crossing96/oncoscreening huggingface dataset:
Comparing Paclitaxel Plus Fluorouracil Versus Cisplatin Plus Fluorouracil in Chemoradiotherapy for Locally Advanced Esophageal Squamous Cell Cancer: A Randomized, Multicenter, Phase III Clinical Trial.	PURPOSE: This trial aimed to assess the efficacy and safety of the paclitaxel plus fluorouracil regimen versus the cisplatin plus fluorouracil regimen in definitive concurrent chemoradiotherapy (dCRT) in patients with locally advanced esophageal squamous cell carcinoma (ESCC). PATIENTS AND METHODS: Patients with locally advanced ESCC were enrolled and randomly assigned to either the paclitaxel plus fluorouracil group or the cisplatin plus fluorouracil group. The patients in the paclitaxel plus fluorouracil group were treated with paclitaxel and fluorouracil one cycle per week in dCRT for five cycles followed by paclitaxel and fluorouracil one cycle per month in consolidation chemotherapy for two cycles. The patients in the cisplatin/5-fluorouracil group were treated with cisplatin and fluorouracil one cycle per month in dCRT for two cycles followed by two cycles in consolidation chemotherapy. The radiotherapy dose was 61.2 Gy delivered in 34 fractions. The primary end point was 3-year overall survival (OS). RESULTS: Four hundred thirty-six patients with ESCC in six centers were recruited at a 1:1 ratio between April 2012 and July 2015. The median follow-up of the surviving patients was 48.7 months (interquartile range, 42.6-60.9). The 3-year OS was 55.4% in the paclitaxel plus fluorouracil group and 51.8% in the cisplatin plus fluorouracil group (hazard ratio, 0.905 [95% CI, 0.698 to 1.172]; P = .448). The 3-year progression-free survival was also not significantly different between the paclitaxel plus fluorouracil group and the cisplatin plus fluorouracil group (43.7% v 45.5%, respectively; hazard ratio, 0.973 [95% CI, 0.762 to 1.243]; P = .828). Compared with the cisplatin plus fluorouracil group, the paclitaxel plus fluorouracil group had significantly lower incidences of acute grade 3 or higher anemia, thrombocytopenia, anorexia, nausea, vomiting, and fatigue (P < .05), but higher incidences of acute grade 3 or higher leukopenia, radiation dermatitis, and radiation pneumonitis (P < .05). CONCLUSION: The paclitaxel plus fluorouracil regimen did not significantly prolong the OS compared with the standard cisplatin plus fluorouracil regimen in dCRT in patients with locally advanced ESCC.	esophagus
Exploratory radiomic features from integrated (18)F-fluorodeoxyglucose positron emission tomography/magnetic resonance imaging are associated with contemporaneous metastases in oesophageal/gastroesophageal cancer.	PURPOSE: The purpose of this study was to determine if (18)F-fluorodeoxyglucose positron emission tomography/magnetic resonance imaging ((18)F-FDG PET/MRI) features are associated with contemporaneous metastases in patients with oesophageal/gastroesophageal cancer. METHODS: Following IRB approval and informed consent, patients underwent a staging PET/MRI following (18)F-FDG injection (326 ± 28 MBq) and 156 ± 23 min uptake time. First-order histogram and second-order grey level co-occurrence matrix features were computed for PET standardized uptake value (SUV) and MRI T1-W, T2-W, diffusion weighted (DWI) and apparent diffusion coefficient (ADC) images for the whole tumour volume. K-means clustering assessed the correlation of feature-pairs with metastases. Multivariate analysis of variance (MANOVA) was performed to assess the statistical separability of the groups identified by feature-pairs. Sensitivity (SN), specificity (SP), positive predictive value (PPV), negative predictive value (NPV), and accuracy (ACC) were calculated for these features and compared with SUV(max), ADC(mean) and maximum diameter alone for predicting contemporaneous metastases. RESULTS: Twenty patients (18 males, 2 female; median 67 years, range 52-86) comprised the final study cohort; ten patients had metastases. Lower second-order SUV entropy combined with higher second-order ADC entropy were the best feature-pair for discriminating metastatic patients, MANOVA p value <0.001 (SN = 80%, SP = 80%, PPV = 80%, NPV = 80%, ACC = 80%). SUV(max) (SN = 30%, SP = 80%, PPV = 60%, NPV = 53%, ACC = 55%), ADC(mean) (SN = 20%, SP = 70%, PPV = 40%, NPV = 47%, ACC = 45%) and tumour maximum diameter (SN = 10%, SP = 90%, PPV = 50%, NPV = 50%, ACC = 50%) had poorer sensitivity and accuracy. CONCLUSION: High ADC entropy combined with low SUV entropy is associated with a higher prevalence of metastases and a promising initial signature for future study.	esophagus
Aberrant p53 Immunostaining in Barrett's Esophagus Predicts Neoplastic Progression: Systematic Review and Meta-Analyses.	Risk stratification of patients with Barrett's esophagus (BE) presently relies on the histopathologic grade of dysplasia found in esophageal biopsies, which is limited by sampling error and inter-pathologist variability. p53 immunostaining of BE biopsies has shown promise as an adjunct tool but is not recommended by American gastroenterology societies, who cite insufficient evidence of its prognostic value. We have conducted a systematic review and meta-analyses to clarify this value. We searched for studies that: (1) used immunohistochemistry to assess p53 expression in esophageal biopsies of BE patients and (2) reported subsequent neoplastic progression. We performed separate meta-analyses of case-control studies and cohort studies. We identified 14 relevant reports describing 8 case-control studies comprising 1435 patients and 7 cohort studies comprising 582 patients. In the case-control study meta-analysis of the risk of neoplasia with aberrant p53 expression, the fixed- and random-effect estimates of average effect size with aberrant p53 expression were OR 3.84, p < .001 (95% CI 2.79-5.27) and OR 5.95, p < .001 (95% CI 2.68-13.22), respectively. In the cohort study meta-analysis, the fixed- and random-effect estimates of average effect size were RR = 17.31, p < .001 (95% CI 9.35-32.08) and RR = 14.25, p < .001 (95% CI 6.76-30.02), respectively. Separate meta-analyses of case-control and cohort studies of BE patients who had baseline biopsies with p53 immunostaining revealed consistent, strong, and significant associations between aberrant p53 immunostaining and progression to high-grade dysplasia or esophageal adenocarcinoma. These findings support the use of p53 immunostaining as an adjunct to routine clinical diagnosis for dysplasia in BE patients.	esophagus
Pembrolizumab alone or in combination with chemotherapy as first-line therapy for patients with advanced gastric or gastroesophageal junction adenocarcinoma: results from the phase II nonrandomized KEYNOTE-059 study.	BACKGROUND: The multicohort, phase II, nonrandomized KEYNOTE-059 study evaluated pembrolizumab ± chemotherapy in advanced gastric/gastroesophageal junction cancer. Results from cohorts 2 and 3, evaluating first-line therapy, are presented. METHODS: Patients ≥ 18 years old had previously untreated recurrent or metastatic gastric/gastroesophageal junction adenocarcinoma. Cohort 3 (monotherapy) had programmed death receptor 1 combined positive score ≥ 1. Cohort 2 (combination therapy) received pembrolizumab 200 mg on day 1, cisplatin 80 mg/m(2) on day 1 (up to 6 cycles), and 5-fluorouracil 800 mg/m(2) on days 1-5 of each 3-week cycle (or capecitabine 1000 mg/m(2) twice daily in Japan). Primary end points were safety (combination therapy) and objective response rate per Response Evaluation Criteria in Solid Tumors version 1.1 by central review, and safety (monotherapy). RESULTS: In the combination therapy and monotherapy cohorts, 25 and 31 patients were enrolled; median follow-up was 13.8 months (range 1.8-24.1) and 17.5 months (range 1.7-20.7), respectively. In the combination therapy cohort, grade 3/4 treatment-related adverse events occurred in 19 patients (76.0%); none were fatal. In the monotherapy cohort, grade 3-5 treatment-related adverse events occurred in seven patients (22.6%); one death was attributed to a treatment-related adverse event (pneumonitis). The objective response rate was 60.0% [95% confidence interval (CI), 38.7-78.9] (combination therapy) and 25.8% (95% CI 11.9-44.6) (monotherapy). CONCLUSIONS: Pembrolizumab demonstrated antitumor activity and was well tolerated as monotherapy and in combination with chemotherapy in patients with previously untreated advanced gastric/gastroesophageal junction adenocarcinoma. CLINICAL TRIAL: ClinicalTrials.gov NCT02335411.	esophagus
Development of a dual-wavelength fluorescent nanoprobe for in vivo and in vitro cell tracking consecutively.	Many imaging probes have been developed for a wide variety of imaging modalities. However, no optical imaging probe could be utilized for both microscopic and whole animal imaging. To fill the gap, the dual-wavelength fluorescent imaging nanoprobe was developed to simultaneously carry both visible-range fluorescent dye and near-infrared (NIR) dye. Emission scan confirms that the nanoprobe exhibits two separate peaks with strong fluorescent intensity in both visible and NIR ranges. Furthermore, the dual-wavelength fluorescent nanoprobe has high photostability and colloidal stability, as well as long shelf-life. In vitro cell culture experiments show that the nanoprobe has the ability to label different types of cells (namely, esophageal, prostate, fibroblast and macrophage cell) for fluorescent microscope imaging. More importantly, cell tracking experiments confirm that cell migration and distribution in various organs can be tracked in real time using in vivo whole-body NIR imaging and in vitro microscopic imaging, respectively.	esophagus
Multiple modulatory activities of Andrographis paniculata on immune responses and xenograft growth in esophageal cancer preclinical models.	BACKGROUND: Esophageal cancer (EC) is a malignant gastrointestinal cancer with high morbidity worldwide and is the fourth leading cause of cancer-related deaths in China. Even though surgery and/or chemotherapy/chemoradiation might achieve good therapeutic response, recurrence rate is high due to cancer metastasis. Hence, the use of alternative adjuvant treatments, such as herbal medicines, for metastatic EC remains a great desire of the patients. Our previous studies have demonstrated the anti-metastatic efficacy of hot water extract of Andrographis paniculata (APW) in human esophageal cancer cells and tumor-bearing nude mice. PURPOSE: In the present study, the immunomodulatory activities of APW were further evaluated in human peripheral blood mononuclear cells (PBMCs) and in a carcinogen-induced esophageal tumorigenesis model using immune-competent C57BL/6 mice. Besides, the inhibitory effects of APW on esophageal cancer cell line-based xenografts and patient-derived xenografts (PDX) were examined so as to illustrate the potential multi-targeted efficacies of APW in esophageal cancer in pre-clinical models. RESULTS: In vitro results showed that APW could stimulate proliferation of PBMCs, as well as TNF-α and IFN-γproductions. In mice with 4-nitroquinoline 1-oxide-induced tumorigenesis, 21-day oral treatment with APW (1600 mg/kg) decreased the level of dysplasia in esophagus and significantly modulated the population of regulatory T cells. The cytokines productions by spleen lymphocytes of APW-treated mice were shifted towards normal resting state (i.e. unchallenged with carcinogen). Furthermore, APW treatment suppressed the growth of cell line-based xenografts by significantly increasing apoptosis in tumors, without causing severe body weight loss as chemotherapeutics did. Most importantly, the inhibitory effects of APW treatment on esophageal patient-derived xenografts growth were demonstrated for the first time. Besides, several diterpenes were detected in the plasma after oral administration of APW in mice, suggesting that multi-components of APW were bioavailable and might have contributed towards the varied pharmacological activities demonstrated in our studies. CONCLUSION: APW was shown to possess anti-tumor, anti-metastatic and immunomodulatory activities in esophageal cancer cell-based and animal models, including immunocompromised mice model and clinically relevant PDX model. Our findings illustrated the potential multi-targeted efficacies of APW in esophageal cancer management.	esophagus
Meta-analysis of risk factors and complications associated with atrial fibrillation after oesophagectomy.	BACKGROUND: Oesophagectomy is associated with high morbidity and mortality rates. New-onset atrial fibrillation (AF) is a frequent complication following oesophagectomy. Several studies have explored whether new-onset AF is associated with adverse events after oesophagectomy. METHODS: This review was performed according to PRISMA guidelines. Eligible studies were identified through a search of PubMed, Scopus and Cochrane CENTRAL databases up to 25 November 2018. A meta-analysis was conducted with the use of random-effects modelling. The I(2) statistic was used to assess for heterogeneity. RESULTS: In total, 53 studies including 9087 patients were eligible for analysis. The overall incidence of postoperative AF was 16·5 per cent. Coronary artery disease and hypertension were associated with AF, whereas diabetes, smoking and chronic obstructive pulmonary disease were not. Patients with AF had a significantly higher risk of overall postoperative adverse events than those without fibrillation (odds ratio (OR) 5·50, 95 per cent c.i. 3·51 to 8·30), including 30-day mortality (OR 2·49, 1·70 to 3·64), anastomotic leak (OR 2·65, 1·53 to 4·59) and pneumonia (OR 3·42, 2·39 to 4·90). CONCLUSION: Postoperative AF is frequently observed in patients undergoing oesophagectomy for cancer. It is associated with an increased risk of death and postoperative complications.	esophagus
Predictors of dysplastic and neoplastic progression of Barrett’s esophagus.	BACKGROUND: It is unknown why some cases of Barrett’s esophagus progress to invasive malignant disease rapidly while others do so more slowly or not at all. The aim of this study was to identify demographic and endoscopic factors that predict dysplastic and neoplastic progression in patients with Barrett’s esophagus. METHODS: Patients with Barrett’s esophagus who were assessed in 2000–2010 were assessed for inclusion in this retrospective study. Demographic and endoscopic variables were collected from an endoscopy database and the medical chart. Dysplastic and neoplastic progression was examined by time-to-event analysis. We used Cox proportional hazard regression modelling and generalized estimating equation methods to identify variables that were most predictive of neoplastic progression. RESULTS: A total of 518 patients had Barrett’s esophagus confirmed by endoscopy and pathology and at least 2 surveillance visits. Longer Barrett’s esophagus segment (≥ 3 cm) (odds ratio [OR] 1.2, 95% confidence interval [CI] 1.1–1.3) and increased age (≥ 60 yr) (OR 3.5, 95% CI 1.7–7.4) were independent predictors of progression from nondysplasia to dysplastic or neoplastic grades. Presence of mucosal irregularities (OR 8.6, 95% CI 2.4–30.4) and increased age (OR 5.1, 95% CI 1.6–16.6) were independent predictors of progression from nondysplasia to high-grade dysplasia or adenocarcinoma. CONCLUSION: Increased age, longer Barrett’s segment and presence of mucosal irregularities were associated with increased risk of dysplastic and neoplastic progression. In addition to dysplasia, these factors may help stratify patients according to risk of neoplastic progression and be used to individualize surveillance. More prospective studies with larger samples are required to validate these results.	esophagus
Differences in Esophageal Cancer Surgery in Terms of Surgical Approach and Extent of Lymphadenectomy: Findings of an International Survey.	INTRODUCTION: Esophagectomy and lymphadenectomy are essential parts of the multimodal treatment of esophageal carcinoma with curative intent. Treatment regimens vary globally and are subject to debate. A global survey was designed to gain insight into current practice. METHODS: Fifty-seven international expert upper gastrointestinal surgeons received a personal invitation to participate in the survey, which focused on demographics and experience; extent of lymphadenectomy in adeno and squamous cell carcinoma; use of classification systems; neoadjuvant therapy; surgical approach; and specimen handling. RESULTS: The response rate was 88% (50/57 surgeons), with a mean age of 51.6 years and a median number of 15 years of experience in esophageal surgery. The variety in the extent of lymphadenectomy in proximal, middle and distal squamous cell carcinoma, and Siewert I, II and III adenocarcinoma, was considerable. The number of different combinations of lymph node (LN) stations that were resected in the same tumor was high, while the number of surgeons who removed the exact same combination of LN stations was low. Illustrative is Siewert I adenocarcinoma, in which 27 unique combinations of LN stations were resected, with a maximum of two surgeons performing the exact same dissection. Use of neoadjuvant therapy, surgical approach, and specimen handling also show great variety among participants. CONCLUSION: There is no uniform, worldwide strategy for surgical treatment of esophageal cancer. The extent of lymphadenectomy shows great variation for both histologic types. An international observational study is needed to provide evidence on the distribution pattern of lymph node metastases in esophageal cancer and the necessary extent of lymphadenectomy.	esophagus
Population pharmacokinetic modeling and simulation of HPPH in Chinese patients with esophageal carcinoma.	1. 2-[1-Hexyloxyethyl]-2-devinyl pyropheophorbide-a (HPPH), a second-generation photosensitizer, has been widely employed in photodynamic therapy (PDT) for the treatment of malignant lesions. The objective of this study was to characterize the pharmacokinetics of HPPH in Chinese patients using a population pharmacokinetic (PopPK) approach.2. For the first time, a PopPK model of HPPH for Chinese (n = 20) was developed (registration number: CTR20160425). The pharmacokinetics of HPPH was described by a three-compartment model with linear elimination. Through the stepwise addition (p < 0.05) and backward elimination (p < 0.001) approach, fat-free mass (FFM) was identified to be the most significant covariate and V(1) increased with FFM. Visual predictive check (VPC) was employed for the evaluation of the final model. Subsequent full covariate analysis indicated that FFM has considerable impact (∼30%) on HPPH exposure and fat mass also has a modest (∼25%) impact.3. The simulations suggested that a dose adjustment of HPPH may be necessary for Chinese and the dose of 3 mg/m(2) should be appropriate. HPPH exposure increases with fat mass while being inversely related to FFM. HPPH-PDT for overweight patients should be monitored with more caution and PDT conditions should be optimized if necessary.	esophagus
Prognostic Significance of Low Body Mass Index and Betel-Quid Use in the 5-Year Survival Rates of Esophageal Squamous Cell Carcinoma Patients.	AIM: This study aimed to examine the relationship between clinicopathological features, varied malnutrition criteria, and survival in esophageal squamous cell carcinoma (ESCC) patients. METHODS: Six malnutrition criteria (body mass index (BMI) < 18.5 kg/m(2), serum albumin level < 3.5 g/dL, neutrophil-to-lymphocyte ratio (NLR) > 3.5, platelet-to-lymphocyte ratio (PLR) > 17, prognostic nutrition index (PNI) < 40, and blood total lymphocyte count (TLC) < 1,600 cells/mm(3)) were measured in 205 ESCC patients at the time of diagnosis. Malnutrition status and clinicopathological features were tested for prognostic effects on the 5-year survival rate. RESULTS: Malnutrition rates vary according to nutrition assessment tools, ranging from 21.5% based on BMI < 18.5 kg/m(2) to 67.8% based on PNI < 40. These rates are associated with increased inflammation, but they showed no difference among various tumor stages. After adjustment of demographic variables and comorbid status, advanced tumor stage, low BMI at diagnosis, and betel quid use showed prognostic significance in the 5-year survival rate based on a multivariate logistic regression analysis. CONCLUSIONS: Different nutrition assessment criteria produced different malnutrition rates. Advanced tumor stage, low BMI at diagnosis, and betel quid use were independent prognostic factors for worse survival of ESCC patients.	esophagus
Clinical significance of LOXL4 expression and features of LOXL4-associated protein-protein interaction network in esophageal squamous cell carcinoma.	Lysyl oxidase-like 4 (LOXL4), a member of the LOX family proteins, catalyzes oxidative deamination of lysine residues in collagen and elastin, which are responsible for maintaining extracellular matrix homeostasis. In this study, the mRNA expression of LOXL4 in seven esophageal squamous cell carcinoma (ESCC) cell lines and 15 ESCC pairs of clinical samples were examined. Furthermore, LOXL4 protein levels in the ESCC cell lines were determined using western blotting. With the use of immunofluorescence, LOXL4 was observed to be localized primarily in the cytoplasm, but was also present in the nucleus. In addition, the results indicated that the upregulated expression of LOXL4 was associated with poor survival in patients with ESCC even following curative resection (P = 0.010). Similar Kaplan-Meier estimator curves for proteins that interact with LOXL4, SUV39H1 (P = 0.014) and COL2A1 (P = 0.011), were plotted. The analyses based on the protein-protein interaction network depicted the expression of LOXL4 and its associated proteins as well as their functions, suggesting that LOXL4 and its associated proteins may serve a significant role in the development and progression of ESCC. In conclusion, the results of the present study suggest that LOXL4 is a potential biomarker for patients with ESCC, as well as SUV39H1 and COL2A1, and high expression levels of these genes are associated with poor prognosis in patients with ESCC.	esophagus
Second primary lung cancer in United States Cancer Survivors, 1992-2008.	PURPOSE: Lung cancer is common and lethal, and can occur in survivors of previous cancers. We sought to describe the incidence and mortality attributable to second primary lung cancers (SPLC) among survivors of other cancers, and to identify survivors at highest risk. METHODS: We identified adults diagnosed with a localized malignancy from non-pulmonary cancer sites from surveillance, epidemiology, and end results (SEER) data from 1992 to 2008. We explored factors associated with the incidence and death from SPLC using bivariable and multivariable models. Finally, we compared standardized incidence rates for SPLC in our cohort with the control arm of the National Lung Screening Trial (NLST), a randomized lung cancer screening trial. RESULTS: We identified 1,450,837 survivors of non-pulmonary cancers, of whom 25,472 developed SPLC at a mean (SD) follow-up of 5.7 (3.6) years. Over half (57%) of patients with SPLC died of the disease. Survivors of cancer of the hypopharynx, oropharynx, tonsil, and larynx, experienced SPLC at standardized incidence rates which greatly exceeded that observed in the control arm of the NLST (572/100,000 person-years). Additionally, survivors of bladder and esophageal cancer had rates that approached the NLST control arm rate. Increasing age and being divorced/widowed/separated were independent risk factors for SPLC in most primary cancer types. CONCLUSION: The incidence of SPLC in survivors of certain primary cancers greatly exceeds the rate observed in the control arm of the NLST. Further study could help determine if screening for lung cancer in these cancer survivors could prevent death from lung cancer.	esophagus