bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of efficacy between immune checkpoint inhibitors and irinotecan-based chemotherapy as third-line treatment for patients with advanced gastric cancer: A Korean real-world multicenter study (KCSG ST22-06).
Authors: Lim Sung Hee , Kim Jae-Joon , Im Hyeon-Su , Han Hye Sook , Kim In-Ho , Koo Dong-Hoe , Cho Jang Ho , Maeng Chi Hoon , Lee Min-Young , Lee Hyo Jin , Kim Jwa Hoon , Park Sang Gon , Jung Joo Young , Shin Seong Hoon , Kim Ki Hyang , Lee Keun-Wook , Rha Sun Young 
Published: June 2023

e16047 Background: Immune checkpoint inhibitor (ICI) or irinotecan-based chemotherapy are frequently used after paclitaxel plus ramucirumab as second-line treatment for patients with recurrent and/or metastatic gastric cancer (RMGC). This study aimed to compare the efficacy between ICI and irinotecan-based chemotherapy as third-line treatment in patients with RMGC. Methods: We retrospectively reviewed patients with RMGC, whose third-line treatment started between July 2019 and June 2021 at 17 centers in South Korea. The ICI group included patients who received nivolumab or pembrolizumab and the irinotecan-based chemotherapy group included those patients who received irinotecan or FOLFIRI. Results: A total of 363 patients (129 in the ICI group and 234 in the irinotecan-based chemotherapy group) were analyzed. The median progression-free survival (PFS) was 2.2 and 2.9 months in the ICI and irinotecan-based chemotherapy groups, respectively. The median overall survival (OS) was 5.5 months (95% CI, 3.6-7.4) in the ICI group and 6.0 months (95% CI, 4.8-7.0) in the irinotecan-based chemotherapy group [HR 0.97 (95% CI, 0.75-1.25); P=0.786]. Multivariable Cox-regression analysis showed that weight loss, peritoneal metastasis, low serum sodium, low serum albumin and short duration of second-line treatment were associated with inferior OS ( P<0.05), meanwhile microsatellite instability-high (MSI-H)/mismatch repair-deficient (MMR-D) tumor was an independent prognostic factor for superior OS. The ICI group showed significantly longer OS than the irinotecan-based chemotherapy group in patients without peritoneal metastasis [HR 0.54 (95% CI 0.30-0.99); P=0.047)]. Whereas the irinotecan-based chemotherapy group showed significantly longer OS in patients without PD-L1 expression [HR 1.62 (95% CI 1.03-2.55); P=0.037] than the ICI group. Conclusions: No significant difference in survival outcome was observed between ICI and irinotecan-based chemotherapy as third-line treatment for patients with RMGC. ICI might be preferred for patients without peritoneal metastasis and irinotecan-based chemotherapy for patients with tumors without PD-L1 expression.
Phase I/II study of nab-paclitaxel combined with S-1 as adjuvant chemotherapy in diffuse type of stage III gastric or gastroesophageal junction adenocarcinoma.
Authors: Cui Yuehong , Wei Jia , Yu Yiyi , Xu Bei , Wu Jing , Xu Xiaojing , Liu Tianshu 
Published: June 2023

e16064 Background: Diffuse type (Lauren's classification) of gastric adenocarcinoma (GAC) or gastroesophageal junction adenocarcinoma (GEJ) has a poorer prognosis than intestinal type of GAC or GEJ. Studies have shown that nab-paclitaxel combined with S-1 has a synergistic anti-tumor effect on advanced gastric cancer. We designed this trial to evaluate the efficacy and safety of nab-paclitaxel plus S-1 as adjuvant chemotherapy in diffuse type of stage III GAC or GEJ. Methods: This study was a multi-center, open-label, phase I/II study. The results of the phase I dose escalation study have already been reported, and the recommended phase II dose (RP2D) of nab-paclitaxel is 260mg/m2. Patients with stage III diffuse type GAC or GEJ after D2 dissection and achieved R0 resection were included in this study. S-1 monotherapy was used as adjuvant therapy in the first cycle. If absence of grade3/4 treatment-related adverse events (AEs) of S-1 monotherapy, nab-paclitaxel (260mg/m2, d1, q3w) and S-1 [body surface area (BSA) <1.25 m2, 80mg/d; BSA 1.25–1.5 m2, 100mg/d; BSA >1.5 m2, 120mg/d; d1-14, q3w] were administered for 6 cycles. Then patients still received S-1 monotherapy for 8 cycles. In phase II study, the primary endpoint was 1-year disease free survival (DFS) rate, and the secondary endpoints were 3-year DFS rate and safety. Results: From January 2021 to February 2023, a total of 42 patients were enrolled in this analysis (3 patients in nab-paclitaxel 260mg/m2 dose group in phase I and 39 patients in phase II). The median age (range) was 53 (29~69) years, 18 patients (42.86%) were stage IIIA, 10 patients (23.81%) were stage IIIB and 14 patients (33.33%) were stage IIIC. The median follow-up time was 13.26 months. As of January 2023, 12 patients experienced recurrence. The 1-year-DFS rate was 74.07%, median DFS and 3-year-DFS rate were not reached. The incidence of adverse effects (AEs) was 78.57% (33/42), and the rate of grade 3-4 AEs was 42.86% (18/42). The most common AEs were neutropenia and leukopenia. In addition, we performed next generation sequencing (NGS) for 5 relapsed patients, and 5 non-relapsed patients who were matched to the relapsed patients. The results showed that the mutant rates of tumor supressor gene CDH1, ARID1A, KMT2D, and TP53 in non-relapsed patients were higher than that in relapsed patients. The positive rate of ctDNA were 60% in relapsed patients, but no ctDNA was detected in non-relapsed patients. Conclusions: Adjuvant chemotherapy with nab-paclitaxel and S-1 followed by S-1 monotherapy exhibited promising clinical efficacy, with acceptable tolerability. This study deserves further investigation and follow up for diffuse type of GAC or GEJ. Clinical trial information: NCT03977220 .
Co-mutation-based subtyping of Chinese patients with gastric cancer.
Authors: Huang He , Wang Zhimin , Chen Hao , Cheng Yafei , Liu Hui , Bai Shaoxiong , Huo Yaoliang , Zeng Yanwu , Lu Leilei 
Published: June 2023

e16070 Background: The incidence of gastric cancer is decreasing globally, in contrast, that of Chinese patients has been increased from 35.9% to 48.3%. In-depth investigation of the characteristic of Chinese gastric cancer patients could help to understand the disease mechanism and improve the treatment of gastric cancer. Methods: Tumor tissues were obtained from 96 Chinese gastric cancer patients and tested by high-coverage ( > 1000x) panel sequencing containing 624 cancer-related genes. Genomic mutations including substitutions, insertions, deletions, rearrangements, fusions, and copy number variations were called. Genes were clustered based on their co-mutation relationship in all samples. Patients with gene mutations in each cluster were classified into corresponding groups. The properties of each patient group were characterized, including genomic features, age, gender, stage, LAUREN type, and grade. Results: The most mutated genes were TP53, ERBB4, LRP1B, and CDH1 in our cohort. A higher proportion of female patients had TP53 mutations compared to male patients. Mutations in ALK, KMT2C, and LRP2 were positively associated with microsatellite-instable, and that in ERBB4 and PIK3CA were positively associated with high tumor mutation burden (TMB). Four gene clusters (1, 2, 3, and 4) were identified based on the co-mutation relationship between genes. Cluster 1 included FAT4, APC, OBSCN, and GATA3; Cluster 2 included FGF3, CCND1, FGF19, and GATA4; Cluster 3 included BLK, FAM135B, and DLC1; and Cluster 4 included ATRX, KMT2D, STAG2, and EGFR. Patients were classified into the four patient groups (I, II, III, and IV) accordingly when mutations in the corresponding gene cluster were found. Further association analysis indicated that: Group I was associated with adenocarcinoma subtype; Group II was negatively associated with LAUREN type 2; Group III was associated with high TMB; Cluster IV was associated with microsatellite-instable. Conclusions: This study utilized gene co-mutations to classify gastric cancer patients into subgroups with unique clinical characteristics. Further study on the etiology, treatment, and prognosis of these groups of patients is needed.
A propensity score–matched analysis to evaluate the benefit of adjuvant therapy on disease progression of esophageal squamous cell carcinoma after R0 esophagectomy.
Authors: Cao Yuqin , Hu Qingqing , Zhang Yajie , Li Chengqiang , Zhou Yuan , Zhang Yongjing , Qiu Hong , Li Hecheng 
Published: June 2023

e16071 Background: The impact of adjuvant therapy (AT) on patients’ disease progression with esophageal squamous cell carcinoma (ESCC) after R0 resection remains controversial in clinical practice. The study aims to evaluate the benefits of AT on recurrence or death through propensity score (PS) matched analyses. Methods: A cohort of patients who have undergone R0 esophagectomy without neoadjuvant therapy for ESCC was identified at the tertiary hospital in China between 2013 and 2020. Patients’ demographic, clinical, surgical, pathological and follow-up data were retrieved from a prospectively maintained database. PS for each patient was calculated by the generalized linear regression model including all potential confounders (age, sex, body mass index, smoking history, alcohol consumption, Eastern Cooperative Oncology Group performance score, baseline comorbidities, hospitalization days, tumor location, size, pathological stage T, N and differentiation grade). PS was stratified into four groups (PS < 0.20, 0.20≤PS < 0.30, 0.30≤PS < 0.40, and PS≥0.40) based on distributions. Patients with and without AT were matched by the nearest neighbor PS with caliper 0.05 to evaluate rates of recurrence-free survival (RFS) for overall patients and patients across four PS groups. RFS was defined as the time from date of curative surgery to the time of recurrence or death. Results: In total, 523 patients were identified and 162 (30.9%) of those patients received AT. A total of 312 (60.0%) patients experienced recurrence or death with a median follow-up of 4.15 years (interquartile range: 2.92-4.73 years). Patients with younger ages, shorter hospitalization, larger tumor size, advanced pathological T and N stages, poorly differentiated tumors were more likely to receive AT (all p < 0.05). The mean PS was 0.39 (standard deviation [SD] 0.16) for AT group and 0.27 (SD 0.15) for non-AT group. A total of 274 patients (137 AT and 137 non-AT) were matched. Before matching, AT group tended to have a worse RFS compared with non-AT group (median RFS: 1.84 years vs 2.67 years, p = 0.06). However, after PS matching, AT group showed a significantly better RFS compared with non-AT group (median RFS: 2.41 vs. 1.89 years, p = 0.02). In the subgroup analyses, the benefits of AT were mostly consistent with the whole group, except for patients with PS < 0.20 where AT tended to have worse RFS. Moreover, for PS≥0.40 subgroup, a significantly better RFS was observed in AT group compared with non-AT group (median RFS: 3.52 vs. 1.53 years, p < 0.01). Conclusions: Adjuvant therapy had a benefit on delaying disease progression for Chinese patients with ESCC after R0 esophagectomy, especially for patients with a higher PS score.
Effect of reducing the number of neoadjuvant chemoimmunotherapy cycles on clinical efficacy in locally advanced PD-L1 positive gastric cancer: A single center phase 2 study.
Authors: Zhao Lingdi , Jiang Zhiqiang , Huang Jinxi , Li Zhimeng , Fu Qiang , Ren Yingkun , Zhao Yuzhou , Zhang Bin , Wan Xiangbin , Shang Chuang , Kong Ye , Liu Jialin , Li Zhi , Gao Quanli 
Published: June 2023

e16074 Background: The standard therapeutic recommendation is neoadjuvant chemotherapy with FLOT regimen following radical resection in patients with locally advanced gastric cancer. It is not clear whether neoadjuvant anti-PD-1 antibody plus FLOT regimen could improve the pathological complete response (pCR) rate and how to combine anti-PD-1 antibody and FLOT regimen. We conduct this phase II study to explore this problem (NCT 04891016). Methods: This study is a prospective clinical study, patients are randomly enrolled into the experiment group and the control group according to the random number method. The patients in the experiment group receive standard dose of FLOT regimen plus toripalimab every three weeks, toripalimab is administered on third day in each cycle, after three cycles operation is performed. The patients in the control group receive standard dose of FLOT regimen plus toripalimab every two weeks, toripalimab is administered on the first day in each cycle, after four cycles operation is performed. The primary endpoint is pCR and the secondary endpoint is recurrence-free survival. Results: From June 2021 until present, 57 patients with locally advanced gastric cancer were enrolled in this study, including 28 patients in the experiment group and 29 in the control group. Three patients in the experiment group and two in the control group withdrew from the study as to the influence of COVID-19’s epidemic or personal reason. One patient in the experiment group postponed operation due to immune-related thrombocytopenia. The remaining 51 patients completed the prescribed chemotherapy plus toripalimab and operation, and all the operations were R0 resection. Among these 51 patients, pCR was got in 16 patients and the pCR rate was 31.4%, MPR rate was 66.7%. Further analysis according to the expression of PD-L1 is shown. The overall incidence of adverse events was 93%. The incidence and severity of myelosuppression in the experiment group were lower than those in the control group. Among all the patients received R0 resection, 6 patients experienced recurrence and the remaining are still kept in recurrence-free status. The recurrence-free survival is not available at present. Conclusions: 1) Neoadjuvant therapy with FLOT plus toripalimab is safe and effective in locally advanced gastric cancer. 2) Postponing the use of toripalimab when combined with FLOT as neoadjuvant regimen in locally advanced gastric cancer patients with PD-L1 CPS ≥1 could reduce the number of chemotherapy cycles and thus reduce the adverse events of chemotherapeutic drugs, while the dose intensity of chemotherapy is import in patients with PD-L1 CPS ＜1. Clinical trial information: NCT04891016 .[Table: see text]
Induction immunochemotherapy conversion rate and survival outcomes versus chemotherapy in initially unresectable esophageal squamous cell carcinoma.
Authors: Huang Shujie , Wang Sichao , Gao Zhen , Zeng Ruijie , Xu Wei , Tang Yong , Tang Jiming , Ben Xiaosong , Zhang Dongkun , Xie Liang , Zhou HaiYu , Chen Gang , Fu Junhui , Kong Feng-Ming Spring , Qiao Guibin 
Published: June 2023

e16077 Background: Currently, no comparative study has been reported to elucidate whether the addition of immunotherapy in the induction setting could improve treatment efficacy and prolong the overall survival of initially-unresectable locally advanced esophageal squamous cell carcinoma (iuESCC). This study aimed to compare surgical conversion rate and short-term overall survival in induction chemotherapy (iC) and induction immunochemotherapy (iIC) for patients with iuESCC. Methods: In this multicenter retrospective cohort study, patients with the guideline-defined unresectable disease were included at four high-volume institutions. The primary endpoints were conversion surgical rate and overall survival (OS). Pathological complete response (pCR) was defined as the disappearance of tumor cells in the primary lesion site. Multivariate cox regression analysis was used to identify the independent significant prognostic factors associated with OS. The stabilized inverse probability of treatment weighting (IPTW) was applied to confirm the survival comparison between iIC and iC cohorts. Results: A total of 309 patients (150 in iIC and 159 in iC cohort) were included. A significantly higher conversion surgical rate was observed in iIC cohort (iIC vs. iC: 127/150, 84.7% vs. 79/159, 49.7%, P < 0.001). In terms of pathological response, the rates of pCR were 22.0% and 5.1% in the iIC and the iC cohort, respectively (P = 0.001). A significant difference in OS was observed between iIC (not reached) and iC cohorts (median [95% CI]: 36.3 [27.2 – 45.5] months). The stabilized IPTW yielded similar results. Regimen (iIC vs. iC, HR 0.215, 95% CI: 0.102 - 0.454, P < 0.001) and operation (Yes vs. No, HR 0.262, 95% CI: 0.161 - 0.427, P < 0.001) were the significant prognostic factors for OS. Further, subgroup analysis revealed that significantly higher OS was seen in iIC cohort than that in the iC cohort (P = 0.003) in patients who had non-pCR disease. Conclusions: Immunochemotherapy plus conversion surgery in the induction setting had higher pathological response rate and better OS in iuESCC patients. Moreover, this combined modality also contributed to improving OS in patients with residual tumor burden. This study provided evidence for future randomized control trial designs.
Outcomes of Helicobacter pylori (HP) infection in esophageal cancer (EC): A 5-year nationwide analysis.
Authors: Vikash Sindhu , Vikash Fnu , Mehta Ansh , Bteich Fernand , Al Hamed Rama , Neupane Karun , Bazarbachi Abdul-Hamid , Hammami M Bakri , Esagian Stepan M. , Narvel Hiba , Atalla Eleftheria , Vegivinti Charan Thej Reddy , Gor Rajvi , Shah Nishi , Shastri Aditi , Steidl Ulrich G , Verma Amit , Sica Alejandro R. , Kaubisch Andreas , Goel Sanjay 
Published: June 2023

e16079 Background: EC is a fatal condition, and recent literature suggests the association of HP with esophageal adenocarcinoma. In this study, we elucidate the outcomes of HP infection in EC. Methods: This is a retrospective longitudinal study from 2016-2020, using the nationwide inpatient sample database in the United States (US). Patients with EC with and without HP infection were selected. The baseline characteristics were compared using a T-test and Chi-Square. Multivariate regression analysis was applied to estimate the outcomes (length of hospital stay (LOS), mortality, and morbidity) while adjusting for patient and hospital confounders. We used STATA Version 17.0 for data analysis. The p-value was set at p < 0.05 for statistical significance. Results: In total, 69,144 patients with esophageal cancer were identified; among them, 0.3% (n= 220) had an HP infection. The highest prevalence of cases was seen in the Southern US (35.7%). The average LOS was 3.39 days (p = 0.01), and reduced mortality (p = 0.002). The Charlson comorbidity index (CCI) score was 3 or more for 74.2% (p=0.005). With regards to outcomes, 16.4% (p< 0.05) had esophageal obstruction, 20.2% (p< 0.05) had anemia, and 8% (p < 0.01) underwent esophagectomy. However, no significant differences in the rates of hematemesis 4.4% (p=0.15), melena 2.5% (p=0.28), or esophageal perforation 1.2% (p=0.45) were reported (Table 1). When compared to patients with HP infection, no statistically significant difference was found in the outcomes. Conclusions: Our study indicates a significantly increased prevalence of EC in the southern regions of the US, which may be attributed to regional differences in lifestyle, diet, and access to healthcare. The study population was predominantly admitted with a CCI score of 3, highlighting the burden of comorbid conditions. EC patients had decreased LOS and mortality trends in the past 5 years. Moreover, EC was associated with higher rates of esophageal obstruction and anemia. However, no effect on hematemesis, melena, and esophageal perforation was appreciated, and no statistically significant difference was found in the outcomes of EC with HP infection.[Table: see text]
Circulating tumor DNA in individuals with stomach adenocarcinoma (STAD) to detect MMR-related gene alterations.
Authors: Zhang Shi , Wang Guoqiang , Zhong Beiping , Fang Name , Zhou Aiwei , Liang Minchao , Li Yingqiang , Jing Zhang , Cheng Shaochen 
Published: June 2023

e16083 Background: Stomach adenocarcinoma (STAD) ranks as the second incidence rate in China. The MisMatch Repair (MMR), composed of MLH1, MSH2, MSH3, MSH6, and PMS2, is a critical mechanism for repairing DNA error. In case of microsatellite instability (MSI), the MMR system is capable of repairing the mismatches. MSI-high (MSI-H) is created as a result of deficient mismatch repair (dMMR). A numerous studies have established the clinical importance of both MSI and MMR for the diagnosis, prognosis, and treatment of STAD. Circulating tumor DNA (ctDNA) provides a non-invasive method for the diagnosis and prognosis of cancer. The examination of MMR-related gene mutations in STAD can serve as a means of evaluating the utility of ctDNA in detecting. Methods: MMR-related genes list was collected from relevant literature. The clinical and genetic mutation data of 441 STAD samples were obtained from cBioPortal. Kaplan-Meier survival analysis was used to evaluate the total survival rate (OS) of the published STAD data set. 680 STAD patients with TP53 mutation were screened and analyzed from the HapLab database. Results: An analysis of the TCGA data indicated that 356 patients had wild-type MMR genes and 85 had MMR mutations. MSH3 mutations accounted for 19.27% of the overall mutations and 42.35% of patients with MMR mutations, with a total of 36 patients. In terms of OS, patients with MMR gene mutations had a better prognosis compared to those with wild-type genes (log-rank test, p-value = 0.028). In the single-gene prognostic analysis, patients with MSH3 mutations had better prognosis (p-value 0.0004), while no statistical differences were found in other genes. In the monitoring of 680 HapLab STAD patients using ctDNA, 12.35% (84/680) had MMR mutations in their tumor tissue. After treatment, the proportion of TP53 mutations detected in patients was 11.91% (81/680), while the proportion of MMR mutations was 3.57% (3/84). Conclusions: The results of survival analysis showed a significant association between the mutation status of MMR and STAD. Monogenic MSH3 mutations was highly associated with the better survival, and circulating tumor DNA in blood highlight the importance of detecting MMR mutations in STAD patients. ctDNA provides a non-invasive method for the assessment of prognosis in STAD patients through the analysis of MMR gene mutations.