bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adjuvant chemotherapy for gastric cancer patients with mismatch repair deficiency or microsatellite instability.
Authors: Nie Run-Cong , Yuan Shu-Qiang , Kim Jin Won , Wang Yun , Chen Guoming , Zhou Jie , Chen Yingbo , Chen Yingbo , Zhou Zhiwei , Cai Muyan , Li Yuanfang 
Published: June 2021

e16004 Background: Mismatch repair deficient (dMMR) or microsatellite instability-high (MSI-H) serves as a predictor poor response to adjuvant chemotherapy in stage II colon cancer patients. Our objective was to investigate the efficacy of adjuvant chemotherapy in dMMR/MSI-H gastric cancer (GC). Methods: We searched literatures through December, 2020 to identify clinical studies that reported survival comparing adjuvant chemotherapy with surgery alone in dMMR/MSI-H GCs. Two approaches were used to pool the hazard ratio (HR) of survival: (1) If Kaplan-Meier curves and number at risk were provided, individual patient data were extracted. Cox models were used to calculate the HR with 95% confidence interval (CI); (2) for study-level data, pooled HR was estimated using fixed/random-effects models. Results: Six clinical studies were identified. For dMMR/MSI-H versus mismatch repair proficient (pMMR)/microsatellite stable (MSS)/microsatellite instability-low (MSI-L), the estimated 5-years DFS were 74.2% versus 51.5% (HR, 0.44; 95% CI, 0.32-0.62; P < 0.001); the estimated 5-years OS were 60.8% versus 50.1% (HR, 0.72; 95% CI, 0.60-0.88; P = 0.001). At study-level data, the pooled HRs were 0.42 for DFS (95% CI, 0.31-0.57; P < 0.001) and 0.66 for OS (95% CI, 0.32-1.38; P = 0.268). For adjuvant chemotherapy versus observation in dMMR/MSI-H, the estimated 5-years DFS were 76.1% versus 73.3% (HR, 0.72; 95% CI, 0.45-1.15; P = 0.171); the estimated 5-years OS were 74.9% versus 60.2% (HR, 0.60; 95% CI, 0.44-0.83; P = 0.001). Significant survival differences were also observed at study-level. Conclusions: This study further suggested adjuvant chemotherapy could be beneficial even in dMMR/MSI-H GC patients.
A phase 1b multicenter study of trifluridine/tipiracil (FTD/TPI) in combination with irinotecan (IRI) in patients (pts) with metastatic or unresectable gastric and gastroesophageal adenocarcinoma (mGEC) after at least one line of treatment with a fluoropyrimidine and platinum (FP) containing regimen.
Authors: Dayyani Farshid , Tam Kit Wah , Kim Edward Jae-Hoon , Ejadi Samuel , Lee Fa Chyi , Valerin Jennifer B. , Taylor Thomas H. , Cho May Thet 
Published: June 2021

e16006 Background: FTD/TPI, an antimetabolite, is approved for treatment of refractory mGEC. This study sought to determine whether the combination of FTD/TPI with IRI (“TASIRI”) was safe and effective in mGEC previously treated with FP. Methods: This investigator‐initiated, multicenter, open‐label, single-dose level, single‐arm phase 1b study enrolled pts with mGEC previously treated with at least one line of FP containing regimen. FTD/TPI was given at 25 mg/m2 twice daily on days 1 to 5 with 180 mg/m2 IRI on day 1 of a 14‐day cycle. The primary endpoint was progression-free survival at six months (mo) (PFS-6). The aim was to show an improvement of PFS-6 from 15% to at least 30% based on historical controls. Results: At the time of data-cutoff (03Feb2021), 23 pts were screened and ultimately 20 pts were treated. The study met its primary endpoint. With a median follow-up of 9.8 mo (range 0.7 – 17), 8 pts are still on treatment and 4 pts have died. PFS-6 is 53.9% (lower limit of 95% CI: 28%). Median PFS and overall survival are 6.9 mo and not reached, respectively. At the time of data-cutoff, data were available for 13 pts with measurable disease by RECIST criteria and at least 1 on-treatment scan. Of those, 11 had stable disease and 2 had progressive disease as best response (5 pts had tumor shrinkage < 30%), therefore the disease control rate was 84.6%. The most common any grade (G) treatment related adverse events (TRAE) were nausea (n = 14, 70%), diarrhea (n = 9, 45%), and fatigue (n = 8, 40%). G3-4 TRAE in > 5% of pts were anemia (17%) and neutropenia (9%). 2 serious TRAE were reported: G4 febrile neutropenia (n = 1) and G3 hypotension (n = 1). There was no G5 TRAE. Conclusions: The combination of TASIRI showed encouraging clinical activity with a meaningful improvement in PFS-6 compared to historic controls. TASIRI was well tolerated and no new safety signals were seen. TASIRI warrants further investigation for patients with refractory mGEC and limited treatment options. Updated results with longer follow-up will be presented at the meeting. Clinical trial information: NCT04074343.
Preoperative chemotherapy combined with PD-1 inhibitor in locally advanced operable or potentially resectable esophageal squamous cell carcinoma: A real world study.
Authors: Wu Puyuan , Wang Tao , Chen Baojun , Shi Minke , Zhou Yong , Huang Bin , Wu Nandie , Qi Liang , Wang Lifeng , Wei Jia , Liu Baorui , Ren Wei 
Published: June 2021

e16010 Background: Preoperative therapy of esophageal squamous cell carcinoma (ESCC) is stepping into the era of combined therapy with PD-1 inhibitor after the success of PD-1 antibodies in the first-line and second-line treatment for advanced ESCC. This single center study retrospectively analyzed the efficacy and safety of preoperative chemotherapy combined with PD-1 antibody in patients with locally advanced operable or potentially resectable ESCC in the real world. Methods: The study enrolled operable or potentially resectable locally advanced ESCC patients treated with preoperative chemotherapy combined with PD-1 inhibitor in our center from April 2020 to December 2020. The treatment regimen were 2 to 4 cycles of paclitaxel liposome (135̃175 mg/m2) or albumin paclitaxel (180mg/m2) plus nedaplatin (75mg/m2) or lobaplatin (30mg/m2) combined with PD-1 inhibitors (toripalimab 13/20, sintilimab 3/20, pembrolizumab 2/20, camrelizumab 1/20, tislelizumab 1/20) with standard therapeutic dose followed by tumor response assessment and surgery. The primary end point were safety, tumor response and complete pathological response (pCR) rate. Results: A total of 20 patients including 17 males and 3 females, of which median age was 65 and 85% were stage III-IVA (AJCC 8th), were included in the study. Of all the patients, 18 patients accomplished 2 cycles of therapy and had safety assessment, 13 patients underwent surgery, 2 patients were waiting for operations and 2 patients achieving partial response rejected surgery and were prepared for radical chemoradiotherapy. Treatment-related adverse events exceeding grade 3 levels included leukopenia 5.6% (1/18), neutropenia 16.7% (3/18), thrombocytopenia 5.6% (1/18), and immune hepatitis 5.6% (1/18). There was no severe surgery-related complication. Objective response rate (ORR) was 70.6% (12/17), and disease control rate (DCR) was 100% (17/17). R0 resection rate was 92.3% (12/13), the pCR rate was 15.4% (2/13), and 61.5% (8/13) of the patients had downstaged to the ypT1-2N0M0 I stage. One patient finally reached a pCR after switching to preoperative chemoradiotherapy because of progression after treatment of chemotherapy and PD-1 inhibitor. Conclusions: Preoperative chemotherapy combined PD-1 inhibitor treatment was well tolerated and had high efficacy in locally advanced operable and potential resectable ESCC. Since the study included some potentially resectable patients with late staging, the pCR rate may be lowered. The further study aims to find the efficient biomarker including PD-L1 expression and CD8+ T cell infiltration. Moreover, well-designed randomized prospective trials for better evidence are required.
The microbial characteristics of patients with esophageal squamous cell carcinoma before and after immunotherapy.
Authors: Zuo Jing , Lv Wenjing , Wang Yudong , Fan Zhisong , Feng Li , Wang Long , Zhang Xue , Han Jing , Jiang Da 
Published: June 2021

e16016 Background: Esophageal squamous cell carcinoma (ESCC) is a common malignancy without effective therapy. Immune checkpoint–oriented immunotherapies have shown considerable promise and the advent of esophageal microbiome provides researchers with new ideas. Methods: DNA was extracted from blood, oral mucosal, saliva, urine, fecal samples from 20 ESCC patients before and after immunotherapy. Total microbial genomic DNA samples were extracted using an OMEGA Soil DNA Kit (D5625-01). The V3–V4 regions of bacterial 16S rRNA genes were amplified by PCR using the forward primer and the reverse primer and were sequenced with Illumina MiSeq platform. In order to comprehensively evaluate the α diversity of microbial communities, we used Chao1 and Observed Species indices to characterize the richness, Shannon and Simpson indices to characterize the diversity. PCoA were used to analyze differences in β diversity. Functions of 16S rRNA sequences were predicted using the PICRUSt2 and KEGG databases. Results: A comparison of blood, oral mucosal, saliva, urine, fecal samples of ESCC patients before and after immunotherapy showed that α diversity was not statistically significant. In terms of β diversity, no statistically significant differences were detected within blood, oral mucosal, saliva, urine, fecal samples of ESCC patients before and after immunotherapy. In ESCC patients treated before immunotherapy, the α diversity and β diversity of blood, oral mucosal, saliva, urine, fecal samples were different, and in ESCC patients treated after immunotherapy had the same rule. At the phylum level, the top 5 microbes in ESCC patients before and after immunotherapy were Proteobacteria, Firmicutes, Bacteroidetes, Actinobacteria, Fusobacteria. At the genus level, the top 5 microbes in ESCC patients before immunotherapy were Aquabacterium, Streptococcus, Prevotella, Veillonella, Bacteroides, and in ESCC patients after immunotherapy were Aquabacterium, Streptococcus, Prevotella, Faecalibacterium, Veillonella. In terms of the microbial functions in ESCC patients before and after immunotherapy, the metabolic pathways accounted for the most. Conclusions: This study is conducive to exploring new mechanisms for tumor cells to evade host immune surveillance, providing new ideas and new strategies for the microecology-based immunotherapy of ESCC.
Camrelizumab combined with SOX regimen in the first-line treatment of unresectable advanced or recurrent gastric cancer: A single-arm, prospective, open clinical study.
Authors: Han Zhengxiang 
Published: June 2021

e16017 Camrelizumab combined with SOX regimen in the first-line treatment of unresectable advanced or recurrent gastric cancer£ºA single-arm, prospective, open clinical study. Background: Gastric cancer is one of the most common malignant tumors of the digestive system. In China, 80% of patients with gastric cancer are already in advanced or locally advanced stage at the time of detection. Even after receiving radical gastrectomy, more than half of patients will have local recurrence or distant metastasis, and the 5-year survival rate of patients with gastric cancer with metastasis is less than 10%.In recent years, more and more evidence supports the application of immune checkpoint inhibitors in advanced gastric cancer.In 2020, PD-1 was approved for advanced gastric cancer receiving second-line or above treatment in China, which is an affirming of the efficacy of PD-1 in the clinical treatment of gastric cancer. Immunotherapy combined with conventional chemotherapy, this study aims to explore the efficacy and safety of PD1 combined with chemotherapy in the treatment of first-line gastric cancer. Methods: This was a single center, prospective clinical study conducted at the Affiliated Hospital of Xuzhou Medical University, Jiangsu Province.Patients with newly treated unresectable advanced or recurrent gastric or gastroesophageal junction adenocarcinoma were enrolled.All enrolled subjects were treated with camrelizumab combined with SOX regimen every 3 weeks.The primary endpoint was progression-free survival (PFS).Secondary endpoints were overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety.This study was registered at Chictr.org.cn with the number Chictr2000029691. Results: The study plans to enroll 30 patients, and 16 patients have been included in the study from March 2020 to December 2020. Among them, 7 patients can be evaluated, 14 males, 2 females, ECOG score 0 or 1. Of the 7 patients who can be evaluated for efficacy, 1 achieved PR and 5 achieved SD, ORR was 14.29%, and DCR was 85.71 %. This is the early stage of data analysis, PFS has not yet reached, and the side effects are mild, mainly with grade 1 adverse reactions. The most common AEs are neutropenia (3/7) and decreased appetite (2/7). There were no treatment-related deaths. Conclusions: This study provides preliminary evidence for the first-line treatment of unresectable advanced or recurrent gastric or gastroesophageal junction adenocarcinoma with camrelizumab combined with chemotherapy. The current number of enrolled cases is small, but the preliminary effect of immunotherapy combined with chemotherapy in first-line patients with advanced gastric cancer can still be seen. This trial will further explore the clinical efficacy and safety of immunotherapy in the first-line gastric cancer. Clinical trial information: ChiCTR2000029691.
Molecular characterization of amplification of 11q13 region in patients with operable esophageal squamous cell carcinoma.
Authors: Liu Shuoyan , Wang Feng , Wang Peiyuan , Chen Yujie , Chen Peng , He Hao , Chen Xiaofeng , Zhang Derong , Shi Jialong 
Published: June 2021

e16053 Background: The efficacy of programmed cell death 1 (PD-1) targeted therapy had showed effective treatment in patients (pts) with locally advanced or metastatic esophageal squamous cell carcinoma (ESCC). Meanwhile some studies have shown that PD-1 as neoadjuvant therapy showed promising anti-tumor activity with acceptable tolerance for locally advanced ESCC. Previous studies have shown genomic amplification of 11q13 region may serve as a negative predictive marker for ESCC patients receiving anti-PD-1 based immunotherapy. However, related molecular characterization study of amplification of 11q13 region in patients with operable ESCC is rare reported. Methods: The study recruited pts with operable ESCC whose tissues were send to perform target-capture deep sequencing with the pan-cancer panel and immunohistochemistry of PD-L1 with 22C3 assay. Pair-wise comparison of TMB and PD-L1 was analyzed in pts with 11q13 amplification and pts without 11q13 amplification. Results: 58 operable ESCC pts (cT1-T3N0) were enrolled, median age at diagnosis was 63 years(yrs) (45-73). Copy number analysis identified 30 out of 58 (52%) patients with amplifications of four genes located in chromosome 11q13 region, including CCND1(Cyclin D1) and fibroblast growth factor family members ( FGF3/4/19). Among the 11q13 amplification cohort, four genes amplified together were occurred in 27(90%) pts, 1(3%) patient had amplification of three genes ( CCND1 and FGF3/4), 2 (7%) pts had amplification of one gene that are FGF3 and CCND1 respectively. The prevalence rate of 11q13 amplification was not significantly different between older age (≥ 63 yrs) and young age ( < 63 yrs). Among 58 pts with TMB evaluated, median TMB was 5.76 muts/Mb (range: 0 - 20.16 muts/Mb). The prevalence of TMB-H and microsatellite instability was 12% (7/58) and 0% (0/58). TMB and expression of PD-L1 showed no significantly difference between 11q13 amplification cohort and 11q13 wild cohort. The most frequently mutated genes were TP53 (96.7%, 29/30 pts), NOTCH1 (33.3%, 10/30 pts), CDKN2A (23.3%, 7/30 pts) and MLL2 (20%, 6/30 pts) in 11q13 amplification cohort, while TP53 (89.3%, 25/28), NOTCH1 (39.3%,11/28), MLL2 (28.6%, 8/28), FAT1 (25%,7/28) were the most frequently mutated genes in 11q13 wild cohort. Conclusions: Amplification of 11q13 region was a high prevalence event in operable ESCC and there was show no age bias. Molecular characterization of amplification of 11q13 region in patients receiving PD-1 as neoadjuvant therapy before surgery may be meaningful.
Prevalence-adjusted trends in U.S. healthcare spending on upper gastrointestinal cancers, 1996 to 2016.
Authors: Stukalin Igor , Ahmed Newaz Shubidito , Fundytus Adam Michael , Singh Siddharth , Ma Christopher 
Published: June 2021

e16064 Background: Upper gastrointestinal cancers are rising in prevalence and associated with high healthcare costs. We estimated trends in the US healthcare spending in patients with esophageal and stomach cancer between 1996 and 2016. Methods: We used data on national healthcare spending developed by the Institute for Health Metrics and Evaluations Disease Expenditure Project. Corresponding prevalence of esophageal and stomach cancer was estimated from the Global Burden of Diseases Study. Prevalence-adjusted, temporal trends in the US healthcare spending in patients with upper gastrointestinal cancer, stratified by age and setting of care (ambulatory, inpatient, emergency department, pharmaceutical prescriptions, nursing care and government administration) were calculated using joinpoint regression, expressed as annual percent change (APC) with 95% confidence intervals. Results: Overall, annual US healthcare spending on esophageal cancer increased from $0.76 billion (95% CI 0.68-0.86) in 1996 to $1.06 billion (95% CI 0.88-1.29) in 2016, although after adjusting for increasing prevalence, there was a significant decrease in per capita spending of -0.4%/year (95% CI -0.7%, -0.1%). Annual US healthcare spending on stomach cancer increased from $1.23 billion (95% CI $1.14 billion - $1.34 billion) in 1996 to $1.49 billion (95% CI $1.20 billion - $2.03 billion) in 2016. Per capita spending increased by 1.8%/year (95% CI 1.4%, 2.1%) between 1996 and 2011, followed by a decrease in gastric cancer-related per capita spending after 2011 (APC -4.4%/year [95% CI -5.8%, -2.9%]). Inpatient care was the largest contributor to total cost of both cancers between 1996-2016: 61.9% for esophageal cancer and 73.1% in gastric cancer in 2016. The rising price and intensity of care (defined as the cost per encounter) was the largest driver of change from 1996-2016 for both cancers, accounting for $0.28 billion (95% CI 0.12-0.41) for esophageal cancer and $0.95 billion (95% CI 0.41-1.39) for stomach cancer. Conclusions: After adjusting for rising prevalence, US per capita healthcare spending on esophageal cancer has decreased significantly since 1996, while per capita spending on gastric cancer has remained stable. Inpatient care was the most significant contributor to costs for both cancers over the time period studied.
Prognostic value of subclassification of pT2 stage in patients with gastric cancer.
Authors: He Kang , Wang Xiaohua , Chen Cheng , Jiang Yingying , Shi Yue , Chen Qianying , Zhu Jingni , Sun Yan , Zhou Guoren , Lu Jianwei 
Published: June 2021

e16070 Background: The data about prognosis difference of patients with pT2 stage gastric cancer (GC) after radical surgery is diverse. The latest TNM staging system does not define details for the pT2 stage subclassification. The purpose of this study is to investigate the survival difference according to depth of tumor muscularis propria involvement and find biomarker to reinforce the prognostic and therapy-guided ability of TNM staging system. Methods: A total of 380 patients with pT2 GC after radical surgery were retrospectively analyzed, including 185 in sMP (superficial muscularis propria) group and 195 in dMP (deep muscularis propria) group. The log-rank test was used to identify survival outcomes. Independent factors were identified by multivariable Cox proportional hazard model for OS. Results: The overall survival (OS) of patients in sMP group was significantly better than patients in dMP group (P = 0.007). On multivariate analysis, age (＜60 vs ≥60: P = 0.004, HR, 2.075(95%CI: 1.261-3.414)), primary location (P = 0.002, U vs M: 0.985(0.509-1.909); U vs L: 0.400(0.235-0.680)), depth of tumor invasion (sMP vs dMP: P = 0.050, 1.584(1.261-3.414), pN stage (P = 0.000, N0 vs N1: 2.304(1.364-3.890); N0 vs N2: 1.879(0.967-3.652); N0 vs N3: 5.335(2.533-11.237)), expression of p53 (negative vs positive: P = 0.016, 1.793(1.117-2.879)) were independent prognostic factors for the OS. In pN0 stage tumor, the sMP group had a significantly better OS than the dMP group (P = 0.014). When classified as N+, there was no obviously difference of OS between two groups (P = 0.384). When patients were stratified according to the depth of tumor invasion and pN stage, the OS was not significant difference between dMPN0 group and sMPN1-2 group (P = 0.100), the OS of patients with adjuvant chemotherapy were statistically better than those without in dMPN0 group (P = 0.045), but not significance in sMPN1-2 group (P = 0.486). After further grouping according to adjuvant chemotherapy status, in comparison to sMPN1-2 patients, dMPN0 patients with adjuvant chemotherapy had better OS (P = 0.015), but not significance in patients without (P = 0.599). Upon stratification according to the expression of p53, in p53-positive group, greater OS could be observed in patients with sMPN0 than patients with dMPN0 (P = 0.002). Similar OS could be seen between dMPN0 patients with p53-positive and T2N1-2 patients (P = 0.872). Conclusions: For pT2 gastric cancer patients, there were differences in survival outcomes for sMP and dMP invasion. The prognosis of dMPN0 patients were similar to patients with sMPN1-2, and dMPN0 patients who accepted adjuvant chemotherapy had an improved prognosis than those without. Appropriate adjuvant chemotherapy should be considered for patients with dMPN0 stage. In addition, positive expression of p53 could be potential factors to identify the different prognoses for patients with pT2 gastric cancers.
Cost-effectiveness analysis of gastric cancer management using perioperative chemotherapy versus adjuvant chemoradiation therapy.
Authors: Prasath Vishnu , Quinn Patrick L. , Oliver Joseph B. , Mahmoud Omar , Jaloudi Mohammed , Akkaraju Vikas , Arjani Simran , Ahlawat Sushil , Chokshi Ravi 
Published: June 2021

e16079 Background: The most commonly used treatment options for gastric cancer include complete resection with adequate margins with either perioperative chemotherapy (PCT) or adjuvant chemoradiotherapy (CRT). While both treatment strategies have shown superiority over surgical resection alone, it is not clear which treatment strategy is more optimal. Methods: Our decision tree model was built to analyze the survival and costs associated with the two major management methods: perioperative chemotherapy and adjuvant chemoradiation therapy. Costs were obtained from Medicare reimbursement rates using a third-party payer perspective. Our model’s effectiveness was represented using quality-adjusted life years (QALYs). Our analysis tested the robustness of our conclusions by utilizing one-way, two-way, and probabilistic sensitivity analyses. Results: PCT was the preferred treatment strategy for diagnosed gastric cancer over CRT, with a cost of $54,326.10 and 4.08 QALYs. CRT was the costliest economic strategy with a cost of $77,987.52 and 4.28 QALYs and an ICER of 115,907.48. We set a threshold of $100,000 per QALYs gained which CRT surpassed making PCT the preferred treatment modality. Over 100,000 simulations, 51.4% of simulations favored PCT. CRT became favored when CRT non-curative procedure rates rose 3% higher than PCT non-curative procedure rates and when PCT complication rates rose 15% higher than CRT complication rates. Conclusions: In our simulated patients with diagnosed gastric cancer, the most cost-effective treatment strategy was PCT. We see cost-effectiveness alternating to favor CRT with changes in non-curative procedure rates and adjuvant therapy complication rates.[Table: see text]