crossing96/oncoscreening huggingface dataset:
Total FDG lesion number on PET/CT predicts survival of esophageal carcinoma patients with recurrence following curative surgery.	BACKGROUND: Total lesion number is a prognostic determinant in recurrent esophageal cancer, but this requires multiple tests. Here, we investigated the prognostic value of total FDG lesion number obtained from a single PET/CT study. METHODS: Subjects were 153 esophageal squamous cell carcinoma patients with loco-regional or distant recurrence following curative surgery. FDG PET/CT performed within 30 days was inspected for abnormal FDG uptake lesions using a SUVmax of 3.0 as threshold for significance. Prognostic associations were assessed by Cox proportional hazards regression and Kaplan-Meier analysis. RESULTS: PET/CT showed significant local FDG lesions in 49.0%, regional lesions in 78.4%, and distant lesions in 44.4% of patients. Among 73 patients with loco-regional recurrence, 54 had 0-3 and 19 had ≥4 FDG lesions. Among 80 patients with distant recurrence, 31 had 0-3 and 49 had ≥4 FDG lesions. During a median follow-up of 11.8 months, 99 deaths occurred. Univariate variables associated with poor survival included ≥4 FDG lesions and no treatment for loco-regional recurrence and no treatment for distant recurrence. Kaplan Meier analysis showed worse survival for ≥4 than 0-3 FDG lesions in patients with loco-regional recurrence (15.6 vs. 32.1 months; P=0.009), but not in those with distant recurrence. Significant independent predictors of poor survival were ≥4 FDG lesions and no treatment for loco-regional recurrence and no treatment for distant recurrence. CONCLUSIONS: Total FDG lesion number assessed by PET/CT is a significant independent prognostic factor in esophageal cancer patients with loco-regional recurrence following curative surgery.	esophagus
Randomized phase 2 study of gemcitabine and cisplatin with or without vitamin supplementation in patients with advanced esophagogastric cancer.	PURPOSE: Preclinical research and prior clinical observations demonstrated reduced toxicity and suggested enhanced efficacy of cisplatin due to folic acid and vitamin B12 suppletion. In this randomized phase 2 trial, we evaluated the addition of folic acid and vitamin B12 to first-line palliative cisplatin and gemcitabine in patients with advanced esophagogastric cancer (AEGC). METHODS: Patients with AEGC were randomized to gemcitabine 1250 mg/m(2) (i.v. days 1, 8) and cisplatin 80 mg/m(2) (i.v. day 1) q 3 weeks with or without folic acid (450 µg/day p.o.) and vitamin B12 (1000 µg i.m. q 9 weeks). The primary endpoint was response rate (RR). Secondary endpoints included overall survival (OS), time to progression (TTP), toxicity, and exploratory biomarker analyses. Cisplatin sensitivity and intracellular platinum levels were determined in adenocarcinoma cell lines cultured under high and low folate conditions in vitro. RESULTS: Adenocarcinoma cells cultured in medium with high folate levels were more sensitive to cisplatin and this was associated with increased intracellular platinum levels. In the randomized phase 2 clinical trial, which ran from October 2004 to September 2013, treatment was initiated in 78 of 82 randomized pts, 39 in each study arm. The RR was similar; 42.1% for supplemented patients vs. 32.4% for unsupplemented patients; p = 0.4. Median OS and TTP were 10.0 and 5.9 months for supplemented vs. 7.7 and 5.4 months for unsupplemented patients (OS, p = 0.9; TTP, p = 0.9). Plasma homocysteine was lower in the supplemented group [n = 20, 6.9 ± 1.6 (mean ± standard error of mean, SEM) µM; vs. 12.5 ± 4.0 µM; p < 0.001]. There was no significant difference in the C(max) of gemcitabine and cisplatin in the two treatment groups. CONCLUSION: Folic acid and vitamin B12 supplementation do not improve the RR, PFS, or OS of cisplatin and gemcitabine in patients with AEGC.	esophagus
Impact of Sarcopenia in Patients with Unresectable Locally Advanced Esophageal Cancer Receiving Chemoradiotherapy.	BACKGROUND: Esophageal cancer often involves direct invasion of adjacent organs and patient survival rates are low. Sarcopenia has been reported to be associated with a poor prognosis in several types of malignancies. However, the impact of sarcopenia on the long-term survival of patients with unresectable locally advanced esophageal cancer remains unclear. PATIENTS AND METHODS: A total of 48 patients undergoing definitive chemoradiotherapy at our Institution from October 2012 to December 2015 were enrolled; their data were compared according to patient skeletal muscle index (SMI): low SMI (sarcopenia group), n=34; normal SMI (non-sarcopenia group), n=14. RESULTS: There were no significant differences in the incidence of severe adverse events and dose reduction rate between the two groups. The incidence of nutritional support was significantly higher in the groups with sarcopenia than in the non-sarcopenia group (44.1% vs. 7.1%, p=0.077). Response rates were significantly lower in the sarcopenia group than in the non-sarcopenia group (43.8% vs. 78.6%, p=0.025). The overall survival rate in the group with sarcopenia was significantly lower than that in the non-sarcopenia group (3-year: 36.95% vs. 63.9%, p=0.018). CONCLUSION: Sarcopenia prior to treatment may worsen the long-term survival of patients with unresectable locally advanced esophageal cancer. Further well-designed prospective trials are needed to estimate whether adequate nutritional support has a favorable impact on therapeutic outcomes in this population.	esophagus
Routine pre- and post-neoadjuvant chemotherapy fitness testing is not indicated for oesophagogastric cancer surgery.	Introduction There is a known correlation between anaerobic threshold (AT) during cardiopulmonary exercise testing and development of cardiopulmonary complications in high-risk patients undergoing oesophagogastric cancer surgery. This study aimed to assess the value of routine retesting following neoadjuvant chemotherapy. Methods Patients undergoing neoadjuvant chemotherapy with subsequent oesophagogastric cancer surgery with pre- and post-neoadjuvant chemotherapy cardiopulmonary exercise data were identified from a prospectively maintained database. Measured cardiopulmonary exercise variables included AT and maximum oxygen uptake at peak exercise (VO(2) peak). Anaerobic threshold values within 1 ml/kg/minute were considered static. Patients were grouped into AT ranges of less than 9 ml/kg/minute, 9-11 ml/kg/minute and greater than 11 ml/kg/minute. Outcome measures were unplanned intensive care stay, postoperative cardiovascular morbidity and mortality. Results Between May 2008 and August 2017, 42 patients from 675 total resections were identified, with a mean age of 65 years (range 49-84 years). Mean pre-neoadjuvant chemotherapy AT was 11.07 ml/kg/minute (standard deviation, SD, 3.24 ml/kg/minute, range 4.6-19.3 ml/kg/minute) while post-neoadjuvant chemotherapy AT was 11.19 ml/kg/minute (SD 3.05 ml/kg/minute, range 5.2-18.1 ml/kg/minute). Mean pre-neoadjuvant chemotherapy VO(2) peak was 17.13 ml/kg/minute, while post-chemotherapy this mean fell to 16.59 ml/kg/minute. Some 44.4% of patients with a pre-chemotherapy AT less than 9 ml/kg/minute developed cardiorespiratory complications compared with 42.2% of those whose AT was greater than 9 ml/kg/minute (P = 0.914); 63.6% of patients in the post-neoadjuvant chemotherapy group with an AT less than 9 ml/kg/minute developed cardiorespiratory complications. There was no correlation between direction of change in AT and outcome. Conclusion In our patient population, neoadjuvant chemotherapy does not appear to result in a significant mean reduction in cardiorespiratory fitness. Routine pre- and post-neoadjuvant chemotherapy cardiopulmonary exercise testing is currently not indicated; however, larger studies are required to demonstrate this conclusively.	esophagus
Andecaliximab/GS-5745 Alone and Combined with mFOLFOX6 in Advanced Gastric and Gastroesophageal Junction Adenocarcinoma: Results from a Phase I Study.	Purpose: Matrix metalloproteinase-9 (MMP9) is implicated in protumorigenic processes. Andecaliximab (GS-5745, a monoclonal antibody targeting MMP9) was evaluated as monotherapy and in combination with mFOLFOX6.Patients and Methods: Three dosages of andecaliximab monotherapy [200, 600, and 1800 mg i.v. every 2 weeks (q2w)] were investigated in patients with advanced solid tumors (n = 13 in a 3+3 design). After determining a recommended dose, patients with advanced HER2-negative gastric/gastroesophageal junction (GEJ) adenocarcinoma (n = 40) received 800 mg andecaliximab + mFOLFOX6 q2w. Pharmacokinetics, pharmacodynamics, safety, and efficacy were assessed.Results: Andecaliximab monotherapy demonstrated no dose-limiting toxicity (DLT) in any cohort, displaying target-mediated drug disposition at the lowest dose (200 mg) and linear pharmacokinetics at higher doses. Based on target engagement, recommended doses for further study are 800 mg q2w or 1,200 mg q3w. Maximal andecaliximab target binding, defined as undetectable andecaliximab-free MMP9 in plasma, was observed in the gastric/GEJ adenocarcinoma cohort. We observed no unusual toxicity, although there were four deaths on study not attributed to andecaliximab treatment. In first-line patients (n = 36), median progression-free survival (PFS) was 9.9 months [95% confidence interval (CI), 5-13.9 months], and the overall response rate (ORR) was 50%. Among all patients (n = 40), median PFS was 7.8 (90% CI, 5.5-13.9) months, and ORR was 48%, with a median duration of response of 8.4 months.Conclusions: Andecaliximab monotherapy achieved target engagement without DLT. Andecaliximab + mFOLFOX6 showed encouraging clinical activity without additional toxicity in patients with HER2-negative gastric/GEJ adenocarcinoma. A phase III study evaluating mFOLFOX6 ± andecaliximab in this setting is ongoing. Clin Cancer Res; 24(16); 3829-37. ©2018 AACR.	esophagus
Systematic review and meta-analysis of the effectiveness of radiofrequency ablation in low grade dysplastic Barrett's esophagus.	BACKGROUND: Barrett's esophagus (BE) is a premalignant condition characterized by replacement of the esophageal lining with metastatic columnar epithelium, and its management when complicated by low grade dysplasia (LGD) is controversial. This systematic review and meta-analysis aimed to determine the efficacy of radiofrequency ablation (RFA) in patients with LGD. METHODS: MEDLINE, EMBASE, and Web of Science were searched for studies including patients with BE-associated LGD receiving RFA (January 1990 to May 2017). The outcome measures were complete eradication of intestinal metaplasia (CE-IM) and dysplasia (CE-D), rates of progression to high grade dysplasia (HGD) or cancer, and recurrence. RESULTS: Eight studies including 619 patients with LGD (RFA = 404, surveillance = 215) were analyzed. After a median follow-up of 26 months (range 12 - 44 months), the overall pooled rates of CE-IM and CE-D after RFA were 88.17 % (95 % confidence interval [CI] 88.13 % - 88.20 %; P < 0.001) and 96.69 % (95 %CI 96.67 % - 96.71 %; P < 0.001), respectively. When compared with surveillance, RFA resulted in significantly lower rates of progression to HGD or cancer (odds ratio [OR] 0.07, 95 %CI 0.02 - 0.22). The pooled recurrence rates of IM and dysplasia were 5.6 % (95 %CI 5.57 - 5.63; P < 0.001) and 9.66 % (95 %CI 9.61 - 9.71; P < 0.001), respectively. CONCLUSIONS: RFA safely eradicates IM and dysplasia and reduces the rates of progression from LGD to HGD or cancer in the short term.	esophagus
The relationship between esophageal cancer, chagasic megaesophagus and HPV: myths, tales or reality?	A supposed role for persistent high-risk human papillomavirus (HPV) infection in esophageal squamous cell carcinoma (ESCC) etiology has been suggested by a number of studies. Concomitantly, megaesophagus induced by the Trypanosoma cruzi cell-cycle activity also shows a potential association with ESCC. This review discusses esophageal cancer and the potential association between chagasic megaesophagus and HPV as risk factors for ESCC development.	esophagus
Surgery for metastases for esophageal-gastric cancer in the real world: Data from the AGAMENON national registry.	INTRODUCTION: The effect of surgery for metastases in patients with esophagogastric cancer is unknown, given the lack of randomized clinical trials; likewise, the criteria for selecting eligible patients remain to be determined. METHODS: This registry evaluates the results of patients with advanced adenocarcinoma of the stomach, distal esophagus, or gastro-esophageal junction from 32 centers. To assess selection criteria and prognostic factors, a state arrival extended Markov proportional hazards (PH) model was used. RESULTS: 1792 subjects were analyzed, 5% of whom (n = 92) underwent surgery for metastasis. The most common surgeries were peritoneal (29%), hepatic (24%), and distant lymph nodes (11%). Subjects chosen for metastasectomy had higher survival rates, HR 0.34 (95% CI, 0.06-0.80, p = 0.021). Patients who underwent surgery had a mOS since metastasectomy of 16.7 months (95% CI, 12.5-22.4). The 1- and 3-year relapse rates following R0 resection were 58% and 65%, respectively. Median time since R0 metastasectomy until relapse was 8.4 months (95% CI, 7.6-23.7). The 3-year OS after surgery was 30.6% (95% CI, 19.3-40.4). Duration of chemotherapy prior to surgery (months) increased mortality (HR 1.04 [95% CI, 1.01-1.07]), p = 0.009. The only significant interaction involved the use of anti-HER2 therapy. CONCLUSION: The AGAMENON registry suggests that subjects with limited metastatic disease, selected on a clinical basis, can benefit from early surgeries. Prospective trials are needed to confirm these data.	esophagus
Effects of tumor-associated macrophages on the proliferation and migration of esophageal cancer-associated lymphatic endothelial cells.	The aim of this study was to explore whether M2 macrophages can be transformed into M1 macrophages, and to investigate the effect of different types of macrophages on the proliferation, migration and ring-forming ability of esophageal cancer-related lymphatic endothelial cell (LEC). Human monocytic leukemia cell line (THP-1 cell) was induced to differentiate to M1 macrophages (M1 group) and M2 macrophages (M2 group), and co-cultured with esophageal cancer-associated LEC. The individual esophageal cancer co-cultured with LEC was used as control. Different types of macrophages were observed by Cell counting kit-8 (CCK-8). Enzyme-linked immunosorbent assay (ELISA) was used to detect the VEGF-C concentration; the expression of VEGFR-3 protein and its mRNA was detected by Western blot and qRT-PCR, respectively. The positive rate of the M1 group induced by IFN-γ and LPS was significantly higher than that of M2 macrophages (48.57%5.98% vs 25.83%1.95%). The expression of VEGF-C in the supernatant of the M2 group was higher than that in the control group, but no significant differences regarding the expression of VEGF-C between M1 and control groups were found. In addition, the expression of VEGFR-3 on both mRNA and protein in esophageal cancer-related LEC of the M2 group was significantly higher than those in the control group; however, the M1 group had a significantly lower VEGFR-3 level on both mRNA and protein than the control group. Human M2 macrophages can be transformed into M1 macrophages, and can promote the proliferation, migration and ring-forming ability of esophageal cancer-associated LEC.	esophagus
Implication of Highly Cytotoxic Natural Killer Cells for Esophageal Squamous Cell Carcinoma Treatment.	Esophageal squamous cell carcinoma (ESCC) is an aggressive upper gastrointestinal cancer and effective treatments are limited. Previous studies reported that natural killer (NK) cells expanded by coculturing with K562-mb15-41BBL feeder cells, a genetically modified K562 leukemia cell line that expresses membrane-bound interleukin (IL)-15 and 41BBL ligand, were highly proliferative and highly cytotoxic. Here, we investigated the potential of expanded NK cells for ESCC treatment. We analyzed both genetic and surface expression levels of NKG2D ligands (NKG2DLs) in ESCC using publicly available microarray data sets and ESCC cell lines. The cytotoxicity of resting and of IL-2-activated NK cells against ESCC cell lines was compared with that of expanded NK cells. We then also investigated the effect of epithelial mesenchymal transition (EMT) inducers, GSK3β inhibitor and epidermal growth factor, on NKG2DLs expressions. As a result, MICA and MICB were significantly overexpressed in ESCC compared with adjacent normal tissues and surface NKG2DLs were expressed in ESCC cell lines. Expanded NK cells were much potent than IL-2-activated and resting NK cells against ESCC cell lines. Blocking of NKG2D with anti-NKG2D monoclonal antibody dampened expanded NK cell cytotoxicity, suggesting that the NKG2DLs-NKG2D interaction is crucial for NK cells to eliminate ESCC cells. EMT inducers concurrently induced EMT and NKG2DLs expression in ESCC cell lines rendering transitioned cells more sensitive to expanded NK cells. In conclusion, expanded NK cells were highly cytotoxic against NKG2DLs-expressing ESCC cells, particularly the EMT phenotype. These results provide a strong rationale for clinical use of these NK cells in ESCC patients.	esophagus
The vanillin derivative 6-bromine-5-hydroxy-4-methoxybenzaldehyde induces aberrant mitotic progression and enhances radio-sensitivity accompanying suppression the expression of PLK1 in esophageal squamous cell carcinoma.	Esophageal squamous cell carcinoma (ESCC) is the most common form of esophageal cancer in China. Since chemotherapy is the standard clinical intervention for advanced ESCC, the development of highly effective and minimal/non-toxic drugs is essential to improve the clinical outcome and prognosis of the patients. A novel derivative of vanillin, 6-bromine-5-hydroxy-4-methoxybenzaldehyde (BVAN08), has been recently reported to activate different cell death pathways in cancer cells. In this study, we demonstrate that BVAN08 exhibits a potent anti-proliferation effect on ESCC cells (TE-1 and ECA-109) by inhibiting the expression of PLK1, an important mitotic kinase. Consistent with this, BVAN08 induces mitotic arrest and chromosomal misalignment in ESCC cells. The disruption of microtubule nucleation around centrosomes is also observed in BVAN08 treated ESCC cells. Furthermore, BVAN08 enhances radio-sensitivity of ESCC cells by prolonging DNA damage repair. These findings underscore the potential value of BVAN08 in cancer therapeutics and demonstrate the underlying mechanism by which BVAN08 induces mitotic catastrophe and enhances radio-sensitivity in ESCC cells.	esophagus
Evaluation of p53 protein expression in Barrett esophagus.	BACKGROUND: Loss of heterozygosity of p53 along with aneuploidy is deemed to be the early molecular steps in Barrett metaplasia-dysplasia-adenocarcinoma sequence. Objective biomarkers need to be used along with microscopy for risk stratification to predict the progression of Barrett esophagus (BE) to carcinoma. AIM: This study aims to study p53 protein expression in dysplasia and correlate the same with morphology in BE. MATERIALS AND METHODS: A time-bound study was conducted from January 2011 to June 2015. All esophageal biopsies showing histological evidence of columnar epithelium with the presence of goblet cells were included. The cases which showed dysplasia were graded on hematoxylin and eosin stain. Evaluation of p53 immunohistochemistry staining was done on all the cases of BE. Dysplasia was correlated with the expression of p53 using Chi-square value (χ(2)) and Fischer's exact test wherever appropriate. P < 0.05 was considered to be statistically significant. RESULTS: Of 829 esophageal biopsies received, 119 were endoscopically suspected to be BE, of which 85 cases were confirmed on microscopy. In our study, there were 75 cases negative for dysplasia (88.2%), 8 with low-grade dysplasia (LGD) (9.4%), and two with high-grade dysplasia (HGD) (2.4%). Three cases of BE had associated adenocarcinoma. Immunostaining with p53 done on all the 85 cases showed positive staining in all cases with LGD, one with HGD and two with adenocarcinoma. In the present study, immunostaining with p53 showed 90% sensitivity, 89.3% specificity, positive predictive value of 52.9%, and negative predictive value of 98.5%. CONCLUSION: The technical simplicity, easy availability, and comparatively lower cost enhance the role of p53 as a biomarker in risk stratification for patients with BE.	esophagus
Origins of Metaplasia in Barrett's Esophagus: Is this an Esophageal Stem or Progenitor Cell Disease?	The incidence of esophageal adenocarcinoma has been increasing in Western countries over the past several decades. Though Barrett's esophagus, in which the normal esophageal squamous epithelium is replaced with metaplastic intestinalized columnar cells due to chronic damage from gastroesophageal reflux, is accepted as the requisite precursor lesion for esophageal adenocarcinoma, the Barrett's esophagus cell of origin and the molecular mechanism underlying esophageal epithelial metaplasia remain controversial. Much effort has been dedicated towards identifying the Barrett's esophagus cell of origin since this could lead to more effective prevention and treatment strategies for both Barrett's esophagus and esophageal adenocarcinoma. Previously, it was hypothesized that terminally differentiated esophageal squamous cells might undergo direct conversion into specialized intestinal columnar cells via the process of transdifferentiation. However, there is increasing evidence that stem and/or progenitor cells are molecularly reprogrammed through the process of transcommitment to differentiate into the columnar cell lineages that characterize Barrett's esophagus. Given that Barrett's esophagus originates at the gastroesophageal junction, the boundary between the distal esophagus and gastric cardia, potential sources of these stem and/or progenitor cells include columnar cells from the squamocolumnar junction or neighboring gastric cardia, native esophageal squamous cells, native esophageal cuboidal or columnar cells from submucosal glands or ducts, or circulating bone marrow-derived cells. In this review, we focus on native esophageal specific stem and/or progenitor cells and detail molecular mediators of transcommitment based on recent insights gained from novel mouse models and clinical observations from patients.	esophagus
First Report of Dramatic Tumor Responses with Ramucirumab and Paclitaxel After Progression on Pembrolizumab in Two Cases of Metastatic Gastroesophageal Adenocarcinoma.	Checkpoint inhibitors targeted at programmed cell death-1 receptor (PD-1) and its ligand (PD-L1) can result in significant benefit to a small proportion of patients with cancer, including those with tumors of the stomach and gastroesophageal junction. These drugs are now approved for several solid tumors, including the recent accelerated approval of pembrolizumab for gastroesophageal adenocarcinomas in the third-line setting and beyond based on the KEYNOTE-059 phase II trial. Data are lacking on the efficacy of chemotherapy after progression on PD-1 blockade in metastatic gastroesophageal adenocarcinoma. This report describes the exceptional response of two patients who received ramucirumab plus paclitaxel after progressive disease on pembrolizumab. This early clinical observation suggests that the sequence of administration of PD-1 blockade and chemotherapy may be important in this disease.	esophagus