crossing96/oncoscreening huggingface dataset:
Circulating tumor DNA predicts outcome in metastatic gastroesophageal cancer.	BACKGROUND: Circulating tumor DNA (ctDNA) has predictive and prognostic value in localized and metastatic cancer. This study analyzed the prognostic value of baseline and on-treatment ctDNA in metastatic gastroesophageal cancer (mGEC) using a region-specific next generation sequencing (NGS) panel. METHODS: Cell free DNA was isolated from plasma of patients before start of first-line palliative systemic treatment and after 9 and 18 weeks. Two NGS panels were designed comprising the most frequently mutated genes and targetable mutations in GEC. Tumor-derived mutations in matched metastatic biopsies were used to validate that the sequencing panels assessed true tumor-derived variants. Tumor volumes were calculated from baseline CT scans and correlated to variant allele frequency (VAF). Survival analyses were performed using univariable and multivariable Cox-regression analyses. RESULTS: ctDNA was detected in pretreatment plasma in 75% of 72 patients and correlated well with mutations in metastatic biopsies (86% accordance). The VAF correlated with baseline tumor volume (Pearson's R 0.53, p < 0.0001). Detection of multiple gene mutations at baseline in plasma was associated with worse overall survival (OS, HR 2.16, 95% CI 1.10-4.28; p = 0.027) and progression free survival (PFS, HR 2.71, 95% CI 1.28-5.73; p = 0.009). OS and PFS were inferior in patients with residual detectable ctDNA after 9 weeks of treatment (OS: HR 4.95, 95% CI 1.53-16.04; p = 0.008; PFS: HR 4.08, 95% CI 1.31-12.75; p = 0.016). CONCLUSION: Based on our NGS panel, the number of ctDNA mutations before start of first-line chemotherapy has prognostic value. Moreover, residual ctDNA after three cycles of systemic treatment is associated with inferior survival.	esophagus
Severity of oEsophageal Anastomotic Leak in patients after oesophagectomy: the SEAL score.	BACKGROUND: Anastomotic leak (AL) is a common but severe complication after oesophagectomy. It is unknown how to determine the severity of AL objectively at diagnosis. Determining leak severity may guide treatment decisions and improve future research. This study aimed to identify leak-related prognostic factors for mortality, and to develop a Severity of oEsophageal Anastomotic Leak (SEAL) score. METHODS: This international, retrospective cohort study in 71 centres worldwide included patients with AL after oesophagectomy between 2011 and 2019. The primary endpoint was 90-day mortality. Leak-related prognostic factors were identified after adjusting for confounders and were included in multivariable logistic regression to develop the SEAL score. Four classes of leak severity (mild, moderate, severe, and critical) were defined based on the risk of 90-day mortality, and the score was validated internally. RESULTS: Some 1509 patients with AL were included and the 90-day mortality rate was 11.7 per cent. Twelve leak-related prognostic factors were included in the SEAL score. The score showed good calibration and discrimination (c-index 0.77, 95 per cent c.i. 0.73 to 0.81). Higher classes of leak severity graded by the SEAL score were associated with a significant increase in duration of ICU stay, healing time, Comprehensive Complication Index score, and Esophagectomy Complications Consensus Group classification. CONCLUSION: The SEAL score grades leak severity into four classes by combining 12 leak-related predictors and can be used to the assess severity of AL after oesophagectomy.	esophagus
Folate Receptor 4-Expressing T cell Is Associated with Disease-Free Survival in Patients with Esophageal Squamous Cell Carcinoma.	BACKGROUND: Folic acid receptor 4 (FR4) significantly downregulates the expression of regular T cells (Treg) and improves the effect of chemotherapy and PD-1/PD-L1 inhibitors. However, the FR4 expression in squamous cell carcinoma (ESCC) remains unclear. METHODS: Patients with primary ESCC who visited our hospital between 1(st) February 2012 and 30(th) September 2016 were enrolled in this study. FR4 expressions in ESCC patients were detected by immunohistochemistry staining, and the association with clinical characteristics and the overall survival (OS) or disease-free survival (DFS) was analyzed. RESULTS: One hundred and forty-eight qualified cases of ESCC patients were retrieved, including 34 females. Ninety-four cases had lymph node metastasis (63.51%), 104 patients received adjuvant therapy (70.27%), and the rate of FR4 positive was 67.57% (100/148). Among FR4 positive patients, 75 cases received adjuvant therapy, and patients who received chemotherapy were significantly better than that of patients who did not receive chemotherapy. In patients with FR4 negative expression, 48 cases received adjuvant therapy, which was significantly worse than that of patients who did not receive chemotherapy. CONCLUSIONS: Postoperative adjuvant chemotherapy prolonged the survival in FR4 positive ESCC patients, whereas adjuvant therapy in patients with FR4 negative needs to be further improved.	esophagus
Incidence and survival of patients with oligometastatic esophagogastric cancer: A multicenter cohort study.	PURPOSE/OBJECTIVE: This multicenter study assessed the incidence and survival of patients with esophagogastric cancer and oligometastatic disease (OMD) in two tertiary referral cancer centers in The Netherlands and Switzerland. MATERIALS/METHODS: Between 2010 and 2021, patients with metastatic esophagogastric cancer were identified. Patients with de-novo OMD were included (first-time diagnosis of ≤5 distant metastases on (18)F-FDG-PET/CT). Control of the primary tumor was considered in patients who underwent primary tumor resection or definitive chemoradiotherapy without locoregional recurrence. Treatment of OMD was categorized into (1) systemic therapy, (2) local treatment (stereotactic body radiotherapy or metastasectomy), (3) local plus systemic therapy, or (4) best supportive care. The primary outcomes were overall survival (OS) and independent prognostic factors for OS. Independent prognostic factors for OS were analyzed using multivariable Cox proportional hazard models. RESULTS: In total, 830 patients with metastatic esophagogastric cancer were identified of whom 200 patients with de-novo OMD were included (24%). The majority of included patients had esophageal cancer (73%) with adenocarcinoma histology (79%) and metachronous OMD (52%). The primary tumor was controlled in 68%. Treatment of OMD was systemic therapy (25%), local treatment (43%), local plus systemic therapy (13%), or best supportive care (18%). Median follow-up was 14 months (interquartile range: 7-27). Median OS was 16 months (95% CI: 13-21). Improved OS was independently associated with local plus systemic therapy compared with systemic therapy alone (hazard ratio [HR] 0.47, 95% confidence interval [CI]: 0.25-0.87). Worse OS was independently associated with squamous cell carcinoma (HR 1.70, 95% CI: 1.07-2.74), bone oligometastases (HR 2.44, 95% CI: 1.28-4.68), brain oligometastases (HR 1.98, 95% CI: 1.05-4.69), and two metastatic locations (HR 2.07, 95% CI: 1.04-4.12). Median OS after local plus systemic therapy was 35 months (95% CI: 22-NA) as compared with 13 months (95% CI: 9-21, p < 0.001) after systemic therapy alone for OMD. CONCLUSION: Patients with metastatic esophagogastric cancer present in 25% with de-novo OMD. Local treatment of OMD plus systemic therapy was independently associated with long-term OS and independently improved OS when compared with systemic therapy alone. Randomized controlled trials are warranted to confirm these results.	esophagus
Clinical relevance of tertiary lymphoid structures in esophageal squamous cell carcinoma.	BACKGROUND: Tertiary lymphoid structures (TLSs) have been reported to be involved in immune responses in many carcinomas. This study investigated the significance of TLSs in esophageal squamous cell carcinoma, focusing on TLS maturation. METHODS: The relationships of TLSs with clinicopathological features of 236 patients who underwent curative surgery for stage 0-IV esophageal squamous cell carcinoma were investigated. Mature TLSs, in which the germinal center formation was rich in CD23(+) cells, were classified as TLSs containing a germinal center (GC-TLSs). GC-TLS densities were measured, and CD8(+) cells were counted. The prognostic impact of GC-TLSs was assessed by Kaplan-Meier plots using the log-rank test for the relapse-free survival. A comparative study of GC-TLSs was performed using the Wilcoxon rank sum test. The relationship between GC-TLSs and CD8(+) cells was examined by Spearman's rank correlation coefficient test. RESULTS: TLSs were located mainly at the invasive margin of the tumor in cases with esophageal squamous cell carcinoma. Among the patients treated with neoadjuvant chemotherapy, those with advanced disease had a better prognosis in the GC-TLS high-density group than did those in the GC-TLS low-density group. Patients in whom neoadjuvant chemotherapy was effective had more GC-TLSs than those in whom it was less effective. The density of GC-TLSs and the number of tumor-infiltrating CD8(+) cells were higher in patients treated with neoadjuvant chemotherapy than in those without chemotherapy, and a weak correlation between the density of GC-TLSs and the number of tumor-infiltrating CD8(+) cells was observed. Moreover, co-culturing of PBMCs with an anticancer drug-treated esophageal squamous cell carcinoma cell line increased the CD20 and CD23 expression in PBMCs in vitro. CONCLUSION: TLS maturation may be important for evaluating the local tumor immune response in patients treated with neoadjuvant chemotherapy for esophageal squamous cell carcinoma. The present results suggest that TLS maturation may be a useful target for predicting the efficacy of immunotherapy, including immune checkpoint inhibitor treatment for esophageal squamous cell carcinoma.	esophagus
CT-based radiomics nomogram may predict local recurrence-free survival in esophageal cancer patients receiving definitive chemoradiation or radiotherapy: A multicenter study.	BACKGROUND AND PURPOSE: To establish and validate a contrast-enhanced computed tomography-based hybrid radiomics nomogram for prediction of local recurrence-free survival (LRFS) in esophageal squamous cell cancer (ESCC) patients receiving definitive (chemo)radiotherapy in a multicenter setting. MATERIALS AND METHODS: This retrospective study included 302 ESCC patients from Xijing Hospital receiving definitive (chemo)radiotherapy, which were randomly assigned to the training (n = 201) and internal validation sets (n = 101). And 74 and 21 ESCC patients from the other two centers were used as the external validation set (n = 95). A hybrid radiomics nomogram was established by integrating clinical factors, radiomic signature and deep-learning signature in training set and was tested in two validation sets. RESULTS: The deep-learning signature showed better prognostic performance than radiomic signature for predicting LRFS in training (C-index: 0.73 vs 0.70), internal (Cindex: 0.72 vs 0.64) and external validation sets (C-index: 0.72 vs 0.63), which could stratify patients into high and low-risk group with different prognosis (cut-off value: -0.06). Low-risk groups had better LRFS than high-risk groups in training (p < 0.0001; 2-y LRFS 71.1% vs 33.0%), internal (p < 0.01; 2-y LRFS 58.8% vs 34.8%) and external validation sets (p < 0.0001; 2-y LRFS 61.9% vs 22.4%), respectively. The hybrid radiomics nomogram established by integrating radiomic signature, deep-learning signature with clinical factors including T stage and concurrent chemotherapy outperformed any one or two combinations in training (C-index: 0.82), internal (Cindex: 0.78), and external validation sets (C-index: 0.76). Calibration curves showed good agreement. CONCLUSIONS: The hybrid radiomics based on pretreatment contrast-enhanced computed tomography provided a promising way to predict local recurrence of ESCC patients receiving definitive (chemo)radiotherapy.	esophagus
(89)Zr-Labeled High-Density Lipoprotein Nanoparticle PET Imaging Reveals Tumor Uptake in Patients with Esophageal Cancer.	Nanomedicine holds promise for the delivery of therapeutic and imaging agents to improve cancer treatment outcomes. Preclinical studies have demonstrated that high-density lipoprotein (HDL) nanoparticles accumulate in tumor tissue on intravenous administration. Whether this HDL-based nanomedicine concept is feasible in patients is unexplored. Using a multimodal imaging approach, we aimed to assess tumor uptake of exogenously administered HDL nanoparticles in patients with esophageal cancer. Methods: The HDL mimetic CER-001 was radiolabeled using (89)Zr to allow for PET/CT imaging. Patients with primary esophageal cancer staged T2 and above were recruited for serial (89)Zr-HDL PET/CT imaging before starting chemoradiation therapy. In addition, patients underwent routine (18)F-FDG PET/CT and 3-T MRI scanning (diffusion-weighted imaging/intravoxel incoherent motion imaging and dynamic contrast-enhanced MRI) to assess tumor glucose metabolism, tumor cellularity and microcirculation perfusion, and tumor vascular permeability. Tumor biopsies were analyzed for the expression of HDL scavenger receptor class B1 and macrophage marker CD68 using immunofluorescence staining. Results: Nine patients with adenocarcinoma or squamous cell carcinoma underwent all study procedures. After injection of (89)Zr-HDL (39.2 ± 1.2 [mean ± SD] MBq), blood-pool SUV(mean) decreased over time (11.0 ± 1.7, 6.5 ± 0.6, and 3.3 ± 0.5 at 1, 24, and 72 h, respectively), whereas liver and spleen SUV(mean) remained relatively constant (4.1 ± 0.6, 4.0 ± 0.8, and 4.3 ± 0.8 at 1, 24, and 72 h, respectively, for the liver; 4.1 ± 0.3, 3.4 ± 0.3, and 3.1 ± 0.4 at 1, 24, and 72 h, respectively, for the spleen) and kidney SUV(mean) markedly increased over time (4.1 ± 0.9, 9.3 ± 1.4, and 9.6 ± 2.0 at 1, 24, and 72 h, respectively). Tumor uptake (SUV(peak)) increased over time (3.5 ± 1.1 and 5.5 ± 2.1 at 1 and 24 h, respectively [P = 0.016]; 5.7 ± 1.4 at 72 h [P = 0.001]). The effective dose of (89)Zr-HDL was 0.523 ± 0.040 mSv/MBq. No adverse events were observed after the administration of (89)Zr-HDL. PET/CT and 3-T MRI measures of tumor glucose metabolism, tumor cellularity and microcirculation perfusion, and tumor vascular permeability did not correlate with tumor uptake of (89)Zr-HDL, suggesting that a specific mechanism mediated the accumulation of (89)Zr-HDL. Immunofluorescence staining of clinical biopsies demonstrated scavenger receptor class B1 and CD68 positivity in tumor tissue, establishing a potential cellular mechanism of action. Conclusion: To our knowledge, this was the first (89)Zr-HDL study in human oncology. (89)Zr-HDL PET/CT imaging demonstrated that intravenously administered HDL nanoparticles accumulated in tumors of patients with esophageal cancer. The administration of (89)Zr-HDL was safe. These findings may support the development of HDL nanoparticles as a clinical delivery platform for drug agents. (89)Zr-HDL imaging may guide drug development and serve as a biomarker for individualized therapy.	esophagus
Pre-treatment CRP and Albumin Determines Prognosis for Unresectable Advanced Oesophageal Cancer.	BACKGROUND/AIM: Nutritional disorders due to cancer-related weight loss, such as cancer-impaired food passage, are prominent in many cases of advanced oesophageal cancer. Here, we investigated the nutritional factors that most affect the therapeutic effect and prognosis of unresectable oesophageal cancer. PATIENTS AND METHODS: One hundred four patients diagnosed with cT4b oesophageal squamous cell carcinoma were included in this study. The values of C-reactive protein/albumin ratio, Glasgow Prognostic Score, prognostic nutritional index, neutrophil/lymphocyte ratio and platelet/lymphocyte ratio were calculated from the pre-treatment blood sampling results of the patients who received chemoradiotherapy, and the therapeutic effect and prognosis were analysed. RESULTS: High- C-reactive protein/albumin group and Glasgow Prognostic Score 1 or 2 group correlated with a significantly worse prognosis compared with the low- C-reactive protein/albumin group and Glasgow Prognostic Score 0 group regarding both disease-specific survival and overall survival. CONCLUSION: Evaluation of pre-treatment CRP and albumin levels in locally advanced oesophageal cancer leads to useful prognostic prediction.	esophagus
Does VO(2)peak Provide a Prognostic Value in Esophagectomy and Gastrectomy for Post-operative Outcomes?	BACKGROUND/AIM: Esophagectomy and gastrectomy are procedures with considerable physical burden and intense post-operative care of which the patient's physical condition seems to be a relevant predictor. The gold standard of the cardiorespiratory fitness is the peak oxygen consumption (VO(2)peak). This pilot study examined the prognostic value of VO(2)peak on post-surgery outcomes in esophageal and gastric cancer patients. PATIENTS AND METHODS: In this prospective cross-sectional study, patients scheduled for esophagectomy or gastrectomy were examined 24 h before the surgery regarding their VO(2)peak. The post-operative complications according to Clavien-Dindo grade IIIb/IV/V, Intensive-Care-Unit days, and overall hospital stay were documented following surgery. In a subset, body weight changes from surgery until hospital discharge and first aftercare visit were recorded. RESULTS: The functional capacity was significantly reduced in 34/35 of the included patients compared to matched norm-values (p<0.01). The only significant correlation was found between VO(2)peak values and body weight change from surgery to the first aftercare visit. A subgroup comparison of patients with a VO(2)peak <17 ml/min/kg and ≥17 ml/min/kg suggested small, non-significant differences in post-surgery outcomes and significant differences in the body weight change from surgery to hospital discharge, favoring the higher-VO(2)peak subgroup. CONCLUSION: The impaired functional capacity following esophagectomy or gastrectomy may strengthen the rational for exercise programs during neoadjuvant and pre-surgery phases. The prognostic value of VO(2)peak on post-operative outcomes remains uncertain due to noticeable descriptive differences, but no significant correlations, potentially limited by the smallsized population. Nonetheless, a correlation between VO(2)peak and body weight change post-surgery was observed and indicates a potential prognostic value of VO(2)peak.	esophagus
Long Non-coding RNAs With In Vitro and In Vivo Efficacy in Preclinical Models of Esophageal Squamous Cell Carcinoma Which Act by a Non-microRNA Sponging Mechanism.	Esophageal squamous cell carcinoma is a type of cancer with dismal prognosis. Surgery, chemo- and radiation therapy, as well as immune checkpoint-blocking immunotherapy lead to limited improvement of survival of patients; therapy resistance and recurrencies hamper these treatment modalities. Therefore, the identification of new targets and treatment approaches is of paramount importance. We have searched the literature and identified 7 down-regulated and 16 up-regulated non-coding RNAs, which showed efficacy in preclinical esophageal squamous cell carcinoma-related in vitro and in vivo models, and discuss their diverse mode of actions. We excluded long non-coding RNAs, which act by sponging of microRNAs. It is presently unclear whether long non-coding RNA/protein, DNA and RNA interactions can be targeted with small molecules. We describe reconstitution therapy and inhibition of the corresponding long non-coding RNAs with small interfering RNAs and antisense oligonucleotides. Also, we discuss emerging targets for treatment of esophageal squamous cell carcinoma.	esophagus
Phosphodiesterase type 5 inhibitors enhance chemotherapy in preclinical models of esophageal adenocarcinoma by targeting cancer-associated fibroblasts.	The chemotherapy resistance of esophageal adenocarcinomas (EACs) is underpinned by cancer cell extrinsic mechanisms of the tumor microenvironment (TME). We demonstrate that, by targeting the tumor-promoting functions of the predominant TME cell type, cancer-associated fibroblasts (CAFs) with phosphodiesterase type 5 inhibitors (PDE5i), we can enhance the efficacy of standard-of-care chemotherapy. In ex vivo conditions, PDE5i prevent the transdifferentiation of normal fibroblasts to CAF and abolish the tumor-promoting function of established EAC CAFs. Using shotgun proteomics and single-cell RNA-seq, we reveal PDE5i-specific regulation of pathways related to fibroblast activation and tumor promotion. Finally, we confirm the efficacy of PDE5i in combination with chemotherapy in close-to-patient and in vivo PDX-based model systems. These findings demonstrate that CAFs drive chemotherapy resistance in EACs and can be targeted by repurposing PDE5i, a safe and well-tolerated class of drug administered to millions of patients world-wide to treat erectile dysfunction.	esophagus
MiR-4739 inhibits the malignant behavior of esophageal squamous cell carcinoma cells via the homeobox C10/vascular endothelial growth factor A/phosphatidylinositol 3-kinase/AKT pathway.	Esophageal cancer is a lethal disease, and emerging evidence has shown that microRNAs are involved in its development, progression, and clinical outcome. MicroRNAs are potential biomarkers for esophageal squamous cell carcinoma (ESCC), and may be useful in advanced RNA therapy for ESCC. This study was conducted to evaluate the molecular mechanism of miR-4739 in ESCC. Reverse transcription-quantitative polymerase chain reaction and western blotting were performed to measure RNA and protein levels. Transwell assay, Cell Counting Kit-8 assay, cytometry analysis, and human umbilical vein endothelial cell tube formation assay were conducted to determine the molecular function of miR-4739 in ESCC. Potential targets of miR-4739 were predicted using bioinformatics tools and confirmed in ESCC cells using a luciferase reporter and RNA pulldown assay. Finally, we performed immunohistochemistry to evaluate the effects of administering agomir-4739 to a mouse model of ESCC. MiR-4739 expression was downregulated in ESCC tissues and cells. MiR-4739 overexpression inhibited cell proliferation, migration, and invasion, and promoted apoptosis of ESCC cells. Furthermore, vascular endothelial growth factor A expression was downregulated by miR-4739 mimics in ESCC cells. MiR-4739 negatively regulated homeobox C10 expression. Additionally, agomir-4739 inhibited tumor growth and angiogenesis in vivo. We demonstrated that miR-4739 overexpression exerted an inhibitory effect on ESCC cells by preventing the expression of homeobox C10 via the vascular endothelial growth factor A/phosphatidylinositol 3-kinase/AKT pathway, indicating the potential of this microRNA as a treatment target in ESCC.	esophagus