Background: In gastric solid-type poorly differentiated adenocarcinoma (PDA), the role of microsatellite instability and immune escape mechanism remains unclear. The current study aimed to elucidate the clinical significance of mismatch repair (MMR) status, genome profile, C-X-C motif chemokine receptor 2 (CXCR2) expression, and myeloid-derived suppressor cell (MDSC) infiltration in solid-type PDA.
Methods: In total, 102 primary solid-type PDA cases were retrieved, and classified into 46 deficient-MMR (dMMR) and 56 proficient-MMR (pMMR) cases based on immunohistochemistry (IHC) and polymerase chain reaction-based molecular testing results. The mRNA expression profiles (NanoString nCounter Assay) of stage-matched dMMR (n = 6) and pMMR (n = 6) cases were examined. The CXCR2 expression and MDSC infiltration (CD11b- and CD33-positive cells) were investigated via IHC in all solid-type PDA cases.
Results: mRNA analysis revealed several differentially expressed genes and differences in biological behavior between the dMMR (n = 46) and pMMR (n = 56) groups. In the multivariate analysis, the dMMR status was significantly associated with a longer disease-free survival (hazard ratio = 5.152, p = 0.002) and overall survival (OS) (hazard ratio = 5.050, p = 0.005). CXCR2-high expression was significantly correlated with a shorter OS in the dMMR group (p = 0.018). A high infiltration of CD11b- and CD33-positive cells was significantly correlated with a shorter OS in the pMMR group (p = 0.022, 0.016, respectively).
Conclusions: dMMR status can be a useful prognostic predictor, and CXCR2 and MDSCs can be novel therapeutic targets in patients with solid-type PDA.
{"title":"Clinicopathological significance of microsatellite instability and immune escape mechanism in patients with gastric solid-type poorly differentiated adenocarcinoma.","authors":"Shinya Umekita, Daisuke Kiyozawa, Kenichi Kohashi, Shinichiro Kawatoko, Taisuke Sasaki, Eikichi Ihara, Eiji Oki, Masafumi Nakamura, Yoshihiro Ogawa, Yoshinao Oda","doi":"10.1007/s10120-024-01474-w","DOIUrl":"10.1007/s10120-024-01474-w","url":null,"abstract":"<p><strong>Background: </strong>In gastric solid-type poorly differentiated adenocarcinoma (PDA), the role of microsatellite instability and immune escape mechanism remains unclear. The current study aimed to elucidate the clinical significance of mismatch repair (MMR) status, genome profile, C-X-C motif chemokine receptor 2 (CXCR2) expression, and myeloid-derived suppressor cell (MDSC) infiltration in solid-type PDA.</p><p><strong>Methods: </strong>In total, 102 primary solid-type PDA cases were retrieved, and classified into 46 deficient-MMR (dMMR) and 56 proficient-MMR (pMMR) cases based on immunohistochemistry (IHC) and polymerase chain reaction-based molecular testing results. The mRNA expression profiles (NanoString nCounter Assay) of stage-matched dMMR (n = 6) and pMMR (n = 6) cases were examined. The CXCR2 expression and MDSC infiltration (CD11b- and CD33-positive cells) were investigated via IHC in all solid-type PDA cases.</p><p><strong>Results: </strong>mRNA analysis revealed several differentially expressed genes and differences in biological behavior between the dMMR (n = 46) and pMMR (n = 56) groups. In the multivariate analysis, the dMMR status was significantly associated with a longer disease-free survival (hazard ratio = 5.152, p = 0.002) and overall survival (OS) (hazard ratio = 5.050, p = 0.005). CXCR2-high expression was significantly correlated with a shorter OS in the dMMR group (p = 0.018). A high infiltration of CD11b- and CD33-positive cells was significantly correlated with a shorter OS in the pMMR group (p = 0.022, 0.016, respectively).</p><p><strong>Conclusions: </strong>dMMR status can be a useful prognostic predictor, and CXCR2 and MDSCs can be novel therapeutic targets in patients with solid-type PDA.</p>","PeriodicalId":12684,"journal":{"name":"Gastric Cancer","volume":null,"pages":null},"PeriodicalIF":7.4,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140027875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: This randomized phase II study explored the superiority of trastuzumab plus S-1 plus cisplatin (SP) over SP alone as neoadjuvant chemotherapy (NAC) for HER2-positive resectable gastric cancer with extensive lymph node metastasis.
Methods: Eligible patients with HER2-positive gastric or esophagogastric junction cancer and extensive lymph node metastasis were randomized to receive three or four courses of preoperative chemotherapy with SP (arm A) or SP plus trastuzumab (arm B). Following gastrectomy, adjuvant chemotherapy with S-1 was administered for 1 year in both arms. The primary endpoint was overall survival, and the sample size was 130 patients in total. The trial is registered with the Japan Registry of Clinical Trials, jRCTs031180006.
Results: This report elucidates the early endpoints, including pathological findings and safety. The study was terminated early due to slow patient accruals. In total, 46 patients were allocated to arm A (n = 22) and arm B (n = 24). NAC was completed in 20 patients (91%) in arm A and 23 patients (96%) in arm B, with similar incidences of grade 3-4 hematological and non-hematological adverse events. Objective response rates were 50% in arm A and 84% in arm B (p = 0·065). %R0 resection rates were 91% and 92%, and pathological response rates (≥ grade 1b in Japanese classification) were 23% and 50% (p = 0·072) in resected patients, respectively.
Conclusions: Trastuzumab can be safely added to platinum-containing doublet chemotherapy as NAC, and it has the potential to contribute to higher antitumor activity against locally advanced, HER2-positive gastric or esophagogastric junction cancer with extensive nodal metastasis.
研究背景这项随机II期研究探讨了曲妥珠单抗加S-1加顺铂(SP)作为HER2阳性可切除胃癌伴广泛淋巴结转移的新辅助化疗(NAC)优于单用SP的情况:符合条件的HER2阳性胃癌或食管胃交界处癌且有广泛淋巴结转移的患者被随机分配接受三或四个疗程的术前SP化疗(A组)或SP加曲妥珠单抗化疗(B组)。胃切除术后,两组患者均接受为期一年的S-1辅助化疗。主要终点是总生存期,样本量为 130 例患者。该试验已在日本临床试验注册中心(JRCTs031180006)注册:本报告阐明了早期终点,包括病理结果和安全性。由于患者招募缓慢,研究提前结束。共有 46 名患者被分配到 A 组(22 人)和 B 组(24 人)。A组有20名患者(91%)完成了新农合治疗,B组有23名患者(96%)完成了新农合治疗,3-4级血液学和非血液学不良反应发生率相似。A组的客观反应率为50%,B组为84%(P = 0-065)。%R0切除率分别为91%和92%,切除患者的病理反应率(日本分类≥1b级)分别为23%和50%(p = 0-072):结论:曲妥珠单抗可作为 NAC 安全添加到含铂双联化疗中,并有可能提高对局部晚期、HER2 阳性、广泛结节转移的胃癌或食管胃交界癌的抗肿瘤活性。
{"title":"Early endpoints of a randomized phase II trial of preoperative chemotherapy with S-1/CDDP with or without trastuzumab followed by surgery for HER2-positive resectable gastric or esophagogastric junction adenocarcinoma with extensive lymph node metastasis: Japan Clinical Oncology Group study JCOG1301C (Trigger Study).","authors":"Masanori Tokunaga, Nozomu Machida, Junki Mizusawa, Seiji Ito, Hiroshi Yabusaki, Motohiro Hirao, Masaya Watanabe, Hiroshi Imamura, Takahiro Kinoshita, Takushi Yasuda, Jun Hihara, Haruhiko Fukuda, Takaki Yoshikawa, Narikazu Boku, Masanori Terashima","doi":"10.1007/s10120-024-01467-9","DOIUrl":"10.1007/s10120-024-01467-9","url":null,"abstract":"<p><strong>Background: </strong>This randomized phase II study explored the superiority of trastuzumab plus S-1 plus cisplatin (SP) over SP alone as neoadjuvant chemotherapy (NAC) for HER2-positive resectable gastric cancer with extensive lymph node metastasis.</p><p><strong>Methods: </strong>Eligible patients with HER2-positive gastric or esophagogastric junction cancer and extensive lymph node metastasis were randomized to receive three or four courses of preoperative chemotherapy with SP (arm A) or SP plus trastuzumab (arm B). Following gastrectomy, adjuvant chemotherapy with S-1 was administered for 1 year in both arms. The primary endpoint was overall survival, and the sample size was 130 patients in total. The trial is registered with the Japan Registry of Clinical Trials, jRCTs031180006.</p><p><strong>Results: </strong>This report elucidates the early endpoints, including pathological findings and safety. The study was terminated early due to slow patient accruals. In total, 46 patients were allocated to arm A (n = 22) and arm B (n = 24). NAC was completed in 20 patients (91%) in arm A and 23 patients (96%) in arm B, with similar incidences of grade 3-4 hematological and non-hematological adverse events. Objective response rates were 50% in arm A and 84% in arm B (p = 0·065). %R0 resection rates were 91% and 92%, and pathological response rates (≥ grade 1b in Japanese classification) were 23% and 50% (p = 0·072) in resected patients, respectively.</p><p><strong>Conclusions: </strong>Trastuzumab can be safely added to platinum-containing doublet chemotherapy as NAC, and it has the potential to contribute to higher antitumor activity against locally advanced, HER2-positive gastric or esophagogastric junction cancer with extensive nodal metastasis.</p>","PeriodicalId":12684,"journal":{"name":"Gastric Cancer","volume":null,"pages":null},"PeriodicalIF":7.4,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139502341","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-01Epub Date: 2024-02-28DOI: 10.1007/s10120-024-01477-7
Su Youn Nam, Junwoo Jo, Seong Woo Jeon
Background: The relationship between high-density lipoprotein cholesterol (HDL-C) and gastroesophageal cancer is not constant.
Methods: In this population-based cohort study, 4.518 million cancer-free individuals among those who underwent national cancer screening in 2010 were enrolled and followed up until December 2017. HDL-C level was classified into eight groups at 10 mg/dL intervals. The risk of gastroesophageal cancers by HDL-C was measured using adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs).
Results: During 8 years of follow-up, 38,362 gastric and 3022 esophageal cancers developed. Low HDL-C level was associated with an increased risk of gastric cancer; aHR was 1.19 (95% CI 1.09-1.30) for HDL-C < 30 mg/dL, 1.07 (95% CI 1.03-1.12) for HDL-C of 30-39 mg/dL, and 1.07 (95% CI 1.03-1.12) for HDL-C of 40-49 mg/dL comparing to HDL-C of 60-69 mg/dL. HDL-C was positively associated with esophageal cancer risk; aHR was 1.30 (1.12-1.51) for HDL-C of 70-79 mg/dL, 1.84 (1.53-2.22) for HDL-C of 80-89 mg/dL, 2.10 (1.67-2.61) for HDL-C ≥ 90 mg/dL. These site-specific effects of HDL-C were robust in sensitivity analyses. The range of HDL-C for the lowest cancer risk was different by sex and site. The hazardous effect of low HDL-C on gastric cancer was prominent in never and past smokers, and extremely high HDL-C increased gastric cancer risk (aHR 1.19; 95% CI 1.04-1.36) only in current smokers. Unfavorable effect of high HDL-C on gastroesophageal cancer risk was remarkable in smokers.
Conclusions: Low HDL-C increased the risk of gastric cancer, wherein high HDL-C was associated with esophageal cancer risk with discrepancies by sex and smoking status.
{"title":"Discrepant effect of high-density lipoprotein cholesterol on esophageal and gastric cancer risk in a nationwide cohort.","authors":"Su Youn Nam, Junwoo Jo, Seong Woo Jeon","doi":"10.1007/s10120-024-01477-7","DOIUrl":"10.1007/s10120-024-01477-7","url":null,"abstract":"<p><strong>Background: </strong>The relationship between high-density lipoprotein cholesterol (HDL-C) and gastroesophageal cancer is not constant.</p><p><strong>Methods: </strong>In this population-based cohort study, 4.518 million cancer-free individuals among those who underwent national cancer screening in 2010 were enrolled and followed up until December 2017. HDL-C level was classified into eight groups at 10 mg/dL intervals. The risk of gastroesophageal cancers by HDL-C was measured using adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs).</p><p><strong>Results: </strong>During 8 years of follow-up, 38,362 gastric and 3022 esophageal cancers developed. Low HDL-C level was associated with an increased risk of gastric cancer; aHR was 1.19 (95% CI 1.09-1.30) for HDL-C < 30 mg/dL, 1.07 (95% CI 1.03-1.12) for HDL-C of 30-39 mg/dL, and 1.07 (95% CI 1.03-1.12) for HDL-C of 40-49 mg/dL comparing to HDL-C of 60-69 mg/dL. HDL-C was positively associated with esophageal cancer risk; aHR was 1.30 (1.12-1.51) for HDL-C of 70-79 mg/dL, 1.84 (1.53-2.22) for HDL-C of 80-89 mg/dL, 2.10 (1.67-2.61) for HDL-C ≥ 90 mg/dL. These site-specific effects of HDL-C were robust in sensitivity analyses. The range of HDL-C for the lowest cancer risk was different by sex and site. The hazardous effect of low HDL-C on gastric cancer was prominent in never and past smokers, and extremely high HDL-C increased gastric cancer risk (aHR 1.19; 95% CI 1.04-1.36) only in current smokers. Unfavorable effect of high HDL-C on gastroesophageal cancer risk was remarkable in smokers.</p><p><strong>Conclusions: </strong>Low HDL-C increased the risk of gastric cancer, wherein high HDL-C was associated with esophageal cancer risk with discrepancies by sex and smoking status.</p>","PeriodicalId":12684,"journal":{"name":"Gastric Cancer","volume":null,"pages":null},"PeriodicalIF":7.4,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139982792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-01Epub Date: 2024-03-02DOI: 10.1007/s10120-024-01487-5
Dag Holmberg, Joonas H Kauppila, Johannes Asplund, Wilhelm Leijonmarck, Fredrik Mattsson, Jesper Lagergren
Background: Studies have suggested that medication with statins improves survival in patients with gastric cancer, but methodological issues have limited the interpretability and prohibited conclusive results. We aimed to provide valid evidence as to whether statin use improves survival of gastric adenocarcinoma.
Methods: This nationwide and population-based cohort study included virtually all patients who underwent curatively intended surgery (gastrectomy) for gastric adenocarcinoma in Sweden between 2006 and 2015 with follow-up throughout 2019 for disease-specific mortality and 2020 for all-cause mortality. Data came from medical records and national healthcare registries. The exposure was statin use during the year prior to gastrectomy which was compared to no such use during the same period. The outcomes were 5-year disease-specific mortality (main) and 5-year all-cause mortality (secondary). Multivariable Cox regression provided hazard ratios (HR) with 95% confidence intervals (CI), adjusted for age, sex, education, calendar year, comorbidity, low-dose aspirin use, tumour sublocation, pathological tumour stage, neoadjuvant chemotherapy, annual surgeon volume, and surgical radicality.
Results: Among 1515 participating patients, the mean age was 69 years and 58.4% were men. Statin use, identified in 399 (26.3%) patients, was not associated with any statistically significantly decreased 5-year disease-specific mortality (HR 0.99, 95% CI 0.82-1.21) or 5-year all-cause mortality (HR 0.94, 95% CI 0.79-1.12). No risk reductions were found across subgroups of age, sex, aspirin user status, or tumour stage, or in patients with long-term preoperative of postoperative use of statins, all with point estimates close to 1.
Conclusions: Perioperative use of statins does not seem to improve the 5-year survival in patients who undergo gastrectomy with curative intent for gastric adenocarcinoma in Sweden.
背景:研究表明,他汀类药物可提高胃癌患者的生存率,但由于方法学问题,其可解释性受到限制,无法得出结论。我们旨在为他汀类药物是否能提高胃腺癌患者的生存率提供有效证据:这项基于人口的全国性队列研究纳入了 2006 年至 2015 年期间在瑞典接受胃腺癌根治性手术(胃切除术)的几乎所有患者,并在 2019 年和 2020 年分别对其疾病特异性死亡率和全因死亡率进行了随访。数据来自医疗记录和国家医疗登记。研究对象是胃切除术前一年使用他汀类药物的患者,并与同期未使用他汀类药物的患者进行比较。研究结果为5年疾病特异性死亡率(主要)和5年全因死亡率(次要)。经调整年龄、性别、教育程度、日历年、合并症、低剂量阿司匹林使用情况、肿瘤亚定位、肿瘤病理分期、新辅助化疗、外科医生年工作量和手术根治率后,多变量考克斯回归得出了危险比(HR)及95%置信区间(CI):在 1515 名参与研究的患者中,平均年龄为 69 岁,58.4% 为男性。399名(26.3%)患者使用了他汀类药物,但5年疾病特异性死亡率(HR 0.99,95% CI 0.82-1.21)或5年全因死亡率(HR 0.94,95% CI 0.79-1.12)均未出现统计学意义上的显著下降。在不同年龄、性别、阿司匹林使用者状况或肿瘤分期的亚组中,或在术前术后长期使用他汀类药物的患者中,均未发现风险降低的情况,其点估计值均接近1.结论:在瑞典,围手术期使用他汀类药物似乎并不能提高胃腺癌根治性胃切除术患者的5年生存率。
{"title":"Statin use in relation to long-term survival after gastrectomy for gastric adenocarcinoma: a Swedish population-based cohort study.","authors":"Dag Holmberg, Joonas H Kauppila, Johannes Asplund, Wilhelm Leijonmarck, Fredrik Mattsson, Jesper Lagergren","doi":"10.1007/s10120-024-01487-5","DOIUrl":"10.1007/s10120-024-01487-5","url":null,"abstract":"<p><strong>Background: </strong>Studies have suggested that medication with statins improves survival in patients with gastric cancer, but methodological issues have limited the interpretability and prohibited conclusive results. We aimed to provide valid evidence as to whether statin use improves survival of gastric adenocarcinoma.</p><p><strong>Methods: </strong>This nationwide and population-based cohort study included virtually all patients who underwent curatively intended surgery (gastrectomy) for gastric adenocarcinoma in Sweden between 2006 and 2015 with follow-up throughout 2019 for disease-specific mortality and 2020 for all-cause mortality. Data came from medical records and national healthcare registries. The exposure was statin use during the year prior to gastrectomy which was compared to no such use during the same period. The outcomes were 5-year disease-specific mortality (main) and 5-year all-cause mortality (secondary). Multivariable Cox regression provided hazard ratios (HR) with 95% confidence intervals (CI), adjusted for age, sex, education, calendar year, comorbidity, low-dose aspirin use, tumour sublocation, pathological tumour stage, neoadjuvant chemotherapy, annual surgeon volume, and surgical radicality.</p><p><strong>Results: </strong>Among 1515 participating patients, the mean age was 69 years and 58.4% were men. Statin use, identified in 399 (26.3%) patients, was not associated with any statistically significantly decreased 5-year disease-specific mortality (HR 0.99, 95% CI 0.82-1.21) or 5-year all-cause mortality (HR 0.94, 95% CI 0.79-1.12). No risk reductions were found across subgroups of age, sex, aspirin user status, or tumour stage, or in patients with long-term preoperative of postoperative use of statins, all with point estimates close to 1.</p><p><strong>Conclusions: </strong>Perioperative use of statins does not seem to improve the 5-year survival in patients who undergo gastrectomy with curative intent for gastric adenocarcinoma in Sweden.</p>","PeriodicalId":12684,"journal":{"name":"Gastric Cancer","volume":null,"pages":null},"PeriodicalIF":7.4,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11016510/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140012559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-01Epub Date: 2024-03-18DOI: 10.1007/s10120-024-01491-9
Zhe Wang, Da Li, Cheng Zhang
{"title":"Ethnic‑specific associations between body mass index and gastric cancer: a Mendelian randomization study in European and Korean populations.","authors":"Zhe Wang, Da Li, Cheng Zhang","doi":"10.1007/s10120-024-01491-9","DOIUrl":"10.1007/s10120-024-01491-9","url":null,"abstract":"","PeriodicalId":12684,"journal":{"name":"Gastric Cancer","volume":null,"pages":null},"PeriodicalIF":7.4,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140157953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: It remains unclear whether addition of docetaxel to the combination of a platinum and fluoropyrimidine could provide more clinical benefits than doublet chemotherapies in the perioperative treatment for locally advanced gastric/gastro-esophageal junction (LAG/GEJ) cancer in Asia. In this randomized, phase 2 study, we assessed the efficacy and safety of perioperative docetaxel plus oxaliplatin and S-1 (DOS) versus oxaliplatin plus S-1 (SOX) in LAG/GEJ adenocarcinoma patients.
Methods: Patients with cT3-4 Nany M0 G/GEJ adenocarcinoma were randomized (1:1) to receive 4 cycles of preoperative DOS or SOX followed by D2 gastrectomy and another 4 cycles of postoperative chemotherapy. The primary endpoint was major pathological response (MPR).
Results: From Aug, 2015 to Dec, 2019,154 patients were enrolled and 147 patients included in final analysis, with a median age of 60 (26-73) years. DOS resulted in significantly higher MPR (25.4 vs. 11.8%, P = 0.04). R0 resection rate, the 3-year PFS and 3-year OS rates were 78.9 vs. 61.8% (P = 0.02), 52.3 vs. 35% (HR 0.667, 95% CI: 0.432-1.029, Log rank P = 0.07) and 57.5 vs. 49.2% (HR 0.685, 95% CI: 0.429-1.095, Log rank P = 0.11) in the DOS and SOX groups, respectively. Patients who acquired MPR experienced significantly better survival. DOS had similar tolerance to SOX.
Conclusions: Perioperative DOS improved MPR significantly and tended to produce longer PFS compared to SOX in LAG/GEJ cancer in Asia, and might be considered as a preferred option for perioperative chemotherapy and worth further investigation.
背景:在亚洲,在局部晚期胃癌/胃食管交界处癌(LAG/GEJ)围手术期治疗中,在铂类和氟嘧啶类药物的组合中添加多西他赛是否能比双药化疗带来更多临床益处,目前仍不清楚。在这项随机2期研究中,我们评估了多西他赛+奥沙利铂和S-1(DOS)与奥沙利铂+S-1(SOX)在LAG/GEJ腺癌患者围手术期的疗效和安全性:cT3-4 Nany M0 G/GEJ腺癌患者随机(1:1)接受4个周期的术前DOS或SOX治疗,然后进行D2胃切除术和4个周期的术后化疗。主要终点为主要病理反应(MPR):2015年8月至2019年12月,154名患者入组,147名患者纳入最终分析,中位年龄为60(26-73)岁。DOS导致的MPR明显更高(25.4% vs. 11.8%,P = 0.04)。DOS组和SOX组的R0切除率、3年PFS和3年OS率分别为78.9% vs. 61.8%(P = 0.02)、52.3% vs. 35%(HR 0.667,95% CI:0.432-1.029,Log rank P = 0.07)和57.5% vs. 49.2%(HR 0.685,95% CI:0.429-1.095,Log rank P = 0.11)。获得 MPR 的患者生存率明显更高。DOS与SOX的耐受性相似:亚洲 LAG/GEJ 癌患者围手术期 DOS 能明显改善 MPR,与 SOX 相比,DOS 往往能延长 PFS,可作为围手术期化疗的首选方案,值得进一步研究。
{"title":"Perioperative chemotherapy with docetaxel plus oxaliplatin and S-1 (DOS) versus oxaliplatin plus S-1 (SOX) for the treatment of locally advanced gastric or gastro-esophageal junction adenocarcinoma (MATCH): an open-label, randomized, phase 2 clinical trial.","authors":"Zhichao Jiang, Yibin Xie, Wen Zhang, Chunxia Du, Yuxin Zhong, Yuelu Zhu, Liming Jiang, Lizhou Dou, Kang Shao, Yongkun Sun, Qi Xue, Yantao Tian, Shugeng Gao, Dongbing Zhao, Aiping Zhou","doi":"10.1007/s10120-024-01471-z","DOIUrl":"10.1007/s10120-024-01471-z","url":null,"abstract":"<p><strong>Background: </strong>It remains unclear whether addition of docetaxel to the combination of a platinum and fluoropyrimidine could provide more clinical benefits than doublet chemotherapies in the perioperative treatment for locally advanced gastric/gastro-esophageal junction (LAG/GEJ) cancer in Asia. In this randomized, phase 2 study, we assessed the efficacy and safety of perioperative docetaxel plus oxaliplatin and S-1 (DOS) versus oxaliplatin plus S-1 (SOX) in LAG/GEJ adenocarcinoma patients.</p><p><strong>Methods: </strong>Patients with cT3-4 N<sub>any</sub> M0 G/GEJ adenocarcinoma were randomized (1:1) to receive 4 cycles of preoperative DOS or SOX followed by D2 gastrectomy and another 4 cycles of postoperative chemotherapy. The primary endpoint was major pathological response (MPR).</p><p><strong>Results: </strong>From Aug, 2015 to Dec, 2019,154 patients were enrolled and 147 patients included in final analysis, with a median age of 60 (26-73) years. DOS resulted in significantly higher MPR (25.4 vs. 11.8%, P = 0.04). R0 resection rate, the 3-year PFS and 3-year OS rates were 78.9 vs. 61.8% (P = 0.02), 52.3 vs. 35% (HR 0.667, 95% CI: 0.432-1.029, Log rank P = 0.07) and 57.5 vs. 49.2% (HR 0.685, 95% CI: 0.429-1.095, Log rank P = 0.11) in the DOS and SOX groups, respectively. Patients who acquired MPR experienced significantly better survival. DOS had similar tolerance to SOX.</p><p><strong>Conclusions: </strong>Perioperative DOS improved MPR significantly and tended to produce longer PFS compared to SOX in LAG/GEJ cancer in Asia, and might be considered as a preferred option for perioperative chemotherapy and worth further investigation.</p>","PeriodicalId":12684,"journal":{"name":"Gastric Cancer","volume":null,"pages":null},"PeriodicalIF":7.4,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11016518/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140059122","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-01Epub Date: 2024-03-09DOI: 10.1007/s10120-024-01486-6
Yilin Li, Lei Jiang, Yang Chen, Yanyan Li, Jiajia Yuan, Jialin Lu, Zizhen Zhang, Shengde Liu, Xujiao Feng, Jiaxin Xiong, Yan Jiang, Xiaotian Zhang, Jian Li, Lin Shen
Background: Gastric cancer with peritoneal metastasis (PM-GC), recognized as one of the deadliest cancers. However, whether and how the tumor cell-extrinsic tumor microenvironment (TME) is involved in the therapeutic failure remains unknown. Thus, this study systematically assessed the immunosuppressive tumor microenvironment in ascites from patients with PM-GC, and its contribution to dissemination and immune evasion of ascites-disseminated tumor cells (aDTCs).
Methods: Sixty-three ascites and 43 peripheral blood (PB) samples from 51 patients with PM-GC were included in this study. aDTCs in ascites and circulating tumor cells (CTCs) in paired PB were immunophenotypically profiled. Using single-cell RNA transcriptional sequencing (scRNA-seq), crosstalk between aDTCs and the TME features of ascites was inspected. Further studies on the mechanism underlying aDTCs-immune cells crosstalk were performed on in vitro cultured aDTCs.
Results: Immune cells in ascites interact with aDTCs, prompting their immune evasion. Specifically, we found that the tumor-associated macrophages (TAMs) in ascites underwent a continuum lineage transition from cathepsinhigh (CTShigh) to complement 1qhigh (C1Qhigh) TAM. CTShigh TAM initially attracted the metastatic tumor cells to ascites, thereafter, transitioning terminally to C1Qhigh TAM to trigger overproliferation and immune escape of aDTCs. Mechanistically, we demonstrated that C1Qhigh TAMs significantly enhanced the expression of PD-L1 and NECTIN2 on aDTCs, which was driven by the activation of the C1q-mediated complement pathway.
Conclusions: For the first time, we identified an immunosuppressive macrophage transition from CTShigh to C1Qhigh TAM in ascites from patients with PM-GC. This may contribute to developing potential TAM-targeted immunotherapies for PM-GC.
{"title":"Specific lineage transition of tumor-associated macrophages elicits immune evasion of ascitic tumor cells in gastric cancer with peritoneal metastasis.","authors":"Yilin Li, Lei Jiang, Yang Chen, Yanyan Li, Jiajia Yuan, Jialin Lu, Zizhen Zhang, Shengde Liu, Xujiao Feng, Jiaxin Xiong, Yan Jiang, Xiaotian Zhang, Jian Li, Lin Shen","doi":"10.1007/s10120-024-01486-6","DOIUrl":"10.1007/s10120-024-01486-6","url":null,"abstract":"<p><strong>Background: </strong>Gastric cancer with peritoneal metastasis (PM-GC), recognized as one of the deadliest cancers. However, whether and how the tumor cell-extrinsic tumor microenvironment (TME) is involved in the therapeutic failure remains unknown. Thus, this study systematically assessed the immunosuppressive tumor microenvironment in ascites from patients with PM-GC, and its contribution to dissemination and immune evasion of ascites-disseminated tumor cells (aDTCs).</p><p><strong>Methods: </strong>Sixty-three ascites and 43 peripheral blood (PB) samples from 51 patients with PM-GC were included in this study. aDTCs in ascites and circulating tumor cells (CTCs) in paired PB were immunophenotypically profiled. Using single-cell RNA transcriptional sequencing (scRNA-seq), crosstalk between aDTCs and the TME features of ascites was inspected. Further studies on the mechanism underlying aDTCs-immune cells crosstalk were performed on in vitro cultured aDTCs.</p><p><strong>Results: </strong>Immune cells in ascites interact with aDTCs, prompting their immune evasion. Specifically, we found that the tumor-associated macrophages (TAMs) in ascites underwent a continuum lineage transition from cathepsin<sup>high</sup> (CTS<sup>high</sup>) to complement 1q<sup>high</sup> (C1Q<sup>high</sup>) TAM. CTS<sup>high</sup> TAM initially attracted the metastatic tumor cells to ascites, thereafter, transitioning terminally to C1Q<sup>high</sup> TAM to trigger overproliferation and immune escape of aDTCs. Mechanistically, we demonstrated that C1Q<sup>high</sup> TAMs significantly enhanced the expression of PD-L1 and NECTIN2 on aDTCs, which was driven by the activation of the C1q-mediated complement pathway.</p><p><strong>Conclusions: </strong>For the first time, we identified an immunosuppressive macrophage transition from CTS<sup>high</sup> to C1Q<sup>high</sup> TAM in ascites from patients with PM-GC. This may contribute to developing potential TAM-targeted immunotherapies for PM-GC.</p>","PeriodicalId":12684,"journal":{"name":"Gastric Cancer","volume":null,"pages":null},"PeriodicalIF":7.4,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11016508/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140068330","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Laparoscopy-assisted gastrectomy (LG) is rapidly gaining popularity owing to its minimal invasiveness. Previous studies have found that compared with two-dimensional (2D)-LG, three-dimensional (3D)-LG showed better short-term outcomes. However, the long-term oncological outcomes in patients with locally resectable gastric cancer (GC) remain controversial.
Methods: In this noninferiority, open-label, randomized clinical trial, a total of 438 eligible GC participants were randomly assigned in a 1:1 ratio to either 3D-LG or 2D-LG from January 2015 to April 2016. The primary endpoint was operating time, while the secondary endpoints included 5-year overall survival (OS), disease-free survival (DFS), and recurrence pattern.
Results: Data from 401 participants were included in the per-protocol analysis, with 204 patients in the 3D group and 197 patients in the 2D group. The 5-year OS and DFS rates were comparable between the 3D and 2D groups (5-year OS: 70.6% vs. 71.1%, Log-rank P = 0.743; 5-year DFS: 68.1% vs. 69.0%, log-rank P = 0.712). No significant differences were observed between the 3D and 2D groups in the 5-year recurrence rate (28.9% vs. 28.9%, P = 0.958) or recurrence time (mean time, 22.6 vs. 20.5 months, P = 0.412). Further stratified analysis based on the type of gastrectomy, postoperative pathological staging, and preoperative BMI showed that the 5-year OS, DFS, and recurrence rates of the 3D group in each subgroup were similar to those of the 2D group (all P > 0.05).
Conclusions: For patients with locally resectable GC, 3D-LG performed by experienced surgeons in high-volume professional institutions can achieve long-term oncological outcomes comparable to those of 2D-LG.
背景:腹腔镜辅助胃切除术(LG)因其微创性而迅速普及。以往的研究发现,与二维(2D)胃切除术相比,三维(3D)胃切除术的短期疗效更好。然而,局部可切除胃癌(GC)患者的长期肿瘤治疗效果仍存在争议:在这项非劣效性、开放标签、随机临床试验中,从2015年1月到2016年4月,共有438名符合条件的GC参与者按1:1的比例被随机分配到3D-LG或2D-LG中。主要终点是手术时间,次要终点包括5年总生存期(OS)、无病生存期(DFS)和复发模式:来自401名参与者的数据被纳入按方案分析,其中三维组204名患者,二维组197名患者。三维组和二维组的 5 年 OS 和 DFS 率相当(5 年 OS:70.6% vs. 71.1%,Log-rank P = 0.743;5 年 DFS:68.1% vs. 69.0%,Log-rank P = 0.712)。在5年复发率(28.9% vs. 28.9%,P = 0.958)或复发时间(平均时间22.6个月 vs. 20.5个月,P = 0.412)方面,3D组和2D组之间未观察到明显差异。根据胃切除术类型、术后病理分期和术前体重指数进行的进一步分层分析表明,各亚组中三维组的5年OS、DFS和复发率与二维组相似(P均>0.05):结论:对于局部可切除的 GC 患者,由经验丰富的外科医生在大样本量的专业机构进行 3D-LG 治疗,可获得与 2D-LG 相媲美的长期肿瘤治疗效果:NCT02327481 ( http://clinicaltrials.gov ).
{"title":"Long-term oncological outcomes of 3D versus 2D laparoscopic gastrectomy for gastric cancer: a randomized clinical trial.","authors":"Qing Zhong, Jun-Yu Chen, Zhi-Xin Shang-Guan, Zhi-Yu Liu, Guang-Tan Lin, Dong Wu, Yi-Ming Jiang, Jia-Bin Wang, Jian-Xian Lin, Qi-Yue Chen, Ju-Li Lin, Jian-Wei Xie, Ping Li, Jun Lu, Chang-Ming Huang, Chao-Hui Zheng","doi":"10.1007/s10120-024-01470-0","DOIUrl":"10.1007/s10120-024-01470-0","url":null,"abstract":"<p><strong>Background: </strong>Laparoscopy-assisted gastrectomy (LG) is rapidly gaining popularity owing to its minimal invasiveness. Previous studies have found that compared with two-dimensional (2D)-LG, three-dimensional (3D)-LG showed better short-term outcomes. However, the long-term oncological outcomes in patients with locally resectable gastric cancer (GC) remain controversial.</p><p><strong>Methods: </strong>In this noninferiority, open-label, randomized clinical trial, a total of 438 eligible GC participants were randomly assigned in a 1:1 ratio to either 3D-LG or 2D-LG from January 2015 to April 2016. The primary endpoint was operating time, while the secondary endpoints included 5-year overall survival (OS), disease-free survival (DFS), and recurrence pattern.</p><p><strong>Results: </strong>Data from 401 participants were included in the per-protocol analysis, with 204 patients in the 3D group and 197 patients in the 2D group. The 5-year OS and DFS rates were comparable between the 3D and 2D groups (5-year OS: 70.6% vs. 71.1%, Log-rank P = 0.743; 5-year DFS: 68.1% vs. 69.0%, log-rank P = 0.712). No significant differences were observed between the 3D and 2D groups in the 5-year recurrence rate (28.9% vs. 28.9%, P = 0.958) or recurrence time (mean time, 22.6 vs. 20.5 months, P = 0.412). Further stratified analysis based on the type of gastrectomy, postoperative pathological staging, and preoperative BMI showed that the 5-year OS, DFS, and recurrence rates of the 3D group in each subgroup were similar to those of the 2D group (all P > 0.05).</p><p><strong>Conclusions: </strong>For patients with locally resectable GC, 3D-LG performed by experienced surgeons in high-volume professional institutions can achieve long-term oncological outcomes comparable to those of 2D-LG.</p><p><strong>Registration number: </strong>NCT02327481 ( http://clinicaltrials.gov ).</p>","PeriodicalId":12684,"journal":{"name":"Gastric Cancer","volume":null,"pages":null},"PeriodicalIF":7.4,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139912412","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-01Epub Date: 2024-03-04DOI: 10.1007/s10120-024-01485-7
Gerardo A Vitiello, Vetri Sudar Jayaprakasam, Laura H Tang, Mark A Schattner, Yelena Y Janjigian, Geoffrey Y Ku, Steven B Maron, Heiko Schoder, Steven M Larson, Mithat Gönen, Jashodeep Datta, Daniel G Coit, Murray F Brennan, Vivian E Strong
Background: PET-CT-based patient metabolic profiling is a novel concept to incorporate patient-specific metabolism into gastric cancer care.
Methods: Staging PET-CTs, demographics, and clinicopathologic variables of gastric cancer patients were obtained from a prospectively maintained institutional database. PET-CT avidity was measured in tumor, liver, spleen, four paired muscles, and two paired fat areas in each patient. The liver to rectus femoris (LRF) ratio was defined as the ratio of SUVmean of liver to the average SUVmean of the bilateral rectus femoris muscles. Kaplan-Meier and Cox-proportional hazards models were used to identify the impact of LRF ratio on OS.
Results: Two hundred and one patients with distal gastroesophageal (48%) or gastric (52%) adenocarcinoma were included. Median age was 65 years, and 146 (73%) were male. On univariate analysis, rectus femoris PET-CT avidity and LRF ratio were significantly associated with overall survival (p < 0.05). LRF ratio was significantly higher in males, early-stage cancer, patients with an ECOG 0 or 1 performance status, patients with albumin > 3.5 mg/dL, and those with moderately differentiated tumor histology. In multivariable regression, gastric cancer stage, albumin, and LRF ratio were significant independent predictors of overall survival (LRF ratio HR = 0.73 (0.56-0.96); p = 0.024). Survival curves showed that the prognostic impact of LRF was associated with metastatic gastric cancer (p = 0.009).
Conclusions: Elevated LRF ratio, a patient-specific PET-CT-based metabolic parameter, was independently associated with an improvement in OS in patients with metastatic gastric cancer. With prospective validation, LRF ratio may be a useful, host-specific metabolic parameter for prognostication in gastric cancer.
{"title":"Patient metabolic profile defined by liver and muscle <sup>18</sup>F-FDG PET avidity is independently associated with overall survival in gastric cancer.","authors":"Gerardo A Vitiello, Vetri Sudar Jayaprakasam, Laura H Tang, Mark A Schattner, Yelena Y Janjigian, Geoffrey Y Ku, Steven B Maron, Heiko Schoder, Steven M Larson, Mithat Gönen, Jashodeep Datta, Daniel G Coit, Murray F Brennan, Vivian E Strong","doi":"10.1007/s10120-024-01485-7","DOIUrl":"10.1007/s10120-024-01485-7","url":null,"abstract":"<p><strong>Background: </strong>PET-CT-based patient metabolic profiling is a novel concept to incorporate patient-specific metabolism into gastric cancer care.</p><p><strong>Methods: </strong>Staging PET-CTs, demographics, and clinicopathologic variables of gastric cancer patients were obtained from a prospectively maintained institutional database. PET-CT avidity was measured in tumor, liver, spleen, four paired muscles, and two paired fat areas in each patient. The liver to rectus femoris (LRF) ratio was defined as the ratio of SUV<sub>mean</sub> of liver to the average SUV<sub>mean</sub> of the bilateral rectus femoris muscles. Kaplan-Meier and Cox-proportional hazards models were used to identify the impact of LRF ratio on OS.</p><p><strong>Results: </strong>Two hundred and one patients with distal gastroesophageal (48%) or gastric (52%) adenocarcinoma were included. Median age was 65 years, and 146 (73%) were male. On univariate analysis, rectus femoris PET-CT avidity and LRF ratio were significantly associated with overall survival (p < 0.05). LRF ratio was significantly higher in males, early-stage cancer, patients with an ECOG 0 or 1 performance status, patients with albumin > 3.5 mg/dL, and those with moderately differentiated tumor histology. In multivariable regression, gastric cancer stage, albumin, and LRF ratio were significant independent predictors of overall survival (LRF ratio HR = 0.73 (0.56-0.96); p = 0.024). Survival curves showed that the prognostic impact of LRF was associated with metastatic gastric cancer (p = 0.009).</p><p><strong>Conclusions: </strong>Elevated LRF ratio, a patient-specific PET-CT-based metabolic parameter, was independently associated with an improvement in OS in patients with metastatic gastric cancer. With prospective validation, LRF ratio may be a useful, host-specific metabolic parameter for prognostication in gastric cancer.</p>","PeriodicalId":12684,"journal":{"name":"Gastric Cancer","volume":null,"pages":null},"PeriodicalIF":7.4,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140021413","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}