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Zhao S, Sun D, Yu H, Wang M, Xu B, Wang Y, Hu F, Wang X, Zhang J, Wang Y, Chai J. Oxaliplatin accelerates immunogenic cell death by activating the cGAS/STING/TBK1/IRF5 pathway in gastric cancer. FEBS J 2025. [PMID: 40260556 DOI: 10.1111/febs.70102] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2023] [Revised: 11/11/2024] [Accepted: 04/07/2025] [Indexed: 04/23/2025]
Abstract
Immunogenic cell death is a tumor cell death involving both innate and adaptive immune responses. Given the published findings that oxaliplatin causes the secretion of high mobility group box 1 (HMGB1) from cancer cells, which is necessary for the initiation of immunogenic cell death, we investigated whether oxaliplatin plays an anticancer role in gastric cancer by inducing immunogenic cell death and further explored its mechanism. We found that oxaliplatin inhibited viability and induced pyroptosis, immunogenic cell death, the production of reactive oxygen species, mitochondrial permeability transition pore (mPTP) opening, and cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) axis activation in gastric cancer cells. Suppressing mPTP opening (cyclosporine treatment), depleting mitochondrial DNA (mtDNA; ethidium bromide treatment), or STING downregulation (H151 or si-STING treatment) reversed cGAS/STING pathway activation and the increased immunogenic cell death induced by oxaliplatin in MKN-45 and AGS cells. Moreover, oxaliplatin induced immunogenic cell death via activating the cGAS/STING/TANK-binding kinase 1 (TBK1; also known as serine/threonine-protein kinase TBK1)/interferon regulatory factor 5 (IRF5) pathway. In conclusion, oxaliplatin treatment could induce immunogenic cell death and mPTP opening and activate the cGAS/STING/TBK1/IRF5 pathway in gastric cancer cells.
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Affiliation(s)
- Siwei Zhao
- Department of Gastrointestinal Surgery, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China
| | - Dong Sun
- Department of Gastrointestinal Surgery, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China
| | - Hang Yu
- Department of Gastrointestinal Surgery, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China
| | - Menglin Wang
- Department of Plastic Surgery, The First Affiliated Hospital, Dalian Medical University, China
| | - Botao Xu
- Department of Gastrointestinal Surgery, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China
| | - Yufei Wang
- Department of Gastrointestinal Surgery, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China
| | - Fangqi Hu
- Department of Gastrointestinal Surgery, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China
| | - Xiaofeng Wang
- Department of Gastrointestinal Surgery, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China
| | - Jiazi Zhang
- Department of Gastrointestinal Surgery, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China
| | - Yongsheng Wang
- Department of Breast Surgery, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China
| | - Jie Chai
- Department of Gastrointestinal Surgery, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China
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Mu X, Fan Y, Xu J, Xie R. Exploration of the optimal regimen of gastric mucosal cleansing medication for the H. pylori population before ME-NBI screening: study protocol for a single-center, single-blind, randomized controlled trial. Front Med (Lausanne) 2025; 12:1516271. [PMID: 40241907 PMCID: PMC12000017 DOI: 10.3389/fmed.2025.1516271] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2024] [Accepted: 03/17/2025] [Indexed: 04/18/2025] Open
Abstract
Objective Magnifying endoscopy combined with narrow-band imaging endoscopy is an emerging method for early gastric cancer screening and diagnosis However, its effectiveness is closely related to the cleaning quality of the gastric mucosal preparation. H. pylori infection is a major risk factor for inadequate gastric mucosa cleaning quality preparation. Multiple medications are useful in helping patients with gastric mucosal cleansing preparations. This randomized controlled trial study protocol aims to investigate the effect of different combinations of medications on the quality of gastric mucosal cleansing in an H. pylori-infected population. Methods This study is a prospective, randomized, single-blind, single-center trial. The subjects are patients who require magnifying endoscopy combined with narrow-band imaging and have evidence of H. pylori infection (a non-invasive diagnostic 13C urea breath test was used to examine the study subjects). These patients will be randomly assigned to the control group (Group A) and the experimental groups (Groups B, C, D, E, and F). Each group will consist of 44 patients, with a total of 264 patients expected to be enrolled. The core content of the drug preparation regimen for each group is as follows: Group A (control group) will take 10 ml of simethicone before the examination; Group B (experimental group) will take 20,000 units of pronase before the examination; Group C (experimental group) will take 600 mg of N-acetylcysteine before the examination; Group D (experimental group) will take 10 ml of simethicone +20,000 units of pronase before the examination; Group E (experimental group) will take 10 ml of simethicone + 600 mg of N-acetylcysteine before the examination; Group F (experimental group) will take 10 ml of simethicone + 20,000 units of pronase + 1 g of sodium bicarbonate before the examination. All group medications will be dissolved in 50 ml of warm water at 20-40°C. All patients will fast for ≥6 h and abstain from drinking for 2 h before the examination. The primary endpoint is the gastric mucosa cleanliness score. Secondary endpoints include the early detection rate of gastric cancer, polyp detection rate, adenoma detection rate, procedure time, number of irrigations, patient medication compliance, preoperative anxiety, incidence of adverse reactions, overall patient satisfaction, and willingness to undergo the examination again. Implications The results of this research project are aimed at improving the quality of gastric mucosal cleansing preparations in the H. pylori population to meet the demand for early diagnosis and treatment prevention screening for early gastric cancer screening. The implementation of the results of the study and their inclusion in the guidelines may reduce economic expenditures by reflecting a reduced need for social and health care services. Clinical Trial registration Chinese Clinical Trial Registry (ChiCTR). Number of identification: (ChiCTR2400087510).
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Affiliation(s)
- Xinyi Mu
- Department of Nursing, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China
| | - Yi Fan
- Department of Endoscopy, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China
| | - Jingyu Xu
- Nursing College, Zunyi Medical University, Zunyi, Guizhou, China
| | - Rui Xie
- Department of Endoscopy and Digestive System, Guizhou Provincial People's Hospital, Guiyang, Guizhou, China
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Wang HT, Chiu CF, Yang HR, Jeng LB, Bai EJ, Chen TH, Yeh CC, Chu CL, Bai LY. Adjuvant chemotherapy for stage II and III gastric adenocarcinoma: A retrospective analysis with long-term follow-up. J Formos Med Assoc 2025; 124:311-319. [PMID: 38719675 DOI: 10.1016/j.jfma.2024.04.020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2023] [Revised: 01/16/2024] [Accepted: 04/30/2024] [Indexed: 04/02/2025] Open
Abstract
BACKGROUND Whether adjuvant chemotherapy should be different for patients with stage II and III gastric cancer is unknown. METHODS We retrospectively analyzed the effects of adjuvant chemotherapy on the outcomes of 140 and 256 patients with stage II and III gastric cancer, respectively, between January 2008 and December 2018. Chemotherapies were stratified as fluoropyrimidine plus platinum versus fluoropyrimidine alone, tegafur/gimeracil/octeracil (S-1)-containing versus non-S-1-containing regimens, and S-1 plus cisplatin versus S-1 alone. RESULTS The median age of patients was 67.0 (range 24.6-98.8) years. With a median follow-up of 105 months, recurrence occurred in 32 (22.9%) and 130 (50.8%) patients with stage II and III disease, respectively. Adjuvant chemotherapy was administered as fluoropyrimidine monotherapy to 68 (48.6%) and 73 (28.5%) patients, fluoropyrimidine plus platinum to 9 (6.4%) and 104 (40.6%) patients, and none to 63 (45.0%) and 79 (30.9%) patients with stage II and III gastric cancer, respectively. Doublet chemotherapy was associated with longer disease-free survival (DFS) (26.5 vs. 15.2 months, P = 0.001) and overall survival (OS) (41.2 vs. 22.0 months, P < 0.001) than fluoropyrimidine monotherapy for stage IIIB-IIIC disease. Furthermore, S-1-containing regimens prolonged DFS (57.4 vs. 21.9 months, P = 0.044) and OS (81.4 vs. 28.6 months, P = 0.023) compared with non-S-1-containing chemotherapy in stage III disease. CONCLUSION Although fluoropyrimidine monotherapy is feasible for stage II-IIIA disease, doublet chemotherapy is significantly associated with longer survival than monotherapy for stage IIIB-IIIC disease. S-1-containing regimens might lead to longer survival than non-S-1-containing chemotherapy in stage III gastric cancer.
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Affiliation(s)
- Hsiu-Tzu Wang
- Division of Hematology and Oncology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Chang-Fang Chiu
- Division of Hematology and Oncology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan; College of Medicine, School of Medicine, China Medical University, Taichung, Taiwan; Cancer Center, China Medical University Hospital, Taichung, Taiwan
| | - Horng-Ren Yang
- College of Medicine, School of Medicine, China Medical University, Taichung, Taiwan; Department of Surgery, China Medical University Hospital, Taichung, Taiwan
| | - Long-Bin Jeng
- Department of Surgery, China Medical University Hospital, Taichung, Taiwan
| | - En-Jia Bai
- Bachelor of Science in Kinesiology, Exercise Science, The University of Texas at Austin, TX, 78712, USA
| | - Te-Hong Chen
- College of Medicine, School of Medicine, China Medical University, Taichung, Taiwan; Department of Surgery, China Medical University Hospital, Taichung, Taiwan
| | - Chun-Chieh Yeh
- College of Medicine, School of Medicine, China Medical University, Taichung, Taiwan; Department of Surgery, China Medical University Hospital, Taichung, Taiwan
| | - Chien-Lun Chu
- Cancer Center, China Medical University Hospital, Taichung, Taiwan
| | - Li-Yuan Bai
- Division of Hematology and Oncology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan; College of Medicine, School of Medicine, China Medical University, Taichung, Taiwan.
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Wang FY, Huang XM, Cao YQ, Cao J, Song M, Fang ZJ, Huang XE. Comparison of PSOX (paclitaxel, oxaliplatin, S-1) and SOX (oxaliplatin, S-1) as postoperative adjuvant chemotherapy for stage II-III gastric cancer. World J Surg Oncol 2025; 23:75. [PMID: 40055779 PMCID: PMC11887138 DOI: 10.1186/s12957-025-03723-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2024] [Accepted: 02/16/2025] [Indexed: 05/13/2025] Open
Abstract
BACKGROUND Adjuvant chemotherapy is the conventional treatment for stage II and III gastric cancer(GC). Postoperative doublet chemotherapy has consistently shown improved survival outcomes in advanced-stage GC patients compared to single-agent regimens. Triplet regimens have shown significant survival benefits in the perioperative settings. This retrospective study evaluated the efficacy and safety of paclitaxel/S-1/oxaliplatin (PSOX) compared to S-1/oxaliplatin (SOX) as postoperative adjuvant chemotherapy in stage II-III GC patients following D2 gastrectomy. METHODS A retrospective review was conducted on patients with histologically confirmed stage II-III gastric cancer who underwent D2 gastrectomy at Jiangsu Cancer Hospital, categorizing them into two groups. A total of 75 patients were included in PSOX group and 81 patients in the SOX group between April 2018 and August 2021. Patients in PSOX group received paclitaxel (120 mg/m2), oxaliplatin (100 mg/m2) and S-1 (80 - 60 mg/d) per cycle, while those patients in SOX group were administrated oxaliplatin (130 mg/m2) and S-1 (80-120 mg/d) per cycle. Patients from both groups were matched in a 1:1 ratio using propensity scores to assess differences in disease-free survival (DFS) and safety. RESULTS The 3-year DFS rate was 78.2% for the PSOX group and 74.0% for the SOX group (P = 0.355), with a hazard ratio for peritoneal relapse of 0.287 (95% CI, 0.090-0.915; P = 0.035). Subgroup analysis indicated that stage IIIC GC patients in the PSOX group had a higher DFS rate than those in the SOX group(P = 0.032). Grade 3 or 4 adverse events, as per the National Cancer Institute Common Toxicity Criteria, such as leucopenia (10.6% vs. 4.5%), neutropenia (10.6% vs. 9.1%), nausea/vomiting (4.5% vs. 3.0%), and diarrhea (4.5% vs. 3.0%) were relatively common in the PSOX group compared to the SOX group, with no statistically significant differences between the two groups. CONCLUSION Our findings suggested that adjuvant PSOX chemotherapy offers superior survival benefits compared to the SOX regimen in patients with staged IIIC GC after D2 gastrectomy. The incidence of adverse events with PSOX chemotherapy was comparable to that of SOX chemotherapy.
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Affiliation(s)
- Fei-Yu Wang
- Department of Medical Oncology, The Affiliated Cancer Hospital of Nanjing Medical University & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research, Nanjing, 210009, China
| | - Xiang-Ming Huang
- Department of Oncology, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210028, China
| | - Yu-Qing Cao
- Department of Medical Oncology, The Affiliated Cancer Hospital of Nanjing Medical University & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research, Nanjing, 210009, China
| | - Jie Cao
- Department of Medical Oncology, The Affiliated Cancer Hospital of Nanjing Medical University & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research, Nanjing, 210009, China
| | - Meng Song
- Department of Medical Oncology, The Affiliated Cancer Hospital of Nanjing Medical University & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research, Nanjing, 210009, China
| | - Zhi-Jun Fang
- Department of Oncology, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210028, China.
- Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, 210028, China.
| | - Xin-En Huang
- Department of Medical Oncology, The Affiliated Cancer Hospital of Nanjing Medical University & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research, Nanjing, 210009, China.
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Zhang X, Liang H, Li Z, Xue Y, Wang Y, Zhou Z, Yu J, Bu Z, Chen L, Du Y, Wang X, Wu A, Li G, Su X, Xiao G, Cui M, Wu D, Chen L, Wu X, Zhou Y, Zhang L, Dang C, He Y, Zhang Z, Sun Y, Li Y, Chen H, Bai Y, Wang Y, Yu P, Zhu G, Suo J, Jia B, Li L, Huang C, Li F, Ye Y, Xu H, Wang X, Yuan Y, E J, Ying X, Yao C, Shen L, Ji J. Perioperative or postoperative adjuvant oxaliplatin with S-1 versus adjuvant oxaliplatin with capecitabine in patients with locally advanced gastric or gastro-oesophageal junction adenocarcinoma undergoing D2 gastrectomy (RESOLVE): final report of a randomised, open-label, phase 3 trial. Lancet Oncol 2025; 26:312-319. [PMID: 39952264 DOI: 10.1016/s1470-2045(24)00676-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2024] [Revised: 11/21/2024] [Accepted: 11/22/2024] [Indexed: 02/17/2025]
Abstract
BACKGROUND The multicentre RESOLVE trial examined the efficacy of perioperative and postoperative S-1 and oxaliplatin (SOX) compared with postoperative capecitabine and oxaliplatin (CapOx) in gastric or gastro-oesophageal junction cancer. Initial analyses did not encompass overall survival owing to the immature data. This paper provides an updated analysis of the survival data from the RESOLVE trial. METHODS In this randomised, open-label, phase 3 study, participants aged 18 years or older with cT4a N+ M0 or cT4b Nany M0 gastric or gastro-oesophageal junction adenocarcinoma who were feasible for D2 lymphadenectomy and had a Karnofsky performance score of 70 or higher were enrolled. Participants were randomly assigned in a 1:1:1 ratio via an interactive web response system, stratified by participating centres and Lauren classification, to receive adjuvant CapOx (eight postoperative cycles of intravenous oxaliplatin 130 mg/m2 on day 1 of each 21-day cycle plus oral capecitabine 1000 mg/m2 twice a day on days 1-14, adjuvant SOX (eight postoperative cycles of intravenous oxaliplatin 130 mg/m2 on day 1 of each 21-day cycle plus oral S-1 40-60 mg twice a day on days 1-14), or perioperative SOX (intravenous oxaliplatin 130 mg/m2 on day 1 of each 21-day cycle plus oral S-1 40-60 mg twice a day for three cycles preoperatively and five cycles postoperatively followed by three cycles of S-1 monotherapy. The primary endpoint, assessed in the modified intention-to-treat population, was 3-year disease-free survival to assess the superiority of perioperative-SOX compared with adjuvant-CapOx and the non-inferiority (hazard ratio [HR] non-inferiority margin of 1·33) of adjuvant-SOX compared with adjuvant-CapOx, and has been reported previously. This final report focuses on the secondary endpoint of 5-year overall survival, also assessed in the modified intention-to-treat population. Other secondary endpoints-R0 resection rate and safety-were not updated in this analysis. The study is registered at ClinicalTrials.gov, NCT01534546, and is complete. FINDINGS Between Aug 15, 2012, and Feb 28, 2017, 1094 patients were enrolled and randomly assigned, of whom 1022 participants were included in the modified intention-to-treat population: 345 (259 male, 86 female) in the adjuvant-CapOx group, 340 (238 male, 102 female) in the adjuvant-SOX group, and 337 (271 male, 66 female) in the perioperative-SOX group. As of April 7, 2022, the median duration of follow-up was 62·8 months (IQR 52·0-75·1). The 5-year overall survival rates were 52·1% (95% CI 46·3-57·5) for the adjuvant-CapOx group, 61·0% (55·3-66·2) for the adjuvant-SOX group, and 60·0% (54·2-65·3), for the perioperative-SOX group. Overall survival was significantly prolonged with perioperative-SOX (HR 0·79; 95% CI 0·62-1·00, p=0·049) and adjuvant-SOX (HR 0·77, 0·61-0·98, p=0·033), compared with adjuvant-CapOx. INTERPRETATION Consistent with the initial analysis of 3-year disease-free survival, the extended 5-year overall survival analysis from the RESOLVE trial confirmed the survival advantage of perioperative-SOX and adjuvant-SOX compared with the standard adjuvant-CapOx regimen. The SOX regimen, given perioperatively or as an adjuvant treatment, emerges as a potential standard treatment modality for locally advanced gastric or gastro-oesophageal junction cancer management in Asian patients. FUNDING The National Key Research and Development Program of China, the National Natural Science Foundation of China, the Capital's Funds for Health Improvement and Research, the Beijing Natural Science Foundation, National Natural Science Foundation of China, the Beijing Natural Science Foundation, Taiho, Hengrui Pharmaceutical and Sanofi-Aventis. TRANSLATION For the Chinese translation of the abstract see Supplementary Materials section.
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Affiliation(s)
- Xiaotian Zhang
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing, China
| | - Han Liang
- Department of Abdominal Oncology Surgery, Tianjin Medical University Cancer Institute & Hospital, Tianjin, China
| | - Ziyu Li
- Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute, Beijing, China
| | - Yingwei Xue
- Department of Gastrointestinal Surgery, Harbin Medical University Cancer Hospital, Harbin, China
| | - Yanong Wang
- Department of Stomach Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Zhiwei Zhou
- Department of Gastric Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China; State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Jiren Yu
- Department of Gastrointestinal Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Zhaode Bu
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing, China
| | - Lin Chen
- Department of General Surgery, Chinese PLA General Hospital, Beijing, China; Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China
| | - Yian Du
- Department of General Surgery, Zhejiang Cancer Hospital, Hangzhou, China
| | - Xinbao Wang
- Department of Hepatopancreatobiliary Surgery, Zhejiang Cancer Hospital, Hangzhou, China
| | - Aiwen Wu
- Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute, Beijing, China
| | - Guoli Li
- Department of General Surgery, Jinling Hospital, Nanjing, China
| | - Xiangqian Su
- Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute, Beijing, China
| | - Gang Xiao
- Department of General Surgery, Beijing Hospital, Beijing, China
| | - Ming Cui
- Beijing Key Laboratory of Carcinogenesis and Translational Research, Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute, Beijing, China
| | - Dan Wu
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China
| | - Li Chen
- Department of General Surgery, Chinese PLA General Hospital, Beijing, China; Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China
| | - Xiaojiang Wu
- Beijing Key Laboratory of Carcinogenesis and Translational Research, Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute, Beijing, China
| | - Yanbing Zhou
- Department of Gastrointestinal Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Lianhai Zhang
- Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute, Beijing, China
| | - Chengxue Dang
- Department of Oncology Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Yulong He
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Zhongtao Zhang
- Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Yihong Sun
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yong Li
- Department of General Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Huanqiu Chen
- Department of General Surgery, Jiangsu Cancer Hospital, Nanjing, China
| | - Yuxian Bai
- Department of Gastrointestinal Oncology, Harbin Medical University Cancer Hospital, Harbin, China
| | - Yakun Wang
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing, China
| | - Peiwu Yu
- Department of General Surgery, The First Hospital Affiliated to Army Medical University, Chongqing, China
| | - Guanbao Zhu
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Jian Suo
- Department of Gastrointestinal Surgery, The First Hospital of Jilin University, Changchun, China
| | - Baoqing Jia
- Department of General Surgery, Chinese PLA General Hospital, Beijing, China
| | - Leping Li
- Department of Gastrointestinal Surgery, Shandong Provincial Hospital, Jinan, China
| | - Changming Huang
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China
| | - Fei Li
- Department of General Surgery, Xuanwu Hospital Capital Medical University, Beijing, China
| | - Yingjiang Ye
- Department of General Surgery, Peking University People's Hospital, Beijing, China
| | - Huimian Xu
- Department of Gastrointestinal Oncology Surgery, The First Hospital of China Medical University, Shenyang, China
| | - Xin Wang
- Department of General Surgery, Peking University First Hospital, Beijing, China
| | - Yannan Yuan
- Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute, Beijing, China
| | - Jianyu E
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
| | - Xiangji Ying
- Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute, Beijing, China
| | - Chen Yao
- Peking University Clinical Research Institute, Peking University First Hospital, Beijing, China
| | - Lin Shen
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing, China.
| | - Jiafu Ji
- Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute, Beijing, China.
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Nishikawa K, Koizumi W, Tsuburaya A, Suzuki M, Morita S, Fujitani K, Akamaru Y, Shimada K, Hosaka H, Nishimura K, Yoshikawa T, Tsujinaka T, Sakamoto J. Differences in efficacy of biweekly irinotecan plus cisplatin versus irinotecan alone in second-line treatment of advanced gastric cancer with or without prior gastrectomy. Int J Clin Oncol 2025; 30:320-329. [PMID: 39585516 DOI: 10.1007/s10147-024-02661-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2024] [Accepted: 11/11/2024] [Indexed: 11/26/2024]
Abstract
BACKGROUND Biweekly irinotecan plus cisplatin combination therapy (BIRIP) and irinotecan monotherapy (IRI) are both expectable second-line chemotherapy (SLC) options for treating advanced gastric cancer (AGC). Although many patients receiving SLC have undergone gastrectomy, the impact of gastrectomy on SLC remains unclear, and the impact of gastrectomy may vary from regimen to regimen. PATIENTS AND METHODS A total of 290 eligible patients registered in two randomized phase III trials evaluating BIRIP (IRI, 60 mg/m2; CDDP, 30 mg/m2, q2w) or IRI (150 mg/m2, q2w) for patients with AGC was classified into the prior gastrectomy subgroup (PGG) or the no gastrectomy subgroup (NGG). We performed a subgroup analysis to evaluate the impact of gastrectomy on second-line BIRIP and IRI. RESULTS The BIRIP demonstrated significantly longer OS (11.1 vs. 6.8 months; HR 0.64; P = 0.026) and PFS (3.7 vs. 2.3 months; HR 0.54; P = 0.003) than the IRI, as well as better ORR (23.5% vs. 7.1%, P = 0.046) and DCR (74.5% vs. 47.6%, P = 0.010) in NGG. Although in PGG, the BIRIP failed to demonstrate differences in OS (13.8 vs. 13.8 months; HR 0.94; P = 0.722), PFS (4.9 vs. 4.5 months; HR 0.82; P = 0.194), ORR (18.3% vs. 20.5%) and DCR (70.4% vs. 65.1%). The incidence of grade 3 or worse adverse events did not differ except for a high incidence of anemia in the BIRIP group in PGG. CONCLUSIONS BIRIP was an effective treatment option that may improve survival outcomes among patients with AGC without previous gastrectomy. CLINICAL TRIAL REGISTRATION UMIN000025367.
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Affiliation(s)
- Kazuhiro Nishikawa
- Cancer Treatment Center, Osaka International Medical & Science Center, Osaka Keisatsu Hospital, 10-31 Kitayama-cho, Tennoji-ku, Osaka, 543-0035, Japan.
| | - Wasaburo Koizumi
- Kitasato University, 1-15-3, Kitasato, Minami-ku, Sagamihara, Kanagawa, 252-0374, Japan
| | - Akira Tsuburaya
- Department of Surgery, AOI Nanasawa Rehabilitation Hospital, Atsugi, Japan
| | - Motoko Suzuki
- Department of Data Science, National Cancer Center Hospital East, Chiba, Japan
| | - Satoshi Morita
- Department of Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of Medicine, 54, Shogoinkawaharacho, Sakyo-ku, Kyoto, 606-8397, Japan
| | - Kazumasa Fujitani
- Department of Surgery, Osaka General Medical Center, 3-1-56, Bandaihigashi,Sumiyoshi-ku, Osaka, 558-0056, Japan
| | - Yusuke Akamaru
- Department of Surgery, Osaka Rosai Hospital, 1179-3 Nagasonecho, Kita-ku, Sakai City, Osaka, 591-8025, Japan
| | - Ken Shimada
- Department of Internal Medicine, Division of Medical Oncology, Showa University Koto Toyosu Hospital, 5-1-38 Toyosu, Koto-ku, Tokyo, 135-8577, Japan
| | - Hisashi Hosaka
- Department of Gastroenterology, Gunma Prefectural Cancer Center, 617-1, Takahayashinishi-cho, Ohta, 373-0828, Japan
| | - Ken Nishimura
- Department of Oncology, Kitasato University Kitasato Institute Hospital, 5-9-1, Shirokane, Minato-ku, Tokyo, 108-8642, Japan
| | - Takaki Yoshikawa
- Department of Gastric Surgery, The National Hospital Organization National Cancer Center Hospital, 5-1-1, Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan
| | | | - Junichi Sakamoto
- Tokai Central Hospital, 4-6-2, Sohara Higashijimacho, Kakamigahara, 504-8601, Japan
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Song N, Zhang X, Su J, Chen L, Jin Q, Liu C, Dai Z. Nature and Determinants of Fear of Cancer Recurrence After Endoscopic Submucosal Dissection for Early Gastric Cancer: A Cross-Sectional Study. Gastroenterol Nurs 2024; 47:358-367. [PMID: 39356122 DOI: 10.1097/sga.0000000000000812] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/06/2023] [Accepted: 02/08/2024] [Indexed: 10/03/2024] Open
Abstract
Gastric cancer is one of the most prevalent tumors in China and other countries, with high morbidity and mortality. Fear of cancer recurrence is common among cancer survivors. Fear of cancer recurrence experiences and psychological interventions have been investigated in breast and other cancers. However, this phenomenon and associated factors have not been evaluated in early gastric cancer survivors in China. The objective of this study was to investigate the nature of fear of cancer recurrence and influencing factors in Chinese patients with early gastric cancer treated with endoscopic submucosal dissection. This cross-sectional study in two centers included 312 early gastric cancer patients who answered self-report questionnaires and were treated with endoscopic submucosal dissection between June 2022 and May 2023 to assess fear of cancer recurrence. Gender, family history of gastrointestinal tumor, tumor recurrence, Helicobacter pylori infection, disease perception, and self-perceived burden were significant factors influencing fear of cancer recurrence (p < .05). More than half of early gastric cancer patients have fear of cancer recurrence, and how to deal with it has become a key issue in the postoperative care of patients. Medical professionals should address these factors to reduce fear of cancer recurrence in at-risk patients.
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Affiliation(s)
- Nian Song
- Nian Song, MD, School of Nursing, Nanjing University of Chinese Medicine, Jiangsu, China
- Xiaotao Zhang, MD, Department of Digestive Endoscopy, the Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
- Jie Su, BD, Department of Digestive Endoscopy, the Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
- Lu Chen, BD, Department of Digestive Endoscopy, the Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
- Qianhong Jin, MD, School of Nursing, Nanjing University of Chinese Medicine, Jiangsu, China
- Chengcheng Liu, MD, School of Nursing, Nanjing University of Chinese Medicine, Jiangsu, China
- Zhengxiang Dai, MD, RN, Department of Hospital-Acquired Infection Control, the Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu, China
| | - Xiaotao Zhang
- Nian Song, MD, School of Nursing, Nanjing University of Chinese Medicine, Jiangsu, China
- Xiaotao Zhang, MD, Department of Digestive Endoscopy, the Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
- Jie Su, BD, Department of Digestive Endoscopy, the Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
- Lu Chen, BD, Department of Digestive Endoscopy, the Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
- Qianhong Jin, MD, School of Nursing, Nanjing University of Chinese Medicine, Jiangsu, China
- Chengcheng Liu, MD, School of Nursing, Nanjing University of Chinese Medicine, Jiangsu, China
- Zhengxiang Dai, MD, RN, Department of Hospital-Acquired Infection Control, the Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu, China
| | - Jie Su
- Nian Song, MD, School of Nursing, Nanjing University of Chinese Medicine, Jiangsu, China
- Xiaotao Zhang, MD, Department of Digestive Endoscopy, the Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
- Jie Su, BD, Department of Digestive Endoscopy, the Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
- Lu Chen, BD, Department of Digestive Endoscopy, the Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
- Qianhong Jin, MD, School of Nursing, Nanjing University of Chinese Medicine, Jiangsu, China
- Chengcheng Liu, MD, School of Nursing, Nanjing University of Chinese Medicine, Jiangsu, China
- Zhengxiang Dai, MD, RN, Department of Hospital-Acquired Infection Control, the Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu, China
| | - Lu Chen
- Nian Song, MD, School of Nursing, Nanjing University of Chinese Medicine, Jiangsu, China
- Xiaotao Zhang, MD, Department of Digestive Endoscopy, the Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
- Jie Su, BD, Department of Digestive Endoscopy, the Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
- Lu Chen, BD, Department of Digestive Endoscopy, the Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
- Qianhong Jin, MD, School of Nursing, Nanjing University of Chinese Medicine, Jiangsu, China
- Chengcheng Liu, MD, School of Nursing, Nanjing University of Chinese Medicine, Jiangsu, China
- Zhengxiang Dai, MD, RN, Department of Hospital-Acquired Infection Control, the Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu, China
| | - Qianhong Jin
- Nian Song, MD, School of Nursing, Nanjing University of Chinese Medicine, Jiangsu, China
- Xiaotao Zhang, MD, Department of Digestive Endoscopy, the Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
- Jie Su, BD, Department of Digestive Endoscopy, the Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
- Lu Chen, BD, Department of Digestive Endoscopy, the Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
- Qianhong Jin, MD, School of Nursing, Nanjing University of Chinese Medicine, Jiangsu, China
- Chengcheng Liu, MD, School of Nursing, Nanjing University of Chinese Medicine, Jiangsu, China
- Zhengxiang Dai, MD, RN, Department of Hospital-Acquired Infection Control, the Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu, China
| | - Chengcheng Liu
- Nian Song, MD, School of Nursing, Nanjing University of Chinese Medicine, Jiangsu, China
- Xiaotao Zhang, MD, Department of Digestive Endoscopy, the Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
- Jie Su, BD, Department of Digestive Endoscopy, the Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
- Lu Chen, BD, Department of Digestive Endoscopy, the Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
- Qianhong Jin, MD, School of Nursing, Nanjing University of Chinese Medicine, Jiangsu, China
- Chengcheng Liu, MD, School of Nursing, Nanjing University of Chinese Medicine, Jiangsu, China
- Zhengxiang Dai, MD, RN, Department of Hospital-Acquired Infection Control, the Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu, China
| | - Zhengxiang Dai
- Nian Song, MD, School of Nursing, Nanjing University of Chinese Medicine, Jiangsu, China
- Xiaotao Zhang, MD, Department of Digestive Endoscopy, the Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
- Jie Su, BD, Department of Digestive Endoscopy, the Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
- Lu Chen, BD, Department of Digestive Endoscopy, the Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
- Qianhong Jin, MD, School of Nursing, Nanjing University of Chinese Medicine, Jiangsu, China
- Chengcheng Liu, MD, School of Nursing, Nanjing University of Chinese Medicine, Jiangsu, China
- Zhengxiang Dai, MD, RN, Department of Hospital-Acquired Infection Control, the Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu, China
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Toji Y, Takeuchi S, Ebihara Y, Kurashima Y, Harada K, Hayashi M, Abe H, Wada H, Yorinaga S, Shichinohe T, Tomaru U, Komatsu Y, Hirano S. Perioperative chemotherapy with nivolumab for HER2-negative locally advanced gastric cancer: a case series. Surg Case Rep 2024; 10:200. [PMID: 39192090 DOI: 10.1186/s40792-024-02001-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2024] [Accepted: 08/15/2024] [Indexed: 08/29/2024] Open
Abstract
BACKGROUND Nivolumab with chemotherapy has been transformative for metastatic gastric cancer (GC). The potential of this regimen for local tumor control could be utilized for perioperative chemotherapy in locally advanced GC with bulky tumors or lymph node metastasis involving other organs. CASE PRESENTATION Five patients with HER2-negative advanced GC were treated with nivolumab and oxaliplatin-based chemotherapy. All patients presented with clinical stage III or IVA GC with tumors in contact with either the pancreas or liver. Following chemotherapy, all tumors demonstrated shrinkage, allowing successful radical gastrectomies including four minimally invasive approach without postoperative complications. Four patients avoided combined resection of other organs. CONCLUSIONS Perioperative chemotherapy with nivolumab was effective for local disease control in this case series. This regimen could be a promising treatment approach for locally advanced GC; however, its survival benefits should be evaluated in clinical trials.
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Affiliation(s)
- Yuta Toji
- Department of Gastroenterological Surgery II, Division of Surgery, Faculty of Medicine, Hokkaido University, West-7, North-15, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan
| | - Shintaro Takeuchi
- Department of Gastroenterological Surgery II, Division of Surgery, Faculty of Medicine, Hokkaido University, West-7, North-15, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan.
| | - Yuma Ebihara
- Department of Gastroenterological Surgery II, Division of Surgery, Faculty of Medicine, Hokkaido University, West-7, North-15, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan
| | - Yo Kurashima
- Department of Gastroenterological Surgery II, Division of Surgery, Faculty of Medicine, Hokkaido University, West-7, North-15, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan
| | - Kazuaki Harada
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Hokkaido University, West-7, North-15, Kita-ku, Sapporo, Hokkaido, 060-8648, Japan
| | - Mariko Hayashi
- Department of Gastroenterological Surgery II, Division of Surgery, Faculty of Medicine, Hokkaido University, West-7, North-15, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan
| | - Hirotake Abe
- Department of Gastroenterological Surgery II, Division of Surgery, Faculty of Medicine, Hokkaido University, West-7, North-15, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan
| | - Hideyuki Wada
- Department of Gastroenterological Surgery II, Division of Surgery, Faculty of Medicine, Hokkaido University, West-7, North-15, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan
| | - Satoko Yorinaga
- Department of Gastroenterological Surgery II, Division of Surgery, Faculty of Medicine, Hokkaido University, West-7, North-15, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan
- Department of Surgical Pathology, Hokkaido University Hospital, West-5, North-14, Kita-ku, Sapporo, Hokkaido, 060-8648, Japan
| | - Toshiaki Shichinohe
- Department of Gastroenterological Surgery II, Division of Surgery, Faculty of Medicine, Hokkaido University, West-7, North-15, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan
| | - Utano Tomaru
- Department of Surgical Pathology, Hokkaido University Hospital, West-5, North-14, Kita-ku, Sapporo, Hokkaido, 060-8648, Japan
| | - Yoshito Komatsu
- Department of Cancer Center, Hokkaido University Hospital, West-5, North-14, Kita-ku, Sapporo, Hokkaido, 060-8648, Japan
| | - Satoshi Hirano
- Department of Gastroenterological Surgery II, Division of Surgery, Faculty of Medicine, Hokkaido University, West-7, North-15, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan
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9
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Gao C, Zhang G, Zheng J, Zheng Y, Lin W, Xu G, You Y, Li D, Wang W. The value of LCI-based modified Kyoto classification risk scoring system in predicting the risk of early gastric cancer. Scand J Gastroenterol 2024; 59:859-867. [PMID: 38578144 DOI: 10.1080/00365521.2024.2338443] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2024] [Revised: 03/21/2024] [Accepted: 03/29/2024] [Indexed: 04/06/2024]
Abstract
OBJECTIVE To study and compare the value of the Kyoto classification risk scoring system and the modified Kyoto classification risk scoring system based on linked color imaging (LCI) in predicting the risk of early gastric cancer. METHODS One hundred and fifty patients with pathologically confirmed non-cardia early gastric cancer by endoscopic LCI and 150 non-gastric cancer patients matched for age and gender were included. Basic patient data and whole gastric endoscopic images under LCI were collected, and the images were scored according to the LCI-based Kyoto classification risk scoring system and the LCI-based modified Kyoto classification risk scoring system. RESULTS Compared with the LCI-based Kyoto classification risk scoring system, the LCI-based modified Kyoto classification risk scoring system had a higher AUC for predicting the risk of early gastric cancer (0.723 vs. 0.784, p = 0.023), with a score of ≥3 being the best cutoff value for predicting the risk of early gastric cancer (sensitivity 61.33%, specificity 86.00%), and scores of 3 to 5 were significantly associated with early gastric carcinogenesis significantly (OR = 9.032, 95% CI: 4.995-16.330, p < 0.001). CONCLUSIONS Compared with the LCI-based Kyoto classification risk scoring system, the LCI-based Kyoto modified classification risk scoring system has a better value for predicting the risk of early gastric cancer, and the score of 3 to 5 is a high-risk factor for the risk of early gastric cancer development, which is more strongly correlated with the risk of early gastric cancer.
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Affiliation(s)
- Chao Gao
- Department of Gastroenterology, 900th Hospital of Joint Logistics Support Force, Fujian Medical University, Fuzhou, China
- Department of Gastroenterology, 900th Hospital of Joint Logistics Support Force, People's Liberation Army, Fuzhou, China
| | - Guanpo Zhang
- Department of Gastroenterology, 900th Hospital of Joint Logistics Support Force, Fujian Medical University, Fuzhou, China
- Department of Gastroenterology, 900th Hospital of Joint Logistics Support Force, People's Liberation Army, Fuzhou, China
| | - Jin Zheng
- Department of Gastroenterology, 900th Hospital of Joint Logistics Support Force, Fujian Medical University, Fuzhou, China
- Department of Gastroenterology, 900th Hospital of Joint Logistics Support Force, People's Liberation Army, Fuzhou, China
| | - Yunmeng Zheng
- Department of Gastroenterology, 900th Hospital of Joint Logistics Support Force, Fujian Medical University, Fuzhou, China
- Department of Gastroenterology, 900th Hospital of Joint Logistics Support Force, People's Liberation Army, Fuzhou, China
| | - Wulian Lin
- Department of Gastroenterology, 900th Hospital of Joint Logistics Support Force, Fujian Medical University, Fuzhou, China
- Department of Gastroenterology, 900th Hospital of Joint Logistics Support Force, People's Liberation Army, Fuzhou, China
| | - Guilin Xu
- Department of Gastroenterology, 900th Hospital of Joint Logistics Support Force, Fujian Medical University, Fuzhou, China
- Department of Gastroenterology, 900th Hospital of Joint Logistics Support Force, People's Liberation Army, Fuzhou, China
| | - Yixiang You
- Department of Gastroenterology, 900th Hospital of Joint Logistics Support Force, Fujian Medical University, Fuzhou, China
- Department of Gastroenterology, 900th Hospital of Joint Logistics Support Force, People's Liberation Army, Fuzhou, China
| | - Dazhou Li
- Department of Gastroenterology, 900th Hospital of Joint Logistics Support Force, Fujian Medical University, Fuzhou, China
- Department of Gastroenterology, 900th Hospital of Joint Logistics Support Force, People's Liberation Army, Fuzhou, China
| | - Wen Wang
- Department of Gastroenterology, 900th Hospital of Joint Logistics Support Force, Fujian Medical University, Fuzhou, China
- Department of Gastroenterology, 900th Hospital of Joint Logistics Support Force, People's Liberation Army, Fuzhou, China
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10
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Liu X, Yan Y, Lu L, Liu Y, Ma J, Wang X, Wang D, Liu B, Liu Z, Zhou X, Cui H, Zhao Z, Li C, Liu J, Li W, Huang Q, Zhao Q, Liu T, Fu W. Comparison of SOX and CAPOX in patients with advanced gastric cancer after laparoscopic D2 gastrectomy: A randomized controlled trial. Cancer Med 2024; 13:e7326. [PMID: 38826114 PMCID: PMC11145022 DOI: 10.1002/cam4.7326] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2023] [Revised: 04/10/2024] [Accepted: 05/12/2024] [Indexed: 06/04/2024] Open
Abstract
BACKGROUND Optimal adjuvant chemotherapy after laparoscopic surgery in gastric cancer (GC) patients is still undefined. We aimed to evaluate the efficacy of S-1 plus oxaliplatin (SOX) and capecitabine plus oxaliplatin (CAPOX) in patients with GC after laparoscopic gastrectomy. METHODS A non-inferiority randomized controlled clinical trial was performed in China. Patients with advanced GC who underwent laparoscopic D2 gastrectomy were randomly assigned to receive SOX and CAPOX regimens. RESULTS In total, 191 patients were screened between May 2018 and June 2019, and 140 (73.3%) were included in the modified intent-to-treat analysis (mITT), of whom 69 and 71 were assigned to the SOX and CAPOX groups, respectively. The SOX group had similar 3-year overall survival (OS) and disease-free survival to the CAPOX group. Subgroup analysis revealed significantly better OS in the SOX group for male patients ([HR] = 0.395; 95% [CI], 0.153-1.019; p = 0.045), age >60 (HR = 0.219; 95% [CI], 0.064-0.753; p = 0.016), tumors in the gastric antrum (HR = 0.273; 95% [CI], 0.076-0.981; p = 0.047), and moderately differentiated tumors (HR = 0.338; 95% [CI], 0.110-1.041; p = 0.041). There were no significant differences observed in terms of adverse events and recurrence patterns between the two groups. CONCLUSION Adjuvant SOX was non-inferior to CAPOX treatments for patients with GC who underwent curative laparoscopic D2 gastrectomy. For male patients, aged >60 years, tumors in the gastric antrum, and moderately differentiated tumors, adjuvant SOX may achieve an improvement compared with CAPOX.
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Affiliation(s)
- Xin Liu
- Department of General SurgeryTianjin Medical University General HospitalTianjinChina
| | - Yongjia Yan
- Department of General SurgeryTianjin Medical University General HospitalTianjinChina
| | - Li Lu
- Department of General SurgeryTianjin Medical University General HospitalTianjinChina
| | - Yang Liu
- Department of General Surgerythe Fourth Affiliated Hospital, Hebei Medical UniversityShijiazhuangChina
| | - Jun Ma
- Department of Digestive Endoscopic and Minimally Invasive SurgeryShanxi Cancer HospitalTaiyuanChina
| | - Xi Wang
- Department of General SurgeryTianjin Medical University General HospitalTianjinChina
| | - Daohan Wang
- Department of General SurgeryTianjin Medical University General HospitalTianjinChina
| | - Bang Liu
- Department of General SurgeryTianjin Medical University General HospitalTianjinChina
| | - Zhuo Liu
- Department of General SurgeryTianjin Medical University General HospitalTianjinChina
| | - Xueying Zhou
- Department of General SurgeryTianjin Medical University General HospitalTianjinChina
| | - He Cui
- Department of General SurgeryTianjin Medical University General HospitalTianjinChina
| | - Zhicheng Zhao
- Department of General SurgeryTianjin Medical University General HospitalTianjinChina
| | - Chuan Li
- Department of General SurgeryTianjin Medical University General HospitalTianjinChina
| | - Jian Liu
- Department of General SurgeryTianjin Medical University General HospitalTianjinChina
| | - Weidong Li
- Department of General SurgeryTianjin Medical University General HospitalTianjinChina
| | - Qing‐Xing Huang
- Department of Digestive Endoscopic and Minimally Invasive SurgeryShanxi Cancer HospitalTaiyuanChina
| | - Qun Zhao
- Department of General Surgerythe Fourth Affiliated Hospital, Hebei Medical UniversityShijiazhuangChina
| | - Tong Liu
- Department of General SurgeryTianjin Medical University General HospitalTianjinChina
| | - Weihua Fu
- Department of General SurgeryTianjin Medical University General HospitalTianjinChina
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11
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Liu C, Lu J, An L. Development and validation of nomograms for predicting the prognosis of early and late recurrence of advanced gastric cancer after radical surgery based on post-recurrence survival. Medicine (Baltimore) 2024; 103:e38376. [PMID: 39259073 PMCID: PMC11142773 DOI: 10.1097/md.0000000000038376] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2023] [Revised: 02/21/2024] [Accepted: 05/06/2024] [Indexed: 09/12/2024] Open
Abstract
In this study, we aimed to explore the risk factors influencing post-recurrence survival (PRS) of early recurrence (ER) and late recurrence (LR) in stage advanced gastric cancer (AGC) patients after radical surgery, respectively, and to develop predictive models in turn. Medical records of 192 AGC patients who recurred after radical gastrectomy were retrospectively reviewed. They were randomly divided into the training and validation set at a ratio of 2:1. Nomograms were built based on risk factors influencing PRS of ER and LR explored by Cox regression analyses, respectively. Concordance index (C-index) values and calibration curves were used to evaluate predictive power of nomograms. Body mass index < 18.5 kg/m2, prealbumin level < 70.1 mg/L, positive lymph nodes ratio ≥ 0.486 and palliative treatment after recurrence were independent risk factors for the prognosis of ER. In contrast, prealbumin level < 170.1 mg/L, CEA ≥ 18.32 μg/L, tumor diameter ≥ 5.5 cm and palliative treatment after recurrence were independent risk factors for the prognosis of LR. The C-index values were 0.801 and 0.772 for ER and LR in the training set, respectively. The calibration curves of validation set showed a C-index value of 0.744 and 0.676 for ER and LR, respectively. Nomograms which were constructed to predict the prognosis of ER and LR of AGC after surgery showed great predictive power and could provide reference for clinicians' treatment strategies to some extent.
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Affiliation(s)
- Chenming Liu
- Department of General Surgery, Shaoxing People’s Hospital, Shaoxing, China
- Zhejiang University School of Medicine, Hangzhou, China
| | - Jialiang Lu
- Department of General Surgery, Shaoxing People’s Hospital, Shaoxing, China
- School of Medicine, Shaoxing University, Shaoxing, China
| | - Liang An
- Department of Gastrointestinal Surgery, Shaoxing People’s Hospital, Shaoxing, China
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12
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Feng T, Jie M, Deng K, Yang J, Jiang H. Targeted plasma proteomic analysis uncovers a high-performance biomarker panel for early diagnosis of gastric cancer. Clin Chim Acta 2024; 558:119675. [PMID: 38631604 DOI: 10.1016/j.cca.2024.119675] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2023] [Revised: 03/30/2024] [Accepted: 04/14/2024] [Indexed: 04/19/2024]
Abstract
BACKGROUND Gastric cancer (GC) is characterized by high morbidity, high mortality and low early diagnosis rate. Early diagnosis plays a crucial role in radically treating GC. The aim of this study was to identify plasma biomarkers for GC and early GC diagnosis. METHODS We quantified 369 protein levels with plasma samples from discovery cohort (n = 88) and validation cohort (n = 50) via high-throughput proximity extension assay (PEA) utilizing the Olink-Explore-384-Cardiometabolic panel. The multi-protein signatures were derived from LASSO and Ridge regression models. RESULTS In the discovery cohort, 13 proteins (GDF15, ITIH3, BOC, DPP7, EGFR, AMY2A, CCDC80, CD163, GPNMB, LTBP2, CTSZ, CCL18 and NECTIN2) were identified to distinguish GC (Stage I-IV) and early GC (HGIN-I) groups from control group with AUC of 0.994 and AUC of 0.998, severally. The validation cohort yielded AUC of 0.930 and AUC of 0.818 for GC and early GC, respectively. CONCLUSIONS This study identified a multi-protein signature with the potential to benefit clinical GC diagnosis, especially for Asian and early GC patients, which may contribute to the development of a less-invasive, convenient, and efficient early screening tool, promoting early diagnosis and treatment of GC and ultimately improving patient survival.
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Affiliation(s)
- Tong Feng
- State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China
| | - Minwen Jie
- Laboratory for Aging and Cancer Research, Frontiers Science Center Disease-related Molecular Network, State Key Laboratory of Respiratory Health and Multimorbidity and National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China
| | - Kai Deng
- Department of Gastroenterology & Hepatology, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China
| | - Jinlin Yang
- Department of Gastroenterology & Hepatology, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China.
| | - Hao Jiang
- Laboratory for Aging and Cancer Research, Frontiers Science Center Disease-related Molecular Network, State Key Laboratory of Respiratory Health and Multimorbidity and National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China.
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13
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Zhao W, Liang Z, Yao Y, Ge Y, An G, Duan L, Yao J. GGT5: a potential immunotherapy response inhibitor in gastric cancer by modulating GSH metabolism and sustaining memory CD8+ T cell infiltration. Cancer Immunol Immunother 2024; 73:131. [PMID: 38748299 PMCID: PMC11096297 DOI: 10.1007/s00262-024-03716-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2023] [Accepted: 04/24/2024] [Indexed: 05/18/2024]
Abstract
PURPOSE The variable responses to immunotherapy observed in gastric cancer (GC) patients can be attributed to the intricate nature of the tumor microenvironment. Glutathione (GSH) metabolism significantly influences the initiation and progression of gastric cancer. Consequently, targeting GSH metabolism holds promise for improving the effectiveness of Immune checkpoints inhibitors (ICIs). METHODS We investigated 16 genes related to GSH metabolism, sourced from the MSigDB database, using pan-cancer datasets from TCGA. The most representative prognosis-related gene was identified for further analysis. ScRNA-sequencing analysis was used to explore the tumor heterogeneity of GC, and the results were confirmed by Multiplex immunohistochemistry (mIHC). RESULTS Through DEGs, LASSO, univariate and multivariate Cox regression analyses, and survival analysis, we identified GGT5 as the hub gene in GSH metabolism with the potential to promote GC. Combining CIBERSORT, ssGSEA, and scRNA analysis, we constructed the immune architecture of GC. The subpopulations of T cells were isolated, revealing a strong association between GGT5 and memory CD8+ T cells. Furthermore, specimens from 10 GC patients receiving immunotherapy were collected. mIHC was used to assess the expression levels of GGT5 and memory CD8+ T cell markers. Our results established a positive correlation between GGT5 expression, the enrichment of memory CD8+ T cells, and a suboptimal response to immunotherapy. CONCLUSIONS Our study identifies GGT5, a hub gene in GSH metabolism, as a potential therapeutic target for inhibiting the response to immunotherapy in GC patients. These findings offer new insights into strategies for optimizing immunotherapy of GC.
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Affiliation(s)
- Wenjing Zhao
- Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
| | - Ziwei Liang
- Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
| | - Yongshi Yao
- Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
| | - Yang Ge
- Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
| | - Guangyu An
- Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
| | - Ling Duan
- Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Jiannan Yao
- Beijing Chaoyang Hospital, Capital Medical University, Beijing, China.
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14
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Qiu L, Yao L, Hu P, He T. Analysis of the detection rate and clinical characteristics of early gastric cancer by painless gastroscopy and ordinary gastroscopy. Medicine (Baltimore) 2024; 103:e38120. [PMID: 38701257 PMCID: PMC11062693 DOI: 10.1097/md.0000000000038120] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/03/2023] [Accepted: 04/12/2024] [Indexed: 05/05/2024] Open
Abstract
OBJECTIVE To investigate the difference of early gastric cancer (EGC) detection rate and endoscopic characteristics between painless and ordinary electronic gastroscopy, and summarize the clinical data of gastric cancer (GC) patients. METHODS Clinical data of 72,000 patients who underwent gastroscopy in the First People Hospital of Huzhou (Zhejiang, China) from January 2016 to December 2021 were retrospectively analyzed. The patients were divided into painless gastroscopy group (observation group, 36,000 cases) and ordinary gastroscopy group (control group, 36,000 cases) according to the examination methods. The detection rate of EGC between the 2 groups and the endoscopic characteristics of EGC lesions between the 2 groups were compared, and the clinical data of GC were summarized. RESULTS Painless gastroscopy is safer than ordinary gastroscopy. The detection rate of GC and EGC in the observation group was significantly higher than that in the control group (P < .05); the difference between the 2 groups in the detection rate of advanced GC was not statistically significant. The average length of EGC lesions in the observation group was significantly shorter than that in the control group (P < .05). The proportion of EGC with lesion length <2.0 cm in the observation group was significantly higher than that in the control group (P < .05). The proportion of EGC lesions with type II morphology, normal or pallor mucosal color, and no rupture in mucosa in the control group were significantly lower than that in the observation group, respectively (P < .05). The proportion of EGC distributed in the cardia, fundus and corpus was higher in the observation group than in the control group (P < .05). The incidence of helicobacter pylori (HP) infection, precancerous diseases, first-degree relatives of GC patients, and risk factors in patients with GC was significantly higher than that in non-GC patients (P < .05), multivariate logistic regression analysis showed that these were independent influencing factors for the occurrence of GC. CONCLUSION Painless gastroscopy can effectively improve the screening and diagnostic efficiency of EGC, especially for EGC lesions that are not easy to expose the site, small in size, superficial, without obvious mucosal color change or without mucosal breakage. Therefore, the value of painless gastroscopy in EGC screening is worth further promotion and research.
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Affiliation(s)
- Lei Qiu
- Departments of Gastroenterology, The First People’s Hospital of Huzhou, Huzhou, Zhejiang, People’s Republic China
| | - Linhua Yao
- Departments of Gastroenterology, The First People’s Hospital of Huzhou, Huzhou, Zhejiang, People’s Republic China
| | - Piwei Hu
- Departments of Pathology, The First People’s Hospital of Huzhou, Huzhou, Zhejiang, People’s Republic China
| | - Tongyun He
- Departments of Anesthesiology, The First People’s Hospital of Huzhou, Huzhou, Zhejiang, People’s Republic China
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15
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Yagi S, Kumagai K, Nunobe S, Ishizuka N, Yamaguchi T, Imai Y, Tsuda M, Haruta S, Fukunaga H, Yamada T, Goto M. Risk factors for early recurrence after radical gastrectomy followed by adjuvant chemotherapy for stage II or III gastric cancer: a multicenter, retrospective study. Jpn J Clin Oncol 2024; 54:403-415. [PMID: 38251775 DOI: 10.1093/jjco/hyad189] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2023] [Accepted: 12/17/2023] [Indexed: 01/23/2024] Open
Abstract
BACKGROUND Radical gastrectomy followed by adjuvant chemotherapy is the standard treatment for stage II or III gastric cancer in Asian countries. Early recurrence during or after adjuvant chemotherapy is associated with poor prognosis; however, risk factors for early recurrence remain unclear. METHODS In this multicenter, retrospective cohort study including six institutions, we evaluated the clinicopathological factors of 553 patients with gastric cancer undergoing gastrectomy followed by adjuvant chemotherapy between 2012 and 2016. Patients were divided into the following groups: early recurrence (recurrence during adjuvant chemotherapy or within 6 months after adjuvant chemotherapy completion) and non-early recurrence, which was further divided into late recurrence and no recurrence. Early-recurrence risk factors were investigated using multivariate Cox proportional hazard model. The chronological changes in the recurrence hazard were also examined for each factor. RESULTS Early recurrence and late recurrence occurred in 83 (15.0%) and 73 (13.2%) patients, respectively. Based on the Cox proportional hazards model, a postoperative serum carcinoembryonic antigen level of ≥5 ng/mL (hazard ratio: 2.220, 95% confidence interval: 1.089-4.526) and a neutrophil-to-lymphocyte ratio of >1.8 (hazard ratio: 2.408, 95% confidence interval: 1.479-3.92) were identified as independent risk factors of early recurrence, but not late recurrence. The recurrence hazard ratios for neutrophil-to-lymphocyte ratio significantly decreased over time (P < 0.001) and carcinoembryonic antigen also had the same tendency (P = 0.08). CONCLUSIONS A carcinoembryonic antigen level of ≥5 ng/mL and a neutrophil-to-lymphocyte ratio of >1.8 are predictors of early recurrence after radical gastrectomy and adjuvant chemotherapy for stage II or III gastric cancer.
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Affiliation(s)
- Shusuke Yagi
- Department of Gastroenterological Surgery, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan
- Department of Surgery, National Center for Global Health and Medicine, Tokyo, Japan
| | - Koshi Kumagai
- Department of Gastroenterological Surgery, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Souya Nunobe
- Department of Gastroenterological Surgery, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Naoki Ishizuka
- Center for Digital Transformation of Health, Graduated School of Medicine, Kyoto University, Kyoto, Japan
| | - Toshifumi Yamaguchi
- Cancer Chemotherapy Center, Osaka Medical and Pharmaceutical University Hospital, Osaka, Japan
| | - Yoshiro Imai
- Department of General and Gastroenterological Surgery, Osaka Medical and Pharmaceutical University Hospital, Osaka, Japan
| | - Masahiro Tsuda
- Department of Gastroenterological Oncology, Hyogo Cancer Center, Akashi, Hyogo, Japan
| | - Shusuke Haruta
- Department of Gastroenterological Surgery, Toranomon Hospital, Tokyo, Japan
| | - Hiroki Fukunaga
- Department of Surgery, Itami City Hospital, Itami, Hyogo, Japan
| | - Takanobu Yamada
- Department of Gastrointestinal Surgery, Kanagawa Cancer Center, Yokohama, Kanagawa, Japan
| | - Masahiro Goto
- Cancer Chemotherapy Center, Osaka Medical and Pharmaceutical University Hospital, Osaka, Japan
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16
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Wang K, Yu Y, Zhao J, Meng Q, Xu C, Ren J, Zhang Y, Wang Y, Wang G. A Retrospective Analysis of the Lauren Classification in the Choice of XELOX or SOX as an Adjuvant Chemotherapy for Gastric Cancer. Curr Gene Ther 2024; 24:147-158. [PMID: 37767800 DOI: 10.2174/0115665232247694230921060213] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2023] [Revised: 08/20/2023] [Accepted: 08/20/2023] [Indexed: 09/29/2023]
Abstract
BACKGROUND We aim to retrospectively explore the guiding value of the Lauren classification for patients who have undergone D2 gastrectomy to choose oxaliplatin plus capecitabine (XELOX) or oxaliplatin plus S-1 (SOX) as a further systemic treatment after the operation. METHODS We collected data of 406 patients with stage III gastric cancer(GC)after radical D2 resection and regularly received XELOX or SOX adjuvant treatment after surgery and followed them for at least five years. According to the Lauren classification, we separated patients out into intestinal type (IT) GC together with non-intestinal type(NIT) GC. According to the chemotherapy regimen, we separated patients into the SOX group together with the XELOX group. RESULTS Among non-intestinal type patients, the 3-year DFS rates in the SOX group and the XELOX group were 72.5%, respectively; 54.5% (P=0.037); The 5-year OS rates were 66.8% and 51.8% respectively (P=0.038), both of which were statistically significant. CONCLUSION The patients of non-intestinal type GC may benefit from the SOX regimen. Differences were counted without being statistically significant with intestinal-type GC in the SOX or XELOX groups.
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Affiliation(s)
- Ke Wang
- Department of Gastrointestinal Medical Oncology, The Third Affiliated Hospital of Harbin Medical University Cancer Hospital, Harbin, China
| | - Yuanyuan Yu
- Department of Gastrointestinal Medical Oncology, The Third Affiliated Hospital of Harbin Medical University Cancer Hospital, Harbin, China
| | - Jian Zhao
- Department of Digestive, Shanxi Province Cancer Hospital/ Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, China
| | - Qianhao Meng
- Department of Gastrointestinal Medical Oncology, The Third Affiliated Hospital of Harbin Medical University Cancer Hospital, Harbin, China
| | - Chang Xu
- Department of Gastrointestinal Medical Oncology, The Third Affiliated Hospital of Harbin Medical University Cancer Hospital, Harbin, China
| | - Jing Ren
- Department of Gastrointestinal Medical Oncology, The Third Affiliated Hospital of Harbin Medical University Cancer Hospital, Harbin, China
| | - Yanqiao Zhang
- Department of Gastrointestinal Medical Oncology, The Third Affiliated Hospital of Harbin Medical University Cancer Hospital, Harbin, China
| | - Yusheng Wang
- Department of Digestive, Shanxi Province Cancer Hospital/ Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, China
| | - Guangyu Wang
- Department of Gastrointestinal Medical Oncology, The Third Affiliated Hospital of Harbin Medical University Cancer Hospital, Harbin, China
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17
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Li S, Wei Y, Sun X, Liu M, Zhu M, Yuan Y, Zhang J, Dong Y, Hu K, Ma S, Zhang X, Xu B, Jiang H, Gan L, Liu T. JUNB mediates oxaliplatin resistance via the MAPK signaling pathway in gastric cancer by chromatin accessibility and transcriptomic analysis. Acta Biochim Biophys Sin (Shanghai) 2023; 55:1784-1796. [PMID: 37337631 PMCID: PMC10679881 DOI: 10.3724/abbs.2023119] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2023] [Accepted: 05/19/2023] [Indexed: 06/21/2023] Open
Abstract
Currently, platinum-containing regimens are the most commonly used regimens for advanced gastric cancer patients, and chemotherapy resistance is one of the main reasons for treatment failure. Thus, it is important to reveal the mechanism of oxaliplatin resistance and to seek effective intervention strategies to improve chemotherapy sensitivity, thereby improving the survival and prognosis of gastric cancer patients. To understand the molecular mechanisms of oxaliplatin resistance, we generate an oxaliplatin-resistant gastric cancer cell line and conduct assay for transposase-accessible chromatin sequencing (ATAC-seq) and RNA sequencing (RNA-seq) for both parental and oxaliplatin-resistant AGS cells. A total of 3232 genomic regions are identified to have higher accessibility in oxaliplatin-resistant cells, and DNA-binding motif analysis identifies JUNB as the core transcription factor in the regulatory network. JUNB is overexpressed in oxaliplatin-resistant gastric cancer cells, and its upregulation is associated with poor prognosis in gastric cancer patients, which is validated by our tissue microarray data. Moreover, chromatin immunoprecipitation sequencing (ChIP-seq) analysis reveals that JUNB binds to the transcriptional start site of key genes involved in the MAPK signaling pathway. Knockdown of JUNB inhibits the MAPK signaling pathway and restores sensitivity to oxaliplatin. Combined treatment with the ERK inhibitor piperlongumine or MEK inhibitor trametinib effectively overcomes oxaliplatin resistance. This study provides evidence that JUNB mediates oxaliplatin resistance in gastric cancer by activating the MAPK pathway. The combination of MAPK inhibitors with oxaliplatin overcomes resistance to oxaliplatin, providing a promising treatment opportunity for oxaliplatin-resistant gastric cancer patients.
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Affiliation(s)
- Suyao Li
- Department of Medical OncologyZhongshan HospitalFudan UniversityShanghai200032China
| | - Yichou Wei
- Department of Medical OncologyZhongshan HospitalFudan UniversityShanghai200032China
| | - Xun Sun
- Department of Medical OncologyZhongshan HospitalFudan UniversityShanghai200032China
| | - Mengling Liu
- Department of Medical OncologyZhongshan HospitalFudan UniversityShanghai200032China
| | - Mengxuan Zhu
- Department of Medical OncologyZhongshan HospitalFudan UniversityShanghai200032China
| | - Yitao Yuan
- Department of Medical OncologyZhongshan HospitalFudan UniversityShanghai200032China
| | - Jiayu Zhang
- Department of Medical OncologyZhongshan HospitalFudan UniversityShanghai200032China
| | - Yu Dong
- Department of Medical OncologyZhongshan HospitalFudan UniversityShanghai200032China
| | - Keshu Hu
- Department of Medical OncologyZhongshan HospitalFudan UniversityShanghai200032China
| | - Sining Ma
- Department of Obstetrics and GynecologyZhongshan HospitalShanghai200032China
| | - Xiuping Zhang
- Department of OncologyZhongshan Hospital (Xiamen)Fudan UniversityXiamen361004China
| | - Bei Xu
- Department of Medical OncologyZhongshan HospitalFudan UniversityShanghai200032China
- Cancer CenterZhongshan HospitalFudan UniversityShanghai200032China
| | - Hesheng Jiang
- Department of SurgerySouthwest HealthcareSouthern California Medical Education ConsortiumTemecula Valley HospitalTemeculaCA92592USA
| | - Lu Gan
- Department of Medical OncologyZhongshan HospitalFudan UniversityShanghai200032China
- Cancer CenterZhongshan HospitalFudan UniversityShanghai200032China
| | - Tianshu Liu
- Department of Medical OncologyZhongshan HospitalFudan UniversityShanghai200032China
- Cancer CenterZhongshan HospitalFudan UniversityShanghai200032China
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18
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Suwa Y, Watanabe J, Suwa H, Ozawa M, Momiyama M, Ishibe A, Nagamine K, Yamagishi S, Ota M, Fukushima T, Sekido H, Saigusa Y, Endo I. Exploratory randomized phase II trial for optimizing treatment dosage and duration of adjuvant S-1 plus oxaliplatin in patients with stage III colon cancer: YCOG1402 (SOAP trial). Ann Gastroenterol Surg 2023; 7:922-931. [PMID: 37927922 PMCID: PMC10623943 DOI: 10.1002/ags3.12687] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/29/2022] [Revised: 03/16/2023] [Accepted: 04/16/2023] [Indexed: 11/07/2023] Open
Abstract
Introduction Conventionally, the recommended duration of adjuvant chemotherapy of colon cancer had been 6 months. The IDEA Collaboration suggested that shortening capecitabin and oxaliplatin (CAPOX) adjuvant chemotherapy may be possible. S-1 and oxaliplatin (SOX) treatment is standard treatment in metastatic colorectal cancer in Japan. The aim of this study was to optimize treatment dosage and duration of adjuvant SOX in stage III colon cancer. Methods This trial was as open-label multi-center randomized phase II study. Patients with stage III colon cancer were randomly assigned to 3 months or 6 months of adjuvant SOX treatment in different doses: 130 mg/m2 (3 months) or 100 mg/m2 (6 months) of oxaliplatin. The primary endpoint was 3-year disease-free survival (DFS) and the null hypothesis for the primary endpoint was that the 3-year DFS was ≤72% in each arm and was tested with a one-sided significance level of 10%. Results Eighty-two patients were assigned to the 6 months arm and 81 to the 3 months arm. The 3-year DFS was 75.0% (80% CI 67.95-80.72, p = 0.282) in the 6 months arm and 76.9% (80% CI 70.1-82.38, p = 0.171) in the 3 months arm. Treatment completion rate and relative dose intensity (RDI) were higher in 3 months than 6 months arm. The adverse events (AE) were similar in both arms. Conclusions The 3-year DFS was not significantly superior to null hypothesis in both 3 months and 6 months arms for the stage III colon cancer. Primary endpoint was not achieved. The SOX regimen was not feasible in long-term outcomes.
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Affiliation(s)
- Yusuke Suwa
- Department of Surgery, Gastroenterological CenterYokohama City University Medical CenterYokohamaJapan
| | - Jun Watanabe
- Department of Surgery, Gastroenterological CenterYokohama City University Medical CenterYokohamaJapan
| | - Hirokazu Suwa
- Department of SurgeryYokosuka Kyosai HospitalYokosukaJapan
| | - Mayumi Ozawa
- Department of Gastroenterological SurgeryYokohama City University Graduate School of MedicineYokohamaJapan
| | | | - Atsushi Ishibe
- Department of Gastroenterological SurgeryYokohama City University Graduate School of MedicineYokohamaJapan
| | | | | | - Mitsuyoshi Ota
- Department of SurgeryYokohama City Minato Red Cross HospitalYokohamaJapan
| | - Tadao Fukushima
- Department of SurgerySaiseikai Yokohamashi Nanbu HospitalYokohamaJapan
| | - Hitoshi Sekido
- Department of SurgeryNational Hospital Organization Yokohama Medical CenterYokohamaJapan
| | - Yusuke Saigusa
- Department of BiostatisticsYokohama City University Graduate School of MedicineYokohamaJapan
| | - Itaru Endo
- Department of SurgeryYokosuka Kyosai HospitalYokosukaJapan
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19
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Shuang Y, Wang F, Chen S, Sun F. One case of advanced metastatic gastric cancer achieving pathologic complete response after conversion therapy. Asian J Surg 2023; 46:5174-5175. [PMID: 37543456 DOI: 10.1016/j.asjsur.2023.07.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2023] [Accepted: 07/07/2023] [Indexed: 08/07/2023] Open
Affiliation(s)
- Yongqilin Shuang
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Feng Wang
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Shi Chen
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Kunming Medical University, Kunming, China.
| | - Feng Sun
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Kunming Medical University, Kunming, China.
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20
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Liu C, Tao F, Lu J, Park S, An L. Defining nomograms for predicting prognosis of early and late recurrence in gastric cancer patients after radical gastrectomy. Medicine (Baltimore) 2023; 102:e35585. [PMID: 37861478 PMCID: PMC10589600 DOI: 10.1097/md.0000000000035585] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/12/2023] [Accepted: 09/20/2023] [Indexed: 10/21/2023] Open
Abstract
There are few studies on the predictive factors of early recurrence (ER) and late recurrence (LR) of advanced gastric cancer (GC) after curative surgery. Our study aims to explore the independent predictors influencing the prognosis between ER and LR in patients with advanced GC after curative intent surgery respectively. And we will further develop nomograms for prediction of post recurrence survival (PRS). Data of patients with GC who received radical gastrectomy was retrospectively collected. Recurrence was classified into ER and LR according to the 2 years after surgery as the cutoff value. Multivariate Cox regression analyses were used to explore significant predictors in our analysis. Then these significant predictors were integrated to construct nomograms. The 1-, 2- and 3-year probabilities of PRS in patients with ER were 30.00%, 16.36% and 11.82%, respectively. In contrast, the late group were 44.68%, 23.40%, and 23.30%, respectively. Low body mass index (hazard ratio [HR] = 0.86, P = .001), elevated monocytes count (HR = 4.54, P = .003) and neutrophil-lymphocyte ratio (HR = 1.03, P = .037) at the time of recurrence were risk factors of PRS after ER. Decreased hemoglobin (HR = 0.97, P = .008) and elevated neutrophil-lymphocyte ratio (HR = 1.06, P = .045) at the time of recurrence were risk factors of PRS after LR. The calibration curves for probability of 1-, 2-, and 3-year PRS showed excellent predictive effect. Internal validation concordance indexes of PRS were 0.722 and 0.671 for ER and LR respectively. In view of the different predictive factors of ER and LR of GC, the practical predictive model may help clinicians make reasonable decisions.
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Affiliation(s)
- Chenming Liu
- Department of General Surgery, Shaoxing People’s Hospital, Shaoxing, China
- Zhejiang University School of Medicine, Hangzhou, China
| | - Feng Tao
- Department of Gastrointestinal Surgery, Shaoxing People’s Hospital, Shaoxing, China
| | - Jialiang Lu
- Department of General Surgery, Shaoxing People’s Hospital, Shaoxing, China
- School of Medicine, Shaoxing University, Shaoxing, China
| | - Sungsoo Park
- Department of Surgery, Korea University Medical Center, Anam Hospital, Seoul, South Korea
| | - Liang An
- Department of Gastrointestinal Surgery, Shaoxing People’s Hospital, Shaoxing, China
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21
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Ota M, Saeki H, Uehara H, Matsuda Y, Tsutsumi S, Kusumoto T, Yasui H, Ubukata Y, Yamaguchi S, Orita H, Izawa N, Kakizoe S, Shimokawa M, Yoshizumi T, Kakeji Y, Mori M, Oki E. Phase II clinical trial to study the safety and efficacy of combined S-1 + oxaliplatin therapy as neoadjuvant chemotherapy for locally advanced gastric cancer in older patients. Int J Clin Oncol 2023; 28:1166-1175. [PMID: 37368093 PMCID: PMC10468941 DOI: 10.1007/s10147-023-02373-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2023] [Accepted: 06/16/2023] [Indexed: 06/28/2023]
Abstract
BACKGROUND Gastrectomy with D2 dissection and adjuvant chemotherapy is the standard treatment for locally advanced gastric cancer (LAGC) in Asia. However, administering chemotherapy with sufficient intensity after gastrectomy is challenging. Several trials demonstrated the efficacy of neoadjuvant chemotherapy (NAC). However, limited studies explored the feasibility of NAC-SOX for older patients with LAGC. This phase II study (KSCC1801) evaluated the safety and efficacy of NAC-SOX in patients with LAGC aged ≥ 70 years. METHODS Patients received three cycles of SOX130 (oxaliplatin 130 mg/m2 on day 1, oral S-1 40-60 mg twice daily for two weeks every three weeks) as NAC, followed by gastrectomy with lymph node dissection. The primary endpoint was the dose intensity (DI). The secondary endpoints were safety, R0 resection rate, pathological response rate (pRR), overall survival, and relapse-free survival. RESULTS The median age of 26 enrolled patients was 74.5 years. The median DI in NAC-SOX130 was 97.2% for S-1 and 98.3% for oxaliplatin. Three cycles of NAC were administered in 25 patients (96.2%), of whom 24 (92.3%) underwent gastrectomy with lymphadenectomy. The R0 resection rate was 92.3% and the pRR (≥ grade 1b) was 62.5%. The major adverse events (≥ grade 3) were neutropenia (20.0%), thrombocytopenia (11.5%), anorexia (11.5%), nausea (7.7%), and hyponatremia (7.7%). Postoperative complications of abdominal infection, elevated blood amylase, and bacteremia occurred in one patient each. Severe diarrhea and dehydration caused one treatment-related death. CONCLUSIONS NAC-SOX130 is a feasible therapy for older patients, although systemic management and careful monitoring of adverse events are necessary.
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Affiliation(s)
- Mitsuhiko Ota
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Hiroshi Saeki
- Department of General Surgical Science, Graduate School of Medicine, Gunma University, 3-39-22, Showa-machi, Maebashi, Gunma, 371-8511, Japan.
| | - Hideo Uehara
- Department of Gastroenterological Surgery, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan
| | - Yoshiko Matsuda
- Division of Gastrointestinal Surgery, Department of Surgery, Graduate School of Medicine, Kobe University, Kobe, Japan
| | | | - Tetsuya Kusumoto
- Department of Gastroenterological Surgery and Clinical Research Institute Cancer Research Division, National Kyushu Medical Center, Fukuoka, Japan
| | - Hisateru Yasui
- Department of Medical Oncology, Kobe City Medical Center General Hospital, Kobe, Japan
| | - Yasunari Ubukata
- Department of General Surgical Science, Graduate School of Medicine, Gunma University, Maebashi, Japan
| | - Shohei Yamaguchi
- Department of Surgery, Hiroshima Red Cross Hospital & Atomic Bomb Survivors Hospital, Hiroshima, Japan
| | - Hiroyuki Orita
- Department of Surgery, Nakatsu Municipal Hospital, Nakatsu, Japan
| | - Naoki Izawa
- Department of Clinical Oncology, St. Marianna University School of Medicine, Kawasaki, Japan
| | - Saburo Kakizoe
- Department of Surgery, Ilikai Medical INC Kakizoe Hospital, Hirado, Japan
| | - Mototsugu Shimokawa
- Department of Biostatistics, Yamaguchi University Graduate School of Medicine, Ube, Japan
| | - Tomoharu Yoshizumi
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Yoshihiro Kakeji
- Division of Gastrointestinal Surgery, Department of Surgery, Graduate School of Medicine, Kobe University, Kobe, Japan
| | - Masaki Mori
- Tokai University School of Medicine, Isehara, Japan
| | - Eiji Oki
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
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22
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Fujimoto D, Taniguchi K, Takashima J, Kobayashi H. Postoperative Early Body Weight Loss Is a Risk Factor for Recurrence in Patients with pStage III Gastric Cancer. Oncology 2023; 101:705-713. [PMID: 37494910 DOI: 10.1159/000532089] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2022] [Accepted: 07/14/2023] [Indexed: 07/28/2023]
Abstract
INTRODUCTION The goal of this study was to determine whether postoperative early body weight loss (EWL) after radical gastrectomy is a risk factor for recurrence in patients with pathological stage III (pStage III) gastric cancer who received postoperative adjuvant chemotherapy, which included tegafur/gimeracil/oteracil (S-1). METHODS Patients who underwent gastrectomy for gastric cancer were identified from a prospectively managed gastric cancer database. We analyzed 58 consecutive patients who underwent radical gastrectomy with D2 lymph node dissection for confirmed pStage III gastric cancer treated postoperatively with adjuvant chemotherapy including S-1 between 2010 and 2019. Clinical and pathologic characteristics, baseline body mass index (BMI), and postoperative weights were extracted. Weight changes were evaluated from the preoperative period to the start of adjuvant chemotherapy. EWL was defined as % BMI change = (preoperative BMI - postoperative BMI at the start of adjuvant chemotherapy) × 100/preoperative BMI. RESULTS Of the 58 consecutive patients who underwent radical resection for gastric cancer, 72.4% were male, with a mean age of 65.5 years, and a mean preoperative BMI of 21.2 (range: 15.4-29.1) kg/m2. The degree of EWL was found to be closely correlated to compliance with adjuvant chemotherapy. Multivariate analysis by Cox proportional hazard analysis revealed that EWL was an independent factor for relapse-free survival (RFS), and patients with an EWL of 15.9% or more severe had poorer RFS. CONCLUSION EWL above a certain rate at the start of adjuvant chemotherapy was a predictor of poor compliance with adjuvant chemotherapy and a high risk of disease recurrence in patients with pStage III gastric cancer.
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Affiliation(s)
- Daisuke Fujimoto
- Department of Surgery, Teikyo University Hospital, Mizonokuchi, Kawasaki, Japan
| | - Keizo Taniguchi
- Department of Surgery, Teikyo University Hospital, Mizonokuchi, Kawasaki, Japan
| | - Junpei Takashima
- Department of Surgery, Teikyo University Hospital, Mizonokuchi, Kawasaki, Japan
| | - Hirotoshi Kobayashi
- Department of Surgery, Teikyo University Hospital, Mizonokuchi, Kawasaki, Japan
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23
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Sato C, Kawakami H, Tanaka R, Satake H, Inoue K, Kimura Y, Fujita J, Kawabata R, Chiba Y, Satoh T, Nakagawa K. Survival impact of microsatellite instability in stage II gastric cancer patients who received S-1 adjuvant monotherapy after curative resection. Sci Rep 2023; 13:10826. [PMID: 37402831 DOI: 10.1038/s41598-023-37870-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2023] [Accepted: 06/28/2023] [Indexed: 07/06/2023] Open
Abstract
Adjuvant S-1 monotherapy is the standard of care for stage II gastric cancer (GC) after curative resection in Japan, but its efficacy for microsatellite instability-high (MSI-H) tumors has remained unknown. Among a multi-institutional cohort of patients with stage II GC who underwent R0 resection followed by S-1 adjuvant chemotherapy between February 2008 and December 2018, we assessed MSI status with an MSI-IVD Kit (Falco). MSI status was assessable for 184 (88.5%) of the 208 enrolled patients, with MSI-H being identified in 24 (13.0%) individuals. Although neither relapse-free survival (RFS) (hazard ratio [HR] = 1.00, p = 0.997) nor overall survival (OS) (HR = 0.66, p = 0.488) differed between MSI-H versus microsatellite-stable (MSS) patients, MSI-H patients showed a nonsignificant but better RFS (HR = 0.34, p = 0.064) and OS (HR = 0.22, p = 0.057) than did MSS patients after adjustment for background characteristics by propensity score (PS) analysis. Gene expression analysis in the PS-matched cohort suggested that recurrence was associated with the immunosuppressive microenvironment in MSI-H tumors but with expression of cancer/testis antigen genes in MSS tumors. Our data reveal a better adjusted survival for MSI-H versus MSS stage II GC treated with S-1 adjuvant therapy, and they suggest that mechanisms of recurrence differ between MSI-H and MSS tumors.
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Affiliation(s)
- Chihiro Sato
- Department of Medical Oncology, Kindai University Faculty of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama, Japan
- Laboratory of Molecular Immunology, Institute for Quantitative Biosciences, The University of Tokyo, Bunkyo, Japan
| | - Hisato Kawakami
- Department of Medical Oncology, Kindai University Faculty of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama, Japan.
| | - Ryo Tanaka
- Department of General and Gastrointestinal Surgery, Osaka Medical and Pharmaceutical University, Takatsuki, Japan
| | - Hironaga Satake
- Cancer Center, Kansai Medical University Hospital, Hirakata, Japan
- Department of Medical Oncology, Kochi Medical School, Kochi, Japan
| | - Kentaro Inoue
- Department of Surgery, Kansai Medical University Hospital, Hirakata, Japan
| | - Yutaka Kimura
- Department of Surgery, Faculty of Medicine, Kindai University, Osaka-Sayama, Japan
- Department of Surgery, Kindai University Nara Hospital, Ikoma, Japan
| | - Junya Fujita
- Department of Surgery, Yao Municipal Hospital, Yao, Japan
- Department of Surgery, Sakai City Medical Center, Sakai, Japan
| | - Ryohei Kawabata
- Department of Surgery, Sakai City Medical Center, Sakai, Japan
- Department of Surgery, Osaka Rosai Hospital, Sakai, Japan
| | - Yasutaka Chiba
- Clinical Research Center, Kindai University Hospital, Osaka-Sayama, Japan
| | - Taroh Satoh
- Center for Cancer Genomics and Precision Medicine, Osaka University Hospital, Suita, Japan
| | - Kazuhiko Nakagawa
- Department of Medical Oncology, Kindai University Faculty of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama, Japan
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Takahari D, Katai H, Takashima A, Izawa N, Ishizuka N, Ohashi M, Mikami S, Wakatsuki T, Nakayama I, Chin K, Ida S, Kumagai K, Nunobe S, Iwasa S, Shoji H, Wada T, Doi A, Yoshikawa T, Sano T, Boku N, Yamaguchi K. Perioperative TAS-118 plus oxaliplatin in patients with locally advanced gastric cancer: APOLLO-11 study. Gastric Cancer 2023; 26:614-625. [PMID: 37029843 PMCID: PMC10285008 DOI: 10.1007/s10120-023-01388-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/17/2022] [Accepted: 03/27/2023] [Indexed: 04/09/2023]
Abstract
BACKGROUND We investigated the feasibility of perioperative chemotherapy with S-1 and leucovorin (TAS-118) plus oxaliplatin in patients with locally advanced gastric cancer. METHODS Patients with clinical T3-4N1-3M0 gastric cancer received four courses of TAS-118 (40-60 mg/body, orally, twice daily for seven days) plus oxaliplatin (85 mg/m2, intravenously, day one) every two weeks preoperatively followed by gastrectomy with D2 lymphadenectomy, followed by postoperative chemotherapy with either 12 courses of TAS-118 monotherapy (Step 1) or eight courses of TAS-118 plus oxaliplatin (Step 2). The primary endpoints were completion rates of preoperative chemotherapy with TAS-118 plus oxaliplatin and postoperative chemotherapy with TAS-118 monotherapy (Step 1) or TAS-118 plus oxaliplatin (Step 2). RESULTS Among 45 patients enrolled, the preoperative chemotherapy completion rate was 88.9% (90% CI 78.0-95.5). Major grade ≥ 3 adverse events (AEs) were diarrhoea (17.8%) and neutropenia (8.9%). The R0 resection rate was 95.6% (90% CI 86.7-99.2). Complete pathological response was achieved in 6 patients (13.3%). Dose-limiting toxicity was not observed in 31 patients receiving postoperative chemotherapy (Step 1, n = 11; Step 2, n = 20), and completion rates were 90.9% (95% CI 63.6-99.5) for Step 1 and 80.0% (95% CI 59.9-92.9) for Step 2. No more than 10% of grade ≥ 3 AEs were observed in patients receiving Step 1. Hypokalaemia and neutropenia occurred in 3 and 2 patients, respectively, receiving Step 2. The 3-year recurrence-free and overall survival rates were 66.7% (95% CI 50.9-78.4) and 84.4% (95% CI 70.1-92.3), respectively. CONCLUSIONS Perioperative chemotherapy with TAS-118 plus oxaliplatin with D2 gastrectomy is feasible.
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Affiliation(s)
- Daisuke Takahari
- Department of Gastroenterological Chemotherapy, Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan.
| | - Hitoshi Katai
- Department of Gastric Surgery, National Cancer Center Hospital, Tokyo, Japan
| | - Atsuo Takashima
- Department of Gastrointestinal Medical Oncology, National Cancer Center Hospital, Tokyo, Japan
| | - Naoki Izawa
- Department of Clinical Oncology, St. Marianna University School of Medicine, Kawasaki, Japan
| | - Naoki Ishizuka
- Department of Clinical Planning and Strategy, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Manabu Ohashi
- Department of Gastroenterological Surgery, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Shinya Mikami
- Department of Gastrointestinal and General Surgery, St. Marianna University School of Medicine, Kawasaki, Japan
| | - Takeru Wakatsuki
- Department of Gastroenterological Chemotherapy, Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan
| | - Izuma Nakayama
- Department of Gastroenterological Chemotherapy, Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan
| | - Keisho Chin
- Department of Gastroenterological Chemotherapy, Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan
| | - Satoshi Ida
- Department of Gastroenterological Surgery, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Koshi Kumagai
- Department of Gastroenterological Surgery, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Souya Nunobe
- Department of Gastroenterological Surgery, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Satoru Iwasa
- Department of Gastrointestinal Medical Oncology, National Cancer Center Hospital, Tokyo, Japan
| | - Hirokazu Shoji
- Department of Gastrointestinal Medical Oncology, National Cancer Center Hospital, Tokyo, Japan
| | - Takeyuki Wada
- Department of Gastric Surgery, National Cancer Center Hospital, Tokyo, Japan
| | - Ayako Doi
- Department of Clinical Oncology, St. Marianna University School of Medicine, Kawasaki, Japan
| | - Takaki Yoshikawa
- Department of Gastric Surgery, National Cancer Center Hospital, Tokyo, Japan
| | - Takeshi Sano
- Department of Gastroenterological Surgery, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Narikazu Boku
- Department of Gastrointestinal Medical Oncology, National Cancer Center Hospital, Tokyo, Japan
| | - Kensei Yamaguchi
- Department of Gastroenterological Chemotherapy, Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan
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Xu B, He P, Wang Y, Wang H, Zhang J, Zhu J, Pu W, Chen H. PDT for Gastric Cancer - the view from China. Photodiagnosis Photodyn Ther 2023; 42:103366. [PMID: 36841280 DOI: 10.1016/j.pdpdt.2023.103366] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2022] [Revised: 02/19/2023] [Accepted: 02/21/2023] [Indexed: 02/27/2023]
Abstract
The incidence rate and mortality of gastric cancer remain elevated. Traditionally, surgical treatment (including endoscopic surgery and traditional surgery), chemotherapy, targeted therapy, and immunotherapy were used for the treatment of gastric cancer. Although the emergence of targeted therapy and immunotherapy can effectively prolong the survival of some patients with gastric cancer and improve the quality of life of patients after chemotherapy or surgery, the overall survival rate of gastric cancer has not been significantly improved. Photodynamic therapy is a local photochemical therapy with the advantages of high safety, few adverse reactions, and repeatability, although it may cause some toxic reactions. There are some differences between East and West in the treatment of gastric cancer with PDT, and most earlier studies concentrated on using PDT alone. However, some studies have indicated that PDT may enhance the efficacy of chemotherapy and other medications. This paper summarizes the study on the use of PDT and its combination therapy in gastric cancer, which is anticipated to offer novel thoughts for the treatment of gastric cancer.
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Affiliation(s)
- Bo Xu
- The Second Clinical Medical College of Lanzhou University, 730030, China
| | - Puyi He
- The Second Clinical Medical College of Lanzhou University, 730030, China
| | - Yunpeng Wang
- The Second Clinical Medical College of Lanzhou University, 730030, China
| | - Haiyun Wang
- The Second Clinical Medical College of Lanzhou University, 730030, China
| | - Jing Zhang
- The Second Clinical Medical College of Lanzhou University, 730030, China
| | - Jingyu Zhu
- The Second Clinical Medical College of Lanzhou University, 730030, China
| | - Weigao Pu
- The Second Clinical Medical College of Lanzhou University, 730030, China
| | - Hao Chen
- NHC Key Laboratory of Diagnosis and Therapy of Gastrointestinal Tumor, Gansu Provincial Hospital, Lanzhou 730000, China; Department of Oncology, The second hospital of Lanzhou University, 730030, China; Gansu Key Laboratory of digestive system tumor, The second hospital of Lanzhou University, 730030, China.
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26
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Li YF, Zhang WB, Gao YY. Prognostic effect of excessive chemotherapy cycles for stage II and III gastric cancer patients after D2 + gastrectomy. World J Gastrointest Surg 2023; 15:32-48. [PMID: 36741062 PMCID: PMC9896498 DOI: 10.4240/wjgs.v15.i1.32] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/18/2022] [Revised: 11/04/2022] [Accepted: 12/14/2022] [Indexed: 01/17/2023] Open
Abstract
BACKGROUND According to relevant investigation and analysis, there are few research studies on the effect of excessive chemotherapy cycles after D2 gastrectomy on the survival of patients with gastric cancer.
AIM To determine whether excessive chemotherapy cycles provide extra survival benefits, reduce recurrence rate, and improve survival rate in patients with stage II or III gastric cancer.
METHODS We analyzed and summarized 412 patients with stage II gastric cancer and 902 patients with stage III gastric cancer who received D2 gastrectomy plus adjuvant chemotherapy or neoadjuvant chemotherapy. Analysis and comparison at a ratio of 1:1 is aimed at reducing realistic baseline differences (n = 97 in each group of stage II, n = 242 in each group of stage III). Progression-free survival, overall survival and recurrence were the main outcome indicators.
RESULTS When the propensity score was matched, the baseline features of stage II and III gastric cancer patients were similar between the two groups. After a series of investigations, Kaplan-Meier found that the progression-free survival and overall survival of stage II and III gastric cancer patients were consistent between the two groups. The local metastasis rate (P = 0.002), total recurrence rate (P < 0.001) and distant metastasis rate (P = 0.001) in the ≥ 9 cycle group of stage III gastric cancer were statistically lower than those in the < 9 cycle group. The interaction analysis by Cox proportional hazard regression model showed that intestinal type, proximal gastrectomy, and ≥ 6 cm maximum diameter of tumor had a higher risk of total mortality in the < 9 cycles group.
CONCLUSION Overall, ≥ 9 chemotherapy cycles is not recommended for patients with stage II and stage III gastric cancer because it has an insignificant role in the prognosis of gastric cancer. However, for patients with stage III gastric cancer, ≥ 9 cycles of chemotherapy was shown to significantly decrease recurrence.
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Affiliation(s)
- Yi-Fan Li
- Department of General Surgery, Shanxi Province Cancer Hospital, Taiyuan 030013, Shanxi Province, China
| | - Wen-Bing Zhang
- Endoscopy Center, Shanxi Province Cancer Hospital, Taiyuan 030013, Shanxi Province, China
| | - Yu-Ye Gao
- Department of Gastrointestinal Surgery, Peking University Cancer Hospital and Institute, Beijing 00010, China
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Long non-coding RNA ZNF674-AS1 antagonizes oxaliplatin resistance of gastric cancer via regulating EZH2-mediated methylation of CHST7. Aging (Albany NY) 2022; 14:5523-5536. [PMID: 35802620 PMCID: PMC9320539 DOI: 10.18632/aging.204165] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2022] [Accepted: 06/27/2022] [Indexed: 12/24/2022]
Abstract
Chemoresistance leads the cause of poor outcome of patients with gastric cancer (GC). Long non-coding RNAs (LncRNAs) is intimately involved in the regulation of tumorigenesis and progression. Here, we demonstrated ZNF674-AS1 was down-regulated in oxaliplatin (OXA)-resistant tissues and cell lines, lower level of ZNF674-AS1 predicted poor prognosis of GC patients. Besides, forced expression of ZNF674-AS1 not only reduced cell viability, colony formation, expression of drug-resistant markers but also promoted cell apoptosis of OXA-resistant GC cells, exposed to oxaliplatin. Silence of ZNF674-AS1 exhibited an opposite effects on OXA resistance of GC cells. Further mechanistic research showed that ZNF674-AS1 interacted with EZH2, led to higher methylation level of target gene CHST7. In addition, functional experiments verified that depletion of CHST7 re-sensitized OXA-resistant GC cells to OXA. Thus, our results indicated that ZNF674-AS1 suppressed OXA resistance of GC through EZH2-mediated inhibition of CHST7, providing potential theoretic basis and therapeutic strategy for chemoresistant GC.
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28
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Peng W, Dai J, Liu CC, Liu D, Xiao H. Body Mass Index and Prognosis of Patients With Stage II/III Gastric Cancer After Curative Gastrectomy: Completion of Perioperative Adjuvant Chemotherapy May Be a Confounding Factor. Front Oncol 2022; 12:899677. [PMID: 35769709 PMCID: PMC9234174 DOI: 10.3389/fonc.2022.899677] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2022] [Accepted: 05/16/2022] [Indexed: 12/04/2022] Open
Abstract
Objective To investigate the association between body mass index (BMI) and overall survival (OS) of patients with stage II/III gastric cancer (GC) after radical gastrectomy, and evaluate the potential influence of perioperative adjuvant chemotherapy (PAC). Methods Medical records of 2,510 consecutive stage II/III GC patients who underwent curative resection between November 2010 and December 2020 were retrospectively reviewed. The optimal cutoff value of BMI for OS was determined by X-tile. The independent predictive factors for completeness of PAC were identified using univariate and multivariate logistic regression analyses. Cox regression analyses assessed the association among BMI, completeness of PAC, and OS. Results Of the 2,510 patients, 813 cases with BMI < 20.3 kg/m2 were classified as belonging in the low BMI group. Further analyses confirmed that low BMI was an independent predictor for incomplete PAC (< 6 cycles, n = 920) and poorer OS (hazard ratio: 1.317, 95% confidence interval: 1.162-1.494, P < 0.001), but neo-adjuvant chemotherapy (NAC) was a protective factor. An additive effect was found in those with both low BMI and incomplete PAC, as they had even worse OS. However, in patients with low BMI, completion of PAC (≥ 6 cycles) significantly improved OS, which became comparable to that in the high BMI group (P = 0.143). Conclusions Low preoperative BMI independently affects completion of PAC and prognosis of patients with stage II/III GC, but completing PAC can compensate for the adverse influence of low BMI on OS. Thus, strategies designed to ensure the completion of PAC, such as NAC and nutritional support, should be further investigated.
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Affiliation(s)
- Wei Peng
- Gastroenterology and Urology Department II, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China
| | - Jing Dai
- Gastroenterology and Urology Department II, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China
| | - Chao-chan Liu
- Gastroenterology and Urology Department II, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China
| | - Dian Liu
- Department of Lamphoma and Abdominal Radiotherapy, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China
| | - Hua Xiao
- Department of Hepatobiliary and Intestinal Surgery, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China
- Department of Gastroduodenal and Pancreatic Surgery, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China
- *Correspondence: Hua Xiao,
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29
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Association among prognostic nutritional index, post-operative infection and prognosis of stage II/III gastric cancer patients following radical gastrectomy. Eur J Clin Nutr 2022; 76:1449-1456. [PMID: 35354923 PMCID: PMC9550621 DOI: 10.1038/s41430-022-01120-7] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2021] [Revised: 03/02/2022] [Accepted: 03/10/2022] [Indexed: 12/02/2022]
Abstract
Background/objective To investigate the influence of pre-operative immunological and nutritional status, assessed by the prognostic nutritional index (PNI) score, on post-operative infection, and the potential additive effects of low PNI and infection on prognosis after radical resection of stage II/III gastric cancer (GC). Methods The medical records of 2352 consecutive stage II/III GC patients who underwent radical gastrectomy were retrospectively reviewed. The independent predictors for infections were identified using univariate and multivariate analyses. Cox regression analysis was used to assess any associations between PNI, infection and OS. Results A total of 160 (6.8%) cases developed infections and low PNI (< 43.9) was confirmed as an independent predictor. Both PNI < 43.9 and infections independently predicted poor OS (hazard ratio: 1.163, 95% confidence interval: 1.007–1.343; HR: 1.347, 95%CI: 1.067–1.700), and an additive effect was confirmed as patients with both low PNI and infection had worst OS. Further stratified analyses showed that complete peri-operative adjuvant chemotherapy (PAC, ≥ 6 cycles) could significantly improve OS in patients with low PNI and/or infection, which was comparable to those with PNI ≥ 43.9 and/or infection (P = 0.160). Conclusions Infection was the most common complication after gastrectomy and PNI < 43.9 was identified as an independent predictor. Low PNI was associated with poorer OS in stage II/III GC, independent of infections, and low PNI and infections had a synergistic effect that was associated with worst OS. However, complete PAC could significantly improve OS in these patients. Thus, strategies to decrease infection and complete PAC should be further investigated.
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Toyota K, Mori M, Hirahara S, Yoshioka S, Kubota H, Yano R, Kobayashi H, Hashimoto Y, Sakashita Y, Yokoyama Y, Murakami Y, Miyamoto K. Nutritional Status Indicators Affecting the Tolerability of Postoperative Chemotherapy After Total Gastrectomy in Patients With Gastric Cancer. J Gastric Cancer 2022; 22:56-66. [PMID: 35425654 PMCID: PMC8980594 DOI: 10.5230/jgc.2022.22.e5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2021] [Revised: 02/14/2022] [Accepted: 02/15/2022] [Indexed: 12/24/2022] Open
Affiliation(s)
- Kazuhiro Toyota
- Department of Surgery, Hiroshima Memorial Hospital, Hiroshima, Japan
| | - Masayuki Mori
- Department of Surgery, Hiroshima Memorial Hospital, Hiroshima, Japan
| | - Satoshi Hirahara
- Department of Surgery, Hiroshima Memorial Hospital, Hiroshima, Japan
| | - Shoko Yoshioka
- Department of Surgery, Hiroshima Memorial Hospital, Hiroshima, Japan
| | - Haruna Kubota
- Department of Surgery, Hiroshima Memorial Hospital, Hiroshima, Japan
| | - Raita Yano
- Department of Surgery, Hiroshima Memorial Hospital, Hiroshima, Japan
| | | | - Yasushi Hashimoto
- Department of Surgery, Hiroshima Memorial Hospital, Hiroshima, Japan
| | | | - Yujiro Yokoyama
- Department of Surgery, Hiroshima Memorial Hospital, Hiroshima, Japan
| | - Yoshiaki Murakami
- Department of Surgery, Hiroshima Memorial Hospital, Hiroshima, Japan
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Imamura H, Matsuyama J, Nishikawa K, Endo S, Kawase T, Kimura Y, Fukui J, Kawada J, Kurokawa Y, Fujitani K, Sakai D, Kawakami H, Tsujinaka T, Shimokawa T, Matsubara Y, Satoh T, Furukawa H. Effects of an oral elemental nutritional supplement in gastric cancer patients with adjuvant S-1 chemotherapy after gastrectomy: A multicenter, open-label, single-arm, prospective phase II study (OGSG1108). Ann Gastroenterol Surg 2021; 5:776-784. [PMID: 34755009 PMCID: PMC8560593 DOI: 10.1002/ags3.12487] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2021] [Revised: 06/21/2021] [Accepted: 06/24/2021] [Indexed: 12/23/2022] Open
Abstract
AIM Post-surgical weight loss influences chemotherapy compliance and may be a risk factor for survival. Intake of an oral elemental nutritional supplement (OENS) can reduce weight loss after gastric cancer (GC) surgery. We assessed whether therapy completion levels would increase in patients receiving postoperative adjuvant chemotherapy in combination with an OENS. METHODS This was a multicenter, open-label, single-arm, phase II study in GC patients who underwent curative total or distal gastrectomy (TG/DG) and received adjuvant S-1 chemotherapy. The primary endpoint was the S-1 completion rate for 1 year with a relative performance (RP) value of ≥70%; secondary endpoints included factors affecting the completion rate of S-1, RP value after eight S-1 courses, S-1 and OENS persistence rates, nutritional index, OENS compliance, and safety. RESULTS In 71 efficacy-evaluable patients, the S-1 completion rate was 69.0% (TG, 68.0%; DG, 69.6%) and the RP value was 87.5 (TG, 89.1; DG, 87.5). Over eight treatment courses, median persistence rates were 89.0% for S-1 and 93.8% for the OENS. The mean OENS compliance was 81.8% at the fourth S-1 course and 52.9% at the eighth course. The incidence of Grade 3 or 4 adverse events was 27.2%, most commonly neutropenia (12.3%). CONCLUSIONS The completion rate of S-1 for 1 year in patients who could take the OENS exceeded the pre-defined threshold level. Randomized controlled trials are warranted to confirm the role of OENS in adjuvant chemotherapy.
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Affiliation(s)
- Hiroshi Imamura
- Department of SurgeryToyonaka Municipal HospitalToyonakaJapan
| | - Jin Matsuyama
- Department of Gastroenterological SurgeryHigashiosaka City Medical CenterHigashiosakaJapan
| | - Kazuhiro Nishikawa
- Department of SurgeryNational Hospital Organization Osaka National HospitalOsakaJapan
| | - Shunji Endo
- Department of Digestive SurgeryKawasaki Medical SchoolOkayamaJapan
| | - Tomono Kawase
- Department of SurgeryToyonaka Municipal HospitalToyonakaJapan
| | - Yutaka Kimura
- Department of SurgeryKindai University Faculty of MedicineOsaka‐SayamaJapan
| | | | - Junji Kawada
- Department of SurgeryOsaka general medical centerOsakaJapan
| | - Yukinori Kurokawa
- Department of Gastroenterological SurgeryOsaka University Graduate School of MedicineSuitaJapan
| | | | - Daisuke Sakai
- Department of Frontier Science for Cancer and ChemotherapyOsaka University Graduate School of MedicineSuitaJapan
| | - Hisato Kawakami
- Department of Medical OncologyKindai University Faculty of MedicineOsaka‐SayamaJapan
| | | | - Toshio Shimokawa
- Clinical Study Support CenterWakayama Medical University HospitalWakayamaJapan
| | | | - Taroh Satoh
- Department of Frontier Science for Cancer and ChemotherapyOsaka University Graduate School of MedicineSuitaJapan
| | - Hiroshi Furukawa
- Department of SurgeryKindai University Faculty of MedicineOsaka‐SayamaJapan
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Zhang SX, Liu W, Ai B, Sun LL, Chen ZS, Lin LZ. Current Advances and Outlook in Gastric Cancer Chemoresistance: A Review. Recent Pat Anticancer Drug Discov 2021; 17:26-41. [PMID: 34587888 DOI: 10.2174/1574892816666210929165729] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2021] [Revised: 08/19/2021] [Accepted: 09/20/2021] [Indexed: 12/11/2022]
Abstract
BACKGROUND Surgical resection of the lesion is the standard primary treatment of gastric cancer. Unfortunately, most patients are already in the advanced stage of the disease when they are diagnosed with gastric cancer. Alternative therapies, such as radiation therapy and chemotherapy, can achieve only very limited benefits. The emergence of cancer drug resistance has always been the major obstacle to the cure of tumors. The main goal of modern cancer pharmacology is to determine the underlying mechanism of anticancer drugs. OBJECTIVE Here, we mainly review the latest research results related to the mechanism of chemotherapy resistance in gastric cancer, the application of natural products in overcoming the chemotherapy resistance of gastric cancer, and the new strategies currently being developed to treat tumors based on immunotherapy and gene therapy. CONCLUSION The emergence of cancer drug resistance is the main obstacle in achieving alleviation and final cure for gastric cancer. Mixed therapies are considered to be a possible way to overcome chemoresistance. Natural products are the main resource for discovering new drugs specific for treating chemoresistance, and further research is needed to clarify the mechanism of natural product activity in patients. .
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Affiliation(s)
- Sheng-Xiong Zhang
- Guangdong Province Work Injury Rehabilitation Hospital, Guangzhou, 510440. China
| | - Wei Liu
- College of Traditional Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, 510006. China
| | - Bo Ai
- Huazhong University of Science and Technology, Wuhan, 430030. China
| | - Ling-Ling Sun
- The First Affiliated Hospital of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, 510405. China
| | - Zhe-Sheng Chen
- Department of Pharmaceutical Sciences, St. John's University, Queens, NY 11439, New York. United States
| | - Li-Zhu Lin
- The First Affiliated Hospital of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, 510405. China
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Michael A, Nath DK. Neoadjuvant and Adjuvant Chemotherapeutic Strategy of Colorectal Mixed Adeno-Neuroendocrine Carcinomas. Cureus 2021; 13:e16645. [PMID: 34458045 PMCID: PMC8384403 DOI: 10.7759/cureus.16645] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/26/2021] [Indexed: 02/03/2023] Open
Abstract
Mixed adeno-neuroendocrine carcinomas (MANEC) is a rare pathological diagnosis characterized by the presence of both adeno-carcinomatous and neuroendocrine differentiation with each component comprising 30% of the tumor. This literature review is aimed at the extraction of all existing clinical studies and reviews on colorectal MANEC so as to ensure that a suitable chemotherapeutic regimen is chosen to improve survival outcomes and prognosis of the disease. Parallel search strategies were employed to extract past 10 years articles from PubMed, PubMed Central and Google Scholar databases. A total of 30 records consisting of one clinical trial, five retrospective cohort studies, one case control study, one case series, 16 case reports and six review papers were shortlisted. Chemotherapeutic regimens that were administered as an adjuvant and a neoadjuvant therapy were analyzed with their survival outcomes. The overall survival rate of those administered with neoadjuvant and adjuvant therapy can be as high as 57.4% and 69%, respectively. Multiple chemotherapeutic regimens were employed in colorectal MANEC and superiority of one regimen over the other can’t be established. Any drug or combination of drugs that is responsive against either of the MANEC components is found to be effective against the tumor. However, excellent responsiveness has been found with 5-fluorouracil regimens as a neoadjuvant therapy and platinum-based combinations as an adjuvant therapy. XELOX, streptozocin and S1 regimens also prove to be drugs of choice in aggressive and metastasized disease conditions. Our analysis allows for improved chemotherapeutic management of individuals with colorectal MANEC and establishes an increased potential for use of streptozocin therapy in the clinical setting. However, newer drugs like amrubicin require further research prior to describing its efficacy in colorectal MANEC.
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Affiliation(s)
- Anita Michael
- Internal Medicine, PSG Institute of Medical Sciences and Research, Coimbatore, IND
| | - Debashis K Nath
- Internal Medicine, Queen Elizabeth Hospital Kings Lynn, King's Lynn, GBR
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Zhang H, Wu J, Yuan J, Li H, Zhang Y, Wu W, Chen W, Wang C, Meng S, Chen S, Huo M, He Y, Zhang C. Ethaselen synergizes with oxaliplatin in tumor growth inhibition by inducing ROS production and inhibiting TrxR1 activity in gastric cancer. JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH : CR 2021; 40:260. [PMID: 34412665 PMCID: PMC8375208 DOI: 10.1186/s13046-021-02052-z] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/04/2020] [Accepted: 02/07/2021] [Indexed: 12/23/2022]
Abstract
Background Oxaliplatin is one of the most commonly used chemotherapeutic agent for the treatment of various cancers, including gastric cancer. It has, however, a narrow therapeutic index due to its toxicity and the occurrence of drug resistance. Hence, it is of great significance to develop novel therapies to potentiate the anti-tumor effect and reduce the toxicity of oxaliplatin. In our previous study, we demonstrated that ethaselen (BBSKE), an inhibitor of thioredoxin reductase, effectively inhibited the growth of gastric cancer cells and promoted apoptosis in vitro. In the present study, we investigated whether BBSKE can potentiate the anti-tumor effect of oxaliplatin in gastric cancer in vivo and vitro. Methods Cellular apoptosis and ROS levels were analyzed by flow cytometry. Thioredoxin reductase 1 (TrxR1) activity in gastric cancer cells, organoid and tumor tissues was determined by using the endpoint insulin reduction assay. Western blot was used to analyze the expressions of the indicated proteins. Nude mice xenograft models were used to test the effects of BBSKE and oxaliplatin combinations on gastric cancer cell growth in vivo. In addition, we also used the combined treatment of BBSKE and oxaliplatin in three cases of gastric cancer Patient-Derived organoid (GC-PDO) to detect the anti-tumor effect. Results We found that BBSKE significantly enhanced oxaliplatin-induced growth inhibition in gastric cancer cells by inhibiting TrxR1 activity. Because of the inhibition of TrxR1 activity, BBSKE synergized with oxaliplatin to enhance the production of ROS and activate p38 and JNK signaling pathways which eventually induced apoptosis of gastric cancer cells. In vivo, we also found that BBSKE synergized with oxaliplatin to suppress the gastric cancer tumor growth in xenograft nude mice model, accompanied by the reduced TrxR1 activity. Remarkably, we found that BBSKE attenuated body weight loss evoked by oxaliplatin treatment. We also used three cases of GC-PDO and found that the combined treatment of BBSKE and oxaliplatin dramatically inhibited the growth and viability of GC-PDO with increased ROS level, decreased TrxR1 activity and enhanced apoptosis. Conclusions This study elucidates the underlying mechanisms of synergistic effect of BBSKE and oxaliplatin, and suggests that the combined treatment has potential value in gastric cancer therapy. Supplementary Information The online version contains supplementary material available at 10.1186/s13046-021-02052-z.
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Affiliation(s)
- Haiyong Zhang
- Digestive Diseases Center, The Seventh Affiliated Hospital, Sun Yat-sen University, 518107, Shenzhen, Guangdong, China.,Department of Gastrointestinal Surgery, The First Affiliated Hospital, Sun Yat-sen University, 510080, Guangzhou, Guangdong, China
| | - Jing Wu
- Digestive Diseases Center, The Seventh Affiliated Hospital, Sun Yat-sen University, 518107, Shenzhen, Guangdong, China
| | - Jinqiu Yuan
- Clinical Research Center, The Seventh Affiliated Hospital, Sun Yat-sen University, 518107, Shenzhen, Guangdong, China
| | - Huafu Li
- Digestive Diseases Center, The Seventh Affiliated Hospital, Sun Yat-sen University, 518107, Shenzhen, Guangdong, China.,Department of Gastrointestinal Surgery, The First Affiliated Hospital, Sun Yat-sen University, 510080, Guangzhou, Guangdong, China
| | - Yawei Zhang
- Digestive Diseases Center, The Seventh Affiliated Hospital, Sun Yat-sen University, 518107, Shenzhen, Guangdong, China.,Department of Gastrointestinal Surgery, The First Affiliated Hospital, Sun Yat-sen University, 510080, Guangzhou, Guangdong, China
| | - Wang Wu
- Digestive Diseases Center, The Seventh Affiliated Hospital, Sun Yat-sen University, 518107, Shenzhen, Guangdong, China.,Department of Gastrointestinal Surgery, The First Affiliated Hospital, Sun Yat-sen University, 510080, Guangzhou, Guangdong, China
| | - Wei Chen
- Department of Pathology, The Seventh Affiliated Hospital, Sun Yat-Sen University, 518107, Shenzhen, Guangdong, China
| | - Chunming Wang
- Digestive Diseases Center, The Seventh Affiliated Hospital, Sun Yat-sen University, 518107, Shenzhen, Guangdong, China.,Department of Gastrointestinal Surgery, The First Affiliated Hospital, Sun Yat-sen University, 510080, Guangzhou, Guangdong, China
| | - Sijun Meng
- Digestive Diseases Center, The Seventh Affiliated Hospital, Sun Yat-sen University, 518107, Shenzhen, Guangdong, China
| | - Songyao Chen
- Digestive Diseases Center, The Seventh Affiliated Hospital, Sun Yat-sen University, 518107, Shenzhen, Guangdong, China
| | - Mingyu Huo
- Digestive Diseases Center, The Seventh Affiliated Hospital, Sun Yat-sen University, 518107, Shenzhen, Guangdong, China.
| | - Yulong He
- Digestive Diseases Center, The Seventh Affiliated Hospital, Sun Yat-sen University, 518107, Shenzhen, Guangdong, China. .,Department of Gastrointestinal Surgery, The First Affiliated Hospital, Sun Yat-sen University, 510080, Guangzhou, Guangdong, China.
| | - Changhua Zhang
- Digestive Diseases Center, The Seventh Affiliated Hospital, Sun Yat-sen University, 518107, Shenzhen, Guangdong, China. .,Department of Gastrointestinal Surgery, The First Affiliated Hospital, Sun Yat-sen University, 510080, Guangzhou, Guangdong, China.
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Zhang X, Liang H, Li Z, Xue Y, Wang Y, Zhou Z, Yu J, Bu Z, Chen L, Du Y, Wang X, Wu A, Li G, Su X, Xiao G, Cui M, Wu D, Chen L, Wu X, Zhou Y, Zhang L, Dang C, He Y, Zhang Z, Sun Y, Li Y, Chen H, Bai Y, Qi C, Yu P, Zhu G, Suo J, Jia B, Li L, Huang C, Li F, Ye Y, Xu H, Wang X, Yuan Y, E JY, Ying X, Yao C, Shen L, Ji J. Perioperative or postoperative adjuvant oxaliplatin with S-1 versus adjuvant oxaliplatin with capecitabine in patients with locally advanced gastric or gastro-oesophageal junction adenocarcinoma undergoing D2 gastrectomy (RESOLVE): an open-label, superiority and non-inferiority, phase 3 randomised controlled trial. Lancet Oncol 2021; 22:1081-1092. [PMID: 34252374 DOI: 10.1016/s1470-2045(21)00297-7] [Citation(s) in RCA: 234] [Impact Index Per Article: 58.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2021] [Revised: 05/10/2021] [Accepted: 05/11/2021] [Indexed: 02/09/2023]
Abstract
BACKGROUND The optimal perioperative chemotherapeutic regimen for locally advanced gastric cancer remains undefined. We evaluated the efficacy and safety of perioperative and postoperative S-1 and oxaliplatin (SOX) compared with postoperative capecitabine and oxaliplatin (CapOx) in patients with locally advanced gastric cancer undergoing D2 gastrectomy. METHODS We did this open-label, phase 3, superiority and non-inferiority, randomised trial at 27 hospitals in China. We recruited antitumour treatment-naive patients aged 18 years or older with historically confirmed cT4a N+ M0 or cT4b Nany M0 gastric or gastro-oesophageal junction adenocarcinoma, with Karnofsky performance score of 70 or more. Patients undergoing D2 gastrectomy were randomly assigned (1:1:1) via an interactive web response system, stratified by participating centres and Lauren classification, to receive adjuvant CapOx (eight postoperative cycles of intravenous oxaliplatin 130 mg/m2 on day one of each 21 day cycle plus oral capecitabine 1000 mg/m2 twice a day), adjuvant SOX (eight postoperative cycles of intravenous oxaliplatin 130 mg/m2 on day one of each 21 day cycle plus oral S-1 40-60 mg twice a day), or perioperative SOX (intravenous oxaliplatin 130 mg/m2 on day one of each 21 day plus oral S-1 40-60 mg twice a day for three cycles preoperatively and five cycles postoperatively followed by three cycles of S-1 monotherapy). The primary endpoint, assessed in the modified intention-to-treat population, 3-year disease-free survival to assess the superiority of perioperative-SOX compared with adjuvant-SOX and the non-inferiority (hazard ratio non-inferiority margin of 1·33) of adjuvant-SOX compared with adjuvant-CapOx. Safety analysis were done in patients who received at least one dose of the assigned treatment. This study is registered with ClinicalTrials.gov, NCT01534546. FINDINGS Between Aug 15, 2012, and Feb 28, 2017, 1094 patients were screened and 1022 (93%) were included in the modified intention-to-treat population, of whom 345 (34%) patients were assigned to the adjuvant-CapOx, 340 (33%) patients to the adjuvant-SOX group, and 337 (33%) patients to the perioperative-SOX group. 3-year disease-free survival was 51·1% (95% CI 45·5-56·3) in the adjuvant-CapOx group, 56·5% (51·0-61·7) in the adjuvant-SOX group, and 59·4% (53·8-64·6) in the perioperative-SOX group. The hazard ratio (HR) was 0·77 (95% CI 0·61-0·97; Wald p=0·028) for the perioperative-SOX group compared with the adjuvant-CapOx group and 0·86 (0·68-1·07; Wald p=0·17) for the adjuvant-SOX group compared with the adjuvant-CapOx group. The most common grade 3-4 adverse events was neutropenia (32 [12%] of 258 patients in the adjuvant-CapOx group, 21 [8%] of 249 patients in the adjuvant-SOX group, and 30 [10%] of 310 patients in the perioperative-SOX group). Serious adverse events were reported in seven (3%) of 258 patients in adjuvant-CapOx group, two of which were related to treatment; eight (3%) of 249 patients in adjuvant-SOX group, two of which were related to treatment; and seven (2%) of 310 patients in perioperative-SOX group, four of which were related to treatment. No treatment-related deaths were reported. INTERPRETATION Perioperative-SOX showed a clinically meaningful improvement compared with adjuvant-CapOx in patients with locally advanced gastric cancer who had D2 gastrectomy; adjuvant-SOX was non-inferior to adjuvant-CapOx in these patients. Perioperative-SOX could be considered a new treatment option for patients with locally advanced gastric cancer. FUNDING National Key Research and Development Program of China, Beijing Scholars Program 2018-2024, Peking University Clinical Scientist Program, Taiho, Sanofi-Aventis, and Hengrui Pharmaceutical. TRANSLATION For the Chinese translation of the abstract see Supplementary Materials section.
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Affiliation(s)
- Xiaotian Zhang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China
| | - Han Liang
- Department of Gastric Surgery, Tianjin Medical University Cancer Institute & Hospital, Tianjin, China
| | - Ziyu Li
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China
| | - Yingwei Xue
- Department of Gastrointestinal Surgery, Harbin Medical University Cancer Hospital, Harbin, China
| | - Yanong Wang
- Department of Gastric Surgery, Fudan University Shanghai Cancer Centre, Shanghai, China
| | - Zhiwei Zhou
- Department of Gastric Surgery, Sun Yat-sen University Cancer Centre, State Key Laboratory of Oncology in South China, Collaborative Innovation Centre for Cancer Medicine, Guangzhou, China
| | - Jiren Yu
- Department of Gastrointestinal Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Zhaode Bu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China
| | - Lin Chen
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China
| | - Yian Du
- Department of Gastric Surgery and Department of Hepatopancreatobiliary Surgery, Zhejiang Cancer Hospital, Hangzhou, China
| | - Xinbao Wang
- Department of Gastric Surgery and Department of Hepatopancreatobiliary Surgery, Zhejiang Cancer Hospital, Hangzhou, China
| | - Aiwen Wu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China
| | - Guoli Li
- Department of General surgery, Nanjing Jinling Hospital, Nanjing, China
| | - Xiangqian Su
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China
| | - Gang Xiao
- Department of General Surgery, Beijing Hospital, Beijing, China
| | - Ming Cui
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China
| | - Dan Wu
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China
| | - Li Chen
- Department of General Surgery, Chinese PLA General Hospital, Beijing, China
| | - Xiaojiang Wu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China
| | - Yanbing Zhou
- Department of Gastrointestinal Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Lianhai Zhang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China
| | - Chengxue Dang
- Department of Oncology Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Yulong He
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Zhongtao Zhang
- Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Yihong Sun
- Department of General Surgery, Zhongshan Hospital, Fudan University, Guangzhou, China
| | - Yong Li
- Department of General Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Huanqiu Chen
- Department of General Surgery, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, and The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, China
| | - Yuxian Bai
- Department of Gastrointestinal Oncology, Harbin Medical University Cancer Hospital, Harbin, China
| | - Changsong Qi
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China
| | - Peiwu Yu
- Department of General Surgery, The First Hospital Affiliated to Army Medical University, Chongqing, China
| | - Guanbao Zhu
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Jian Suo
- Department of Gastrointestinal Surgery, The First Hospital of Jilin University, Changchun, China
| | - Baoqing Jia
- Department of General Surgery, Chinese PLA General Hospital, Beijing, China
| | - Leping Li
- Department of Gastrointestinal Surgery, Shandong Provincial Hospital, Jinan, China
| | - Changming Huang
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China
| | - Fei Li
- Department of General Surgery, Xuanwu Hospital Capital Medical University, Beijing, China
| | - Yingjiang Ye
- Department of General Surgery, Peking University People's Hospital, Beijing, China
| | - Huimian Xu
- Department of Gastrointestinal Oncology Surgery, The First Hospital of China Medical University, Shenyang, China
| | - Xin Wang
- Department of General Surgery, Peking University First Hospital, Beijing, China
| | - Yannan Yuan
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China
| | - Jian-Yu E
- Wilmer Eye Institute, Johns Hopkins University School of Medicine and Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
| | - Xiangji Ying
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China
| | - Chen Yao
- Peking University Clinical Research Institute, Peking University First Hospital, Beijing, China
| | - Lin Shen
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China.
| | - Jiafu Ji
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China.
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Yen CC, Shan YS, Chao YJ, Liao TK, Chen IS, Huang HY, Liu IT, Yen CJ. Surgery alone, adjuvant tegafur/gimeracil/octeracil (S-1), or platinum-based chemotherapies for resectable gastric cancer: real-world experience and a propensity score matching analysis. BMC Cancer 2021; 21:796. [PMID: 34243732 PMCID: PMC8268293 DOI: 10.1186/s12885-021-08487-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2021] [Accepted: 06/08/2021] [Indexed: 11/30/2022] Open
Abstract
Background Adjuvant chemotherapy has changed the paradigm in resectable gastric cancer. S-1 is an oral chemotherapeutic with promising efficacy in Asia. However, comparisons with close observation or platinum-based doublets post D2 gastrectomy have been less reported, notably on real-world experiences. Methods We retrospectively evaluated patients with D2-dissected stage IB-III gastric cancer who received S-1 (S-1, n = 67), platinum-based doublets (P, n = 145) and surgery with close observation (OBS, n = 221) from Jan 2008 to Oct 2018. A propensity score matching was used to compare for recurrence-free (RFS) and overall survivals (OS) in patients who had a locally-advanced disease (T3–4 or lymph node-positive). Adverse reactions, dosage, and associated factors for S-1 are also discussed. Results In a median follow-up time of 51.9 months, adjuvant S-1 monotherapy was associated with an intermediate survival as compared with P and OBS (median RFS/OS: S-1 vs. P, 20.9/35.8 vs. 31.2/50.5 months, HR = 1.76/2.14, p = 0.021/0.008; S-1 vs. OBS, 24.4/40.2 vs. 20.7/27.0 months, HR = 0.62/0.55, p = 0.041/0.024). The survival differences were more prominent in patients with N2–3 diseases. S-1 was well-tolerated with a relative dose intensity of 73.6%, a median duration of 8.3 months and associated with less adverse reactions as compared with P. S-1 monotherapy was selected by physicians based on age, lymph node stage, serum carcinoembryonic antigen and disease stage. Conclusions Adjuvant S-1 correlated with intermediate survival outcomes between OBS and P but conferred fewer adverse reactions as compared with P. Patients with a moderate risk of recurrence had comparable survivals when treated with S-1 while platinum-based doublets were favored in advanced cases. The study provides additional information about adjuvant S-1 in patients with selected risk of recurrence. Supplementary Information The online version contains supplementary material available at 10.1186/s12885-021-08487-z.
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Affiliation(s)
- Chih-Chieh Yen
- Division of Hematology/ Oncology, Department of Internal Medicine, National Cheng Kung University Hospital Douliou Branch, Yunlin, Taiwan.,Institute of Clinical Medicine, School of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Yan-Shen Shan
- Institute of Clinical Medicine, School of Medicine, National Cheng Kung University, Tainan, Taiwan.,Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Ying-Jui Chao
- Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Ting-Kai Liao
- Department of Surgery, National Cheng Kung University Hospital Douliou Branch, YunLin, Taiwan
| | - I-Shu Chen
- Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
| | - Hsuan-Yi Huang
- Division of Colorectal Surgery, Department of Surgery, Chi Mei Medical Center, Tainan, Taiwan
| | - I-Ting Liu
- Department of Oncology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, No. 138, Sheng-Li Road, Tainan, 70403, Taiwan
| | - Chia-Jui Yen
- Department of Oncology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, No. 138, Sheng-Li Road, Tainan, 70403, Taiwan.
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Inoue H, Kosuga T, Kubota T, Konishi H, Shiozaki A, Okamoto K, Fujiwara H, Otsuji E. Significance of a preoperative systemic immune-inflammation index as a predictor of postoperative survival outcomes in gastric cancer. World J Surg Oncol 2021; 19:173. [PMID: 34118953 PMCID: PMC8199826 DOI: 10.1186/s12957-021-02286-3] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2020] [Accepted: 06/03/2021] [Indexed: 12/17/2022] Open
Abstract
Background Since inflammation and the immune system contribute to the development and progression of malignancies, parameters that reflect a host’s immune-inflammatory status may be useful prognostic indicators of gastric cancer (GC). The present study examined the clinical significance of a preoperative systemic immune-inflammation index (SII) for predicting postoperative survival outcomes in GC. Methods A total of 447 patients who underwent curative gastrectomy for GC were included in the present study. SII was calculated as platelet count × neutrophil count/lymphocyte count. The prognostic impact of preoperative SII was examined using univariate and multivariate analyses. Results Preoperative SII ranged between 105 and 4455 (median 474), and the optimal cutoff value for predicting overall survival (OS) was 395 based on a receiver operating characteristic curve. The 5-year OS rate of the SII ≥ 395 group was 80.0%, which was significantly worse than that (92.7%) of the SII < 395 group (p < 0.001). The multivariate analysis identified SII ≥ 395 (hazard ratio [HR] 2.95; 95% confidence interval [CI] 1.49–6.39; p = 0.001), heart disease (HR 2.14, 95% CI 1.07–4.07), C-reactive protein ≥ 0.5 (HR 2.45, 95% CI 1.15–4.94), pT4 (HR 4.46, 95% CI 2.44–8.14), and pN+ (HR 4.02, 95% CI 2.10–7.93) as independent predictors of worse OS. Peritoneal recurrence was more frequent in the high SII group than in the low SII group (p = 0.028). Conclusion Preoperative SII may be a useful predictor of postoperative survival outcomes in GC. The meticulous surveillance of GC relapse, particularly peritoneal dissemination, is necessary for patients with SII ≥ 395 even after curative gastrectomy. Supplementary Information The online version contains supplementary material available at 10.1186/s12957-021-02286-3.
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Affiliation(s)
- Hiroyuki Inoue
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto, 602-8566, Japan
| | - Toshiyuki Kosuga
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto, 602-8566, Japan. .,Department of Surgery, Saiseikai Shiga Hospital, Ritto, Shiga, Japan.
| | - Takeshi Kubota
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto, 602-8566, Japan
| | - Hirotaka Konishi
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto, 602-8566, Japan
| | - Atsushi Shiozaki
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto, 602-8566, Japan
| | - Kazuma Okamoto
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto, 602-8566, Japan
| | - Hitoshi Fujiwara
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto, 602-8566, Japan
| | - Eigo Otsuji
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto, 602-8566, Japan
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Xiao H, Xiao Y, Chen P, Quan H, Luo J, Huang G. Association Among Blood Transfusion, Postoperative Infectious Complications, and Cancer-Specific Survival in Patients with Stage II/III Gastric Cancer After Radical Gastrectomy: Emphasizing Benefit from Adjuvant Chemotherapy. Ann Surg Oncol 2021; 28:2394-2404. [PMID: 32929601 PMCID: PMC7940152 DOI: 10.1245/s10434-020-09102-4] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2020] [Accepted: 08/16/2020] [Indexed: 12/15/2022]
Abstract
OBJECTIVES This study was designed to investigate the potential additive influence of perioperative blood transfusion (BTF) and postoperative infections on cancer-specific survival (CSS) in patients with stage II/III gastric cancer (GC) after radical gastrectomy. METHODS The medical records of 2114 consecutive stage II/III GC patients who underwent curative resection and planned to receive adjuvant chemotherapy (AC) were retrospectively reviewed. The independent predictive factors for infections were identified using univariate and multivariate analyses. Cox regression analysis was used to assess any associations between BTF, infection and CSS. RESULTS A total of 507 (24.0%) received perioperative BTF and 148 (7.0%) developed infections with BTF being identified as an independent predictor for infections. Both BTF and infections independently predicted poor CSS (hazard ratio [HR]: 1.193, 95% confidence interval [CI] 1.007-1.414; HR 1.323, 95% CI 1.013-1.727) and an additive effect was confirmed as patients who had both BTF and infection had even worse CSS. Further stratified analyses showed that complete AC (≥ 6 cycles) could significantly improve CSS in patients who had BTF and/or infection, which was comparable to those without BTF and/or infection (P = 0.496). CONCLUSIONS Infection was the most common complication after gastrectomy and BTF was identified as an independent risk factor. BTF was associated with shorter CSS in stages II/III GC, independent of infections, and receiving BTF and developing infections had an additive effect that was associated with even worse CSS. However, complete AC could significantly improve CSS in these patients. Thus, strategies designed to ensure the completion of AC, such as neoadjuvant chemotherapy, should be further investigated.
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Affiliation(s)
- Hua Xiao
- Department of Hepatobiliary and Intestinal Surgery, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China
- Department of Gastroduodenal and Pancreatic Surgery, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China
| | - Yanping Xiao
- Department of Admissions and Employment, Changsha Health Vocational College, Changsha, Hunan, China
| | - Pan Chen
- Department of Hepatobiliary and Intestinal Surgery, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China
| | - Hu Quan
- Department of Hepatobiliary and Intestinal Surgery, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China
| | - Jia Luo
- Department of Hepatobiliary and Intestinal Surgery, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China.
| | - Gang Huang
- Department of Gastroduodenal and Pancreatic Surgery, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China.
- Department of Orthopedics, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China.
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Su H, Zhao M, Zhang J, Dai Z. Dosimetric effects related to collimator angle optimization in intensity‐modulated radiotherapy planning for gastric cancer. PRECISION RADIATION ONCOLOGY 2021. [DOI: 10.1002/pro6.1108] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Affiliation(s)
- Huan‐fan Su
- Department of Medical Imaging Jiangxi Medical College Shangrao China
| | - Man Zhao
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Shenzhen China
| | - Jun Zhang
- Department of Radiotherapy Zhongnan Hospital of Wuhan University Wuhan China
| | - Zhi‐tao Dai
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Shenzhen China
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Li X, Huang Q, Lei Y, Zheng X, Dai S, Leng W, Liu M. Locally advanced gastroesophageal junction cancer with pathological complete response to neoadjuvant therapy: a case report and literature review. ANNALS OF TRANSLATIONAL MEDICINE 2021; 9:513. [PMID: 33850910 PMCID: PMC8039689 DOI: 10.21037/atm-21-434] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
Most gastric cancer and gastroesophageal junction carcinoma (GEJ) patients are already in the advanced stage at the time of diagnosis. Thus, the probability of radical gastrectomy is low, and surgical treatment alone has a poor prognosis due to the high recurrence rate. In order to reduce the recurrence and distant metastasis after surgery, there have been many attempts made to improve the perioperative treatment of advanced localized gastric cancer, but no uniform criteria exist. Over recent years, immunotherapy has revolutionized cancer treatment, and immune checkpoint inhibitors (ICIs) have shown excellent efficacy across various types of tumors, becoming a potential treatment after surgery, chemotherapy, radiotherapy, and targeted therapy. However, the efficacy of single-agent ICIs for gastric cancer is still unsatisfactory. As comprehensive, chemotherapy-based treatment has become the standard care for locally advanced gastric cancer, exploring combination treatment with immune checkpoint inhibitors (ICIs) may be valuable to improving survival outcomes. Here, we report a 66-year-old male with dysphagia diagnosed with GEJ and was defined as clinical stage (cT4N2M0) and Siewert type II, characterized as mismatch repair proficient (pMMR) and programmed cell death ligand-1 (PD-L1) negative; surprisingly, with anti-PD-1 antibody plus SOX (S-1: a combination of tegafur, gimeracil, and oteracil+ oxaliplatin) as perioperative therapy, the patient achieved pathological complete remission (pCR), which indicates that the addition of ICIs to chemotherapy as a perioperative comprehensive treatment might provide a promising strategy option for GEJ. In addition, we review the current status of perioperative comprehensive treatment, in hope that this may provide some reference value for clinical decision-making.
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Affiliation(s)
- Xiaoying Li
- Department of Abdominal Oncology, West China Hospital, Sichuan University, Chengdu, China
| | - Qian Huang
- Department of Abdominal Oncology, West China Hospital, Sichuan University, Chengdu, China
| | - Yanna Lei
- Department of Abdominal Oncology, West China Hospital, Sichuan University, Chengdu, China
| | - Xiufeng Zheng
- Department of Abdominal Oncology, West China Hospital, Sichuan University, Chengdu, China
| | - Shuang Dai
- Department of Abdominal Oncology, West China Hospital, Sichuan University, Chengdu, China
| | - Weibing Leng
- Department of Abdominal Oncology, West China Hospital, Sichuan University, Chengdu, China
| | - Ming Liu
- Department of Abdominal Oncology, West China Hospital, Sichuan University, Chengdu, China
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A Phase II Study Demonstrates No Feasibility of Adjuvant Treatment with Six Cycles of S-1 and Oxaliplatin in Resectable Esophageal Adenocarcinoma, with ERCC1 as Biomarker for Response to SOX. Cancers (Basel) 2021; 13:cancers13040839. [PMID: 33671266 PMCID: PMC7922275 DOI: 10.3390/cancers13040839] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2021] [Accepted: 02/07/2021] [Indexed: 12/15/2022] Open
Abstract
Simple Summary Neoadjuvant chemoradiotherapy followed by surgery is currently standard of care in esophageal adenocarcinoma. However, prognosis remains dismal. The aim of our study was to assess the feasibility of administering six cycles of adjuvant S-1 and oxaliplatin following neoadjuvant chemoradiotherapy and esophagectomy. Although six cycles of adjuvant S-1 and oxaliplatin were not feasible in pretreated patients, mainly due to toxicity, efficacy results were promising compared to a propensity-score matched cohort. Exploratory biomarker analyses demonstrated potential benefit for patients with Excision repair cross-complementation group 1 (ERCC1) negative tumor expression. A proteomics biomarker model provided valuable information for prediction of survival and pharmacokinetics of 5-FU showed a correlation with treatment-related toxicity. Although it remains unclear if additional chemotherapy should be provided in the adjuvant setting, subgroups such as patients with ERCC1 negativity, could potentially benefit from this treatment option based on our exploratory biomarker research. Abstract We assessed the feasibility of adjuvant S-1 and oxaliplatin following neoadjuvant chemoradiotherapy (nCRT) and esophagectomy. Patients treated with nCRT (paclitaxel, carboplatin) and esophagectomy received six 21-day cycles with oxaliplatin (130 mg/m2) on day 1 and S-1 (25 mg/m2 twice daily) on days 1–14. The primary endpoint was feasibility, defined as ≥50% completing treatment. We performed exploratory propensity-score matching to compare survival, ERCC1 and Thymidylate Synthase (TS) immunohistochemistry analyses, proteomics biomarker discovery and 5-FU pharmacokinetic analyses. Forty patients were enrolled and 48% completed all adjuvant cycles. Median dose intensity was 98% for S-1 and 62% for oxaliplatin. The main reason for early discontinuation was toxicity (67%). The median recurrence-free and overall survival were 28.3 months and 40.8 months, respectively (median follow-up 29.1 months). Survival was not significantly prolonged compared to a matched cohort (p = 0.09). Patients with ERCC1 negative tumor expression had significantly better survival compared to ERCC1 positivity (p = 0.01). Our protein signature model was predictive of survival [p = 0.04; Area under the curve (AUC) 0.80]. Moreover, 5-FU pharmacokinetics significantly correlated with treatment-related toxicity. To conclude, six cycles adjuvant S-1 and oxaliplatin were not feasible in pretreated esophageal adenocarcinoma. Although the question remains whether additional treatment with chemotherapy should be provided in the adjuvant setting, subgroups such as patients with ERCC1 negativity could potentially benefit from adjuvant SOX based on our exploratory biomarker research.
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Cheng X, Wu D, Xu N, Chen L, Yan Z, Chen P, Zhou L, Yu J, Cui J, Li W, Wang C, Feng W, Wei Y, Yu P, Du Y, Ying J, Xu Z, Yang L, Zhang Y. Adjuvant albumin-bound paclitaxel combined with S-1 vs. oxaliplatin combined with capecitabine after D2 gastrectomy in patients with stage III gastric adenocarcinoma: a phase III multicenter, open-label, randomized controlled clinical trial protocol. BMC Cancer 2021; 21:56. [PMID: 33435909 PMCID: PMC7802165 DOI: 10.1186/s12885-020-07772-7] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2020] [Accepted: 12/26/2020] [Indexed: 12/23/2022] Open
Abstract
BACKGROUND Surgery is the only treatment option for operable gastric cancer. The CLASSIC and ACTS-GC studies showed that the 5-year overall survival (OS) of patients with stage III gastric cancer undergoing D2 gastrectomy is still very low. Whether adjuvant nanoparticle albumin-bound paclitaxel (nab-paclitaxel) combined chemotherapy is more effective than the XELOX standard adjuvant chemotherapy in patients with stage III gastric cancer has not been confirmed. METHODS This is a multicenter, open-label, phase III clinical study. In this trial, 616 patients with locally advanced stage III gastric cancer that underwent curative D2 radical surgery and achieved R0 are planned to be included. Patients will be randomized 1:1 to nab-paclitaxel combined with S-1 (AS) vs. oxaliplatin combined with capecitabine (XELOX). XELOX group: Patients assigned to the XELOX group received eight 3-week cycles of oral capecitabine (1000 mg/m2) twice daily on days 1-14 of each cycle plus intravenous oxaliplatin 130 mg/m2 on day 1 of each cycle. AS group: AS group received eight 3-week cycles of oral S-1 (80-120 mg) (< 1.25 m2, 40 mg; 1.25 to < 1.5 m2, 50 mg; and > 1.5 m2, 60 mg) twice daily on days 1-14 plus intravenous nab-paclitaxel 120 mg/m2 on days 1 and 8 of each cycle. The primary endpoint was the 3-year disease-free survival (3-year-DFS) defined as the time from randomisation to the time of recurrence of the original gastric cancer, development of a new gastric cancer, or death from any cause. The secondary endpoints were the overall survival, (defined as the time from the date of randomisation to date of death from any cause) and safety (any adverse event). DISCUSSION Compared with previous studies, this study includes nab-paclitaxel based on S-1 adjuvant chemotherapy, which is expected to achieve better efficacy and lower toxicity than the standard treatment. This study is the first clinical study to evaluate the safety and efficacy of nab-paclitaxel combined with S-1 in patients with stage III gastric cancer after D2 radical resection. TRIAL REGISTRATION This clinical trial has been registered with ClinicalTrials.gov, registration number: NCT04135781 , on October 20th, 2019.
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Affiliation(s)
- Xiangdong Cheng
- Department of Abdominal Surgery, Zhejiang Cancer Hospital (University of Chinese Academy of Sciences Cancer Hospital), Zhejiang, China.
| | - Dan Wu
- Department of General Surgery, Second Affiliated Hospital of Medical College of Zhejiang University, Zhejiang, China
| | - Nong Xu
- Department of Oncology, First Affiliated Hospital of Medical College of Zhejiang University, Zhejiang, China
| | - Luchuan Chen
- Department of Gastrointestinal Oncology Surgery, Fujian Provincial Cancer Hospital, Fuzhou, Fujian, China
| | - Zhilong Yan
- Department of Gastrointestinal Surgery, Ningbo First Hospital, Zhejiang, China
| | - Ping Chen
- Department of Gastrointestinal Surgery, Ningbo Second Hospital, Zhejiang, China
| | - Lei Zhou
- Department of General Surgery, China-Japan Friendship Hospital, Beijing, China
| | - Jianfa Yu
- Department of Gastrointestinal Surgery, Zhejiang Provincial Hospital of Traditional Chinese Medicine, Zhejiang, China
| | - Jiuwei Cui
- Oncology Central, First Hospital of Jilin University, Jilin, China
| | - Wei Li
- Oncology Central, First Hospital of Jilin University, Jilin, China
| | - Chang Wang
- Oncology Central, First Hospital of Jilin University, Jilin, China
| | - Wenming Feng
- Department of Hepatobiliary Pancreatic Surgery, Huzhou First People's Hospital, Zhejiang, China
| | - Yunhai Wei
- Department of Hepatobiliary Pancreatic Surgery, Huzhou Central Hospital (Zhejiang University Huzhou Hospital), Zhejiang, China
| | - Pengfei Yu
- Department of Abdominal Surgery, Zhejiang Cancer Hospital (University of Chinese Academy of Sciences Cancer Hospital), Zhejiang, China
| | - Yian Du
- Department of Abdominal Surgery, Zhejiang Cancer Hospital (University of Chinese Academy of Sciences Cancer Hospital), Zhejiang, China
| | - Jieer Ying
- Department of Abdominal Surgery, Zhejiang Cancer Hospital (University of Chinese Academy of Sciences Cancer Hospital), Zhejiang, China
| | - Zhiyuan Xu
- Department of Abdominal Surgery, Zhejiang Cancer Hospital (University of Chinese Academy of Sciences Cancer Hospital), Zhejiang, China
| | - Litao Yang
- Department of Abdominal Surgery, Zhejiang Cancer Hospital (University of Chinese Academy of Sciences Cancer Hospital), Zhejiang, China
| | - Yunli Zhang
- Department of Abdominal Surgery, Zhejiang Cancer Hospital (University of Chinese Academy of Sciences Cancer Hospital), Zhejiang, China
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Oh SE, An JY, Choi MG, Lee JH, Sohn TS, Bae JM. Comparison of Long-Term Efficacy in S-1 and Capecitabine With Oxaliplatin as Adjuvant Chemotherapy for Patients With Gastric Cancer After Curative Surgery: A Retrospective, Single-Center Observational Study. Technol Cancer Res Treat 2021; 20:15330338211039679. [PMID: 34605706 PMCID: PMC8493307 DOI: 10.1177/15330338211039679] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2021] [Accepted: 07/27/2021] [Indexed: 12/23/2022] Open
Abstract
Purpose: Various adjuvant chemotherapies have been introduced for gastric cancer patients after gastrectomy with D2 lymph node dissection. Although the mainstream regimen of adjuvant chemotherapy in Korea includes S-1 monotherapy (TS-1) and capecitabine with oxaliplatin (XELOX), few studies have compared the long-term efficacies of these 2 regimens. Methods: Between January 2010 and June 2017, 2021 patients were diagnosed with gastric cancer and underwent curative resection with adjuvant chemotherapy at our institution. Of 1461 patients with stage IB-III gastric cancer, 825 received TS-1 and 636 received XELOX as adjuvant chemotherapy. We retrospectively reviewed their medical records and analyzed the postoperative 5-year overall survival (OS) and disease-free survival (DFS) of these 2 groups. Results: The patients in the XELOX group had more advanced stage of cancer than the TS-1 group (stages III and II: 56.6% and 43.1%, respectively, in XELOX and 35.3% and 57.0% in TS-1; P < .001). The DFS did not differ significantly between the 2 study groups at any pathologic stage. The OS differed significantly only at pathologic stages IIA (P = .024) and IIB (P = .015). In a multivariate analysis of stage II patients, type of regimen was an independent prognostic factor of OS (XELOX vs TS-1; hazard ratio: 0.47, 95% confidence interval: 0.25-0.89, P = .021). Conclusion: There were similar long-term efficacies between these 2 regimens in advanced gastric cancer patients who underwent curative surgery. However, the XELOX regimen might be favorable for OS of stage II patients.
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Affiliation(s)
- Sung E. Oh
- Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Ji Y. An
- Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Min-Gew Choi
- Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Jun H. Lee
- Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Tae S. Sohn
- Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Jae M. Bae
- Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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Nakao T, Kaneko R, Tanaka H, Kobayashi S, Omori R, Yano Y, Kamada K, Ikehara T, Sato Y, Igarashi Y. Contribution of chemotherapy to improved prognosis in stage 4 gastric cancer: trend analysis of a regional population-based cancer registry in Japan. Int J Clin Oncol 2020; 26:378-386. [PMID: 33151441 DOI: 10.1007/s10147-020-01820-9] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2020] [Accepted: 10/15/2020] [Indexed: 12/12/2022]
Abstract
OBJECTIVES Little is known about time trends in the prognosis of gastric cancer (GC), since the introduction of new chemotherapeutic agents. This study aimed to analyze how the increased number of available chemotherapeutic options affected the prognosis of GC and which patient types benefited within in a large population. METHODS From a population-based cancer registry in Japan, 35,751 cases of GC were identified. Of these, 8214 cases were stage 4. The time trend for 3-year survival in stage 4 GC according to patient characteristics (age and tumor location) was estimated in relation to the introduction of new anticancer drugs. Multiple imputation was performed for sensitivity analysis to strengthen the missing data. In addition, we estimated the 5-year survival rate for distal-GC (DGC) and proximal-GC (PGC), and the hazard ratio (HR) was estimated by Cox proportional hazard model. RESULTS Improvement of overall survival was accelerated in stage 4 cases over time. The prognosis was improved from 11.4% to 13.2%, subsequent to the approval of several oncologic drugs since 2009. Younger patients were more likely to have improved survival rates in response to the increase in chemotherapy options (< 60-year-old, 5.4%: 60-70, 2.2%; 70-80, 0.3%) from 2007 to 2015. The HR for DGC vs. PGC was 1.11 (95% CI 1.08-1.15), and PGC showed a higher rate of improved outcomes (2.4% vs. 0.6%). CONCLUSIONS This analysis showed that improvement in the GC survival rate was accelerated by the introduction of new chemotherapeutic strategies and it was most evident among younger patients and in patients with PGC.
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Affiliation(s)
- Tomomi Nakao
- Department of Gastroenterology, Kanto Rosai Hospital, 1-1 Kizukisumiyoshi-cho, Nakahara-ku, Kawasaki, Kanagawa, 211-8510, Japan.,Division of Gastroenterology and Hepatology, Department of Internal Medicine (Omori), School of Medicine, Faculty of Medicine, Toho University, 6-11-1 Omorinishi, Ota-ku, Tokyo, 143-8541, Japan
| | - Rena Kaneko
- Department of Gastroenterology, Kanto Rosai Hospital, 1-1 Kizukisumiyoshi-cho, Nakahara-ku, Kawasaki, Kanagawa, 211-8510, Japan. .,Department of Public Health, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.
| | - Hirokazu Tanaka
- Department of Public Health, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.,Department of Public Health, Erasmus University Medical Center, 3000 CA, Rotterdam, The Netherlands
| | - Shunsuke Kobayashi
- Department of Gastroenterology, Kanto Rosai Hospital, 1-1 Kizukisumiyoshi-cho, Nakahara-ku, Kawasaki, Kanagawa, 211-8510, Japan.,Division of Gastroenterology and Hepatology, Department of Internal Medicine (Omori), School of Medicine, Faculty of Medicine, Toho University, 6-11-1 Omorinishi, Ota-ku, Tokyo, 143-8541, Japan
| | - Risa Omori
- Department of Gastroenterology, Kanto Rosai Hospital, 1-1 Kizukisumiyoshi-cho, Nakahara-ku, Kawasaki, Kanagawa, 211-8510, Japan
| | - Yuichiro Yano
- Department of Gastroenterology, Kanto Rosai Hospital, 1-1 Kizukisumiyoshi-cho, Nakahara-ku, Kawasaki, Kanagawa, 211-8510, Japan
| | - Kentaro Kamada
- Department of Gastroenterology, Kanto Rosai Hospital, 1-1 Kizukisumiyoshi-cho, Nakahara-ku, Kawasaki, Kanagawa, 211-8510, Japan
| | - Takashi Ikehara
- Department of Gastroenterology, Kanto Rosai Hospital, 1-1 Kizukisumiyoshi-cho, Nakahara-ku, Kawasaki, Kanagawa, 211-8510, Japan.,Division of Gastroenterology and Hepatology, Department of Internal Medicine (Omori), School of Medicine, Faculty of Medicine, Toho University, 6-11-1 Omorinishi, Ota-ku, Tokyo, 143-8541, Japan
| | - Yuzuru Sato
- Department of Gastroenterology, Kanto Rosai Hospital, 1-1 Kizukisumiyoshi-cho, Nakahara-ku, Kawasaki, Kanagawa, 211-8510, Japan
| | - Yoshinori Igarashi
- Division of Gastroenterology and Hepatology, Department of Internal Medicine (Omori), School of Medicine, Faculty of Medicine, Toho University, 6-11-1 Omorinishi, Ota-ku, Tokyo, 143-8541, Japan
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Yu S, Wang Y, Cheng X, Lv M, Cui Y, Li W, Yu Y, Li Q, Liu T. Prognosis of Adjuvant SOX vs XELOX Chemotherapy for Gastric Cancer After D2 Gastrectomy in Chinese Patients. Cancer Manag Res 2020; 12:10091-10101. [PMID: 33116865 PMCID: PMC7568598 DOI: 10.2147/cmar.s270387] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2020] [Accepted: 09/19/2020] [Indexed: 12/24/2022] Open
Abstract
Introduction To compare the prognosis of adjuvant SOX (S-1 and oxaliplatin) vs XELOX (capecitabine and oxaliplatin) chemotherapy in Chinese patients with gastric cancer (GC) after D2 gastrectomy. Methods This was a real-world study of patients with GC (stages II-III) who underwent D2 gastrectomy and received adjuvant SOX or XELOX between 01/2010 and 06/2017 in Zhongshan Hospital affiliated to Fudan University. The patients were matched by propensity score matching. The primary and secondary endpoints were disease-free survival (DFS) and overall survival (OS), respectively. Adverse events (AEs) were compared. Results A total of 552 patients were included. The median follow-up time was 24.9 months. There were no differences in DFS (median, 44.4 vs 41.2 months; HR=1.17, 95% CI: 0.92-1.48) and OS (median, 61.5 vs 65.3 months; HR=1.01, 95% CI: 0.73-1.39) between the XELOX and SOX groups. Both DFS and OS had no significant differences between SOX and XELOX for all subgroups based on sex (P=0.949, P=0.990), age (P=0.303, P=0.392), Lauren type (P=0.362, P=0.573), type of gastrectomy (P=0.607 P=0.989), and pathological TNM stage (P=0.899, P=0.888). A total of 86 patients in the SOX subgroup (34.2%) experienced AEs, similar to the rate found in the XELOX subgroup (104 patients or 41.4%; P=0.098). Discussion The results suggested that adjuvant SOX chemotherapy has similar survival benefits compared to XELOX chemotherapy in Chinese patients with pathological stage II or III GC after D2 gastrectomy.
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Affiliation(s)
- Shan Yu
- Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China
| | - Yan Wang
- Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China
| | - Xi Cheng
- Department of Medical Oncology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, People's Republic of China
| | - Minzhi Lv
- Department of Biostatistics, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China
| | - Yuehong Cui
- Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China
| | - Wei Li
- Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China
| | - Yiyi Yu
- Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China
| | - Qian Li
- Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China
| | - Tianshu Liu
- Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China.,Center of Evidence-Based Medicine, Fudan University, Shanghai, People's Republic of China
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Wakatsuki K, Matsumoto S, Migita K, Kunishige T, Nakade H, Miyao S, Sho M. Risk Factors and Risk Scores for Predicting Early Recurrence After Curative Gastrectomy in Patients with Stage III Gastric Cancer. J Gastrointest Surg 2020; 24:1758-1769. [PMID: 31325135 DOI: 10.1007/s11605-019-04327-5] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2019] [Accepted: 07/08/2019] [Indexed: 02/03/2023]
Abstract
BACKGROUND We revealed patients with pathological stage (pStage) III gastric cancer (GC) who had early recurrence within 12 months after curative surgery. We identified risk factors for predicting early recurrence in patients with pStage III GC who underwent curative gastrectomy. METHODS Between January 2007 and December 2016, 758 patients underwent gastrectomy in our institution. This retrospective study included 96 patients with pStage III who were divided into two groups: early recurrence within 12 months (ERec) and non-ERec (nERec). We investigated clinicopathological differences between ERec and nERec and extracted risk factors, and constructed risk scores for ERec. RESULTS Of the 96 patients, 20 (20.8%) were ERec and 76 (79.2%) were nERec. Pathological lymph node metastasis (pN) ≥ 14 (P = 0.03), preoperative carbohydrate antigen 19-9 (CA19-9) ≥ 37 IU/ml (P = 0.02), and blood loss (BL) ≥ 445 ml (P < 0.01) were independent risk factors for ERec in the multivariate analysis. In subgroup analysis, tumor size, clinical lymph node metastasis (cN), and CA19-9 were extracted for preoperative predictors for ERec. Risk scores were assigned to tumor size (< 65 mm, 0; ≥ 65 mm, 1), cN (cN-, 0; cN+, 2), and CA19-9 (< 37 IU/ml, 0; ≥ 37 IU/ml, 2). High-risk group (score, 4, 5) for ERec had significantly shorter relapse-free survival than those with low-risk group (score, 0-3) (P = 0.02). CONCLUSIONS We found pN ≥ 14, CA19-9 ≥ 37 IU/ml, and BL ≥ 445 ml were independent risk factors for ERec after curative gastrectomy in pStage III GC. Our risk score system may be useful to select patients with high risk of ERec preoperatively.
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Affiliation(s)
- Kohei Wakatsuki
- Department of Surgery, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8522, Japan.
| | - Sohei Matsumoto
- Department of Surgery, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8522, Japan
| | - Kazuhiro Migita
- Department of Surgery, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8522, Japan
| | - Tomohiro Kunishige
- Department of Surgery, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8522, Japan
| | - Hiroshi Nakade
- Department of Surgery, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8522, Japan
| | - Shintaro Miyao
- Department of Surgery, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8522, Japan
| | - Masayuki Sho
- Department of Surgery, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8522, Japan
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Lee CM, Yoo MW, Son YG, Oh SJ, Kim JH, Kim HI, Park JM, Hur H, Jee YS, Hwang SH, Jin SH, Lee SE, Park JH, Seo KW, Park S, Kim CH, Jeong IH, Lee HH, Choi SI, Lee SI, Kim CY, Kim IH, Son MW, Pak KH, Kim S, Lee MS, Min JS. Long-term Efficacy of S-1 Monotherapy or Capecitabine Plus Oxaliplatin as Adjuvant Chemotherapy for Patients with Stage II or III Gastric Cancer after Curative Gastrectomy: a Propensity Score-Matched Multicenter Cohort Study. J Gastric Cancer 2020; 20:152-164. [PMID: 32595999 PMCID: PMC7311213 DOI: 10.5230/jgc.2020.20.e13] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/19/2019] [Revised: 03/11/2020] [Accepted: 03/11/2020] [Indexed: 12/23/2022] Open
Abstract
PURPOSE To compare long-term disease-free survival (DFS) between patients receiving tegafur/gimeracil/oteracil (S-1) or capecitabine plus oxaliplatin (CAPOX) adjuvant chemotherapy (AC) for gastric cancer (GC). MATERIALS AND METHODS This retrospective multicenter observational study enrolled 983 patients who underwent curative gastrectomy with consecutive AC with S-1 or CAPOX for stage II or III GC at 27 hospitals in Korea between February 2012 and December 2013. We conducted propensity score matching to reduce selection bias. Long-term oncologic outcomes, including DFS rate over 5 years (over-5yr DFS), were analyzed postoperatively. RESULTS The median and longest follow-up period were 59.0 and 87.6 months, respectively. DFS rate did not differ between patients who received S-1 and CAPOX for pathologic stage II (P=0.677) and stage III (P=0.899) GC. Moreover, hazard ratio (HR) for recurrence did not differ significantly between S-1 and CAPOX (reference) in stage II (HR, 1.846; 95% confidence interval [CI], 0.693-4.919; P=0.220) and stage III (HR, 0.942; 95% CI, 0.664-1.337; P=0.738) GC. After adjustment for significance in multivariate analysis, pT (4 vs. 1) (HR, 11.667; 95% CI, 1.595-85.351; P=0.016), pN stage (0 vs. 3) (HR, 2.788; 95% CI, 1.502-5.174; P=0.001), and completion of planned chemotherapy (HR, 2.213; 95% CI, 1.618-3.028; P<0.001) were determined as independent prognostic factors for DFS. CONCLUSIONS S-1 and CAPOX AC regimens did not show significant difference in over-5yr DFS after curative gastrectomy in patients with stage II or III GC. The pT, pN stage, and completion of planned chemotherapy were prognostic factors for GC recurrence.
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Affiliation(s)
- Chang Min Lee
- Department of Surgery, Korea University College of Medicine, Seoul, Korea
| | - Moon-Won Yoo
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Young-Gil Son
- Department of Surgery, Keimyung University Dongsan Hospital, Keimyung University School of Medicine, Daegu, Korea
| | - Sung Jin Oh
- Department of Surgery, Inje University Haeundae Paik Hospital, Inje University College of Medicine, Busan, Korea
| | - Jong-Han Kim
- Department of Surgery, Korea University College of Medicine, Seoul, Korea
| | - Hyoung-Il Kim
- Department of Surgery, Yonsei University College of Medicine, Seoul, Korea
| | - Joong-Min Park
- Department of Surgery, Chung-Ang University College of Medicine, Seoul, Korea
| | - Hoon Hur
- Department of Surgery, Ajou University School of Medicine, Suwon, Korea
| | - Ye Seob Jee
- Department of Surgery, Dankook University Hospital, Cheonan, Korea
| | - Sun-Hwi Hwang
- Department of Surgery, Pusan National University Yangsan Hospital, Yangsan, Korea
| | - Sung-Ho Jin
- Department of Surgery, Korea Cancer Center Hospital, Seoul, Korea
| | - Sang Eok Lee
- Department of Surgery, Konyang University Hospital, Daejeon, Korea
| | - Ji-Ho Park
- Department of Surgery, Gyeongsang National University Hospital, Jinju, Korea
| | - Kyung Won Seo
- Department of Surgery, Kosin University College of Medicine, Busan, Korea
| | - Sungsoo Park
- Department of Surgery, Korea University College of Medicine, Seoul, Korea
| | - Chang Hyun Kim
- Department of Surgery, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Incheon, Korea
| | - In Ho Jeong
- Department of Surgery, Jeju National University Hospital, Jeju, Korea
| | - Han Hong Lee
- Department of Surgery, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Sung Il Choi
- Department of Surgery, Kyung Hee University Hospital at Gangdong, Seoul, Korea
| | - Sang-Il Lee
- Department of Surgery, Chungnam National University College of Medicine, Daejeon, Korea
| | - Chan Young Kim
- Department of Surgery, Chonbuk National University College of Medicine, Jeonju, Korea
| | - In-Hwan Kim
- Department of Surgery, Daegu Catholic University College of Medicine, Daegu, Korea
| | - Myoung-Won Son
- Department of Surgery, Soonchunhyang University Cheonan Hospital, Cheonan, Korea
| | - Kyung Ho Pak
- Department of Surgery, Hallym University Dongtan Sacred Heart Hospital, Hwaseong, Korea
| | - Sungsoo Kim
- Department of Surgery, Jeju National University Hospital, Jeju, Korea
| | - Moon-Soo Lee
- Department of Surgery, Eulji University Hospital, Daejeon, Korea
| | - Jae-Seok Min
- Department of Surgery, Dongnam Institute of Radiological and Medical Sciences, Cancer Center, Busan, Korea
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Five-year outcomes of a phase II study of adjuvant chemotherapy with S-1 plus docetaxel for stage III gastric cancer after curative D2 gastrectomy (OGSG1002). Gastric Cancer 2020; 23:520-530. [PMID: 31667688 DOI: 10.1007/s10120-019-01023-w] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/11/2019] [Accepted: 10/20/2019] [Indexed: 02/07/2023]
Abstract
BACKGROUND Adjuvant S-1 monotherapy is standard of care for stage II and III gastric cancer (GC), but there is still a need to improve the efficacy of treatment for stage III disease. We conducted phase II study of eight cycles of S-1 plus docetaxel (DS) followed by S-1 monotherapy for up to 1 year after D2 gastrectomy for stage III GC. PATIENTS AND METHODS Sixty-two patients with stage III GC were enrolled. They received oral S-1 (80 mg/m2/day) for 2 consecutive weeks and intravenous docetaxel (40 mg/m2) on day 1, repeated every 3 weeks for 8 cycles, followed by S-1 until 1 year postgastrectomy. Treatment safety, tolerability, and survival were evaluated. RESULTS The completion rate for eight cycles of DS therapy was 77.4% [95% confidence interval (CI) 65.0-87.1%]. Subsequent S-1 monotherapy for 1 year was feasible in 71.0% (95% CI 58.1-81.8%) of patients. The incidence of neutropenia, leukopenia, anorexia, and fatigue of grade 3 or higher was 10% or higher. There were no treatment-related deaths. The 5-year overall survival (OS) and disease-free survival (DFS) rates were 72.4% (95% CI 62.1-84.5%) and 60.0% (95% CI 48.8-73.9%), respectively. Subgroup analyses by disease stage showed 5-year OS and DFS rates of 74.5% (95% CI 60.7-91.5%) and 59.3% (95% CI 43.8-80.2%) for stage IIIA and 70.0% (95% CI 55.4-88.5%) and 60.0% (95% CI 44.8-80.4%) for stage IIIB, respectively. CONCLUSIONS Adjuvant eight cycles of DS therapy might be safe and manageable and has promising OS and DFS for stage III GC.
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Jiang Z, Sun Y, Zhang W, Cui C, Yang L, Zhou A. Comparison of S-1 plus oxaliplatin (SOX) and capecitabine plus oxaliplatin (XELOX) as adjuvant chemotherapies for stage II and III gastric cancer after D2 resection: A single-center retrospective study. Asia Pac J Clin Oncol 2020; 16:180-186. [PMID: 32077628 PMCID: PMC7318315 DOI: 10.1111/ajco.13321] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2019] [Accepted: 01/23/2020] [Indexed: 12/27/2022]
Abstract
Background Capecitabine plus oxaliplatin (XELOX) as adjuvant therapy for gastric cancer (GC) reduces cancer recurrence and improves survival. S‐1 plus oxaliplatin (SOX) is well‐tolerated and effective against advanced GC, and also be used widely in adjuvant treatment. However, data comparing SOX and XELOX as adjuvant treatments are lacking. Method Data on treatment modalities, adverse events, recurrence and metastasis were collected from 180 patients with stage II and III GC, who received SOX or XELOX after D2 gastrectomy between January 2012 and December 2015, and analyzed retrospectively. The primary endpoint was 3‐year disease‐free survival (DFS) rate. Results Median follow was 52.9 months; 3‐year DFS rate and overall survival (OS) rate were 75.2% and 67.6% (P = 0.359) and 81.2% and 83.3% (P = 0.77) in the SOX and XELOX groups, respectively. There was no significant difference in peritoneal metastasis rates in the SOX and XELOX groups (8.6% vs 15%, respectively; P = 0.232). Compound recurrent disease was associated with significantly shorter OS. Multivariate analysis identified metastatic lymph node ratio (LNR) as an independent prognostic factor for OS (P = 0.036; hazard ratio = 2.875; 95% confidence interval, 1.069–7.729); the LNR ≥17% group had inferior 3‐year OS rate to the LNR <17% group (P = 0.001). The incidence of grades 3 and 4 adverse events was similar in both groups; however, grade ≥2 hand–foot syndrome was significantly less frequent in the SOX group (P = 0.01). Conclusion SOX has similar survival benefits to XELOX and is well‐tolerated in Chinese patients with GC following D2 gastrectomy.
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Affiliation(s)
- Zhichao Jiang
- National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yongkun Sun
- National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Wen Zhang
- National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Chengxu Cui
- National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Lin Yang
- National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Aiping Zhou
- National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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Tokunaga M, Sato Y, Nakagawa M, Aburatani T, Matsuyama T, Nakajima Y, Kinugasa Y. Perioperative chemotherapy for locally advanced gastric cancer in Japan: current and future perspectives. Surg Today 2020; 50:30-37. [PMID: 31612329 PMCID: PMC6954129 DOI: 10.1007/s00595-019-01896-5] [Citation(s) in RCA: 55] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2019] [Accepted: 09/20/2019] [Indexed: 12/24/2022]
Abstract
The standard treatment for locally advanced gastric cancer differs across the world. In western countries, perioperative chemotherapy or postoperative adjuvant chemoradiotherapy are the preferred treatment options, whereas in Asia, D2 gastrectomy followed by postoperative adjuvant chemotherapy is standard. In Japan, adjuvant chemotherapy with S-1 is the standard treatment for pStage II gastric cancer, whereas adjuvant chemotherapy with a doublet regimen is preferred for pStage III gastric cancer. The efficacy of preoperative neoadjuvant chemotherapy using S-1 plus cisplatin, has been investigated in selected patients with expected poor survival outcomes. To expand the indications for neoadjuvant chemotherapy, a clinical trial investigating the efficacy of preoperative S-1 plus oxaliplatin in patients with cStage III (cT3-4N1-3) gastric cancer (JCOG1509) is ongoing in Japan. The addition of immune checkpoint inhibitors to cytotoxic chemotherapy also seems promising and is being investigated in international randomized clinical trials. Although we have to await the final results of these studies, preoperative neoadjuvant chemotherapy is a promising treatment strategy and likely to become standard treatment for locally advanced gastric cancer in Japan.
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Affiliation(s)
- Masanori Tokunaga
- Department of Gastrointestinal Surgery, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, Japan.
| | - Yuya Sato
- Department of Gastrointestinal Surgery, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, Japan
| | - Masatoshi Nakagawa
- Department of Gastrointestinal Surgery, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, Japan
| | - Tomoki Aburatani
- Department of Gastrointestinal Surgery, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, Japan
| | - Takatoshi Matsuyama
- Department of Gastrointestinal Surgery, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, Japan
| | - Yasuaki Nakajima
- Department of Gastrointestinal Surgery, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, Japan
| | - Yusuke Kinugasa
- Department of Gastrointestinal Surgery, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, Japan
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