Gastric Cancer最新文献

{"title":"Multi-omics sequencing of gastroesophageal junction adenocarcinoma reveals prognosis-relevant key factors and a novel immunogenomic classification.","authors":"Zhao Ma, Mengting Li, Fuqiang Li, Kui Wu, Xianxian Wu, Tian Luo, Na Gao, Huijuan Luo, Zhilin Sui, Zhentao Yu, Hongjing Jiang, Xiaobin Shang, Chuangui Chen, Jie Yue, Fianbiao Meng, Xiaofeng Duan, Bo Xu","doi":"10.1007/s10120-025-01585-y","DOIUrl":"https://doi.org/10.1007/s10120-025-01585-y","url":null,"abstract":"<p><strong>Background: </strong>Gastroesophageal junction adenocarcinoma (GEJAC) exhibits distinct molecular characteristics due to its unique anatomical location. We sought to investigate effective and reliable molecular classification of GEJAC to guide personalized treatment.</p><p><strong>Methods: </strong>We analyzed the whole genomic, transcriptomic, T-cell receptor repertoires, and immunohistochemical data in 92 GEJAC patients and delineated the landscape of genetic and immune alterations. In addition to COSMIC nomenclature, the de novo nomenclature was also utilized to define signatures and investigate their correlation with survival. A novel molecular subtype was developed and validated in other cohorts.</p><p><strong>Results: </strong>We found 30 mutated driver genes, 7 novel genomic signatures, 3 copy-number variations, and 2 V-J gene usages related to prognosis that were not identified in previous study. A high frequency of COSMIC-SBS-384-1 and De novo-SV-32-A was associated with more neoantigen generation and a better survival. Using 19 molecular features, we identified three immune-related subtypes (immune inflamed, intermediate, and deserted) with discrete profiles of genomic signatures, immune status, and clinical outcome. The immune deserted subtype (27.2%) was characterized by an earlier KRAS mutation, worse immune reaction, and prognosis than the other two subtypes. The immune inflamed subtypes exhibited the highest levels of neoantigens, TCR/pMHC-binding strength, CD8 + T-cell infiltration, IFN-α/γ response pathways, and survival rate.</p><p><strong>Conclusions: </strong>These results emphasize the immune reaction and prognostic value of novel molecular classifications based on multi-omics data and provide a solid basis for better management of GEJAC.</p>","PeriodicalId":12684,"journal":{"name":"Gastric Cancer","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143065238","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}

{"title":"Differential impact of frailty on surgical and non-surgical site complications in patients with gastric cancer undergoing gastrectomy.","authors":"Katsunobu Sakurai, Naoshi Kubo, Tatsuro Tamura, Tsuyoshi Hasegawa, Yutaka Tamamori, Junya Nishimura, Yasuhito Iseki, Takafumi Nishii, Toru Inoue, Masakazu Yashiro, Yukio Nishiguchi, Tsubasa Bito, Kiyoshi Maeda","doi":"10.1007/s10120-025-01590-1","DOIUrl":"https://doi.org/10.1007/s10120-025-01590-1","url":null,"abstract":"<p><strong>Background: </strong>The aim of this study was to determine the differential impact of frailty on surgical site complications (SSCs) and non-surgical site complications (non-SSCs) in gastric cancer (GC) patients undergoing gastrectomy.</p><p><strong>Methods: </strong>In this study, frailty was assessed preoperatively using a frailty index (FI) in 395 patients scheduled for gastrectomy for GC between January 2016 and December 2023. Patients were divided into two groups (high FI vs. low FI) to examine the impact of frailty on SSC and non-SSC.</p><p><strong>Results: </strong>Overall complication and non-SSC rates were significantly higher in the high FI group, but the two groups had similar rates of SSC. In multivariate analysis, high FI, high BMI, and male were independent risk factors for non-SSC. The incidence of non-SSC was 0% in patients with no applicable risk factors, 3.6% in patients with one applicable risk factor, 13.0% in patients with two applicable risk factors, and 37.1% in patients with all three risk factors (Cochran-Armitage trend test, p < 0.001). The area under the curve (AUC) of the risk prediction model using these three variables to predict non-SSC was 0.760.</p><p><strong>Conclusions: </strong>High FI was an independent risk factor for non-SSC in patients undergoing gastrectomy for GC. Our developed non-SSC risk model combining FI, BMI, and sex effectively identifies individuals at increased risk for non-SSC in GC patients.</p>","PeriodicalId":12684,"journal":{"name":"Gastric Cancer","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143058787","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}

{"title":"Cardiovascular and thromboembolic outcomes with immune checkpoint inhibitors in gastroesophageal cancer: a propensity score-matched cohort study.","authors":"Furkan Bahar, Betul Ibis, Sena Cakir Colak, Akshat Banga, Junmin Song, Yu-Cheng Chang, Kuan-Yu Chi, Yu Chang, Cho-Hung Chiang, Cho-Han Chiang","doi":"10.1007/s10120-025-01582-1","DOIUrl":"https://doi.org/10.1007/s10120-025-01582-1","url":null,"abstract":"<p><strong>Background: </strong>Immune checkpoint inhibitors (ICIs) have been associated with an increased risk of cardiovascular and thromboembolic events. However, the incidence of cardiovascular and thromboembolic events associated with ICIs in gastroesophageal cancers is unknown.</p><p><strong>Methods: </strong>We performed a propensity score-matched cohort study using the TriNetX Analytics Network database, which comprises de-identified data from over 130 participating healthcare institutions. Patients who received ICI and chemotherapy were compared with those who received only chemotherapy. The primary outcomes were cardiovascular events including pericarditis, myocarditis, heart failure, myocardial infarction, ischemic stroke, atrial fibrillation, conduction disorders as well as venous thromboembolism (VTE) within 1-year of ICI or chemotherapy. We matched the cohorts based on predetermined variables including demographics, metastatic disease, chemotherapy, underlying comorbidities, and the use of cardiovascular and lipid-lowering medications.</p><p><strong>Results: </strong>We identified 1,448 patients who received ICI and chemotherapy and 11,966 patients who received chemotherapy only. After matching, 1,425 patients remained in each cohort. The mean age was 63.1 ± 12.7 years in the ICI and chemotherapy cohort and 62.9 ± 12.1 years in the chemotherapy-only cohort. ICI was associated with a higher incidence of pericarditis (45.6 vs. 30.9 cases per 1000 patient-years; HR 1.51 [95% CI 1.03-2.22]) and VTE (102.5 vs. 75.1 cases per 1000 patient-years; HR 1.40 [95% CI 1.09-1.80]). The incidence of other cardiovascular outcomes were similar between the two cohorts.</p><p><strong>Conclusion: </strong>In this cohort study, the use of ICI and chemotherapy was associated with an approximately 40-50% increased risk of pericarditis and VTE than patients on chemotherapy only.</p>","PeriodicalId":12684,"journal":{"name":"Gastric Cancer","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143004254","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}

{"title":"A Japanese family of hereditary diffuse gastric cancer with a germline pathogenic variant of CTNN1A detected via comprehensive genome profiling.","authors":"Takeshi Kawakami, Hiroyuki Matsubayashi, Yoshimi Kiyozumi, Rina Harada, Eiko Ishihara, Masao Yoshida, Hiroyuki Ono, Etsuro Bando, Masakuni Serizawa, Takashi Sugino","doi":"10.1007/s10120-025-01583-0","DOIUrl":"https://doi.org/10.1007/s10120-025-01583-0","url":null,"abstract":"<p><p>CTNNA1 codes α-1 catenin, a molecule that functions in intercellular adhesion in combination with E-cadherin (coded by CDH1). A germline pathogenic variant (GPV) of CTNNA1 increases the risk of hereditary diffuse gastric cancer (HDGC); however, this GPV has not been reported in Japan. A 35-year-old Japanese man with an advanced gastric cancer underwent comprehensive genome profiling (CGP), which led to the detection of a CTNNA1 GPV (p.Q662*). His gastric cancer tissues demonstrated a loss of α-1 catenin expression. His mother with a history of gastric signet-ring cell carcinoma had undergone genetic counseling 2 years ago, because of her broad family history of young-onset gastric cancer. Then, she had undergone germline multigene panel testing (MGPT) that included CDH1 but not CTNNA1, and no GPV had been detected. Here, Japanese precision cancer medicine revealed a GPV of a gene rarely associated with HDGC, that could not be detected by common MGPTs.</p>","PeriodicalId":12684,"journal":{"name":"Gastric Cancer","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143004250","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}

{"title":"Minimum resection length to ensure a pathologically negative distal margin and a larger remnant stomach for esophagogastric junction cancer.","authors":"Qingjiang Hu, Manabu Ohashi, Motonari Ri, Rie Makuuchi, Tomoyuki Irino, Masaru Hayami, Takeshi Sano, Souya Nunobe","doi":"10.1007/s10120-025-01581-2","DOIUrl":"https://doi.org/10.1007/s10120-025-01581-2","url":null,"abstract":"<p><strong>Background: </strong>Ensuring a pathologically negative distal margin (DM) and preserving a larger remnant stomach is important for proximal gastrectomy (PG) in patients with esophagogastric junction (EGJ) cancer. However, the minimum DM length for ensuring negative margins has not been identified.</p><p><strong>Methods: </strong>We enrolled patients undergoing PG or total gastrectomy for EGJ cancer. A parameter ΔDM, representing the pathological extension distally beyond the gross tumor boundary, was evaluated. The maximum ΔDM, which indicates the minimum length ensuring a pathologically negative DM, was determined in all patients. Subgroup analyses were performed according to factors associated with ΔDM > 10 mm. The possible incidences of pathologically positive DM based on gross DM length were also calculated.</p><p><strong>Results: </strong>Among 253 eligible patients, the maximum ΔDM was 55 mm. Growth and pathological types were significantly associated with ΔDM > 10 mm. In subgroup analyses, the maximum ΔDM was 30/20/55 mm for the superficial/expansive/infiltrative growth types, and 55/40 mm for the differentiated/undifferentiated types. In the infiltrative growth type alone, the maximum ΔDM remained 55/40 mm for the differentiated/undifferentiated types. However, even if the gross DM length was reduced to 30 mm, the possible incidence of pathologically positive DM only increased to 2.6% in the infiltrative differentiated type.</p><p><strong>Conclusion: </strong>We recommend a minimum DM length of 30/20/55 mm for the superficial/expansive/ infiltrative growth types. Specifically in the infiltrative growth type, we alternatively recommend 30/40 mm for the differentiated/undifferentiated types, with a mandatory intraoperative frozen section analysis. Mini-abstract This study proposes a distal margin length for safe resection of esophagogastric junction cancer, ensuring pathologically negative margins while preserving a larger remnant stomach, based on growth and pathological types.</p>","PeriodicalId":12684,"journal":{"name":"Gastric Cancer","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143004257","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}

{"title":"Morbidity and quality of life of totally laparoscopic versus laparoscopy-assisted distal gastrectomy for early gastric cancer: a multi-center prospective randomized controlled trial (CKLASS01).","authors":"Yu Zhang, Ziyu Li, Yantao Tian, Jiang Yu, Jieti Wang, Changmin Lee, Kuan Wang, Xianli He, Qing Qiao, Gang Ji, Zekuan Xu, Li Yang, Hao Xu, Xiaohui Du, Xiangqian Su, Jiadi Xing, Zhaojian Niu, Linghua Zhu, Su Yan, Yong Li, Junjiang Wang, Zhengrong Li, Yongliang Zhao, Jun You, Changqing Jing, Lin Fan, Yian Du, Gaoping Zhao, Wu Song, Yi Xuan, Mingde Zang, Jie Chen, Sungsoo Park, Hua Huang","doi":"10.1007/s10120-024-01561-y","DOIUrl":"10.1007/s10120-024-01561-y","url":null,"abstract":"<p><strong>Background: </strong>There is a paucity of confirmatory randomized controlled trials (RCTs) comparing the effectiveness of totally laparoscopic distal gastrectomy (TLDG) vs laparoscopy-assisted distal gastrectomy (LADG) for early gastric cancer (EGC).</p><p><strong>Methods: </strong>A phase III, prospective, multi-center RCT was conducted, wherein patients (n = 442) with clinical stage I gastric cancer eligible for laparoscopic distal gastrectomy were randomized 1:1 to the TLDG or the LADG group. Postoperative morbidity and quality of life (QoL) were compared.</p><p><strong>Results: </strong>In total, 422 patients were assessed (TLDG, 216; LADG, 206) in the modified intention-to-treat (mITT) analysis. The morbidity rate did not differ significantly between the two groups (TLDG, 6.0%; LADG, 5.8%; P = 0.93). The 90-day mortality rate was comparable between the groups (TLDG, 0.5%; LADG, 0.0%; P > 0.99). TLDG was significantly associated with a lower pain score compared with LADG in patients with a BMI of ≥ 25 kg/m² (P = 0.002) at 24 h postoperatively. Moreover, TLDG significantly improved QoL in terms of C30 social functioning at 3 and 6 months (P = 0.03 and P = 0.04), C30 global health status at 3 months (P = 0.02), and STO22 body image at 3 months (P = 0.01), with differences dissipating at 12 months.</p><p><strong>Conclusions: </strong>TLDG is not superior to LADG in terms of postoperative morbidity and mortality, but it provides better C30 social functioning at 3 and 6 months, C30 global health status and STO22 body image at 3 months, and reduces early postoperative pain for patients with a BMI of ≥ 25 kg/m².</p><p><strong>Trial registration: </strong>ClinicalTrials.gov: NCT03393182.</p>","PeriodicalId":12684,"journal":{"name":"Gastric Cancer","volume":" ","pages":"131-144"},"PeriodicalIF":6.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142582824","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}

{"title":"Advantages of adjuvant chemotherapy using S-1 following minimally invasive gastrectomy for gastric cancer versus open surgery: a propensity score-matched analysis.","authors":"Motonari Ri, Naoki Nishie, Manabu Ohashi, Shota Fukuoka, Kensei Yamaguchi, Rie Makuuchi, Masaru Hayami, Tomoyuki Irino, Takeshi Sano, Souya Nunobe","doi":"10.1007/s10120-024-01565-8","DOIUrl":"10.1007/s10120-024-01565-8","url":null,"abstract":"<p><strong>Background: </strong>It is essential to ensure optimal adherence to adjuvant chemotherapy regimens following gastric cancer surgery. However, treatment intensity for S-1 as adjuvant chemotherapy has not as yet been compared between minimally invasive (MI) and open (Open) surgery.</p><p><strong>Methods: </strong>We retrospectively compared dose modification of adjuvant S-1 between MI and Open surgery in patients undergoing R0 gastrectomy for gastric or esophago-gastric junction cancer at the Cancer Institute Hospital Tokyo, Japan, during the period from 2012 to 2022, and receiving S-1 for pStage II or S-1 plus docetaxel for pStage III as adjuvant chemotherapy. Propensity score matching (PSM) was conducted to adjust for possible confounders.</p><p><strong>Results: </strong>In total, 323 patients were initially included. After PSM, 158 patients remained, 79 in each group. The adjuvant chemotherapy completion rates were similar in the two groups. However, the proportion of patients who required S-1 dose reduction was significantly lower in the MI than in the Open group (43.0% vs. 65.8%, p = 0.004). In addition, the MI group had significantly fewer patients requiring suspension of S-1 than the Open group (46.8% vs. 64.6%, p = 0.025). Moreover, the frequency of adverse events of grade ≥ 3 was significantly lower in the MI than in the Open group (17.7% vs. 31.7%, p = 0.042).</p><p><strong>Conclusions: </strong>In adjuvant chemotherapy for gastric cancer, minimally invasive surgery may offer better treatment intensity for oral S-1 administration than open surgery.</p>","PeriodicalId":12684,"journal":{"name":"Gastric Cancer","volume":" ","pages":"122-130"},"PeriodicalIF":6.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142604159","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}

{"title":"Correction: Real-world effectiveness and safety of trastuzumab-deruxtecan in Japanese patients with HER2-positive advanced gastric cancer (EN-DEAVOR study).","authors":"Hisato Kawakami, Koki Nakanishi, Akitaka Makiyama, Hirotaka Konishi, Satoshi Morita, Yukiya Narita, Naotoshi Sugimoto, Keiko Minashi, Motohiro Imano, Rin Inamoto, Yasuhiro Kodera, Hiroki Kume, Keita Yamaguchi, Wataru Hashimoto, Kei Muro","doi":"10.1007/s10120-024-01570-x","DOIUrl":"10.1007/s10120-024-01570-x","url":null,"abstract":"","PeriodicalId":12684,"journal":{"name":"Gastric Cancer","volume":" ","pages":"62"},"PeriodicalIF":6.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11706912/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142739243","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}

{"title":"Short-term outcomes of a phase II trial of perioperative capecitabine plus oxaliplatin therapy for advanced gastric cancer with extensive lymph node metastases (OGSG1701).","authors":"Yutaka Kimura, Naotoshi Sugimoto, Shunji Endo, Ryohei Kawabata, Jin Matsuyama, Atsushi Takeno, Masato Nakamura, Hiroki Takeshita, Hironaga Satake, Shigeyuki Tamura, Daisuke Sakai, Hisato Kawakami, Yukinori Kurokawa, Toshio Shimokawa, Taroh Satoh","doi":"10.1007/s10120-024-01564-9","DOIUrl":"10.1007/s10120-024-01564-9","url":null,"abstract":"<p><strong>Background: </strong>The prognosis of advanced gastric cancer (GC) with extensive lymph node (LN) metastasis treated with surgery alone remains poor. We conducted a multicenter phase II study to evaluate the efficacy and safety of perioperative capecitabine plus oxaliplatin (CapeOx) therapy in patients with advanced GC with extensive LN metastases.</p><p><strong>Patients and methods: </strong>Patients with histologically proven HER2-negative or unknown gastric adenocarcinoma with paraaortic LN (PALN) metastases and/or bulky LN metastases located at the celiac axis, common hepatic artery, and/or splenic artery were included in the study. Patients received three cycles of preoperative CapeOx every 3 weeks, followed by five cycles of postoperative CapeOx after gastrectomy with D2 or D2 + including PALN dissection. The primary endpoint was the response rate (RR) according to the RECIST v1.0 criteria.</p><p><strong>Results: </strong>Thirty patients from 14 institutions were enrolled from September 2017 to June 2022. Complete response, partial response, stable disease, and progressive disease occurred in zero, 20, eight, and one patient, respectively. One patient was not evaluated. The RR was 66.7% (90% confidence interval, 50.1-80.7%; one-sided P = 0.049). The preoperative chemotherapy completion rate and the curative resection rate were 96.7% and 93.3%, respectively. The minor (grade ≥ 1b) pathological RR was 66.7%. Grade 3 adverse events of preoperative chemotherapy included neutropenia in 3.3%, anemia in 6.7%, and anorexia in 10.0%. One treatment-related death occurred due to postoperative complications.</p><p><strong>Conclusion: </strong>Preoperative CapeOx chemotherapy showed a favorable RR, curative resection rate, and acceptable adverse events in patients with advanced GC with extensive LN metastasis.</p><p><strong>Registration number: </strong>UMIN000028749 and jRCTs051180186.</p>","PeriodicalId":12684,"journal":{"name":"Gastric Cancer","volume":" ","pages":"112-121"},"PeriodicalIF":6.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142618666","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}

{"title":"Circulating tumor DNA predicts recurrence and survival in patients with resectable gastric and gastroesophageal junction cancer.","authors":"Cecilie Riis Iden, Salah Mohammad Mustafa, Nadia Øgaard, Tenna Henriksen, Sarah Østrup Jensen, Lise Barlebo Ahlborn, Kristian Egebjerg, Lene Baeksgaard, Rajendra Singh Garbyal, Mette Kjølhede Nedergaard, Michael Patrick Achiam, Claus Lindbjerg Andersen, Morten Mau-Sørensen","doi":"10.1007/s10120-024-01556-9","DOIUrl":"10.1007/s10120-024-01556-9","url":null,"abstract":"<p><strong>Background: </strong>Gastric and gastroesophageal junction (GEJ) cancer represents a significant global health challenge, with high recurrence rates and poor survival outcomes. This study investigates circulating tumor DNA (ctDNA) as a biomarker for assessing recurrence risk in patients with resectable gastric and GEJ adenocarcinomas (AC).</p><p><strong>Methods: </strong>Patients with resectable gastric and GEJ AC, undergoing perioperative chemotherapy and surgery, were prospectively enrolled. Serial plasma samples were collected at baseline, after one cycle of chemotherapy, after preoperative chemotherapy, and after surgery. ctDNA was assessed by a ddPCR test (TriMeth), which targets the gastrointestinal cancer-specific methylation patterns of the genes C9orf50, KCNQ5, and CLIP4.</p><p><strong>Results: </strong>ctDNA analysis was performed on 229 plasma samples from 86 patients. At baseline, ctDNA was detected in 56% of patients, which decreased to 37% following one cycle of chemotherapy, 25% after preoperative chemotherapy and 15% after surgical resection. The presence of ctDNA after one cycle of chemotherapy was associated with reduced recurrence-free survival (RFS) (HR = 2.54, 95% confidence interval (CI) 1.33-4.85, p = 0.005) and overall survival (OS) (HR = 2.23, 95% CI 1.07-4.62, p = 0.032). Similarly, ctDNA after surgery was associated with significantly shorter RFS (HR = 6.22, 95% CI 2.39-16.2, p < 0.001) and OS (HR = 6.37, 95% CI 2.10-19.3, p = 0.001). Multivariable regression analysis confirmed ctDNA after surgery as an independent prognostic factor (p < 0.001).</p><p><strong>Conclusion: </strong>ctDNA analysis has the potential to identify patients at elevated risk of recurrence, thus providing personalized treatment strategies for patients with resectable gastric and GEJ cancer. Further validation in larger cohorts and ctDNA-guided interventions are needed for future clinical use.</p>","PeriodicalId":12684,"journal":{"name":"Gastric Cancer","volume":" ","pages":"83-95"},"PeriodicalIF":6.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11706848/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142377757","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}