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Zheng HL, Zhang LK, Zheng HH, Lv CB, Xu BB, Lin GT, Chen QY, Lin JX, Zheng CH, Huang CM, Xie JW. Timing of postoperative chemotherapy and prognosis in neoadjuvant-treated gastric cancer patients: a multicenter real-world cohort study. Ann Med 2025; 57:2500690. [PMID: 40329795 PMCID: PMC12064125 DOI: 10.1080/07853890.2025.2500690] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/02/2024] [Revised: 03/27/2025] [Accepted: 04/14/2025] [Indexed: 05/08/2025] Open
Abstract
BACKGROUND The optimal time to chemotherapy (TTC) in locally advanced gastric cancer (LAGC) patients treated with neoadjuvant chemotherapy (NLAGC) remains unclear. METHODS Consecutive 524 patients with NLAGC between Jan. 2010 and Dec. 2022 were identified. Patients were categorized into three groups: TTC < 6w, 6w ≤ TTC ≤ 8w, and TTC > 8w. Survival analysis was conducted using the Cox proportional hazards model to assess the impact of TTC on gastric cancer-specific mortality (GCSM) and all-cause mortality (ACM). Cumulative competing risk curves were employed to evaluate the incidence of competing events. RESULTS Overall, 451 patients were included.Cumulative competing risk curves showed that the 3-year ACM and GCSM were significantly lower in the 6w ≤ TTC ≤ 8w group (ACM: 19.7% vs. 37.2% vs. 39.7%, GCSM: 19.7% vs. 35.2% vs. 38.8%) compared to the TTC < 6w and TTC > 8w groups. Compared to patients with 6w ≤ TTC ≤ 8w, those with TTC < 6w or >8w had an increased risk of GCSM (HR: 2.792 and HR: 2.343, respectively) and ACM (HR: 3.102 and HR: 2.719, respectively) after adjusting for confounders. Furthermore, 6w ≤ TTC ≤ 8w had later peak recurrence compared to TTC < 6w and TTC > 8w (Peak months: 9.7 vs. 4.3 vs. 3.1). CONCLUSION A postoperative chemotherapy timing of 6-8 weeks was associated with better survival and delayed recurrence in NLAGC patients. These findings suggest that the 6-8 week time-window should be a key timeframe for personalized postoperative adjuvant chemotherapy decisions.
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Affiliation(s)
- Hua-Long Zheng
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
- Fujian Provincial Minimally Invasive Medical Center, Fuzhou, Fujian, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
| | - Ling-Kang Zhang
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
- Fujian Provincial Minimally Invasive Medical Center, Fuzhou, Fujian, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
| | - Hong-Hong Zheng
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
- Fujian Provincial Minimally Invasive Medical Center, Fuzhou, Fujian, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
| | - Chen-Bin Lv
- Department of Gastrointestinal Surgery, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, Fujian, China
| | - Bin-Bin Xu
- Department of Digestive Endoscopy, Fuzhou University Affiliated Provincial Hospital, Fujian Provincial Hospital, Fuzhou, Fujian, China
| | - Guang-Tan Lin
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
- Fujian Provincial Minimally Invasive Medical Center, Fuzhou, Fujian, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
| | - Qi-Yue Chen
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
- Fujian Provincial Minimally Invasive Medical Center, Fuzhou, Fujian, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
| | - Jian-Xian Lin
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
- Fujian Provincial Minimally Invasive Medical Center, Fuzhou, Fujian, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
| | - Chao-Hui Zheng
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
- Fujian Provincial Minimally Invasive Medical Center, Fuzhou, Fujian, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
| | - Chang-Ming Huang
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
- Fujian Provincial Minimally Invasive Medical Center, Fuzhou, Fujian, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
| | - Jian-Wei Xie
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
- Fujian Provincial Minimally Invasive Medical Center, Fuzhou, Fujian, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
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Zhang ZQ, Zhong Q, Sun YQ, Ma YB, Ding FH, Wu D, Xue MQ, Desiderio J, Yu JH, Wu J, Zheng CH, Li P, Chen QY, Huang CM, Xie JW. The minimum number of lymph node retrieval in gastric cancer patients after neoadjuvant therapy: An international multi-institute cohort study. Surgery 2025; 183:109373. [PMID: 40328160 DOI: 10.1016/j.surg.2025.109373] [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: 09/23/2024] [Revised: 02/22/2025] [Accepted: 04/01/2025] [Indexed: 05/08/2025]
Abstract
BACKGROUND The minimum number of retrieved lymph nodes for radical gastrectomy after neoadjuvant therapy remains controversial. The objective of this study was to determine the minimum threshold for retrieved lymph nodes in patients with gastric cancer after neoadjuvant therapy to accurately evaluate staging and prognosis. METHODS Multivariate models were employed to investigate the correlation between the number of retrieved lymph nodes and survival outcomes and stage migration. The hazard ratio curves for each retrieved lymph node count compared with 1 retrieved lymph node (as a reference), including overall survival and disease-specific survival, were fitted using a LOWESS smoother, and the structural break points were determined by Chow test. RESULTS This international multicenter study analyzed the clinicopathological data of 2,490 patients with gastric cancer who underwent gastrectomy after neoadjuvant therapy. The median follow-up period for the overall population was 90.0 months, with a median of 22 retrieved lymph nodes. The study demonstrated that a greater number of retrieved lymph nodes was linked to a greater probability of detecting positive lymph nodes (odds ratio, 1.005; P = .030) as well as improved overall survival and disease-specific survival (overall survival: hazard ratio, 0.988; P < .001 and disease-specific survival: hazard ratio, 0.987; P < .001). The cutoff point analysis identified 24 as the minimum number of retrieved lymph nodes. The 5-year overall survival rate was significantly greater in the group with ≥24 retrieved lymph nodes (46.0%) compared with the group with 16-23 retrieved lymph nodes (35.3%) and the group with <16 retrieved lymph nodes group (29.3%) (P < .001). Similar trends were observed with regard to disease-specific survival. The time-dependent area under the curve analysis revealed that the group with ≥24 retrieved lymph nodes exhibited superior predictive performance for overall survival and disease-specific survival compared to the group with <24 retrieved lymph nodes, on the basis of ypN staging (overall survival: time-dependent areas under the receiver operating characteristic curve≥24, 0.71 vs time-dependent areas under the receiver operating characteristic curve<24, 0.67; disease-specific survival: time-dependent areas under the receiver operating characteristic curve≥24, 0.72 vs time-dependent areas under the receiver operating characteristic curve<24, 0.68). CONCLUSION The minimum number of retrieved lymph nodes for evaluation prognosis and reducing stage migration in patients with gastric cancer who undergo radical gastrectomy after neoadjuvant therapy was 24.
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Affiliation(s)
- Zhi-Quan Zhang
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China; Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou, China
| | - Qing Zhong
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China; Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou, China
| | - Yu-Qin Sun
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China; Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou, China; Department of Gastrointestinal Surgery, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, China
| | - Yu-Bin Ma
- Gastrointestinal Surgery, Qinghai University Affiliated Hospital, Xining, China
| | - Fang-Hui Ding
- General Surgery Department, The First Hospital of Lanzhou University, Lanzhou, China
| | - Dong Wu
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China; Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou, China
| | - Meng-Qi Xue
- Public Health School, Fujian Medical University, Fuzhou, Fujian, China
| | - Jacopo Desiderio
- Department of Digestive Surgery, St. Mary's Hospital, University of Perugia, Terni, Italy
| | - Jun-Hua Yu
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China; Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou, China; Department of General Surgery, The Quzhou Affiliated Hospital of Wenzhou University, Quzhou, China
| | - Ju Wu
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China; Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou, China; Department of General Surgery, Affiliated Zhongshan Hospital of Dalian University, Dalian, China
| | - Chao-Hui Zheng
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China; Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou, China
| | - Ping Li
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China; Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou, China
| | - Qi-Yue Chen
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China; Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou, China
| | - Chang-Ming Huang
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China; Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou, China
| | - Jian-Wei Xie
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China; Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou, China.
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Sun F, Gao X, Li T, Zhao X, Zhu Y. Tumor immune microenvironment remodeling after neoadjuvant therapy in gastric cancer: Update and new challenges. Biochim Biophys Acta Rev Cancer 2025; 1880:189350. [PMID: 40355011 DOI: 10.1016/j.bbcan.2025.189350] [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: 11/23/2024] [Revised: 05/05/2025] [Accepted: 05/08/2025] [Indexed: 05/14/2025]
Abstract
Gastric cancer (GC) is a malignant tumor with one of the highest morbidity and death rates in the world. Neoadjuvant therapy, including neoadjuvant chemotherapy (NAC) and NAC combined with immunotherapy, can improve the resection and long-term survival rates. However, not all patients respond well to neoadjuvant therapy. It has been confirmed that immune cells in the tumor immune microenvironment, including T cells, B cells, and natural killer cells, can affect the efficacy of neoadjuvant therapy. This paper summarizes current preclinical and clinical evidence to more fully describe the effects of neoadjuvant therapy on the immune microenvironment of GC, to provide the impetus to identify biomarkers to predict the potency of neoadjuvant therapy, and to identify the mechanisms of drug resistance, which should promote the development of individualized and accurate treatments for GC patients.
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Affiliation(s)
- Fujing Sun
- Department of Pathology, Affiliated Cancer Hospital of Dalian University of Technology (Liaoning Cancer Hospital and Institute, Cancer Hospital of China Medical University), Shenyang, China
| | - Xiaozhuo Gao
- Department of Pathology, Affiliated Cancer Hospital of Dalian University of Technology (Liaoning Cancer Hospital and Institute, Cancer Hospital of China Medical University), Shenyang, China
| | - Tianming Li
- Department of Pathology, Affiliated Cancer Hospital of Dalian University of Technology (Liaoning Cancer Hospital and Institute, Cancer Hospital of China Medical University), Shenyang, China
| | - Xiaoyan Zhao
- Graduate School, Dalian Medical University, Dalian, China
| | - Yanmei Zhu
- Department of Pathology, Affiliated Cancer Hospital of Dalian University of Technology (Liaoning Cancer Hospital and Institute, Cancer Hospital of China Medical University), Shenyang, China.
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Chen QX, Zhang YB, Zeng WM, Cai YC, Lv CB, Lian MQ, Huang RJ, Lian MJ, Lian WL, Xu QH, Sun YQ, Cai LS. Efficacy and safety of sintilimab combined with nab-paclitaxel plus S-1 for neoadjuvant treatment of locally advanced gastric cancer. World J Gastrointest Surg 2025; 17:106361. [DOI: 10.4240/wjgs.v17.i6.106361] [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: 02/24/2025] [Revised: 03/28/2025] [Accepted: 05/13/2025] [Indexed: 05/30/2025] Open
Abstract
BACKGROUND Gastric cancer is a leading global cause of cancer mortality, with poor survival in locally advanced stages. While immune checkpoint inhibitors (ICIs) like sintilimab have improved outcomes in advanced disease, their role as neoadjuvant therapy remains understudied. This study investigates sintilimab combined with nab-paclitaxel/S-1 as preoperative treatment for locally advanced gastric cancer (LAGC), addressing an unmet need for effective neoadjuvant strategies.
AIM To explore the efficacy and safety of combination treatment with sintilimab and nab-paclitaxel plus S-1 as neoadjuvant therapy for LAGC.
METHODS Clinical data from 82 patients diagnosed with LAGC, who underwent preoperative treatment and surgery between April 2020 and December 2022, were included. Patients were divided into 2 groups according to treatment regimen: ICI (sintilimab + nab-paclitaxel + S-1; and non-ICI (nab-paclitaxel + S-1). Imaging and pathological efficacy, intra- and postoperative conditions, molecular subtypes, short-term survival outcomes, and safety were compared between the 2 groups.
RESULTS Imaging evaluation of therapeutic efficacy revealed that the inclusion of ICI yielded a significantly higher complete response rate (13.2% vs 0.0%; P = 0.048), and objective response rate (69.8% vs 31.0%, P = 0.001) compared with non-ICI treatment. Pathological evaluation revealed that the ICI group exhibited a significantly higher pathological complete response rate (13.2% vs 0.0%; P = 0.048) and major pathological response rate (35.8% vs 13.8%; P = 0.041) than those in the non-ICI group. The two-year disease-free survival rate in the ICI group was greater than that in the non-ICI group (83.0% vs 55.2%; P = 0.043). The use of ICI did not increase the incidence of adverse reactions (47.2% vs 41.4%; P = 0.614) or perioperative adverse events (18.9% vs 13.8%; P = 0.761).
CONCLUSION The combination of sintilimab with nab-paclitaxel + S-1 for neoadjuvant treatment of LAGC improved efficacy in patients without increasing adverse drug reactions and perioperative adverse events, suggesting that this treatment regimen is safe and feasible.
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Affiliation(s)
- Qiu-Xian Chen
- Department of General Surgery, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou 363000, Fujian Province, China
| | - Yong-Bin Zhang
- Department of General Surgery, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou 363000, Fujian Province, China
| | - Wei-Ming Zeng
- Department of General Surgery, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou 363000, Fujian Province, China
| | - Yi-Chen Cai
- College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, Nanjing 211816, Jiangsu Province, China
| | - Chen-Bin Lv
- Department of General Surgery, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou 363000, Fujian Province, China
| | - Ming-Qiao Lian
- Department of General Surgery, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou 363000, Fujian Province, China
| | - Rong-Jie Huang
- Department of General Surgery, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou 363000, Fujian Province, China
| | - Ming-Jie Lian
- Department of General Surgery, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou 363000, Fujian Province, China
| | - Wei-Long Lian
- Department of General Surgery, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou 363000, Fujian Province, China
| | - Qian-Hui Xu
- Department of General Surgery, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou 363000, Fujian Province, China
| | - Yu-Qin Sun
- Department of General Surgery, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou 363000, Fujian Province, China
| | - Li-Sheng Cai
- Department of General Surgery, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou 363000, Fujian Province, China
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Marrelli D, Carbone L, Poto GE, Fusario D, Gjoka M, Andreucci E, Piccioni SA, Calomino N, Sandini M, Roviello F. Minimally invasive lymphadenectomy for gastric cancer: Could the robotic approach provide any benefits than laparoscopy? World J Gastrointest Oncol 2025; 17:104015. [DOI: 10.4251/wjgo.v17.i6.104015] [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: 12/06/2024] [Revised: 03/19/2025] [Accepted: 03/20/2025] [Indexed: 06/13/2025] Open
Abstract
Gastrectomy is the cornerstone of treatment for gastric cancer. Since the introduction of minimally invasive techniques, the main challenge for surgeons has been to achieve the same surgical radicality, adequate lymphadenectomy, and negative resection margins as with the open approach. Previous Eastern trials showed non-inferiority of laparoscopic gastrectomy, whereas Western trials reported a higher number of complications. This may depend on the different eligibility criteria to select patients and surgeons. Currently, the increased availability of robotic systems has led to renewed enthusiasm. We present a critical review of published randomized control trials (up to October 2024) to investigate the real benefits of robotic compared to open and laparoscopic approaches. Robotic gastrectomy has shown similar oncological outcomes in survival and lymph node retrieval, particularly in suprapancreatic stations, with the advantage of a more acceptable rate of pancreatic fistula and feasible anastomotic reconstruction. Some clinical situations, such as postchemotherapy interstitial fibrosis and distortion of anatomical planes, may increase the technical difficulty. Only four published trials assessed the implications of a pre-operative therapy, with no robotic surgery cases. Robotic systems may reduce intraoperative blood loss, the risk of conversion and allow more extensive lymphadenectomies in cancers with a high risk of extraperigastric metastases, or with clinically proven para-aortic node metastases, although clinical trials evaluating robotic gastrectomy after neoadjuvant therapy have not yet been published.
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Affiliation(s)
- Daniele Marrelli
- Department of Medicine Surgery and Neuroscience, University of Siena, Siena 53100, Tuscany, Italy
- Department of Oncology, Azienda Ospedaliera Universitaria Senese, Siena 53100, Tuscany, Italy
| | - Ludovico Carbone
- Department of Medicine Surgery and Neuroscience, University of Siena, Siena 53100, Tuscany, Italy
| | - Gianmario Edoardo Poto
- Department of Medicine Surgery and Neuroscience, University of Siena, Siena 53100, Tuscany, Italy
| | - Daniele Fusario
- Department of Medicine Surgery and Neuroscience, University of Siena, Siena 53100, Tuscany, Italy
| | - Mattheus Gjoka
- Department of Medicine Surgery and Neuroscience, University of Siena, Siena 53100, Tuscany, Italy
| | - Eleonora Andreucci
- Department of Medicine Surgery and Neuroscience, University of Siena, Siena 53100, Tuscany, Italy
| | - Stefania Angela Piccioni
- Department of Medicine Surgery and Neuroscience, University of Siena, Siena 53100, Tuscany, Italy
- Department of Oncology, Azienda Ospedaliera Universitaria Senese, Siena 53100, Tuscany, Italy
| | - Natale Calomino
- Department of Oncology, Azienda Ospedaliera Universitaria Senese, Siena 53100, Tuscany, Italy
| | - Marta Sandini
- Department of Medicine Surgery and Neuroscience, University of Siena, Siena 53100, Tuscany, Italy
| | - Franco Roviello
- Department of Medicine Surgery and Neuroscience, University of Siena, Siena 53100, Tuscany, Italy
- Department of Oncology, Azienda Ospedaliera Universitaria Senese, Siena 53100, Tuscany, Italy
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Gundavda K, Rajasimman AS, Patkar S, Chhatrala R, Baheti AD, Haria P, Kolhe M, Bhandare M, Chaudhari V, Shrikhande SV. Correlation between Tomographic and Histopathological Staging in Upfront Resected Gastric Cancer: Enhancing Diagnostic Accuracy in the Era of Perioperative Therapy. J Gastrointest Cancer 2025; 56:123. [PMID: 40425902 PMCID: PMC12116807 DOI: 10.1007/s12029-025-01245-5] [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] [Accepted: 05/05/2025] [Indexed: 05/29/2025]
Abstract
PURPOSE This study aimed to assess the diagnostic accuracy of multidetector contrast-enhanced computerised tomography (MDCT) and to establish a correlation between radiological and histopathological staging in upfront resected localised gastric cancers (GC). METHODS All consecutive patients of resectable, localised GC who underwent upfront elective resection between 2010 and 2022 were included. The initial clinical staging determined during multidisciplinary meetings was compared with the pathological stage obtained after surgery. Subsequently, a retrospective, blinded review was conducted to assign a revised clinical staging, and accuracy was correlated. RESULTS The analysis of 138 patients revealed varying accuracy of MDCT in determining the T stage (66.9% for T1/T2, 64.6% for T3, and 87.2% for T4) and N stage (60.8% for N0, 63.7% for N1, and 83.2% for N2). The accuracy for stage group ranged from 71 to 78.65%. There was weak agreement observed between the T, N, and overall stage on clinicopathological correlation. However, a blinded radiology review by oncoradiologists resulted in improved accuracy, particularly in T1/T2 disease, and also improved pathological stage correlation. CONCLUSIONS Although MDCT is a valuable initial staging tool for gastric cancer, we found weak agreement between the clinical and the pathological stages in upfront resected gastric cancers. By implementing an expert radiology review and standardising scanning and reporting protocols, we can significantly improve the accuracy and correlation of MDCT with pathology, even for T1/T2 disease. This may help in better selecting patients for upfront surgery versus perioperative chemotherapy, especially in resource-constrained settings.
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Affiliation(s)
- Kaival Gundavda
- Department of Gastrointestinal and Hepatobiliary-Pancreatic Surgery, Department of Surgical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute (HBNI), Mumbai, Maharashtra, India
| | - Aishvarya Shri Rajasimman
- Department of Radiodiagnosis, Tata Memorial Hospital, Homi Bhabha National Institute (HBNI), Mumbai, Maharashtra, India
| | - Shraddha Patkar
- Department of Gastrointestinal and Hepatobiliary-Pancreatic Surgery, Department of Surgical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute (HBNI), Mumbai, Maharashtra, India.
| | - Renish Chhatrala
- Department of Gastrointestinal and Hepatobiliary-Pancreatic Surgery, Department of Surgical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute (HBNI), Mumbai, Maharashtra, India
| | - Akshay D Baheti
- Department of Radiodiagnosis, Tata Memorial Hospital, Homi Bhabha National Institute (HBNI), Mumbai, Maharashtra, India
| | - Purvi Haria
- Department of Radiodiagnosis, Tata Memorial Hospital, Homi Bhabha National Institute (HBNI), Mumbai, Maharashtra, India
| | - Manjushree Kolhe
- Department of Biostatistics, Tata Memorial Hospital, Homi Bhabha National Institute (HBNI), Mumbai, Maharashtra, India
| | - Manish Bhandare
- Department of Gastrointestinal and Hepatobiliary-Pancreatic Surgery, Department of Surgical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute (HBNI), Mumbai, Maharashtra, India
| | - Vikram Chaudhari
- Department of Gastrointestinal and Hepatobiliary-Pancreatic Surgery, Department of Surgical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute (HBNI), Mumbai, Maharashtra, India
| | - Shailesh V Shrikhande
- Department of Gastrointestinal and Hepatobiliary-Pancreatic Surgery, Department of Surgical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute (HBNI), Mumbai, Maharashtra, India
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Wan G, Wang Q, Yang L, Xu G. Gastric Carcinoma Patients with Advanced Pathological Lymph Node Stage Benefit from Postoperative Radiotherapy: A Retrospective Analysis. J Gastrointest Cancer 2025; 56:122. [PMID: 40402361 DOI: 10.1007/s12029-025-01219-7] [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] [Accepted: 03/28/2025] [Indexed: 05/23/2025]
Abstract
BACKGROUND The relationship between regional pathological lymph node status and the benefit of postoperative radiotherapy for gastric cancer remains controversial. METHODS This study included all surgically treated patients diagnosed with positive histology and more than 15 examined lymph nodes between January 2007 and December 2019, using data from the SEER database. Patients who received adjuvant chemotherapy were compared by propensity score matching (PSM), with overall survival (OS) as the primary endpoint and adjuvant radiotherapy (RT) as the only variable. Results of subgroup analyses are presented in a forest plot. RESULTS We firstly analyzed the number of patients receiving adjuvant RT and observed a gradual decline from 2000 to 2021. A total of 1882 patients were included from 2007 to 2019, with 1301 (69.1%) in the adjuvant RT group and 581 (30.9%) in the no-adjuvant RT group. After PSM, each group included 573 patients. Overall, adjuvant RT did not significantly improve 3-year OS (55.5% vs. 51.1%, p = 0.07). However, in subgroups of patients with pathologic lymph node metastasis (pN3-stage), aged 55-70 years, with tumor size > 89 mm and T3-stage, adjuvant RT was associated with improved outcome (p < 0.05). Further PSM and survival analysis based on different pathological lymph node stages suggested an association between adjuvant RT and outcomes. Improved survival outcomes were observed in pathologically lymph node positive (pN +) and pN3 groups, but no similar effects were seen in pN1 and pN2 groups. For pN0 patients, although no statistical significance was found, the data suggest that adjuvant RT may not provide additional benefit. CONCLUSION Adjuvant RT was associated with significantly better prognosis in pN3-stage patients. More researches are needed to further validate the role of adjuvant RT in gastric cancer.
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Affiliation(s)
- Guangmin Wan
- Department of Radiation Oncology, The Affiliated Cancer Hospital of Zhengzhou University &Henan Cancer Hospital, Zhengzhou, 450008, China
| | - Quan Wang
- Department of Radiation Oncology, The Affiliated Cancer Hospital of Zhengzhou University &Henan Cancer Hospital, Zhengzhou, 450008, China
| | - Lu Yang
- Department of Radiation Oncology, The Affiliated Cancer Hospital of Zhengzhou University &Henan Cancer Hospital, Zhengzhou, 450008, China
| | - Gang Xu
- Department of Radiation Oncology, The Affiliated Cancer Hospital of Zhengzhou University &Henan Cancer Hospital, Zhengzhou, 450008, China.
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Nakayama I. Therapeutic strategy for scirrhous type gastric cancer. Jpn J Clin Oncol 2025:hyaf081. [PMID: 40403741 DOI: 10.1093/jjco/hyaf081] [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: 02/26/2025] [Accepted: 05/09/2025] [Indexed: 05/24/2025] Open
Abstract
Scirrhous-type gastric cancer (SGC) is a rare but well-recognized subset of resectable gastric cancer (GC), accounting for ⁓10% of cases. Despite its long history of clinical recognition dating back to the pre-1900s, SGC remains one of the most challenging GC subtypes to treat. Traditionally, SGC has been clinically defined as Borrmann type 4 GC, with histological classifications such as signet ring cell carcinoma or diffuse-type histology serving as alternative diagnostic criteria. Therapeutic advancements for SGC have largely focused on locally advanced or oligometastatic disease, yet no SGC-specific treatment has been established. The phase III JCOG0501 trial failed to demonstrate a survival benefit of neoadjuvant S-1 plus cisplatin for Borrmann type 4 and large type 3 GC. Recent developments in biomarker-driven therapies may redefine SGC by molecular subtypes, with CLDN18.2-targeted therapy emerging as a potential option for some SGC cases. However, as the landscape of medical oncology evolves, SGC may not remain a distinct therapeutic entity. The focus should shift toward understanding the intrinsic biology of SGC. Treatment development for SGC is expected to continue advancing, becoming increasingly stratified based on molecular abnormalities while maintaining a commitment to addressing unmet needs, such as early-onset GC and GC with symptomatic peritoneal dissemination.
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Affiliation(s)
- Izuma Nakayama
- Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwanoha 6-5-1, Kashiwa, 277-8577, Japan
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Agnes A, Boldrini L, Perillo F, Tran HE, Brizi MG, Ricci R, Lenkowicz J, Votta C, Biondi A, Manfredi R, Valentini V, D'Ugo DM, Persiani R. Radiomic-based models are able to predict the pathologic response to different neoadjuvant chemotherapy regimens in patients with gastric and gastroesophageal cancer: a cohort study. World J Surg Oncol 2025; 23:183. [PMID: 40350424 PMCID: PMC12067740 DOI: 10.1186/s12957-025-03828-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2025] [Accepted: 04/25/2025] [Indexed: 05/14/2025] Open
Abstract
BACKGROUND There is a clinical need to identify early predictors for response to neoadjuvant chemotherapy (NAC) in patients with gastric and gastroesophageal junction cancer (GC and GEJC). Radiomics involves extracting quantitative features from medical images. This study aimed to apply radiomics to build prediction models for the response to NAC. METHODS All consecutive patients with non-metastatic GC and GEJC undergoing NAC and surgical resection in an Italian high-volume referral center between 2005 and 2021 were considered eligible. In patients selected, the CT scans performed upon staging were reviewed to segment the tumor and extract radiomic features using MODDICOM. The primary endpoint was to develop and validate radiomic-based predictive models to identify major responders (MR: tumor regression grade TRG 1-2) and non-responders (NR: TRG 4-5) to NAC. Following an initial feature selection, radiomic and combined radiomic-clinicopathologic prediction models were built for the MR or NR status based on logistic regressions. Internal validation was performed for each model. Radiomic models (in the entire case series and according to NAC regimens) were evaluated using the receiver operating characteristic area under the curve (AUC), sensitivity, and negative predictive value (NPV). RESULTS The study included 77 patients undergoing NAC and subsequent tumor resection. The MR prediction model after all types of NAC (AUC of 0.876, CI 95% 0.786 - 0.966, sensitivity 83%, and NPV 96%) was based on a statistical feature. The models predicting NR among patients undergoing epirubicin with cisplatin and fluorouracil (ECF), epirubicin with oxaliplatin and capecitabin (EOX), or fluorouracil with oxaliplatin and docetaxel (FLOT) (AUC 0.760, CI 95% 0.639-0.882), oxaliplatin-based chemotherapy (AUC 0.810, CI 95% 0.692-0.928), and FLOT (AUC 0.907, CI 95% 0.818 - 0.995) were based on statistical, morphological and textural features. CONCLUSIONS The developed radiomic models resulted promising in predicting the response to different neoadjuvant chemotherapy strategies. Once further implemented on larger datasets, they could be valuable and cost-effective instruments to target multimodal treatment in patients with GC.
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Affiliation(s)
- Annamaria Agnes
- Catholic University of the Sacred Heart, Largo F. Vito n.1, Rome, 00168, Italy
- Department of Medical and Surgical Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Largo A. Gemelli n. 8, Rome, 00168, Italy
| | - Luca Boldrini
- Catholic University of the Sacred Heart, Largo F. Vito n.1, Rome, 00168, Italy
- Department of Diagnostic Imaging, Oncological Radiotherapy and Hematology, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Largo A. Gemelli n. 8, Rome, 00168, Italy
| | - Federica Perillo
- Catholic University of the Sacred Heart, Largo F. Vito n.1, Rome, 00168, Italy
| | - Huong Elena Tran
- Department of Diagnostic Imaging, Oncological Radiotherapy and Hematology, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Largo A. Gemelli n. 8, Rome, 00168, Italy
| | - Maria Gabriella Brizi
- Catholic University of the Sacred Heart, Largo F. Vito n.1, Rome, 00168, Italy
- Department of Diagnostic Imaging, Oncological Radiotherapy and Hematology, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Largo A. Gemelli n. 8, Rome, 00168, Italy
| | - Riccardo Ricci
- Catholic University of the Sacred Heart, Largo F. Vito n.1, Rome, 00168, Italy
- Department of Women, Children and Public Health Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Largo A. Gemelli n. 8, Rome, 00168, Italy
| | - Jacopo Lenkowicz
- Department of Diagnostic Imaging, Oncological Radiotherapy and Hematology, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Largo A. Gemelli n. 8, Rome, 00168, Italy
| | - Claudio Votta
- Department of Diagnostic Imaging, Oncological Radiotherapy and Hematology, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Largo A. Gemelli n. 8, Rome, 00168, Italy
| | - Alberto Biondi
- Catholic University of the Sacred Heart, Largo F. Vito n.1, Rome, 00168, Italy.
- Department of Medical and Surgical Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Largo A. Gemelli n. 8, Rome, 00168, Italy.
| | - Riccardo Manfredi
- Catholic University of the Sacred Heart, Largo F. Vito n.1, Rome, 00168, Italy
- Department of Diagnostic Imaging, Oncological Radiotherapy and Hematology, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Largo A. Gemelli n. 8, Rome, 00168, Italy
| | - Vincenzo Valentini
- Catholic University of the Sacred Heart, Largo F. Vito n.1, Rome, 00168, Italy
- Department of Diagnostic Imaging, Oncological Radiotherapy and Hematology, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Largo A. Gemelli n. 8, Rome, 00168, Italy
| | - Domenico M D'Ugo
- Catholic University of the Sacred Heart, Largo F. Vito n.1, Rome, 00168, Italy
- Department of Medical and Surgical Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Largo A. Gemelli n. 8, Rome, 00168, Italy
| | - Roberto Persiani
- Catholic University of the Sacred Heart, Largo F. Vito n.1, Rome, 00168, Italy
- Department of Medical and Surgical Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Largo A. Gemelli n. 8, Rome, 00168, Italy
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Zhong Q, Weng CM, Jiang MC, Sun YQ, Li BL, Zhao W, Zhang HX, Zhang ZQ, Ma YB, Wu SC, Ye W, Wu J, Du H, Zheng CH, Li P, Chen QY, Huang CM, Xie JW. Patterns of Survival and Recurrence in Poor Responders to Neoadjuvant Therapy for Gastric Cancer: A Real-World Multicenter Study. Ann Surg Oncol 2025:10.1245/s10434-025-17396-5. [PMID: 40329137 DOI: 10.1245/s10434-025-17396-5] [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: 11/01/2024] [Accepted: 04/13/2025] [Indexed: 05/08/2025]
Abstract
BACKGROUND Neoadjuvant therapy (NAT) is increasingly used in locally advanced gastric cancer (LAGC), but a significant proportion of patients respond poorly, causing adverse outcomes. Few studies have specifically examined the prognosis of this subgroup. This study aimed to analyze survival and recurrence in poor responders to guide follow-up and treatment strategies. METHODS This multicenter retrospective study included patients with LAGC who received NAT. Tumor regression was graded following the Becker system, defining TRG 2-3 as poor response. Outcomes were assessed for overall survival (OS), recurrence-free survival (RFS), and recurrence patterns. RESULTS 648 patients were included: 341 with TRG 2 and 307 with TRG 3. In the entire cohort, the 3-year OS and RFS were 54.6% and 55.2%, respectively. Recurrence occurred in 299 patients, with the following recurrence patterns: distant metastasis (26.1%, n = 78), peritoneal metastasis (21.1%, n = 63), locoregional recurrence (18.7%, n = 56), and multiple-site recurrence (18.4%, n = 55). Liver metastasis was significantly higher in the TRG 3 group than in the TRG 2 group (14.1% versus 5.3%, P = 0.010). ypN+ was the most significant independent risk factor for recurrence (OR = 2.73, 95% CI 1.83-4.08, P < 0.001); an increasing number of positive lymph nodes led to higher 3-year cumulative mortality in patients. Despite poor response to NAT, completing over four adjuvant chemotherapy cycles was associated with improved survival outcomes. CONCLUSION Poor NAT responders in LAGC have high recurrence rates, particularly in the first year post-surgery, with ypN+ status being the strongest predictor of recurrence. Completing over four cycles of AC was associated with survival improvement in this group.
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Affiliation(s)
- Qing Zhong
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
| | - Cai-Ming Weng
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
| | - Mei-Chen Jiang
- Department of Pathology, Fujian Medical University Union Hospital, Fuzhou, China
| | - Yu-Qin Sun
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
- Department of Gastrointestinal Surgery, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, China
| | - Bao-Long Li
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
- Department of General Surgery, The Fifth Affiliated Hospital, Southern Medical University, Guangzhou, China
| | - Wei Zhao
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
- General Hospital of Ningxia Medical University, Yinchuan, China
| | - Hao-Xiang Zhang
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
| | - Zhi-Quan Zhang
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
| | - Yu-Bin Ma
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
- Department of Gastrointestinal Surgery, Affiliated Hospital of Qinghai University, Xining, China
| | - Shi-Chao Wu
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
- Gastrointestinal Surgery Unit 2, Putian First Hospital of Fujian Medical University, Putian, China
| | - Wen Ye
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
- Department of Gastrointestinal Surgery, Longyan First Affiliated Hospital of Fujian Medical University, Longyan, China
| | - Ju Wu
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
- Department of General Surgery, Affiliated Zhongshan Hospital of Dalian University, Dalian, China
| | - He Du
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
- Department of Gastrointestinal Surgery, Affiliated Hospital of Qinghai University, Xining, China
| | - Chao-Hui Zheng
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
| | - Ping Li
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
| | - Qi-Yue Chen
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China.
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China.
| | - Chang-Ming Huang
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China.
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China.
| | - Jian-Wei Xie
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China.
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China.
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Weng CM, Zhong Q, Sun YQ, Liu ZY, Ma YB, Zhang ZQ, Zhang HX, Zhu JY, Ye W, Wu J, Du H, Zheng CH, Li P, Chen QY, Huang CM, Xie JW. A novel ypN-TRG staging system for gastric cancer patients after neoadjuvant therapy based on the metro-ticket paradigm: a multicenter and large sample retrospective analysis. Gastric Cancer 2025; 28:465-477. [PMID: 39918688 DOI: 10.1007/s10120-025-01586-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/14/2024] [Accepted: 01/15/2025] [Indexed: 03/03/2025]
Abstract
BACKGROUND Conventional ypT category evaluates the depth of invasion after neoadjuvant therapy (NAT) for gastric cancer (GC) and has limited prognostic value. Tumor regression grade (TRG) measures the extent of tumor response to treatment, and when combined with the ypN category, it may enhance the prediction of patient outcomes. This study aims to develop a new staging system by integrating TRG and ypN category to better evaluate the prognosis of GC patients receiving NAT. METHODS This retrospective analysis included 962 patients who underwent radical gastrectomy after NAT, with 513 in the development cohort (from one center) and 449 in the external validation cohort (from five centers). The ypN-TRG staging system was established by calculating the distance from the origin on a cartesian plane incorporating the ypN (x-axis) stage and TRG (y-axis) grade, and five sub-stages were delineated. RESULTS In the development cohort, 3-year overall survival rates according to ypN-TRG stage I, IIA, IIB, IIIA, IIB were 87.6%, 80.2%, 70.7%, 47.3%, 21.5%, p < 0.01. Compared with ypTNM, the ypN-TRG staging system performed better in terms of the prognostic discrimination power (C-index), goodness-of-fit (AIC, BIC), model improvement (NRI, IDI), and model stability (time-AUC). Multivariate Cox regression analysis confirmed the superiority of ypN-TRG over ypTNM staging. In the external validation cohort, ypN-TRG staging was a better predictor of OS and DFS in patients with GC. CONCLUSIONS The ypN-TRG staging system is superior to the AJCC eighth edition ypTNM staging system in accurately assessing the prognosis of patients with GC after NAT.
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Affiliation(s)
- Cai-Ming Weng
- Department of Gastric Surgery, Fujian Medical University Union Hospital, No.29 Xin-Quan Road, Fuzhou, 350001, Fujian, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, 350001, Fujian, China
| | - Qing Zhong
- Department of Gastric Surgery, Fujian Medical University Union Hospital, No.29 Xin-Quan Road, Fuzhou, 350001, Fujian, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, 350001, Fujian, China
| | - Yu-Qin Sun
- Department of Gastric Surgery, Fujian Medical University Union Hospital, No.29 Xin-Quan Road, Fuzhou, 350001, Fujian, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, 350001, Fujian, China
- Department of Gastrointestinal Surgery, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, 363000, Fujian, China
| | - Zhi-Yu Liu
- Department of Gastric Surgery, Fujian Medical University Union Hospital, No.29 Xin-Quan Road, Fuzhou, 350001, Fujian, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, 350001, Fujian, China
| | - Yu-Bin Ma
- Department of Gastrointestinal Surgery, Affiliated Hospital of Qinghai University, Xining, 810000, Qinghai, China
| | - Zhi-Quan Zhang
- Department of Gastric Surgery, Fujian Medical University Union Hospital, No.29 Xin-Quan Road, Fuzhou, 350001, Fujian, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, 350001, Fujian, China
| | - Hao-Xiang Zhang
- Department of Gastric Surgery, Fujian Medical University Union Hospital, No.29 Xin-Quan Road, Fuzhou, 350001, Fujian, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, 350001, Fujian, China
| | - Ji-Yun Zhu
- Department of Gastric Surgery, Fujian Medical University Union Hospital, No.29 Xin-Quan Road, Fuzhou, 350001, Fujian, China
- Hepatopancreatobiliary Surgery Department, The First Affiliated Hospital of Ningbo University, Ningbo, 315000, Zhejiang, China
| | - Wen Ye
- Department of Gastrointestinal Surgery, Longyan First Hospital Affiliated to, Fujian Medical University, Longyan, 364000, Fujian, China
| | - Ju Wu
- Department of Gastric Surgery, Fujian Medical University Union Hospital, No.29 Xin-Quan Road, Fuzhou, 350001, Fujian, China
- Department of General Surgery, Affiliated Zhongshan Hospital of Dalian University, Dalian, 116000, Liaoning, China
| | - He Du
- Department of Gastrointestinal Surgery, Affiliated Hospital of Qinghai University, Xining, 810000, Qinghai, China
| | - Chao-Hui Zheng
- Department of Gastric Surgery, Fujian Medical University Union Hospital, No.29 Xin-Quan Road, Fuzhou, 350001, Fujian, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, 350001, Fujian, China
| | - Ping Li
- Department of Gastric Surgery, Fujian Medical University Union Hospital, No.29 Xin-Quan Road, Fuzhou, 350001, Fujian, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, 350001, Fujian, China
| | - Qi-Yue Chen
- Department of Gastric Surgery, Fujian Medical University Union Hospital, No.29 Xin-Quan Road, Fuzhou, 350001, Fujian, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, 350001, Fujian, China
| | - Chang-Ming Huang
- Department of Gastric Surgery, Fujian Medical University Union Hospital, No.29 Xin-Quan Road, Fuzhou, 350001, Fujian, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, 350001, Fujian, China
| | - Jian-Wei Xie
- Department of Gastric Surgery, Fujian Medical University Union Hospital, No.29 Xin-Quan Road, Fuzhou, 350001, Fujian, China.
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, 350001, Fujian, China.
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Chen W, Cai Z, Li J, Li Z, Xu Z, Wu J, Liu F, Zhao H, Xu Y. Five-year survival outcome of laparoscopic D2 lymphadenectomy plus complete mesogastrium excision for patients with stage II/III gastric cancer without invasion of the squamocolumnar junction. Surgery 2025; 181:109290. [PMID: 40068362 DOI: 10.1016/j.surg.2025.109290] [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: 08/06/2024] [Revised: 12/30/2024] [Accepted: 02/01/2025] [Indexed: 04/30/2025]
Abstract
BACKGROUND Gastric cancer patients without invasion of the squamocolumnar junction have a low probability of extragastric mesenteric metastasis, and the survival benefit of conducting D2 lymphadenectomy plus complete mesogastrium excision is unclear in this group of patients. METHODS This was a retrospective analysis of patients with stage II/III gastric cancer without invasion of the squamocolumnar junction who underwent laparoscopic radical surgery for gastric cancer at the First Hospital of Putian City, Fujian Province, from January 2014 to May 2019. Five-year disease-free survival was the primary outcome, and 5-year overall survival and the recurrence pattern were the secondary outcomes. Morbidity, mortality, and surgery-related outcomes within 30 days of surgery were also analyzed. RESULTS This study included 366 patients, 133 in the D2 lymphadenectomy group and 233 in the D2 lymphadenectomy plus complete mesogastrium excision group. There was no statistically significant difference in 5-year disease-free survival and overall survival in the D2 lymphadenectomy plus complete mesogastrium excision group compared with the D2 lymphadenectomy group (P > .05). Regarding recurrence pattern, the D2 lymphadenectomy group had a higher rate of local recurrence (12.3% and 38.3%, P = .001). In subgroup analysis, patients with stage III and T3-4aN1-3 gastric cancer in the D2 lymphadenectomy plus complete mesogastrium excision group had significantly better 5-year disease-free survival compared with the D2 lymphadenectomy group (P < .05). CONCLUSION Laparoscopic D2 lymphadenectomy plus complete mesogastrium excision not only decreased the local recurrence rate of stage II/III gastric cancer without invasion of the squamocolumnar junction, but it also improved the 5-year disease-free survival of patients with stage III and T3-4aN1-3 gastric cancer without invasion of the squamocolumnar junction.
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Affiliation(s)
- Weixiang Chen
- The School of Clinical Medicine, Fujian Medical University, Fuzhou, Fujian, China; Gastrointestinal Surgery Unit 1, The First Hospital of Putian City, Putian, Fujian, China
| | - Zhiming Cai
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
| | - Junpeng Li
- Gastrointestinal Surgery Unit 1, The First Hospital of Putian City, Putian, Fujian, China
| | - Zhixiong Li
- Gastrointestinal Surgery Unit 1, The First Hospital of Putian City, Putian, Fujian, China
| | - Zhengnan Xu
- The School of Clinical Medicine, Fujian Medical University, Fuzhou, Fujian, China; Gastrointestinal Surgery Unit 1, The First Hospital of Putian City, Putian, Fujian, China
| | - Jihuang Wu
- Gastrointestinal Surgery Unit 1, The First Hospital of Putian City, Putian, Fujian, China
| | - Feng Liu
- The School of Clinical Medicine, Fujian Medical University, Fuzhou, Fujian, China; Gastrointestinal Surgery Unit 1, The First Hospital of Putian City, Putian, Fujian, China
| | - Hongrui Zhao
- The School of Clinical Medicine, Fujian Medical University, Fuzhou, Fujian, China; Gastrointestinal Surgery Unit 1, The First Hospital of Putian City, Putian, Fujian, China
| | - Yanchang Xu
- Gastrointestinal Surgery Unit 1, The First Hospital of Putian City, Putian, Fujian, China.
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13
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Sundar R, Nakayama I, Markar SR, Shitara K, van Laarhoven HWM, Janjigian YY, Smyth EC. Gastric cancer. Lancet 2025:S0140-6736(25)00052-2. [PMID: 40319897 DOI: 10.1016/s0140-6736(25)00052-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/20/2024] [Revised: 11/13/2024] [Accepted: 01/09/2025] [Indexed: 05/07/2025]
Abstract
Gastric cancer remains a major health challenge worldwide, with nearly 1 million new cases annually contributing to more than 650 000 deaths. Epidemiologically, gastric cancer shows substantial geographical variation in incidence, with higher rates in Asia, South America, and eastern Europe, and a rapid increase in early-onset cases among people younger than 50 years. Key risk factors for gastric cancer include Helicobacter pylori infection, diet, obesity, smoking, and genetic predisposition. Early detection through comprehensive diagnostic procedures is crucial for optimising treatment outcomes. Standard treatment approaches for locally advanced gastric cancer include surgical resection, particularly D2 lymphadenectomy, complemented by chemotherapy and radiotherapy. There is increasing implementation of minimally invasive surgical techniques for operable disease and integration of immune checkpoint inhibitors and targeted therapies for advanced stages. Emerging therapies, such as novel targeted treatments and next-generation immunotherapies, show promise in improving survival and quality of life. Future directions in the management of gastric cancer focus on precision medicine, continued advancement in immunotherapy, novel early detection methods, and a multidisciplinary approach to care. These strategies aim to enhance the overall effectiveness of treatment and prognosis worldwide.
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Affiliation(s)
- Raghav Sundar
- Department of Medicine, Section of Medical Oncology, Yale School of Medicine, New Haven, CT, USA; Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Department of Haematology-Oncology, National University Cancer Institute, Singapore
| | - Izuma Nakayama
- Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan
| | - Sheraz R Markar
- Surgical Intervention Trials Unit, Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK
| | - Kohei Shitara
- Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan
| | - Hanneke W M van Laarhoven
- Cancer Center Amsterdam, Imaging and Biomarkers, Amsterdam, Netherlands; Department of Medical Oncology, Amsterdam UMC Location University of Amsterdam, Amsterdam, Netherlands
| | - Yelena Y Janjigian
- Department of Medicine, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY, USA
| | - Elizabeth C Smyth
- Oxford NIHR Biomedical Research Centre, Churchill Hospital, Oxford, UK.
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14
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Wu T, Zhou J, He W, Jin L, Li T, Gong T, Liu X. An injectable multimodal thiolated carboxymethyl cellulose hydrogel for advanced gastric cancer treatment. Int J Biol Macromol 2025; 306:141546. [PMID: 40020807 DOI: 10.1016/j.ijbiomac.2025.141546] [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: 09/17/2024] [Revised: 02/14/2025] [Accepted: 02/25/2025] [Indexed: 03/03/2025]
Abstract
Chemotherapy is a standard preoperative treatment for locally advanced resectable gastric cancer (GC). However, its efficacy is often limited by the high intracellular glutathione (GSH) levels in tumor cells, which diminish the effectiveness of chemotherapeutic agents. In this study, we developed a GSH-sensitive injectable hydrogel, T-CMC@Fe3+(5-FU + GOx), incorporating ferric ions (Fe3+), glucose oxidase (GOx), and 5-fluorouracil (5-FU) for advanced GC multimodal treatment. The hydrogel synergistically enhances anti-tumor activity through multiple mechanisms, including chemodynamic therapy, starvation therapy, and chemotherapy. Thiolated carboxymethyl cellulose (T-CMC) was synthesized by grafting L-cysteine onto carboxymethyl cellulose, with successful preparation confirmed by XPS, FTIR, and 13C NMR characterizations. The T-CMC@Fe3+ hydrogel demonstrated responsive degradation of GSH and exhibited favorable biocompatibility in co-culture experiments with GES-1 cells. In vitro analyses revealed that the T-CMC@Fe3+(5-FU + GOx) hydrogel significantly enhanced anti-tumor efficacy compared to chemotherapy alone, reducing cell viability to 12.28 ± 2.88 % after 48 h. In vivo studies using cell-derived and patient-derived xenograft models further confirmed its potent anti-tumor effects, with a marked reduction in tumor volume by 14 days (8.12 ± 4.89 mm3). These findings highlight the potential of the T-CMC@Fe3+(5-FU + GOx) hydrogel as a novel and effective strategy for enhancing GC treatment through its multimodal therapeutic approach.
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Affiliation(s)
- Tao Wu
- College of Medicine and Biological Information Engineering, Northeastern University; Shenyang 110169, China; Department of Biomedical Engineering, Shenyang University of Technology, Shenyang 110870, China; Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang 110840, China
| | - Jingqiu Zhou
- College of Medicine and Biological Information Engineering, Northeastern University; Shenyang 110169, China; Department of Biomedical Engineering, Shenyang University of Technology, Shenyang 110870, China; Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang 110840, China
| | - Wanli He
- Department of Biomedical Engineering, Shenyang University of Technology, Shenyang 110870, China
| | - Lei Jin
- Department of Biomedical Engineering, Shenyang University of Technology, Shenyang 110870, China
| | - Tenghui Li
- Department of Surgical Oncology and General Surgery, The First Hospital of China Medical University; Shenyang 110001, China; Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, China Medical University; Shenyang 110001, China.
| | - Tianxing Gong
- Department of Biomedical Engineering, Shenyang University of Technology, Shenyang 110870, China.
| | - Xu Liu
- Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang 110840, China.
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15
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Ortego M, Arrizibita O, Martinez-Lage A, Atienza ÁV, Álvarez Gigli L, Ruiz O, Subtil JC, Zabalza M, Valentí V, Tortajada A, Hidalgo MJ, Sayar O, Rodriguez J. Neoadjuvant Chemoradiotherapy in Locally Advanced Gastric Adenocarcinoma: Long-Term Results and Statistical Algorithm to Predict Individual Risk of Relapse. Cancers (Basel) 2025; 17:1530. [PMID: 40361455 PMCID: PMC12070951 DOI: 10.3390/cancers17091530] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2025] [Revised: 04/25/2025] [Accepted: 04/27/2025] [Indexed: 05/15/2025] Open
Abstract
BACKGROUND The purpose of this study was to evaluate the long-term outcomes of patients with locally advanced gastric adenocarcinoma (LAGC) intended to receive induction chemotherapy, chemoradiation and surgery and to develop an algorithm to estimate the individual risk of relapse in a population-based setting. METHODS Patients with LAGC (cT3-4 and/or N+) were retrospectively evaluated. A pathological response was graded according to the Becker criteria. The nodal regression grade was assessed by a 4-point scale (A-D). A comprehensive analysis of 155 individual patient variables was performed, and logistic regression (LR) was utilized to develop a predictive model for relapse risk. RESULTS From 2010 to 2024, 48 patients were analyzed. After a median follow-up of 49 months (range, 12-212), the 5-year actuarial PFS and OS rates were 44% and 48%, respectively. Four variables were identified as the most relevant features for training the LR model. Scores for the model accuracy, sensitivity and specificity (mean +/- sd) were 0.79 +/- 0.12, 0.74 +/- 0.221 and 0.88 +/- 0.14, respectively. For a validation dataset, the figures were 0.78, 0.88 and 0.73, respectively. CONCLUSIONS This neoadjuvant strategy seems to correlate with a favorable long-term outcome in a subset of intestinal-type LAGA patients who achieve ypN0 features.
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Affiliation(s)
- Miguel Ortego
- Department of Medical Oncology, Clínica Universidad de Navarra, 31008 Pamplona, Spain; (M.O.); (Á.V.A.); (A.T.); (M.J.H.)
| | - Olast Arrizibita
- Department of Mathematics and Statistic, NNBi, 31110 Noain, Spain; (O.A.); (O.R.); (M.Z.); (O.S.)
| | - Adriana Martinez-Lage
- Department of Radiation Oncology, Clínica Universidad de Navarra, 31008 Pamplona, Spain;
| | - Ángel Vizcay Atienza
- Department of Medical Oncology, Clínica Universidad de Navarra, 31008 Pamplona, Spain; (M.O.); (Á.V.A.); (A.T.); (M.J.H.)
| | - Laura Álvarez Gigli
- Department of Pathology, Clínica Universidad de Navarra, 31008 Pamplona, Spain;
| | - Oskitz Ruiz
- Department of Mathematics and Statistic, NNBi, 31110 Noain, Spain; (O.A.); (O.R.); (M.Z.); (O.S.)
| | - José Carlos Subtil
- Department of Gastroenterology, Clínica Universidad de Navarra, 31008 Pamplona, Spain;
| | - Maialen Zabalza
- Department of Mathematics and Statistic, NNBi, 31110 Noain, Spain; (O.A.); (O.R.); (M.Z.); (O.S.)
| | - Victor Valentí
- Department of GI Surgery, Clínica Universidad de Navarra, 31008 Pamplona, Spain;
| | - Ana Tortajada
- Department of Medical Oncology, Clínica Universidad de Navarra, 31008 Pamplona, Spain; (M.O.); (Á.V.A.); (A.T.); (M.J.H.)
| | - María José Hidalgo
- Department of Medical Oncology, Clínica Universidad de Navarra, 31008 Pamplona, Spain; (M.O.); (Á.V.A.); (A.T.); (M.J.H.)
| | - Onintza Sayar
- Department of Mathematics and Statistic, NNBi, 31110 Noain, Spain; (O.A.); (O.R.); (M.Z.); (O.S.)
| | - Javier Rodriguez
- Department of Medical Oncology, Clínica Universidad de Navarra, 31008 Pamplona, Spain; (M.O.); (Á.V.A.); (A.T.); (M.J.H.)
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16
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Back J, Sallinen V, Bonsdorff A, Kokkola A, Puolakkainen P. Short- and long-term outcomes after perioperative EOX therapy versus upfront surgery for gastric cancer: a single-centre propensity score-matched cohort study. BMC Surg 2025; 25:184. [PMID: 40296071 PMCID: PMC12039105 DOI: 10.1186/s12893-025-02919-4] [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: 09/26/2024] [Accepted: 04/14/2025] [Indexed: 04/30/2025] Open
Abstract
INTRODUCTION Despite radical surgery, gastric cancer (GC) survival rates remain low in Western countries. Randomised trials suggest that perioperative chemotherapy downstages disease, improving long-term survival without increasing complications. We compared outcomes for upfront surgery (US) versus surgery combined with perioperative EOX (epirubicin, oxaliplatin, capecitabine) therapy for short- and long-term survival. METHODS We analysed 310 patients who underwent curative intent gastrectomy for GC at a single tertiary centre from 2006 to 2017. Patients were assigned to the EOX group (n = 105) or the US group (n = 205). Propensity score matching (PSM) was utilised to balance baseline characteristics, clinical stage, surgery type, and histology. Short-term outcomes included the Comprehensive Complication Index (CCI) and 30-day mortality, while long-term outcomes were overall survival (OS), disease-specific survival (DSS), and disease-free survival (DFS). RESULTS After PSM, 102 patients remained in each group. The EOX group exhibited significantly lower preoperative haemoglobin levels compared to the US group, but other baseline characteristics were comparable. Tumour-related outcomes favoured the EOX group, with significantly smaller tumours (P < 0.001), fewer metastatic lymph nodes (P = 0.004), and lower tumour stages overall. Splenectomy was more common in the US group (40.2% versus 23.5%, P = 0.011). Postoperative complications were similar between groups, although ICU admissions were more frequent in the EOX group (16.7% versus 6.9%, P = 0.030). Thirty-day mortality rates were low and comparable (1.0% in the EOX group versus 2.0% in the US group, P = 1.000). Long-term outcomes, including overall survival (OS), disease-specific survival (DSS), and disease-free survival (DFS), showed no significant differences between the groups. CONCLUSIONS Perioperative EOX therapy is as safe as upfront surgery and significantly reduces metastatic lymph nodes and tumour size, suggesting its role in downstaging the disease. However, despite these promising oncological responses, this benefit does not translate into improved long-term survival.
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Affiliation(s)
- Johan Back
- Department of Abdominal Surgery, Helsinki University Hospital and University of Helsinki, Meilahti Tower Hospital, Building 1, Haartmaninkatu 4, PO Box 340, Helsinki, 00029 HUS, Finland.
| | - Ville Sallinen
- Department of Abdominal Surgery, Helsinki University Hospital and University of Helsinki, Meilahti Tower Hospital, Building 1, Haartmaninkatu 4, PO Box 340, Helsinki, 00029 HUS, Finland
- Department of Transplantation and Liver Surgery, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
| | - Akseli Bonsdorff
- Department of Abdominal Surgery, Helsinki University Hospital and University of Helsinki, Meilahti Tower Hospital, Building 1, Haartmaninkatu 4, PO Box 340, Helsinki, 00029 HUS, Finland
| | - Arto Kokkola
- Department of Abdominal Surgery, Helsinki University Hospital and University of Helsinki, Meilahti Tower Hospital, Building 1, Haartmaninkatu 4, PO Box 340, Helsinki, 00029 HUS, Finland
| | - Pauli Puolakkainen
- Department of Abdominal Surgery, Helsinki University Hospital and University of Helsinki, Meilahti Tower Hospital, Building 1, Haartmaninkatu 4, PO Box 340, Helsinki, 00029 HUS, Finland
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17
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Wang XD, Su XQ, Gao H. Association of Sijunzi decoction plus chemotherapy with gastrointestinal function and serum markers in patients after gastric carcinoma surgery. World J Gastrointest Surg 2025; 17:100800. [PMID: 40291867 PMCID: PMC12019030 DOI: 10.4240/wjgs.v17.i4.100800] [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: 12/20/2024] [Revised: 01/24/2025] [Accepted: 02/25/2025] [Indexed: 03/29/2025] Open
Abstract
BACKGROUND The deleterious effects of surgical trauma and subsequent postoperative complications pose significant challenges to the smooth recovery of patients after gastric cancer (GC) resection despite the substantial curative benefits provided by surgical interventions for GC. Hence, the investigation of more optimal and efficacious treatment approaches has become an urgent necessity in the medical community. AIM To investigate the association of Sijunzi decoction plus chemotherapy with the gastrointestinal function and serum markers of patients after GC surgery. METHODS This study included patients who underwent GC surgery from June 2022 to February 2024. The control group included 45 patients who received chemotherapy (oxaliplatin + calcium folinate + 5-fluorouracil), whereas the research group consisted of 54 patients who received Sijunzi decoction therapy in addition to the treatment administered in the control group. Comparative analyses were conducted from the following perspectives: Gastrointestinal function (defecation time, intestinal gas discharge time, and hospitalization time), serum markers [carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 125, and CA199], nutritional indicators [total protein (TP) and transferrin (TRF), traditional Chinese medicine (TCM) syndrome score, and grades III-IV adverse events (gastrointestinal reactions, renal/liver function impairment, and myelosuppression). RESULTS The two groups demonstrated similar defecation time (P > 0.05), but the intestinal gas discharge time and hospitalization time were significantly shortened in the research group (P < 0.05). Further, the research group exhibited significant CEA, CA125, and CA199 reductions after treatment, which were lower compared to the control group, as well as notable increases in TP and TRF that were statistically higher than the control group (all P < 0.05). Furthermore, the research group demonstrated an evident decrease in TCM syndrome scores in areas, such as poor appetite, epigastric distension and pain, fatigue and weakness (P < 0.01), and abdominal distension after eating, which are notably lower than those in the control group (P < 0.01), with a comparable incidence of grades III-IV adverse events (P > 0.05). CONCLUSION Our research results indicate that Sijunzi decoction plus chemotherapy exerts a good rehabilitation-promoting effect on gastrointestinal function in patients after GC surgery and significantly downregulates abnormally increased CEA, CA125, and CA199 levels.
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Affiliation(s)
- Xiao-Dong Wang
- Department of Oncology, Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Shenyang 110032, Liaoning Province, China
| | - Xiao-Qing Su
- Department of Traditional Chinese Medicine, Tawan Community Health Service Center, Shenyang 110032, Liaoning Province, China
| | - Hong Gao
- Department of Oncology, Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Shenyang 110032, Liaoning Province, China
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18
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Kan L, Yu Y, Wang Y, Shi L, Fan T, Chen H, Ren C. The application of organoids in investigating immune evasion in the microenvironment of gastric cancer and screening novel drug candidates. Mol Cancer 2025; 24:125. [PMID: 40287758 PMCID: PMC12032790 DOI: 10.1186/s12943-025-02328-4] [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: 12/09/2024] [Accepted: 04/10/2025] [Indexed: 04/29/2025] Open
Abstract
Gastric cancer (GC) is a prevalent digestive system tumor, the fifth most diagnosed cancer worldwide, and a leading cause of cancer deaths. GC is distinguished by its pronounced heterogeneity and a dynamically evolving tumor microenvironment (TME). The lack of accurate disease models complicates the understanding of its mechanisms and impedes the discovery of novel drugs. A growing body of evidence suggests that GC organoids, developed using organoid culture technology, preserve the genetic, phenotypic, and behavioral characteristics. GC organoids hold significant potential for predicting treatment responses in individual patients. This review provides a comprehensive overview of the current clinical treatment strategies for GC, as well as the history, construction and clinical applications of organoids. The focus is on the role of organoids in simulating the TME to explore mechanisms of immune evasion and intratumoral microbiota in GC, as well as their applications in guiding clinical drug therapy and facilitating novel drug screening. Furthermore, we summarize the limitations of GC organoid models and underscore the need for continued technological advancements to benefit both basic and translational oncological research.
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Affiliation(s)
- Liuyue Kan
- Department of Laboratory Medicine, Medical College, Yangzhou University, Yangzhou, China
| | - Ying Yu
- Department of Laboratory Medicine, Medical College, Yangzhou University, Yangzhou, China
| | - Yaxue Wang
- Department of Laboratory Medicine, Medical College, Yangzhou University, Yangzhou, China
| | - Lei Shi
- Department of General Surgery, Northern Jiangsu People's Hospital Affiliated to Yangzhou University, No. 98 Western Nantong Road, Yangzhou, 225001, China
| | - Tingyuan Fan
- Department of Laboratory Medicine, Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou, China
| | - Hui Chen
- Department of Geriatrics, Northern Jiangsu People's Hospital Affiliated to Yangzhou University, No. 98 Western Nantong Road, Yangzhou, 225001, China.
- Northern Jiangsu People's Hospital Affiliated to Yangzhou University, No. 98, Western Nantong Road, Yangzhou, 225001, China.
| | - Chuanli Ren
- Department of Laboratory Medicine, Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou, China.
- Department of Laboratory Medicine, The Yangzhou Clinical Medical College of Xuzhou Medical University, Yangzhou, China.
- The Yangzhou Clinical Medical College of Xuzhou Medical University, No. 98, Western Nantong Road, Yangzhou, 225001, China.
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19
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Lu YM, Ye ZB, Wang HK, Zhong WH, Shao XX, Hu HT, Jiang YJ, Li WY, Tian YT. Comparative outcomes of laparoscopic and open gastrectomy for T4b gastric cancer with transverse colon or mesentery invasion: a dual-center retrospective analysis. World J Surg Oncol 2025; 23:150. [PMID: 40259398 PMCID: PMC12012946 DOI: 10.1186/s12957-025-03809-y] [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: 02/17/2025] [Accepted: 04/13/2025] [Indexed: 04/23/2025] Open
Abstract
BACKGROUND The safety and feasibility of laparoscopic surgery for T4b gastric cancer with transverse colon or mesocolon invasion remain insufficiently characterized. This study aimed to compare the surgical outcomes of laparoscopic and open gastrectomy in individuals with T4b gastric cancer involving these anatomical structures. METHODS A retrospective cohort study was conducted across two centers, including 53 individuals with T4b gastric cancer involving the transverse colon or mesocolon who underwent curative-intent surgery between January 2011 and December 2019. Participants were divided into two groups based on the surgical approach: laparoscopic surgery (n = 32) and open surgery (n = 21). Perioperative outcomes, postoperative complications, and survival outcomes were evaluated and compared. RESULTS Baseline characteristics were comparable between the groups. The laparoscopic approach demonstrated significantly reduced intraoperative blood loss compared to open surgery (92.5 ± 101.9 mL vs. 147.6 ± 76.6 mL, p = 0.039). No significant differences were observed in operating time (187.8 ± 52.7 vs. 185.9 ± 52.3 min, p = 0.896), R0 resection rates (93.8% vs. 90.5%, p = 0.659), lymph node yield, or length of postoperative hospital stay. The incidence of postoperative complications was similar between the groups (10.3% vs. 10.5%, p = 0.986). Additionally, mean overall survival (31.4 vs. 27.2 months, p = 0.506) and progression-free survival (26.1 vs. 23.5 months, p = 0.573) did not differ significantly. CONCLUSIONS Laparoscopic gastrectomy with combined resection appears to be a feasible and safe alternative to open surgery for selected individuals with T4b gastric cancer involving the transverse colon or mesocolon. This approach achieves similar perioperative and long-term clinical outcomes compared to open surgery.
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Affiliation(s)
- Yi-Ming Lu
- Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 17 Panjiayuannanli, Chaoyang District, Beijing, 100021, China
| | - Zhi-Bin Ye
- Department of Gastrointestinal Surgery, Hebei General Hospital, No. 348 Heping West Road, Shijiazhuang, 050000, Hebei, China
| | - Hai-Kuo Wang
- Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 17 Panjiayuannanli, Chaoyang District, Beijing, 100021, China
| | - Wen-Hui Zhong
- Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 17 Panjiayuannanli, Chaoyang District, Beijing, 100021, China
| | - Xin-Xin Shao
- Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 17 Panjiayuannanli, Chaoyang District, Beijing, 100021, China
| | - Hai-Tao Hu
- Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 17 Panjiayuannanli, Chaoyang District, Beijing, 100021, China
| | - Yu-Juan Jiang
- Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 17 Panjiayuannanli, Chaoyang District, Beijing, 100021, China
| | - Wang-Yao Li
- Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 17 Panjiayuannanli, Chaoyang District, Beijing, 100021, China
| | - Yan-Tao Tian
- Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 17 Panjiayuannanli, Chaoyang District, Beijing, 100021, China.
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20
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Li JJ, Rogers JE, Waters RE, Gan Q, Blum Murphy M, Ajani JA. Evolution of Therapeutics for Locally Advanced Upper Gastrointestinal Adenocarcinoma. Cancers (Basel) 2025; 17:1307. [PMID: 40282483 PMCID: PMC12025458 DOI: 10.3390/cancers17081307] [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: 03/07/2025] [Revised: 04/01/2025] [Accepted: 04/09/2025] [Indexed: 04/29/2025] Open
Abstract
Upper gastrointestinal (GI) malignancies, including esophageal, gastroesophageal junction (GEJ), and gastric adenocarcinomas, remain a major global health concern, with poor overall survival and high recurrence rate despite aggressive treatment. Patients with very early tumors (cT1a) can benefit from endoscopic therapy. However, patients with locally advanced disease require multimodal therapies that may combine surgery, radiation, and systemic therapies. This review provides a comprehensive overview of recent advancements in the treatment of locally advanced upper GI adenocarcinomas. Surgical resection remains the cornerstone of curative treatment, with perioperative chemotherapy emerging as the standard of care. While preoperative chemoradiation has demonstrated some benefits in esophageal and GEJ cancers, recent data suggest a more limited role for radiation going forward. Immunotherapy has shown some promise in both the adjuvant and perioperative settings but has yet to establish definitive survival benefit. The integration of HER2-targeted therapies into treatment regimens for HER2-positive locally advanced gastroesophageal cancers has not yielded significant improvements, underscoring the need for more effective strategies. Ongoing research focuses on better predictive biomarkers, personalized treatment approaches, and potential organ preservation strategies for patients achieving a clinical complete response. Continued advancements in treatment modalities and precision medicine are critical to improving survival for patients with locally advanced upper GI adenocarcinomas.
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Affiliation(s)
- Jenny J. Li
- Department of Gastrointestinal Medical Oncology, University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA; (M.B.M.); (J.A.A.)
| | - Jane E. Rogers
- Department of Pharmacy Clinical Program, University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA;
| | - Rebecca E. Waters
- Department of Anatomical Pathology, University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA; (R.E.W.); (Q.G.)
| | - Qiong Gan
- Department of Anatomical Pathology, University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA; (R.E.W.); (Q.G.)
| | - Mariela Blum Murphy
- Department of Gastrointestinal Medical Oncology, University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA; (M.B.M.); (J.A.A.)
| | - Jaffer A. Ajani
- Department of Gastrointestinal Medical Oncology, University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA; (M.B.M.); (J.A.A.)
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21
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Bao Z, Jia N, Zhang Z, Hou C, Yao B, Li Y. Prospects for the application of pathological response rate in neoadjuvant therapy for gastric cancer. Front Oncol 2025; 15:1528529. [PMID: 40291912 PMCID: PMC12021903 DOI: 10.3389/fonc.2025.1528529] [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: 11/15/2024] [Accepted: 03/24/2025] [Indexed: 04/30/2025] Open
Abstract
With the annual increase in the incidence and mortality rates of gastric cancer, it has gradually become one of the significant threats to human health. Approximately 90% of gastric cancer patients are diagnosed with adenocarcinoma. Although the 5-year survival rate for early-stage gastric cancer can exceed 90%, due to its concealed symptoms, less than half of the patients are eligible for radical surgical treatment upon diagnosis. For gastric cancer patients receiving palliative treatment, the current expected survival time is only about one year. In China, the majority of gastric cancer patients, accounting for about 80% of the total, are in the locally advanced stage. For these patients, radical surgery remains the primary treatment option; however, surgery alone is often inadequate in controlling tumor progression. In the pivotal MAGIC study, the recurrence rate was as high as 75%, and similar results were obtained in the French ACCORD07-FFCD9703 study. Numerous clinical trials are currently exploring preoperative neoadjuvant therapy for patients with locally advanced gastric cancer. Data indicates that preoperative neoadjuvant therapy can not only reduce the size of the local tumor but also shrink surrounding lymph nodes, thereby downstaging the tumor and improving the R0 resection rate. Additionally, it can decrease tumor cell activity and eliminate potential micrometastases. The emergence of various immunotherapies has ushered in a new era for neoadjuvant treatment options for gastric cancer.
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Affiliation(s)
| | | | - Zhidong Zhang
- The Third Department of Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
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22
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Floris M, Angioi A, Liscia N, Ghidini M, Cinque A, Puzzoni M, Pani A, Lepori N, Scartozzi M, Dettori M, Cabiddu G, Testoni P, Cascinu S, Mazza E, Trevisani F. Preoperatory FLOT Regimen for Gastroesophageal Cancer and Renal Function: A New Onco-Nephrological Perspective. Kidney Blood Press Res 2025; 50:398-407. [PMID: 40203812 DOI: 10.1159/000545638] [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: 09/30/2024] [Accepted: 02/13/2025] [Indexed: 04/11/2025] Open
Abstract
BACKGROUND The FLOT regimen, a combination of fluorouracil, leucovorin, oxaliplatin, and docetaxel, is a standard treatment for gastric and esophagogastric junction cancers, but concerns exist about its potential renal toxicity. The exact prevalence and severity of renal toxicity need to be well documented, and this knowledge gap could impact the optimal use of the FLOT regimen in clinical practice. We aimed to evaluate the renal toxicity profile of the FLOT regimen with a specific focus on acute kidney disease (AKD) onset in a real-life setting and explore associated risk factors. METHODS We conducted a multicenter retrospective study involving 96 patients treated with preoperatory FLOT. The incidence of AKD and potential risk factors were identified. RESULTS AKD occurred in 3 patients (incidence rate of 0.0122 cases/month of follow-up). Oral antidiabetic agents and prostate hypertrophy emerged as significant predictors of AKD. CONCLUSION AKD is uncommon in patients treated with the preoperatory FLOT regimen. Our findings highlight the importance of diligent renal function monitoring and appropriate preventive strategies in patients undergoing FLOT treatment. These results encourage the conduction of further studies and clinical experience in larger populations and patients with lower baseline estimated glomerular filtration rate.
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Affiliation(s)
- Matteo Floris
- Department of Nephrology, Dialysis, and Transplantation, ARNAS G. Brotzu, Cagliari, Italy
| | - Andrea Angioi
- Department of Nephrology, Dialysis, and Transplantation, ARNAS G. Brotzu, Cagliari, Italy
| | - Nicole Liscia
- Department of Medical Oncology Ospedale San Raffaele, Vita-Salute University San Raffaele, Comprehensive Cancer Center, Milan, Italy
| | - Michele Ghidini
- Medical Oncology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | | | - Marco Puzzoni
- Medical Oncology Unit, University Hospital and University of Cagliari, Cagliari, Italy
| | - Antonello Pani
- Department of Nephrology, Dialysis, and Transplantation, ARNAS G. Brotzu, Cagliari, Italy
- Department of Medical Science and Public Health, University of Cagliari, Cagliari, Italy
| | - Nicola Lepori
- Department of Nephrology, Dialysis, and Transplantation, ARNAS G. Brotzu, Cagliari, Italy
- Department of Medical Science and Public Health, University of Cagliari, Cagliari, Italy
| | - Mario Scartozzi
- Medical Oncology Unit, University Hospital and University of Cagliari, Cagliari, Italy
| | - Manuela Dettori
- Medical Oncology Unit, Azienda Ospedaliera Brotzu, Ospedale Businco, Cagliari, Italy
| | - Gianfranca Cabiddu
- Department of Nephrology, Dialysis, and Transplantation, ARNAS G. Brotzu, Cagliari, Italy
- Department of Medical Science and Public Health, University of Cagliari, Cagliari, Italy
| | - Paola Testoni
- Department of Nephrology, Dialysis, and Transplantation, ARNAS G. Brotzu, Cagliari, Italy
| | - Stefano Cascinu
- Department of Medical Oncology Ospedale San Raffaele, Vita-Salute University San Raffaele, Comprehensive Cancer Center, Milan, Italy
| | - Elena Mazza
- Department of Medical Oncology Ospedale San Raffaele, Vita-Salute University San Raffaele, Comprehensive Cancer Center, Milan, Italy
| | - Francesco Trevisani
- Division of Experimental Oncology, Urological Research Institute (URI), IRCCS San Raffaele Scientific Institute, Milan, Italy
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Miura T, Yashima T, Takaya E, Taniyama Y, Sato C, Okamoto H, Ozawa Y, Ishida H, Unno M, Ueda T, Kamei T. Multimodal deep-learning model using pre-treatment endoscopic images and clinical information to predict efficacy of neoadjuvant chemotherapy in esophageal squamous cell carcinoma. Esophagus 2025; 22:207-214. [PMID: 39792350 DOI: 10.1007/s10388-025-01106-x] [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: 10/26/2023] [Accepted: 01/05/2025] [Indexed: 01/12/2025]
Abstract
BACKGROUND Neoadjuvant chemotherapy is standard for advanced esophageal squamous cell carcinoma, though often ineffective. Therefore, predicting the response to chemotherapy before treatment is desirable. However, there is currently no established method for predicting response to neoadjuvant chemotherapy. This study aims to build a deep-learning model to predict the response of esophageal squamous cell carcinoma to preoperative chemotherapy by utilizing multimodal data integrating esophageal endoscopic images and clinical information. METHODS 170 patients with locally advanced esophageal squamous cell carcinoma were retrospectively studied, and endoscopic images and clinical information before neoadjuvant chemotherapy were collected. Endoscopic images alone and endoscopic images plus clinical information were each analyzed with a deep-learning model based on ResNet50. The clinical information alone was analyzed using logistic regression machine learning models, and the area under a receiver operating characteristic curve was calculated to compare the accuracy of each model. Gradient-weighted Class Activation Mapping was used on the endoscopic images to analyze the trend of the regions of interest in this model. RESULTS The area under the curve by clinical information alone, endoscopy alone, and both combined were 0.64, 0.55, and 0.77, respectively. The endoscopic image plus clinical information group was statistically more significant than the other models. This model focused more on the tumor when trained with clinical information. CONCLUSIONS The deep-learning model developed suggests that gastrointestinal endoscopic imaging, in combination with other clinical information, has the potential to predict the efficacy of neoadjuvant chemotherapy in locally advanced esophageal squamous cell carcinoma before treatment.
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Affiliation(s)
- Takuma Miura
- Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-Machi, Aoba-Ku, Sendai, Miyagi, 980-8574, Japan.
| | - Takumi Yashima
- Department of Clinical Imaging, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Eichi Takaya
- AI Lab, Tohoku University Hospital, Sendai, Japan
| | - Yusuke Taniyama
- Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-Machi, Aoba-Ku, Sendai, Miyagi, 980-8574, Japan
| | - Chiaki Sato
- Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-Machi, Aoba-Ku, Sendai, Miyagi, 980-8574, Japan
| | - Hiroshi Okamoto
- Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-Machi, Aoba-Ku, Sendai, Miyagi, 980-8574, Japan
| | - Yohei Ozawa
- Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-Machi, Aoba-Ku, Sendai, Miyagi, 980-8574, Japan
| | - Hirotaka Ishida
- Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-Machi, Aoba-Ku, Sendai, Miyagi, 980-8574, Japan
| | - Michiaki Unno
- Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-Machi, Aoba-Ku, Sendai, Miyagi, 980-8574, Japan
| | - Takuya Ueda
- Department of Clinical Imaging, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Takashi Kamei
- Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-Machi, Aoba-Ku, Sendai, Miyagi, 980-8574, Japan
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Hu Q, Shi J, Yang X. FLOT x8 for Gastric Cancer: Progress or Premature Optimism? J Surg Oncol 2025; 131:769-772. [PMID: 39628084 DOI: 10.1002/jso.28028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2024] [Accepted: 11/20/2024] [Indexed: 05/31/2025]
Affiliation(s)
- Qiang Hu
- School of Integrated Chinese and Western Medicine, Zhejiang Chinese Medicine University, Hangzhou, China
- Department of general surgery, Tongde Hospital of Zhejiang Province, Hangzhou, China
| | - Jianfeng Shi
- Department of general surgery, Tongde Hospital of Zhejiang Province, Hangzhou, China
| | - Xiyin Yang
- Department of Traditional Chinese Medicine, Community Health Service Center of Guali Town of Xiaoshan, Hangzhou, China
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Liu B, Shen C, Yin X, Jiang T, Han Y, Yuan R, Yin Y, Cai Z, Zhang B. Perioperative chemotherapy for gastric cancer patients with microsatellite instability or deficient mismatch repair: A systematic review and meta-analysis. Cancer 2025; 131:e35831. [PMID: 40159317 DOI: 10.1002/cncr.35831] [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: 07/04/2024] [Revised: 11/28/2024] [Accepted: 02/17/2025] [Indexed: 04/02/2025]
Abstract
BACKGROUND The efficacy of perioperative chemotherapy for deficient mismatch repair or microsatellite instability-high (dMMR/MSI-H) gastric cancer (GC) remains controversial. METHODS This study was preregistered with the PROSPERO platform (CRD42023494276), and studies comparing perioperative chemotherapy with surgery alone in resectable dMMR/MSI-H GC were included. Hazard ratios (HRs) and their 95% confidence intervals (CIs) of survival outcomes were extracted. A random-effects model was used in the pooled analysis. RESULTS Twenty-two studies, which encompassed approximately 1600 patients with dMMR/MSI-H GC, were included. The results indicated that perioperative chemotherapy does not significantly improve overall survival (OS) (HR, 0.85; 95% CI, 0.58-1.26) and disease-free survival (DFS) (HR, 0.77; 95% CI, 0.53-1.12) in dMMR/MSI-H GC. In the subgroup analysis, adjuvant chemotherapy was not associated with improved OS (HR, 0.83; 95% CI, 0.50-1.37) but was associated with improved DFS (HR, 0.64; 95% CI, 0.43-0.96). However, the benefit of adjuvant chemotherapy for DFS was not significant in the pooled analysis of multivariable-adjusted results. Similar results were observed for neoadjuvant chemotherapy (OS: HR, 0.84; 95% CI, 0.44-1.57; DFS: HR, 1.13; 95% CI, 0.50-2.53). Additionally, stage stratification analysis demonstrated no significant survival benefit of adjuvant chemotherapy for stage II (OS: HR, 0.77; 95% CI, 0.31-1.90) or stage III (OS: HR, 0.72; 95% CI, 0.36-1.46) dMMR/MSI-H GC. CONCLUSIONS Despite indications that adjuvant chemotherapy may improve DFS in the subgroup analysis, this benefit was not sustained in multivariate assessments. Overall, the pooled results indicate that perioperative chemotherapy does not significantly improve OS or DFS in patients with resectable dMMR/MSI-H GC, and therefore such treatment may be spared in these patients.
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Affiliation(s)
- Baike Liu
- Gastric Cancer Center, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Chaoyong Shen
- Gastric Cancer Center, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Xiaonan Yin
- Gastric Cancer Center, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Tianxiang Jiang
- Gastric Cancer Center, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Yihui Han
- Gastric Cancer Center, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Ruiwan Yuan
- Department of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Yuan Yin
- Gastric Cancer Center, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China
- Department of Gastrointestinal Surgery, West China Xiamen Hospital, Sichuan University, Xiamen, China
| | - Zhaolun Cai
- Gastric Cancer Center, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Bo Zhang
- Gastric Cancer Center, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China
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SPACE-FLOT Investigators, Liu DS, Lee MM, Hall K, Watson DI, Ferri L, So J, Donohoe CL, Michael M, Tebbutt NC, Wong DJ, Duong CP, Bright T, Aly A, Gill S, Cheng C, Goh SK, Read M, Tan J, Stevens S, Wong E, Ooi G, Lam YH, Lee E, Williams D, Jackett L, Chan K, Smith G, Chan DL, Merrett N, Gananadha S, Kanhere H, Kennedy L, Smithers M, Thomas J, Bozin M, Chong L, Mori K, Johnson MA, Martin SA, Usatoff V, Jacobs R, Al-Habbal Y, Liew CH, Huynh F, Bohmer R, Pande G, Daruwalla J, Ballal M, Lee D, Ranjan R, MacCormick AD, Wilkins J, Pattison S, Evennett N, Wilkins J, Robertson J, Pang M, Gordon A, Bann S, Lim YK, Samarasam I, Gurunathan R, Yeung J, Allison F, Siblini A, Griffiths EA, Phillips AW, Prasad P, Markar S, Chidambaram S, Chan D, Murphy T, Reynolds J, Nilsson M, Klevebro F, Piessen G, Lerooy J, Wijnhoven B, van der Zijden C, van Hillegersberg R, Triemstra L, Ruurda J, van Berge Henegouwen MI, Gisbertz SS, Lombardi PM, Edmondson A, Wei JQ, Lorenzo A, Alhayo S, Narendra A, Rahim A, Ho R, Granger J, Tran S, Koullouros M, Nguyen A, McVeay C, Gan SW, Hopping E, et alSPACE-FLOT Investigators, Liu DS, Lee MM, Hall K, Watson DI, Ferri L, So J, Donohoe CL, Michael M, Tebbutt NC, Wong DJ, Duong CP, Bright T, Aly A, Gill S, Cheng C, Goh SK, Read M, Tan J, Stevens S, Wong E, Ooi G, Lam YH, Lee E, Williams D, Jackett L, Chan K, Smith G, Chan DL, Merrett N, Gananadha S, Kanhere H, Kennedy L, Smithers M, Thomas J, Bozin M, Chong L, Mori K, Johnson MA, Martin SA, Usatoff V, Jacobs R, Al-Habbal Y, Liew CH, Huynh F, Bohmer R, Pande G, Daruwalla J, Ballal M, Lee D, Ranjan R, MacCormick AD, Wilkins J, Pattison S, Evennett N, Wilkins J, Robertson J, Pang M, Gordon A, Bann S, Lim YK, Samarasam I, Gurunathan R, Yeung J, Allison F, Siblini A, Griffiths EA, Phillips AW, Prasad P, Markar S, Chidambaram S, Chan D, Murphy T, Reynolds J, Nilsson M, Klevebro F, Piessen G, Lerooy J, Wijnhoven B, van der Zijden C, van Hillegersberg R, Triemstra L, Ruurda J, van Berge Henegouwen MI, Gisbertz SS, Lombardi PM, Edmondson A, Wei JQ, Lorenzo A, Alhayo S, Narendra A, Rahim A, Ho R, Granger J, Tran S, Koullouros M, Nguyen A, McVeay C, Gan SW, Hopping E, Thomson I, Barbour A, Gotley D, Frankel A, Patel R, Chew SJH, Lah K, Gill S, Barnett SA, Muralidharan V, Phillips S, Jamel W, Ko BK, Joglekar S, Rajagopalan A, Jaya J, Chung YC, Peeroo S, Bak M, Tiong J, Zhou Z, Crowe A, Newbold R, Trainor B, Pac Soo ML, Khandelwal V, Eikelboom N, Kim K, Moran E, Hammerschlag J, Desmond B, D'Souza J, Lu J, McLay-Barnes R, Gower A, Choi J, Lim YK, Wood D, Whytock K, Surendran S, Paul N, Khan H F, Chia DKA, Leong EKF, Ijner T, Lin YTL, Liew MS, Jaretzke H, Dempster N, Bhanot K, Mian A, Mastoridis S, Gibbons B, Owen-Smith S, Walmsley J, Al Azzawi M, Doyle E, Okamura Y, Keywani K, Ferrari G, Gualtierotti M, De Martini P, Bushati F. Pathological response guides adjuvant 5-fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) chemotherapy in surgically resected gastro-oesophageal cancer (SPACE-FLOT): international cohort study. Br J Surg 2025; 112:znaf056. [PMID: 40156891 DOI: 10.1093/bjs/znaf056] [Show More Authors] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2024] [Revised: 02/11/2025] [Accepted: 02/20/2025] [Indexed: 04/01/2025]
Abstract
BACKGROUND Many patients with locally advanced gastro-oesophageal cancers are unable to complete adjuvant 5-fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) chemotherapy, raising questions about its therapeutic utility. The aim of this study was to examine whether pathological response to neoadjuvant FLOT can guide its adjuvant use. METHODS Patients with non-metastatic gastro-oesophageal adenocarcinoma who received neoadjuvant FLOT and underwent surgery from 1 January 2017 to 1 January 2022 from 43 hospitals across 12 countries were analysed. Pathological response was assessed using tumour regression grading systems, trichotomized into minimal responders (MR; worst category), complete responders (CR; pCR), and partial responders (PR; between MR and CR). Survival outcomes of patients who did and did not receive adjuvant FLOT were compared using Kaplan-Meier, Cox regression, propensity score matched, and sensitivity analysis. RESULTS A total of 1887 patients (459 MR, 221 CR, and 1207 PR) were evaluated. The median follow-up was 25.5 (interquartile range 15.0-39.1) months. In the MR group, there was no difference in disease-free survival (DFS; HR 1.03 (95% c.i. 0.78 to 1.36), P = 0.836) between those who did and did not receive adjuvant FLOT. Whilst there was a difference in non-adjusted OS, this became statistically non-significant after adjusting for baseline characteristics (HR 0.96 (95% c.i. 0.70 to 1.30), P = 0.801). In the CR group, there was no difference in DFS (HR 0.88 (95% c.i. 0.41 to 1.85), P = 0.724) or OS (HR 0.69 (95% c.i. 0.31 to 1.54), P = 0.343) between those who did and did not receive adjuvant FLOT. In the PR group, adjuvant FLOT conferred a significant DFS (HR 0.68 (95% c.i. 0.55 to 0.86), P < 0.001) and OS (HR 0.55 (95% c.i. 0.44 to 0.69), P < 0.001) benefit. CONCLUSION Pathological response to neoadjuvant FLOT may guide the use of adjuvant FLOT, enabling personalized approaches to treatment.
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Pu W, Li S, Zhang J, Huang J, Li J, Jiang Y, Xu Z, Yi F, Lan Y, Xiao Q, Chen W, Jin J. The efficacy and safety of PD-1/PD-L1 inhibitors in combination with chemotherapy as a first-line treatment for unresectable, locally advanced, HER2-negative gastric or gastroesophageal junction cancer: a meta-analysis of randomized controlled trials. Front Immunol 2025; 16:1566939. [PMID: 40207218 PMCID: PMC11979168 DOI: 10.3389/fimmu.2025.1566939] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2025] [Accepted: 03/11/2025] [Indexed: 04/11/2025] Open
Abstract
Background Immune checkpoint inhibitors (ICIs) plus fluorouracil-based chemotherapy (Chemo) have been approved as an initial treatment strategy for metastatic or recurrent human epidermal growth factor receptor 2 (HER2)-negative gastric cancer (GC) or gastroesophageal junction cancer (GEJC). However, since programmed cell death protein-1 (PD-1) or its ligand 1 (PD-L1) inhibitors have just recently been investigated for the treatment of unresectable GC/GEJC, there is ongoing debate regarding their safety and effectiveness for prespecified subgroups. The purpose of this research is to establish a foundation toward stratified decision-making by methodically assessing the merits and drawbacks of PD-1/PD-L1 inhibitors combined with chemo in the clinical utilization of advanced HER2-negative GC/GEJC according to certain prominent large-scale randomized controlled trials (RCTs). In addition, we limitedly explored the favorable short-term efficacy of PD-1/CTLA-4 bispecific antibodies for the above-mentioned tumors. Methods The researchers retrieved several databases, including PubMed, Embase, Web of Science, ClinicalTrials.gov, and the Cochrane Library, to collect all the relevant literature published since the establishment of the databases until October 30, 2024, and then screened to determine the qualified literature and extracted the relevant information. We only included RCTs for PD-1/PD-L1 inhibitors with or without chemo in advanced GC or GEJC. The primary endpoints were overall survival (OS), progression-free survival (PFS), and objective response rate (ORR). A subgroup analysis for the median overall survival (mOS) was conducted for the following variables: microsatellite instability (MSI) status, PD-L1 expression, combined positive scores (CPS), metastasis status, and primary tumor location. When moderate heterogeneity was found, a random-effect model was applied. The outcome indicators were then statistically analyzed, taking advantage of Review Manager 5.4. Hazard ratio (HR) and risk ratio (RR) were selected as the effect values for statistical analysis. Results A total of 7 eligible RCTs and 6537 participants were included in this meta-analysis. Combining PD-1/PD-L1 inhibitors with chemo significantly improved patients' OS compared with chemo alone, especially in the tumor cell PD-L1 expression ≥ 1% [HR = 0.62, 95% CI (0.48, 0.81); a p-value = 0.0004], PD-L1 CPS ≥ 10 [HR = 0.66, 95% CI (0.57, 0.77); a p-value < 0.00001], and MSI-H subgroups [HR = 0.40, 95% CI (0.28, 0.59); a p-value < 0.00001]. Moreover, distinct primary tumor location (GC or GEJC) and the presence of liver metastases could also benefit from the additive or sustained effect of anti-cancer chemo-immunotherapy. Conclusion For patients with advanced HER2-negative GC/GEJC, PD-1/PD-L1 inhibitors in combination with chemo have almost demonstrated consistent synergistic anti-tumor benefits to survival outcomes when compared to chemo alone. However, the subgroup analysis in this meta-study revealed that neither PD-L1 expression level nor MSI status could fully predict the efficacy of the dual treatment model but faced a higher possibility of serious treatment-related adverse events (sTRAEs), particularly in the synchronous therapy arm. Therefore, urging the need for more investigations into the development of collaborative prognostic forecasting models for achieving precise stratification, established harmonized testing standards and methods for PD-L1 expression and positivity, optimal CPS threshold for benefits, as well as alternative molecular biomarkers for the reason that certain indicators alone may not discriminate responders clearly. Lastly, dual anti-therapy might be a useful tactic for the population with low PD-L1 expression in the future.
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Affiliation(s)
- Wenji Pu
- Department of Clinical Oncology, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China
- 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
- Medical Department of Shenzhen University/General Hospital of Shenzhen University/Academy of Clinical Medicine of Shenzhen University, Shenzhen, China
| | - Shasha Li
- Department of Clinical Oncology, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China
| | - Jinliang Zhang
- Department of Clinical Oncology, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China
| | - Jijie Huang
- Department of Clinical Oncology, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China
| | - Jishi Li
- Department of Clinical Oncology, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China
| | - Yong Jiang
- Department of Clinical Oncology, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China
| | - Zhiyuan Xu
- Department of Clinical Oncology, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China
| | - Fan Yi
- Department of Clinical Oncology, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China
| | - Yuling Lan
- Department of Clinical Oncology, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China
| | - Qin Xiao
- 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
| | - Wenqi Chen
- Department of Clinical Oncology, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China
| | - Jing Jin
- 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
- State Key Laboratory of Molecular Oncology and Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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Lin Y, Lan Y, Zheng Y, Ma M. Dual-energy CT for evaluating the tumor regression grade of gastric cancer after neoadjuvant chemotherapy. Eur Radiol 2025:10.1007/s00330-025-11508-1. [PMID: 40100398 DOI: 10.1007/s00330-025-11508-1] [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: 09/04/2024] [Revised: 01/19/2025] [Accepted: 02/14/2025] [Indexed: 03/20/2025]
Abstract
OBJECTIVES To evaluate the clinical value of dual-energy CT (DECT) parameters in estimating tumor regression grade (TRG) of gastric cancer after neoadjuvant chemotherapy (NAC). MATERIALS AND METHODS In this retrospective study, the patients with pathologically confirmed gastric cancer were classified into two groups based on TRG results: the effective group and the ineffective group. DECT parameters, including iodine concentration (IC), normalized iodine concentration (NIC), and slope of the energy spectrum curve (λ), were obtained. Quantitative parameters and their change rates were compared before and after chemotherapy. The receiver operating characteristic (ROC) curves were plotted. RESULTS A total of 54 patients were included and divided into the effective group (n = 21) and the ineffective group (n = 33). After NAC, the change rates of parameters in the venous phase (%ΔIC-v, %ΔNIC-v, and %Δλ-v) were notably higher in the effective group were higher than in the ineffective group (all p < 0.05). The consistency between the response evaluation criteria in solid tumors version 1.1 (RECIST 1.1) and TRG was fair, with a Kappa value of 0.299 (p < 0.05). The %ΔIC-v, %ΔIC-d, %ΔNIC-v, %ΔNIC-d, and %Δλ-v exhibited moderate or strong correlations with TRG, with correlation coefficients (r) of -0.624, -0.475, -0.766, -0.516, and -0.431, respectively (all p < 0.05). %ΔNIC-v achieved a significantly greater area under the curve (AUC) compared to RECIST 1.1 (AUC, 0.877; 95% CI: 0.772-0.957; vs AUC, 0.649; 95% CI: 0.496-0.803; p < 0.05) for estimating TRG in gastric cancer. CONCLUSION DECT parameters, particularly %ΔNIC-v, show promise in assessing the efficacy of NAC for gastric cancer. KEY POINTS Question Two-dimensional morphological change is insufficient for accurately assessing the pathological TRG following NAC in gastric cancer. Findings DECT parameters show higher preoperative predictive efficacy than RECIST 1.1 for TRG in gastric cancer. Clinical relevance DECT-derived quantitative parameters offer a reliable and noninvasive tool for the preoperative prediction of pathological response in gastric cancer patients undergoing NAC.
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Affiliation(s)
- Yuying Lin
- Department of Radiology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial Hospital, Fuzhou, China
| | - Yanfen Lan
- Department of Radiology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial Hospital, Fuzhou, China
| | - Yunyan Zheng
- Department of Radiology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial Hospital, Fuzhou, China
| | - Mingping Ma
- Department of Radiology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial Hospital, Fuzhou, China.
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Li TH, Sun X, Li CG, Yin YP, Tao KX. Hypercoagulation after neoadjuvant immunochemotherapy as a new prognostic indicator in patients with locally advanced gastric cancer undergoing surgery. World J Gastrointest Oncol 2025; 17:100927. [PMID: 40092957 PMCID: PMC11866221 DOI: 10.4251/wjgo.v17.i3.100927] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2024] [Revised: 12/06/2024] [Accepted: 12/25/2024] [Indexed: 02/14/2025] Open
Abstract
BACKGROUND Coagulation status is closely related to the progression of malignant tumors. In the era of neoadjuvant immunochemotherapy (NICT), the prognostic utility of coagulation indicators in patients with locally advanced gastric cancer (LAGC) undergoing new treatments remains to be determined. AIM To determine whether hypercoagulation is an effective prognostic indicator in patients with LAGC who underwent radical resection after NICT. METHODS A retrospective analysis of clinical data from 104 patients with LAGC, who underwent radical resection after NICT between 2020 and 2023, was performed. D-dimer and fibrinogen concentrations were measured one week before NICT, and again one week before surgery, to analyze the association between these two indicators and their combined indices [non-hypercoagulation (D-dimer and fibrinogen concentrations within the upper limit of normal) vs hypercoagulation (D-dimer or fibrinogen concentrations above the upper limit of normal)] with prognosis. After radical resection, patients were followed-up periodically. The median follow-up duration was 21 months. RESULTS Data collected after NICT revealed that the three-year overall survival (OS) and disease-free survival (DFS) rates the non-hypercoagulation group were significantly better than those in the hypercoagulation group [94.4% vs 78.0% (P = 0.019) and 87.0% vs 68.0% (P = 0.027), respectively]. Multivariate analysis indicated that hypercoagulation after NICT was an independent factor for poor postoperative OS [hazard ratio (HR) 4.436, P = 0.023] and DFS (HR 2.551, P = 0.039). Pre-NICT data demonstrated no statistically significant difference in three-year OS between the non-hypercoagulation and hypercoagulation groups (88.3% vs 84.1%, respectively; P = 0.443). CONCLUSION Hypercoagulation after NICT is an effective prognostic indicator in patients with LAGC undergoing radical gastrectomy.
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Affiliation(s)
- Tian-Hao Li
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
| | - Xiong Sun
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
| | - Cheng-Guo Li
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
| | - Yu-Ping Yin
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
| | - Kai-Xiong Tao
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
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Yu X, Cui R, Guo P. Evaluation of the efficacy and safety of toripalimab combination therapy for treatment of advanced gastric cancer: a meta-analysis. INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL PATHOLOGY 2025; 18:96-109. [PMID: 40226111 PMCID: PMC11982770 DOI: 10.62347/gzow5960] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/06/2024] [Accepted: 02/12/2025] [Indexed: 04/15/2025]
Abstract
BACKGROUND To systematically evaluate the efficacy and safety of combination therapy with toripalimab in the treatment of advanced gastric cancer (GC). METHODS We conducted a thorough search for relevant studies in PubMed, Embase, Cochrane Library, and Web of Science. Effect estimates were computed utilizing Stata software (version 14.0) and either random or fixed effects models, as applicable. A subgroup analysis was undertaken to assess the effect of various combination therapies on overall response rate (ORR). Begg and Egger's tests were employed to assess publication bias. RESULTS The study consisted of 8 trials, which included 277 participants with advanced gastric cancer. The overall ORR was 41.4% (95% CI, 32.4%-50.3%), with a disease control rate (DCR) of 83.6% (95% CI, 74.6%-92.7%), a median overall survival (mOS) of 11.0 months (95% CI, 9.6-12.4), and a median progression-free survival (mPFS) of 4.2 months (95% CI, 2.5-6.0) for the combination therapy with toripalimab. Subgroup analysis revealed that the combination of toripalimab and chemotherapy achieved a greater ORR compared to the non-chemotherapy group, with ORR rates of 49.8% (95% CI, 42.2%-57.4%) and 31.9% (95% CI, 26.7%-37.1%), respectively. The combination therapy with toripalimab led to adverse events (AEs) of any grade at 94.0% of cases (95% CI, 89.5%-98.5%) and grade 3 AEs at 32.4% (95% CI, 17.8%-47.1%). The sensitivity analysis indicated that no single study affected the overall results. CONCLUSIONS Combination therapy of toripalimab can improve clinical efficacy, although with increased but manageable toxicity. Additional clinical trials are required to assess comprehensively the efficacy and safety of alternative toripalimab regimens. The review agreement has been recorded with PROSPERO (CRD42024585696).
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Affiliation(s)
- Xinlin Yu
- Department of Oncology, Affiliated Hospital Chengdu UniversityChengdu, Sichuan, China
| | - Ran Cui
- Department of Emergency, The First People’s Hospital of NeijiangNeijiang, Sichuan, China
| | - Ping Guo
- Department of Cardiology, Affiliated Hospital Chengdu UniversityChengdu, Sichuan, China
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Ou H, Zhuang J, Jian M, Zheng X, Wu T, Cheng H, Qian R. Perioperative versus adjuvant chemotherapy for resectable gastric cancer: a meta-analysis of randomized controlled trials. Front Oncol 2025; 15:1432596. [PMID: 40115020 PMCID: PMC11922704 DOI: 10.3389/fonc.2025.1432596] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2024] [Accepted: 02/17/2025] [Indexed: 03/22/2025] Open
Abstract
Objectives To report the latest systematic review and meta-analysis of randomized controlled trials (RCT) to compare perioperative versus adjuvant chemotherapy for resectable gastric cancer. Methods We conducted a systematic literature retrieval via PubMed, Embase, Web of Science, and Cochrane until April, 2024 for RCT which compared perioperative versus adjuvant chemotherapy for resectable gastric cancer. Outcomes measured were overall survival (OS) and progression-free survival (PFS). Results 5 RCTs including 2,735 patients were included for meta-analysis. Meta-analysis revealed a significant longer PFS in the neoadjuvant chemotherapy (NAC) group (HR: 0.77; 95% CI: 0.69, 0.85; P<0.00001) compared with adjuvant chemotherapy (AC) group. Subgroup analysis found that there was still a significant superiority of NAC in female (HR: 0.53; 95% CI: 0.40, 0.70; P<0.0001) and cN+ (HR: 0.77; 95% CI: 0.67, 0.89; P=0.0005) patients, while the superiority disappeared in male (HR: 0.87; 95% CI: 0.74, 1.01; P=0.07) and cN- patients (HR: 0.91; 95% CI: 0.46, 1.78; P=0.77). In addition, meta-analysis observed a trend towards improved OS with NAC (HR: 0.86; 95% CI: 0.70, 1.07; P = 0.17), and sensitivity analysis demonstrated instability in OS. Conclusions NAC can significantly prolong PFS in patients with resectable gastric cancer compared to AC, and the benefit is more significant in women and cN+ patients. Besides, our analysis indicated that NAC has a potential to improve OS compared with AC. Systematic review registration https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024546165.
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Affiliation(s)
- Haiya Ou
- Department of Gastroenterology, Shenzhen Bao'an Chinese Medicine Hospital, Guangzhou University of Chinese Medicine, Shenzhen, China
| | - Jiamei Zhuang
- Department of Nephrology, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, China
| | - Mingwei Jian
- Department of Gastroenterology, Shenzhen Bao'an Chinese Medicine Hospital, Guangzhou University of Chinese Medicine, Shenzhen, China
| | - Xinyi Zheng
- Department of Gastroenterology, Shenzhen Bao'an Chinese Medicine Hospital, Guangzhou University of Chinese Medicine, Shenzhen, China
| | - Tingping Wu
- Department of Gastroenterology, Shenzhen Bao'an Chinese Medicine Hospital, Guangzhou University of Chinese Medicine, Shenzhen, China
| | - Honghui Cheng
- Department of Gastroenterology, Shenzhen Bao'an Chinese Medicine Hospital, Guangzhou University of Chinese Medicine, Shenzhen, China
| | - Rui Qian
- Department of Gastroenterology, Shenzhen Bao'an Chinese Medicine Hospital, Guangzhou University of Chinese Medicine, Shenzhen, China
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Gan X, Jia Y, Shan F, Ying X, Li S, Zhang Y, Pang F, Li Z. Comprehensive evaluation of tumor response better evaluates the efficacy of neoadjuvant chemotherapy and predicts the prognosis in gastric cancer - a post hoc analysis of a single-center randomized controlled trial. BMC Cancer 2025; 25:401. [PMID: 40045265 PMCID: PMC11884205 DOI: 10.1186/s12885-024-13372-6] [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: 04/06/2024] [Accepted: 12/19/2024] [Indexed: 03/09/2025] Open
Abstract
BACKGROUND Perioperative chemotherapy combined with D2 radical gastrectomy has been proven to be the standard treatment for local advanced gastric cancer. However, tumor regression grading (TRG) is the only neoadjuvant chemotherapy (NACT) response evaluation criterion recommended by the NCCN guideline for gastric cancer (GC). Given TRG's limitations, we aim to explore a better comprehensive response evaluation method in this study. METHODS Clinical information of 96 GC patients who received NACT was collected prospectively. Clinicopathological variables predictive of the response to NACT were identified by comparing the pre- and post-NACT examination results. The correlations between the response mode and long-term survival rate were assessed. RESULTS Univariate Cox regression analysis showed that CT-based evaluation of the primary lesion thickness (CT-thickness) and tumor markers (TMs) were significantly associated with prognosis. The comprehensive evaluation method, including CT-thickness, TRG, and TMs, was constructed and proved to have a higher Harrell's C index. Significant differences in overall survival (OS) and recurrence-free survival (RFS) were observed between responders and non-responders distinguished by the comprehensive evaluation method. CONCLUSIONS The combination of CT-thickness, TRG, and TMs could be used to construct a pragmatic NACT efficacy evaluation method with both high sensitivity and specificity, which could facilitate clinical decision-making, NACT-related clinical research conduction, and efficacy predictive biomarker exploration.
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Affiliation(s)
- Xuejun Gan
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), gastrointestinal surgery of department, Peking University Cancer Hospital & Institute, Beijing, 100142, China
| | - Yongning Jia
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, gastrointestinal surgery of department, Peking University Cancer Hospital & Institute, Beijing, 100142, China
| | - Fei Shan
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, gastrointestinal surgery of department, Peking University Cancer Hospital & Institute, Beijing, 100142, China
| | - Xiangji Ying
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), gastrointestinal surgery of department, Peking University Cancer Hospital & Institute, Beijing, 100142, China
| | - Shuangxi Li
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), gastrointestinal surgery of department, Peking University Cancer Hospital & Institute, Beijing, 100142, China
| | - Yan Zhang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), gastrointestinal surgery of department, Peking University Cancer Hospital & Institute, Beijing, 100142, China
| | - Fei Pang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), gastrointestinal surgery of department, Peking University Cancer Hospital & Institute, Beijing, 100142, China
| | - Ziyu Li
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), gastrointestinal surgery of department, Peking University Cancer Hospital & Institute, Beijing, 100142, China.
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Kelly NJ, Shafique N, Tortorello GN, Vargas G, Miura JT, Karakousis GC. Total Gastrectomy for Gastric Malignancy: Trends Over 15 Years in Major Morbidity, Mortality, and Patient Selection From The National Surgical Quality Improvement Program. J Surg Oncol 2025; 131:624-629. [PMID: 39539107 PMCID: PMC12065443 DOI: 10.1002/jso.27990] [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: 09/08/2024] [Accepted: 10/12/2024] [Indexed: 11/16/2024]
Abstract
INTRODUCTION We examined trends in major morbidity and mortality following total gastrectomy for malignancy in a national cohort. METHODS The National Surgical Quality Improvement Program was used to identify patients who underwent total gastrectomy for malignancy from 2007 to 2021. Joinpoint regression was used to determine annual percent changes (APCs) in thirty-day postoperative major morbidity, mortality, and length of stay (LOS). Major morbidity included deep and organ space surgical site infection, venous thromboembolism, cardiac event, pneumonia, acute renal failure, sepsis, and respiratory failure. RESULTS Of 3515 patients, the median age was 65 years (IQR = 55-73), 59% were male, and 57.9% were White. Major morbidity was 23%, which did not change over time (APC = -1.4, 95% CI = -3.4 to 0.58), nor were there changes in individual morbidities with time. The most common morbidities were organ space surgical site infection (9.2%) and pneumonia (8.5%). Mortality rate in the study cohort was 2.7% and did not change (APC = -6.2, 95% CI = -13.0 to 1.1). LOS (median 9 days) also did not vary with time (APC = -2.3, 95% CI = -7.8 to 3.9). There was an increase in patients with diabetes (21.6% vs. 11.2%, p < 0.05), BMI ≥ 30 (31.1% vs. 18.2%, p < 0.05), and ASA IV-V status (11.6% vs. 3.5%, p < 0.05). CONCLUSION Morbidity and mortality following total gastrectomy for malignancy have not significantly changed over the last fifteen years. While this may in part be explained by increased patient comorbidity, efforts should be made to improve patient selection and mitigate postoperative complications to allow for timely adjuvant therapies.
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Affiliation(s)
- Nicholas J. Kelly
- Department of SurgeryUniversity of PennsylvaniaPhiladelphiaPennsylvaniaUSA
| | - Neha Shafique
- Department of SurgeryUniversity of PennsylvaniaPhiladelphiaPennsylvaniaUSA
| | | | - Gracia Vargas
- Department of SurgeryUniversity of PennsylvaniaPhiladelphiaPennsylvaniaUSA
| | - John T. Miura
- Department of SurgeryUniversity of PennsylvaniaPhiladelphiaPennsylvaniaUSA
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Yee EJ, Read J, Ziogas IA, Stuart CM, Olsen J, Kim SS, Mitchell JD, Meguid RA, McCarter MD, Mungo B. More May Not Be Better: Comparison of Oncologic Outcomes Following Induction Chemotherapy Plus Chemoradiation and Chemoradiation Alone for Esophageal Adenocarcinoma. J Surg Oncol 2025; 131:598-606. [PMID: 39501511 DOI: 10.1002/jso.27952] [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: 09/14/2024] [Accepted: 09/21/2024] [Indexed: 05/11/2025]
Abstract
INTRODUCTION The oncologic benefit of induction chemotherapy (IC) before chemoradiation (CRT) compared to CRT alone for locally advanced esophageal and gastroesophageal junction (GEJ) adenocarcinoma is not well defined. We hypothesized that IC with CRT would improve survival and pathologic complete response rate compared to CRT alone. METHODS A retrospective review of patients with biopsy proven esophageal or GEJ adenocarcinoma treated with preoperative CRT and IC + CRT and surgical resection from 2007 to 2023 at a single institution was performed. First order outcomes were overall survival and pathologic complete response rate; secondary outcomes included disease-free survival and distant metastasis failure. Subgroup analyses were conducted based on baseline characteristics and tumor-specific features. Survival analysis was performed with Kaplan-Meier curves with log-rank tests and Cox regression analysis. RESULTS Of 205 patients that met inclusion criteria, 76 (38%) patients underwent IC + CRT. There were no significant differences in demographic or tumor-specific characteristics between the two cohorts. There were no differences in the median overall survival between CRT and IC + CRT groups (47 months vs. not reached, p = 0.194). The rate of pathologic complete response in the overall cohort was 22%; IC + CRT was not associated with higher complete tumor response than CRT alone (20% vs. 23%, p = 0.557). There were no significant differences in any of the secondary outcomes between the two treatment paradigms. CONCLUSIONS We could not detect added oncologic benefit in survival or pathologic complete response with IC over CRT alone for resectable esophageal and GEJ cancer. Biomarker driven prospective studies exploring the optimal perioperative treatment regimens are warranted.
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Affiliation(s)
- Elliott J Yee
- Department of Surgery, University of Colorado School of Medicine Anschutz Medical Campus, Aurora, Colorado, USA
| | - Jake Read
- Department of Surgery, University of Colorado School of Medicine Anschutz Medical Campus, Aurora, Colorado, USA
| | - Ioannis A Ziogas
- Department of Surgery, University of Colorado School of Medicine Anschutz Medical Campus, Aurora, Colorado, USA
| | - Christina M Stuart
- Department of Surgery, University of Colorado School of Medicine Anschutz Medical Campus, Aurora, Colorado, USA
| | - Jeffrey Olsen
- Department of Radiation Oncology, University of Colorado School of Medicine Anschutz Medical Campus, Aurora, Colorado, USA
| | - Sunnie S Kim
- Division of Hematology/Oncology, Department of Medicine, University of Colorado School of Medicine Anschutz Medical Campus, Aurora, Colorado, USA
| | - John D Mitchell
- Department of Surgery, University of Colorado School of Medicine Anschutz Medical Campus, Aurora, Colorado, USA
| | - Robert A Meguid
- Department of Surgery, University of Colorado School of Medicine Anschutz Medical Campus, Aurora, Colorado, USA
| | - Martin D McCarter
- Department of Surgery, University of Colorado School of Medicine Anschutz Medical Campus, Aurora, Colorado, USA
| | - Benedetto Mungo
- Department of Surgery, University of Colorado School of Medicine Anschutz Medical Campus, Aurora, Colorado, USA
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Jiang W, Zhang B, Xu J, Xue L, Wang L. Current status and perspectives of esophageal cancer: a comprehensive review. Cancer Commun (Lond) 2025; 45:281-331. [PMID: 39723635 PMCID: PMC11947622 DOI: 10.1002/cac2.12645] [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: 07/01/2024] [Revised: 12/08/2024] [Accepted: 12/10/2024] [Indexed: 12/28/2024] Open
Abstract
Esophageal cancer (EC) continues to be a significant global health concern, with two main subtypes: esophageal squamous cell carcinoma and esophageal adenocarcinoma. Prevention and changes in etiology, improvements in early detection, and refinements in the treatment have led to remarkable progress in the outcomes of EC patients in the past two decades. This seminar provides an in-depth analysis of advances in the epidemiology, disease biology, screening, diagnosis, and treatment landscape of esophageal cancer, focusing on the ongoing debate surrounding multimodality therapy. Despite significant advancements, EC remains a deadly disease, underscoring the need for continued research into early detection methods, understanding the molecular mechanisms, and developing effective treatments.
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Affiliation(s)
- Wei Jiang
- Department of Radiation OncologyNational Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeShenzhenGuangdongP. R. China
| | - Bo Zhang
- Department of Medical OncologyNational Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingP. R. China
| | - Jiaqi Xu
- Department of PathologyNational Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingP. R. China
| | - Liyan Xue
- Department of PathologyNational Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingP. R. China
| | - Luhua Wang
- Department of Radiation OncologyNational Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeShenzhenGuangdongP. R. China
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He J, Zhang B, Zhou S, Yang Y, Han Z, Wu T, Qiao Q, Yang H, He X, Wang N. Phase II study of perioperative camrelizumab and XELOX for locally advanced gastric or gastroesophageal junction adenocarcinoma. Cancer Sci 2025; 116:736-743. [PMID: 39656600 PMCID: PMC11875781 DOI: 10.1111/cas.16425] [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: 05/17/2024] [Revised: 11/15/2024] [Accepted: 11/24/2024] [Indexed: 12/17/2024] Open
Abstract
Immune checkpoint inhibitors combined with chemotherapy have shown promising efficacy in treating gastric or gastroesophageal junction (G/GEJ) adenocarcinoma in the neoadjuvant setting. This phase II trial (NCT05715632) aimed to investigate the efficacy and safety of perioperative camrelizumab plus XELOX in patients with locally advanced G/GEJ adenocarcinoma. Treatment-naive patients with cT3-4aN1-3 M0 resectable locally advanced G/GEJ adenocarcinoma were recruited to receive camrelizumab (200 mg, intravenously) on Day 1 combined with XELOX (oxaliplatin at 130 mg/m2 on Day 1 and capecitabine at 1000 mg/m2 on Days 1-14) every 3 weeks for four cycles, followed by surgery and adjuvant camrelizumab combined with XELOX every 3 weeks for four cycles. The primary endpoint was the pathological complete response (pCR; ypT0N0) rate. From September 2020 to January 2023, 46 patients were enrolled, and all patients completed neoadjuvant therapy. Among them, 43 underwent D2 resection. In the intention-to-treat population, pCR was achieved in nine patients (19.6%, 95% confidence interval [CI]: 9.9%-34.4%), and the major pathological response was achieved in 25 patients (54.3%, 95% CI: 39.2%-68.8%). The objective response rate was 69.6%, of which 12 patients achieved a complete response and 20 patients achieved a partial response. The 1-year event-free survival and disease-free survival rates were both 93.1%. Treatment-related adverse events (TRAEs) occurred in 42 (91.3%) patients, and grade 3 TRAEs occurred in nine (19.6%) patients. No grades 4-5 TRAEs were observed. Perioperative camrelizumab combined with XELOX showed promising pathological response with an acceptable safety profile in patients with resectable locally advanced G/GEJ adenocarcinoma.
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Affiliation(s)
- Jiaxing He
- Department of General SurgeryAir Force Medical University Tangdu HospitalXi'anChina
| | - Bo Zhang
- Department of General SurgeryAir Force Medical University Tangdu HospitalXi'anChina
| | - Shuai Zhou
- Department of General SurgeryAir Force Medical University Tangdu HospitalXi'anChina
| | - Ying Yang
- Department of General SurgeryAir Force Medical University Tangdu HospitalXi'anChina
| | - Zhuo Han
- Department of General SurgeryAir Force Medical University Tangdu HospitalXi'anChina
| | - Tao Wu
- Department of General SurgeryAir Force Medical University Tangdu HospitalXi'anChina
| | - Qing Qiao
- Department of General SurgeryAir Force Medical University Tangdu HospitalXi'anChina
| | - Haicheng Yang
- Department of General SurgeryAir Force Medical University Tangdu HospitalXi'anChina
| | - Xianli He
- Department of General SurgeryAir Force Medical University Tangdu HospitalXi'anChina
| | - Nan Wang
- Department of General SurgeryAir Force Medical University Tangdu HospitalXi'anChina
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Malekzada F, Vladimiriov M, Leitz M, Michel J, Nimzewski F, Hoeppner J. Neoadjuvant treatment of esophageal cancer: chemotherapy, chemoradiation, immunotherapy, and future trends of therapy. Innov Surg Sci 2025; 10:3-9. [PMID: 40144785 PMCID: PMC11934940 DOI: 10.1515/iss-2023-0005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2023] [Accepted: 10/07/2024] [Indexed: 03/28/2025] Open
Abstract
In the Western hemisphere, nonmetastatic locally advanced esophageal carcinoma is mostly treated in multimodal therapy protocols according to current therapy guidelines. In squamous cell carcinoma of the esophagus, neoadjuvant chemoradiation is the favorable option. Unimodal surgical and chemoradiation treatment alternatives show inferior results on this entity. For locally advanced adenocarcinoma of the esophagus perioperative chemotherapy and neoadjuvant chemoradiation have been competing treatment approaches in the recent past. Both are evidence based (class I evidence) and superior compared to unimodal surgery. However, the latest results of head-to-head comparative therapy studies show superior overall survival results for the FLOT regimen of perioperative chemotherapy. Furthermore, immunotherapy and targeted therapy with monoclonal antibodies have become a strong focus of current clinical research. Nivolumab as well as trastuzumab are already an important part of the current standard therapies. In both entities - SCC and AC - a significant quota of patients shows a locoregional complete remission of the tumor in the specimen after modern neoadjuvant therapy and surgical resection. The addition of immunotherapy and targeted therapy to neoadjuvant therapy further increases complete remission rates in defined subgroups according to the results of current studies. Currently, three prospective randomized trials are ongoing on the subject of future possibilities for organ-preserving concepts in case of complete clinical remission ("surgery as needed," "watch and wait"). It is to be expected for the future that curative short-term and long-term treatment results in locally advanced esophageal carcinoma will significantly improve, particularly due to the additional possibilities of immunotherapy and organ-preserving therapy concepts in postneoadjuvant complete remission.
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Affiliation(s)
- Freschta Malekzada
- Department of Surgery, University Medical Center Schleswig-Holstein, Campus Lübeck, Lübeck, Germany
| | - Miljana Vladimiriov
- Department of Surgery, Bielefeld University, Medical School and University Medical Center OWL, Klinikum Lippe, Detmold, Germany
| | - Michael Leitz
- Department of Surgery, Bielefeld University, Medical School and University Medical Center OWL, Klinikum Lippe, Detmold, Germany
| | - Julia Michel
- Department of Surgery, Bielefeld University, Medical School and University Medical Center OWL, Klinikum Lippe, Detmold, Germany
| | - Fabian Nimzewski
- Department of Surgery, Bielefeld University, Medical School and University Medical Center OWL, Klinikum Lippe, Detmold, Germany
| | - Jens Hoeppner
- Department of Surgery, Bielefeld University, Medical School and University Medical Center OWL, Klinikum Lippe, Detmold, Germany
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Dehal A, Woo Y, Glazer ES, Davis JL, Strong VE. D2 Lymphadenectomy for Gastric Cancer: Advancements and Technical Considerations. Ann Surg Oncol 2025; 32:2129-2140. [PMID: 39589578 DOI: 10.1245/s10434-024-16545-6] [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: 09/09/2024] [Accepted: 11/05/2024] [Indexed: 11/27/2024]
Abstract
Lymphadenectomy (LND) is a crucial component of the curative surgical treatment of gastric cancer (GC). The LND serves to both accurately stage the disease and offer therapeutic benefits. At the time of "curative-intent" gastrectomy, D2 LND is the optimal treatment for patients with locally advanced GC due to its survival benefits and acceptable morbidity. Mastery of the technical aspects of LND, especially D2, requires significant training, adequate case volume, and expertise. This review discusses key aspects of D2 LND, including its status as the standard treatment for locally advanced GC, definition and anatomic borders, technical details, and controversial topics such as splenic hilar dissection and omentectomy. The application of indocyanine green (ICG) fluorescence imaging to elucidate the drainage patterns of GC and to facilitate lymph node (LN) identification is briefly reviewed. Finally, GC standardization and centralization, including surgical treatment, are discussed.
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Affiliation(s)
- Ahmed Dehal
- Department of General Surgery, Southern California Permanente Medical Group, Department of Clinical Sciences, Kaiser Permanente School of Medicine, Los Angeles, CA, USA.
| | - Yanghee Woo
- Division of Surgical Oncology, Department of Surgery, City of Hope Comprehensive Cancer Center, Duarte, CA, USA
| | - Evan S Glazer
- Department of Surgery, University of Tennessee Health Science Center, Memphis, TN, USA
| | - Jeremey L Davis
- Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
| | - Vivian E Strong
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
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Rencuzogullari A, Karahan SN, Selcukbiricik F, Lacin S, Taskin OC, Saka B, Karahacioglu D, Gurses B, Ozoran E, Uymaz DS, Ozata IH, Saglam S, Bugra D, Balik E. The New Era of Total Neoadjuvant FLOT Therapy for Locally Advanced, Resectable Gastric Cancer: A Propensity-Matched Comparison With Standard Perioperative Therapy. J Surg Oncol 2025; 131:417-426. [PMID: 39400342 PMCID: PMC12044282 DOI: 10.1002/jso.27934] [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: 06/07/2024] [Revised: 08/28/2024] [Accepted: 09/17/2024] [Indexed: 10/15/2024]
Abstract
BACKGROUND The FLOT 4-AIO trial established the docetaxel-based regimen's superiority over epirubicin-based triplet therapy in terms of survival rates and acceptable toxicity for locally advanced resectable gastric (LARGC). Yet, fewer than half of the patients achieved completion of eight prescribed FLOT cycles. We proposed that administering all FLOT cycles in the form of total neoadjuvant therapy may improve completion rates and downstaging. This study contrasted total neoadjuvant therapy (FLOT x8) with standard neoadjuvant therapy (FLOT 4+4) for patients LARGC adenocarcinoma who underwent curative resection with routine D2 lymphadenectomy, focusing on histopathological outcomes, toxicity, and survival outcomes. METHODS We reviewed patients with histologically confirmed advanced clinical stage cT2 or higher, nodal positive stage (cN+), or both, with resectable gastric tumors and no distant metastases (January 2017 to July 2023). We divided patients into two groups, FLOT 4+4 and FLOT x8; FLOT 4+4 patients underwent four preoperative and four postoperative bi-weekly cycles of docetaxel, oxaliplatin, leucovorin, and fluorouracil, while FLOT x8 patients received all eight cycles preoperatively after a gradual practice change starting from January 2020. Propensity score matching adjusted for age, clinical stage, tumor location, and histology. RESULTS Of the 77 patients in the FLOT x8 group, 37 were propensity-matched to an equal number in the FLOT 4+4 group. Demographics, duration of surgery, and hospital stay showed no significant differences between the groups. The FLOT x8 group exhibited a significantly higher all-cycle completion rate at 89.1% compared to FLOT 4+4's 67.6% (p < 0.01). Both groups demonstrated comparable hematological and non-hematological toxicity rates, Clavien-Dindo ≥ 3 complications, and CAP tumor regression grades. The mean number of harvested lymph nodes was 42.5 and 41.2 in the FLOT 4+4 and FLOT x8 groups, respectively. Similar rates of disease-free survival and overall survival were noted in both groups, despite a trend toward a higher pathological complete response rate, albeit not statistically significant (8.1% vs. 18.9%, p = 0.29), in the FLOT x8 group at a median follow-up of 36 months. CONCLUSION Total neoadjuvant therapy with the FLOT x8 protocol corresponds to higher treatment completion rates, a safety profile similar to standard perioperative therapy, and a twofold increase in complete pathological response. Further research on long-term oncological outcomes is needed to confirm the effectiveness of total neoadjuvant therapy.
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Affiliation(s)
| | - Salih Nafiz Karahan
- Department of General Surgery, School of MedicineKoç UniversityIstanbulTurkey
| | - Fatih Selcukbiricik
- Department of Medical Oncology, School of MedicineKoç UniversityIstanbulTurkey
| | - Sahin Lacin
- Department of Medical Oncology, School of MedicineKoç UniversityIstanbulTurkey
| | - Orhun Cig Taskin
- Department of Pathology, School of MedicineKoç UniversityIstanbulTurkey
| | - Burcu Saka
- Department of Pathology, School of MedicineKoç UniversityIstanbulTurkey
| | | | - Bengi Gurses
- Department of Radiology, School of MedicineKoç UniversityIstanbulTurkey
| | - Emre Ozoran
- Department of General Surgery, School of MedicineKoç UniversityIstanbulTurkey
| | - Derya Salim Uymaz
- Department of General Surgery, School of MedicineKoç UniversityIstanbulTurkey
| | - Ibrahim Halil Ozata
- Department of General Surgery, School of MedicineKoç UniversityIstanbulTurkey
| | - Sezer Saglam
- Department of Medical OncologyDemiroglu Bilim UniversityIstanbulTurkey
| | - Dursun Bugra
- Department of General Surgery, School of MedicineKoç UniversityIstanbulTurkey
- Department of General SurgeryAmerican HospitalIstanbulTurkey
| | - Emre Balik
- Department of General Surgery, School of MedicineKoç UniversityIstanbulTurkey
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Xu G, Liu T, Shen J, Guan Q. Neoadjuvant therapy with immune checkpoint inhibitors in combination with chemotherapy vs . chemotherapy alone in HER2(-) locally advanced gastric cancer: A propensity score-matched cohort study. Chin Med J (Engl) 2025; 138:459-471. [PMID: 38420853 PMCID: PMC11845188 DOI: 10.1097/cm9.0000000000003028] [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: 10/18/2023] [Indexed: 03/02/2024] Open
Abstract
BACKGROUND This study aims to compare the efficacy between neoadjuvant immune checkpoint inhibitors (ICIs) plus chemotherapy vs . chemotherapy, and neoadjuvant triplet vs . doublet chemotherapeutic regimens in locally advanced gastric/esophagogastric junction cancer (LAGC). METHODS We included LAGC patients from 47 hospitals in China's National Cancer Information Database (NCID) from January 2019 to December 2022. Using propensity score matching (PSM), we retrospectively analyzed the efficacy between neoadjuvant ICIs plus chemotherapy vs . chemotherapy alone, and neoadjuvant triplet vs . doublet chemotherapeutic regimens. The primary study result was the pathologic complete response (pCR) rate. The secondary study results were disease-free survival (DFS) and overall survival (OS). RESULTS A total of 1205 LAGC patients were included. After PSM, the ICIs plus chemotherapy and the chemotherapy cohorts had 184 patients each, while the doublet and triplet chemotherapy cohorts had 246 patients each. The pCR rate (14.13% vs . 7.61%, χ2 = 4.039, P = 0.044), and the 2-year (77.60% vs . 61.02%, HR = 0.67, 95% con-fidence interval [CI] 0.43-0.98, P = 0.048) and 3-year (70.55% vs . 61.02%, HR = 0.58, 95% CI 0.32-0.93, P = 0.048) DFS rates in the ICIs plus chemotherapy cohort were improved compared to those in the chemotherapy cohort. No significant increase was observed in the OS rates at both 1 year and 2 years. The pCR rates, DFS rates at 1-3 years, and OS rates at 1-2 years did not differ significantly between the doublet and triplet cohorts, respectively. No differences were observed in postoperative complications between any of the group comparisons. CONCLUSIONS Neoadjuvant ICIs plus chemotherapy improved the pCR rate and 2-3 years DFS rates of LAGC compared to chemotherapy alone, but whether short-term benefit could translate into long-term efficacy is unclear. The triplet regimen was not superior to the doublet regimen in terms of efficacy. The safety after surgery was similar between either ICIs plus chemotherapy and chemotherapy or the triplet and the doublet regimen.
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Affiliation(s)
- Gehan Xu
- The First Clinical Medical College of Lanzhou University, Lanzhou, Gansu 730000, China
| | - Tianjiao Liu
- Department of Medical Data, Beijing Yiyong Technology Co., Ltd., Beijing 100102, China
| | - Jingyi Shen
- The First Clinical Medical College of Lanzhou University, Lanzhou, Gansu 730000, China
| | - Quanlin Guan
- Department of Oncology Surgery, The First Hospital of Lanzhou University, Lanzhou, Gansu 730000, China
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Serra F, Valerio F, Pedrazzoli P, Viganò J, Caccialanza R, Cicognini D, Pagani A, Corallo S. Real-life effectiveness of FLOT in resectable gastric cancer: existing challenges. Drugs Context 2025; 14:2024-10-7. [PMID: 40017727 PMCID: PMC11867168 DOI: 10.7573/dic.2024-10-7] [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: 10/30/2024] [Accepted: 12/27/2024] [Indexed: 03/01/2025] Open
Abstract
Background Gastric cancer has a high mortality rate. Therapeutic management must be multidisciplinary to offer the patient the best, personalized strategy. Patients and methods We performed an observational study to evaluate the pathological response, survival and nutritional status in patients with resectable gastric cancer and candidates for perioperative chemotherapy with the fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT) regimen versus other regimens. The primary endpoints were pathological response rate, care continuity rate and survival outcomes. A total of 96 patients attending the Hospital "Policlinico San Matteo" in Pavia (Italy) between January 2012 and August 2022 were selected for the study. Results Regarding pathological response rates, the best rate (TRG-0) was recorded in the FLOT group with a percentage of 6.2% compared with 4.7% in the NO-FLOT arm (p=0.052). The highest failure rate to complete the post-operative phase was 75% in the NO-FLOT group and only 25% in the FLOT group (p=0.007). Survival outcomes were better in the FLOT group with a median disease-free survival of 30 versus 22.2 months (p=0.586). Conclusions Despite the limitations, the results obtained were consistent with the medical literature and confirmed the effectiveness of the FLOT chemotherapy in real life. Nevertheless, some questions remain: the application in elderly patients, the addition of immunotherapy in patients with microsatellite instability or with high PD-L1 levels, comparison with chemoradiotherapy in junctional cancers and real cure rates. The FLOT regimen has revolutionized the treatment of resectable gastric cancer, but caution is needed before considering it an absolute standard of care.
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Affiliation(s)
- Francesco Serra
- Internal Medicine and Medical Therapy Department, University of Pavia, Pavia, Italy
- Medical Oncology Unit, Hospital Policlinico San Matteo of Pavia, Pavia, Italy
| | - Federica Valerio
- Internal Medicine and Medical Therapy Department, University of Pavia, Pavia, Italy
- Medical Oncology Unit, Hospital Policlinico San Matteo of Pavia, Pavia, Italy
| | - Paolo Pedrazzoli
- Internal Medicine and Medical Therapy Department, University of Pavia, Pavia, Italy
- Medical Oncology Unit, Hospital Policlinico San Matteo of Pavia, Pavia, Italy
| | - Jacopo Viganò
- General Surgery Unit, Hospital Policlinico San Matteo of Pavia, Pavia, Italy
| | - Riccardo Caccialanza
- Dietetics and Clinical Nutrition Unit, Hospital Policlinico San Matteo of Pavia, Pavia, Italy
| | - Daniela Cicognini
- Internal Medicine and Medical Therapy Department, University of Pavia, Pavia, Italy
- Medical Oncology Unit, Hospital Policlinico San Matteo of Pavia, Pavia, Italy
| | - Anna Pagani
- Internal Medicine and Medical Therapy Department, University of Pavia, Pavia, Italy
- Medical Oncology Unit, Hospital Policlinico San Matteo of Pavia, Pavia, Italy
| | - Salvatore Corallo
- Internal Medicine and Medical Therapy Department, University of Pavia, Pavia, Italy
- Medical Oncology Unit, Hospital Policlinico San Matteo of Pavia, Pavia, Italy
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Geng Y, Zhao J, Li Y, Li Y. Adjuvant treatment after neoadjuvant chemoradiotherapy and surgery in patients with esophageal squamous cell carcinoma: a real-world study. Ther Adv Med Oncol 2025; 17:17588359251316179. [PMID: 39957805 PMCID: PMC11829303 DOI: 10.1177/17588359251316179] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2024] [Accepted: 01/09/2025] [Indexed: 02/18/2025] Open
Abstract
Background Neoadjuvant chemoradiotherapy (NCRT) combined with surgery is the standard treatment option for patients with locally advanced esophageal squamous cell carcinoma (ESCC). However, whether adjuvant chemotherapy (AC) administered postoperatively has a survival benefit remains inconclusive. Objectives To investigate whether AC is necessary after NCRT and esophagectomy and determine which patients might benefit from it. Design A retrospective study. Methods This retrospective study examined patients with ESCC treated with NCRT followed by radical esophagectomy at three hospitals between March 2016 and December 2022. Patients were assigned into the adjuvant and non-adjuvant therapy groups based on whether they received postoperative AC, allowing the comparison of disease-free survival (DFS) and overall survival (OS) between the two groups. In addition, based on whether postoperative pathology indicated pathological complete response (pCR), patients were classified into the pCR and non-pCR populations, with DFS and OS separately analyzed for each subgroup. Results Overall, 218 eligible patients were enrolled. No significant advantage was found in DFS (p = 0.540) and OS (p = 0.058) between the adjuvant and non-adjuvant therapy groups. In the non-pCR population, the adjuvant therapy groups had a significant advantage in DFS (p = 0.046) and OS (p = 0.011) compared to the non-adjuvant therapy group. However, in the pCR population, no significant advantage was found in DFS (p = 0.490) and OS (p = 0.110) analyses between the adjuvant and non-adjuvant therapy groups. Conclusion In the real world, patients with ESCC who underwent NCRT combined with radical esophagectomy and whose postoperative pathology was pCR did not benefit from AC. However, AC significantly improved DFS and OS in patients whose postoperative pathology did not reach pCR.
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Affiliation(s)
- Yuxin Geng
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China
| | - Junfeng Zhao
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China
| | - Ying Li
- Department of Respiratory Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China
| | - Yintao Li
- Department of Respiratory Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, 440 Jiyan Road, Huaiyin District, Jinan, Shandong 250000, China
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Jang T, Kim GP, George TJ. Select updates from ASCO and ESMO 2024 for gastrointestinal cancer care. Oncologist 2025; 30:oyaf020. [PMID: 39998903 PMCID: PMC11853594 DOI: 10.1093/oncolo/oyaf020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2024] [Accepted: 01/16/2025] [Indexed: 02/27/2025] Open
Abstract
BACKGROUND Gastrointestinal (GI) malignancies remain the culprit behind a substantial portion of cancer-related mortality worldwide, and outcomes for patients with advanced or metastatic GI cancers remain poor despite continued efforts to improve care. In 2024, the ongoing clinical trials to optimize and improve GI cancer care showcased progress in molecular diagnostics, systemic therapies, and localized treatment approaches, providing hope for continued progress toward improved patient outcomes. MATERIALS AND METHODS This review summarizes selected updates in GI cancer care from the 2024 ASCO and ESMO Annual Meetings, including both positive and negative trials that, while not universally practice-changing, contribute to shaping GI cancer care, clinical management, or address key questions in the field. The selected trials cover early detection and diagnostic advances, perioperative management, metastatic disease management, and immune checkpoint inhibitor (ICI)'s emerging role in GI cancer. RESULTS Various clinical trials in perioperative management and their results continue to reshape or strengthen the current treatment paradigms. The use of ICIs for microsatellite instability-high colorectal cancer (CRC) presented a notable advancement with the potential to improve patient outcomes. Localized treatments such as thermal ablation appear to benefit some patients with CRC and liver metastases. CONCLUSIONS The collection of trial results presented at the 2024 ASCO and ESMO Annual Meetings denote the ongoing efforts of the medical and scientific community for optimizing GI cancer care. The ongoing efforts of the GI cancer research and patient community provide hope for continued progress toward improved patient outcomes and new standards of care.
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Affiliation(s)
- Tim Jang
- University of Florida Health Cancer Center, Gainesville, FL 32608, United States
- Department of Medicine, University of Florida College of Medicine, Gainesville, FL 32608, United States
| | - George P Kim
- University of Florida Health Cancer Center, Gainesville, FL 32608, United States
- Department of Medicine, University of Florida College of Medicine, Gainesville, FL 32608, United States
| | - Thomas J George
- University of Florida Health Cancer Center, Gainesville, FL 32608, United States
- Department of Medicine, University of Florida College of Medicine, Gainesville, FL 32608, United States
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Sugiyama K, Gordon A, Popat S, Okines A, Larkin J, Chau I. Is pathological response an adequate surrogate marker for survival in neoadjuvant therapy with immune checkpoint inhibitors? ESMO Open 2025; 10:104122. [PMID: 39874902 PMCID: PMC11808614 DOI: 10.1016/j.esmoop.2024.104122] [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: 06/20/2024] [Revised: 12/17/2024] [Accepted: 12/18/2024] [Indexed: 01/30/2025] Open
Abstract
Pathological response (PR) is an oncological outcome measure that indicates the therapeutic response to neoadjuvant therapy. In clinical trials involving neoadjuvant or perioperative interventions, overall survival and disease/event-free survival are typically the primary outcome measures. Although some evidence suggests that pathological complete response (pCR) can serve as a surrogate marker for the primary endpoint in prospective trials, it remains uncertain whether pCR is a true surrogate marker for patients with cancer undergoing curative resection across all solid tumours. Here, we review the role of PR as a surrogate marker and its associated methodological issues in the era of perioperative immune checkpoint inhibitors.
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Affiliation(s)
- K Sugiyama
- Gastrointestinal Unit, Department of Medicine, Royal Marsden Hospital, London and Surrey, UK; Department of Medical Oncology, NHO Nagoya Medical Center, Nagoya, Aichi, Japan
| | - A Gordon
- Gastrointestinal Unit, Department of Medicine, Royal Marsden Hospital, London and Surrey, UK
| | - S Popat
- Lung Unit, Department of Medicine, Royal Marsden Hospital, London and Surrey, UK
| | - A Okines
- Breast Unit, Department of Medicine, Royal Marsden Hospital, London and Surrey, UK
| | - J Larkin
- Skin Unit, Department of Medicine, Royal Marsden Hospital, London and Surrey, UK
| | - I Chau
- Gastrointestinal Unit, Department of Medicine, Royal Marsden Hospital, London and Surrey, UK.
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Su F, Huang X, Yin J, Tang H, Tan L, Shen Y. Nodal Downstaging of Esophageal Cancer After Neoadjuvant Therapy: A Cohort Study and Meta-Analysis. Cancer Med 2025; 14:e70664. [PMID: 39918200 PMCID: PMC11803740 DOI: 10.1002/cam4.70664] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2024] [Revised: 12/08/2024] [Accepted: 01/28/2025] [Indexed: 02/11/2025] Open
Abstract
BACKGROUND In esophageal cancer, the ypN0 status after induction therapy could be categorized into two primary groups: "natural N0" (cN0/ypN0) and "down-staged N0" (cN+/ypN0). The assessment of cN status is typically based on clinical imagination or pathological regression. However, there is no standardized method for evaluating cN/ypN status. This study aims to investigate the prognosis of patients with cN+/ypN0 using both assessment methods through a cohort study and meta-analysis. METHODS A prospectively maintained database encompassing esophageal cancer patients undergoing induction therapy followed by radical esophagectomy was comprehensively reviewed. The prognostic significance of cN+/ypN0 across two evaluation methods was quantified. Additionally, a meta-analysis using data from previous studies was conducted. RESULTS 578 patients were identified from the cohort analysis, with 342 classified as ypN0 and 236 as ypN+. When evaluated with clinical imagination, patients with cN+/ypN0 had survival outcomes comparable to those with natural N0 but significantly better than those with ypN+ (p < 0.001). Using pathological nodal regression, cN+/ypN0 patients showed superior overall survival compared to ypN+ patients (p = 0.0043), although their disease-free survival was notably inferior to that of natural N0 patients (p = 0.0088). A meta-analysis of 20 previous studies confirmed the prognostic value of cN+/ypN0 status in both clinical imagination and pathological regression. CONCLUSIONS For esophageal cancer patients receiving neoadjuvant, cN+/ypN0 status, assessed through both clinical imagination and pathological regression, serves as a significant prognostic factor. It holds precedence over ypN+ yet falls short of the natural N0. The pre-treatment categorizations warrant recognition as a novel and pertinent staging metric.
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Affiliation(s)
- Feng Su
- Department of Thoracic Surgery, Zhongshan HospitalFudan UniversityShanghaiChina
| | - Xu Huang
- Department of Thoracic Surgery, Zhongshan HospitalFudan UniversityShanghaiChina
| | - Jun Yin
- Department of Thoracic Surgery, Zhongshan HospitalFudan UniversityShanghaiChina
| | - Hang Tang
- Department of Thoracic Surgery, Zhongshan HospitalFudan UniversityShanghaiChina
| | - Lijie Tan
- Department of Thoracic Surgery, Zhongshan HospitalFudan UniversityShanghaiChina
| | - Yaxing Shen
- Department of Thoracic Surgery, Zhongshan HospitalFudan UniversityShanghaiChina
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Lordick F, Mauer ME, Stocker G, Cella CA, Ben-Aharon I, Piessen G, Wyrwicz L, Al-Haidari G, Fleitas-Kanonnikoff T, Boige V, Lordick Obermannová R, Martens UM, Gomez-Martin C, Thuss-Patience P, Arrazubi V, Avallone A, Shiu KK, Artru P, Brenner B, Buges Sanchez C, Chau I, Lorenzen S, Daum S, Sinn M, Merelli B, van Grieken NCT, Nilsson M, Collienne M, Giraut A, Smyth E. Adjuvant immunotherapy in patients with resected gastric and oesophagogastric junction cancer following preoperative chemotherapy with high risk for recurrence (ypN+ and/or R1): European Organisation of Research and Treatment of Cancer (EORTC) 1707 VESTIGE study. Ann Oncol 2025; 36:197-207. [PMID: 39542422 DOI: 10.1016/j.annonc.2024.10.829] [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: 09/29/2024] [Revised: 10/31/2024] [Accepted: 10/31/2024] [Indexed: 11/17/2024] Open
Abstract
BACKGROUND Patients with gastro-oesophageal adenocarcinoma with tumour-positive lymph nodes (ypN+) or positive surgical margins (R1) following neoadjuvant chemotherapy and resection are at high risk of recurrence. Adjuvant nivolumab is effective in oesophageal/oesophagogastric junction cancer and residual pathological disease following chemoradiation and surgery. Immune checkpoint inhibition has shown efficacy in advanced gastro-oesophageal cancer. We hypothesised that nivolumab/ipilimumab would be more effective than adjuvant chemotherapy in high-risk (ypN+ and/or R1) patients with gastro-oesophageal adenocarcinoma following neoadjuvant chemotherapy and resection. PATIENTS AND METHODS VESTIGE was an academic international, multicentre, open-label, randomised phase II trial evaluating the efficacy of adjuvant nivolumab/ipilimumab versus chemotherapy in gastro-oesophageal adenocarcinoma at high risk of recurrence. Patients were randomised 1 : 1 to receive standard adjuvant chemotherapy (same regimen as neoadjuvant) or nivolumab 3 mg/kg intravenously (i.v.) every 2 weeks plus ipilimumab 1 mg/kg i.v. every 6 weeks for 1 year. Key inclusion criteria included ypN+ and/or R1 status after neoadjuvant chemotherapy plus surgery. The primary endpoint was disease-free survival in the intent-to-treat population. Secondary endpoints included overall survival, locoregional and distant failure rates, and safety according to National Cancer Institute Common Terminology Criteria for Adverse Events v5.0. RESULTS The independent Data Monitoring Committee reviewed data from 189 of the planned 240 patients in June 2022 and recommended stopping recruitment due to futility. At the time of final analysis, median follow-up was 25.3 months for 195 patients (98 nivolumab/ipilimumab and 97 chemotherapy). Median disease-free survival for the nivolumab/ipilimumab group was 11.4 months [95% confidence interval (CI) 8.4-16.8 months] versus 20.8 months (95% CI 15.0-29.9 months) for the chemotherapy group, hazard ratio 1.55 (95% CI 1.07-2.25, one-sided P = 0.99). The 12-month disease-free survival rates were 47.1% and 64.0%, respectively. There were no toxicity concerns or excess early discontinuations. CONCLUSION Nivolumab/ipilimumab did not improve disease-free survival compared with chemotherapy in patients with ypN+ and/or R1 gastro-oesophageal adenocarcinoma following neoadjuvant chemotherapy and surgery.
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Affiliation(s)
- F Lordick
- Department of Medicine (Oncology, Gastroenterology, Hepatology, Pulmonology), University of Leipzig Medical Center, Comprehensive Cancer Center Central Germany (CCCG), Leipzig, Germany.
| | - M E Mauer
- European Organisation for Research and Treatment of Cancer (EORTC) Headquarters, Brussels, Belgium
| | - G Stocker
- Department of Medicine (Oncology, Gastroenterology, Hepatology, Pulmonology), University of Leipzig Medical Center, Comprehensive Cancer Center Central Germany (CCCG), Leipzig, Germany
| | - C A Cella
- Istituto Europeo di Oncologia, IRCCS, Milan, Italy
| | - I Ben-Aharon
- Department of Oncology, Rambam Health Care Campus, Haifa, Israel
| | - G Piessen
- CHRU de Lille-Hôpital Huriez, Lille, France
| | - L Wyrwicz
- Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland
| | - G Al-Haidari
- Oslo University Hospital-Ullevaal Hospital, Oslo, Norway
| | - T Fleitas-Kanonnikoff
- Hospital Clinico Universitario De Valencia, Incliva Biomedical Research Institute, Valencia, Spain
| | - V Boige
- Department of Cancer Medicine, Institut Gustave Roussy, Villejuif, France
| | - R Lordick Obermannová
- Department of Comprehensive Cancer Care, Masaryk Memorial Cancer Institute and Faculty of Medicine, Masaryk University, Brno, Czech Republic
| | - U M Martens
- Department of Oncology, SLK-Kliniken Heilbronn, Heilbronn, Germany
| | | | - P Thuss-Patience
- Charité-Universitäetsmedizin Berlin-Charité Campus Virchow-Klinikum, Berlin, Germany
| | - V Arrazubi
- Hospital Universitario de Navarra, Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain
| | - A Avallone
- Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale, Naples, Italy
| | - K K Shiu
- University College Hospital, London, UK
| | - P Artru
- Hôpital Privé Jean Mermoz, Lyon, France
| | - B Brenner
- Rabin Medical Center, Beilinson Hospital, Petach Tikva, Israel
| | - C Buges Sanchez
- Department of Medical Oncology, ICO-Badalona (Catalan Institute of Oncology-Badalona), Barcelona, Spain
| | - I Chau
- Royal Marsden Hospital, London, UK
| | - S Lorenzen
- Department of Haematology and Oncology, Klinikum rechts der Isar, Technische Universitaet Muenchen, Munich, Germany
| | - S Daum
- Charité-Universitäetsmedizin Berlin-Charité Campus Benjamin-Franklin, Berlin, Germany
| | - M Sinn
- University Medical Center Hamburg-Eppendorf, Center of Oncology, Hamburg, Germany
| | - B Merelli
- Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy
| | - N C T van Grieken
- Department of Pathology, Amsterdam UMC, location VUmc, Cancer Center Amsterdam, VU University, Amsterdam, The Netherlands
| | - M Nilsson
- Division of Surgery and Oncology, Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, Solna, Sweden; Department of Upper Abdominal Diseases, Karolinska University Hospital, Stockholm, Sweden
| | - M Collienne
- European Organisation for Research and Treatment of Cancer (EORTC) Headquarters, Brussels, Belgium
| | - A Giraut
- European Organisation for Research and Treatment of Cancer (EORTC) Headquarters, Brussels, Belgium
| | - E Smyth
- Oxford NIHR Biomedical Research Centre, Churchill Hospital, Oxford, UK
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Li C, Tian Y, Zheng Y, Yuan F, Shi Z, Yang L, Chen H, Jiang L, Wang X, Zhao P, Zhang B, Wang Z, Zhao Q, Dong J, Lian C, Xu S, Zhang A, Zheng Z, Wang K, Dang C, Wu D, Chen J, Xue Y, Liang B, Cheng X, Wang Q, Chen L, Xia T, Liu H, Xu D, Zhuang J, Wu T, Zhao X, Wu W, Wang H, Peng J, Hou Z, Zheng R, Chen Y, Yin K, Zhu Z. Pathologic Response of Phase III Study: Perioperative Camrelizumab Plus Rivoceranib and Chemotherapy Versus Chemotherapy for Locally Advanced Gastric Cancer (DRAGON IV/CAP 05). J Clin Oncol 2025; 43:464-474. [PMID: 39383487 PMCID: PMC11776878 DOI: 10.1200/jco.24.00795] [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: 04/12/2024] [Revised: 08/01/2024] [Accepted: 09/05/2024] [Indexed: 10/11/2024] Open
Abstract
PURPOSE This multicenter, randomized phase III trial evaluated the efficacy and safety of perioperative camrelizumab (an anti-PD-1 antibody) plus low-dose rivoceranib (a VEGFR-2 inhibitor) and S-1 and oxaliplatin (SOX) (SOXRC), high-dose rivoceranib plus SOX (SOXR), and SOX alone (SOX) for locally advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma. METHODS Patients with T3-4aN + M0 G/GEJ adenocarcinoma were randomly assigned (1:1:1) to receive perioperative treatment with SOXRC, SOXR, or SOX. The primary end points were pathologic complete response (pCR) and event-free survival. The Independent Data Monitoring Committee recommended stopping enrollment in the SOXR group on the basis of the safety data of the first 103 randomly assigned patients in the three groups. The patients were then randomly assigned 1:1 to the SOXRC or SOX groups. This report presents the pCR results obtained per protocol for the first 360 randomly assigned patients who had the opportunity for surgery in the SOXRC and SOX groups. RESULTS In the SOXRC and SOX groups, of the 180 patients in each group, 99% and 98% of patients received neoadjuvant therapy, 91% and 94% completed planned neoadjuvant therapy, and 86% and 87% underwent surgery, respectively. The pCR was significantly higher in the SOXRC group at 18.3% (95% CI, 13.0 to 24.8) compared with 5.0% (95% CI, 2.3 to 9.3) in the SOX group (difference of 13.7%; 95% CI, 7.2 to 20.1; odds ratio of 4.5 [95% CI, 2.1 to 9.9]). The one-sided P value was <.0001, crossing the prespecified statistical significance threshold of P = .005. Surgical complications and grade ≥3 neoadjuvant treatment-related adverse events were 27% versus 33% and 34% versus 17% for SOXRC and SOX, respectively. CONCLUSION The SOXRC regimen significantly improved pCR compared with SOX alone in patients with G/GEJ adenocarcinoma with a tolerable safety profile.
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Affiliation(s)
- Chen Li
- Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China
| | - Yantao Tian
- Pancreatogastric Surgery, Cancer Hospital Chinese Academy of Medical Sciences, Beijing, China
| | - Yanan Zheng
- Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China
| | - Fei Yuan
- Department of Pathology, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China
| | - Zheng Shi
- Gastrointestinal Surgery, Shanghai Changhai Hospital, Shanghai, China
| | - Lin Yang
- Medical Oncology, Cancer Hospital Chinese Academy of Medical Sciences, Beijing, China
| | - Hao Chen
- Oncological Surgery, Lanzhou University Second Hospital, Lanzhou, China
| | - Lixin Jiang
- Gastrointestinal Surgery, Yantai Yuhuangding Hospital, Yantai, China
| | - Xixun Wang
- Gastrointestinal Surgery, Yantai Yuhuangding Hospital, Yantai, China
| | - Ping Zhao
- Gastrointestinal Surgery, Sichuan Provincial Cancer Hospital, Chengdu, China
| | - Benyan Zhang
- Department of Pathology, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China
| | - Zhenqiang Wang
- Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China
| | - Qun Zhao
- Gastrointestinal Oncology Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Jianhong Dong
- Minimally Invasive Surgery of Digestive Endoscopy, Shanxi Provincial Cancer Hospital, Taiyuan, China
| | - Changhong Lian
- Gastrointestinal Surgery, HePing Hospital Affiliated to Changzhi Medical College, Changzhi, China
| | - Sanrong Xu
- Department of General Surgery, Affiliated Hospital of Jiangsu University, Zhenjiang, China
| | - Aimin Zhang
- Gastrointestinal Surgery, Affiliated Hospital of Hebei University, Baoding, China
| | - Zhichao Zheng
- Gastric Cancer Surgery, Liaoning Cancer Hospital & Institution, Shenyang, China
| | - Kang Wang
- Gastrointestinal Surgery, Sichuan Provincial People's Hospital, Chengdu, China
| | - Chengxue Dang
- Surgical Oncology, The First Affiliated Hospital of XI'AN Jiaotong University, Xi'an, China
| | - Dan Wu
- Gastrointestinal Surgery, The Second Affiliated Hospital Zhejiang University, School of Medicine, Hangzhou, China
| | - Jian Chen
- Gastrointestinal Surgery, The Second Affiliated Hospital Zhejiang University, School of Medicine, Hangzhou, China
| | - Yingwei Xue
- Gastrointestinal Surgery, Harbin Medical University Affiliated Cancer Hospital, Harbin, China
| | - Bo Liang
- General Surgery, Jilin Guowen Hospital, Changchun, China
| | | | - Qian Wang
- Gastrointestinal Surgery, The Affiliated Hospital of GuiZhou Medical University, Guiyang, China
| | - Luchuan Chen
- Gastrointestinal Cancer Surgery Department, Fujian Provincial Cancer Hospital, Fuzhou, China
| | - Tao Xia
- Gastrointestinal and Pancreatic Surgery, Zhejiang Provincial People's Hospital, Hangzhou, China
| | - Heli Liu
- Gastrointestinal Surgery, Xiangya Hospital Central South University, Changsha, China
| | - Dazhi Xu
- Gastrosurgery, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Jing Zhuang
- General Surgery, Henan Cancer Hospital, Zhengzhou, China
| | - Tao Wu
- General Surgery, Tangdu Hospital of the Fourth Military Medical, Xi'an, China
| | - Xi Zhao
- Colorectal Surgery, Hainan Cancer Hospital, Haikou, China
| | - Wei Wu
- Geriatric Surgery, Xiangya Hospital Central South University, Changsha, China
| | - Hongzhi Wang
- Center of Gastrointestinal Tumor, Hefei Cancer Hospital, Chinese Academy of Sciences, Hefei, China
| | - Junsheng Peng
- Gastrointestinal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Zhiguo Hou
- Jiangsu Hengrui Pharmaceuticals, Shanghai, China
| | | | - Yuting Chen
- Jiangsu Hengrui Pharmaceuticals, Shanghai, China
| | - Kai Yin
- Gastrointestinal Surgery, Shanghai Changhai Hospital, Shanghai, China
| | - Zhenggang Zhu
- Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China
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48
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Waller GC, Khan TM, Correa-Gallego C. Minimally Invasive Gastrectomy. Surg Clin North Am 2025; 105:15-30. [PMID: 39523070 DOI: 10.1016/j.suc.2024.06.003] [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] [Indexed: 11/16/2024]
Abstract
The surgical management of gastric cancer has changed significantly from the first open partial gastrectomy in 1881 to contemporary minimally invasive approaches. The approach has shifted from open surgeries to laparoscopic and robotic-assisted gastrectomies, with evidence of reduced pain, quicker recovery, and lower morbidity with these methods. Multiple randomized trials have confirmed that laparoscopic surgeries yield oncologically safe results. Moreover, robotic surgeries, while more expensive, provide similar outcomes with some procedural benefits. Herein, we discuss surgical techniques, preoperative planning, and postprocedure care, emphasizing the role of careful clinical assessment and tailored surgical approaches based on tumor location and patient condition.
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Affiliation(s)
- Giacomo C Waller
- Divison of Surgical Oncology, Department of Surgery, Icahn School of Medicine at Mount Sinai, 5 East 98th Street, Suite B17, Box #1259, New York, NY 10029-6574, USA. https://twitter.com/gwallermd
| | - Tahsin M Khan
- Department of Surgery, Icahn School of Medicine at Mount Sinai, 5 East 98th Street, New York, NY 10029-6574, USA
| | - Camilo Correa-Gallego
- Divison of Surgical Oncology, Department of Surgery, Icahn School of Medicine at Mount Sinai, 5 East 98th Street, Suite B17, Box #1259, New York, NY 10029-6574, USA.
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49
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Srikumar T, Sundar R. Multimodality Treatment for Locally Advanced Gastric Adenocarcinoma. Surg Clin North Am 2025; 105:75-94. [PMID: 39523078 DOI: 10.1016/j.suc.2024.06.007] [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] [Indexed: 11/16/2024]
Abstract
Gastric cancer is prevalent worldwide and is a leading cause of cancer-related death. Patients with GC often present at advanced stages at diagnosis. Patients with locally advanced diseases experience poor survival rates with surgery alone. Multimodality therapy, including peri-operative therapy and adjuvant therapy, has improved outcomes. However, there is no consensus on the optimal treatment approach. Molecular characteristics of GC may help guide treatment choices and studies are currently underway to evaluate other treatment modalities including immunotherapy and targeted therapy.
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Affiliation(s)
- Thejal Srikumar
- Yale University School of Medicine, 333 Cedar Street, New Haven, CT, USA
| | - Raghav Sundar
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, 1E Kent Ridge Road, Singapore 119228, Singapore; Department of Haematology-Oncology, National University Cancer Institute, Singapore.
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50
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Jung JO, Bruns C. [Multimorbid patients in visceral surgery-Upper gastrointestinal tract]. CHIRURGIE (HEIDELBERG, GERMANY) 2025; 96:89-94. [PMID: 39774998 DOI: 10.1007/s00104-024-02221-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 12/03/2024] [Indexed: 01/11/2025]
Abstract
The treatment of multimorbid patients in oncological surgery of the upper gastrointestinal tract requires a differentiated consideration of every single risk factor in order to provide a holistic assessment. This article focuses on pre-existing diseases that are particularly relevant for elective esophageal and gastric surgery and have practical clinical consequences. In this way a differtiation is made between metabolic, vascular, cardiopulmonary and organ-specific risks. The aim of this work is to provide practical guidelines for complex and multimorbid cases. Given the multifactorial interrelationships, the importance of a thorough preoperative evaluation and interdisciplinary management cannot be overemphasized.
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Affiliation(s)
- Jin-On Jung
- Klinik und Poliklinik für Allgemein‑, Viszeral‑, Thorax- und Transplantationschirurgie, Universitätsklinikum Köln, Kerpener Str. 62, 50937, Köln, Deutschland.
| | - Christiane Bruns
- Klinik und Poliklinik für Allgemein‑, Viszeral‑, Thorax- und Transplantationschirurgie, Universitätsklinikum Köln, Kerpener Str. 62, 50937, Köln, Deutschland
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