crossing96/oncoscreening huggingface dataset:
A phase II Study Evaluating Combined Neoadjuvant Cetuximab and Chemotherapy Followed by Chemoradiotherapy and Concomitant Cetuximab in Locoregional Oesophageal Cancer Patients.	BACKGROUND: Pre-operative chemoradiotherapy using a 5-fluorouracil (5-FU)/cisplatin backbone is widely used to improve surgical outcomes in locoregional oesophageal cancer patients, despite a non-negligible failure rate. OBJECTIVE: We evaluated intensification of this approach to improve patient outcomes by adding cetuximab to induction 5-FU/cisplatin/docetaxel (TPF) and to chemoradiotherapy in a phase II study. PATIENTS AND METHODS: Between November 2006 and April 2009, 50 patients with stage II-IVa squamous cell carcinoma (SCC) or adenocarcinoma of the oesophagus or gastro-oesophageal junction initiated three TPF/cetuximab cycles. Six weeks later, patients with response or stabilisation initiated 6 weeks of cisplatin/cetuximab/radiotherapy, followed by surgery. The primary objective was the clinical complete response (cCR) rate after induction therapy plus chemoradiotherapy in intent-to-treat patients. RESULTS: Thirty-eight patients were evaluable after chemoradiotherapy, 84% of whom showed disease control. Six patients (12%) achieved a cCR, with a 54% overall response rate. Twenty-seven patients underwent surgery, 11 of whom (22%; nine SCC, two adenocarcinoma) had a pathological CR (41%). Fifteen patients were alive after a median follow-up of 23.2 months. Median progression-free survival was 12.2 months (95% confidence interval [CI] 1.7-22.8). Median overall survival was 23.4 months (95% CI 12.2-36.6) and was significantly longer among the 22 patients with complete resection than in the five patients without (42.1 vs. 24.9 months; p = 0.02, hazard ratio: 3.6, 95% CI 1.1-11.6). The toxicity profile was acceptable. CONCLUSIONS: Neoadjuvant cetuximab/TPF followed by chemoradiotherapy in locoregional oesophageal carcinoma patients is feasible and offers a modest response rate in this trial. The results of combining trimodality neoadjuvant treatment with cetuximab are consistent with the literature. Registration: The study is registered at ClinicalTrials.gov (NCT00733889).	esophagus
The targeted regulation of Gli1 by miR-361 to inhibit epithelia-mesenchymal transition and invasion of esophageal carcinoma cells.	Epithelia-mesenchymal transition (EMT) is critical for invasion and metastasis of esophageal carcinoma. Gli1, a transcriptional factor in Hedgehog pathway, is correlated with EMT, invasion and metastasis of tumors. However, its role in esophageal cancer is still unknown. Bioinformatics analysis revealed relationship between microRNA (miR)-361 and 3'-UTR of Gli1 gene. This study thus investigated the role of miR-361 and Gli1 in invasion and metastasis of esophageal cancer. Both tumor and adjacent tissues were collected from 58 esophageal cancer patients to test the expressions of miR-361 and Gli1, the relationship of which was confirmed by dual-luciferase reporter gene assay. Cultured esophageal cancer cells EC9706 were transfected with mimic NC, miR-361 mimic, si-NC, si-Gli1, miR-361 mimics+si-Glil, pQC or pQC-FU-Gli1. Transwell and colony formation assays were performed for cell invasion and attachment-independent growth. Expressions of Gli1, Snail, E-cadherin and N-cadherin proteins were revealed by Western blotting. The expression of Gli1 was significantly elevated in esophageal cancer tissues, along with lower miR-361 expression which was correlated with TNM stage. MiR-361 inhibited the expression of Gli1 via targeting on 3'-UTR of Gli1 gene. The transfection of miR-361 mimics and/or si-Gli1 significantly suppressed the growth of malignant cells. The over-expression of miR-361 and/or silencing of Gli1 decreased intracellular expression of Gli1, Snail and N-cadherin, and increased E-cadherin expression to suppress EMT and invasion of tumor cells while the opposite effects were obtained by over-expression of Gli1. Abnormal elevation of Gli1 and decrease of miR-361 were found in esophageal cancer tissues. MiR-361 weakened invasion of cancer cells and impeded EMT process via the inhibition of Gli1.	esophagus
Toenail mineral concentration and risk of esophageal squamous cell carcinoma, results from the Golestan Cohort Study.	Studies conducted in China linked selenium deficiency to higher risk of esophageal squamous cell carcinoma (ESCC), but this has not been widely tested outside that selenium-deficient region. The aim of this study was to investigate the association between selenium and other mineral concentrations in toenails and risk of ESCC in a region with high incidence rates. In this nested case-control study, we identified 222 cases of ESCC from the Golestan Cohort Study, Iran, which has followed up 50,045 participants since enrollment (2004-2008). We randomly selected one control for each case matched by age and sex, using incidence density sampling. We used toenail samples collected at baseline to measure the concentration of selenium, zinc, chromium, mercury, and scandium using instrumental neutron activation analysis. Multivariate adjusted logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals. Median nail selenium, zinc, chromium, and mercury levels were 1.01, 74.59, 0.77, and 0.018 μg/g in cases and 1.02, 75.71, 0.71, and 0.023 μg/g in controls, respectively. The adjusted odds ratios comparing each fourth quartile of mineral status versus the first quartile were as follows: selenium = 0.78 (95% CI, 0.41-1.49); zinc=0.80 (95% CI, 0.42-1.53); chromium = 0.91 (95% CI, 0.46-1.80); and mercury=0.61 (95% CI, 0.27-1.38), and all trend tests were non-significant. The nail selenium concentration in our controls reflects relatively high selenium status. No evidence of association between selenium or chromium concentrations in toenails and the risk of ESCC was detected in this population.	esophagus
Genetic Predictors of Response to Systemic Therapy in Esophagogastric Cancer.	The incidence of esophagogastric cancer is rapidly rising, but only a minority of patients derive durable benefit from current therapies. Chemotherapy as well as anti-HER2 and PD-1 antibodies are standard treatments. To identify predictive biomarkers of drug sensitivity and mechanisms of resistance, we implemented prospective tumor sequencing of patients with metastatic esophagogastric cancer. There was no association between homologous recombination deficiency defects and response to platinum-based chemotherapy. Patients with microsatellite instability-high tumors were intrinsically resistant to chemotherapy but more likely to achieve durable responses to immunotherapy. The single Epstein-Barr virus-positive patient achieved a durable, complete response to immunotherapy. The level of ERBB2 amplification as determined by sequencing was predictive of trastuzumab benefit. Selection for a tumor subclone lacking ERBB2 amplification, deletion of ERBB2 exon 16, and comutations in the receptor tyrosine kinase, RAS, and PI3K pathways were associated with intrinsic and/or acquired trastuzumab resistance. Prospective genomic profiling can identify patients most likely to derive durable benefit to immunotherapy and trastuzumab and guide strategies to overcome drug resistance.Significance: Clinical application of multiplex sequencing can identify biomarkers of treatment response to contemporary systemic therapies in metastatic esophagogastric cancer. This large prospective analysis sheds light on the biological complexity and the dynamic nature of therapeutic resistance in metastatic esophagogastric cancers. Cancer Discov; 8(1); 49-58. ©2017 AACR.See related commentary by Sundar and Tan, p. 14See related article by Pectasides et al., p. 37This article is highlighted in the In This Issue feature, p. 1.	esophagus
Beta-elemene treatment is associated with improved outcomes of patients with esophageal squamous cell carcinoma.	PURPOSE: To investigate the therapeutic effects of concurrent preoperative β-elemene treatment in patients with esophageal squamous cell carcinoma who received concurrent chemoradiotherpay followed by surgery. METHOD: The clinicopathological parameters and outcomes of 102 patients with esophageal squamous cell carcinoma were studied and compared between patients treated with and without β-elemene. RESULTS: β-elemene treatment could prolong the overall survival and progression-free survival. The 3-year overall survival rate was also increased by β-elemene treatment. β-elemene treatment was an independent prognostic factor for both overall survival and progression-free survival. Occurrence of toxicities associated with chemoradiotherapy was decreased by β-elemene treatment. CONCLUSIONS: Findings in this study suggested that β-elemene treatment provided survival benefits and reduced chemoradiotherapy-associated toxicities in patients with esophageal squamous cell carcinoma.	esophagus
Cancer Risk Associated With Exposure to Bitumen and Bitumen Fumes: An Updated Systematic Review and Meta-Analysis.	OBJECTIVE: To evaluate whether cancer risks are increased among bitumen (asphalt) workers. METHODS: Systematic review and meta-analysis of cancer risks (lung, upper aerodigestive tract (UADT), esophagus, bladder, kidney, stomach, and skin) and bitumen exposure. Certainty in the epidemiological evidence that bitumen-exposed workers experience increased cancer risks was rated using Grading of Recommendations Assessment, Development and Evaluation criteria. RESULTS: After excluding lower-quality studies, lung cancer risks were not increased among bitumen-exposed workers (meta-relative risk [RR] 0.94, 95% CI 0.74 to 1.20, eight studies). Increased risks of UADT and stomach cancers were observed (meta-RR 1.31, 95% CI 1.03 to 1.67, 10 studies and meta-RR 1.29, 95% CI 1.03 to 1.62, seven studies, respectively). CONCLUSIONS: Except for lung cancer, evidence for increased cancer risks among bitumen-exposed workers was judged to be of low certainty, due to inadequate exposure characterization and unmeasured confounders (coal tar exposure, smoking, and alcohol consumption).	esophagus
Study for reducing lung dose of upper thoracic esophageal cancer radiotherapy by auto-planning: volumetric-modulated arc therapy vs intensity-modulated radiation therapy.	This study aimed to investigate the dosimetric differences and lung sparing between volumetric-modulated arc therapy (VMAT) and intensity-modulated radiation therapy (IMRT) in the treatment of upper thoracic esophageal cancer with T3N0M0 for preoperative radiotherapy by auto-planning (AP). Sixteen patient cases diagnosed with upper thoracic esophageal cancer T3N0M0 for preoperative radiotherapy were retrospectively studied, and 3 plans were generated for each patient: full arc VMAT AP plan with double arcs, partial arc VMAT AP plan with 6 partial arcs, and conventional IMRT AP plan. A simultaneous integrated boost with 2 levels was planned in all patients. Target coverage, organ at risk sparing, treatment parameters including monitor units and treatment time (TT) were evaluated. Wilcoxon signed-rank test was used to check for significant differences (p < 0.05) between datasets. VMAT plans (pVMAT and fVMAT) significantly reduced total lung volume treated above 20 Gy (V(20)), 25 Gy (V(25)), 30 Gy (V(30)), 35 Gy (V(35)), 40 Gy (V(40)), and without increasing the value of V(10), V(13), and V(15). For V(5) of total lung value, pVMAT was similar to aIMRT, and it was better than fVMAT. Both pVMAT and fVMAT improved the target dose coverage and significantly decreased maximum dose for the spinal cord, monitor unit, and TT. No significant difference was observed with respect to V(10) and V(15) of body. VMAT AP plan was a good option for treating upper thoracic esophageal cancer with T3N0M0, especially partial arc VMAT AP plan. It had the potential to effectively reduce lung dose in a shorter TT and with superior target coverage and dose homogeneity.	esophagus
Smoking, Gender, and Overweight Are Important Influencing Factors on Monocytic HLA-DR before and after Major Cancer Surgery.	BACKGROUND: Monocytic human leukocyte antigen D related (mHLA-DR) is essential for antigen-presentation. Downregulation of mHLA-DR emerged as a general biomarker of impaired immunity seen in patients with sepsis and pneumonia and after major surgery. Influencing factors of mHLA-DR such as age, overweight, diabetes, smoking, and gender remain unclear. METHODS: We analyzed 20 patients after esophageal or pancreatic resection of a prospective, randomized, placebo-controlled, double-blind trial (placebo group). mHLA-DR was determined from day of surgery (od) until postoperative day (pod) 5. Statistical analyses were performed using multivariate generalized estimating equation analyses (GEE), nonparametric multivariate analysis of longitudinal data, and univariate post hoc nonparametric Mann-Whitney tests. RESULTS: In GEE, smoking and gender were confirmed as significant influencing factors over time. Univariate analyses of mHLA-DR between smokers and nonsmokers showed lower preoperative levels (p = 0.010) and a trend towards lower levels on pod5 (p = 0.056) in smokers. Lower mHLA-DR was seen in men on pod3 (p = 0.038) and on pod5 (p = 0.026). Overweight patients (BMI > 25 kg/m(2)) had lower levels of mHLA-DR on pod3 (p = 0.039) and pod4 (p = 0.047). CONCLUSION: Smoking is an important influencing factor on pre- and postoperative immune function while postoperative immune function was influenced by gender and overweight. Clinical trial registered with ISRCTN27114642.	esophagus
Cell Signaling Pathway in 12-O-Tetradecanoylphorbol-13-acetate-Induced LCN2 Gene Transcription in Esophageal Squamous Cell Carcinoma.	LCN2 is involved in various cellular functions, including transport of small hydrophobic molecules, protection of MMP9 from proteolytic degradation, and regulating innate immunity. LCN2 is elevated in multiple human cancers, frequently being associated with tumor size, stage, and invasiveness. Our previous studies have shown that LCN2 expression could be induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) in esophageal squamous cell carcinoma (ESCC) by the binding of five nucleoproteins (MISP, KLF10, KLF15, PPP1R18, and RXRβ) at a novel TPA-responsive element (TRE), at -152~-60 bp of the 5' flanking region of the LCN2 promoter. However, much is unknown about whether these proteins can respond to TPA stimulation to regulate LCN2 transactivation and which cell signaling pathways mediate this process. In this study, expression plasmids encoding these five nucleoproteins were stably transfected into EC109 cells. Then, stable transfectant was characterized by a Dual-Luciferase Reporter Assay System. RT-PCR, real-time PCR, western blotting, specific kinase inhibitor treatment, and bioinformatics analyses were applied in this study. We found that MISP, KLF10, KLF15, PPP1R18, and RXRβ proteins could strongly respond to TPA stimulation and activate LCN2 transcriptional expression. MEK, ERK, JNK, and P38 kinases were involved in the LCN2 transactivation. Furthermore, the MEK-ERK signal pathway plays a major role in this biological process but does not involve PKCα signaling.	esophagus
"""Energy-less technique"" with mini-clips for recurrent laryngeal nerve lymph node dissection in prone thoracoscopic esophagectomy for esophageal cancer."	BACKGROUND: Meticulous recurrent laryngeal nerve (RLN) lymph node dissection in thoracoscopic esophagectomy for esophageal cancer often results in RLN paralysis. METHODS: We had attempted to simply cut the vessels around RLN sharply with scissors without using energy device in order to prevent RLN paralysis. However, these procedures often result in minor bleeding. Since we introduced the use of mini-clips for hemostasis before cutting the vessels with scissors, we herein compared the surgical results between before and after the introduction of use of mini-clips. RESULTS: With regard to RLN paralysis, the incidence was 24.0% in the before group; this incidence went down to 5.1% in the after group (P = 0.0259). Moreover, length of hospital stay after surgery was significantly shortened, from 36.1 days to 22.0 days, after the introduction of energy-less techniques with mini-clips (P = 0.0075). CONCLUSIONS: Our data demonstrated that this technique contributed to prevent RLN paralysis and to shorten the patient's length of hospital stay.	esophagus
Prolonged interval between neoadjuvant chemoradiotherapy and esophagectomy does not benefit the outcome in esophageal cancer: a systematic review and meta-analysis.	Whether a prolonged interval between neoadjuvant chemoradiotherapy (nCRT) and esophagectomy could benefits conditions such as rectal cancer, still remains unknown. We therefore performed the current study to evaluate the influence of the interval between nCRT and esophagectomy on the clinical outcomes in patients with esophageal cancer. PubMed and Embase were searched to identify eligible cohort studies. The primary outcome was five-year overall survival (OS), and secondary outcomes included the incidence of anastomotic complications, perioperative mortality, pathologic complete response (pCR) rate, positive circumferential resection margin (CRM) rate, and R0 resection rate. A random-effects model was used for all meta-analyses irrespective of heterogeneity. Ten cohort studies with 2383 patients were included. Overall, the pooled estimate revealed that the prolonged interval has no impact on five-year OS (odds ratio (OR) 0.87, 95% CI 0.66 to 1.14, P = 0.30), with low heterogeneity (PH = 0.78, I2 = 0%). However, it was associated with an increased risk of anastomotic complication (OR 1.71, 95% CI 1.15 to 2.54, P = 0.008), with no effect on perioperative mortality (OR 1.20, 95% CI 0.79 to 1.83, P = 0.40). Additionally, the prolonged interval failed to increase the pCR rate (OR 1.02, 95% CI 0.78 to 1.33, P = 0.89). Even worse, it was correlated with a decreased R0 resection rate (OR 0.60, 95% CI 0.41 to 0.88, P = 0.009) and increased positive CRM rate (OR 2.20, 95% CI 1.44 to 3.36, P < 0.001). This study suggests that the prolonged interval between nCRT and esophagectomy fails to result in better outcomes, and in fact, could worsen clinical outcomes, with increasing anastomotic complications, and undermine resection completeness. However, this conclusion should be treated with caution because of the limitations of retrospective cohort study and substantial clinical heterogeneity. (The study was registered at PRESPERO as CRD42016048210).	esophagus
Treatment results of neoadjuvant chemoradiotherapy followed by radical esophagectomy in patients with initially inoperable thoracic esophageal cancer.	PURPOSE: We evaluated the effectiveness of neoadjuvant chemoradiotherapy (CRT) followed by esophagectomy for cT4 esophageal cancer or lymph node metastases (LNM) invading adjacent structures. MATERIALS AND METHODS: We retrospectively evaluated 42 consecutive patients with thoracic esophageal cancer who underwent CRT followed by esophagectomy between 2008 and 2013. All were initially considered to be unresectable because of cT4 (n = 32) disease or LN invasion (n = 10). Radiotherapy was administered at 41.4 Gy/23 fr with concurrent chemotherapy. At completion of CRT, restaging was performed using computed tomography (CT). RESULTS: All cT4 tumors were downstaged, LNM invading to adjacent structures were considered to be released, and subtotal esophagectomy was performed. The median follow-up period was 42 months. The curative resection (R0) rate was 94% in cT4 group and 70% in LN invasion group. The 3-year overall survival (OS) and 3-year locoregional control (LRC) rates were 65-80% in the cT4 group and 50-67% in LN invasion group, respectively. CONCLUSIONS: The cT4 group showed good rates of R0, OS, and LRC. Surgical resection should be an effective option when downstaging is achieved by CRT for patients with initially inoperable thoracic esophageal cancer.	esophagus
Macrophage migration inhibitory factor promotes tumor aggressiveness of esophageal squamous cell carcinoma via activation of Akt and inactivation of GSK3β.	The pleiotropic pro-inflammatory cytokine, macrophage migration inhibitory factor (MIF), represents an important link between chronic inflammation and tumorigenesis. Although accumulating evidence demonstrates that MIF overexpression is implicated in the development and progression of multiple cancers, including esophageal squamous cell carcinoma (ESCC), the molecular mechanisms underlying its tumor-promoting roles in ESCC remain unclear. In the present study, we observed that MIF is overexpressed in ESCC and correlated significantly with lymph node metastasis, advanced clinical stage, and poor survival of ESCC. MIF knockdown attenuated the proliferation, migration, and invasion of ESCC cells in vitro and in vivo. Moreover, blockage of MIF expression decreased the activation of the Akt, MEK/ERK, and NF-κB pathways and enhanced sensitivity to apoptosis. Meanwhile, repression of MIF expression resulted in activation of glycogen synthase kinase 3 beta (GSK3β) and subsequent decrease of active β-catenin, as well as its downstream targets including cyclin D1, matrix metalloproteinase (MMP)-7, c-myc, and c-Jun. Collectively, our results provided mechanistic insights into the tumor-promoting role of MIF in ESCC, and suggested that MIF represents a potential therapeutic target for treatment of ESCC.	esophagus
Perioperative chemotherapy vs. neoadjuvant chemoradiation in gastroesophageal junction adenocarcinoma : A population-based evaluation of the Munich Cancer Registry.	BACKGROUND: To date, it remains unclear whether locally advanced adenocarcinoma of the gastroesophageal junction (AEG) should be treated with neoadjuvant chemoradiation (nCRT), analogous to esophageal cancer, or with perioperative chemotherapy (pCT), analogous to gastric cancer. The purpose of this study was to analyze the data of the Munich Cancer Registry (MCR) and to compare pCT and nCRT in AEG patients. PATIENTS AND METHODS: A total of 2,992 AEG patients, treated between 1998 and 2014, were included in the study. Baseline and tumor parameters as well as overall survival (OS) and tumor recurrence were compared between 56 patients undergoing nCRT and 64 patients undergoing pCT with UICC stage II/III cancer. In addition, uni- and multivariate analyses using Cox regression models were performed to evaluate the effect of tumor characteristics and treatment regimens on OS. RESULTS: In patients with UICC stage II/III AEG treated with either nCRT or pCT, no significant differences were seen for baseline and tumor characteristics. While there was a significantly higher cumulative incidence of locoregional treatment failure after pCT (32.8%; 95% CI: 18.0-48.4%) compared with nCRT (7.4%; 95% CI: 2.3-16.5%; p = 0.007), there was no significant difference for distant treatment failure (52.9%; 95% CI: 35.4-67.7% and 38.4%; 95% CI: 23.7-52.9%; p = 0.347). When analyzing the whole cohort, patients who received pCT were younger (58.3 years vs. 63.0 years; p = 0.016), had a higher chance of complete tumor resection (81% vs. 67%; p = 0.033), more resected lymph nodes (p = 0.036), and fewer lymph node metastases (p = 0.038) compared with patients who received nCRT. Nevertheless, there was still a strong trend toward a higher incidence of local treatment failure after pCT (25.8%; 95% CI: 14.7-38.3% vs. 12.6%; 95% CI: 5.5-22.8%; p = 0.053). Comparable to the results for patients with UICC stage II/III, no difference was seen for the incidence of distant treatment failure. When excluding patients with UICC stage IV cancer, no significant difference was found for OS. CONCLUSION: For UICC stage II/III carcinoma, nCRT was associated with an improved locoregional tumor control compared with pCT, while no further significant differences were seen between nCRT and pCT for UICC stage II/III AEG. Moreover, there was a strong trend toward improved locoregional tumor control after nCRT when analyzing all patients treated with nCRT or pCT, despite these patients having higher risk factors.	esophagus