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Carbone L, Incognito GG, Incognito D, Nibid L, Caruso G, Berretta M, Taffon C, Palumbo M, Perrone G, Roviello F, Marrelli D. Clinical implications of epithelial-to-mesenchymal transition in cancers which potentially spread to peritoneum. Clin Transl Oncol 2025:10.1007/s12094-024-03837-2. [PMID: 39775727 DOI: 10.1007/s12094-024-03837-2] [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: 11/26/2024] [Accepted: 12/19/2024] [Indexed: 01/11/2025]
Abstract
Epithelial-to-mesenchymal transition (EMT) is a biological process by which epithelial cells increase their motility and acquire invasive capacity. It represents a crucial driver of cancer metastasis and peritoneal dissemination. EMT plasticity, with cells exhibiting hybrid epithelial/mesenchymal states, and its reverse process, mesenchymal-to-epithelial transition (MET), allows them to adapt to different microenvironments and evade therapeutic intervention. Resistance to conventional treatments, including chemotherapy, is a major problem. Therapies targeting EMT may inhibit tumour cell migration and invasion, while affecting normal cells and repair mechanisms, resulting in potential side effects. This paper addresses the question of the impact of EMT status on cancers with potential spread to the peritoneum, which has remained unclear in literature. Relevant studies were selected from 2000 to 2024. Three macrosections were analysed: (i) pathological characteristics, (ii) surgical implications and (iii) oncological therapies. The focus was on survival and peritoneal recurrence time in patients who underwent surgical treatment.
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Affiliation(s)
- Ludovico Carbone
- Unit of Surgical Oncology, Department of Medicine Surgery and Neuroscience, University of Siena, Viale Mario Bracci 16, 53100, Siena, Italy.
| | - Giosuè Giordano Incognito
- Department of General Surgery and Medical Surgical Specialties, University of Catania, 95123, Catania, Italy
| | - Dalila Incognito
- Department of Human Pathology "G. Barresi", School of Specialization in Medical Oncology Unit, University of Messina, 98122, Messina, Italy
| | - Lorenzo Nibid
- Research Unit of Anatomical Pathology, Department of Medicine and Surgery, Università Campus Bio-Medico Di Roma, 00128, Roma, Italy
- Anatomical Pathology Operative Research Unit, Fondazione Policlinico Universitario Campus Bio-Medico, 00128, Roma, Italy
| | - Giuseppe Caruso
- Department of General Surgery and Medical Surgical Specialties, University of Catania, 95123, Catania, Italy
| | - Massimiliano Berretta
- Department of Human Pathology "G. Barresi", School of Specialization in Medical Oncology Unit, University of Messina, 98122, Messina, Italy
- Department of Clinical and Experimental Medicine, University of Messina, 98122, Messina, Italy
| | - Chiara Taffon
- Research Unit of Anatomical Pathology, Department of Medicine and Surgery, Università Campus Bio-Medico Di Roma, 00128, Roma, Italy
- Anatomical Pathology Operative Research Unit, Fondazione Policlinico Universitario Campus Bio-Medico, 00128, Roma, Italy
| | - Marco Palumbo
- Department of General Surgery and Medical Surgical Specialties, University of Catania, 95123, Catania, Italy
| | - Giuseppe Perrone
- Research Unit of Anatomical Pathology, Department of Medicine and Surgery, Università Campus Bio-Medico Di Roma, 00128, Roma, Italy
- Anatomical Pathology Operative Research Unit, Fondazione Policlinico Universitario Campus Bio-Medico, 00128, Roma, Italy
| | - Franco Roviello
- Unit of Surgical Oncology, Department of Medicine Surgery and Neuroscience, University of Siena, Viale Mario Bracci 16, 53100, Siena, Italy
| | - Daniele Marrelli
- Unit of Surgical Oncology, Department of Medicine Surgery and Neuroscience, University of Siena, Viale Mario Bracci 16, 53100, Siena, Italy
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Liveraro GS, Takahashi ME, Lascala F, Lopes LR, Andreollo NA, Mendes MC, Takahashi J, Carvalheira JB. Improving resectable gastric cancer prognosis prediction: A machine learning analysis combining clinical features and body composition radiomics. INFORMATICS IN MEDICINE UNLOCKED 2025; 52:101608. [DOI: 10.1016/j.imu.2024.101608] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2025] Open
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Huang YQ, Huang ZN, Hong QQ, Zhang P, Zhang ZZ, He L, Shang L, Wang LJ, Sun YF, Li ZX, Liu JJ, Ding FH, Lin ED, Fu YA, Lin SM, Chen QY, Zheng CH, Huang CM, Li P. Development of a staging system for hepatoid adenocarcinoma of the stomach based on multicenter data: a retrospective cohort study. Int J Surg 2025; 111:718-727. [PMID: 39316640 PMCID: PMC11745678 DOI: 10.1097/js9.0000000000001768] [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: 03/14/2024] [Accepted: 05/27/2024] [Indexed: 09/26/2024]
Abstract
BACKGROUND Hepatoid adenocarcinoma of the stomach (HAS) is a rare subtype of gastric cancer (GC) with a poor prognosis. Furthermore, the current pathological staging system for HAS does not distinguish it from that for common gastric cancer (CGC). METHODS The clinicopathological data of 251 patients with primary HAS who underwent radical surgery at 14 centers in China from April 2004 to December 2019 and 5082 patients with primary CGC who underwent radical surgery at two centers during the same period were retrospectively analyzed. A modified staging system was established based on the differences in survival. RESULTS After 1:4 propensity score matching (PSM), 228 patients with HAS and 828 patients with CGC were analyzed. Kaplan-Meier (K-M) analysis showed patients with HAS had a poorer prognosis compared with CGC. Multivariate analysis identified pN stage, CEA level, and perineural invasion (PNI) as independent prognostic factors in patients with HAS. A modified pT (mpT) staging was derived using recursive partitioning analysis (RPA) incorporating PNI and pT staging. The modified pathological staging system (mpTNM) integrated the mpT and the eighth American Joint Committee on Cancer (AJCC) pN definitions. Multivariate analysis showed that the mpTNM stage outperformed other pathological variables as independent predictors of OS and RFS in patients with HAS. The mpTNM staging system exhibited significantly higher predictive accuracy for 3-year OS in patients with HAS (0.707, 95% CI: 0.650-0.763) compared to that of the eighth AJCC staging system (0.667, 95% CI: 0.610-0.723, P <0.05). Analysis using the Akaike information criterion favored the mpTNM staging system over the eighth AJCC staging system (824.69 vs. 835.94) regarding the goodness of fit. The mpTNM stages showed improved homogeneity in survival prediction (likelihood ratio: 41.51 vs. 27.10). Comparatively, the mpTNM staging system outperformed the eighth AJCC staging system in survival prediction, supported by improvements in the net reclassification index (NRI: 47.7%) and integrated discrimination improvement (IDI: 0.083, P <0.05). The time-dependent ROC curve showed that the mpTNM staging system consistently outperformed the eighth AJCC staging system with increasing observation time. CONCLUSION The mpTNM staging system exhibited superior postoperative prognostic accuracy for patients with HAS compared to the eighth AJCC staging system.
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Affiliation(s)
- Ying-Qi Huang
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, People’s Republic of China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, People’s Republic of China
| | - Ze-Ning Huang
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, People’s Republic of China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, People’s Republic of China
| | - Qing-Qi Hong
- Department of Gastrointestinal Oncology Surgery, Xiamen Cancer Center, The First Affiliated Hospital of Xiamen University, Xiamen, People’s Republic of China
| | - Peng Zhang
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China
| | - Zi-Zhen Zhang
- Department of Gastrointestinal Surgery, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China
| | - Liang He
- Department of Gastrointestinal Surgery, First Hospital of Jilin University, Changchun, People’s Republic of China
| | - Liang Shang
- Department of Gastrointestinal Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, People’s Republic of China
| | - Lin-Jun Wang
- The First Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of China
| | - Ya-Feng Sun
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, People’s Republic of China
| | - Zhi-Xiong Li
- Gastrointestinal Surgery Unit 1, Teaching Hospital of Putian First Hospital of Fujian Medical University, Putian, People’s Republic of China
| | - Jun-Jie Liu
- Gastrointestinal Department of The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of China
| | - Fang-Hui Ding
- General Surgery Department, The First Hospital of Lanzhou University, Lanzhou, People’s Republic of China
| | - En-De Lin
- Department of General Surgery, Zhongshan Hospital Affiliated with Xiamen University, Xiamen, People’s Republic of China
| | - Yong-An Fu
- Department of Gastrointestinal Surgery, Affiliated Quanzhou First Hospital to Fujian Medical University, Quanzhou, People’s Republic of China
| | - Shuang-Ming Lin
- Department of Gastrointestinal Surgery, Longyan First Hospital Affiliated with Fujian Medical University, Longyan, People’s Republic of China
| | - Qi-Yue Chen
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, People’s Republic of China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, People’s Republic of China
| | - Chao-Hui Zheng
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, People’s Republic of China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, People’s Republic of China
| | - Chang-Ming Huang
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, People’s Republic of China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, People’s Republic of China
| | - Ping Li
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, People’s Republic of China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, People’s Republic of China
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Liu P, Ding P, Guo H, Yang J, Wu H, Wu J, Yang P, Zhao Q. Clinical calculator based on CT and clinicopathologic characteristics predicts short-term prognosis following resection of microsatellite-stabilized diffuse gastric cancer. Abdom Radiol (NY) 2024; 49:2165-2176. [PMID: 38727742 DOI: 10.1007/s00261-024-04350-4] [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: 03/27/2024] [Revised: 04/15/2024] [Accepted: 04/17/2024] [Indexed: 07/30/2024]
Abstract
PURPOSE Although microsatellite stability/Epithelial-mesenchymal transition (MSS/EMT) subtypes have been reported in multiple cancer prognosis studies, strong confounding factors between MSS/EMT (usually with Lauren's diffuse phenotype) and diffuse gastric cancer (GC) may obscure the independent prognostic value of diffuse GC. Additionally, recent studies suggest a strong correlation between mural stratification based on CT and diffuse GC. This study aims to investigate potential prognostic factors of MSS diffuse GC using mural stratification and to develop a risk assessment model. METHODS This retrospective study included 131 patients with MSS diffuse GC who underwent radical surgery. Univariate and multivariate Cox proportional hazards regression analysis was used to identify model predictors and construct a nomogram for overall survival (OS) and recurrence-free survival (RFS) risks. The model's performance was evaluated using ROC, accuracy, and C-index. Internal validation of the model was conducted using the bootstrap resampling method. RESULTS Among 131 cases, 60 cases (45.8%) exhibited grade 2 mural stratification, which correlated with a poorer tumor prognosis and a more invasive phenotype. Furthermore, a nomogram for predicting OS and RFS prognosis was established based on multivariate results (age, extranodal invasion, mural stratification, and/or P53). The nomogram demonstrated excellent performance, with an AUC of 0.859 (95% CI 0.794-0.924) for OS and 0.859 (95% CI 0.789-0.929) for RFS. Internal validation using 1000 bootstrap samples yielded AUC values of 0.845 and 0.846 for OS and RFS, respectively. CONCLUSION Grade 2 mural stratification based on CT imaging revealed a more aggressive invasive phenotype, characterized by increased LN metastasis, higher rates of peritoneal metastasis, and a poorer short-term prognosis. Furthermore, the CT phenotype-based nomogram demonstrates favorable discrimination and calibration, enabling convenient individual short-term prognostic evaluation following resection of MSS diffuse GC.
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Affiliation(s)
- Pengpeng Liu
- The Third Department of Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, 050011, Hebei, China
- Hebei Key Laboratory of Precision Diagnosis and Comprehensive Treatment of Gastric Cancer, Shijiazhuang, 050011, China
| | - Ping'an Ding
- The Third Department of Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, 050011, Hebei, China
- Hebei Key Laboratory of Precision Diagnosis and Comprehensive Treatment of Gastric Cancer, Shijiazhuang, 050011, China
| | - Honghai Guo
- The Third Department of Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, 050011, Hebei, China
- Hebei Key Laboratory of Precision Diagnosis and Comprehensive Treatment of Gastric Cancer, Shijiazhuang, 050011, China
| | - Jiaxuan Yang
- The Third Department of Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, 050011, Hebei, China
- Hebei Key Laboratory of Precision Diagnosis and Comprehensive Treatment of Gastric Cancer, Shijiazhuang, 050011, China
| | - Haotian Wu
- The Third Department of Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, 050011, Hebei, China
- Hebei Key Laboratory of Precision Diagnosis and Comprehensive Treatment of Gastric Cancer, Shijiazhuang, 050011, China
| | - Jiaxiang Wu
- The Third Department of Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, 050011, Hebei, China
- Hebei Key Laboratory of Precision Diagnosis and Comprehensive Treatment of Gastric Cancer, Shijiazhuang, 050011, China
| | - Peigang Yang
- The Third Department of Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, 050011, Hebei, China
- Hebei Key Laboratory of Precision Diagnosis and Comprehensive Treatment of Gastric Cancer, Shijiazhuang, 050011, China
| | - Qun Zhao
- The Third Department of Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, 050011, Hebei, China.
- Hebei Key Laboratory of Precision Diagnosis and Comprehensive Treatment of Gastric Cancer, Shijiazhuang, 050011, China.
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Furukawa K, Hatakeyama K, Terashima M, Urakami K, Koseki Y, Fujiya K, Tanizawa Y, Bando E, Yamaguchi K. Molecular features and prognostic factors of locally advanced microsatellite instability-high gastric cancer. Gastric Cancer 2024; 27:760-771. [PMID: 38744779 DOI: 10.1007/s10120-024-01506-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/03/2023] [Accepted: 05/03/2024] [Indexed: 05/16/2024]
Abstract
BACKGROUND Microsatellite instability-high (MSI-H) tumors are distinct molecular subtypes in gastric cancer. However, a few studies have comprehensively reported the molecular features of MSI-H tumors and their prognostic factors in locally advanced gastric cancer. This study aimed to clarify the molecular features and prognostic factors of locally advanced MSI-H gastric cancer. METHODS This study included 499 patients with locally advanced gastric cancer who underwent radical gastrectomy. We evaluated the MSI status and compared with previously published whole-exome sequencing, panel sequencing, and gene expression profiling data. Clinicopathological characteristics and molecular profiles were compared between patients with MSI-H and microsatellite stable (MSS) gastric cancer. A subgroup analysis of survival was performed in patients with MSI-H gastric cancer. RESULTS MSI-H tumors were detected in 79 of 499 patients (15.8%). MSI-H tumors were associated with an increased tumor mutational burden, MLH1 downregulation, CD274 (PD-L1) upregulation, and enrichment of cell cycle pathways. Among patients with MSI-H gastric cancer, the disease-specific survival (DSS) tended to be better in the surgery plus tegafur, gimeracil, and oteracil potassium (S-1) adjuvant chemotherapy group than in the surgery alone group, especially for stage III patients. Furthermore, DSS was better in the T cell-inflamed gene expression signature-high group, and it tended to be worse in the non-solid type poorly differentiated adenocarcinoma group. CONCLUSIONS The molecular features and prognostic factors of locally advanced MSI-H gastric cancer were clarified. S-1 adjuvant chemotherapy appears to be beneficial, and the T cell-inflamed gene expression signature and histopathological type are prognostic factors in MSI-H tumors.
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Affiliation(s)
- Kenichiro Furukawa
- Division of Gastric Surgery, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka, 411-8777, Japan
| | - Keiichi Hatakeyama
- Cancer Multiomics Division, Shizuoka Cancer Center Research Institute, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka, 411-8777, Japan
| | - Masanori Terashima
- Division of Gastric Surgery, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka, 411-8777, Japan.
| | - Kenichi Urakami
- Cancer Diagnostics Research Division, Shizuoka Cancer Center Research Institute, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka, 411-8777, Japan
| | - Yusuke Koseki
- Division of Gastric Surgery, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka, 411-8777, Japan
| | - Keiichi Fujiya
- Division of Gastric Surgery, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka, 411-8777, Japan
| | - Yutaka Tanizawa
- Division of Gastric Surgery, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka, 411-8777, Japan
| | - Etsuro Bando
- Division of Gastric Surgery, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka, 411-8777, Japan
| | - Ken Yamaguchi
- Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka, 411-8777, Japan
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Matsuoka T, Yashiro M. Bioinformatics Analysis and Validation of Potential Markers Associated with Prediction and Prognosis of Gastric Cancer. Int J Mol Sci 2024; 25:5880. [PMID: 38892067 PMCID: PMC11172243 DOI: 10.3390/ijms25115880] [Citation(s) in RCA: 16] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2024] [Revised: 05/23/2024] [Accepted: 05/25/2024] [Indexed: 06/21/2024] Open
Abstract
Gastric cancer (GC) is one of the most common cancers worldwide. Most patients are diagnosed at the progressive stage of the disease, and current anticancer drug advancements are still lacking. Therefore, it is crucial to find relevant biomarkers with the accurate prediction of prognoses and good predictive accuracy to select appropriate patients with GC. Recent advances in molecular profiling technologies, including genomics, epigenomics, transcriptomics, proteomics, and metabolomics, have enabled the approach of GC biology at multiple levels of omics interaction networks. Systemic biological analyses, such as computational inference of "big data" and advanced bioinformatic approaches, are emerging to identify the key molecular biomarkers of GC, which would benefit targeted therapies. This review summarizes the current status of how bioinformatics analysis contributes to biomarker discovery for prognosis and prediction of therapeutic efficacy in GC based on a search of the medical literature. We highlight emerging individual multi-omics datasets, such as genomics, epigenomics, transcriptomics, proteomics, and metabolomics, for validating putative markers. Finally, we discuss the current challenges and future perspectives to integrate multi-omics analysis for improving biomarker implementation. The practical integration of bioinformatics analysis and multi-omics datasets under complementary computational analysis is having a great impact on the search for predictive and prognostic biomarkers and may lead to an important revolution in treatment.
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Affiliation(s)
- Tasuku Matsuoka
- Department of Molecular Oncology and Therapeutics, Osaka Metropolitan University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 5458585, Japan;
- Institute of Medical Genetics, Osaka Metropolitan University, 1-4-3 Asahi-machi, Abeno-ku, Osaka 5458585, Japan
| | - Masakazu Yashiro
- Department of Molecular Oncology and Therapeutics, Osaka Metropolitan University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 5458585, Japan;
- Institute of Medical Genetics, Osaka Metropolitan University, 1-4-3 Asahi-machi, Abeno-ku, Osaka 5458585, Japan
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Marrelli D, Piccioni SA, Carbone L, Petrioli R, Costantini M, Malagnino V, Bagnacci G, Rizzoli G, Calomino N, Piagnerelli R, Mazzei MA, Roviello F. Posterior and Para-Aortic (D2plus) Lymphadenectomy after Neoadjuvant/Conversion Therapy for Locally Advanced/Oligometastatic Gastric Cancer. Cancers (Basel) 2024; 16:1376. [PMID: 38611054 PMCID: PMC11010857 DOI: 10.3390/cancers16071376] [Citation(s) in RCA: 18] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2024] [Revised: 03/29/2024] [Accepted: 03/29/2024] [Indexed: 04/14/2024] Open
Abstract
Super-extended (D2plus) lymphadenectomy after chemotherapy has been reported in only a few studies. This retrospective study evaluates survival outcomes in a Western cohort of locally advanced or oligometastatic gastric cancer patients who underwent D2plus lymphadenectomy after neoadjuvant chemotherapy. A total of 97 patients treated between 2010 and 2022 were included. Of these, 62 had clinical stage II/III disease, and 35 had stage IV disease. Most patients (65%) received preoperative DOC/FLOT chemotherapy. The mean number of lymph nodes harvested was 39. Pathological positive nodes in the posterior/para-aortic stations occurred in 17 (17.5%) patients. Lymphovascular invasion, ypN stage, clinical stage, and perineural invasion were predictive factors for positive posterior/para-aortic nodes. Postoperative complications occurred in 21 patients, whereas severe complications (grade III or more) occurred in 9 cases (9.3%). Mortality rate was 1%. Median overall survival (OS) was 59 months (95% CI: 13-106), with a five-year survival rate of 49 ± 6%; the five-year OS after R0 surgery was 60 ± 7%. In patients with positive posterior/para-aortic nodes, the median OS was 15 months (95% CI: 13-18). D2plus lymphadenectomy after chemotherapy for locally advanced or oligometastatic gastric cancer is feasible and associated with low morbidity/mortality rates. The incidence of pathological metastases in posterior/para-aortic nodes is not negligible even after systemic chemotherapy, with poor long-term survival.
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Affiliation(s)
- Daniele Marrelli
- Unit of General Surgery and Surgical Oncology, Department of Medicine, Surgery and Neurosciences, University of Siena, 53100 Siena, Italy; (S.A.P.); (L.C.); (G.R.); (R.P.); (F.R.)
| | - Stefania Angela Piccioni
- Unit of General Surgery and Surgical Oncology, Department of Medicine, Surgery and Neurosciences, University of Siena, 53100 Siena, Italy; (S.A.P.); (L.C.); (G.R.); (R.P.); (F.R.)
| | - Ludovico Carbone
- Unit of General Surgery and Surgical Oncology, Department of Medicine, Surgery and Neurosciences, University of Siena, 53100 Siena, Italy; (S.A.P.); (L.C.); (G.R.); (R.P.); (F.R.)
| | - Roberto Petrioli
- Unit of Medical Oncology, Department of Medicine, Surgery and Neurosciences, University of Siena, 53100 Siena, Italy;
| | - Maurizio Costantini
- Pathology Unit, University Hospital of Siena, 53100 Siena, Italy; (M.C.); (V.M.)
| | - Valeria Malagnino
- Pathology Unit, University Hospital of Siena, 53100 Siena, Italy; (M.C.); (V.M.)
| | - Giulio Bagnacci
- Unit of Diagnostic Imaging, Department of Medicine, Surgery and Neurosciences, University of Siena, 53100 Siena, Italy; (G.B.); (M.A.M.)
| | - Gabriele Rizzoli
- Unit of General Surgery and Surgical Oncology, Department of Medicine, Surgery and Neurosciences, University of Siena, 53100 Siena, Italy; (S.A.P.); (L.C.); (G.R.); (R.P.); (F.R.)
| | - Natale Calomino
- Unit of Kidney Transplantation, Department of Medicine, Surgery and Neurosciences, University of Siena, 53100 Siena, Italy;
| | - Riccardo Piagnerelli
- Unit of General Surgery and Surgical Oncology, Department of Medicine, Surgery and Neurosciences, University of Siena, 53100 Siena, Italy; (S.A.P.); (L.C.); (G.R.); (R.P.); (F.R.)
| | - Maria Antonietta Mazzei
- Unit of Diagnostic Imaging, Department of Medicine, Surgery and Neurosciences, University of Siena, 53100 Siena, Italy; (G.B.); (M.A.M.)
| | - Franco Roviello
- Unit of General Surgery and Surgical Oncology, Department of Medicine, Surgery and Neurosciences, University of Siena, 53100 Siena, Italy; (S.A.P.); (L.C.); (G.R.); (R.P.); (F.R.)
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Díaz del Arco C, Fernández Aceñero MJ, Ortega Medina L. Liquid biopsy for gastric cancer: Techniques, applications, and future directions. World J Gastroenterol 2024; 30:1680-1705. [PMID: 38617733 PMCID: PMC11008373 DOI: 10.3748/wjg.v30.i12.1680] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2023] [Revised: 02/01/2024] [Accepted: 03/08/2024] [Indexed: 03/28/2024] Open
Abstract
After the study of circulating tumor cells in blood through liquid biopsy (LB), this technique has evolved to encompass the analysis of multiple materials originating from the tumor, such as nucleic acids, extracellular vesicles, tumor-educated platelets, and other metabolites. Additionally, research has extended to include the examination of samples other than blood or plasma, such as saliva, gastric juice, urine, or stool. LB techniques are diverse, intricate, and variable. They must be highly sensitive, and pre-analytical, patient, and tumor-related factors significantly influence the detection threshold, diagnostic method selection, and potential results. Consequently, the implementation of LB in clinical practice still faces several challenges. The potential applications of LB range from early cancer detection to guiding targeted therapy or immunotherapy in both early and advanced cancer cases, monitoring treatment response, early identification of relapses, or assessing patient risk. On the other hand, gastric cancer (GC) is a disease often diagnosed at advanced stages. Despite recent advances in molecular understanding, the currently available treatment options have not substantially improved the prognosis for many of these patients. The application of LB in GC could be highly valuable as a non-invasive method for early diagnosis and for enhancing the management and outcomes of these patients. In this comprehensive review, from a pathologist's perspective, we provide an overview of the main options available in LB, delve into the fundamental principles of the most studied techniques, explore the potential utility of LB application in the context of GC, and address the obstacles that need to be overcome in the future to make this innovative technique a game-changer in cancer diagnosis and treatment within clinical practice.
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Affiliation(s)
- Cristina Díaz del Arco
- Department of Surgical Pathology, Health Research Institute of the Hospital Clínico San Carlos, Hospital Clínico San Carlos, Madrid 28040, Spain
- Department of Legal Medicine, Psychiatry and Pathology, Universidad Complutense de Madrid, Madrid 28040, Spain
| | - M Jesús Fernández Aceñero
- Department of Surgical Pathology, Health Research Institute of the Hospital Clínico San Carlos, Hospital Clínico San Carlos, Madrid 28040, Spain
- Department of Legal Medicine, Psychiatry and Pathology, Universidad Complutense de Madrid, Madrid 28040, Spain
| | - Luis Ortega Medina
- Department of Surgical Pathology, Health Research Institute of the Hospital Clínico San Carlos, Hospital Clínico San Carlos, Madrid 28040, Spain
- Department of Legal Medicine, Psychiatry and Pathology, Universidad Complutense de Madrid, Madrid 28040, Spain
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Díaz del Arco C, Fernández Aceñero MJ, Ortega Medina L. Molecular Classifications in Gastric Cancer: A Call for Interdisciplinary Collaboration. Int J Mol Sci 2024; 25:2649. [PMID: 38473896 PMCID: PMC10931799 DOI: 10.3390/ijms25052649] [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: 01/11/2024] [Revised: 02/21/2024] [Accepted: 02/22/2024] [Indexed: 03/14/2024] Open
Abstract
Gastric cancer (GC) is a heterogeneous disease, often diagnosed at advanced stages, with a 5-year survival rate of approximately 20%. Despite notable technological advancements in cancer research over the past decades, their impact on GC management and outcomes has been limited. Numerous molecular alterations have been identified in GC, leading to various molecular classifications, such as those developed by The Cancer Genome Atlas (TCGA) and the Asian Cancer Research Group (ACRG). Other authors have proposed alternative perspectives, including immune, proteomic, or epigenetic-based classifications. However, molecular stratification has not yet transitioned into clinical practice for GC, and little attention has been paid to alternative molecular classifications. In this review, we explore diverse molecular classifications in GC from a practical point of view, emphasizing their relationships with clinicopathological factors, prognosis, and therapeutic approaches. We have focused on classifications beyond those of TCGA and the ACRG, which have been less extensively reviewed previously. Additionally, we discuss the challenges that must be overcome to ensure their impact on patient treatment and prognosis. This review aims to serve as a practical framework to understand the molecular landscape of GC, facilitate the development of consensus molecular categories, and guide the design of innovative molecular studies in the field.
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Affiliation(s)
- Cristina Díaz del Arco
- Department of Legal Medicine, Psychiatry and Pathology, School of Medicine, Complutense University of Madrid, 28040 Madrid, Spain; (M.J.F.A.); (L.O.M.)
- Department of Pathology, Hospital Clínico San Carlos, Health Research Institute of the Hospital Clínico San Carlos (IdISSC), 28040 Madrid, Spain
| | - María Jesús Fernández Aceñero
- Department of Legal Medicine, Psychiatry and Pathology, School of Medicine, Complutense University of Madrid, 28040 Madrid, Spain; (M.J.F.A.); (L.O.M.)
- Department of Pathology, Hospital Clínico San Carlos, Health Research Institute of the Hospital Clínico San Carlos (IdISSC), 28040 Madrid, Spain
| | - Luis Ortega Medina
- Department of Legal Medicine, Psychiatry and Pathology, School of Medicine, Complutense University of Madrid, 28040 Madrid, Spain; (M.J.F.A.); (L.O.M.)
- Department of Pathology, Hospital Clínico San Carlos, Health Research Institute of the Hospital Clínico San Carlos (IdISSC), 28040 Madrid, Spain
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10
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Zeng W, Zhu J, Zeng D, Guo J, Huang G, Zeng Y, Wang L, Bin J, Liao Y, Shi M, Liao W. Epigenetic Modification-Associated Molecular Classification of Gastric Cancer. J Transl Med 2023; 103:100170. [PMID: 37150296 DOI: 10.1016/j.labinv.2023.100170] [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: 01/07/2023] [Revised: 04/02/2023] [Accepted: 04/20/2023] [Indexed: 05/09/2023] Open
Abstract
Epigenetic modification is involved in tumorigenesis and cancer progression. We developed an epigenetic modification-associated molecular classification of gastric cancer (GC) to identify signature genes that accurately predict prognosis and the efficacy of immunotherapy. Least absolute shrinkage and selection operator and multivariate Cox regression analysis were conducted to develop an epigenetic modification-associated molecular classification. We investigated the significance of PIP4P2, an independent prognostic factor of the classification system, in predicting the prognosis and immunotherapy efficacy of patients with GC. The epigenetic modification-associated molecular classification was highly associated with the clinicopathological characteristics of patients and the existing classification of GC. PIP4P2 was highly expressed in GC tissue and tumor-associated macrophages. High PIP4P2 expression in GC tissue-induced tumor progression by activating PI3K/AKT signal transduction had a negative impact on immunotherapy efficacy. High expression of PIP4P2 in macrophages was correlated with poor prognosis in patients with GC. PIP4P2 is an independent unfavorable prognostic factor of epigenetic modification-associated molecular classification, is involved in tumorigenic progression, and is essential for assessing the prognosis and immunotherapy efficacy of GC.
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Affiliation(s)
- Wei Zeng
- Department of Oncology, First Peoples Hospital of Shunde, Shunde Hospital of Southern Medical University, Shunde, China; Department of Hematology and Oncology, Shenzhen University General Hospital, Shenzhen University, Shenzhen, China
| | - Jinfeng Zhu
- Department of General Surgery, Shenzhen University General Hospital, Shenzhen University, Shenzhen, China
| | - Dongqiang Zeng
- Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, China; Guangdong Province Key Laboratory of Molecular Tumor Pathology, Southern Medical University, Guangzhou, China
| | - Jian Guo
- Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, China; Guangdong Province Key Laboratory of Molecular Tumor Pathology, Southern Medical University, Guangzhou, China
| | - Genjie Huang
- Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, China; Guangdong Province Key Laboratory of Molecular Tumor Pathology, Southern Medical University, Guangzhou, China
| | - Yu Zeng
- Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, China; Guangdong Province Key Laboratory of Molecular Tumor Pathology, Southern Medical University, Guangzhou, China
| | - Ling Wang
- Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, China; Guangdong Province Key Laboratory of Molecular Tumor Pathology, Southern Medical University, Guangzhou, China
| | - Jianping Bin
- Department of Cardiology, State Key Laboratory of Organ Failure Research, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Yulin Liao
- Department of Cardiology, State Key Laboratory of Organ Failure Research, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Min Shi
- Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, China; Guangdong Province Key Laboratory of Molecular Tumor Pathology, Southern Medical University, Guangzhou, China
| | - Wangjun Liao
- Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, China; Guangdong Province Key Laboratory of Molecular Tumor Pathology, Southern Medical University, Guangzhou, China.
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11
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Koseki Y, Hatakeyama K, Terashima M, Nagashima T, Urakami K, Ohshima K, Aizawa D, Sugino T, Furukawa K, Fujiya K, Tanizawa Y, Bando E, Okamura Y, Akiyama Y, Yamaguchi K. Molecular profile of poorly cohesive gastric carcinoma with special reference to survival. Gastric Cancer 2023; 26:553-564. [PMID: 37036539 DOI: 10.1007/s10120-023-01390-5] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2022] [Accepted: 04/01/2023] [Indexed: 04/11/2023]
Abstract
BACKGROUND Patients with poorly cohesive gastric carcinoma (PCC) are known to have poor survival. However, detailed molecular biology of PCC has not been elucidated, except for mutations in CDH1 and RHOA. Additionally, the molecular profiles of signet-ring cell carcinoma (SRC) have not been fully investigated. We aimed to investigate the association between molecular profiles and survival in PCC and PCC subtypes. METHODS The present study included 455 patients with gastric adenocarcinoma underwent radical gastrectomy. Whole-exome sequencing and gene expression profiling were conducted. Patients were classified according to the WHO classification as PCC or non-PCC, with PCC being further classified into SRC, combined, and PCC not-otherwise-specified (NOS). Clinicopathological factors and survival were compared with molecular profiles. RESULTS Of the patients, 159 were classified with PCC, while 296 were classified with non-PCC. Among PCC, 44 were classified with SRC, 64 with combined, and 51 with PCC-NOS. Mutations in CDH1 and RHOA were remarkably more frequent in PCC than in non-PCC. PCC had worse overall survival (OS) and disease-specific survival (DSS) compared to non-PCC. For PCC, the SRC group had good OS and DSS, whereas PCC-NOS classification with CDH1 mutations was associated with extremely poor survival. In the PCC-NOS and combined groups, patients with mutations in the extracellular domain 1 of CDH1 had poor survival. CONCLUSIONS Our findings suggest that PCC has poorer survival than non-PCC. Accumulation of CDH1 and RHOA mutations are unique profiles in PCC. Among PCC, CDH1 mutations may play a crucial role in the survival of non-SRC PCC.
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Affiliation(s)
- Yusuke Koseki
- Division of Gastric Surgery, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-Cho, Sunto-Gun, Shizuoka, 411-8777, Japan
- Division of Digestive Surgery, Department of Surgery, School of Medicine, Nihon University, Tokyo, Japan
| | - Keiichi Hatakeyama
- Cancer Multiomics Division, Shizuoka Cancer Center Research Institute, Shizuoka, Japan
| | - Masanori Terashima
- Division of Gastric Surgery, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-Cho, Sunto-Gun, Shizuoka, 411-8777, Japan.
| | - Takeshi Nagashima
- Cancer Diagnostics Research Division, Shizuoka Cancer Center Research Institute, Shizuoka, Japan
- SRL Inc., Tokyo, Japan
| | - Kenichi Urakami
- Cancer Diagnostics Research Division, Shizuoka Cancer Center Research Institute, Shizuoka, Japan
| | - Keiichi Ohshima
- Medical Genetics Division, Shizuoka Cancer Center Research Institute, Shizuoka, Japan
| | - Daisuke Aizawa
- Division of Pathology, Shizuoka Cancer Center, Shizuoka, Japan
| | - Takashi Sugino
- Division of Pathology, Shizuoka Cancer Center, Shizuoka, Japan
| | - Kenichiro Furukawa
- Division of Gastric Surgery, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-Cho, Sunto-Gun, Shizuoka, 411-8777, Japan
| | - Keiichi Fujiya
- Division of Gastric Surgery, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-Cho, Sunto-Gun, Shizuoka, 411-8777, Japan
| | - Yutaka Tanizawa
- Division of Gastric Surgery, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-Cho, Sunto-Gun, Shizuoka, 411-8777, Japan
| | - Etsuro Bando
- Division of Gastric Surgery, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-Cho, Sunto-Gun, Shizuoka, 411-8777, Japan
| | - Yukiyasu Okamura
- Division of Digestive Surgery, Department of Surgery, School of Medicine, Nihon University, Tokyo, Japan
| | - Yasuto Akiyama
- Immunotherapy Division, Shizuoka Cancer Center Research Institute, Shizuoka, Japan
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12
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Marano L, Verre L, Carbone L, Poto GE, Fusario D, Venezia DF, Calomino N, Kaźmierczak-Siedlecka K, Polom K, Marrelli D, Roviello F, Kok JHH, Vashist Y. Current Trends in Volume and Surgical Outcomes in Gastric Cancer. J Clin Med 2023; 12:2708. [PMID: 37048791 PMCID: PMC10094776 DOI: 10.3390/jcm12072708] [Citation(s) in RCA: 40] [Impact Index Per Article: 20.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2023] [Revised: 03/27/2023] [Accepted: 04/03/2023] [Indexed: 04/08/2023] Open
Abstract
Gastric cancer is ranked as the fifth most frequently diagnosed type of cancer. Complete resection with adequate lymphadenectomy represents the goal of treatment with curative intent. Quality assurance is a crucial factor in the evaluation of oncological surgical care, and centralization of healthcare in referral hospitals has been proposed in several countries. However, an international agreement about the setting of "high-volume hospitals" as well as "minimum volume standards" has not yet been clearly established. Despite the clear postoperative mortality benefits that have been described for gastric cancer surgery conducted by high-volume surgeons in high-volume hospitals, many authors have highlighted the limitations of a non-composite variable to define the ideal postoperative period. The textbook outcome represents a multidimensional measure assessing the quality of care for cancer patients. Transparent and easily available hospital data will increase patients' awareness, providing suitable elements for a more informed hospital choice.
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Affiliation(s)
- Luigi Marano
- Department of Medicine, Surgery and Neuroscience, University of Siena, 53100 Siena, Italy
| | - Luigi Verre
- Department of Medicine, Surgery and Neuroscience, University of Siena, 53100 Siena, Italy
| | - Ludovico Carbone
- Department of Medicine, Surgery and Neuroscience, University of Siena, 53100 Siena, Italy
| | - Gianmario Edoardo Poto
- Department of Medicine, Surgery and Neuroscience, University of Siena, 53100 Siena, Italy
| | - Daniele Fusario
- Department of Medicine, Surgery and Neuroscience, University of Siena, 53100 Siena, Italy
| | | | - Natale Calomino
- Department of Medicine, Surgery and Neuroscience, University of Siena, 53100 Siena, Italy
| | - Karolina Kaźmierczak-Siedlecka
- Department of Medical Laboratory Diagnostics-Fahrenheit Biobank BBMRI.pl, Medical University of Gdansk, 80-308 Gdańsk, Poland
| | - Karol Polom
- Department of Surgical Oncology, Medical University of Gdansk, 80-308 Gdańsk, Poland
| | - Daniele Marrelli
- Department of Medicine, Surgery and Neuroscience, University of Siena, 53100 Siena, Italy
| | - Franco Roviello
- Department of Medicine, Surgery and Neuroscience, University of Siena, 53100 Siena, Italy
| | - Johnn Henry Herrera Kok
- Department of General and Digestive Surgery, Complejo Asistencial Universitario de León, 24071 León, Spain
| | - Yogesh Vashist
- Organ Transplant Center of Excellence, King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia
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13
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Marrelli D, Marano L, Ambrosio MR, Carbone L, Spagnoli L, Petrioli R, Ongaro A, Piccioni S, Fusario D, Roviello F. Immunohistochemical Markers of the Epithelial-to-Mesenchymal Transition (EMT) Are Related to Extensive Lymph Nodal Spread, Peritoneal Dissemination, and Poor Prognosis in the Microsatellite-Stable Diffuse Histotype of Gastric Cancer. Cancers (Basel) 2022; 14:6023. [PMID: 36551509 PMCID: PMC9776345 DOI: 10.3390/cancers14246023] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2022] [Revised: 12/03/2022] [Accepted: 12/05/2022] [Indexed: 12/13/2022] Open
Abstract
Background: Although the prognostic value of the epithelial-to-mesenchymal transition (EMT) in gastric cancer has been reported in several studies, the strong association with the diffuse type may represent a confounding factor. Our aim is to investigate potential correlations among EMT status, tumor advancement, and prognosis in diffuse gastric cancer. Methods: Between 1997 and 2012, 84 patients with microsatellite-stable (MSS) diffuse-type tumors underwent surgery. The EMT phenotype was assessed with the E-cadherin, CD44, and zinc finger E-box binding homeobox 1 (ZEB-1) immunohistochemical markers. Results: Forty-five out of 84 cases (54%) were EMT-positive; more advanced nodal status (p = 0.010), pTNM stage (p = 0.032), and vascular invasion (p = 0.037) were observed in this group. The median numbers of positive nodes (13 vs. 5) and involved nodal stations (4 vs. 2) were higher in the EMT-positive group. The cancer-related survival time was 26 months in EMT-positive cases vs. 51 in negative cases, with five-year survival rates of 17% vs. 51%, respectively (p = 0.001). The EMT status had an impact on the prognosis of patients with <70 years, R0 resections, or treatment with adjuvant chemotherapy. Tumor relapses after surgery and peritoneal spread were significantly higher in the EMT-positive tumors. Conclusions: EMT status, when assessed through immunohistochemistry, identified an aggressive phenotype of MSS diffuse-type tumors with extensive lymph nodal spread, peritoneal dissemination, and worse long-term outcomes.
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Affiliation(s)
- Daniele Marrelli
- Department of Medicine, Surgery and Neurosciences, Unit of General Surgery and Surgical Oncology, University of Siena, Strade Delle Scotte 14, 53100 Siena, Italy
| | - Luigi Marano
- Department of Medicine, Surgery and Neurosciences, Unit of General Surgery and Surgical Oncology, University of Siena, Strade Delle Scotte 14, 53100 Siena, Italy
| | | | - Ludovico Carbone
- Department of Medicine, Surgery and Neurosciences, Unit of General Surgery and Surgical Oncology, University of Siena, Strade Delle Scotte 14, 53100 Siena, Italy
| | - Luigi Spagnoli
- Pathology Unit, Azienda Sanitaria Toscana Nord-Ovest, Via Cocchi 1, 56121 Pisa, Italy
| | - Roberto Petrioli
- Department of Medicine, Surgery and Neurosciences, Unit of Medical Oncology, University of Siena, Strade Delle Scotte 14, 53100 Siena, Italy
| | - Alessandra Ongaro
- Department of Medicine, Surgery and Neurosciences, Unit of General Surgery and Surgical Oncology, University of Siena, Strade Delle Scotte 14, 53100 Siena, Italy
| | - Stefania Piccioni
- Department of Medicine, Surgery and Neurosciences, Unit of General Surgery and Surgical Oncology, University of Siena, Strade Delle Scotte 14, 53100 Siena, Italy
| | - Daniele Fusario
- Department of Medicine, Surgery and Neurosciences, Unit of General Surgery and Surgical Oncology, University of Siena, Strade Delle Scotte 14, 53100 Siena, Italy
| | - Franco Roviello
- Department of Medicine, Surgery and Neurosciences, Unit of General Surgery and Surgical Oncology, University of Siena, Strade Delle Scotte 14, 53100 Siena, Italy
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14
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Zhang Z, Liu Z, Chen Z. Comparison of Treatment Efficacy and Survival Outcomes Between Asian and Western Patients With Unresectable Gastric or Gastro-Esophageal Adenocarcinoma: A Systematic Review and Meta-Analysis. Front Oncol 2022; 12:831207. [PMID: 35321436 PMCID: PMC8936077 DOI: 10.3389/fonc.2022.831207] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2021] [Accepted: 02/15/2022] [Indexed: 12/02/2022] Open
Abstract
Background Gastric cancer and gastro-esophageal adenocarcinoma are geographically heterogeneous diseases. Previous studies suggested that Asian and Western patients with late-stage gastric or gastro-esophageal adenocarcinoma possess distinct survival outcomes. However, the interregional differences of multiple systemic therapies in unresectable diseases have not been comprehensively described. Materials and Methods We searched PubMed-MEDLINE, Embase, Web of Science and Cochrane Library from inception to 31 October 2021 and reviewed major conference abstracts for controlled trials of systemic therapies in unresectable gastric or gastro-esophageal adenocarcinoma that reported hazard ratios stratified by geographical region. The primary measurements were overall survival and progression-free survival. The pooled hazard ratios and 95% confidence intervals for overall survival and progression-free survival in Asian and Western populations were calculated using a random effect model. A linear regression model was adopted to compare the overall survival and progression-free survival between Asian and Western patients. Results A total of 9033 patients from 20 studies were included for analysis. Immunotherapy was associated with an improvement in the overall survival for both Asian (hazard ratio, 0.80; 95% confidence interval, 0.65–0.98) and Western (hazard ratio, 0.90; 95% confidence interval, 0.81–1.00) patients, with no significant difference between the two groups (P = 0.32). Trends of survival benefit with anti-HER2 therapy and anti-angiogenic therapy versus control were observed in both Asian and Western patients, although statistical significance was not denoted. Subgroup analyses yielded a statistically superior overall survival of Asian versus Western patients in trials that investigated first-line immunotherapy (P = 0.04). Due to the linear regression analyses with scatter plot graphs, Asian patients showed a higher overall survival, but not progression-free survival, than Western patients irrespective of treatment type. Conclusion Asian and Western patients with unresectable gastric or gastro-esophageal adenocarcinoma show similar responses to systemic therapies with limited interregional differences. Exceptionally, first-line immunotherapy could elicit superior survival among Asian populations. In addition, Asian patients with gastric or gastro-esophageal adenocarcinoma display a superior OS compared with Western counterparts.
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Affiliation(s)
- Zhening Zhang
- Department of General Surgery, Peking University First Hospital, Beijing, China
- Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research, Peking University Cancer Hospital and Institute, Beijing, China
| | - Zining Liu
- Department of General Surgery, Peking University First Hospital, Beijing, China
- Department of Gastrointestinal Cancer Center, Key Laboratory of Carcinogenesis and Translational Research, Peking University Cancer Hospital and Institute, Beijing, China
| | - Zeyang Chen
- Department of General Surgery, Peking University First Hospital, Beijing, China
- *Correspondence: Zeyang Chen,
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