bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of hyperlipidemia in patients with a history of colon cancer.
Authors: Tarar Zahid , Zafar Muhammad Usman , Ghous Ghulam , Farooq Umer , Ahluwalia Arjan 
Published: June 2021

e15603 Background: The most common cancer of the digestive system is colorectal cancer. 5-year survival rate of early-stage colon cancer is > 90% whereas it is only 10% for patients with distant metastases. Recent studies have shown that lipids influence a tumor’s metastatic capabilities. High fat diet has also been linked with colon cancer. In this study, we try to understand the effect of hyperlipidemia in patients with a history of colon cancer. Methods: This is a retrospective study examining data from the National Inpatient Sample (NIS) Database of the year 2018. We identified patients with any history of Colon cancer using their specific ICD-10 codes. Additionally, we queried for ICD10 codes for hyperlipidemia. Primary outcome was inpatient mortality. Secondary outcome was hospital length of stay and total charge. Utilizing STATA MP 16.1 we performed multivariate logistic regression analysis. Various comorbidities including previous history of coronary artery disease, peripheral artery disease, stroke, smoking, diabetes, hypertension and chemotherapy were incorporated into the analysis. Additionally, hospital demographics were included in the analysis as well including race, hospital bed size teaching status, location, region, insurance and patient income. Data was considered statistically significant if p-value was < 0.05. Results: The total number of patients included in this study were 34,792. They were all adults age > 18 years. Approximately 49% were females. Mean age was 67 years and average hospital length of stay was 6.5 days. After running multivariable analysis for inpatient mortality, we noted that patients with hyperlipidemia had lower odds of mortality (Odds Ratio (OR) 0.64, 95% Confidence Intervals (CI) 0.56 – 0.73). Higher odds of mortality were seen in patients with coronary artery disease (OR 1.23, 95% CI 1.05 – 1.44). Among racial distributions, Blacks had higher odds of mortality when compared with White (OR 1.3, 95% CI 1.1 – 1.5). Hispanics had lower odds of inpatient mortality compared to Whites (OR 0.8, 95% CI 0.6 – 0.9). The odds of mortality were higher with increasing age (OR 1.025, 95% CI 1.02 – 1.031) and lower among females (0.82, 95% CI 0.73 – 0.91). Among secondary outcomes, hyperlipidemia did not affect the hospital length of stay or cost. Several factors increased the hospital length of stay which included any history of coronary artery disease, peripheral artery disease, or diabetes. In addition, patients admitted over the weekend had a higher length of stay. Conclusions: In this study, we find that hyperlipidemia is associated with lower mortality in patients with colon cancer. This could be possible because patients with hyperlipidemia are on statin therapy. This indirectly could point to a potential benefit of statins in colon cancer. Hyperlipidemia does not affect hospital length of stay or cost.
The anti-cancer effect of statins in obese esophageal cancer patients undergoing esophagectomy.
Authors: Abdelfatah Eihab N , Kukar Moshim , Mukherjee Sarbajit , Groman Adrienne , Yendamuri Saikrishna S. 
Published: June 2021

e16012 Background: In addition to lowering lipid levels and treating atherosclerotic disease, statins have demonstrated anti-inflammatory and anti-tumor activity in various cancer types. We evaluate this effect in esophageal cancer patients undergoing esophagectomy. Methods: All patients undergoing esophagectomy for esophageal cancer at Roswell Park Comprehensive Cancer Center between March 2007 and December 2015 were included. The association between pre-surgery statin use with overall survival (OS), disease-specific survival (DSS) and recurrence-free survival (RFS) was analyzed using Cox proportional hazards regression, with age, sex, American Society of Anesthesia (ASA) score, neoadjuvant therapy, surgical technique, tumor stage, histology, and grade considered in multivariable analyses. Survival analyses were independently performed for body mass index (BMI)-based patient subgroups. Results: 212 patients met inclusion criteria for this study. Median follow up period was 36 months. Estimated five-year RFS for the patient cohort overall was 55.7% and estimated five-year DSS was 53.9%. Estimated five-year OS was 45.4%. There was no significant association between statin use and outcomes of esophagectomy patients overall. However, in subgroup analysis analyzing patients by BMI category, there was a significant association between statin use and outcomes in patients with BMI ≥ 30 (n = 95 patients). Multivariate analysis in obese patients demonstrated an association of statins with improved OS (HR 0.52, p = 0.049), DSS (HR 0.46, p = 0.034) and RFS (HR 0.43, p = 0.036). The other variables significantly associated with outcome measures were stage ≥ 2 (OS HR 2.36, p = 0.010; RFS HR 2.50, p = 0.018; DSS HR 2.51, p = 0.011) and ASA score ≥ 3 (RFS HR 2.26, p = 0.037; DSS HR 2.33, p = 0.019). Conclusions: Statin use is associated with improved RFS, DSS and OS of obese patients undergoing esophagectomy for esophageal cancer. This novel finding suggests an interaction between the pathophysiologic state of obesity and the pleiotropic effects of statins. BMI could be explored as a potential biomarker for adjunctive statin use in future trials.[Table: see text]
Discovery and validation of methylation signatures in circulating cell-free DNA for early detection of esophageal cancer: A case-control study.
Authors: Zhuang Weitao , Ben Xiao-song , Li Chengcheng , Xu Jiayue , Tian Dan , Zhou Zihao , Chen Gang , Deng Cheng , Tang Jiming , Shi Ruiqing , Xie Liang , Zhang Dongkun , Zhou Haiyu , Li Bingsi , Zhang Zhihong , Liu Hao , Wang Guoqiang , Cai Shangli , Qiao Gui-Bin 
Published: June 2021

e16027 Background: The pivotal goal of esophageal cancer (ESCA) screening is to identify early-stage cancer or precancerous lesions when curable treatments are available. Methylation of circulating-free DNA (cfDNA) has shown promising results in the early detection of multiple tumors recently. Here we conducted a prospective study to investigate the performance of cfDNA methylation in the early detection of ESCA. Methods: Specific methylation markers for ESCA were identified and optimized based on 24 esophageal tumor and its corresponding adjacent tissues. Age-matched participants with ESCA (n = 136), benign esophageal disease (n = 21) and healthy controls (n = 126) were randomized into the training and testing sets to develop an early-detection classifier. Results: In total, 921 differentiated methylation blocks (DMBs) between tumor and adjacent tissues were identified, of which 679 (73.7%) showed higher methylation level and 242 (26.3%) had lower methylation level in tumor tissues. In the training set, the specificity of the model built with these DMBs was 94.1% (95% CI, 85.5%−98.4%) and the sensitivity was 86.0% (95% CI, 72.2%−94.8%). The sensitives increased with stages, which were 77.8% (95% CI, 39.8%−97.2%), 90.9% (95% CI, 58.7%−99.8%), 83.3% (95% CI, 51.7%−97.9%) and 100.0% (95%CI, 63.1%−100.0%) for stage I-IV, respectively. Similar results were observed in the testing set with area under curve (AUC) of 0.932 (95% CI, 0.887−0.977). Conclusions: The cfDNA methylation profiles distinguished ESCAs from healthy individuals and benign esophageal diseases with promising sensitivity and specificity. Consideration of the potential value of early detection in ESCAs, further evaluation in larger prospective studies is warranted.
Camrelizumab combined with paclitaxel and nedaplatin as neoadjuvant therapy for locally advanced esophageal squamous cell carcinoma (ESPRIT): A phase Ⅱ, single-arm, exploratory research.
Authors: Ma Jianqun , Zhang Jinfeng , Yang Yingnan , Zheng Dayong , Wang Xiaoyuan , Liang Hao , Zhang Luquan , Xin Yanzhong , Ling Xiaodong , Fang Chengyuan , Jiang Hao , Zheng Wei 
Published: June 2021

e16033 Background: Camrelizumab has been approved as a standard therapy in the second-line treatment of esophageal squamous cell carcinoma (ESCC). This study aimed to explore the efficacy and safety of camrelizumab combined with commonly used neoadjuvant chemotherapy (paclitaxel and platinum) in neoadjuvant treatment of ESCC. Methods: In this single-arm, phase Ⅱ study, patients with advanced ESCC who were expected to receive neoadjuvant therapy followed by radical surgery were recruited. The patients received 2-4 cycles of camrelizumab (200mg, iv, q3w) in combination with paclitaxel (155mg/m2, iv, q3w) and nedaplatin (80mg/m2, iv, q3w) as neoadjuvant therapy, and the therapeutic effects were determined every 2 cycles. The radical surgery was performed on patients whose tumors were evaluated as resectable. The primary endpoint was pCR, and the secondary endpoints were objective response rate (ORR) and disease control rate (DCR). Results: From May 2020 to January 2021, 24 patients with a median age of 60.5 years (50-73) were enrolled. Among them, 21 patients were available for efficacy analysis, of which 1 achieved complete response (CR), 7 achieved partial response (PR), and 13 had stable disease (SD). The ORR was 38.1% and DCR was 100%. The tumor in 10 patients shrank significantly after neoadjuvant therapy and these patients preferred radiotherapy instead of surgery as the radical therapeutic method. 2 patients abandoned surgery because of personal reasons. 2 patients were in the process of neoadjuvant therapy and had not undergone surgery yet. The remaining 7 patients underwent radical surgery and 4 patients (57.14%) achieved pCR (pT0N0M0). The main treatment-related grade 3/4 adverse event (AE) was neutropenia (1/21). All the AEs were manageable. The average intraoperative blood loss was 221mL and the average hospitalization time after operation was 12.7 days (range 8-19 days). No anastomotic leakage and treatment-related death occurred. Conclusions: Camrelizumab in combination with paclitaxel and platinum as a neoadjuvant therapy was well tolerated. The pCR rate of 57.14% was higher than the expected 40%. This encouraging result promoted us to continue this phase Ⅱ study. Clinical trial information: ChiCTR2000033761.
Clinical effectiveness of apatinib at different doses in patients with advanced gastric cancer as the third-line or further treatment: Results from a post-marketing phase IV study.
Authors: Li Jin , Qin Shukui , Wen Lu , Wang Junsheng , Deng Wenying , Guo Weijian , Jia Tongfu , Zhao Qun , Zhang Guifang , He Yifu , Zhong Haijun , Ba Yi , Lin Xiaoyan , Yang Jianwei , Zhao Jun , Bai Yuxian , Sun Guogui , Wu Yongjuan , Wang Meng , Sun Ying 
Published: June 2021

e16037 Background: Apatinib, a highly selective VEGFR2 inhibitor, has shown a clinical benefit as third-line or further-line treatment in patients with gastric cancer in a randomized phase III study with the initial dose of 850mg. However, the study was conducted in a small scale (n = 267) under standardized conditions. Here, we assessed exposure and effectiveness of apatinib at different doses using data collected from a post-marketing phase IV study that included a broader patient population with a larger sample size. Methods: Patients with advanced or metastatic advanced gastric cancer or gastroesophageal junction adenocarcinoma who were aged 18-75 with ECOG performance status of 0-2 and failed at least two lines of chemotherapy were enrolled. Apatinib was recommended with an initial dose of 850 mg q.d orally, while the initial dose was determined at the discretion of the investigators. Administration of apatinib regarding the initial dose, duration of treatment, dose modification, average daily exposure dose (ADED) and its effect on progression-free survival (PFS) and overall survival (OS) were analyzed. Results: A total of 2004 patients were included in the intention-to-treat population. The median age was 59 (range, 19-85) years, 71.8% of patients were male, 84.2% had ECOG performance status of 0-1; 96.4% had stage IV disease, and 98.8% had metastases, among which 34.2% with more than 2 metastases. Five patients did not receive therapy. Compared to 5.5% of patients with the initial dose > 500mg, 94.1% was given at the initial dose≤500mg; 8.6% had ADED > 500mg and 91.1% had ADED ≤500mg. The median duration of treatment was 56 days. Treatment interruption and discontinuation, and dose reduction occurred in 34.4%, 24.5%, and 13.7% of patients due to adverse events, respectively. Survival analyses in the initial dose ≤500mg/ > 500mg subgroups showed median PFS of 2.6 months (95%CI 2.20-2.79) vs 2.7 months (95% CI 1.91-3.32), median OS of 5.6 months (95% CI 5.26-5.95) vs 5.9 months (95% CI 4.40-6.87). In the ADED ≤500mg/ > 500mg subgroups, the median PFS was 2.6 months (95% CI 2.14-2.76) vs 3.0 months (95% CI 2.27-3.61), and median OS was 5.7 months (95% CI 5.32-6.08) vs 6.1 months (95% CI 5.36-7.72). Conclusions: In conclusion, more than 90% of the patients received a lower dose regimen, which indicate dosage of 500mg or lower is a tolerated exposure. Furthermore, dose at 500mg or lower produced similar efficacy to that more than 500mg. Clinical trial information: NCT02426034.
Effects of formula composed of active monomers of removing heat and phlegm prescription on malignant phenotypes and growth signaling in esophageal carcinoma cells.
Authors: Si Fuchun , Wang Wenbin 
Published: June 2021

e16051 Background: Esophageal carcinoma (EC) ranks seventh in the incidence of malignant tumors and the sixth mortality worldwide. Removing heat and phlegm prescription(RHPP, composed of Rhizoma Dioscoreae Nipponicae, Rhizoma Paridis, Saponin, Rhizoma Bolbostemmae) was an effective formula screened from 531 Chinese herbs for treating EC in our previous study. The purpose of this study is to further track, isolate, purify and identify the active monomers of RHPP, study the effect of each active monomer on Eca109, EC9706, EC-1, TE-1 four EC cells and the signaling mechanism, then optimize and compose new active monomers formula and study its mechanism on EC cells. Methods: The active monomer of RHPP was extracted, separated and identified by ethanol extractioncolumn, chromatography, recrystallization, HPLC, spectroscopic method,etc. The effects of four kinds of active monomers and their composed formula on the proliferation, migration, clone formation, cell cycle and signal pathway proteins expression of Eca109 cell, EC9706 cell and TE-1 cell were investigated by MTT assay, RTCA assay, soft agar assay, flow cytometry and western blot analysis. Results: Four active monomers were identified from Rhizoma Dioscoreae Nipponicae (CSL), Saponin (ZJ), Rhizoma Bolbostemmae (TBM), Rhizoma Paridis (CL) respectively with molecular weights of 868, 1003, 1365, 854.5, and corresponding molecular formulas of C45H72O16, C50H82O20, C64H100O31 and C44H70O16(China patient No. ZL202010136431.6). Four active monomers significantly affected the cell morphology, proliferation, migration, cloning ability, cell cycle of four EC cells. The IC50 values of the active monomer of CSL, ZJ, TBM and CL for Eca109 were 1.29±0.12, 2.42±0.09, 1.93±0.09, 3.04±0.28μg/ml respectively; for EC9706 were 1.41±0.02, 5.94±0.45, 1.97±0.09, 0.63±0.04μg/ml respectively; for TE-1 were 3.72±0.28, 35.58±0.58, 7.90±0.41, 1.85±0.09μg/ml respectively; for EC-1 were 1.11±0.14, 3.56±0.28, 1.23±0.02, 0.61±0.02μg/ml respectively. Four active monomers could downregulate EGFR, PLC-γ1, and PKCα protein expression. Using the baseline proportional increase and decrease design method to compose new removing heat prescription(RH), removing phlegm prescription(RP) and removing heat and phlegm prescription (RHPP), the ratio of each drug monomer in RH, RP and RHPP were mCSL: mCL = 6: 4, mZJ: mTBM = 3: 7, mCSL: mCL: mZJ: mTBM = 48: 32: 6: 14. RH, RP and RHPP all could inhibit the proliferation, migration, cloning ability, cell cycle of four EC cells. Conclusions: The four active monomers and new composed RHPP all can inhibit the proliferation of EC9706, Eca109, TE-1, EC-1 four EC cells, which have close relationship with EGFR, PLC-γ1, and PKCαproteins expression. This study provides new formula and basis for the development of anti-esophageal carcinoma drugs in traditional Chinese medicine.
A noninvasive gastric cancer Her2 test using surrogate methylation markers.
Authors: Liu Xin , Ye Gengtai , Cui Chunhui , Li Hui , Yang Ting , Lei Xuetao , Zhang Guofan , Zheng Boyang , Xie Lang , Lei Xiaotian , Wu Chaorui , Song Xinjian , Yu Jiang , Chen Zhiwei , Fan Jianbing 
Published: June 2021

e16084 Background: There are 10-20% of gastric cancer (GC) with overexpressed Her2. Her2 status remains an essential biomarker for guiding the trastuzumab (Herceptin) therapy, a monoclonal antibody approved for the first-line treatment of late-stage Her2-positive GC. Although IHC, together with FISH, is comprehensively applied to verify Her2 status on tissue samples, an accurate blood test is highly desirable due to the inaccessibility of tissue samples, especially in very late stage GC patients as well as tumor heterogeneity of tissue biopsy. Detecting copy number aberration of Her2 gene in cell-free DNA (cfDNA) gains a lot of interest for its non-invasive approach. However, the limited signal-to-noise ratio poses a great challenge for the accuracy and robustness of the tests (either targeted sequencing or ddPCR). Here, we report a non-invasive test for Her2 status verification based on novel surrogate DNA methylation markers. Methods: Genome-wide DNA methylation sequencing was performed in 30 Her2-negative (IHC 0/1+) and 44 Her2-positive (IHC 3+) tissue samples to identify Her2-overexpression-specific methylation markers. Then we analyzed the performance of these candidate markers using methylation-specific quantitative PCR (qMSP) in plasma samples collected from 102 GC patients before surgical treatment. A Her2-status diagnostic model was built and further validated in a multi-center, prospective cohort (n = 150). The concordance of Her2 status between GC plasma and matching tissue samples (IHC/FISH) was determined. Results: We first discovered 102 statistically significant methylation markers of Her2 status in tissue. Out of these candidate markers, a 3-marker diagnostic model was built and validated on plasma samples, which could discriminate Her2-positive from Her2-negative GC patients with high sensitivity (86.7%) and specificity (96.8%). The overall plasma-tissue concordance of this liquid biopsy test was 95.3%. Furthermore, the Her2-status test was able to classify Her2 2+ status (IHC) into either Her2-negative or Her2-positive status, which was confirmed by conventional FISH test. Conclusions: Overall, the cfDNA-based test is a novel, accurate and noninvasive approach for determining Her2 status in GC patients. The high concordance with IHC/FISH results of this blood test holds great promise as an auxiliary method for guiding Her2-targeted therapy in GC patients. A clinical trial is undergoing to validate this test in the phase-2 clinical trial of a Her2-targeted drug (for GC) in China.
Combining radiation therapy with anti-PD-1 for patients with advanced hepatocellular carcinoma: An open-label, single-center, single-arm clinical study.
Authors: Li Jian-Xu , Su Ting-Shi , Lin Xiao-Feng , Chen Yi-Tian , Liang Shi-Xiong , Xiang Bang-De 
Published: June 2021

e16117 Combining radiation therapy with anti-PD-1 for patients with advanced hepatocellular carcinoma: an open-label, single-center, single-arm clinical study Jian-Xu Li, Ting-Shi Su, Xiao-Feng Lin, Yi-Tian Chen, Shi-Xiong Liang, Bang-De Xiang; Guangxi Medical University Cancer Hospital, Nanning, China Abstract Research Funding: Jiangsu Hengrui Pharmaceuticals Co., Ltd., Shanghai, China. Guangxi Medical and Health Appropriate Technology Development and Application Project (No. S2019039), Guangxi, China. Background: Based on the results of recent studies, the PD-1 monoclonal antibodies have been approved to treat the patients with advanced hepatocellular carcinoma (HCC) by the FDA. Radiation therapy (RT) can enhance responsiveness to PD-1 monoclonal antibody by potential mechanisms. A phase Ⅱa study was conducted to assess the safety and the efficacy of combining RT with anti-PD-1 for patients with advanced hepatocellular carcinoma. Methods: Patients with advanced HCC were eligible. Stereotactic body radiation therapy (SBRT) were adopted, and the dose of radiation were Dt-PGTV 30-50 Gy/10fractions. Camrelizumab (200mg) were given intravenously every 3 weeks since the first day of RT until disease progression, or intolerable toxicity. Adverse events (AEs) and objective response rate (ORR) were summarized to assess the safety and efficacy. Results: From April 2020 to November 2020, 17 patients were enrolled (median age 54, range 32-69). 15 (88%) patients were male. 14 (82%) had ECOG performance score of 0. All the patients had Child-Pugh score A. 16 patients staged as Barcelona Clinic Liver Cancer staging C or China Liver Cancer staging Ⅲ. Extrahepatic metastases were identified in 11 (65%) patients. 13 (77%) patients were Hepatitis B virus infected. 15 (88%) patients had previously 2 lines or more chemotherapy. 9 (53%) patients had Alpha-fetoprotein level≥400 ng/ml. The ORR was 47%. The best response assessed by RECIST 1.1 was partial response (8 patients). Four patients had grade 3 immune-related adverse events (irAEs), including increased aspartate aminotransferase and alanine transaminase (n =1)，decreased hemoglobin (n =1)，decreased platelet count (n =1)，decreased neutrophil count (n =1). All grade 3 irAEs were mitigated with proper treatment. None treatment-related deaths occurred. Conclusions: In this study, RT combined with anti-PD-1 had an acceptable safety profile and indicated an effective treatment option in patients with unresectable HCC. Clinical trial information: NCT04193696. Clinical trial information: NCT04193696.
A single-arm, multicenter, open-label phase 2 trial of surufatinib in patients with unresectable or metastatic biliary tract cancer.
Authors: Bai Yuxian , Xu Jianming , Sun Huichuan , Bai Chunmei , Jia Ru , Li Yi , Zhang Wenjie , Liu Lei , Huang Cheng , Guan Mei , Zhou Jinghong , Su Weiguo 
Published: June 2021

e16123 Background: Several clinical studies of vascular endothelial growth factor/vascular endothelial growth factor receptor (VEGF/VEGFR) therapy as second-line treatment for biliary tract cancer (BTC) has demonstrated moderate efficacy. In this study, surufatinib was evaluated as a second-line VEGFR therapy in BTC patients. Methods: This was a single-arm, multi-center, open-label phase 2 study conducted in China. The study enrolled eligible BTC patients who progressed after fist-line chemotherapy. Patients received surufatinib monotherapy as second-line treatment, at doses of 300 mg, once daily, in 28-day cycles. Tumor assessments were performed every 8 weeks ± 7 days according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Results: As of Nov. 30, 2018, a total of 39 BTC patients, including 29 (74.4%) with intrahepatic cholangiocarcinoma, 5 (12.8%) with extrahepatic cholangiocarcinoma, and 5 (12.8%) with gallbladder cancer, were enrolled and treated with surufatinib. Sixteen-week progression-free survival (PFS) rate was 46.33% (95% confidence interval [CI], 24.38‒65.73), with median PFS of 3.7 months and median overall survival (OS) of 6.9 months. In addition, results from subgroup and post-hoc analyses suggested the trends of better clinical efficacy in patients with tumor locations inside the liver, or with lower baseline values of CA19-9 (≤ 1000 IU/mL) and CEA (≤ 3 ng/mL). The top three treatment-related adverse events (TRAEs) with severity of Grade ≥ 3 included blood bilirubin increased (20.5%), hypertension (17.9%), and proteinuria (12.8%). Conclusions: When applied in the treatment of BTC patients, surufatinib monotherapy has offered moderate clinical efficacy and has demonstrated favorable tolerability and safety profiles. Moreover, surufatinib further boosting the antitumor effects of cancer immunotherapy is desirable. Clinical trial information: NCT02966821.