Abstract Topic Esophageal Cancer: Molecular Biology/Pathology Background With the advancement of personalized medicine, multi-target drug development has garnered significant attention, particularly for complex diseases such as cancer. This study aims to identify potential dual-target inhibitors against Epidermal Growth Factor Receptor (EGFR) and Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), two proteins whose aberrant activation is closely associated with tumorigenesis and progression in various cancers. Methods We collected IC50 values of active compounds for EGFR and PIK3CA from the BindingDB database, which were then standardized to pIC50 values using RDKit. A total of 2048 Extended-Connectivity Fingerprints (ECFPs) were calculated to serve as molecular descriptors. Various machine learning models, including Support Vector Machine (SVM), Decision Tree, Random Forest, Gradient Boosting, K-Nearest Neighbors, and LightGBM, were developed. The optimal model parameters were determined using ten-fold cross-validation and grid search, and model performance was assessed by Mean Absolute Error (MAE), Mean Squared Error (MSE), and the R-squared (R2) value. Results The SVM model demonstrated the best performance and was selected to predict activities for both EGFR and PIK3CA. Conclusion The natural product compounds CNP0456830 and CNP0467494 exhibited the lowest binding free energies for both EGFR and PIK3CA, identifying them as the most promising dual-target inhibitors. This study offers a new direction and a potential therapeutic strategy for personalized drug design in cancer treatment.

BACKGROUND:The optimal extent of lymphadenectomy following neoadjuvant chemoimmunotherapy (nCIT) for esophageal squamous cell carcinoma (ESCC) remains unclear. Current recommendations are largely derived from neoadjuvant chemoradiotherapy cohorts, and their applicability in the era of immunotherapy is unclear. This study evaluated the association between lymph node dissection (LND) yield and disease-free survival (DFS) in patients with ESCC treated with nCIT. METHODS:This retrospective multicenter cohort study included 465 patients with ESCC who underwent nCIT followed by radical esophagectomy at six hospitals in China between January 2019 and December 2023. The median follow-up was 40.7 months. The total number of dissected lymph nodes was analyzed in relation to DFS. The restricted mean survival time at 5 years was estimated by using random survival Forest-based models, with subgroup analyses by posttherapy pathological stage (ypT/ypN). RESULTS:A higher lymph node yield was associated with improved DFS, although the relationship was nonlinear and varied by pathological subgroup. In patients with ypT0-2N0 disease, DFS improved with increasing LND up to approximately 20-30 lymph nodes, after which the benefit plateaued. In patients with residual nodal disease (ypN1-3), higher lymph node yields were associated with longer DFS, with greater yields observed in more advanced disease stages. Across all subgroups, lower lymph node yields were consistently associated with inferior DFS. CONCLUSIONS:In this multicenter cohort of patients with ESCC treated with nCIT, lymph node yield was associated with DFS in a stage-dependent manner, suggesting its potential role as a postoperative quality indicator for surgical lymphadenectomy after nCIT.

Abstract Topic Esophageal Cancer: Molecular Biology/Pathology Background To use bioinformatics methods to evaluate the prognostic value of Programmed Cell Death Related Genes (PCDRGs) in esophageal carcinoma (EC), and to explore the development and immune regulatory mechanisms of EC from multiple perspectives. Methods Using TCGA, GSE53622 data sets, and downloaded key regulatory genes of 18 PCD patterns, combined with 10 different machine learning methods to develop a prediction model, named this model ‘Characteristics of Cell Deaths’ (CDS). Seven prognosis-related genes were screened out by the model. The correlationbetween these seven genes and EC was analyzed. Results The PCDRGs prognostic model developed using the StepCox[both] + RSF method performed the best. CDS showed significant and powerful performance in predicting EC clinical outcomes and was able to serve as an independent risk factor in TCGA and GEO datasets. Conclusion This study successfully developed a novel EC PCDRGs model, which could predict the prognosis and drug treatment sensitivity of EC patients in the future based on further validation.

Abstract Topic Esophageal Cancer: Surgical Treatment of Esophageal Cancer – technique Background Robot-assisted minimally invasive esophagectomy (RAMIE) is increasingly adopted, yet comparative patient-reported outcome (PRO) data against conventional minimally invasive esophagectomy (MIE) remains scarce. We aimed to compare perioperative PROs, including quality of life, nutritional status, cough-related quality of life, and anxiety, between RAMIE and MIE for esophageal squamous cell carcinoma (ESCC). Methods We enrolled 214 patients with ESCC who underwent RAMIE (n = 47) or conventional MIE (n = 167) from an ongoing prospective cohort study. PROs were assessed using the EQ-5D-5L, PG-SGA, Leicester Cough Questionnaire (LCQ), and Self-rating Anxiety Scale (SAS). A 1:1 propensity score-matched (PSM) analysis was performed to balance baseline covariates. Nutritional trajectory was tracked from admission through discharge using serial PG-SGA assessments. Results Before PSM, the RAMIE group had significantly higher preoperative PG-SGA scores at admission (5.18 ± 3.32 vs 4.09 ± 3.01, P = 0.015) and pre-surgery (5.44 ± 3.69 vs 3.78 ± 2.88, P = 0.006), indicating worse baseline nutritional status. However, PG-SGA scores at discharge were comparable (4.56 ± 2.74 vs 4.42 ± 2.28, P = 0.931), demonstrating nutritional convergence. No significant differences were observed in EQ-5D-5L utility index (0.92 vs 0.93, P = 0.934), LCQ total score (121.6 vs 122.6, P = 0.751), or SAS standard score (45.4 vs 45.4, P = 0.551). The RAMIE group had a higher anastomotic leak rate (14.9% vs 4.8%, P = 0.025) but no Clavien-Dindo grade ≥III complications. Conclusion RAMIE and conventional MIE achieved comparable perioperative PROs in ESCC patients. Despite worse baseline nutritional status in the RAMIE group, nutritional recovery by discharge was equivalent. These findings support RAMIE as a viable alternative with comparable patient-centered outcomes, though the higher anastomotic leak rate warrants further investigation.

Abstract Topic Esophageal Cancer: Surgical Treatment of Esophageal Cancer Background Preoperative risk stratification for esophagectomy complications relies on clinical prediction models; however, their discriminative performance in multi-institutional settings remains poorly defined. We hypothesized that standard preoperative variables would demonstrate limited predictive validity across heterogeneous surgical cohorts. Methods We analyzed 2,490 patients undergoing esophagectomy across four institutions in Asia (total n=2,490; individual center n range 75–1,012). Four outcomes were studied: recurrent laryngeal nerve palsy (RLNP), anastomotic leak (AL), pulmonary complications (PC), and vocal cord palsy (VCP). Logistic regression models with bootstrap-validated odds ratios (1,000 iterations) were evaluated by 5-fold cross-validated AUC. SHAP (SHapley Additive exPlanations) via Gradient Boosting Machines quantified variable importance. Decision curve analysis (DCA) assessed net clinical benefit across threshold probabilities 2–70%. Association between tumor location and each complication was assessed using chi-squared tests. Results All prediction models demonstrated poor-to-fair discrimination: RLNP AUC 0.533, AL AUC 0.586, PC AUC 0.676, and VCP AUC 0.556. Tumor location was the only statistically significant categorical predictor of RLNP—upper/cervical location was associated with higher RLNP incidence compared to middle thoracic tumors (39.1% vs. 28.0%; OR 1.22, 95%CI 1.05–1.42; p=0.009). No significant association was observed between tumor location and AL, PC, or VCP. DCA demonstrated negligible clinical net benefit for RLNP and AL models; only the PC model provided modest benefit (max net benefit gain +0.057) at threshold probabilities of 5–20%. SHAP analysis identified FEV1%, PNI score, and BMI as the highest-importance variables for RLNP prediction, with tumor location ranking sixth—indicating that location contributes a statistically real but clinically modest signal. Conclusion Standard preoperative variables are insufficient for individualized risk stratification of RLNP, anastomotic leak, or vocal cord palsy after esophagectomy. Statistical significance (p=0.009 for location–RLNP association) does not translate to clinically meaningful predictive power (AUC 0.533). Tumor location should be incorporated into RLNP preoperative counseling. Improved prediction will require prospective integration of real-time intraoperative data. Pulmonary complication risk approaches clinically actionable prediction (AUC 0.676) and may guide respiratory prehabilitation targeting.

Abstract Topic Esophageal Cancer: Adjuvant and Neo-Adjuvant Therapies Background The survival benefit of neoadjuvant therapy for esophageal squamous cell carcinoma (ESCC) remains controversial, as landmark trials were conducted predominantly in adenocarcinoma populations. This study evaluated the association between neoadjuvant therapy and long-term survival in a large international multicenter ESCC cohort using propensity score methods and multivariable Cox regression. Methods We retrospectively analyzed 2,449 patients with ESCC who underwent curative esophagectomy at five institutions across three countries (Japan, China, and South Korea) between 2008 and 2022. Patients receiving neoadjuvant therapy (n=941) were compared with a surgery-first cohort (n=880) after excluding 41 cases with inconsistent survival data. Propensity score matching (PSM) 1:1 was performed using nearest-neighbor matching (caliper=0.1 SD of logit propensity score) with exact matching on center, adjusting for sex, age, clinical T and N stage. Inverse probability of treatment weighting (IPTW) with trimming (1st–99th percentile) served as a sensitivity analysis. Center-stratified univariate and multivariable Cox proportional hazards regression were applied. Primary endpoints were overall survival (OS) and disease-free survival (DFS). Results In analysis, neoadjuvant therapy appeared protective for OS (HR 0.60, 95% CI 0.48–0.75, p<0.001) while DFS was worse (HR 1.57, 95% CI 1.34–1.84, p<0.001). This discordant finding reversed after center-stratified Cox regression, revealing substantial confounding by center. Univariate analysis showed neoadjuvant therapy was associated with worse OS (HR 2.22, 95% CI 1.75–2.83, p<0.001) and DFS (HR 2.31, 95% CI 1.89–2.82, p<0.001). Multivariable analysis confirmed neoadjuvant therapy as an independent predictor of worse OS (HR 1.48, 95% CI 1.11–1.96, p=0.007) and DFS (HR 1.39, 95% CI 1.09–1.77, p=0.007). PSM yielded 255 pairs; after matching, neoadjuvant therapy was associated with worse OS (HR 1.56, 95% CI 1.05–2.30, p=0.027) and DFS (HR 1.60, 95% CI 1.18–2.19, p=0.003). IPTW sensitivity analysis yielded consistent results (OS: HR 2.21, 95% CI 1.74–2.82; DFS: HR 2.30, 95% CI 1.89–2.81; both p<0.001). Conclusion In this international multicenter analysis of 2,449 ESCC patients, neoadjuvant therapy was not associated with improved survival after esophagectomy and remained an independent predictor of worse OS and DFS across univariate, multivariable, PSM, and IPTW analyses. These findings underscore the critical importance of histology-specific evidence and support the urgent need for contemporary randomized controlled trials designed specifically for ESCC populations.

Abstract Topic Esophageal Cancer: Surgical Treatment of Esophageal Cancer – early outcomes and complications Background Postoperative complications following oesophagectomy occur in 25–60% of patients, yet traditional patient-reported outcome (PRO) assessment relies on standardised questionnaires with limited reliability, particularly among elderly patients with low health literacy. We aimed to develop and externally validate a multimodal artificial intelligence (AI) system that automates PRO assessment from natural patient conversations and provides early warning of major postoperative complications. Methods We conducted a prospective observational study at a tertiary cancer center, enrolling consecutive patients undergoing esophagectomy.The development cohort (Centre 1, n=196) and the temporally independent external validation cohort (Centre 2, n=103) were recruited sequentially. Using the validated Patient Symptom Assessment for Oesophageal Cancer (PSA-ESO) instrument, we collected trimodal recordings (video, audio, text) at up to 25 timepoints per patient, yielding 6,813 evaluable assessments. We fine-tuned the Qwen2.5-Omni-7B multimodal large language model with LoRA adaptation for two tasks: automated PRO symptom grading (Task A) and Temporal Transformer-based early warning of Clavien-Dindo grade II or higher complications (Task B). In a prospective implementation substudy (n=62), we evaluated the clinical impact of real-time alerts on time-to-intervention. Results In the external validation cohort, the trimodal PRO assessment achieved a weighted kappa of 0.801 (95% CI 0.73–0.87) and ICC of 0.858 against expert consensus, significantly outperforming audio-text bimodal (kappa 0.754, p<0.0001) and text-only (kappa 0.689, p<0.0001) configurations. The early warning model achieved an AUROC of 0.873 (95% CI 0.82–0.93) with a mean detection lead time of 28.7 hours before clinical diagnosis. The system detected 76.1% of symptom under-reporting cases. In the implementation substudy, real-time alerts reduced median time-to-intervention from 14.2 hours to 6.8 hours (p=0.003) and were associated with shorter ICU stays (3.1 vs 5.4 days, p=0.028). Conclusion An end-to-end multimodal AI system can accurately automate PRO assessment from natural patient conversations and provide clinically meaningful early warning for postoperative complications, with external validation confirming generalisability across cohorts. This conversation-based approach represents a paradigm shift from questionnaire-based PRO evaluation in surgical oncology, with particular relevance for populations with limited health literacy.

Background The prognostic relevance of type 2 diabetes in esophageal cancer patients undergoing neoadjuvant therapy followed by surgery remains unclear. This study assessed whether type 2 diabetes influences perioperative outcomes and long-term survival. Methods A total of 1099 patients who received neoadjuvant therapy followed by surgery at three high-volume institution in China from 2013 to 2024 were included. The diagnosis of type 2 diabetes was based on American Diabetes Association criteria. A 1:4 propensity score matching was performed using the R software. Baseline characteristics, perioperative outcomes, overall survival and progression-free survival were compared. Results After 1:4 matching, 114 patients in the diabetic group and 456 patients in the non-diabetic group were compared. No significant differences were found between non-diabetic and diabetic group regarding length of stay (9 days vs 9 days, P = 0.856), re-operation (2.2% vs 0.9%, P = 0.594), re-admission (1.5% vs 1.8%, P > 0.990), total complications (45.0% vs 51.8%, P = 0.231), or specific complications. At a median follow-up of 1086 days, the 2-year overall survival between non-diabetic and diabetic group was 73.9% vs 77.2%, and the 3-year overall survival was 62.4% vs 67.8% [hazard ratio: 0.840, 95% CI: 0.570–1.220, P = 0.356]. After a median follow-up of 927 days, the 2-year progression-free survival of the two groups was 73.2% vs 65.1%, and the 3-year progression-free survival was 65.2% vs 62.4% [hazard ratio: 1.130, 95% CI: 0.780–1.630, P = 0.529]. Conclusions Type 2 diabetes does not adversely affect perioperative outcomes or long-term survival in esophageal cancer patients undergoing neoadjuvant therapy and surgery.

Background:To evaluate the impact of Body Mass Index (BMI) on survival and postoperative complications in older patients with esophageal squamous cell carcinoma (ESCC) following esophagectomy, we designed this study. Materials and methods:We retrospectively analyzed 469 patients aged ≥70 years with thoracic ESCC who underwent esophagectomy at Sichuan Cancer Hospital (May 2016-August 2021). Patients were grouped by WHO BMI categories: underweight (<18.5 kg/m2), normal (18.5-24.9 kg/m2), and overweight/obese (≥25 kg/m2). Primary outcomes were overall survival (OS) and disease-free survival (DFS); secondary outcomes included Clavien-Dindo grade III-IV complications. Kaplan-Meier, Cox models, and restricted cubic splines (RCS) were used. Results:Median follow-up was 47.5 months; R0 resection was achieved in 96.4%. BMI distribution: 7.3% low, 76.8% normal, 16.0% high. Median OS was 44.9 months overall, with no significant OS or DFS differences among BMI groups. RCS demonstrated a significant U-shaped association between continuous BMI and survival: protective ranges were approximately 21.9-27.0 kg/m2 for OS (P non-linearity = 0.014) and 20.2-27.2 kg/m2 for DFS (P non-linearity = 0.033). Conclusion:In elderly ESCC patients after esophagectomy, BMI does not independently influence OS or DFS, though low BMI is associated with specific serious complications. Perioperative optimization-particularly nutritional support for underweight patients-remains essential.

Abstract Topic Esophageal Cancer: Surgical Treatment of Esophageal Cancer – long term outcomes Background Esophageal cancer remains a significant global health burden. While surgical and oncologic factors influencing survival after esophagectomy are well studied, the potential impact of surgical timing and medical staff burnout on long-term outcomes remains underexplored. This study investigates whether the month of esophagectomy and esophageal surgery personnel burnout affect survival in esophageal squamous cell carcinoma (ESCC). Methods A retrospective cohort of ESCC patients who underwent esophagectomy between January 2010 and December 2017 was analyzed from a single-center esophageal cancer case management database. Patients were stratified into twelve monthly subgroups based on the month of surgery. Survival outcomes were assessed using Kaplan–Meier analysis, Cox proportional hazards regression, and restricted mean survival time (RMST). Propensity score matching (PSM) was employed to adjust for confounding variables including age, sex, tumor stage, and neoadjuvant therapy. Additionally, a cross-sectional survey was conducted from 2024 to 2025 to evaluate burnout levels among 409 esophageal surgery professionals using the Maslach Burnout Inventory–Human Services Survey (MBI-HSS), with monthly stratification to examine the temporal relationship between staff burnout patterns and surgical outcomes. Results Among 2,758 ESCC patients who underwent esophagectomy, those operated in February had the poorest survival, with a median survival time (MST) of 34.17 months compared to 45.23 months for non-February surgeries (HR: 0.833, 95% CI: 0.677–1.025, P=0.084). The 3- and 5-year overall survival rates were lower for February (47% and 36%) versus other months (56% and 45%). Conversely, April and June surgeries yielded superior outcomes (MST: 61.44 and 63.60 months, respectively). Burnout survey data (n=409) revealed a striking inverse pattern: February showed mild burnout (EE: 16.69, DP: 5.63), coinciding with the Chinese New Year holiday period, whereas non-February months demonstrated severe burnout (EE: 30.95, DP: 13.51). This paradoxical finding suggests that lower burnout alone does not predict better outcomes; rather, February’s reduced surgical volume and case complexity may be contributory factors. Conclusion Surgical timing, particularly esophagectomy performed in February, is associated with inferior long-term survival in ESCC patients. The concurrent low burnout levels during this period suggest that reduced surgical volume and altered case selection during the holiday season, rather than staff fatigue, may underlie this disparity. These findings highlight the importance of considering temporal factors in esophagectomy scheduling and warrant further multicenter validation.

Abstract Topic Esophageal Cancer: Surgical Treatment of Esophageal Cancer – early outcomes and complications Background Postoperative complications following esophagectomy are frequent and clinically heterogeneous. Serum C-reactive protein (CRP) is a widely available inflammatory marker, yet its longitudinal trajectory after esophagectomy and its relationship with complication severity have not been systematically characterized. This study aimed to identify distinct postoperative CRP trajectory patterns and evaluate their association with Clavien-Dindo graded complication outcomes. Methods Among 809 consecutive esophagectomy patients at a single center, 131 patients (16.2%) had complete serial CRP measurements on postoperative days (POD) 1, 3, 5, and 7. K-means clustering was applied to identify distinct CRP trajectory groups. Associations between trajectory groups and complications (Clavien-Dindo grading), anastomotic leak, and ICU length of stay were evaluated using chi-square tests, Kruskal-Wallis tests, and multivariable logistic regression. Receiver operating characteristic (ROC) analysis assessed the predictive utility of individual CRP timepoints and derived indicators. Results Three distinct CRP trajectories were identified: Low-Stable (n=86, 65.6%), Moderate-Declining (n=20, 15.3%), and High-Persistent (n=25, 19.1%). Complication rates increased significantly across trajectories: severe complications (CD≥III) occurred in 15.1%, 25.0%, and 56.0% of patients in each group, respectively (p<0.001). The High-Persistent group showed a 5.71-fold increased odds of severe complications on multivariable analysis (OR 5.71, 95%CI 1.99–16.40, p=0.001). CRP on day 7 demonstrated the highest individual discriminative value (AUC=0.671), while the CRP D3/D1 ratio (AUC=0.632) offered the earliest actionable prediction at POD 3. Conclusion Postoperative CRP trajectory patterns are significantly associated with complication severity after esophagectomy. The High-Persistent trajectory identifies a high-risk subgroup, and the D3/D1 ratio enables early risk stratification by POD 3. Prospective studies with larger cohorts are warranted to validate these findings.

Importance:The optimal treatment strategy for locally advanced esophageal squamous cell carcinoma (ESCC) remains controversial. Neoadjuvant chemoradiotherapy (NCRT) followed by surgery and surgery with adjuvant therapy (AT) are commonly used approaches. Objectives:To compare the long-term survival outcomes, safety, and pathological benefits of NCRT followed by surgery vs surgery with AT in patients with locally advanced ESCC, and to evaluate the survival impact of pathological complete response (pCR) in the NCRT subgroup. Design, Setting, and Participants:This prospective, randomized, open-label phase 3 trial was conducted at Sichuan Cancer Hospital, China, between January 2018 and April 2020. Eligible patients were aged 18 to 75 years; had histologically confirmed, resectable, locally advanced thoracic ESCC, staged as cT1N+M0 or cT2-4aNxM0; were expected to survive more than 6 months; and had adequate organ function. Key exclusion included prior malignant neoplasms, distant or cervical lymph node metastasis, contraindications to surgery, and prior gastrectomy precluding reconstruction. Data were analyzed April to December 2024. Interventions:Patients in the NCRT group received intensity-modulated radiotherapy (40 Gy in 20 fractions) with concurrent paclitaxel and carboplatin followed by surgery. Patients in the AT group received an adjuvant chemoradiotherapy regimen designed by a multidisciplinary team. Main Outcomes and Measures:The primary end point was overall survival (OS). Secondary end points included disease-free survival (DFS), pathological outcomes, treatment-related toxic effects, and perioperative complications. Results:A total of 254 patients were initially enrolled; after exclusions and randomization, 118 patients in the NCRT group (median [IQR] age, 62 [54-66] years; 102 [86.4%] male) and 112 patients in the AT group (median [IQR] age, 63 [55-66] years; 97 [86.6%] male) were included in the analysis. After a median (IQR) follow-up of 59.1 (54.4-65.9) months, there were no significant differences in OS or DFS between the groups. The 5-year OS rates were 59.2% (95% CI, 51.0%-68.8%) for the NCRT group and 59.6% (95% CI, 51.2%-69.5%) for the AT group (hazard ratio [HR], 1.01; 95% CI, 0.67-1.51; P = .97). The 5-year DFS rates were 53.1% (95% CI, 44.7%-63.1%) and 56.5% (95% CI, 47.9%-66.7%), respectively (HR, 1.13; 95% CI, 0.77-1.68; P = .53). Subgroup analysis showed that patients achieving pCR in the NCRT group had significantly improved survival outcomes, with a 5-year OS rate of 76.5% (95% CI, 63.5%-92.1%) compared with 52.1% (95% CI, 42.4%-64.1%) for non-pCR patients (HR, 0.39; 95% CI, 0.18-0.82; P = .01). Conclusions and Relevance:In this randomized clinical trial, there were no differences in OS or DFS for patients treated with NCRT followed by surgery or surgery with AT. However, for the patients who achieved pCR with NCRT, there were significant advantages, with markedly improved long-term outcomes. Nevertheless, neoadjuvant chemoradiotherapy did not benefit all patients; for those less likely to respond, the combination of surgery with postoperative AT remains a reasonable strategy. These findings show that it may not be appropriate to universally recommend neoadjuvant chemoradiotherapy for all patients. Trial Registration:ClinicalTrials.gov Identifier: NCT06775652.

e16092 Background: The optimal treatment strategy for locally advanced esophageal squamous cell carcinoma (ESCC) remains uncertain. Although neoadjuvant chemoradiotherapy (NCRT) improves pathological response, its long-term survival advantage over surgery plus adjuvant therapy (AT) is unclear. The impact of these strategies on recurrence patterns and postrecurrence survival (PRS) also requires clarification. Methods: In this prospective, open-label, randomized phase III trial, 245 patients with cT1N+M0 or cT2–4aNxM0 thoracic ESCC (2018–2020) were assigned to NCRT followed by surgery or surgery plus AT; 118 and 112 patients were included in the final analysis. NCRT consisted of IMRT (40 Gy/20 fractions) with weekly paclitaxel and carboplatin. AT was individualized by a multidisciplinary team. The primary endpoint was overall survival (OS); secondary endpoints included disease-free survival (DFS), pathological outcomes, recurrence patterns, recurrence timing, and PRS. Results: After a median follow-up of 59.1 months, OS and DFS did not differ significantly between groups (5-year OS: 59.2% vs 59.6%, HR 1.01, P = 0.97; 5-year DFS: 53.1% vs 56.5%, HR 1.13, P = 0.53). The NCRT group achieved a 28.8% pathological complete response (pCR) rate, and pCR was associated with markedly improved OS (76.5% vs 52.1%; HR 0.39, P = 0.01). Among 230 evaluable patients, the recurrence rate was 33.5% (34.7% vs 32.1%, P = 0.696), with distant metastasis as the predominant pattern. Early recurrence ( < 12 months) occurred in 14.3% of patients and predicted significantly poorer OS (6.1% vs 27.1%; HR 4.22, P < 0.001) and shorter PRS (6.93 vs 10.28 months; HR 1.75, P = 0.026). It was the only independent predictor of PRS. Conclusions: NCRT did not improve long-term survival over surgery plus AT in an unselected ESCC population. Nevertheless, patients achieving pCR experienced substantial benefit. Recurrence remained common, dominated by distant metastasis, and early recurrence was strongly associated with poor PRS. Clinical trial information: NCT06775652 .

Abstract Topic Esophageal Cancer: Other Background Precise segmentation of esophageal squamous cell carcinoma (ESCC) lesions on CT imaging is essential for treatment planning. While the Segment Anything Model for 3D medical images (SAM-Med3D) shows promise, its performance in delineating tumor boundaries remains suboptimal. We propose a prototype-contrast boundary optimization strategy to enhance segmentation accuracy. Methods In this retrospective multicenter study, CT volumetric data from 310 ESCC patients who underwent esophagectomy were collected from two centers (Center A: n=161, July 2018–February 2023; Center B: n=149). Data from Center A were used for training and internal validation, while Center B served as the external testing cohort. We evaluated SAM-Med3D for ESCC lesion segmentation and compared it with state-of-the-art methods including nnU-Net, SegVol, and MedSAM. To address SAM-Med3D’s limitation in boundary delineation, we introduced a prototype-contrast boundary pixel clustering optimization. This approach employs contrastive learning to refine boundary pixel classification by pulling features toward correct class prototypes while pushing them away from incorrect ones. Performance was assessed using Dice Similarity Coefficient (DSC) and 95th percentile Hausdorff Distance (HD95). Results The optimized SAM-Med3D achieved a DSC of 76.23% on internal validation and 73.57% on external testing, representing a 3.11% improvement over the original SAM-Med3D (internal DSC: 73.12%; external DSC: 70.46%). Our method outperformed all baseline approaches: nnU-Net (internal/external DSC: 72.45%/69.18%), SegVol (70.83%/67.52%), and MedSAM (71.26%/68.34%). The optimized model also achieved the lowest HD95 values (internal: 6.48 mm; external: 7.81 mm), indicating superior boundary delineation accuracy. The performance advantage was consistent across both centers, demonstrating robust generalizability. Conclusion The prototype-contrast boundary pixel clustering optimization effectively enhances SAM-Med3D’s capability for ESCC lesion segmentation, achieving superior performance over nnU-Net, SegVol, and MedSAM across multicenter datasets. This approach addresses the critical challenge of accurate tumor boundary delineation and demonstrates strong generalizability, providing a valuable tool for preoperative assessment and surgical planning in ESCC.

BACKGROUND:Patients with nonpathological complete response constitute the majority of esophageal squamous cell carcinoma (ESCC) cases after neoadjuvant therapy, yet the prognostic implications of different pathological outcomes-particularly major pathological response (MPR) combined with lymph node (LN) status-remain poorly defined. This study aimed to elucidate their prognostic value and to refine postoperative evaluation systems. METHODS:This multicenter retrospective cohort study included patients with ESCC from 8 high-volume esophagectomy centers in China who underwent neoadjuvant chemoradiotherapy (nCRT) or neoadjuvant immunochemotherapy (nICT) followed by R0 resection between 2016 and 2023. The primary comparison was between the nCRT and nICT cohorts, with additional planned analyses of pathological response subgroups and pathological stage cohorts (early vs advanced). Propensity score matching was used to balance baseline characteristics, and survival outcomes were compared using Kaplan-Meier and Cox regression analyses. RESULTS:After matching, nICT demonstrated similar pathological complete response (pCR) rates to nCRT but achieved more extensive nodal dissection and significantly reduced distant recurrence (P < .001). Among pathological subtypes, MPR(+)LN(-) yielded the most favorable long-term outcomes, surpassing or equaling those of pCR, whereas MPR(-)LN(+) was associated with the worst prognosis (P < .001). Notably, patients with MPR(+)LN(-) had comparable survival between early- and advanced-stage cohorts, suggesting a reduced prognostic impact of pathological stage and underscoring its strong predictive value. CONCLUSIONS:Patients with MPR and LN negativity had long-term survival comparable to pCR, suggesting that multidimensional pathological evaluation may improve prognostic accuracy. Compared with nCRT, nICT demonstrated improved nodal clearance and systemic disease control across different pathological outcomes.

Abstract Topic Esophageal Cancer: Surgical Treatment of Esophageal Cancer – early outcomes and complications Background The prognostic impact of type 2 diabetes in esophageal cancer patients receiving neoadjuvant therapy followed by surgery remains unclear. We evaluated its association with perioperative outcomes and long-term survival. Methods We retrospectively analyzed 1,099 patients who underwent neoadjuvant therapy followed by surgery between 2013 and 2024 across three high-volume centers. Type 2 diabetes was defined according to American Diabetes Association criteria. A 1:4 propensity score matching analysis was performed to minimize baseline imbalance. Perioperative outcomes, overall survival (OS), and progression-free survival (PFS) were compared between diabetic and non-diabetic patients. Results After matching, 114 diabetic patients were compared with 456 non-diabetic patients. No significant differences were observed in length of hospital stay, re-operation, re-admission, total complications, or specific postoperative morbidities. After a median follow-up of 1,086 days, 2- and 3-year OS rates were 73.9% vs 77.2% and 62.4% vs 67.8%, respectively (HR 0.84, 95% CI 0.57–1.22, P=0.356). After a median follow-up of 927 days, 2- and 3-year PFS rates were 73.2% vs 65.1% and 65.2% vs 62.4%, respectively (HR 1.13, 95% CI 0.78–1.63, P=0.529). Type 2 diabetes was not associated with inferior survival outcomes. Conclusion Type 2 diabetes was not associated with increased perioperative morbidity or impaired long-term survival following neoadjuvant therapy and surgery.

OBJECTIVE:Pathologic complete response (pCR) after neoadjuvant therapy predicts favorable outcomes in esophageal squamous cell carcinoma (ESCC). In this era of neoadjuvant immunochemotherapy (nICT), the prognosis of patients achieving nICT-induced pCR remains unclear. This study aimed to characterize recurrence patterns and identify prognostic factors in this population. METHODS:A multicenter retrospective cohort study was conducted across 26 Chinese centers from 2019 to 2023. Patients with ESCC who underwent surgery after nICT and achieved pCR were included. Prognostic factors for recurrence-free survival (RFS) and overall survival (OS) were evaluated using Cox regression analysis. RESULTS:Among 2135 patients receiving nICT, 474 (22.2%) achieved pCR. After a median follow-up of 32.8 months, 60 patients (12.7%) experienced recurrence, with a median interval of 17.8 months (interquartile range, 8.7-26.7) after surgery. Most recurrences (75%) occurred within 2 years, predominantly as distant metastases (63.3%), with the lung being the most common site. The 2-year RFS and OS were 89.6% and 92.1%, respectively. Advanced clinical nodal stage (cN2-3) was identified as an independent prognostic factor for inferior RFS (adjusted hazard ratio, 1.83; 95% CI, 1.10-3.05; P = .02) but not OS, whereas adjuvant treatment was not associated with improved survival (adjusted hazard ratio, 1.29; 95% CI, 0.69-2.42; P = .42). CONCLUSIONS:Patients with ESCC achieving pCR after nICT exhibited excellent short-term survival but a persistent risk of distant recurrence. Advanced clinical nodal stage is associated with higher recurrence risk, which warrants further validation. Risk-adapted postoperative management may be preferable to routine adjuvant treatment.