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Dinescu VC, Gheorman V, Georgescu EF, Paitici Ș, Bică M, Pătrașcu Ș, Bunescu MG, Popa R, Berceanu MC, Pătrașcu AM, Gheorman LM, Dinescu SN, Udriștoiu I, Gheorman V, Forțofoiu MC, Cojan TȘȚ. Uncovering the Impact of Lymphadenectomy in Advanced Gastric Cancer: A Comprehensive Review. Life (Basel) 2023; 13:1769. [PMID: 37629625 PMCID: PMC10455758 DOI: 10.3390/life13081769] [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: 07/12/2023] [Revised: 08/14/2023] [Accepted: 08/16/2023] [Indexed: 08/27/2023] Open
Abstract
Gastric cancer is a significant health concern worldwide, and lymphadenectomy plays a crucial role in its treatment. However, there is ongoing debate regarding the optimal approach-D1 or D2 lymphadenectomy. This paper aims to synthesize the available evidence by conducting a comprehensive literature review and comparing the advantages and disadvantages of both techniques. The analysis includes studies, clinical trials, and systematic reviews that assess survival outcomes, morbidity, and quality of life. The selected studies revealed different outcomes associated with D1 and D2 lymphadenectomy, including lymph node harvest, disease control, recurrence rates, and overall survival. Postoperative complications also varied between the two techniques. These findings highlight the complex considerations involved in selecting the most suitable lymphadenectomy approach for individual patients. Therefore, the decision requires an individualized assessment that considers the potential benefits and risks of D1 and D2 techniques. A collaborative approach involving interdisciplinary teams is crucial for developing personalized treatment plans that optimize both oncological outcomes and postoperative quality of life.
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Affiliation(s)
- Venera-Cristina Dinescu
- Department of Health Promotion and Occupational Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania;
| | - Veronica Gheorman
- Department of Cardiology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania;
| | - Eugen Florin Georgescu
- Department of Surgery, University of Medicine and Pharmacy of Craiova, 200642 Craiova, Romania; (E.F.G.); (M.B.); (Ș.P.)
| | - Ștefan Paitici
- Department of Surgery, University of Medicine and Pharmacy of Craiova, 200642 Craiova, Romania; (E.F.G.); (M.B.); (Ș.P.)
| | - Marius Bică
- Department of Surgery, University of Medicine and Pharmacy of Craiova, 200642 Craiova, Romania; (E.F.G.); (M.B.); (Ș.P.)
| | - Ștefan Pătrașcu
- Department of Surgery, University of Medicine and Pharmacy of Craiova, 200642 Craiova, Romania; (E.F.G.); (M.B.); (Ș.P.)
| | - Marius Gabriel Bunescu
- Occupational Medicine Department, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania;
| | - Romeo Popa
- Department of Pharmacology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania;
| | - Mihaela Corina Berceanu
- Department of Cardiology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania;
| | - Ana Maria Pătrașcu
- Hematology Department, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Lavinia Maria Gheorman
- Department of Diabetology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania;
| | - Sorin Nicolae Dinescu
- Department of Epidemiology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania;
| | - Ion Udriștoiu
- Department of Psychiatry, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania; (I.U.); (V.G.)
| | - Victor Gheorman
- Department of Psychiatry, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania; (I.U.); (V.G.)
| | - Mircea Cătălin Forțofoiu
- Internal Medicine Department, University of Medicine and Pharmacy of Craiova, Filantropia Hospital of Craiova, 200143 Craiova, Romania;
| | - Tiberiu-Ștefăniță Țenea Cojan
- Department of Surgery, University of Medicine and Pharmacy of Craiova, 200642 Craiova, Romania; (E.F.G.); (M.B.); (Ș.P.)
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Conde Monroy D, Ibañez-Pinilla M, Sabogal JC, Rey Chaves C, Isaza-Restrepo A, Girón F, Vanegas M, Ibañez-Villalba R, Mirow L, Siepmann T. Survival Outcomes of Hepatectomy in Gastric Cancer Liver Metastasis: A Systematic Review and Meta-Analysis. J Clin Med 2023; 12:jcm12020704. [PMID: 36675632 PMCID: PMC9861719 DOI: 10.3390/jcm12020704] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2022] [Revised: 01/09/2023] [Accepted: 01/11/2023] [Indexed: 01/18/2023] Open
Abstract
Gastric cancer liver metastasis (GCLM) is a contraindication for surgical treatment in current guidelines. However, the results of recent studies are questioning this paradigm. We assessed survival outcomes and their predictors following hepatectomy for GCLM in a systematic review of studies published from 2000 to 2022 according to PRISMA guidelines. We identified 42,160 references in four databases. Of these, 55 articles providing data from 1990 patients fulfilled our criteria and were included. We performed a meta-analysis using random-effects models to assess overall survival (OS) and disease-free survival (DFS) at one, three, and five years post-surgery. We studied the impact of potential prognostic factors on survival outcomes via meta-regression. One, three, and five years after surgery, OS was 69.79%, 34.79%, and 24.68%, whereas DFS was 41.39%, 23.23%, and 20.18%, respectively. Metachronous presentation, well-to-moderate differentiation, small hepatic tumoral size, early nodal stage, R0 resection, unilobar compromisation, and solitary lesions were associated with higher overall survival. Metachronous presentation, smaller primary tumoral size, and solitary metastasis were linked to longer DFS. The results of our meta-analysis suggest that hepatectomy leads to favorable survival outcomes in patients with GCLM and provides data that might help select patients who will benefit most from surgical treatment.
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Affiliation(s)
- Danny Conde Monroy
- Department of Surgery, Hospital Universitario Mayor—Méderi, Bogota 110111, Colombia
- Department of Surgery, Faculty of Medicine, Universidad del Rosario, Bogota 111221, Colombia
- Division of Health Care Sciences, Dresden International University, 01067 Dresden, Germany
- Correspondence:
| | - Milciades Ibañez-Pinilla
- Department of Surgery, Hospital Universitario Mayor—Méderi, Bogota 110111, Colombia
- Department of Surgery, Faculty of Medicine, Universidad del Rosario, Bogota 111221, Colombia
- Faculty of Medicine, Fundación Universitaria Sanitas, Bogota 110131, Colombia
| | - Juan Carlos Sabogal
- Department of Surgery, Hospital Universitario Mayor—Méderi, Bogota 110111, Colombia
| | - Carlos Rey Chaves
- Department of Surgery, Faculty of Medicine, Pontificia Universidad Javeriana, Bogota 110231, Colombia
| | - Andrés Isaza-Restrepo
- Department of Surgery, Hospital Universitario Mayor—Méderi, Bogota 110111, Colombia
- Department of Surgery, Faculty of Medicine, Universidad del Rosario, Bogota 111221, Colombia
| | - Felipe Girón
- Department of Surgery, Faculty of Medicine, Universidad del Rosario, Bogota 111221, Colombia
| | - Marco Vanegas
- Department of Surgery, Faculty of Medicine, Universidad del Rosario, Bogota 111221, Colombia
| | | | - Lutz Mirow
- Department of Surgery, Klinikum Chemnitz gGmbH, Medical Campus Chemnitz, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, 09116 Chemnitz, Germany
| | - Timo Siepmann
- Division of Health Care Sciences, Dresden International University, 01067 Dresden, Germany
- Department of Neurology, University Hospital Carl Gustav Carus, Technische Universität Dresden, 01307 Dresden, Germany
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Su PF, Yu JC. Progress in neoadjuvant therapy for gastric cancer (Review). Oncol Lett 2022; 23:172. [PMID: 35497934 PMCID: PMC9019865 DOI: 10.3892/ol.2022.13292] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2021] [Accepted: 03/28/2022] [Indexed: 02/03/2023] Open
Affiliation(s)
- Peng-Fei Su
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, P.R. China
| | - Jian-Chun Yu
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, P.R. China
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Liu ZN, Wang YK, Zhang L, Jia YN, Fei S, Ying XJ, Zhang Y, Li SX, Sun Y, Li ZY, Ji JF. Comparison of tumor regression grading systems for locally advanced gastric adenocarcinoma after neoadjuvant chemotherapy. World J Gastrointest Oncol 2021; 13:2161-2179. [PMID: 35070049 PMCID: PMC8713316 DOI: 10.4251/wjgo.v13.i12.2161] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/12/2021] [Revised: 07/25/2021] [Accepted: 09/17/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Current tumor regression grade (TRG) evaluations are based on various systems which brings confusion for oncologists and pathologists when interpreting results. The recent six-tier system (JGCA2017-TRG) recommended by the Japanese Gastric Cancer Association (JGCA) is worth investigating, as four-tier TRG systems are favored in various parts of the world.
AIM To compare the predictive accuracies of five published TRG systems.
METHODS Data were retrospectively collected from patients with locally advanced gastric cancer (LAGC) who underwent neoadjuvant chemotherapy followed by D2 Lymphadenectomy between January 2005 and January 2014 at our institution. Outcomes were overall survival (OS) and disease-free survival (DFS), which were evaluated separately using the following TRG systems: JGCA2017, JGCA, Becker, AJCC/CAP, and Mandard.
RESULTS All five published TRG systems were independent predictors for OS and DFS. Concordance indices of the JGCA2017, JGCA, Becker, AJCC/CAP-TRG, and Mandard systems were 0.651/0.648 0.652/0.649, 0.693/0.695, 0.688/0.685, and 0.674/0.675 for OS and DFS, respectively. The four-tier Becker system showed the highest c-index, which was significantly greater than that of the six-tier JGCA2017 and five-tier JGCA systems (P < 0.05 in OS and DFS). When residual tumor percentages were reset as: “no residual tumor”, < 10%, < 100%, and “no response”, the rearranged cutoff values achieved a maximum c-index with 0.728 for OS and 0.737 for DFS, which was superior to the other five systems.
CONCLUSION The newly introduced six-tier JGCA-TRG system cannot increase prognostic stratification. The four-tier Becker system is more suitable for LAGC patients. A population-based study is warranted to define the optimal criterion for TRG in LAGC patients.
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Affiliation(s)
- Zi-Ning Liu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Gastrointestinal Cancer Center, Peking University Cancer Hospital and Institute, Beijing 100142, China
| | - Yin-Kui Wang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Gastrointestinal Cancer Center, Peking University Cancer Hospital and Institute, Beijing 100142, China
| | - Li Zhang
- Department of Pathology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing 100142, China
| | - Yong-Ning Jia
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Gastrointestinal Cancer Center, Peking University Cancer Hospital and Institute, Beijing 100142, China
| | - Shan Fei
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Gastrointestinal Cancer Center, Peking University Cancer Hospital and Institute, Beijing 100142, China
| | - Xiang-Ji Ying
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Gastrointestinal Cancer Center, Peking University Cancer Hospital and Institute, Beijing 100142, China
| | - Yan Zhang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Gastrointestinal Cancer Center, Peking University Cancer Hospital and Institute, Beijing 100142, China
| | - Shuang-Xi Li
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Gastrointestinal Cancer Center, Peking University Cancer Hospital and Institute, Beijing 100142, China
| | - Yu Sun
- Department of Pathology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing 100142, China
| | - Zi-Yu Li
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Gastrointestinal Cancer Center, Peking University Cancer Hospital and Institute, Beijing 100142, China
| | - Jia-Fu Ji
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Gastrointestinal Cancer Center, Peking University Cancer Hospital and Institute, Beijing 100142, China
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Yan Y, Yang A, Lu L, Zhao Z, Li C, Li W, Chao J, Liu T, Fong Y, Fu W, Woo Y. Impact of Neoadjuvant Therapy on Minimally Invasive Surgical Outcomes in Advanced Gastric Cancer: An International Propensity Score-Matched Study. Ann Surg Oncol 2020; 28:1428-1436. [PMID: 32862371 DOI: 10.1245/s10434-020-09070-9] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2020] [Accepted: 08/08/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND No international consensus on the treatment of advanced gastric cancer (AGC) exists. In the absence of well-designed, comparative studies between neoadjuvant versus adjuvant strategies, concerns about increased risk of postoperative complications remain barriers to neoadjuvant chemotherapy (NAC) for AGC. We evaluated surgical outcomes of AGC patients who received minimally invasive radical gastrectomy with D2 lymphadenectomy after NAC. METHODS We collected data from two high-volume gastric cancer programs in the United States and China between January 2015 and December 2019 with the last follow-up in February 2020. AGC patients undergoing minimally invasive radical surgery were included. After propensity score-matching, surgical outcomes were analyzed. Risk-factor of complications was analyzed in the whole cohort. RESULTS After 1:1 propensity score-matching, 97 patients were included in each cohort. NAC + surgery cohort was younger (58.2 ± 10.3 vs. 61.3 ± 9.6, P = 0.036) with lower preoperative WBC count (5.7 ± 2.8 vs. 6.9 ± 2.1 × 109/ml) than the surgery upfront cohort. NAC was not a risk-factor for postoperative complications (odds ratio [OR], 0.859; 95% confidence interval [CI], 0.46-1.60; P = 0.633). Overall risk-factors of postoperative complications included age ≥ 60 years (OR, 21.338; 95% CI, 5.00-91.05; P < 0.001), tumor size ≥ 5 cm (OR, 1.24; 95% CI, 1.08-1.83; P < 0.001), operation time ≥ 240 min (OR, 5.53; 95% CI, 1.26-24.26; P = 0.012), and ASA classification ≥ II (OR, 13.14; 95% CI, 4.12-24.73; P < 0.001). CONCLUSIONS NAC before minimally invasive radical gastrectomy with D2 lymphadenectomy does not increase postoperative complications, and these findings support broader application of NAC and MIS for AGC. Additional studies are required to determine the effect of NAC on long-term survival.
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Affiliation(s)
- Yongjia Yan
- Division of Surgical Oncology, Department of Surgery, City of Hope National Comprehensive Cancer Center, Duarte, CA, USA.,Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, China
| | - Annie Yang
- Division of Surgical Oncology, Department of Surgery, City of Hope National Comprehensive Cancer Center, Duarte, CA, USA
| | - Li Lu
- Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, China
| | - Zhicheng Zhao
- Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, China
| | - Chuan Li
- Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, China
| | - Weidong Li
- Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, China
| | - Joseph Chao
- Department of Medical Oncology and Therapeutics Research, City of Hope National Medical Center, Duarte, CA, USA
| | - Tong Liu
- Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, China
| | - Yuman Fong
- Division of Surgical Oncology, Department of Surgery, City of Hope National Comprehensive Cancer Center, Duarte, CA, USA
| | - Weihua Fu
- Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, China.
| | - Yanghee Woo
- Division of Surgical Oncology, Department of Surgery, City of Hope National Comprehensive Cancer Center, Duarte, CA, USA. .,Cancer Immunotherapeutics Program, Beckman Research Institute, City of Hope, Duarte, CA, USA.
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Zhu Z, Gong YB, Xu HM. Neoadjuvant therapy strategies for advanced gastric cancer: Current innovations and future challenges. Chronic Dis Transl Med 2020; 6:147-157. [PMID: 32908968 PMCID: PMC7451732 DOI: 10.1016/j.cdtm.2020.03.004] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2019] [Indexed: 12/15/2022] Open
Abstract
Gastric cancer, which has a high incidence and poor prognosis, remains a therapeutic challenge. Recently, neoadjuvant therapy has attracted increasing attention due to high recurrence rate and low survival rate after resection in most patients with advanced stage. Clinical trials show that neoadjuvant approaches confer a significant survival advantage for resectable locally advanced gastric cancer. The specific advantages of chemoradiotherapy compared with chemotherapy have not been clarified; optimal regimens and cycles, particularly in the preoperative setting, should be studied further; and trials aimed at determining the role of targeted and immunological therapies should be conducted.
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Affiliation(s)
- Zhi Zhu
- Department of Surgical Oncology, The First Hospital of China Medical University, Shenyang, Liaoning 110001, China
| | - Ying-Bo Gong
- Department of Surgical Oncology, The First Hospital of China Medical University, Shenyang, Liaoning 110001, China
| | - Hui-Mian Xu
- Department of Surgical Oncology, The First Hospital of China Medical University, Shenyang, Liaoning 110001, China
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Terashima M, Iwasaki Y, Mizusawa J, Katayama H, Nakamura K, Katai H, Yoshikawa T, Ito Y, Kaji M, Kimura Y, Hirao M, Yamada M, Kurita A, Takagi M, Boku N, Sano T, Sasako M. Randomized phase III trial of gastrectomy with or without neoadjuvant S-1 plus cisplatin for type 4 or large type 3 gastric cancer, the short-term safety and surgical results: Japan Clinical Oncology Group Study (JCOG0501). Gastric Cancer 2019; 22:1044-1052. [PMID: 30827001 DOI: 10.1007/s10120-019-00941-z] [Citation(s) in RCA: 87] [Impact Index Per Article: 14.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2018] [Accepted: 02/15/2019] [Indexed: 02/07/2023]
Abstract
BACKGROUND The prognosis of patients with linitis plastica (type 4) and large (≥ 8 cm) ulcero-invasive-type (type 3) gastric cancer is extremely poor, even after extended surgery and adjuvant chemotherapy. Given the promising results of our previous phase II study evaluating neoadjuvant chemotherapy (NAC) with S-1 plus cisplatin (JCOG0210), we performed a phase III study to confirm the efficacy of NAC in these patients, with the safety and surgical results are presented here. METHODS Eligible patients were randomized to gastrectomy plus adjuvant chemotherapy with S-1 (Arm A) or NAC followed by gastrectomy + adjuvant chemotherapy (Arm B). The primary endpoint was the overall survival (OS). This trial is registered at the UMIN Clinical Trials Registry as C000000279. RESULTS From February 2007 to July 2013, 300 patients were randomized (Arm A 149, Arm B 151). NAC was completed in 133 patients (88%). Major grade 3/4 adverse events during NAC were neutropenia (29.3%), nausea (5.4%), diarrhea (4.8%), and fatigue (2.7%). Gastrectomy was performed in 147 patients (99%) in Arm A and 139 patients (92%) in Arm B. The operation time was significantly shorter in Arm B than in Arm A (median 255 vs. 240 min, respectively; p = 0.024). There were no significant differences in Grade 2-4 morbidity and mortality (25.2% and 1.3% in Arm A and 15.8% and 0.7% in Arm B, respectively). CONCLUSIONS NAC for type 4 and large type 3 gastric cancer followed by D2 gastrectomy can be safely performed without increasing the morbidity or mortality.
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Affiliation(s)
- Masanori Terashima
- Division of Gastric Surgery, Shizuoka Cancer Center, 1007 Monagakubo, Nagaizumi-cho, Sunto-gun, Nagaizumi, Shizuoka, 411-8777, Japan.
| | - Yoshiaki Iwasaki
- Department of Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan
| | - Junki Mizusawa
- JCOG Data Center/Operations Office, National Cancer Center Hospital, Tokyo, Japan
| | - Hiroshi Katayama
- JCOG Data Center/Operations Office, National Cancer Center Hospital, Tokyo, Japan
| | - Kenichi Nakamura
- JCOG Data Center/Operations Office, National Cancer Center Hospital, Tokyo, Japan
| | - Hitoshi Katai
- Department of Gastric Surgery, National Cancer Center Hospital, Tokyo, Japan
| | - Takaki Yoshikawa
- Department of Gastrointestinal Surgery, Kanagawa Cancer Center Hospital, Yokohama, Japan
| | - Yuichi Ito
- Department of Gastroenterological Surgery, Aichi Cancer Center Hospital, Nagoya, Japan
| | - Masahide Kaji
- Department of Surgery, Toyama Prefectural Central Hospital, Toyama, Japan
| | - Yutaka Kimura
- Department of Surgery, Sakai City Hospital, Sakai, Japan
| | - Motohiro Hirao
- Department of Surgery, National Hospital Organization Osaka National Hospital, Osaka, Japan
| | - Makoto Yamada
- Department of Surgery, Gifu Municipal Hospital, Gifu, Japan
| | - Akira Kurita
- Department of Surgery, National Hospital Organization Shikoku Cancer Center, Matsuyama, Japan
| | - Masakazu Takagi
- Department of Surgery, Shizuoka General Hospital, Shizuoka, Japan
| | - Narikazu Boku
- Department of Gastrointestinal Oncology, National Cancer Center Hospital, Tokyo, Japan
| | - Takeshi Sano
- Department of Gastroenterological Surgery, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Mitsuru Sasako
- Department of Surgery, Hyogo College of Medicine, Kobe, Japan
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Chelakkot PG, Ravind R, Sruthi K, Menon D. Treatment in resectable non-metastatic adenocarcinoma of stomach: Changing paradigms. Indian J Cancer 2019; 56:74-80. [PMID: 30950450 DOI: 10.4103/ijc.ijc_375_18] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
Adjuvant treatment in gastric adenocarcinoma has been a challenge for the treating specialists, and despite several trials, a clear consensus is yet to be defined. The higher propensity for lymph nodal involvement and locoregional recurrences led to the hypothesis that locoregional and systemic treatments need to be equally aggressive to achieve better outcomes in the management of gastric adenocarcinoma. Regional, ethnic, and biological differences between the Eastern and Western population are also found to reflect in the tumor behavior and its response to treatment. The MAGIC (Medical Research Council Adjuvant Gastric Infusional Chemotherapy), Intergroup 0116, ACTS-GC (Adjuvant Chemotherapy Trial of S-1 for Gastric Cancer), CLASSIC (Capecitabine and Oxaliplatin Adjuvant Study in Stomach Cancer), ARTIST (Adjuvant Chemoradiation Therapy in Stomach Cancer), and the recently published CRITICS (Chemoradiotherapy after Induction Chemotherapy in Cancer of the Stomach) trials were a few of the randomized controlled trials that tried to give a clearer perspective of this tumor, though it still remains a dilemma. A study incorporating the tumor and demographic factors along with the availability of skilled talent and resources might generate an answer.
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Affiliation(s)
- Prameela G Chelakkot
- Department of Oncology, Sevana Hospital and Research Centre, Pattambi, Palakkad District, Kerala, India
| | - Rahul Ravind
- Department of Medical Oncology, Tata Memorial Hospital, Mumbai, Maharashtra, India
| | - K Sruthi
- Department of Radiation Oncology, Amrita Institute of Medical Sciences, Amrita Vishwa Vidyapeetham, Amrita University, Cochin, Kerala, India
| | - Durgapoorna Menon
- Department of Radiation Oncology, Aster Hospital, Cochin, Kerala, India
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9
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Coccolini F, Fugazzola P, Ansaloni L, Sartelli M, Cicuttin E, Leandro G, De' Angelis GL, Gaiani F, Di Mario F, Tomasoni M, Catena F. Advanced gastric cancer: the value of systemic and intraperitoneal chemotherapy. ACTA BIO-MEDICA : ATENEI PARMENSIS 2018; 89:104-109. [PMID: 30561427 PMCID: PMC6502214 DOI: 10.23750/abm.v89i8-s.7904] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Subscribe] [Scholar Register] [Received: 11/28/2018] [Indexed: 12/20/2022]
Abstract
Several possibilities in treating advanced gastric cancer exist. Radical surgery associated with chemotherapy represents the cornerstone. Which one is more effective among neoadjuvant, adjuvant or perioperative chemotherapy is still a matter of debate. Several innovative results showed the necessity to keep increasingly into consideration the intraperitoneal administration of chemotherapies. Moreover, classical drugs and their ways of administration should be combined with the new ones to improve results. Lastly the prevention of recurrence should be considered: one possibility is to administer intraperitoneal chemotherapy earlier in the therapeutic algorithm.
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Affiliation(s)
- Federico Coccolini
- Emergency, General and Trauma Surgery dept., Bufalini hospital, Cesena, Italy.
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10
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Luo H, Wu L, Huang M, Jin Q, Qin Y, Chen J. Postoperative morbidity and mortality in patients receiving neoadjuvant chemotherapy for locally advanced gastric cancers: A systematic review and meta-analysis. Medicine (Baltimore) 2018; 97:e12932. [PMID: 30412102 PMCID: PMC6221738 DOI: 10.1097/md.0000000000012932] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
AIM To investigate the postoperative morbidity and mortality for neoadjuvant chemotherapy (NAC) plus surgery compared with surgery alone. METHODS PubMed and Embase were searched to capture the incidence of any postoperative complications, pulmonary complications, anastomotic leakage, surgical site infections, and postoperative mortality in randomized clinical trials comparing NAC plus surgery with surgery alone. The meta-analyses were performed with a random effects model. RESULTS Nine relevant studies were included. Comparing NAC with surgery alone, there were no increases in any postoperative complications, pulmonary complications, anastomotic leakage, surgical site infections, or postoperative mortality attributable to NAC. Sensitivity analysis suggested a possible increased risk of any postoperative complications compared with surgery alone: the risk difference 0.056 (95% confidence interval -0.032 to 0.145). Severe complications such as anastomotic leakage and pulmonary complications were similar in the 2 groups. CONCLUSIONS NAC for gastric cancer does not increase the risk of postoperative morbidity and mortality compared with surgery alone.
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Affiliation(s)
- Huiyu Luo
- Affiliated Tumor Hospital of Guangxi Medical University
| | - Liucheng Wu
- Department of Gastrointestinal Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Guangxi Autonomous Region, China
| | - Mingwei Huang
- Department of Gastrointestinal Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Guangxi Autonomous Region, China
| | - Qinwen Jin
- Department of Gastrointestinal Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Guangxi Autonomous Region, China
| | - Yuzhou Qin
- Department of Gastrointestinal Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Guangxi Autonomous Region, China
| | - Jiansi Chen
- Department of Gastrointestinal Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Guangxi Autonomous Region, China
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Machlowska J, Maciejewski R, Sitarz R. The Pattern of Signatures in Gastric Cancer Prognosis. Int J Mol Sci 2018; 19:1658. [PMID: 29867026 PMCID: PMC6032410 DOI: 10.3390/ijms19061658] [Citation(s) in RCA: 56] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2018] [Revised: 05/26/2018] [Accepted: 05/30/2018] [Indexed: 02/05/2023] Open
Abstract
Gastric cancer is one of the most common malignancies worldwide and it is a fourth leading cause of cancer-related death. Carcinogenesis is a multistage disease process specified by the gradual procurement of mutations and epigenetic alterations in the expression of different genes, which finally lead to the occurrence of a malignancy. These genes have diversified roles regarding cancer development. Intracellular pathways are assigned to the expression of different genes, signal transduction, cell-cycle supervision, genomic stability, DNA repair, and cell-fate destination, like apoptosis, senescence. Extracellular pathways embrace tumour invasion, metastasis, angiogenesis. Altered expression patterns, leading the different clinical responses. This review highlights the list of molecular biomarkers that can be used for prognostic purposes and provide information on the likely outcome of the cancer disease in an untreated individual.
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Affiliation(s)
- Julita Machlowska
- Department of Human Anatomy, Medical University of Lublin, 20-090 Lublin, Poland.
| | - Ryszard Maciejewski
- Department of Human Anatomy, Medical University of Lublin, 20-090 Lublin, Poland.
| | - Robert Sitarz
- Department of Human Anatomy, Medical University of Lublin, 20-090 Lublin, Poland.
- Department of Surgery, St. John's Cancer Center, 20-090 Lublin, Poland.
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12
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Long B, Yu ZY, Li Q, Du HR, Wang ZJ, Zhan H, Jiao ZY. A systematic review and network meta-analysis protocol of neoadjuvant treatments for patients with gastric cancer. Medicine (Baltimore) 2018; 97:e0392. [PMID: 29642200 PMCID: PMC5908618 DOI: 10.1097/md.0000000000010392] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/12/2018] [Accepted: 03/21/2018] [Indexed: 01/19/2023] Open
Abstract
BACKGROUND National Comprehensive Cancer Network (NCCN) guidelines recommend surgery, chemotherapy, and radiation therapy for gastric cancer patients. Neoadjuvant treatments as the administration of therapeutic agents before a main treatment gained in more and more attention. However, the role of neoadjuvant treatments is still controversial. The main aim of this systematic review and network meta-analysis is to assess the relative efficacy of different neoadjuvant treatment regimens for gastric cancer using network meta-analysis method. METHODS We will search 5 electronic databases to identify randomized controlled trials (RCTs) and non-RCTs compared the efficacy differences of surgery alone (S), preoperative chemotherapy follow by surgery (CTS), preoperative radiotherapy follow by surgery (RTS), and preoperative chemoradiotherapy follow by surgery (CRTS) for patients with gastric cancer. The risk of bias tool from the Cochrane Handbook version 5.1.0 will be used to assess the risk of bias of RCTs, and the risk of bias in nonrandomized studies of interventions (ROBINS-I) for non-RCTs. Data will be analyzed using R-3.4.1 software. RESULTS AND CONCLUSION The results of present network meta-analysis will estimate the relative efficacy among all interventions and rank the interventions even if head-to-head comparisons are lacking and will provide more evidence for clinicians, researchers, and patients in the management of gastric cancer.Protocol registration number: CRD42017074956.
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Affiliation(s)
- Bo Long
- Department of First General Surgery, Lanzhou University Second Hospital
| | - Ze-yuan Yu
- Department of First General Surgery, Lanzhou University Second Hospital
| | - Qiong Li
- Department of Endocrinology, Lanzhou University First Hospital, Lanzhou, China
| | - Heng-rui Du
- Department of First General Surgery, Lanzhou University Second Hospital
| | - Zhen-jiang Wang
- Department of First General Surgery, Lanzhou University Second Hospital
| | - Hao Zhan
- Department of First General Surgery, Lanzhou University Second Hospital
| | - Zuo-yi Jiao
- Department of First General Surgery, Lanzhou University Second Hospital
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Duan S, Yin J, Bai Z, Zhang Z. Effects of taxol resistance gene 1 on the cisplatin response in gastric cancer. Oncol Lett 2018; 15:8287-8294. [PMID: 29805561 PMCID: PMC5950176 DOI: 10.3892/ol.2018.8390] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2017] [Accepted: 02/12/2018] [Indexed: 12/28/2022] Open
Abstract
Cisplatin is used to treat multiple types of solid tumor, including gastric cancer. Although cisplatin initially exhibits good efficacy, therapeutic failure often occurs owing to the development of chemoresistance. To the best of our knowledge, the underlying mechanism of cisplatin resistance remains unknown. The aim of the present study was to assess whether taxol resistance gene 1 (TXR1) has a role in cisplatin response in gastric cancer. The expression of TXR1 in fresh-frozen tissues of patients with gastric cancer who were sensitive or resistance to cisplatin was assessed. The level of TXR1 expression was significantly higher in cisplatin-resistant specimens than that in cisplatin-sensitive specimens. Next, the gastric cancer SGC-7901 cell line was exposed to cisplatin to establish a cisplatin-resistance subline, termed SGC-7901/DDP, which exhibited a 6-fold increases in the level of resistance. TXR1 expression was elevated in SGC-7901/DDP cells. Overexpression of TXR1 induced cisplatin resistance in SGC-7901 cells. Downregulation of TXR1 reversed the drug resistance caused by elevation of TXR1 expression in SGC-7901/DDP cells. Animal experiments proved the effect of TXR1 in inducing cisplatin resistance in vivo. Further investigation revealed that TXR1 regulated cisplatin resistance via apoptosis. In conclusion, TXR1 is worthy of further in-depth study as a potential therapeutic target in patients with gastric cancer.
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Affiliation(s)
- Shuquan Duan
- Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing Key Laboratory of Cancer Invasion and Metastasis Research and National Clinical Research Center for Digestive Diseases, Beijing 100050, P.R. China
| | - Jie Yin
- Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing Key Laboratory of Cancer Invasion and Metastasis Research and National Clinical Research Center for Digestive Diseases, Beijing 100050, P.R. China
| | - Zhigang Bai
- Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing Key Laboratory of Cancer Invasion and Metastasis Research and National Clinical Research Center for Digestive Diseases, Beijing 100050, P.R. China
| | - Zhongtao Zhang
- Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing Key Laboratory of Cancer Invasion and Metastasis Research and National Clinical Research Center for Digestive Diseases, Beijing 100050, P.R. China
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14
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Ho VKY, Jansen EPM, Wijnhoven BPL, Neelis KJ, van Sandick JW, Verhoeven RHA, Lemmens VEP, van Laarhoven HWM. Adjuvant Chemoradiotherapy for Non-Pretreated Gastric Cancer. Ann Surg Oncol 2017; 24:3647-3657. [PMID: 28831737 DOI: 10.1245/s10434-017-6048-3] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2017] [Indexed: 01/17/2023]
Abstract
BACKGROUND While the curative approach to gastric cancer includes perioperative regimens in several countries, a substantial proportion of patients may not receive treatment prior to surgery. This study examines the adjuvant provision of chemoradiotherapy (CRT) for non-pretreated patients with cancer of the stomach including the gastric cardia. METHODS All surgically treated patients with primary adenocarcinoma of the stomach and gastric cardia diagnosed between January 2004-December 2013 were selected from the Netherlands Cancer Registry. Patients who did not receive neoadjuvant treatment were included. Early gastric cancers (cT1), postoperative deaths within 90 days, patients with metastatic disease (M1), patients who received adjuvant chemotherapy and patients with macroscopic tumor after surgery (R2) were excluded. RESULTS Some 3277 patients underwent surgery, and 99 patients (3%) received adjuvant CRT. Treatment was more often administered in patients with a younger age (<65 years) and a high socioeconomic status (SES), in case of non-cardia cancer, positive lymph nodes, and positive resection margins (R1). Median survival time was 28 months (95% CI 17-39), compared to 35 months (95% CI 33-38) in CRT-naïve patients. After adjustment for confounders, a small net benefit for adjuvant CRT was found (hazard ratio, HR: 0.75, 95% CI 0.58-0.96). In subgroup analyses, benefit was most pronounced for patients with seven or more lymph metastases. CONCLUSIONS Marginal survival benefit was observed for adjuvant CRT in gastric cancer patients who did not receive neoadjuvant treatment. Treatment could be considered for patients with disease involving nodal invasion and those left with microscopic residual disease after surgery.
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Affiliation(s)
- V K Y Ho
- Departments of Registry and Research, Netherlands Comprehensive Cancer Organization (IKNL), Utrecht, The Netherlands.
| | - E P M Jansen
- Department of Radiotherapy, Antoni van Leeuwenhoek Hospital/Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - B P L Wijnhoven
- Department of Surgery, Erasmus University Medical Center, Rotterdam, The Netherlands
| | - K J Neelis
- Department of Radiotherapy, Leiden University Medical Center, Leiden, The Netherlands
| | - J W van Sandick
- Department of Surgery, Antoni van Leeuwenhoek Hospital/Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - R H A Verhoeven
- Departments of Registry and Research, Netherlands Comprehensive Cancer Organization (IKNL), Utrecht, The Netherlands
| | - V E P Lemmens
- Departments of Registry and Research, Netherlands Comprehensive Cancer Organization (IKNL), Utrecht, The Netherlands.,Department of Public Health, Erasmus University Medical Center, Rotterdam, The Netherlands
| | - H W M van Laarhoven
- Department of Medical Oncology, Academic Medical Center, Amsterdam, The Netherlands
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15
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Preoperative Chemotherapy for Gastric Cancer: Personal Interventions and Precision Medicine. BIOMED RESEARCH INTERNATIONAL 2016; 2016:3923585. [PMID: 28105420 PMCID: PMC5220419 DOI: 10.1155/2016/3923585] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 07/28/2016] [Accepted: 12/04/2016] [Indexed: 12/26/2022]
Abstract
In spite of the declining incidence of gastric cancer (GC) in recent years, the mortality rate is still high. The asymptomatic nature and nonspecific clinical manifestations combined with the lack of efficient screening programs delay the diagnosis of GC. Therefore, the prevalence of advanced gastric cancer (AGC) has prompted the need for aggressive and intensive treatment options. Among the various treatment options for AGC, surgery is still the mainstay. However, the efficacy of surgery alone is not established. Results from multiple randomized controlled trials suggest that preoperative chemotherapy is promising intervention for the treatment and management of AGC. The main objective of neoadjuvant chemotherapy is to downstage or control micrometastasis in resectable tumor before surgery. On the other hand, conversion chemotherapy refers to surgical treatment aiming at R0 resection after chemotherapy for originally nonresectable or marginally resectable tumors. Nevertheless, preoperative chemoradiotherapy is considered beneficial for AGC patients. Over the last few decades, the combination of chemotherapy and targeted therapy prior to surgery demonstrated great results for the treatment of AGC. The rapid developments in genomics and proteomics have heralded the era of precision medicine. The combination of preoperative chemotherapy and precision medicine may enhance survival in AGC patients.
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16
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Russell MC. Comparison of neoadjuvant versus a surgery first approach for gastric and esophagogastric cancer. J Surg Oncol 2016; 114:296-303. [PMID: 27511285 DOI: 10.1002/jso.24293] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2016] [Accepted: 04/11/2016] [Indexed: 01/24/2023]
Abstract
Gastric cancer remains a significant worldwide health concern. While surgery is required for cure, all but the earliest of cancers will require multimodality therapy. Chemotherapy and chemoradiation in the neoadjuvant and adjuvant settings have shown to improve overall survival, but the sequencing of treatment is controversial. As healthcare expenses surge, it is increasingly important to impart value to these treatments. This review will look at the intersection of effective treatment and costs for gastric cancer. J. Surg. Oncol. 2016;114:296-303. © 2016 Wiley Periodicals, Inc.
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Affiliation(s)
- Maria C Russell
- Department of Surgery, Emory University Hospital, Atlanta, Georgia
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17
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Samalin E, Ychou M. Neoadjuvant therapy for gastroesophageal adenocarcinoma. World J Clin Oncol 2016; 7:284-292. [PMID: 27298768 PMCID: PMC4896896 DOI: 10.5306/wjco.v7.i3.284] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2015] [Accepted: 04/11/2016] [Indexed: 02/06/2023] Open
Abstract
Gastric and esophageal adenocarcinomas are one of the main causes of cancer-related death worldwide. While the incidence of gastric adenocarcinoma is decreasing, the incidence of gastroesophageal junction adenocarcinoma is rising rapidly in Western countries. Considering that surgical resection is currently the major curative treatment, and that the 5-year survival rate highly depends on the pTNM stage at diagnosis, gastroesophageal adenocarcinoma management is very challenging for oncologists. Several treatment strategies are being evaluated, and among them systemic chemotherapy, to decrease recurrences and improve overall survival. The MAGIC and FNCLCC-FFCD trials showed a survival benefit of perioperative chemotherapy in patients with operable gastric and lower esophageal cancer, and these results had an impact on the European clinical practice. New strategies, including induction chemotherapy followed by preoperative chemoradiotherapy, targeted therapies in combination with perioperative chemotherapy and the new cytotoxic regimens, are currently assessed to improve current standards and help developing patient-tailored therapeutic interventions.
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Biondi A, Lirosi MC, D’Ugo D, Fico V, Ricci R, Santullo F, Rizzuto A, Cananzi FCM, Persiani R. Neo-adjuvant chemo(radio)therapy in gastric cancer: Current status and future perspectives. World J Gastrointest Oncol 2015; 7:389-400. [PMID: 26690252 PMCID: PMC4678386 DOI: 10.4251/wjgo.v7.i12.389] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2015] [Revised: 07/03/2015] [Accepted: 10/15/2015] [Indexed: 02/05/2023] Open
Abstract
In the last 20 years, several clinical trials on neoadjuvant chemotherapy and chemo-radiotherapy as a therapeutic approach for locally advanced gastric cancer have been performed. Even if more data are necessary to define the roles of these approaches, the results of preoperative treatments in the combined treatment of gastric adenocarcinoma are encouraging because this approach has led to a higher rate of curative surgical resection. Owing to the results of most recent randomized phase III studies, neoadjuvant chemotherapy for locally advanced resectable gastric cancer has satisfied the determination of level I evidence. Remaining concerns pertain to the choice of the optimal therapy regimen, strict patient selection by accurate pre-operative staging, standardization of surgical procedures, and valid criteria for response evaluation. New well-designed trials will be necessary to find the best therapeutic approach in pre-operative settings and the best way to combine old-generation chemotherapeutic drugs with new-generation molecules.
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Nakajima T, Fujii M. What make differences in the outcome of adjuvant treatments for resected gastric cancer? World J Gastroenterol 2014; 20:11567-11573. [PMID: 25206264 PMCID: PMC4155350 DOI: 10.3748/wjg.v20.i33.11567] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/23/2013] [Revised: 01/09/2014] [Accepted: 04/09/2014] [Indexed: 02/06/2023] Open
Abstract
After a long history of Dark Age of adjuvant chemotherapy for gastric cancer, definite evidences of survival benefit from adjuvant treatment have been reported since 2000s. These survival benefits are likely attributed to something new approach different from pervious studies. In 2001, South West Oncology Group INT0116 trial yielded survival benefit in curatively resected gastric cancer patients with postoperative chemoradiotherapy [5-fluorouracil (5-FU) + Leucovorin + radiotherapy], followed by positive result by MAGIC Trial, employing peri-operative(pre- and postoperative chemotherapy with Epirubicin, cisplatin (CDDP), 5-fluorouracil (ECF) regimen in patients with curative resection. A novel drug [S1: ACTS-GC (Adjuvant chemotherapy trial of TS-1 for gastric cancer) in 2007], or new drug combination chemotherapys [CDDP + 5-FU: FNCLCC/FFCD (Federation Nationale des Centres de Lutte contre le cancer/Federation Francophone de Cancerologie Digestive) in 2011, Capecitabine + Oxaliplatin: CLASSIC in 2012] also produced positive results in terms of improved prognosis. Neoadjuvant or perioperative chemotherapy, novel anti-cancer drugs, and chemoradiotherapy might be the key words to develop further improvement in the adjuvant treatment of resectable gastric cancer. Moreover, it is not new but still true to stress the importance of D2 surgery as the baseline treatment in order to minimize the amount of residual tumor after surgery.
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20
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Batista TP, Santos CADAL, Almeida GFG. Perioperative chemotherapy in locally advanced gastric cancer. ARQUIVOS DE GASTROENTEROLOGIA 2014; 50:236-42. [PMID: 24322198 DOI: 10.1590/s0004-28032013000200042] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/02/2013] [Accepted: 04/29/2013] [Indexed: 03/03/2023]
Abstract
Gastric cancer is one of the most common cancers and a main cause of cancer-related death worldwide, since the majority of patients suffering of this malignancy are usually faced with a poor prognosis due to diagnosis at later stages. In order to improve treatment outcomes, the association of surgery with chemo and/or radiotherapy (multimodal therapy) has become the standard treatment for locally advanced stages. However, despite several treatment options currently available for management of these tumors, perioperative chemotherapy has been mainly accepted for the comprehensive therapeutic strategy including an appropriated D2-gastrectomy. This manuscript presents a (nonsystematic) critical review about the use of perioperative chemotherapy, with a special focus on the drugs delivery.
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Affiliation(s)
- Thales Paulo Batista
- Instituto de Medicina Integral Professor Fernando Figueira, Faculdade Pernambucana de Saúde
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21
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Zhang CD, Zeng YJ, Li HW, Zhao ZM, Zhang JK, Dai DQ. Neoadjuvant Chemotherapy for Nonmetastatic Esophago-Gastric Adenocarcinomas: A Systematic Review and Meta-Analysis. Cancer Invest 2013; 31:421-31. [DOI: 10.3109/07357907.2013.802801] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
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Liao Y, Yang ZL, Peng JS, Xiang J, Wang JP. Neoadjuvant chemotherapy for gastric cancer: a meta-analysis of randomized, controlled trials. J Gastroenterol Hepatol 2013; 28:777-82. [PMID: 23425049 DOI: 10.1111/jgh.12152] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 01/11/2013] [Indexed: 12/27/2022]
Abstract
BACKGROUND AND AIM Although the effect of neoadjuvant chemotherapy in gastric cancer has been extensively studied, the data of survival benefit are still controversial. The purpose of this work was to assess the effectiveness of neoadjuvant chemotherapy followed by surgery in patients with gastric cancer. METHODS We searched systematically electronic through the databases of PUBMED, EMBASE, China Biological Medicine, and China National Knowledge Infrastructure Whole Article for studies published from 1975. Two reviewers independently evaluated the relevant reports and searched manually reference from these reports for additional trials. Outcomes assessed by meta-analysis included overall survival rate, progression-free survival rate, R0 resection rate, downstaging effect, postoperative complications, and perioperative mortality. RESULTS Six randomized, controlled trials with 781 patients were included in the meta-analysis. Odds ratio (95% confidence interval; P-value), expressed as neoadjuvant chemotherapy and surgery versus surgery alone, was 1.16 (0.85-1.58; P = 0.36) for overall survival, 1.24 (0.78-1.96; P = 0.36) for R0 resection, 1.25 (0.75-2.09; P = 0.39) for postoperative complications, and 3.60 (0.59-22.45; P = 0.17) for perioperative mortality. CONCLUSIONS Compared with surgery alone, neoadjuvant chemotherapy followed by surgery was not associated with a higher rate of overall survival or complete resection (R0 resection). It does not increase treatment-related morbidity and mortality. This meta-analysis did not demonstrate a survival benefit for the combination of neoadjuvant chemotherapy and surgery.
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Affiliation(s)
- Yi Liao
- Department of Gastrointestinal Surgery, the Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
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23
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Traitement préopératoire des adénocarcinomes oesogastriques. ONCOLOGIE 2013. [DOI: 10.1007/s10269-013-2267-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
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Knight G, Earle CC, Cosby R, Coburn N, Youssef Y, Malthaner R, Wong RKS. Neoadjuvant or adjuvant therapy for resectable gastric cancer: a systematic review and practice guideline for North America. Gastric Cancer 2013; 16:28-40. [PMID: 22467061 DOI: 10.1007/s10120-012-0148-3] [Citation(s) in RCA: 46] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2011] [Accepted: 02/16/2012] [Indexed: 02/07/2023]
Abstract
BACKGROUND Gastric cancer is a global health problem accounting for 10% of all new cancer cases and 12% of all cancer deaths worldwide. Many clinical trials and meta-analyses have explored the value of neoadjuvant or adjuvant chemotherapy and radiation therapy in gastric cancer; however, these studies have produced conflicting results. The purpose of this guidance document was to determine whether patients with resectable gastric cancer should receive neoadjuvant or adjuvant therapy in addition to surgery. Outcomes of interest were overall survival, disease-free survival, and adverse events. METHODS A systematic review was undertaken to inform recommendations regarding neoadjuvant and adjuvant therapy in resectable gastric cancer in Ontario, Canada. MEDLINE and EMBASE databases, as well as American Society of Clinical Oncology (ASCO) annual meeting proceedings and American Society for Therapeutic Radiology and Oncology (ASTRO) proceedings were systematically searched from 2002 to 2010. Oral fluoropyrimidine trials were excluded owing to the unavailability of these agents in North America. RESULTS Overall, 22 randomized controlled trials (RCTs), 13 meta-analyses, and two secondary analyses were included. The systematic review informed the development of a clinical practice guideline with the following recommendations. Postoperative 5-fluorouracil-based chemoradiotherapy based on the Macdonald approach or perioperative ECF (epirubicin, cisplatin, fluorouracil) chemotherapy based on the Cunningham/MAGIC (Medical Research Council Adjuvant Gastric Infusional Chemotherapy) approach are both acceptable standards of care in North America. Choice of treatment should be made on a case-by-case basis. Adjuvant chemotherapy is a reasonable option for those patients for whom the Macdonald and MAGIC protocols are contraindicated. All patients with resectable gastric cancer should undergo a pretreatment multidisciplinary assessment to determine the best plan of care. CONCLUSIONS Overall survival in patients with resectable gastric cancer is significantly improved with the use of either postoperative chemoradiation (Macdonald approach) or perioperative ECF (MAGIC protocol).
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Affiliation(s)
- Greg Knight
- Grand River Regional Cancer Centre, 835 King Street West, P O Box 9056, Kitchener, ON, N2G 1G3, Canada.
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Rostom Y, Zaghloul H, Khedr G, El-Shazly W, Abd-Allah D. Docetaxel-Based Preoperative Chemoradiation in Localized Gastric Cancer: Impact of Pathological Complete Response on Patient Outcome. J Gastrointest Cancer 2012; 44:162-9. [DOI: 10.1007/s12029-012-9449-3] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
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Rausei S, Dionigi G, Rovera F, Boni L, Valerii C, Giavarini L, Frattini F, Dionigi R. A decade in gastric cancer curative surgery: Evidence of progress (1999-2009). World J Gastrointest Surg 2012; 4:45-54. [PMID: 22530078 PMCID: PMC3332221 DOI: 10.4240/wjgs.v4.i3.45] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/12/2011] [Revised: 11/04/2011] [Accepted: 11/12/2011] [Indexed: 02/06/2023] Open
Abstract
To investigate the progress in evidence-based surgical treatment of non-metastatic gastric cancer, we reviewed the last ten years’ literature. The data used in this review were identified by searches made on MEDLINE, Current Contents, PubMed, and other references taken from relevant original articles (on prospective and retrospective studies) concerning gastric cancer surgery. Only papers published in English between January 1999 and December 2009 were selected. Data from ongoing studies were obtained in December 2009, from the trials registry of the United States National Institutes of Health (http://www.clinicaltrial.gov). The citations list was presented according to evidence based relevance (i.e., randomized controlled trials, prospective studies, retrospective series). In the last ten years, many challenges have been faced relating to the extension of gastric resection and nodal dissection as well as surgical timing, but we found only limited evidence, regardless of latitude of study. The ongoing phase-III trials may provide answers that will be valid for the coming decades, and which may bring definitive answers for the currently unresolved questions.
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Affiliation(s)
- Stefano Rausei
- Stefano Rausei, Gianlorenzo Dionigi, Francesca Rovera, Luigi Boni, Caterina Valerii, Luisa Giavarini, Francesco Frattini, Renzo Dionigi, Department of Surgical Sciences, University of Insubria, 21100 Varese, Italy
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Li ZY, Koh CE, Bu ZD, Wu AW, Zhang LH, Wu XJ, Wu Q, Zong XL, Ren H, Tang L, Zhang XP, Li JY, Hu Y, Shen L, Ji JF. Neoadjuvant chemotherapy with FOLFOX: improved outcomes in Chinese patients with locally advanced gastric cancer. J Surg Oncol 2011; 105:793-9. [PMID: 22189752 DOI: 10.1002/jso.23009] [Citation(s) in RCA: 47] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2011] [Accepted: 11/24/2011] [Indexed: 12/17/2022]
Abstract
BACKGROUND Although the role of peri-operative chemotherapy is established in the treatment of locally advanced gastric cancer, the optimal regime remains to be determined. FOLFOX has been used in palliative setting with good response rates but its role in a neoadjuvant setting is not well established. METHODS This is a prospective non-randomized study comparing peri-operative FOLFOX versus adjuvant FOLFOX in patients with resectable locally advanced gastric cancer. Response to chemotherapy was assessed according to WHO criteria and pathological changes. Kaplan-Meier log rank test was used to calculate and compare survival differences. RESULTS There were 73 patients (neoadjuvant = 36). Complete and partial response was observed in 2 (6%) and 21 (64%) patients, respectively. Four-year overall survival (OS) in the neoadjuvant arm was 78% versus 51% in the adjuvant arm (P = 0.031). Subgroup analysis found R0 resection (86% vs. 55%, P = 0.011) and patients with proximal cancers (87% vs. 14%, P < 0.001) to have improved OS. The most common side effect was grade 1-2 leukopenia. There were no grade 3 neuropathies, grade 4 cytopaenias, or treatment related deaths. CONCLUSION Peri-operative treatment with FOLFOX shows promise in patients with resectable locally advanced gastric cancer. It warrants further evaluation and should be considered an alternative to peri-operative ECF.
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Affiliation(s)
- Zi-Yu Li
- Department of Gastrointestinal Surgery, Beijing Cancer Hospital and Institute, Peking University School of Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Beijing, China
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Li ZY, Shan F, Zhang LH, Bu ZD, Wu AW, Wu XJ, Zong XL, Wu Q, Ren H, Ji JF. Complications after radical gastrectomy following FOLFOX7 neoadjuvant chemotherapy for gastric cancer. World J Surg Oncol 2011; 9:110. [PMID: 21942969 PMCID: PMC3204253 DOI: 10.1186/1477-7819-9-110] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2011] [Accepted: 09/26/2011] [Indexed: 12/25/2022] Open
Abstract
BACKGROUND This study assessed the postoperative morbidity and mortality occurring in the first 30 days after radical gastrectomy by comparing gastric cancer patients who did or did not receive the FOLFOX7 regimen of neoadjuvant chemotherapy. METHODS We completed a retrospective analysis of 377 patients after their radical gastrectomies were performed in our department between 2005 and 2009. Two groups of patients were studied: the SURG group received surgical treatment immediately after diagnosis; the NACT underwent surgery after 2-6 cycles of neoadjuvant chemotherapy. RESULTS There were 267 patients in the SURG group and 110 patients in the NACT group. The NACT group had more proximal tumours (P = 0.000), more total/proximal gastrectomies (P = 0.000) and longer operative time (P = 0.005) than the SURG group. Morbidity was 10.0% in the NACT patients and 17.2% in the SURG patients (P = 0.075). There were two cases of postoperative death, both in the SURG group (P = 1.000). No changes in complications or mortality rate were observed between the SURG and NACT groups. CONCLUSION The FOLFOX7 neoadjuvant chemotherapy is not associated with increased postoperative morbidity, indicating that the FOLFOX7 neoadjuvant chemotherapy is a safe choice for the treatment of local advanced gastric cancer.
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Affiliation(s)
- Zi-Yu Li
- Department of Surgery, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University School of Oncology, Beijing Cancer Hospital & Institute, Beijing 100142, China
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29
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Mariette C, Piessen G, Briez N, Gronnier C, Triboulet JP. Oesophagogastric junction adenocarcinoma: which therapeutic approach? Lancet Oncol 2010; 12:296-305. [PMID: 21109491 DOI: 10.1016/s1470-2045(10)70125-x] [Citation(s) in RCA: 128] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
Gastric and oesophageal cancers are among the leading causes of cancer-related death worldwide. By contrast with the decreasing prevalence of gastric cancer, incidence and prevalence of oesophagogastric junction adenocarcinoma (OGJA) are rising rapidly in developed countries. We provide an update about treatment strategies for resectable OGJA. Here we review findings from the latest randomised trials and meta-analyses, and propose guidelines regarding endoscopic, surgical, and perioperative treatments. Through a team approach, members from all diagnostic and therapeutic disciplines, such as gastroenterologists, surgeons, oncologists, radiologists, and radiotherapists, can effectively administer a range of treatment modalities.
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Affiliation(s)
- Christophe Mariette
- Department of Digestive and Oncological Surgery, University Hospital C Huriez, Lille, France.
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30
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Biondi A, Persiani R, Cananzi F, Zoccali M, Vigorita V, Tufo A, D’Ugo D. R0 resection in the treatment of gastric cancer: Room for improvement. World J Gastroenterol 2010; 16:3358-70. [PMID: 20632437 PMCID: PMC2904881 DOI: 10.3748/wjg.v16.i27.3358] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Gastric carcinoma is one of the most frequent malignancies in the world and its clinical behavior especially depends on the metastatic potential of the tumor. In particular, lymphatic metastasis is one of the main predictors of tumor recurrence and survival, and current pathological staging systems reflect the concept that lymphatic spread is the most relevant prognostic factor in patients undergoing curative resection. This is compounded by the observation that two-thirds of gastric cancer in the Western world presents at an advanced stage, with lymph node metastasis at diagnosis. All current therapeutic efforts in gastric cancer are directed toward individualization of therapeutic protocols, tailoring the extent of resection and the administration of preoperative and postoperative treatment. The goals of all these strategies are to improve prognosis towards the achievement of a curative resection (R0 resection) with minimal morbidity and mortality, and better postoperative quality of life.
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31
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Hur H, Park CH. [Surgical treatment of gastric carcinoma]. THE KOREAN JOURNAL OF GASTROENTEROLOGY = TAEHAN SOHWAGI HAKHOE CHI 2009; 54:83-98. [PMID: 19696536 DOI: 10.4166/kjg.2009.54.2.83] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
The gastric cancer is the most common cancer in Korea. The only treatment modality showing improved survival for gastric cancer is curative surgical resection, which comprises the resection of stomach, proper lymphadenectomy, and reconstruction. However, specific surgical procedures should be decided according to the location of the cancer, advancement of the tumor, and patients condition. Surgical treatment for gastric cancer has been developed toward two directions that are minimal invasive surgery for early gastric cancer and multi-disciplinary approach for advanced gastric cancer. Laparoscopic surgery for early gastric cancer has been accepted for minimally invasive surgery. Moreover, the advancement of diagnostic tools to assess biological aggressiveness of the tumor enables physicians to perform endoscopic resection or minimized resection for early gastric cancer. Recently, surgeons try to extend the application of laparoscopic gastric resection and D2 lymphadenectomy to advanced gastric cancer. However, technical and oncological evidences based on clinical trials should be filed up before adopting it as a standard therapy. In case of advanced gastric cancer, in addition to radical surgery, various treatment modalities including chemotherapy, radiation, and molecular target therapy also have been applied in many clinical trials. However, it should be stressed that a prerequisite for precise evaluation of the efficacy of these combined treatment modalities would be the standardization of surgical procedure.
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Affiliation(s)
- Hoon Hur
- Division of Gastrointestinal Surgery, Department of Surgery, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
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32
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Gastric cancer. Crit Rev Oncol Hematol 2009; 71:127-64. [PMID: 19230702 DOI: 10.1016/j.critrevonc.2009.01.004] [Citation(s) in RCA: 324] [Impact Index Per Article: 20.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2008] [Revised: 01/08/2009] [Accepted: 01/15/2009] [Indexed: 02/08/2023] Open
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33
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D'Ugo D, Rausei S, Biondi A, Persiani R. Preoperative treatment and surgery in gastric cancer: friends or foes? Lancet Oncol 2009; 10:191-5. [PMID: 19185837 DOI: 10.1016/s1470-2045(09)70021-x] [Citation(s) in RCA: 39] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Until 2006, most reports of preoperative (neoadjuvant) treatments for gastric carcinoma were inconclusive and produced confusing results due to inhomogeneous treatment regimens, selection of patients, and response assessment. Since publication of the results from the MAGIC trial, substantial scientific evidence has suggested the benefits of perioperative (preoperative and postoperative) chemotherapy to locally advanced gastric cancer. To date, this phase III trial, coupled with preliminary data from other published reports on neoadjuvant chemotherapy and radiotherapy, supports the theoretical advantages of preoperative treatment for gastric carcinoma, thus introducing the concept of delayed surgery. Neoadjuvant treatment of resectable, locally advanced tumours might improve patients' outcomes and postpone the need for curative resection, but it also exposes patients to the risk of tumour progression.
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Affiliation(s)
- Domenico D'Ugo
- First Surgical Division, Department of Surgery, Catholic University of Rome, Rome, Italy
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34
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Does tumor size have an impact on gastric cancer? A single institute experience. Langenbecks Arch Surg 2008; 394:631-5. [PMID: 18791731 DOI: 10.1007/s00423-008-0417-0] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2008] [Accepted: 08/25/2008] [Indexed: 12/12/2022]
Abstract
PURPOSE The present study investigated the prognostic significance of tumor size in gastric carcinoma patients. METHODS Nine hundred seventy-three gastric carcinoma patients who underwent curative gastrectomy were included and hospital records were reviewed to determine the relationship between tumor size and survival. RESULTS First, the patients were divided based on the mean value of the tumor size in respective stages to control selection bias. Only in stages I and III was tumor size a significant independent prognostic factor. Second, we analyzed the appropriate cutoff value for the large tumor. The minimum criterion for a large tumor, which was determined by the receiver-operating characteristic curve for cancer-related death, was 3.5 cm. There were significant differences between patients with large and small tumors with respect to depth of invasion, number of lymph node metastasis, and stage of disease. CONCLUSIONS Tumor size serves as an indicator of prognosis in gastric cancer patients and a tumor size of 3.5 cm can be used as a significant lower limit of standard size criterion.
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35
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Moehler M, Lyros O, Gockel I, Galle PR, Lang H. Multidisciplinary management of gastric and gastroesophageal cancers. World J Gastroenterol 2008; 14:3773-80. [PMID: 18609699 PMCID: PMC2721432 DOI: 10.3748/wjg.14.3773] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/08/2008] [Revised: 05/19/2008] [Accepted: 05/26/2008] [Indexed: 02/06/2023] Open
Abstract
Carcinomas of the stomach and gastroesophageal junction are among the five top leading cancer types worldwide. In spite of radical surgical R0 resections being the basis of cure of gastric cancer, surgery alone provides long-term survival in only 30% of patients with advanced International Union Against Cancer (UICC) stages in Western countries because of the high risk of recurrence and metachronous metastases. However, recent large phase-III studies improved the diagnostic and therapeutic options in gastric cancers, indicating a more multidisciplinary management of the disease. Multimodal strategies combining different neoadjuvant and/or adjuvant protocols have clearly improved the gastric cancer prognosis when combined with surgery with curative intention. In particular, the perioperative (neoadjuvant, adjuvant) chemotherapy is now a well-established new standard of care for advanced tumors. Adjuvant therapy alone should be carefully discussed after surgical resection, mainly in individual patients with large lymph node positive tumors when neoadjuvant therapy could not be done. The palliative treatment options have also been remarkably improved with new chemotherapeutic agents and will further be enhanced with targeted therapies such as different monoclonal antibodies. This article reviews the most relevant literature on the multidisciplinary management of gastric and gastroesophageal cancer, and discusses future strategies to improve locoregional failures.
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36
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Samalin E, Ychou M. Le point sur les traitements adjuvants et néoadjuvants des adénocarcinomes œsogastriques. ONCOLOGIE 2008. [DOI: 10.1007/s10269-008-0845-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
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37
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Abstract
Despite the recent decline in the incidence of gastric cancer in North America and Western Europe, treatment remains a challenging problem for oncologists. Surgery is the primary modality for managing early-stage disease, but most patients who undergo a curative resection develop locoregional or distant recurrence. Consequently, there has been great interest in evaluating strategies to prevent recurrences and improve overall mortality. This article is a review of data on adjuvant and neoadjuvant treatment approaches for gastric cancer, including radiotherapy, chemotherapy, and chemoradiotherapy. Compared with surgery alone, the North American Intergroup 0116 trial demonstrated a clear survival benefit with the administration of a postoperative regimen of 5-fluorouracil, leucovorin, and external beam radiation therapy, and these findings have made concurrent chemoradiation a standard of care in patients with resected gastric cancer. More recently, the British Medical Research Council Adjuvant Gastric Cancer Infusional Chemotherapy (MAGIC) study found that preoperative and postoperative administration of epirubicin, cisplatin, and 5-fluorouracil significantly improved survival beyond surgery alone. Thus, after decades of negative studies, 2 successful strategies in localized gastric cancer are now available. Ongoing and proposed trials include the current Intergroup study (Cancer and Leukemia Group B 80101), which is assessing the role of a potentially more active postoperative chemoradiation regimen. The proposed MAGIC-B study will examine the role of adding bevacizumab to perioperative chemotherapy, and the planned CRITICS study by the Dutch Gastric Cancer Group will evaluate the role of postoperative chemoradiation in combination with preoperative chemotherapy.
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Affiliation(s)
- Kimmie Ng
- Dana-Farber Cancer Institute, Boston, MA 02115, USA.
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38
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Moehler M, Galle PR, Gockel I, Junginger T, Schmidberger H. The multidisciplinary management of gastrointestinal cancer. Multimodal treatment of gastric cancer. Best Pract Res Clin Gastroenterol 2007; 21:965-81. [PMID: 18070698 DOI: 10.1016/j.bpg.2007.10.003] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Although radical surgical R0 resections are the basis of cure for gastric cancer, surgery alone only provides long-term survival in 20-30% of patients with advanced-stage disease. Thus, in Western and European countries, advanced gastric cancer has a high risk of recurrence and metachronous metastases. Very recently, multimodal strategies combining different neoadjuvant and/or adjuvant protocols have improved the prognosis of gastric cancer when combined with surgery with curative intent. As used in palliative regimens, the combination of cisplatin with intravenous or oral fluoropyrimidines has been the integral component of such (neo)adjuvant strategies. However, the cytotoxic agents docetaxel, oxaliplatin and irinotecan and new targeted biologicals such as cetuximab, bevacizumab or panitumumab are currently under investigation, with or without irradiation, in multimodal treatment regimens. These studies may further increase R0 resection rates, and prolong disease-free and overall survival times in the treatment of advanced gastric cancer. This article reviews the most relevant literature on multimodal treatment of gastric cancer, and discusses future strategies to improve locoregional failures.
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Affiliation(s)
- Markus Moehler
- First Department of Internal Medicine, Johannes Gutenberg University of Mainz, Langenbeckstrasse 1, 55101 Mainz, Germany.
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39
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de Maat MFG, van de Velde CJH, Umetani N, de Heer P, Putter H, van Hoesel AQ, Meijer GA, van Grieken NC, Kuppen PJK, Bilchik AJ, Tollenaar RAEM, Hoon DSB. Epigenetic silencing of cyclooxygenase-2 affects clinical outcome in gastric cancer. J Clin Oncol 2007; 25:4887-94. [PMID: 17971584 DOI: 10.1200/jco.2006.09.8921] [Citation(s) in RCA: 59] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
PURPOSE Overexpression of cyclooxygenase-2 (COX-2) in gastric cancer has been shown to enhance tumor progression. We investigated whether silencing by promoter region hypermethylation of the COX-2 gene contributes to disease outcome in gastric cancer. MATERIALS AND METHODS COX-2 methylation status was initially assessed by capillary array electrophoresis methylation-specific polymerase chain reaction (CAE-MSP) and COX-2 protein expression by immunohistochemistry (IHC) in 40 primary gastric cancer tissues in a pilot study. Prognostic end points of correlative studies of COX-2 methylation status were time to recurrence, overall survival, and standard clinicopathologic features. CAE-MSP analysis was then validated in a second independent gastric cancer population (n = 137). RESULTS COX-2 methylation was detected in 23% and 28% of the pilot and validation patient groups, respectively. COX-2 expression (IHC) in gastric tumors inversely correlated with COX-2 gene methylation status in the pilot study (P = .02). COX-2 methylation in tumors was significantly associated with lower T, N, and TNM stage in the validation patient group (P = .02, P = .006, and P = .008, respectively). Patients with COX-2 methylated tumors had significantly longer time to recurrence and improved overall survival in a multivariate analysis in the validation patient group (hazard ratio[HR], 0.49; 95% CI, 0.24% to 0.99%; HR, 0.62; 95% CI, 0.38% to 0.99%, respectively). CONCLUSION Hypermethylation of COX-2 gene promoter was identified as an independent prognostic factor in gastric cancer patients. The results suggest promoter hypermethylation to be an important regulatory mechanism of COX-2 expression in gastric cancer and an important prognostic biomarker.
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Affiliation(s)
- Michiel F G de Maat
- Department of Molecular Oncology and Division of Gastrointestinal Surgery, John Wayne Cancer Institute, Santa Monica, CA 90404, USA
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Abstract
Although gastric cancer is still a worldwide major public health concern, it remains relatively uncommon in the Western countries. Despite improvement in surgical morbidity and mortality, as well as significant advancement of chemotherapy and radiotherapy options, the survival for gastric cancer has not significantly improved over the past decades. In the United States, standard of care for localized resectable gastric cancer is with adjuvant chemoradiotherapy. In this article, we summarize salient randomized and phase II and III clinical trials representing current treatment for gastric cancer.
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Affiliation(s)
- Alexandria T Phan
- University of Texas MD Anderson Cancer Center, GI Medical Oncology Department, 1515 Holcombe Boulevard, Mailbox 426, Houston, TX 77030, USA.
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41
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Wu AW, Xu GW, Wang HY, Ji JF, Tang JL. WITHDRAWN: Neoadjuvant chemotherapy versus none for resectable gastric cancer. Cochrane Database Syst Rev 2007; 2007:CD005047. [PMID: 17943834 PMCID: PMC10658827 DOI: 10.1002/14651858.cd005047.pub3] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
BACKGROUND Gastric cancer is a major cause of cancer death, and many patients are only diagnosed when the cancer has reached an advanced stage. Neoadjuvant chemotherapy (NAC), that is, chemotherapy administered shortly before surgical treatment, could provide a method of increasing the possibility of complete resection and survival. OBJECTIVES To evaluate the effect of neoadjuvant chemotherapy versus none for patients with resectable gastric cancer in terms of efficacy and toxicity. SEARCH STRATEGY Electronic databases including Cochrane Library, MEDLINE, EMBASE, CancerLit, Chinese Biomedical Literature Database (CBMDISC) and ongoing clinical trials as well as handsearching of conference proceedings, were searched to retrieve relevant data. SELECTION CRITERIA Randomized controlled clinical trials of neoadjuvant chemotherapy on resectable gastric cancer. DATA COLLECTION AND ANALYSIS We identified a total of 36 published citations or meeting abstracts. Thirty-two items were excluded. Of the four remaining studies, three stated random allocation but the method of randomization was unclear. Two of these employed allocation concealment by sealed envelope which was controlled by an independent party. None of the trials was double blind. All trials presented a detailed description of the number of withdrawals, dropouts and losses to follow-up. MAIN RESULTS Of the four clinical trials enrolled, there were 250 and 332 cases in total, with 106 and 126 deaths at the end of follow-up in the NAC and control group, respectively. The OR (odds ratio) was 1.05 (95%CI: 0.73-1.50), which was not statistically significant. Of the evaluable 129 patients receiving NAC, 28.7% demonstrated either a complete or a partial response. Two studies of NAC in resectable gastric cancer had resection rate data available for analysis The R0 resection rate in the NAC group was comparable to that in the control (OR: 0.96 (95%CI: 0.51-1.83)). The morbidity and mortality of NAC varied with the regimens used preoperatively. Of the 129 patients included in the analyzed studies, some acceptable toxicity was observed. AUTHORS' CONCLUSIONS There is no definite evidence of the effectiveness of NAC in resectable gastric cancer, in terms of improvements in patient survival, in the trials we reviewed. Neoadjuvant chemotherapy should not be used routinely in clinical setting until further results from randomized clinical are available. Neoadjuvant chemotherapy of gastric cancer should be applied under the framework of clinical trials.
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Affiliation(s)
- A W Wu
- Peking University, Surgical Oncology, Fucheng Road, No.52, Haidian District, Beijing, China, 100036.
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42
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Samalin E, Ychou M. Neoadjuvant treatment in upper gastrointestinal adenocarcinomas: new paradigms from old concepts? Curr Opin Oncol 2007; 19:384-9. [PMID: 17545805 DOI: 10.1097/cco.0b013e3281a73674] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
PURPOSE OF REVIEW Despite a decline in the incidence of upper gastrointestinal adenocarcinomas in North America and western Europe during the past century, treatment remains a challenging problem for oncologists. The poor outcome associated with surgical resection with curative intent has generated intensive investigation of combined modality treatment approaches including systemic chemotherapy to prevent recurrences and improve overall mortality. This article reviews data on neoadjuvant and perioperative treatment modalities for upper gastrointestinal adenocarcinomas. RECENT FINDINGS Postoperative chemoradiation is favored in the USA for good performance status patients with resected, high-risk gastric or gastroesophageal junction carcinoma (more stage IA). More recently, the UK Medical Research Council Adjuvant Gastric Infusional Chemotherapy (MAGIC) and Fédération Nationale des Centres de Lutte Contre le Cancer-Fédération Francophone de Cancérologie Digestive trials results, showing survival benefit with perioperative chemotherapy in operable gastric and lower esophageal cancers, have had an impact on the treatment practice in Europe. SUMMARY Novel strategies, involving induction with chemotherapy followed by preoperative chemoradiation, addition of targeted therapies to perioperative chemotherapy or use of new cytotoxic regimens are under evaluation to improve current standards and try to tailor therapeutic strategies.
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Affiliation(s)
- Emmanuelle Samalin
- Department of Digestive Oncology, CRLC Val d'Aurelle, Montpellier, France
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43
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Bueno Muiño C, Puente Vázquez J, Sastre Valera J, García-Sáenz JA, Martín M, García Miralles N, Sánchez-Pernaute A, Díaz-Rubio E. Pathological complete response following docetaxel-based neoadjuvant chemotherapy for locally advanced gastric adenocarcinoma. Clin Transl Oncol 2007; 9:335-8. [PMID: 17525046 DOI: 10.1007/s12094-007-0063-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
Locally advanced gastric adenocarcinoma has a poor outcome. Neoadjuvant treatment is being tested in locally advanced non-resectable tumours and in those resectable tumours with a high risk of recurrence. Efforts to identify prognostic factors and more active and less toxic preoperative regimens are being searched for. We report the case of a patient achieving a complete histopathological complete response following docetaxel- based neoadjuvant chemotherapy.
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Affiliation(s)
- C Bueno Muiño
- Servicio de Oncología Médica, Hospital Clínico San Carlos, Madrid, Spain.
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44
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Wu AW, Xu GW, Wang HY, Ji JF, Tang JL. Neoadjuvant chemotherapy versus none for resectable gastric cancer. Cochrane Database Syst Rev 2007:CD005047. [PMID: 17443566 DOI: 10.1002/14651858.cd005047.pub2] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
BACKGROUND Gastric cancer is a major cause of cancer death, and many patients are only diagnosed when the cancer has reached an advanced stage. Neoadjuvant chemotherapy (NAC), that is, chemotherapy administered shortly before surgical treatment, could provide a method of increasing the possibility of complete resection and survival. OBJECTIVES To evaluate the effect of neoadjuvant chemotherapy versus none for patients with resectable gastric cancer in terms of efficacy and toxicity. SEARCH STRATEGY Electronic databases including Cochrane Library, MEDLINE, EMBASE, CancerLit, Chinese Biomedical Literature Database (CBMDISC) and ongoing clinical trials as well as handsearching of conference proceedings, were searched to retrieve relevant data. SELECTION CRITERIA Randomized controlled clinical trials of neoadjuvant chemotherapy on resectable gastric cancer. DATA COLLECTION AND ANALYSIS We identified a total of 36 published citations or meeting abstracts. Thirty-two items were excluded. Of the four remaining studies, three stated random allocation but the method of randomization was unclear. Two of these employed allocation concealment by sealed envelope which was controlled by an independent party. None of the trials was double blind. All trials presented a detailed description of the number of withdrawals, dropouts and losses to follow-up. MAIN RESULTS Of the four clinical trials enrolled, there were 250 and 332 cases in total, with 106 and 126 deaths at the end of follow-up in the NAC and control group, respectively. The OR (odds ratio) was 1.05 (95%CI: 0.73-1.50), which was not statistically significant. Of the evaluable 129 patients receiving NAC, 28.7% demonstrated either a complete or a partial response. Two studies of NAC in resectable gastric cancer had resection rate data available for analysis The R0 resection rate in the NAC group was comparable to that in the control (OR: 0.96 (95%CI: 0.51-1.83)). The morbidity and mortality of NAC varied with the regimens used preoperatively. Of the 129 patients included in the analyzed studies, some acceptable toxicity was observed. AUTHORS' CONCLUSIONS There is no definite evidence of the effectiveness of NAC in resectable gastric cancer, in terms of improvements in patient survival, in the trials we reviewed. Neoadjuvant chemotherapy should not be used routinely in clinical setting until further results from randomized clinical are available. Neoadjuvant chemotherapy of gastric cancer should be applied under the framework of clinical trials.
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Affiliation(s)
- A W Wu
- Peking University, Surgical Oncology, Fucheng Road, No.52, Haidian District, Beijing, China, 100036.
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45
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Satoh S, Hasegawa S, Ozaki N, Okabe H, Watanabe G, Nagayama S, Fukushima M, Takabayashi A, Sakai Y. Retrospective analysis of 45 consecutive patients with advanced gastric cancer treated with neoadjuvant chemotherapy using an S-1/CDDP combination. Gastric Cancer 2006; 9:129-35. [PMID: 16767369 DOI: 10.1007/s10120-006-0369-4] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2005] [Accepted: 02/14/2006] [Indexed: 02/07/2023]
Abstract
BACKGROUND Standard treatment for highly advanced gastric cancer (AGC) has not been established yet. Neoadjuvant chemotherapy (NAC) represents a promising approach, which may improve the prognosis of AGC. In this study, we analyzed the feasibility and efficacy of NAC with S-1 (TS-1)/cisplatin CDDP in order to design appropriate clinical trials for AGC. METHODS Results for a series of 45 consecutive patients with AGC treated with S-1/CDDP induction chemotherapy since January 2002 were analyzed retrospectively. RESULTS The primary tumor was resected in 36 of the 45 patients (resectability, 80.0%). Progression of the disease during chemotherapy was observed in 1 patient only (2.2%). No treatment-related deaths occurred, and serious adverse effects (grade 3-4) were noted in only 2.2% of the patients. The overall median survival time was 1.82 years. Especially noteworthy is that, in patients with highly advanced disease (pretreatment [c]-stage IV; n = 27), resectability was 66.7% and curative (R0) resection was possible in 10 patients. The median survival times for c-stage IV patients who had total, curative, and noncurative resections were 20.8, 22.3 and 12.6 months, respectively. R0 resection was possible for all c-stage III patients (n = 17), with a 2-year overall survival of 90.9%. The downstaging rate was 55.6% (20/36), resulting in a significantly improved prognosis for the downstaged patients (P = 0.012). CONCLUSION Induction chemotherapy using S-1/CDDP for AGC appears to be a safe and promising treatment. We have therefore started two independent multiinstitutional clinical trials to evaluate the efficacy of this treatment.
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Affiliation(s)
- Seiji Satoh
- Department of Surgery, Kyoto University Hospital, Kyoto 606-8507, Japan
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46
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Starling N, Cunningham D. The role of systemic therapy for localised gastric cancer. Ann Oncol 2006; 17 Suppl 10:x115-21. [PMID: 17018711 DOI: 10.1093/annonc/mdl248] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
Affiliation(s)
- N Starling
- Royal Marsden Hospital, Sutton, Surrey, UK
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47
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Kobayashi O, Tsuburaya A, Yoshikawa T, Osaragi T, Murakami H, Yoshida T, Sairenji M. The efficacy of gastrectomy for large gastric cancer. Int J Clin Oncol 2006; 11:44-50. [PMID: 16508728 DOI: 10.1007/s10147-005-0535-4] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2005] [Accepted: 09/20/2005] [Indexed: 12/29/2022]
Abstract
BACKGROUND Large gastric cancer (LGC) is frequently associated with extended disease, and the role of surgical resection has been debated. We investigated the efficacy of surgical treatment for LGC. METHODS The size of LGC was defined as 8 cm or greater. Four hundred and fifteen patients with LGC who underwent gastrectomy were included. The clinicopathological features, the status of the residual tumor, the incidence and patterns of relapse, and the survival were analyzed. RESULTS Macroscopically, diffuse-type tumors were dominant (60%). The numbers of patients with tumors of T3 or greater, lymph node involvement, and peritoneal metastases were 356 (86%), 359 (87%), and 126 (30%), respectively. One hundred and eighty-eight patients (45%) underwent incomplete tumor resection (R2). The R2/R0 (no residual tumor) ratio was greater than 1 in patients with type 4 tumors and N1 or greater metastasis and in those with type 3 tumors and N2 or greater metastasis. In contrast, T2, type 2, and type 5 tumors were more likely to be completely resected. The 5-year survival for all 415 patients was 26%. The survival rates were inversely related to the tumor type, size, and lymph node metastasis. In the 216 patients with R0, the 5-year survivals of those with pN (International Union Against Cancer [UICC] classification) 0, 1, 2, and 3 were 66%, 56%, 36%, and 5%, respectively (P = 0.001). In 96 of these 216 patients (44%) the tumor recurred, and peritoneal metastasis was the most frequent mode of recurrence (48%). By Cox's proportional hazard model, the tumor size was an independent prognostic factor. CONCLUSION The chance of achieving R0 resection for LGC is low, except for T2, type 2, or type 5 tumors. Primary resection should be avoided for other types of LGC.
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Affiliation(s)
- Osamu Kobayashi
- Department of Gastrointestinal Surgery, Kanagawa Cancer Center, 1-1-2 Nakao, Yokohama, 241-0815, Japan.
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Archie V, Kauh J, Jones DV, Cruz V, Karpeh MS, Thomas CR. Gastric cancer: standards for the 21st century. Crit Rev Oncol Hematol 2006; 57:123-31. [PMID: 16412659 DOI: 10.1016/j.critrevonc.2005.09.004] [Citation(s) in RCA: 18] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2004] [Revised: 08/30/2005] [Accepted: 09/08/2005] [Indexed: 11/21/2022] Open
Abstract
Although the incidence of gastric cancer has been decreasing in the United States, it remains a leading cause of cancer death in the world, only lung cancer causes more deaths worldwide. The combination of relatively low prevalence, lack of pathognomonic symptoms, and lack of defined risk factors are associated with a delay in diagnosis leading to a dismal prognosis. For localized disease, surgery remains a cornerstone of treatment but much controversy remains regarding optimal peri-operative therapy. For advanced disease, several new agents and new combination chemotherapies have offered encouraging results. This paper seeks to review the major topics surrounding gastric cancer and cover the results of recently reported and ongoing trials.
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Affiliation(s)
- Victor Archie
- Department of Radiation Oncology, The David Geffen U.C.L.A. School of Medicine, Jonsson Comprehensive Cancer Center, Los Angeles, CA, USA
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Sastre J, Garcia-Saenz JA, Diaz-Rubio E. Chemotherapy for gastric cancer. World J Gastroenterol 2006; 12:204-13. [PMID: 16482619 PMCID: PMC4066028 DOI: 10.3748/wjg.v12.i2.204] [Citation(s) in RCA: 76] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/09/2005] [Revised: 06/28/2005] [Accepted: 07/08/2005] [Indexed: 02/06/2023] Open
Abstract
Metastatic gastric cancer remains a non-curative disease. Palliative chemotherapy has been demonstrated to prolong survival without quality of life compromise. Many single-agents and combinations have been confirmed to be active in the treatment of metastatic disease. Objective response rates ranged from 10-30% for single-agent therapy and 30-60% for polychemotherapy. Results of phase II and III studies are reviewed in this paper as well as the potential efficacy of new drugs. For patients with localized disease, the role of adjuvant and neoadjuvant chemotherapy and radiation therapy is discussed. Most studies on adjuvant chemotherapy failed to demonstrate a survival advantage, and therefore, it is not considered as standard treatment in most centres. Adjuvant immunochemotherapy has been developed fundamentally in Korea and Japan. A meta-analysis of phase III trials with OK-432 suggested that immunochemotherapy may improve survival of patients with curatively resected gastric cancer. Based on the results of US Intergroup 0116 study, postoperative chemoradiation has been accepted as standard care in patients with resected gastric cancer in North America. However, the results are somewhat confounded by the fact that patients underwent less than a recommended D1 lymph node dissection and the pattern of recurrence suggested a positive effect derived from local radiotherapy without any effect on micrometastatic disease. Neoadjuvant chemotherapy or chemoradiation therapy remains experimental, but several phase II studies are showing promising results. Phase III trials are needed.
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Affiliation(s)
- Javier Sastre
- Servicio de Oncologia Medica, HCU San Carlos, c/Martin Lagos s/n 28040 Madrid, Spain.
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Abstract
Although the incidence of gastric cancer is decreasing, it remains a significant source of cancer-related mortality. Surgery remains the best chance for cure from gastric cancer. Adjuvant and neoadjuvant therapy have played increasing roles in attempting to reduce the disease-specific mortality and prolong survival. In this article, the authors review the literature and summarize the salient points regarding the roles of adjuvant and neoadjuvant therapy for gastric cancer.
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Affiliation(s)
- Ricardo J Gonzalez
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Unit 444, 1515 Holcombe Boulevard, Houston, TX 77030-5235, USA
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