crossing96/oncoscreening huggingface dataset:
First-line treatment of patients with HER2-positive metastatic gastric and gastroesophageal junction cancer.	Fluoropyrimidine+cisplatin/oxaliplatin+trastuzumab therapy is recommended for the first-line treatment of HER2-positive metastatic gastric adenocarcinoma. However, there is no comprehensive study on which platinum-based treatment should be preferred. This study aimed to compare the treatment response and survival characteristics of patients with HER2-positive metastatic gastric or gastroesophageal junction (GEJ) cancer who received fluorouracil, oxaliplatin, and leucovorin (mFOLFOX)+trastuzumab or cisplatin and fluorouracil (CF)+trastuzumab as first-line therapy. It was a multicenter, retrospective study of the Turkish Oncology Group, which included 243 patients from 21 oncology centers. There were 113 patients in the mFOLFOX+trastuzumab arm and 130 patients in the CF+trastuzumab arm. The median age was 62 years in the mFOLFOX+trastuzumab arm and 61 years in the CF+trastuzumab arm (P = 0.495). 81.4% of patients in the mFOLFOX+trastuzumab arm and 83.1% in the CF+trastuzumab arm had gastric tumor localization (P = 0.735). The median progression-free survival (PFS) was significantly higher in the mFOLFOX+trastuzumab arm (9.4 months vs. 7.3 months, P = 0.024). The median overall survival (OS) was similar in both groups (18.4 months vs. 15.1 months, P = 0.640). Maintenance trastuzumab was continued after chemotherapy in 101 patients. In this subgroup, the median OS was 23.3 months and the median PFS was 13.3 months. In conclusion, mFOLFOX+trastuzumab is similar to CF+trastuzumab in terms of the median OS, but it is more effective in terms of the median PFS in the first-line treatment of HER2-positive metastatic gastric and GEJ cancer. The choice of treatment should be made by considering the prominent toxicity findings of the chemotherapy regimens.	esophagus
Concurrent Chemoradiotherapy-Driven Cell Plasticity by miR-200 Family Implicates the Therapeutic Response of Esophageal Squamous Cell Carcinoma.	Esophageal squamous cell carcinoma (ESCC) is a common and fatal malignancy with an increasing incidence worldwide. Over the past decade, concurrent chemoradiotherapy (CCRT) with or without surgery is an emerging therapeutic approach for locally advanced ESCC. Unfortunately, many patients exhibit poor response or develop acquired resistance to CCRT. Once resistance occurs, the overall survival rate drops down rapidly and without proper further treatment options, poses a critical clinical challenge for ESCC therapy. Here, we utilized lab-created CCRT-resistant cells as a preclinical study model to investigate the association of chemoradioresistantresistance with miRNA-mediated cell plasticity alteration, and to determine whether reversing EMT status can re-sensitize refractory cancer cells to CCRT response. During the CCRT treatment course, refractory cancer cells adopted the conversion of epithelial to mesenchymal phenotype; additionally, miR-200 family members were found significantly down-regulated in CCRT resistance cells by miRNA microarray screening. Down-regulated miR-200 family in CCRT resistance cells suppressed E-cadherin expression through snail and slug, and accompany with an increase in N-cadherin. Rescuing expressions of miR-200 family members in CCRT resistance cells, particularly in miR-200b and miR-200c, could convert cells to epithelial phenotype by increasing E-cadherin expression and sensitize cells to CCRT treatment. Conversely, the suppression of miR-200b and miR-200c in ESCC cells attenuated E-cadherin, and that converted cells to mesenchymal type by elevating N-cadherin expression, and impaired cell sensitivity to CCRT treatment. Moreover, the results of ESCC specimens staining established the clinical relevance that higher N-cadherin expression levels associate with the poor CCRT response outcome in ESCC patients. Conclusively, miR-200b and miR-200c can modulate the conversion of epithelial-mesenchymal phenotype in ESCC, and thereby altering the response of cells to CCRT treatment. Targeting epithelial-mesenchymal conversion in acquired CCRT resistance may be a potential therapeutic option for ESCC patients.	esophagus
Identification and Somatic Characterization of the Germline PTEN Promoter Variant rs34149102 in a Family with Gastrointestinal and Breast Tumors.	Genetic variants located in non-coding regions can affect processes that regulate protein expression, functionally contributing to human disease. Germline heterozygous mutations in the non-coding region of the PTEN gene have been previously identified in patients with PTEN hamartoma tumor syndrome (PHTS) diagnosed with breast, thyroid, and/or endometrial cancer. In this study, we report a PTEN promoter variant (rs34149102 A allele) that was identified by direct sequencing in an Italian family with a history of gastroesophageal junction (GEJ) adenocarcinoma and breast cancer. In order to investigate the putative functional role of the rs34149102 A allele variant, we evaluated the status of PTEN alterations at the somatic level. We found that PTEN protein expression was absent in the GEJ adenocarcinoma tissue of the index case. Moreover, we detected the occurrence of copy number loss involving the PTEN rs34149102 major C allele in tumor tissue, revealing that the second allele was somatically inactivated. This variant is located within an active regulatory region of the PTEN core promoter, and in silico analysis suggests that it may affect the binding of the nuclear transcription factor MAZ and hence PTEN expression. Overall, these results reveal the functional role of the PTEN promoter rs34149102 A allele variant in the modulation of PTEN protein expression and highlight its contribution to hereditary cancer risk.	esophagus
Prognostic Relevance of Weight and Weight Loss during Multimodal Therapy for Oesophagogastric Tumours.	The prognostic meaning of weight loss (WL) during standard treatment for operable oesophagogastric cancer is still unclear. The aim of this study is to analyse the prognostic effect of WL during perioperative chemotherapy (PC) for gastric cancer (GC) and oesophageal adenocarcinomas (OAC). We retrospectively analysed data from 128 patients (pts) with GC and OAC who underwent surgery in the context of multimodal treatment with PC. We collected data on WL during different steps of therapy together with other histopathologic and demographic information. We analysed the effects on overall survival (OS) and disease-free survival (DFS). Results: Pts with WL ≥ 5% during neoadjuvant chemotherapy exhibited significantly worse OS compared with pts with WL < 5% (median OS: 23.6 months [95% CI: 4.4−42.9] vs. 63.5 months [95% CI: 50.7−76.2], p = 0.007) and DFS (median DFS: 12.5 months [95% CI: 2.9−22.1] vs. 63.5 months [95% CI: 31.6−95.4], p = 0.016). Pts with WL ≥ 14% during the whole treatment exhibited significantly worse OS compared with pts with WL < 14% (median OS: 43.7 months [95% CI: 13.2−74.2] vs. not reached, p = 0.028) and DFS (median DFS: 34.3 months [95% CI: 14.0−54.5] vs. not reached, p = 0.038). Conclusion: WL patterns during neoadjuvant chemotherapy and during the whole treatment correlate with a significantly worse prognosis in operated pts with curative GC or OAC in the context of a multimodal treatment with PC. A validation of this prognostic effect in prospective studies is warranted.	esophagus
Immunotherapy in Squamous Cell Cancer of the Esophagus.	Treatment of esophageal carcinoma has changed dramatically following several landmark trials, which have proven the benefit of immunotherapy. The selective PD-1 (programmed cell death ligand-1)-inhibitor nivolumab has been shown to improve DFS in the adjuvant therapy setting (CheckMate-577). In the first-line treatment, PD-L1 positive (CPS ≥ 10) squamous cell carcinoma patients (pts) have been shown to have an increased OS following treatment with the PD-1-inhibitor pembrolizumab in combination with chemotherapy (KEYNOTE-590). Nivolumab also improved overall survival in the first line setting either combined with ipilimumab or with chemotherapy (CheckMate 648) compared to chemotherapy alone. In Asian first-line patients, phase III trials investigating camrelizumab (ESCORT 1), toripalimab (JUPITER 06), or sintilimab (ORIENT 15) in addition to chemotherapy also showed significant survival benefits. In the second-line setting, monotherapy with nivolumab (ATTRACTION-03), pembrolizumab (KEYNOTE-181), camrelizumab (ESCORT), and tislelizumab (RATIONALE 302) demonstrated a benefit in OS in comparison to chemotherapy. Here we will review these trials and integrate them into the current treatment algorithm.	esophagus
Network meta-analysis of the optimal time of applying enteral immunonutrition in esophageal cancer patients receiving esophagectomy.	BACKGROUND: Enteral immunonutrition (EIN) has been extensively applied in cancer patients; however, its role in esophageal cancer (EC) patients receiving esophagectomy remains unclear. We performed this network meta-analysis to investigate the impact of EIN on patients undergoing surgery for EC and further determine the optimal time of applying EIN. METHODS: We searched PubMed, EMBASE, Cochrane library, and China National Knowledgement Infrastructure (CNKI) to identify eligible studies. Categorical data was expressed as the odds ratio with 95% confidence interval (CI), and continuous data was expressed as mean difference (MD) with 95% CI. Meta-analysis with head-to-head approach and network meta-analysis was performed to evaluate the impact of EIN on clinical outcomes using RevMan 5.3 and ADDIS V.1.16.8 software. The surface under the cumulative ranking curve (SUCRA) was calculated to rank all nutritional regimes. RESULTS: Total 14 studies involving 1071 patients were included. Meta-analysis with head-to-head approach indicated no difference between EIN regardless of the application time and standard EN (SEN); however, subgroup analyses found that postoperative EIN was associated with decreased incidence of total infectious complications (OR = 0.47; 95%CI = 0.26 to 0.84; p = 0.01) and pneumonia (OR = 0.47; 95%CI = 0.25 to 0.90; p = 0.02) and shortened the length of hospitalization (LOH) (MD =  - 1.01; 95%CI =  - 1.44 to - 0.57; p < 0.001) compared to SEN, which were all supported by network meta-analyses. Ranking probability analysis further indicated that postoperative EIN has the highest probability of being the optimal option in terms of these three outcomes. CONCLUSIONS: Postoperative EIN should be preferentially utilized in EC patients undergoing esophagectomy because it has optimal potential of decreasing the risk of total infectious complications and pneumonia and shortening LOH. OSF REGISTRATION NUMBER: 10.17605/OSF.IO/KJ9UY.	esophagus
Is Prophylactic Cervical Drainage Effective in Patients Undergoing McKeown Esophagectomy Reconstructed Through the Retrosternal Route with Two-Field Lymphadenectomy?	BACKGROUND: McKeown esophagectomy with two-field lymphadenectomy is the treatment of choice for oncologic esophagectomy. A cervical drain is placed in cases after modern two-field lymph node dissection (M2FD) to provide information on anastomotic leakage. However, the necessity of prophylactic cervical drainage during surgery remains unknown. This study aimed to clarify the clinical significance of cervical drainage in patients who underwent McKeown esophagectomy with M2FD. METHODS: A total of 293 patients underwent McKeown surgery with two-field lymphadenectomy at our institute between January 2013 and December 2019. We compared the day of drain removal, amount of drainage volume, and the appearance of drainage fluid between patients with and without anastomotic leakage. RESULTS: McKeown esophagectomy reconstructed through the retrosternal route is 203 patients (69.3%) of all. Nineteen patients (6.5%) experienced anastomotic leakage. The amount of cervical drain discharge was comparable between patients with and without anastomotic leakage. In addition, no purulent or salivary discharge was observed in patients with anastomotic leakage. There was no difference in the median day of drain removal between the groups. The initial clinical findings for the diagnosis of anastomotic leakage were surgical site infection in 10 (52.6%), fever in 5 (26.3%), prolonged inflammation in a blood test in 3 (15.8%), and bloody discharge from the chest tube in 1 (5.3%). There was no mortality due to any cause. CONCLUSION: A prophylactic cervical drain may not be mandatory in patients with esophageal cancer undergoing McKeown esophagectomy reconstructed through the retrosternal route with two-field lymphadenectomy.	esophagus
Prognostic impact of angiotensin-converting enzyme inhibitors and angiotensin receptors blockers in esophageal or gastric cancer patients with hypertension - a real-world study.	BACKGROUND: Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are used in treating cardiovascular diseases. Previous studies indicated that ACEIs/ARBs may benefit cancer patients by inhibiting tumor angiogenesis and proliferation. The effect of ACEIs/ARBs on cancer survival in esophageal and gastric cancer is still unclear. This study is to investigate the association between ACEIs/ARBs usage and esophageal and gastric cancer prognosis. METHODS: This retrospective cohort study identified esophageal and gastric cancer patients during 2008-2016 from the Taiwan Cancer Registry, and obtained medication usage and follow-up information from the National Health Insurance Research Database and Death Registry. Analysis groups were defined as ACEIs/ARBs user or non-user based on the usage of ACEIs/ARBs within the 6 months after cancer diagnosis. The stabilized inverse probability of treatment weighting using propensity scores was applied to balance covariates between study groups. We also used Kaplan-Meier estimates and Cox regression to compare survival outcome and estimate hazard ratios (HRs). RESULTS: We identified 14,463 and 21,483 newly-diagnosed esophageal and gastric cancer patients during 2008-2016. ACEIs/ARBs users were associated with lower risk of cancer-specific mortality, although only significantly in gastric cancer (gastric: adjusted HR = 0.87, 95% CI = 0.78-0.97; esophageal: adjusted HR =0.88, 95% CI = 0.76-1.02). A better survival outcome was observed among patients who received higher cumulative defined daily dose of ACEIs/ARBs. CONCLUSIONS: We found that using ACEIs/ARBs after cancer diagnosis were associated with lower risk of mortality. Our results add to the knowledge of the benefit of ACEIs/ARBs against mortality in individuals with esophageal/gastric cancer patients with hypertension.	esophagus
THE PROGNOSIS OF THE DIFFERENT ESOPHAGEAL NEUROENDOCRINE CARCINOMA SUBTYPES: A POPULATION-BASED STUDY.	BACKGROUND: Neuroendocrine neoplasms are extremely rare and account for 0.4% to 2% of all malignant esophageal neoplasms. The burden of the neuroendocrine histological type on the patients' prognosis and survival is poorly debated. This study aimed to compare the survival rates of primary neuroendocrine neoplasms compared with adenocarcinoma and squamous cell carcinoma of the esophagus. METHODS: This is a retrospective cohort from the Surveillance, Epidemiology, and End Results Program database. Overall survival and cancer-specific survival were evaluated with Kaplan-Meier curves and logrank tests. Proportional Cox regression models were used to evaluate variables related to overall survival. RESULTS: After eligibility criteria, 66,528 patients were selected. The mean follow-up was 22.6 months (SD 35.6). Adenocarcinoma was predominant (62%), followed by squamous cell carcinoma (36%). Large cell carcinoma, small cell carcinoma, and mixed adenoneuroendocrine carcinoma each account for less than 1% each. On the long-term overall survival analysis, esophageal adenocarcinoma showed a better prognosis than all the other histologic types (P-value for logrank test <0.001). With adenocarcinoma as a reference, HR was 1.32 for large cell carcinoma (95%CI 1.2 to 1.45) and 1.37 for small cell carcinoma (95%CI 1.23 to 1.53). The HR was 1.22 for squamous cell carcinoma (95%CI: 1.2 to 1.24); and 1.3 for adenoneuroendocrine carcinoma (95%CI 1.01 to 1.66). For multivariate Cox regression analysis, besides age and stage, the neuroendocrine subtypes large cell carcinoma and small cell carcinoma were considered independent prognostic variables. CONCLUSION: In the esophagus, large cell carcinoma and small cell carcinoma show poorer long-term survival rates than squamous cell carcinoma and adenocarcinoma.	esophagus
A novel nomogram predicting the risk of postoperative pneumonia for esophageal cancer patients after minimally invasive esophagectomy.	BACKGROUND: Pneumonia is a common complication after minimally invasive esophagectomy (MIE), which prolongs hospital stay, adding to the cost and increasing the risk to patients' lives. This study aimed to identify risk factors and establish a predictive nomogram for postoperative pneumonia (PP). METHODS: This case control study included 609 patients with esophageal cancer who underwent MIE between March 2015 and August 2019 in Cancer Hospital, Chinese Academy of Medical Sciences. We randomly divided the data into training and validation sets in the ratio of 7:3 and performed univariate and multivariate logistic regression analyses to acquire independent risk factors of the training set. We constructed a nomogram based on the independent risk factors. The concordance index (C-index), receiver operating characteristic (ROC) curve, calibration plot, and decision curve analysis (DCA) plots were used to evaluate the discrimination of the nomogram. Validation set was applied to confirm the predictive value of the nomogram. RESULTS: In the univariate analysis, age, gender, abdominal procedure method, thoracic operative time, duration of chest tube placement, anastomotic leakage, and recurrent laryngeal nerve palsy were found to be correlated with the incidence of PP. In multivariate analysis, all variables except thoracic operative time were found to be independent risk factors for PP. A nomogram was constructed based on these independent risk factors. The C-index of the training and validation sets was 0.769 and 0.734, respectively, and the areas under the curve (AUC) of ROC curves of the training and validation sets were 0.769 and 0.686, respectively. The calibration plots and DCA plots of the training and validation sets showed the accuracy and predictive value of the nomogram. CONCLUSION: The nomogram could accurately identify the risk factors for PP. We could predict the occurrence of PP based on this nomogram and take corresponding measures to reduce the incidence of PP.	esophagus
Sociodemographic and Facility-Related Disparities in the Delivery of Guideline-Concordant Therapy Among Patients With Esophageal Adenocarcinoma.	PURPOSE: Evidence on health disparities among patients treated with multimodality therapy protocols is still limited. We aimed to evaluate the associations between patient-level and system-level factors and the receipt of guideline-concordant therapy among patients with esophageal adenocarcinoma (EA). METHODS: This is a national cohort study of patients with stage I-III EA in the National Cancer Database (2006-2018) treated with either upfront resection or neoadjuvant therapy followed by surgery. Clinical and pathologic staging data were used for defining guideline-concordant therapy. Logistic regression models were built to identify independent associations between deviations from treatment guidelines and clinical, sociodemographic, and hospital-related factors. RESULTS: Among 18,803 patients with EA treated at 1,049 hospitals, 4,511 had an endoscopic resection, 4,866 had upfront resection, and 9,426 had neoadjuvant therapy followed by surgery. A total of 16,002 patients (85.1%) received guideline-concordant therapy. Patients who were age 70 years or older (odds ratio [OR] 1.35; 95% CI, 1.14 to 1.60), had a Charlson-Deyo modified score of ≥ 1, and were treated at hospitals with a safety-net burden of ≥ 10% (OR 1.13; 95% CI, 1.02 to 1.25) had higher risk of deviations from guidelines, whereas treatment at high-volume facilities (OR 0.84; 95% CI, 0.74 to 0.95) and diagnosis after 2011 decreased this risk. Relative to cT0-1N0 patients, those with cT2N0 disease had the highest risk of deviations from guideline-concordant therapy (OR 3.76; 95% CI, 3.30 to 4.29). Among patients treated at high-volume facilities, safety-net burden over 10% increased the risk of deviations (OR 1.26; 95% CI, 1.01 to 1.57). CONCLUSION: The delivery of guideline-concordant therapy among patients with EA varies significantly across clinical stage groups and is associated with several sociodemographic disparities. This knowledge should be a resource for future quality improvement strategies intended to address inequitable care within vulnerable populations.	esophagus
MLDRL: Multi-loss disentangled representation learning for predicting esophageal cancer response to neoadjuvant chemoradiotherapy using longitudinal CT images.	Accurate prediction of pathological complete response (pCR) after neoadjuvant chemoradiotherapy (nCRT) is essential for clinical precision treatment. However, the existing methods of predicting pCR in esophageal cancer are based on the single stage data, which limits the performance of these methods. Effective fusion of the longitudinal data has the potential to improve the performance of pCR prediction, thanks to the combination of complementary information. In this study, we propose a new multi-loss disentangled representation learning (MLDRL) to realize the effective fusion of complementary information in the longitudinal data. Specifically, we first disentangle the latent variables of features in each stage into inherent and variational components. Then, we define a multi-loss function to ensure the effectiveness and structure of disentanglement, which consists of a cross-cycle reconstruction loss, an inherent-variational loss and a supervised classification loss. Finally, an adaptive gradient normalization algorithm is applied to balance the training of multiple loss terms by dynamically tuning the gradient magnitudes. Due to the cooperation of the multi-loss function and the adaptive gradient normalization algorithm, MLDRL effectively restrains the potential interference and achieves effective information fusion. The proposed method is evaluated on multi-center datasets, and the experimental results show that our method not only outperforms several state-of-art methods in pCR prediction, but also achieves better performance in the prognostic analysis of multi-center unlabeled datasets.	esophagus