crossing96/oncoscreening huggingface dataset:
Health-related quality-of-life outcomes with regorafenib in advanced gastric and esophagogastric junction cancer: results from the INTEGRATE trials.	BACKGROUND: The INTEGRATE trials evaluated regorafenib in advanced gastric and esophagogastric junction cancer (AGOC), a poor prognosis population. In INTEGRATE 1 (I1, phase 2), regorafenib improved progression-free survival (PFS) without a clear excess decline in health-related quality of life (HRQoL). INTEGRATE 2a (I2a, phase 3) demonstrated an overall survival (OS) benefit, alone and in a pre-specified pooled analysis with I1. AIM: To evaluate HRQoL outcomes from I2a and the pooled analysis with I1. METHODS: HRQoL was assessed at baseline, day 1 of each cycle, and every 8 weeks until progression, using EORTC QLQ-C30, EORTC STO22, and the participant Disease and Treatment Assessment (PtDATA). The primary endpoint was deterioration-free survival (DetFS), defined as time to a ≥ 10-point decline in QLQ-C30 physical function (DetFSPF) or global health status (DetFSGHS), progression, or death. Secondary analyses used linear mixed models (LMM). Tertiary analyses used logistic regression to evaluate symptom and side-effect prevalence (PtDATA). Pooled analyses adjusted for trial effects. RESULTS: Of 251 I2a participants, 240 contributed HRQoL data. Regorafenib was superior on DetFSPF (HR = 0.75, 95% CI 0.58-0.99, p = 0.03) and DetFSGHS (HR = 0.68, 95% CI 0.52-0.89, p = 0.004). LMM showed no appreciable differences in HRQoL trajectories. Rash, hand-foot syndrome, numbness, and coping difficulties were more frequent with regorafenib. Pooled analyses confirmed these findings. CONCLUSION: Regorafenib modestly prolonged survival in AGOC without clear HRQoL deterioration. Despite more frequent toxicities, overall HRQoL was preserved. Regorafenib may offer a net clinical benefit when survival and HRQoL preferences are considered.	esophagus
Zinc finger protein 514 promotes esophageal cancer progression by enhancing cell proliferation, migration and invasion.	Esophageal cancer (EC), a malignant tumor occurring in the upper gastrointestinal tract, is the seventh most common cancer worldwide. Zinc finger proteins (ZNFs), the most abundant family of transcription factors in humans, serve an important role in the initiation and progression of various malignant tumors. However, the function of ZNFs in EC remains unclear. The present study aimed to elucidate the role of ZNF514 in the development and progression of EC and to investigate its underlying mechanism. The mRNA and protein expression levels of ZNF514 were assessed using reverse transcription‑quantitative PCR and western blotting. To assess functional roles, multiple cellular assays were performed, including 5‑ethynyl‑2'‑deoxyuridine incorporation, Cell Counting Kit‑8, wound healing, colony formation and Transwell assays. Subsequently, for transcriptomics analysis, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses, Gene Set Enrichment Analysis and Ingenuity Pathway Analysis (IPA) were performed. In EC, ZNF514 exhibited high expression at both the mRNA and protein levels. Additionally, ZNF514 influenced the migration, invasion and proliferation of EC cells. Gene enrichment analyses and IPA demonstrated that ZNF514 knockdown significantly affected multiple signaling pathways, such as Fcγ receptors, the complement system, G‑protein coupled receptors (GPCRs)‑related receptors, the ribosomal S6 kinase (RSK) pathway, Ras/MEK, PI3K/AKT, STAT3, nucleotide‑binding oligomerization domain‑containing protein (NOD) and NF‑κB pathways. In conclusion, the present study indicated that the anticancer mechanisms induced by ZNF514 knockdown may be related to the enhancement of Fcγ receptor and complement system activation, as well as the inhibition of GPCR, RSK, Ras/MEK, PI3K/AKT, STAT3, NOD1/2 and NF‑κB pathways.	esophagus
Esophageal squamous cell carcinoma invading the gastric cardia in a cat.	BACKGROUND: Case reports of primary squamous cell carcinoma (SCC) of the esophagus in cats are limited, and it is considered necessary to accumulate more cases. CASE DESCRIPTION: An 8-year-old spayed female Japanese domestic cat presented with complaints of regurgitation and weight loss for the previous 2 months. A radiographic examination showed that the contrast agent used in the esophagography performed in another veterinary hospital remained inside the esophagus, and a mass lesion on the cranial side of the diaphragm was suspected. Computed tomography examination revealed a mass lesion originating from the caudal esophagus. Esophageal endoscopy revealed a bulging mass in the esophageal mucosa, which was diagnosed by tissue biopsy as SCC. Because hepatic lipidosis was suspected based on CT images, a gastrostomy tube was placed through laparotomy to improve food intake. However, after the gastrostomy tube placement, the blood bilirubin and ammonia concentrations markedly increased, and the cat died 2 days later. Postmortem histopathological examination revealed that the esophageal SCC had invaded the gastric cardia's mucosal and muscular layers. Metastatic lesions were also confirmed in the lymph nodes around the liver. The liver histopathology was compatible with severe hepatic lipidosis, and liver failure was considered the cause of death. CONCLUSION: Although primary SCC of the esophagus in cats is considered a rare disease, it should be considered as a differential diagnosis in patients with severe regurgitation and weight loss. When treating cats with long-term starvation, the progression of potentially fatal hepatic lipidosis should be considered.	esophagus
Survival analysis of additional radiotherapy after endoscopic therapy in patients with T1N0M0 esophageal cancer.	This study aims to investigate prognostic factors in patients with T1N0M0 esophageal cancer (EC) treated with endoscopic therapy (ET) and evaluate the impact of additional radiotherapy (RT) after ET. Data of patients with T1N0M0 EC undergoing ET were extracted from the Surveillance, Epidemiology, and End Results database (2004-2016). Patients were divided into ET and ET + RT groups. Propensity score matching was applied, and survival outcomes were assessed using Kaplan-Meier and Cox regression analyses, with subgroup analyses by T stage. After propensity score matching, 394 patients were included. Compared with ET alone, additional RT was associated with significantly worse overall survival and cancer-specific survival. Age, T stage, and RT were identified as independent prognostic factors. Subgroup analysis indicated that T1a patients did not benefit from RT, while T1b patients showed a slight trend toward improvement, but without statistical significance. Additional RT after ET does not improve survival in T1N0M0 EC, particularly in T1a patients, and may even be detrimental. These findings highlight the importance of individualized treatment and suggest that ET alone remains sufficient for most early-stage cases.	esophagus
Near-Infrared Photoimmunotherapy Targeting Esophagogastric Junction Adenocarcinoma With Fully Human Anti-EpCAM Antibody.	Near-infrared photoimmunotherapy (NIR-PIT) is a tumor-specific treatment using monoclonal antibody (mAb) photosensitizer conjugates, followed by near-infrared light irradiation. This study aimed to identify the optimum target for treating esophagogastric junction (EGJ) adenocarcinoma and to evaluate the efficacy of NIR-PIT using mAbs in preclinical models. Tumor samples from 46 consecutive patients who had undergone surgery without any prior treatment for EGJ adenocarcinoma were assessed for expression and homogeneity of epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), and epithelial cell adhesion molecule (EpCAM) through immunohistochemistry. Results showed positive rates of 22%, 13%, and 98% for EGFR, HER2, and EpCAM, respectively, with EpCAM also demonstrating the highest homogeneity (93%). Therefore, EpCAM was selected as the optimal target for NIR-PIT. The fully human monoclonal antibody targeting EpCAM, adecatumumab, was conjugated with the photosensitizer IR700 at different dye-antibody ratios (DAR2, DAR4, DAR7) and tested on OE19 cells and xenograft mouse models under near-infrared light irradiation. NIR-PIT with adecatumumab-IR700 significantly reduced tumor size and improved prognoses compared to controls, with DAR2 showing the best balance of efficacy and minimal side effects. Notable EpCAM expression and homogeneity underpin EpCAM as a promising target for NIR-PIT in EGJ adenocarcinoma. The fully human anti-EpCAM antibody may be suitable for NIR-PIT in EGJ adenocarcinoma.	esophagus
Genetic Variation in Background Mucosa Across Different Grades of Chronic Esophagitis.	BACKGROUND AND AIM: The risk of cancer in chronic esophagitis varies by the number of Lugol's voiding lesions (LVLs). However, how these mutations differ by LVLs grade remains unclear. We aimed to clarify the genetic characteristics of the background mucosa by LVLs grade with a history of endoscopic treatment for esophageal squamous cell carcinoma (ESCC) or squamous dysplasia (SD). METHODS: A total of 34 patients (28 ESCC, 6 SD) were classified by LVLs grade. Tissues from ESCC/SD and background mucosa were taken endoscopically, and DNA was extracted. Somatic mutations were identified in the esophageal cancer panel. For each mutation, putative drivers were identified by OncoKB, and the gene mutation patterns were compared among the grades. RESULTS: There were LVLs grade B/C = 14/20 cases. Somatic mutation of TP53 was found significantly more frequently in the LVLs than in the background mucosa (88.2% vs. 64.7%, p = 0.043, Fisher's exact test). Somatic mutations of NOTCH1, including putative drivers, were more frequent in the background mucosa than in ESCC/SD (82.3% vs. 44.1%, p = 0.002, Fisher's exact test). There was no significant difference in the percentage of putative drivers of TP53 and NOTCH1 in the background mucosa by LVLs grade B/C (50.0% vs. 35.0%, p = 0.487; 7.1% vs. 5.0%, p = 1.000, Fisher's exact test). CONCLUSION: Regardless of LVLs grade, the background mucosa of patients with chronic esophagitis who already had ESCC or SD had already accumulated the same level of TP53 gene mutations. Even patients with LVLs grade B chronic esophagitis should undergo regular endoscopic examination for early detection of ESCC.	esophagus
Oncological impact of unexpected horizontal tumour spread in oesophagogastric junction cancer.	BACKGROUND: Unexpected horizontal tumour spread towards the proximal and distal margins complicates the assessment of surgical margins in oesophagogastric junction (OGJ) cancer. Its impact on oncological outcomes remains unclear. METHODS: This study retrospectively analysed patients with OGJ adenocarcinoma undergoing proximal or total gastrectomy. Unexpected horizontal tumour spread was measured as the discrepancy between gross and pathological margins proximally (ΔPM) and distally (ΔDM). Clinicopathological features, recurrence-free survival (RFS), and overall survival (OS) were evaluated based on ΔPM and ΔDM. RESULTS: Based on cut-off values identified by time-dependent receiver operating characteristic curve analysis (ΔPM, 8 mm; ΔDM, 3 mm) in 197 patients, patients were classified into four groups: short; long ΔPM; long ΔDM; and both long ΔPM and ΔDM (both-long). RFS was best in the short group and worst in the both-long group. The long ΔPM and long ΔDM groups had intermediate and comparable RFS. Subsequently, patients were categorized into two groups: a short group and a long group, which included patients in the long ΔPM, long ΔDM, and both-long groups. The type of infiltrative growth and postoperative recurrence were significantly associated with the long group. Moreover, the long group had significantly worse RFS and OS than the short group. Multivariate Cox regression analyses identified the long group as an independent risk factor for both RFS and OS. Patients in the long group with clinical lymph node metastasis or tumours located in the proximal 2-cm segment of the OGJ, predominantly in the proximal rather than distal 2-cm segment of the OGJ, or equal involvement in both areas had markedly worse survival outcomes. CONCLUSION: Unexpected horizontal tumour spread, represented by ΔPM and ΔDM, is a strong predictor of poor survival and recurrence in OGJ cancer. Intraoperative assessment of ΔPM and ΔDM using frozen section analysis may be useful in guiding additional resections, particularly when combined with other predictive factors.	esophagus
Perioperative outcomes following neoadjuvant immunochemotherapy in elderly patients with locally advanced esophageal squamous cell carcinoma.	ObjectiveThis study compared the perioperative outcomes following neoadjuvant immunochemotherapy in elderly (≥70 years) and non-elderly patients with esophageal squamous cell carcinoma.MethodsThis retrospective study included patients with locally advanced esophageal squamous cell carcinoma who underwent neoadjuvant immunochemotherapy followed by esophagectomy (July 2020-June 2024). Patients were stratified into elderly (≥70 years) and non-elderly groups. Primary outcomes included 30-day mortality, 90-day mortality, 30-day readmission rate, and R0 resection rate. Secondary outcomes included pathological complete response, major pathological response, post-neoadjuvant pathological tumor/node stages, tumor regression grade, and complications.ResultsAmong 73 patients (25 elderly, 48 non-elderly), no 30-day or 90-day mortality occurred in either group. The 30-day readmission rates (P = 0.331) and R0 resection rates (P > 0.999) were comparable between the two groups. Secondary outcomes, including pathological complete response (P = 0.685), major pathological response (P = 0.417), post-neoadjuvant pathological tumor stage (P = 0.732), post-neoadjuvant pathological node stage (P = 0.124), and tumor regression grade (P = 0.081), also showed no significant differences. The rates of complications, including severe (P = 0.825), pulmonary (P = 0.314), and cardiac (P = 0.269) complications; anastomotic leakage (P > 0.999); recurrent laryngeal nerve palsy (P > 0.999); and wound complications (P > 0.999), were similar between the two groups.ConclusionElderly and non-elderly patients exhibited similar 30- and 90-day mortality, readmission, and R0 resection rates as well as comparable pathological responses and complication profiles following neoadjuvant immunochemotherapy. These findings indicate that age alone cannot exclude elderly patients from receiving neoadjuvant immunochemotherapy, and patients should undergo thorough individualized assessment and optimization.	esophagus
Adjuvant immunotherapy fails to improve survival in ypStage I esophageal cancer after neoadjuvant immunochemotherapy.	BACKGROUNDS: While adjuvant immunotherapy (AIT) is recommended for non-pathological complete response (non-pCR) patients, its role in ypStage I esophageal cancer (EC) patients with low tumor burden remains unclear. The study aims to evaluate the necessity of AIT for esophageal cancer patients achieving ypStage I following neoadjuvant immunochemotherapy (NICT) and surgery. METHODS: This retrospective study analyzed 157 ypStage I (ypT0-2N0M0) EC patients treated with NICT followed by surgery in Sun Yat-sen University Cancer Center between 2019 and 2024. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) adjusted for baseline imbalances between the none adjuvant therapy (NAT, n = 121)  group and AIT (n = 36) group. Survival outcomes analyses and Cox regression analyses were performed. RESULTS: In the unmatched cohorts, 3-year overall survival (3-y OS) was 93.53% (NAT) versus 87.68% (AIT) (p = 0.76), and 3-year disease-free survival (3-y DFS) was 86.38% versus 84.17% (p = 0.60). Post-PSM (OS: 91.95% vs. 87.68%, p = 0.81 and DFS: 88.58% vs. 84.17%, p = 0.45) and IPTW-adjusted analyses (OS: 93.74% vs. 87.76%, p = 0.76 and DFS: 87.96% vs. 79.08%, p = 0.60) confirmed no survival advantage for AIT. Cox regression revealed no significant prognostic value of AIT for OS (unmatched cohorts: HR = 1.29, p = 0.757; PSM: HR = 1.270, p = 0.810; and IPTW: HR = 1.760, p = 0.536) or DFS (unmatched cohorts: HR = 1.320, p = 0.597; PSM: HR = 1.720, p = 0.459; and IPTW: HR = 2.230, p = 0.207). CONCLUSIONS: Patients with ypStage I EC following NICT and surgery might not benefit from AIT. This study provides a hint for the risk-benefit balance of prolonged immunotherapy exposure in ypStage I patients while preserving clinical efficacy. Further studies are warranted.	esophagus
Fc-Engineered B7-H3 Antibody with Prolonged Serum Half-Life for Enhanced Cancer Therapy.	Monoclonal antibodies are revolutionizing the landscape of current cancer treatment, bringing hope to patients with incurable cancers. B7-H3 (CD276) is an attractive therapeutic target for antibody-based therapy due to its low or absent expression in normal tissues and high expression in various types of tumors, including prostate cancer, pancreatic cancer, and high-mortality esophageal squamous cell carcinoma (ESCC). In recent years, various B7-H3-targeting antibodies have been developed for cancer treatment, with a few making their way to clinical trials. One of the lessons learned from these practices is that for effective anticancer treatment, further modification of drug-like properties, particularly serum half-life, is crucial. In this project, we developed a humanized anti-B7-H3 antibody of strong affinity (K(D) = 0.545 nM) through a combined mouse immunization and phage display selection, followed by complementary-determining region grafting. Based on this work, we endeavored to further improve its half-life through engineering its constant fragment (Fc) by substituting two key amino acids, M428L and N434S. The resulting antibody, namely, A172-Hu3-LS, exhibited improved affinity to the neonatal Fc receptor (FcRn) while retaining its cytotoxicity against ESCC cells. Further investigation in the human FcRn transgenic mice demonstrated that this Fc-optimized antibody had a prolonged in vivo half-life (7.9 days) and potent antitumor activity. The significance of this Fc-engineering method lies in its ability to enhance the pharmacokinetic properties of therapeutic antibodies and holds potential for optimizing other therapeutic antibodies, paving the way for more effective and durable cancer treatments. While ESCC was the focus of this study, the broad expression of B7-H3 in various cancers suggests that this work may contribute to the treatment of other B7-H3-expressing tumors.	esophagus
RSK Inhibition Rewires Kinase Networks and Triggers Cascading Pathway Disruption in Esophageal Cancer.	RSK plays a central role in oncogenic signaling, yet its broader regulatory impact in esophageal squamous cell carcinoma (ESCC) remains unclear. We performed integrated phosphoproteomics and kinase-substrate network analysis to elucidate global signaling alterations following RSK inhibition in ESCC cells. In Eca-109 cells, treatment with a moderate concentration of the selective RSK inhibitor SL0101 effectively suppressed proliferation without inducing apoptosis. To elucidate potential compensatory survival mechanisms, we performed integrated proteomic and phosphoproteomic analyses, which revealed that RSK inhibition provokes broad cellular adaptations. Importantly, the magnitude of these effects varied across pathways. Ribosome biogenesis and mitochondrial organization exhibited substantial perturbation primarily at the proteomic level, reflecting system-level dysregulation. Phosphoproteomic analysis revealed that large-magnitude alterations in nuclear transport and mRNA processing, and more subtle, fine-tuned modulation of mitotic fidelity. Kinase activity inference further identified MAPK14, CDK2, SRPK3, AKT1, PLK1, and PIM2 as principal regulators that may regulate compensatory signaling in response to RSK suppression. Taken together, our study reveals that RSK inhibition reprograms kinase networks to enforce stress adaptation, maintaining oncogenic homeostasis despite perturbations. These findings highlight a potential therapeutic window for early intervention strategies, suggesting that combination strategies may enhance the efficacy of RSK-directed therapies in ESCC.	esophagus
New Gene Signature-Based Prognostic Model for Patients With VEGF-Overexpressing Esophageal Squamous Cell Carcinoma.	BACKGROUND AND AIMS: The effects of vascular endothelial growth factor (VEGF) overexpression on the prognosis of patients with esophageal squamous cell carcinoma (ESCC) are still unclear. The aim of this study was to construct and evaluate a mutant gene-based model to predict the prognosis of ESCC patients with VEGF overexpression. METHODS: Samples from 50 ESCC patients with VEGF overexpression were subjected to next-generation sequencing (NGS) to identify gene mutations. The associations between the enrichment of these mutations and patient outcomes were also evaluated in a cohort from The Cancer Genome Atlas. Hazard ratios were identified via the Kaplan-Meier and Cox analyses. A support vector machine recursive feature elimination algorithm was used to construct the model, and receiver operating characteristic analysis was carried out to evaluate its prognostic performance. RESULTS: ESCC patients with FAT1, FGF3, FGF12, and FGF19 mutations; advanced M stage; and high neutrophil counts tended to have poorer prognoses. CONCLUSION: A model based on a four-gene signature effectively predicts the prognosis of ESCC patients.	esophagus
Prior-guided automatic delineation of post-radiotherapy gross tumor volume for esophageal cancer.	BACKGROUND: Integrating post-radiotherapy (RT) CT into longitudinal esophageal cancer response models substantially improves predictive accuracy. However, manual delineation of gross tumor volume (GTV) on post-RT CT is both labor-intensive and time-consuming. PURPOSE: We propose a novel deep learning-based framework that integrates medical physics priors-pre-RT GTV contours and radiotherapy dose distributions-to automatically delineate post-RT GTV. METHODS: A multicenter retrospective cohort of 294 EC patients (225 training, 45 internal validation, 24 external validation) was assembled. Pre-RT CT scans, GTV contours, and dose map were co-registered and cropped to 256 × 256. We implemented an nnU-Net v2 backbone, incorporating high dose region and pre-RT GTV priors via element-wise multiplication and element-wise addition to guide feature extraction. Performance was evaluated using anatomical (Dice, IoU, HD95, ASSD, Precision, Recall) and radiomics analyses (ICC, Pearson correlation, LASSO-Cox, C-index) across internal and external cohorts. RESULTS: In cross-validation, the optimal fold achieved DSC = 0.7809 ± 0.1310, IoU = 0.6486 ± 0.1507, HD95 = 3.6321 ± 2.0942, and ASSD = 1.9673 ± 1.0352 (p < 0.0167 vs. state-of-the-art models). Ablation studies demonstrated that combining two types of medical physics priors outperformed single-prior or no-prior models (internal: DSC = 0.7723 ± 0.1290; external: DSC = 0.7545 ± 0.1058). Radiomic features extracted from automated contours exhibited high reproducibility (78.6% with ICC > 0.75) and strong concordance with manual features (R >  0.8), yielding comparable prognostic performance (C-index Δ nonsignificant). CONCLUSION: By embedding medical physics priors into a self-configuring nnU-Net v2, our method achieves accurate and robust automated delineation of post- RT GTV in EC across multiple centers. This approach has potential to facilitate the construction of treatment response prediction models.	esophagus