crossing96/oncoscreening huggingface dataset:
A phase IIa study of rhLTα-Da in combination with cisplatin and fluorouracil for patients with metastatic esophageal squamous cell carcinoma or gastric adenocarcinoma.	Recombinant human lymphotoxin-α derivative (rhLTα-Da) is a lymphotoxin-α derivative missing 27 N-terminal amino acid residues. This multicenter phase IIa trial was conducted to evaluate the safety, efficacy and pharmacokinetics of rhLTα-Da with cisplatin (DDP) and 5-fluorouracil (5-Fu) for metastatic esophageal squamous cell cancer (ESCC) and gastric adenocarcinoma (GC). Two different rhLTα-Da doses (10 µg/m(2)/d and 20 µg/m(2)/d) in combination with DDP and 5-Fu were evaluated in this study. The first 6 ESCC and 6 GC patients were given 10 µg/m(2)/d rhLTα-Da followed by DDP (15 mg/m(2)/d) and 5-Fu (750 mg/m(2)/d) on days 1-5. The next 6 ESCC and 6 GC patients were given 20 µg/m(2)/d rhLTα-Da after fewer than 2 of the 6 patients who received the 10 µg/m(2)/d dose exhibited dose-limiting rhLTα-Da-related toxicities. The treatment was 21 days a cycle until a maximum of 6. The rhLTα-Da pharmacokinetic analyses were performed. Twelve ESCC and 12 GC patients were enrolled. The toxicities were controllable and reversible. The most common adverse events related to rhLTα-Da were chills (37.5 %, 9/24) and fever (16.7 %, 4/24) (all grades 1-2). The overall response rates in the 10- and 20-µg/m(2)/d groups were 50 % (6/12) and 33.3 % (4/12), respectively, and the overall response rates of the ESCC and GC patients were 66.7 % (8/12) and 16.7 % (2/12), respectively. rhLTα-Da in combination with DDP and 5-Fu exhibited a tolerable toxicity profile. The addition of rhLTα-Da may enhance the anti-tumor efficacy of platinum-based chemotherapy in metastatic ESCC.	esophagus
Pre-treatment assay of 5-fluorouracil degradation rate (5-FUDR) to improve prediction of 5-fluorouracil toxicity in gastro-esophageal cancer.	BACKGROUND: 5-fluorouracil (5-FU) based chemotherapy is the most common first line regimen used in gastric and gastroesophageal junction cancer, but development of severe toxicity is a main concern in the treatment. The present study is aimed to evaluate a novel pre-treatment assay, known as the 5-FU degradation rate (5-FUDR), as a predictive factor for 5-FU toxicity. METHODS: Pre-treatment 5-FUDR and gene polymorphisms related to 5-FU metabolism (DPYDIVS14+1G>A, MTHFRA1298T or C677T, TMYS TSER) were characterized in gastro-esophageal cancer patients. Association with toxicities was retrospectively evaluated, using multivariate logistic regression analysis. RESULTS: 107 gastro-esophageal cancer patients were retrospectively analyzed. No relation between gene polymorphisms and toxicity were detected, while low (< 5th centile) and high (> 95th centile) 5-FUDRs were associated with development of grade 3-4 toxicity (OR 11.14, 95% CI 1.09-113.77 and OR 9.63, 95% CI 1.70-54.55, p = 0.002). CONCLUSIONS: Compared to currently used genetic tests, the pre-treatment 5-FUDR seems useful in identifying patients at risk of developing toxicity.	esophagus
Prognostic value of tumor infiltrating NK cells and macrophages in stage II+III esophageal cancer patients.	The detailed understanding of the immunobiology of tumor microenvironment has recently translated into new therapeutic approach against human cancers. Besides the role of immune cells mediating adaptive immune responses, the tumor infiltrating components of the innate immune system including, neutrophils, mast cells, NK cells, and macrophages, also role importantly in anti-tumor immunity. In our present study, we retrospectively analyzed the prognostic value of the densities of tumor infiltrating NK cells and macrophages in esophageal cancer tissues derived from stage II+III patients. Our results showed that the density of the infiltrating NK cells in tumor stroma was significantly associated with nodal status. In addition, the densities of the infiltrating NK cells in tumor nest, and the infiltrating macrophages in tumor nest as well as in tumor stroma, were significantly associated with patients' postoperative prognoses. Furthermore, the combination of infiltrating NK cells in tumor nest and stroma, or the combination of infiltrating macrophages in tumor nest and stroma, could also be used as important prognostic tool in predicting the survival of the stage II+III esophageal cancer patients.	esophagus
Development and feasibility of a web-based question prompt sheet to support information provision of health-related quality of life topics after oesophageal cancer surgery.	We developed a web-based question prompt sheet (QPS) to support information provision of health-related quality of life (HRQL) topics after oesophageal cancer surgery. The QPS was evaluated and updated in three consecutive studies. In Study 1, eight patients were guided in using the QPS. Feasibility was assessed by cognitive walkthrough, questionnaire and interview. We obtained 430 notes (217 negative, 213 positive) of patients' actions and or remarks, and 91 suggestions. With minor support, most patients were able to use the QPS. In Study 2, forty patients independently used and appraised a modified version of the QPS by questionnaire. All patients deemed the QPS to be usable and useful. In Study 3, 21 patients and three surgeons used the QPS in clinical practice. Clinical feasibility was assessed by the number of QPS sent to the researcher/surgeon. Patients and surgeons were surveyed and the follow-up consultation was audio-recorded. Surgeons were additionally interviewed. Twenty/fourteen patients sent their QPS to the researcher/surgeon. Five QPSs were read by the consultation surgeon. Patients considered the QPS usable and useful. Surgeons considered the QPS of added value and helpful in informing patients, but currently not clinically feasible due to increased consultation time.	esophagus
Subtyping sub-Saharan esophageal squamous cell carcinoma by comprehensive molecular analysis.	Esophageal squamous cell carcinoma (ESCC) is endemic in regions of sub-Saharan Africa (SSA), where it is the third most common cancer. Here, we describe whole-exome tumor/normal sequencing and RNA transcriptomic analysis of 59 patients with ESCC in Malawi. We observed similar genetic aberrations as reported in Asian and North American cohorts, including mutations of TP53, CDKN2A, NFE2L2, CHEK2, NOTCH1, FAT1, and FBXW7. Analyses for nonhuman sequences did not reveal evidence for infection with HPV or other occult pathogens. Mutational signature analysis revealed common signatures associated with aging, cytidine deaminase activity (APOBEC), and a third signature of unknown origin, but signatures of inhaled tobacco use, aflatoxin and mismatch repair were notably absent. Based on RNA expression analysis, ESCC could be divided into 3 distinct subtypes, which were distinguished by their expression of cell cycle and neural transcripts. This study demonstrates discrete subtypes of ESCC in SSA, and suggests that the endemic nature of this disease reflects exposure to a carcinogen other than tobacco and oncogenic viruses.	esophagus
Worldwide Esophageal Cancer Collaboration: pathologic staging data.	We report data-simple descriptions of patient characteristics, cancer categories, and non-risk-adjusted survival-for patients with pathologically staged cancer of the esophagus and esophagogastric junction after resection or ablation with no preoperative therapy from the Worldwide Esophageal Cancer Collaboration (WECC). Thirty-three institutions from six continents submitted de-identified data using standard definitions: demographics, comorbidities, clinical cancer categories, and all-cause mortality from first management decision. Of 13,300 patients, 5,631 had squamous cell carcinoma, 7,558 adenocarcinoma, 85 adenosquamous carcinoma, and 26 undifferentiated carcinoma. Patients were older (62 years) men (80%) with normal body mass index (51%), little weight loss (1.8 kg), 0-2 ECOG performance status (83%), and a history of smoking (70%). Cancers were pT1 (24%), pT2 (15%), pT3 (50%), pN0 (52%), pM0 (93%), and pG2-G3 (78%); most involved distal esophagus (71%). Non-risk-adjusted survival for both squamous cell carcinoma and adenocarcinoma was monotonic and distinctive across pTNM. Survival was more distinctive for adenocarcinoma than squamous cell carcinoma when pT was ordered by pN. Survival for pTis-1 adenocarcinoma was better than for squamous cell carcinoma, although monotonic and distinctive for both. WECC pathologic staging data is improved over that of the 7th edition, with more patients studied and patient and cancer variables collected. These data will be the basis for the 8th edition cancer staging manuals following risk adjustment for patient, cancer, and treatment characteristics, and should direct 9th edition data collection. However, the role of pure pathologic staging as the principal point of reference for esophageal cancer staging is waning.	esophagus
Unexpected Microscopically Positive Proximal Resection Margins in Esophageal Squamous Cell Carcinoma After Chemoradiotherapy: Predictors and Prognostic Significance.	BACKGROUND: Esophageal cancer has the propensity to spread in a longitudinal manner (either proximally or distally), potentially resulting in the unexpected presence of microscopic disease at grossly tumor-free margins. The clinical significance of this phenomenon in patients treated with chemoradiotherapy (CRT) remains unclear. The purpose of this study was to investigate the prevalence, predictors, and prognostic impact of microscopically positive proximal resection margins (PPRMs) in patients with esophageal squamous cell carcinoma (ESCC) who received CRT. METHODS: Between 2000 and 2014, we identified 332 ESCC patients who underwent complete gross resection (R0/R1) following CRT. Patients were divided into two groups according to the status of the proximal resection margins on microscopic examination [negative proximal resection margins (NPRMs) vs PPRMs]. The occurrence of anastomotic leakage (AL) and anastomotic recurrence (AR) served as outcome measures. RESULTS: Sixteen (4.8 %) patients had PPRM. The presence of PPRM was not associated with AL but was a strong predictor of AR (PPRM vs NPRM, 23.1 vs 7 %, respectively, P = 0.033). Multivariate analysis identified a resection margin length <3.5 cm [odds ratio (OR) 4.473, P = 0.022] and salvage resection (OR 3.171, P = 0.045) as independent predictors of PPRM. The estimated PPRM rates were 16.7, 6.3, and 1.3 % for patients with 2, 1, and 0 predictors, respectively. CONCLUSIONS: PPRM occurred in 4.8 % of ESCC patients following CRT and was associated with AR. An intraoperative frozen section margin analysis should be performed in patients carrying risk factors to avoid unexpected PPRM.	esophagus
A Tissue Systems Pathology Test Detects Abnormalities Associated with Prevalent High-Grade Dysplasia and Esophageal Cancer in Barrett's Esophagus.	BACKGROUND: There is a need for improved tools to detect high-grade dysplasia (HGD) and esophageal adenocarcinoma (EAC) in patients with Barrett's esophagus. In previous work, we demonstrated that a 3-tier classifier predicted risk of incident progression in Barrett's esophagus. Our aim was to determine whether this risk classifier could detect a field effect in nondysplastic (ND), indefinite for dysplasia (IND), or low-grade dysplasia (LGD) biopsies from Barrett's esophagus patients with prevalent HGD/EAC. METHODS: We performed a multi-institutional case-control study to evaluate a previously developed risk classifier that is based upon quantitative image features derived from 9 biomarkers and morphology, and predicts risk for HGD/EAC in Barrett's esophagus patients. The risk classifier was evaluated in ND, IND, and LGD biopsies from Barrett's esophagus patients diagnosed with HGD/EAC on repeat endoscopy (prevalent cases, n = 30, median time to HGD/EAC diagnosis 140.5 days) and nonprogressors (controls, n = 145, median HGD/EAC-free surveillance time 2,015 days). RESULTS: The risk classifier stratified prevalent cases and non-progressor patients into low-, intermediate-, and high-risk classes [OR, 46.0; 95% confidence interval, 14.86-169 (high-risk vs. low-risk); P < 0.0001]. The classifier also provided independent prognostic information that outperformed the subspecialist and generalist diagnosis. CONCLUSIONS: A tissue systems pathology test better predicts prevalent HGD/EAC in Barrett's esophagus patients than pathologic variables. The results indicate that molecular and cellular changes associated with malignant transformation in Barrett's esophagus may be detectable as a field effect using the test. IMPACT: A tissue systems pathology test may provide an objective method to facilitate earlier identification of Barrett's esophagus patients requiring therapeutic intervention. Cancer Epidemiol Biomarkers Prev; 26(2); 240-8. ©2016 AACR.	esophagus
Oesophageal carcinoma: comparison of ex vivo high-resolution 3.0 T MR imaging with histopathological findings.	High-resolution magnetic resonance (MR) images clearly depict the normal oesophageal wall as consisting of eight layers, which correlates well with histopathological findings. In 56 (91.8%) of 61 lesions, the depth of oesophageal wall invasion determined through MR imaging was consistent with histopathological staging (r = 0.975, P < 0.001). The sensitivity, specificity and accuracy for the mucosa were 71.4%, 98.1%, and 95.1%, respectively, and the corresponding values for the submucosa were 82.4%, 95.5%, and 91.8%; for the muscularis propria, the sensitivity, specificity and accuracy were 100%, 95.7%, and 96.7%, respectively, and for the adventitia, these values were 100%, 100%, and 100%. The Cohen k values for interobserver agreement were excellent: K = 0.839, P < 0.001 (observer 1 vs. observer 2); K = 0.908, P < 0.001 (observer 1 vs. observer 3); and K = 0.885, P < 0.01 (observer 2 vs. observer 3). High-resolution ex vivo MR images obtained with a 3.0 T scanner can be used to precisely evaluate oesophageal carcinoma invasion and provide good diagnostic sensitivity, specificity and accuracy.	esophagus
Global metabolomics reveals potential urinary biomarkers of esophageal squamous cell carcinoma for diagnosis and staging.	We performed a metabolomics study using liquid chromatography-mass spectrometry (LC-MS) combined with multivariate data analysis (MVDA) to discriminate global urine profiles in urine samples from esophageal squamous cell carcinoma (ESCC) patients and healthy controls (NC). Our work evaluated the feasibility of employing urine metabolomics for the diagnosis and staging of ESCC. The satisfactory classification between the healthy controls and ESCC patients was obtained using the MVDA model, and obvious classification of early-stage and advanced-stage patients was also observed. The results suggest that the combination of LC-MS analysis and MVDA may have potential applications for ESCC diagnosis and staging. We then conducted LC-MS/MS experiments to identify the potential biomarkers with large contributions to the discrimination. A total of 83 potential diagnostic biomarkers for ESCC were screened out, and 19 potential biomarkers were identified; the variations between the differences in staging using these potential biomarkers were further analyzed. These biomarkers may not be unique to ESCCs, but instead result from any malignant disease. To further elucidate the pathophysiology of ESCC, we studied related metabolic pathways and found that ESCC is associated with perturbations of fatty acid β-oxidation and the metabolism of amino acids, purines, and pyrimidines.	esophagus
Phase II study of TP300 in patients with advanced gastric or gastro-oesophageal junction adenocarcinoma.	BACKGROUND: TP300, a recently developed synthetic camptothecin analogue, is a highly selective topoisomerase I inhibitor. A phase I study showed good safety and tolerability. As camptothecins have proven active in oesophago-gastric adenocarcinomas, in this phase II study we assessed the efficacy and safety of TP300 in patients with gastric or gastro-oesophageal junction (GOJ) adenocarcinomas. METHODS: Eligible patients had metastatic or locally advanced gastric or Siewert Types II or III GOJ inoperable adenocarcinoma. Patients were chemotherapy naïve unless this had been administered in the perioperative setting. TP300 was administered as a 1-h intravenous infusion every 3 weeks (a cycle) for up to 6 cycles at a starting dose of 8 mg/m(2) with intra-patient escalation to 10 mg/m(2) from cycle 2 in the absence of dose-limiting toxicity. Tumour responses (RECIST 1.1) were assessed every 6 weeks. Toxicity was recorded by NCI-CTCAE version 3.0. Using a modified two-stage Simon design (Stage I and II), a total of 43 patients were to be included providing there were 3 of 18 patients with objective response in Stage I of the study. RESULTS: In Stage I of the study 20 patients (14 males, 6 females), median age 67 years (range 40 - 82), performance status ECOG 0/1, with GC [14] or GOJ carcinoma [6] were enrolled. Of the 16 evaluable patients, 11 received the planned dose increase to 10 mg/m(2) at cycle 2, 2 decreased to 6 mg/m(2), and 3 continued on 8 mg/m(2). There were no objective responses after 2 cycles of treatment. Twelve patients had stable disease for 1 - 5 months and 4 had progressive disease. Median progression free survival (PFS) was 4.1 months (CI [1.6 - 4.9]), median time to progression (TTP) was 2.9 months (CI [1.4 - 4.2]). Grade 3/4 toxicities (worst grade all cycles) included 7 patients (35 %) with neutropenia, 4 patients (20 %) with anaemia, 2 patients (10 %) with thrombocytopenia, and 3 patients (15 %) with fatigue. This study was terminated at the end of Stage I due to a lack of the required (3/18) responders. CONCLUSIONS: This study of TP300 showed good drug tolerability but it failed to demonstrate sufficient efficacy as measured by radiological response. TRIAL REGISTRATION: EU-CTR 2009-012097-12 2009-09-03.	esophagus
The Rho GTPase RhoE exerts tumor-suppressing effects in human esophageal squamous cell carcinoma via negatively regulating epidermal growth factor receptor.	OBJECTIVES: The objective of this study was to investigate the expression pattern, functions, and possible mechanisms of RhoE/Rnd3, a novel member of the Rho GTPases family, in human esophageal squamous cell carcinoma (ESCC) cells by using molecular and cell-based experiments. MATERIALS AND METHODS: Quantitative polymerase chain reaction and Western blotting were carried out to determine the mRNA and protein expression of RhoE in ESCC cell lines, respectively. Both 3-(4,5-dimethylthiazol-2-yl)-2,5diphenyltetrazoliumbromide (MTT) and flow cytometry were applied to evaluate the effects of RhoE overexpression on ESCC cell growth and apoptosis. Furthermore, Western blotting was used to test the expression of epidermal growth factor receptor (EGFR) and phosphorylated-extracellular signal-regulated kinase (p-ERK) in ESCC cells after RhoE was forced and expressed. RESULTS: RhoE was downregulated in human ESCC tissues. Overexpression of RhoE inhibited cell growth as assessed by MTT assay and induced apoptosis. Importantly, we proved that RhoE could negatively regulate the protein expression of EGFR and p-ERK, suggesting that RhoE might inhibit ESCC progression through the EGFR/ERK pathway. CONCLUSION: Our data supported that RhoE could inhibit cell proliferation and promote apoptosis. Moreover, these tumor-suppressing effects might be acted through the negative regulation of EGFR/ERK signaling.	esophagus
Comparison of Salvage Total Pharyngolaryngectomy and Cervical Esophagectomy Between Hypopharyngeal Cancer and Cervical Esophageal Cancer.	BACKGROUND: Total pharyngolaryngectomy and cervical esophagectomy (TPLCE) after chemoradiotherapy remains a challenge because of the high rate of complications and few available data on outcomes and safety. The purpose of this study was to evaluate the clinical significance of salvage TPLCE and to compare treatment outcomes between hypopharyngeal cancer and cervical esophageal cancer. METHODS: Data from 37 consecutive patients who were diagnosed with potentially resectable hypopharyngeal and cervical esophageal cancer after chemoradiotherapy were retrospectively analyzed. The survival and surgical outcomes were investigated between the hypopharyngeal cancer and cervical esophageal cancer groups. RESULTS: Twenty-six patients were included in hypopharyngeal cancer group and 11 patients were included in cervical esophageal cancer group. The baseline characteristics were balanced between the two groups. Compared to the hypopharyngeal cancer group, the cervical esophageal cancer group had significantly more frequent tracheal-related complications (p < 0.05) and stronger association of distal margin of the cervical esophagus and radiation field with tracheal ischemia after salvage surgery. CONCLUSIONS: Salvage TPLCE can offer the exclusive chance of prolonged survival. Association of tracheal ischemia with salvage TPLCE was seen more frequently for cervical esophageal cancer. Therefore, the indication for salvage TPLCE must be carefully considered to maintain the balance between curability and safety.	esophagus
Evaluation of serum HGF and CK18 levels in patients with esophageal cancer.	Cytokeratins are thought to play a role in apoptosis. Cytokeratin 18 (CK18) is involved in the formation of intracellular cytoskeleton, and has been considered a promising apoptosis marker in gastrointestinal carcinomas. Growth factors, including hepatocyte growth factor (HGF), may provide a microenvironment for malignant cells. In this study, we aimed to compare serum HGF and CK18 levels between esophageal squamous cell carcinoma patients and healthy controls. The study included 41 adult patients (20 male, 21 female) diagnosed with esophageal squamous cell carcinoma, with a mean age of 63.54 ± 10.88 years (range, 41-82 years). We also recruited 39 age and gender-matched healthy control subjects. Venous blood samples were taken; serum HGF and CK18 concentrations were determined via ELISA. Results indicated that serum HGF levels were higher in patients (1.37 ± 0.63 ng/mL) as compared to the healthy subjects (0.41 ± 0.29 ng/mL). Similarly, serum CK18 levels were higher in the patient group (2.53 ± 1.33 ng/mL) than in the control group (0.34 ± 0.23 ng/mL) (P < 0.001). In addition, serum HGF and CK18 levels were positively correlated with metastasis stage, tumor stage, and disease stage of esophageal squamous cell carcinoma. To our knowledge, this is the first study to evaluate serum HGF and CK18 levels in patients with esophageal squamous cell carcinoma. The results suggest that serum CK18 and HGF levels may be used as prognostic and disease monitoring biomarkers of esophageal squamous cell carcinoma.	esophagus