progressively worsening in the 2 months before this admission. Esophagogastroduodenoscopy (EGD) demonstrated an increased difficulty passing through the esophagogastric junction (EGJ) within a 1-month period. High-resolution manometry suggested EGJ outflow obstruction. Chest magnetic resonance imaging and a computed tomography scan showed a small nodule of the upper lobe of the left lung, suspected to be a tuberculosis lesion, no dilated esophagus, mild thickening of the muscle layer of the distal esophagus, and EGJ. An endoscopic ultrasound was performed, and no clues of malignancy were found. After a failed peroral endoscopic myotomy, a nasogastric tube was placed for nutrition support. Multiple biopsies produced normal findings. After 3 sessions of pneumatic dilation, with rapid recurrence of dysphagia and a failed stent replacement, surgical intervention was performed, revealing adenocarcinoma at the EGJ. CONCLUSIONS Pseudoachalasia due to EGJ adenocarcinoma should be suspected in patients without weight loss, regardless of the duration of symptom onset or imaging findings. Surgical exploration may be warranted early in selected patients when a definitive diagnosis of pseudoachalasia remains elusive despite extensive investigation.	esophagus
ARNTL2 regulated the oncogene c-myc and promoted the progression of esophageal cancer through activating ANXA2 transcription.	OBJECTIVE: Aryl hydrocarbon receptor nuclear transporter-like 2 (ARNTL2) can bind to clock circadian regulator (CLOCK) to regulate gene expression and is abnormally expressed in various cancers. Nevertheless, its effects on esophageal cancer (ESCC) are unclear. This work can uncover the intriguing mechanism of ARNTL2 in ESCC. METHODS: Malignant phenotypes including cell proliferation, invasion, migration, and epithelial mesenchymal transition (EMT), were investigated. We established a BALB/c nude mouse (5-6 weeks) model with ESCC to verify the influence of ARNTL2/ANXA2/C-MYC axis. ESCC tissues (n = 100) and paired adjacent normal tissues (n = 100) from patients with ESCC were collected. The recruitment of ARNTL2 and CLOCK in ANXA2 promoter was studied by ChIP and dual-luciferase reporter assay. RIP and RNA pulldown were used to explore the relationship between ANXA2 and C-MYC mRNA. RESULTS: Compared to adjacent normal tissues, ESCC tissues developed the significant increase ARNTL2, ANXA2, and C-MYC. ARNTL2, which interacts with CLOCK, was recruited in ANXA2 promoter and elevated ANXA2. ARNTL2 silence reduced cell proliferation, migration and invasion and inhibited EMT, which was reversed by ANXA2 overexpression. ANXA2 can bind to the 3'UTR of C-MYC transcript; further assays confirmed that ANXA2 increased the protein abundance of C-MYC. ANXA2 knockdown resulted in a decrease in malignant phenotypes, whereas C-MYC overexpression reversed these changes. ARNTL2 silence inhibited the formation, growth and EMT of subcutaneous tumors and suppressed C-MYC; ANXA2 overexpression reversed these alterations. CONCLUSION: ARNTL2 activated the transcription of ANXA2, which interacts with C-MYC transcript, promoting the development of malignant behaviors of ESCC cells.	esophagus
Prognostic role of effective radiation dose to immune cells in esophageal cancer treated with definitive chemoradiation.	BACKGROUND: Radiotherapy for locally advanced esophageal cancer can induce lymphopenia, potentially worsening outcomes. This study examines the association between clinical outcomes and the effective dose to the immune cells (EDIC), a measure of lymphocyte radiation exposure. METHODS: We retrospectively analyzed 107 patients with locally advanced esophageal squamous cell carcinoma treated with definitive concurrent chemoradiotherapy (CCRT). The EDIC was calculated based on the mean lung dose, mean heart dose, and integral total body dose using established models. Patients were stratified into high (n = 42) and low (n = 65) effective dose to the immune cells (EDIC) groups using a cut-off value of 4.28 Gy. Survival outcomes, including overall survival (OS), progression-free survival (PFS), locoregional failure-free survival (LRFS), and distant metastasis-free survival (DMFS), were assessed. RESULTS: The 5-year OS and PFS rates were significantly lower in the high EDIC group than in the low EDIC group (51.9% vs. 66.6%, p = 0.043; 20.8% vs. 31.8%, p = 0.002, respectively). Multivariate analysis identified high EDIC as an independent predictor of poorer OS (hazard ratio (HR): 2.06, 95% confidence interval (CI): 1.1-3.86, p = 0.024) and PFS (HR: 1.7, 95% CI: 1.04-2.78, p = 0.034). Similarly, the 5-year LRFS and DMFS rates were significantly lower in the high EDIC group than in the low EDIC group (24.1% vs. 34.9%, p = 0.003; 29.0% vs. 44.0%, p = 0.018, respectively). CONCLUSION: A higher EDIC is an independent predictor of poor survival in patients with esophageal squamous cell carcinoma undergoing CCRT. Reducing radiation exposure to the immune system through optimized radiation planning and lymphocyte-sparing techniques may improve patient outcomes.	esophagus
Integrating photon with proton dose-response data alters a pulmonary complication model-based patient selection in esophageal cancer.	PURPOSE/OBJECTIVE: To develop a general lung dose-response curve for postoperative pulmonary complications (PPCs) following neoadjuvant chemoradiotherapy (nCRT) and surgery in esophageal cancer (EC), and to assess the impact of including proton therapy (PT) data in normal tissue complication probability (NTCP) model development. MATERIALS AND METHODS: A comprehensive PubMed search (2004-2024) identified studies reporting mean lung dose (MLD) and PPCs after esophagectomy with nCRT. Logistic and probit NTCP models were fitted to study-level or dose-bin data using weighted maximum likelihood optimization, with and without PT data (XT + PT and XT model, respectively). Meta-analysis evaluated other PPCs risk factors. A simulation study on 40 patients with comparative XT and PT plans assessed model-based patient selection, assuming PT referral when Δ NTCP ≥ 10 %. RESULTS: 16 non-overlapping studies were included for review. PPCs incidence was significantly lower in PT versus XT cohort (15.6 % versus 30.7 %, p < 0.001). Both NTCP models showed increasing PPCs risk with rising MLD, with the XT model predicting higher PPCs rate in the low-dose region. Meta-analysis identified histology, surgery approach and pre-RT FEV(1) as significant predictors (p < 0.05). In the simulation study, the XT + PT model predicted lower PPCs risk and subsequently higher Δ NTCP than the XT model (average 16.3 % versus 8.0 %, p < 0.001). Referral decisions differed in 15 of 40 patients (37.5 %), who were redirected to PT only by the XT + PT model. CONCLUSION: Including PT dose-response data into thoracic NTCP models alters pulmonary complication model-based patient selection in EC.	esophagus
Correlation of immune cell subsets in the tumor microenvironment and peripheral blood with immunotherapy response in esophageal squamous cell carcinoma.	BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is commonly diagnosed at an advanced stage, where conventional chemoradiotherapy offers only limited clinical benefit. Immune checkpoint inhibitors targeting the tumor microenvironment (TME) have demonstrated substantial therapeutic potential; however, reliable biomarkers for predicting therapeutic outcomes remain unclear. METHODS: Single-cell RNA sequencing dataset for ESCC was obtained from the GEO database and analyzed using the Seurat R package to evaluate gene expression in tumor and adjacent tissues. Additionally, flow cytometry was used to assess immune cell subsets in peripheral blood samples from patients undergoing immunotherapy. Statistical analyses, including survival analysis and the Kruskal-Wallis test, were conducted to investigate the association between immune cell subsets and treatment efficacy. RESULTS: In tumor tissues, immune subsets were significantly enriched compared with adjacent tissues, including CD8(+) T cells with exhaustion (CD39, TIM3, PD-1) or activation/tissue residency (CD137, CD103) features; CD4(+) T cells with activation (CD134, CD137) or regulatory (FOXP3) phenotypes; and dendritic cells expressing TIM3 or CD103. In peripheral blood, a median change in TIM3(+) CD8(+) T cells of 3.35% was observed following immunotherapy. Patients with changes exceeding this threshold experienced shorter progression-free survival (PFS) compared to those with lower changes (5.0 vs. 8.5 months, P = 0.024). Furthermore, TIM3(+) CD8(+) T cell changes were markedly reduced in patients achieving complete or partial responses compared to those with progressive disease. CONCLUSIONS: TIM3(+) CD8(+) T cells are a promising predictive biomarker for immunotherapy outcomes in ESCC. These findings highlight their potential to guide personalized treatment strategies in clinical practice.	esophagus
Chemoradiotherapy with or Without Anlotinib for Postoperative Lymph Node Recurrence of Esophageal Squamous Cell Carcinoma: A Real-World Observational Study.	PURPOSE: Anlotinib, a tyrosine kinase inhibitor, has shown encouraging anti-tumor activity in esophageal squamous cell carcinoma (ESCC). This study present real-world data on the efficacy and safety of chemoradiotherapy (CRT) plus anlotinib versus CRT alone in patients with lymph node recurrence of ESCC after radical resection. PATIENTS AND METHODS: Patients with lymph node recurrence of ESCC who received CRT with or without anlotinib between January 2017 and December 2019 were retrospectively analyzed. Treatment response, overall survival (OS), progression free survival (PFS) and treatment-related toxicities were compared between groups. Propensity score matching (PSM) analysis was used to balance baseline covariates. RESULTS: A total of 291 ESCC patients with lymph node recurrence received CRT plus anlotinib (n = 76) or CRT alone (n = 215). After PSM, 68 well-balanced patients in each group were included. The partial response rate (58.8% vs 41.2%, p = 0.04) and objective response rate (86.7% vs 61.8%, p = 0.001) were significantly higher in the CRT plus anlotinib group than in the CRT group. Patients in the CRT plus anlotinib group had significantly longer OS (3-year OS, 42.7% vs 23.5%, p = 0.008) and PFS (12-month PFS, 47.1% vs 32.4%, p = 0.026) than those in the CRT group. Multivariate survival analysis revealed that the treatment group (p = 0.007) was an independent predictor of OS. No significant differences were observed in grade 3-4 treatment-related adverse events between the two groups (39.5% vs 30.7%, p = 0.162). CONCLUSION: Compared with CRT alone, the addition of anlotinib to CRT was safe and provided survival benefits in ESCC patients with lymph node recurrence after radical resection.	esophagus
Diagnostic performance of computed tomography short-axis diameter for supraclavicular lymph node metastasis after neoadjuvant chemotherapy for esophageal squamous cell carcinoma.	Esophageal squamous cell carcinoma (ESCC) often metastasizes to supraclavicular lymph nodes (SCLNs), which are potentially curable distant metastases by SCLN dissection during esophagectomy. Prophylactic SCLN dissection should be based on an accurate preoperative assessment of SCLN metastasis. We evaluated 199 patients who received neoadjuvant chemotherapy, followed by esophagectomy with three-field lymph node dissection for ESCC. For each patient, the largest SCLN was measured on the left and right sides. Long- and short-axis diameters of 398 SCLNs were measured using computed tomography (CT), and long-to-short-axis ratio was calculated. Diagnostic accuracies of the long- and short-axis diameters and long-to-short-axis ratio were determined using area under the curve (AUC) of the receiver operating characteristic plot. Of the 199 patients, 16.6% had pathological SCLN metastasis. AUCs of the short-axis diameter had the most significant values in the left and right sides compared with the other variables, at 0.93 (95% confidence interval [CI]: 0.89-0.97) for the left side and 0.92 (95% CI: 0.87-0.97) for the right side. When the short-axis diameter was <5 mm after chemotherapy, negative predictive value was sufficiently high (99.4% and 98.2% for the left and right SCLNs, respectively). In contrast, when the diameter exceeded 8 mm, positive predictive value increased to 71.4% and 83.3% in the left and right SCLNs, respectively. The short-axis diameter of the largest SCLN on CT after neoadjuvant chemotherapy appears to be a helpful indicator for diagnosing SCLN metastasis in patients with ESCC after neoadjuvant chemotherapy.	esophagus