crossing96/oncoscreening huggingface dataset:
Regorafenib combined with irinotecan as second-line treatment in metastatic gastro-oesophageal adenocarcinomas: results of PRODIGE 58-UCGI35-REGIRI Unicancer randomised phase II study.	BACKGROUND: Several options have been evaluated in metastatic gastro-oesophageal adenocarcinomas (mGA) after failure of first-line fluoropyrimidine and platinum-based chemotherapy. Regorafenib (REGO), a receptor tyrosine kinase inhibitor, has shown promising activity as second- and third-line treatment of mGA. PATIENTS AND METHODS: PRODIGE58-UCGI35-REGIRI was a comparative, prospective, phase II, open-label study evaluating the safety and efficacy of REGO [160 mg/day on day 2 (D2)-D8/D16-D22] plus irinotecan (IRI: 180 mg/m(2) intravenously on D1/D15 every 28 days) versus IRI alone in patients with mGA (gastric or gastro-oesophageal junction/tumour Siewert II and III) after failure of first-line fluoropyrimidine and platinum-based chemotherapy. Primary endpoint was overall survival (OS). RESULTS: Forty-four patients were included in the REGIRI arm and 45 in the IRI arm, primary tumours (67.4%) were mainly localised in the gastro-oesophageal junction, and 60.7% patients had synchronous metastases. With a median follow-up of 19.4 months [95% confidence interval (CI) 16.8-29.9 months], median OS was 6.3 months (95% CI 5.2-7.1 months) versus 8.2 months (95% CI 5.2-9.7 months) in the REGIRI versus IRI arms (hazard ratio 1.11, 95% CI 0.70-1.74, P = 0.66). Median progression-free survival was 2.2 months versus 1.9 months, objective response rate 15.9% versus 13.3%, and disease control rate 45.5% versus 33.3%. Grade 3 treatment-related adverse events (AEs) were reported for 52.3% of patients in the REGIRI arm versus 23.3% in the IRI arm with four toxic deaths (two homozygous UGT1A1∗28 patients died from sepsis and thrombotic microangiopathy, and two heterozygous UGT1A1∗1/∗28 patients from diarrhoea and pulmonary embolism), versus one (UGT1A1∗1 wild-type patient died from primary tumour perforation). Main grade ≥3 AEs were diarrhoea (18.2% versus 7.0%), hypertension (9.1% versus 0.0%), asthenia (6.8% versus 0.0%), febrile neutropenia (6.8% versus 0.0%), neutropenia (6.8% versus 11.6%), and weight decrease (6.8% versus 0.0%). CONCLUSIONS: The study was stopped early because of limited efficacy and increased toxicities in the REGIRI arm, possibly due to drug interactions. No optimal sub-population that could benefit from a REGIRI regimen exposure was identified.	esophagus
L1 Capsid Protein Expression in HPV-Positive Barrett Metaplasia-Dysplasia-Adenocarcinoma Lesions.	INTRODUCTION: Human papillomavirus (HPV) has been associated with a subset of Barrett dysplasia and esophageal adenocarcinoma (EAC). The HPV L1 capsid protein has been closely linked to disease regression and is a prognostic factor in HPV-driven cancers of the cervix and anus. METHODS: Thus, we investigated L1 protein expression in HPV-positive patients representing the esophageal squamous-Barrett metaplasia-dysplasia-adenocarcinoma sequence. L1 protein immunohistochemical staining was correlated with p16 overexpression and E6/E7 mRNA in situ hybridization. RESULTS: Of 116 HPV DNA-positive patients ([age range: 19-90, mean [SD], 63.2 [13.5], 88 men and 28 women), 73 (62.9%) were genotype 16, 37 (31.9%) genotype 18, and 6 (5.2%) were genotype 6. L1 staining was identified in 64 individuals: 84.9% (28/33) controls, 94.1% (16/17) Barrett's esophagus, 50% (7/14) low-grade dysplasia, (8/21) 38.1% high-grade dysplasia, and 16.1% (5/31) EAC (adjusted P < 0.0001). Conversely, p16 was present in 9.1% (3/33) of controls, 17.7% (3/17) Barrett's esophagus, 57.1% (8/14) low-grade dysplasia, 61.9% (13/21) high-grade dysplasia, and 64.5% (20/31) of EAC patients ( P < 0.0001). Corresponding figures for E6/E7 mRNA positivity was 6.1% (2/33), 23.5% (4/17), 28.6% (4/14), 38.1% (8/21), and 45.2% (14/31), respectively ( P = 0.008). Expression of HPV-L1 and p16 or L1 and E6/E7 mRNA was largely mutually exclusive. DISCUSSION: HPV L1 capsid expression is incrementally lost with increasing esophageal disease severity as in viral-driven anal and cervical lesions. Utility of L1 alone or in combination with p16 and or E6/E7 mRNA in stratifying HPV-positive patients for treatment should be explored in a prospective longitudinal investigation.	esophagus
Surface-enhanced confocal Raman microscopy to characterize esophageal cancer cell-derived extracellular vesicles and maternal cells.	Exosomes, a subtype of extracellular vesicles, are increasingly recognized as promising biomarkers for human cancers. Rapid detection and classification of esophageal cancer-associated exosomes could significantly improve non-invasive screening for potential patients. This study aims to establish a label-free, direct surface-enhanced Raman scattering (SERS) method to capture characteristic molecular information from both esophageal cancer cells and their corresponding exosomes using confocal Raman microscopy. The results revealed distinct Raman spectra for esophageal cancer cells and their exosomes within the range of 500-1600 cm(-1), with notable signal similarities observed at 506-622, 778-832, 1079-1098, and 1572-1630 cm(-1). In contrast, significant differences were identified in Raman peaks related to nucleic acids (723, 654, 1354 cm(-1)) and proteins (998, 1028, 1354, 1560 cm(-1)). An orthogonal partial least squares discriminant analysis (OPLS-DA) model was utilized to discern subtle variations among these highly similar samples, achieving an accuracy rate of 100%. By comparing the spectral correlations between esophageal cancer cells and their exosomes, this study provides valuable insights into the molecular composition and cellular origins of exosomes. The findings demonstrate the potential of integrating SERS with OPLS-DA for the precise and rapid detection and monitoring of esophageal cancer through exosomal biomarkers, offering a powerful tool for diagnostic applications.	esophagus
Delivery of cancer cell-derived extracellular vesicles modulates the morphology and gene expression of Barrett esophagus and duodenal organoids (Article).	Extracellular vesicles (EVs) facilitate intercellular communication, especially in the signaling mechanisms employed by tumor cells to influence both local and distant cells and tissues. This study investigated the impact of cancer cell-derived EVs (CEVs) on patient-derived organoids. Co-culture experiments examined the morphology, growth, proliferation, and cancer-related gene/miRNA expression in Barrett's esophagus (BE) and duodenal organoids. Our results indicate that CEVs promoted organoid proliferation, increased cancer-related mRNA/miRNA expression, and induced phenotypic changes. Artificial modulation of specific oncomiRNAs in CEVs-such as miR-21 and miR-210, influenced CEV-mediated effects on co-cultured organoid growth. These findings align with EV-mediated transformations in benign organoid models, providing a valuable tool to study EV-associated miRNAs/proteins in gastrointestinal preneoplastic/neoplastic conditions and potentially other organs. This lays a foundation for future research on cancer cell-microenvironment interactions and EV roles in tumorigenesis/metastasis.	esophagus
Type of anastomosis and risk of anastomotic insufficiency after oesophagectomy: a bi-national population-based cohort study.	BACKGROUND: It is uncertain which type of anastomosis carries the lowest risk of anastomotic insufficiency after oesophagectomy for oesophageal cancer. We aimed to compare handsewn with stapled anastomosis (any type, linear or circular), and handsewn end-to-side with handsewn end-to-end anastomosis. METHODS: This bi-national population-based cohort study included almost all patients (>95 %) who underwent oesophagectomy for cancer in Sweden from 2011 to 2020 or in Finland from 2004 to 2016. Multivariable logistic regression produced odds ratios (OR) with 95 % confidence intervals (CI), adjusted for age, sex, comorbidity, tumour histology, neoadjuvant chemo(radio)therapy, surgical approach, anastomosis location, hospital volume, and pathological tumour stage. RESULTS: Among 2166 study patients, 327 (15 %) had anastomotic insufficiency. The risk of anastomotic insufficiency was borderline significantly decreased in handsewn anastomosis compared to stapled anastomosis (OR = 0.79, 95 % CI 0.60-1.05). In patients who underwent minimally invasive oesophagectomy, handsewn anastomosis was associated with a decreased risk compared to stapled anastomosis (OR = 0.55, 95 % CI 0.35-0.85; n = 999), while no such association was found after open oesophagectomy (OR = 1.04, 95 % CI 0.72-1.51; n = 1167). There were no statistically significant associations with anastomotic insufficiency when comparing linear stapled with circular stapled anastomosis (OR = 1.27, 95 % CI 0.70-2.28; n = 736) or handsewn with circular stapled anastomosis (OR = 0.94, 95 % CI 0.63-1.40; n = 1324). Handsewn end-to-side anastomosis was associated with a borderline increased risk of anastomotic insufficiency compared to handsewn end-to-end anastomosis (OR = 1.61, 95 % CI 0.93-2.78; n = 786). CONCLUSIONS: Regarding anastomotic insufficiency, handsewn anastomosis may be favourable compared to stapled in minimally invasive oesophagectomy for oesophageal cancer, while no such benefit was found for open oesophagectomy.	esophagus
Exploring the relationship between postoperative psychological resilience and symptom burden in esophageal cancer patients.	PURPOSE: Psychological resilience (PR) is an important internal resource for alleviating symptom burden in esophageal cancer surgery patients. However, the relationship between PR and symptom burden has not been explored to date. The primary purpose of this study is to determine the relationship between these two variables. METHODS: This multi-center cross-sectional study analyzed data from 486 esophageal cancer surgery patients (2022-2024), assessing symptom burden and PR using the Convalescence Symptom Assessment Scale for Esophagectomy Patients and the Connor-Davidson Resilience Scale. Symptom burden was visualized with radar charts, and network analysis identified the relationship between PR and symptom burden. RESULTS: Esophageal cancer patients experienced a significant symptom burden in the early postoperative period. Network analysis revealed that helplessness (Bridge Strength = 0.23), close and secure relationships (Bridge Strength = 0.21), disturbed sleep (Bridge Strength = 0.11), and pride in your achievements (Bridge Strength = 0.08) were bridge nodes connecting the combination network. Among these, helplessness was identified as a critical factor in initiating and sustaining the relationship between PR and symptom burden. CONCLUSIONS: PR plays a crucial role in alleviating symptom burden. This study identifies the bridge nodes in the combination network of PR and symptom burden in esophageal cancer patients. Implementing interventions targeting these factors may enhance the precision and effectiveness of symptom management.	esophagus
Knockdown NEK7 stimulates anti-tumor immune responses by NLRP3/PD-L1 signaling in esophageal cancer.	BACKGROUND: Esophageal cancer is a prevalent malignancy with limited treatment options. The study aimed to understand the role and mechanism of NEK7 in esophageal cancer development. METHODS: RNA sequencing compared esophageal cancer tissues with adjacent tissues, and real-time PCR validated NEK7 expression. Co-IP identified NLRP3 as NEK7's binding partner. We also study the effects of NEK7 knockdown on cell viability, apoptosis, migration, invasion, and the expression of NLRP3/PD-L1 in esophageal carcinoma cell lines. TIMER 2.0 analyzed immune infiltration. An animal model was used to investigate the impact of NEK7 knockdown on tumor size, survival rates, and immune cell infiltration. Licochalcone B blocked NEK7/NLRP3, enhancing CD8 T cell-mediated tumor killing. PD-1's role in T cell viability was also assessed. RESULTS: NEK7 was observed to be markedly elevated in both tumor tissues of esophageal cancer and EC109 cells. Moreover, silencing NEK7 reduced cell viability, migration, and invasion, while enhancing cell apoptosis in vitro. Knockdown of NEK7 caused a notable reduction in levels of NLRP3 and PD-L1 in EC109 cells. NEK7 expression showed a positive correlation with immune cell infiltration. Knockdown of NEK7 decreased PD-L1 expression, while upregulation of NEK7 increased PD-L1 expression, then reversed by NLRP3 knockdown. In animal studies, NEK7 knockdown reduced tumor size and volume while improving survival. It also promoted CD4 and CD8 T cell infiltration while inhibiting Treg cells and PD-1 + CD4 and CD8 T cells. Licochalcone B blocked NEK7/NLRP3 binding, decreased cell viability of EC109 cells, and enhanced the activity of co-cultured CD8 T cells. Furthermore, Licochalcone B and anti-PD-1 treatment increased the killing ratio of EC109 cells. CONCLUSION: In conclusion, NEK7 is a key regulator in the progression of esophageal cancer and the immune evasion. Targeting the NEK7/NLRP3 pathway may have therapeutic potential for the treatment of esophageal cancer.	esophagus
Postoperative Recurrence Pattern of Clinical Stage I Esophageal Cancer After Esophagectomy with Two- or Three-Field Lymph Node Dissection: Supplementary Analysis from JCOG0502.	BACKGROUND: Although recurrence after curative surgery for cT1bN0M0 clinical stage I (cStage I) esophageal squamous cell carcinoma (ESCC) is not rare, reports of recurrence analyses are sparse. Detailed data on optimal postoperative follow-up evaluation of cStage I ESCC are lacking. This study aimed to evaluate the frequency, characteristics, and predictors of postoperative recurrence in patients with cT1bN0M0 cStage I ESCC. METHODS: The study analyzed 210 patients who underwent surgery for cT1bN0M0 cStage I ESCC and a follow-up computed tomography (CT) examination in the prospective multicenter study, JCOG0502. The study categorized the characteristics of postoperative recurrences such as the recurrence sites and whether regional/non-regional lymph nodes (LNs) and single/multiple organs were involved. Backward elimination was applied (p < 0.2) to identify postoperative recurrence predictors and obtained hazard ratios (HRs) based on Fine and Gray's model. RESULTS: Postoperative recurrence was experienced by 31 patients (14.8%) at one or more of the following sites: regional LNs (n = 18), non-regional LNs (n = 10), lung (n = 2); bone (n = 2), and liver, local recurrence, skin, pleura, pericardium, and other (n = 1 each). In four patients, the first recurrence developed in multiple organs. The median interval between trial registration and the first recurrence was 18.6 months. In multivariable analyses, pathologic nodal metastasis (hazard ratio [HR], 3.29; p = 0.003), tumor location in the upper-thoracic esophagus versus lower-thoracic esophagus (HR, 6.71; p = 0.013), and two-field lymphadenectomy (HR, 4.31; p = 0.001) were independently associated with the development of postoperative recurrence. CONCLUSION: The main postoperative recurrence sites of cT1bN0M0 ESCC are the LNs, but recurrence in non-regional LNs or distant organs is also quite common, indicating the importance of post-surgery systemic follow-up evaluation.	esophagus
Vascularity of the gastric conduit predicts complications after Ivor-Lewis esophagectomy.	BACKGROUND: Anastomotic leakage (AL) contributes to postoperative morbidity and mortality after Ivor-Lewis esophagectomy. Vascular high-risk patients show a significantly increased risk of AL. We previously showed that laparoscopic ischemic conditioning (ISCON) of the stomach prior esophagectomy in these high-risk patients is a safe procedure that induces neoangiogenesis at the anastomotic site. Our data also suggested that this directly impacts on anastomotic healing. To further investigate the hypothesis that gastric conduit vascularization directly influences postoperative morbidity, we evaluated gastric conduit vascularity in a cohort of patients undergoing two-stage esophagectomy prior to the ISCON era. MATERIAL AND METHODS: Seventy-nine patients who underwent two-stage esophagectomy from 2016 to 2021 at our center were retrospectively analyzed from a prospectively maintained database. Microvessel density (MVD) of the gastric conduit at the anastomotic region was evaluated by CD34 staining of the gastric stapler ring. Analysis of microvessel density (MVD) was performed using ImageJ. Patients were stratified into low- and high-MVD groups, and MVD was correlated with clinical outcomes. RESULTS: Patients with a high MVD showed a significantly lower rate of anastomotic leakage (AL) in comparison to patients with low MVD (6.25% vs. 22.58% p=0.043). Furthermore, a high MVD was associated with a lower rate of major complications (Clavien Dindo ≥ IIIb) (12.50% vs. 38.71% p=0.012) and a shorter hospital stay (17.9 days vs. 23.1 days, p=0.045). CONCLUSION: Vascularization of the stomach might function as surgical biomarker of AL in patients undergoing two-stage esophagectomy. Prospective trials have to further substantiate this finding.	esophagus
Concurrent pathological scar: independent risk factor for esophageal stricture after endoscopic submucosal dissection.	BACKGROUND AND AIMS: Esophageal stricture is a common complication after esophageal endoscopic submucosal dissection (ESD). Pathological scars may predict stricture development, but clinical studies exploring their relationship are limited. This study aimed to investigate the link between concurrent pathological scarring and post-ESD esophageal stricture and develop a predictive risk model. METHODS: This retrospective single-center study included patients who underwent ESD for superficial esophageal lesions (SELs) over the past decade. Data on demographics, endoscopy, pathology, and concurrent scarring were collected. Multivariate logistic regression identified risk factors, followed by validation using subgroup analysis and propensity score matching. A nomogram was developed and internally validated. RESULTS: Of 255 patients, 28 (11.0%) developed esophageal stricture. Multivariate logistic regression identified concurrent pathological scarring as an independent risk factor for stricture development (OR 96.520 [10.641-875.536], p < 0.001). Additional risk factors included lesions in the upper esophagus, lesions longer than 4 cm, circumferential involvement over 50%, infiltration depth beyond the epithelium, and muscular layer injury during the procedure. A predictive model incorporating these factors was developed, demonstrating high discriminative ability (AUC 0.943 [0.902-0.984]) with an optimal cutoff of 135.6, sensitivity of 82.4%, and specificity of 94.3%. The calibration curve showed good accuracy. CONCLUSIONS: Concurrent pathological scarring is an independent risk factor for post-ESD esophageal stricture.	esophagus
Biomarker-Driven Approach to the Treatment of Metastatic Gastric or Gastroesophageal Adenocarcinoma.	The last 2 decades have seen a paradigm shift in the treatment landscape of metastatic gastric and gastroesophageal adenocarcinomas, with most of the progress occurring in recent years. Following the pivotal ToGA trial and the approval of trastuzumab for HER2-positive disease, the search for biomarkers has advanced exponentially. Currently, therapies are guided by key biomarkers such as HER2, PD-L1, dMMR/MSI-H, and, most recently, CLDN18.2. FGFR2b is emerging as a potential biomarker in this field. The most recent addition to this therapeutic arsenal is zolbetuximab. Two recent phase III trials have demonstrated survival benefits with the addition of zolbetuximab to frontline chemotherapy. A number of other biomarker-driven clinical trials are in progress, investigating new targeted agents that are expected to further transform the management of gastric or gastroesophageal adenocarcinoma.	esophagus
Preoperative chemoradiotherapy for esophageal or gastroesophageal junction cancer: results from a retrospective study using extended CROSS regimen.	BACKGROUND: The standard of care for locally advanced esophageal cancer includes perioperative chemotherapy or neo-adjuvant chemo-radiotherapy (CRT), followed by surgery. At our institution, a modified neo-adjuvant regimen combining elements from CROSS and CALGB 9781 trials was adopted. This study aimed to assess the impact of our modified regimen on oncological outcomes, toxicity profile and pathological complete response rates compared to the CROSS trial. METHODS: This observational study included patients with esophageal cancer who underwent neo-adjuvant CRT followed by tumor resection at a tertiary care university hospital between 2014 and 2018. The modified radiation therapy consisted of 28 fractions of 1.8 Gy (50.4 Gy in total) with weekly carboplatin/paclitaxel. We assessed mortality over time using the median survival time. The impact of pathological complete response and radiation intensity on mortality was assessed in multivariable Cox regression analysis, adjusting for clinically relevant variables, including sex, age, American Society of Anesthesiologists (ASA) physical status classification system score, tumor and nodal stage, and the histological tumor type. RESULTS: A total of 46 patients were included. Median age was 67 years (IQR 9), 36 patients (78.3%) were male. An ASA score ≥ 3 was reported in 90.7% of the patients. Among the patients, 38 (82.6%) had a clinical tumor stage (cT) of ≥ 3, and 42 (91.3%) showed a positive endo-sonographic nodal stage (uN+). Pathological complete response was found in 7/42 patients (16.7%). Median survival time was 2.7 years (95% CI 1.340-4.084). In multivariable Cox regression analysis, pathological complete response was associated with significantly lower mortality over time (OR 0.152, 95%CI 0.049-0.989, p = 0.048). For larger radiation volumes, a trend towards increased mortality was shown, although not statistically significant (radiation volume/100: OR 1.172, 95%CI 0.987-1.392). CONCLUSIONS: In patients with esophageal cancer undergoing trimodal therapy, the radiation dose escalation to 50.4 Gy was not associated with higher rates of pathological complete response or a survival benefit compared to the results of the CROSS trial. However, multivariable analysis revealed a trend toward increased mortality with larger radiation volumes. Based on these results, using modern radiotherapy techniques such as online adaptive radiotherapy might be more beneficial instead of escalating the radiation dose.	esophagus
Evolving Therapeutics for Resectable Esophageal Adenocarcinoma.	Surgical resection remains the backbone of curative treatment for localized esophageal adenocarcinoma. However, resection alone carries a significant risk of recurrence and is no longer considered an acceptable approach for patients with locally advanced disease. Strategies incorporating perioperative chemotherapy, neoadjuvant chemoradiotherapy, and adjuvant immune checkpoint blockade have significantly improved survival. However, despite these advances, approximately half of all patients with locally advanced disease will experience recurrence and ultimately succumb to their disease. To overcome this innate resistance to cytotoxic therapy, novel strategies are being developed. This review discusses both evidence-based and emerging perioperative approaches and explores potential risk-adapted strategies to individualize perioperative therapy.	esophagus