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Bulut N, Erdem GU, Kapagan T, Erol VB, Sahin T, Yakin M, Bayramgil A, Dülgar Ö. Prognostic impact of histopathological features and serum inflammatory markers in patients with gastric cancer undergoing neoadjuvant therapy. World J Gastrointest Surg 2025; 17:106517. [DOI: 10.4240/wjgs.v17.i6.106517] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2025] [Revised: 04/01/2025] [Accepted: 05/06/2025] [Indexed: 05/30/2025] Open
Abstract
BACKGROUND Neoadjuvant therapies induce tumor regression, resulting in improved surgical resection and pathologic complete response rates, as well as long-term disease-free and overall survival (OS). In addition to the tumor regression score, serum inflammatory markers, including neutrophil, lymphocyte, platelet, and serum albumin levels, are used to determine prognosis.
AIM To investigate the effect of histological features and serum inflammatory markers on the prognosis of gastric cancer following neoadjuvant treatment.
METHODS Neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and serum albumin levels were retrospectively recorded for 177 patients receiving neoadjuvant 5-fluorouracil, leucovorin, oxaliplatin and docetaxel chemotherapy. Disease-free and OS were analyzed based on tumor histopathological features, type of surgery, regression scores, and serum inflammatory markers.
RESULTS Patients over 65 years of age, those with lymphovascular or perineural invasion, hypoalbuminemia, and those who did not receive adjuvant therapy were found to be at higher risk for shorter recurrence/relapse intervals [hazard ratio (HR): 1.64, P = 0.04; HR: 4.20, P < 0.001; HR: 1.87, P = 0.03; HR: 3.5, P < 0.001; and HR: 2.73, P = 0.01, respectively]. Lymphovascular invasion, R1 resection, lack of adjuvant treatment, and hypoalbuminemia negatively influenced OS (HR: 3.68, P < 0.003; HR: 2.37, P = 0.01; HR: 3.99, P < 0.001; and HR: 2.50, P = 0.01, respectively). No effect of NLR and PLR was observed.
CONCLUSION Current neoadjuvant therapies prolong disease-free and OS. The practical application of serum inflammatory markers (NLR and PLR) is limited due to the lack of standard cut-off values. Nutritional status, hypoalbuminemia, and incomplete perioperative chemotherapy have been associated with poor prognosis.
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Affiliation(s)
- Nilufer Bulut
- Department of Medical Oncology, Basaksehir Cam and Sakura City Hospital, Istanbul 34303, Türkiye
| | - Gokmen U Erdem
- Department of Medical Oncology, Basaksehir Cam and Sakura City Hospital, Istanbul 34303, Türkiye
| | - Tanju Kapagan
- Department of Medical Oncology, Basaksehir Cam and Sakura City Hospital, Istanbul 34303, Türkiye
| | - Vedat B Erol
- Department of Medical Oncology, Basaksehir Cam and Sakura City Hospital, Istanbul 34303, Türkiye
| | - Tunahan Sahin
- Department of Medical Oncology, Basaksehir Cam and Sakura City Hospital, Istanbul 34303, Türkiye
| | - Murat Yakin
- Department of Medical Oncology, Basaksehir Cam and Sakura City Hospital, Istanbul 34303, Türkiye
| | - Ayberk Bayramgil
- Department of Medical Oncology, Umraniye Training and Research Hospital, Istanbul 34760, Türkiye
| | - Özgecan Dülgar
- Department of Medical Oncology, Umraniye Training and Research Hospital, Istanbul 34760, Türkiye
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Mitra S, Simson DK, Gehani M, Barik S, Khurana R, Singh S, Talwar V, Goel V, Khurana H, Mishra M, Dewan A, Mukhi MJ. Survival and Recurrence Patterns in Patients With Stomach Adenocarcinoma Receiving Chemotherapy or Chemoradiotherapy After D2 Gastrectomy in a Tertiary Care Cancer Institute: A Retrospective Real-World Evidence Cohort Study. Adv Radiat Oncol 2023; 8:101280. [PMID: 38047217 PMCID: PMC10692297 DOI: 10.1016/j.adro.2023.101280] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2023] [Accepted: 05/23/2023] [Indexed: 12/05/2023] Open
Abstract
Purpose Clinical trials comparing the efficacy of adjuvant chemotherapy (CT) and chemo radiation therapy (CTRT) for stomach adenocarcinoma have reported equivocal results. Hence, the current retrospective cohort study assessed the long-term survival and recurrence outcomes of these therapies, to generate evidence in a real-world scenario. Methods and Materials Pathologically confirmed patients with stomach adenocarcinoma aged ≥18 years who underwent gastrectomy and D2 lymph nodal dissection at a tertiary cancer hospital from January 2010 to October 2017 were enrolled. Hospital-based follow-up was performed until December 2021. Data were gathered from electronic medical records, supplemented by telephonic interviews for patients who could not come for physical follow-up. CT-alone and CTRT cohorts were compared in terms of survival and recurrence outcomes. Results The analysis included 158 patients (mean age, 56.42 years; 63.9% male; CT-alone cohort, 69; CTRT cohort, 89). Patients in the CTRT cohort had significantly worse tumor characteristics at baseline (29.2% had the diffuse type of tumor, 94.4% had stage II or III, 68.5% had lympho-vascular space invasion, and 85.4% had lymph node involvement). Recurrence was observed in 13 (19.7%) of the 76 followed-up patients. Although locoregional recurrence was higher in the CT-alone cohort (7 vs 2), distant metastasis was higher in the CTRT cohort (3 vs 1). The overall 5-year survival was 67.0% (SE, 5.0%) and 5-year recurrence-free survival (RFS) was 75.0% (SE, 5.0%). On multivariate Cox regression, no variable was significantly associated with the overall survival, whereas age, positive lymph nodes without extracapsular extension, and lymph node-negative were significantly associated with RFS. The CTRT cohort had significantly (84.0%) higher RFS (hazard ratio, 0.161; 95% CI, 0.056-0.464; P < .001). Conclusions Patients who received adjuvant CTRT after D2 dissection showed similar overall survival but significantly higher RFS than the CT-alone cohort, despite having worse baseline tumor characteristics.
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Affiliation(s)
- Swarupa Mitra
- Rajiv Gandhi Cancer Institute and Research Center, Delhi, India
| | - David K. Simson
- Rajiv Gandhi Cancer Institute and Research Center, Delhi, India
| | - Manish Gehani
- Department of Biological Sciences, Birla Institute of Technology and Science, Pilani, Hyderabad Campus, India
| | - Soumitra Barik
- Rajiv Gandhi Cancer Institute and Research Center, Delhi, India
| | - Ruparna Khurana
- Holistic Oncology with Patient Empathy (HOPE) Oncology Clinic, New Delhi, India
| | - Shivendra Singh
- Rajiv Gandhi Cancer Institute and Research Center, Delhi, India
| | - Vineet Talwar
- Rajiv Gandhi Cancer Institute and Research Center, Delhi, India
| | - Varun Goel
- Rajiv Gandhi Cancer Institute and Research Center, Delhi, India
| | | | - Manindra Mishra
- Rajiv Gandhi Cancer Institute and Research Center, Delhi, India
| | - Abhinav Dewan
- Rajiv Gandhi Cancer Institute and Research Center, Delhi, India
| | - M. Jwala Mukhi
- Rajiv Gandhi Cancer Institute and Research Center, Delhi, India
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Sato B, Kanda M, Ito S, Mochizuki Y, Teramoto H, Ishigure K, Murai T, Asada T, Ishiyama A, Matsushita H, Nakanishi K, Shimizu D, Tanaka C, Fujiwara M, Murotani K, Kodera Y. Proposal of the Second Cutoff of Serum Carcinoembryonic Antigen Levels to Stratify Patients into Low, Intermediate, and High Risks at Recurrences after Curative Resection of Gastric Cancer. Dig Surg 2023; 40:187-195. [PMID: 37699371 DOI: 10.1159/000533143] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/04/2022] [Accepted: 05/17/2023] [Indexed: 09/14/2023]
Abstract
INTRODUCTION Carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 are widely used for treating various cancers, with cutoff values of 5.0 ng/mL and 37.0 IU/mL, respectively. However, these cutoff values are not for specific diseases or purposes but are uniformly used for any disease and any purpose. It is also unclear as to whether patients are at equal risk of recurrence if they are below the cutoff values. This study aimed to investigate the optimal cutoff of serum tumor markers in the stratification of recurrence risk after curative resection of gastric cancer. METHODS We constructed a nine-center integrated database of patients who received gastrectomy between January 2010 and December 2014 with a 5-year follow-up period. We determined the cutoff value of preoperative serum tumor marker levels correlated with postoperative recurrences and evaluated its performance in risk stratification for recurrences in 948 patients with stage II/III gastric cancer who underwent radical resection. RESULTS The hazard ratio for postoperative recurrences increased at two points of preoperative CEA levels, 3.6 ng/mL and 5.0 ng/mL, which were set as cutoffs. These two cutoffs stratified relapse-free survival into three levels. CONCLUSIONS By adding a second cutoff value for preoperative serum CEA, which was proposed specifically for the prediction of recurrences, patients can be stratified into low-, intermediate-, and high-risk recurrences after curative resection of gastric cancer.
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Affiliation(s)
- Bin Sato
- Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan,
| | - Mitsuro Kanda
- Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Seiji Ito
- Department of Gastroenterological Surgery, Aichi Cancer Center, Nagoya, Japan
| | | | - Hitoshi Teramoto
- Department of Surgery, Yokkaichi Municipal Hospital, Yokkaichi, Japan
| | | | - Toshifumi Murai
- Department of Surgery, Ichinomiya Municipal Hospital, Ichinomiya, Japan
| | - Takahiro Asada
- Department of Surgery, Gifu Prefectural Tajimi Hospital, Tajimi, Japan
| | | | | | - Koki Nakanishi
- Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Dai Shimizu
- Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Chie Tanaka
- Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Michitaka Fujiwara
- Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan
- Department of Medical Equipment and Supplies Management, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Kenta Murotani
- Biostatistics Center, Graduate School of Medicine, Kurume University, Kurume, Japan
| | - Yasuhiro Kodera
- Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan
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Eads JR, Halfdanarson TR, Asmis T, Bellizzi AM, Bergsland EK, Dasari A, El-Haddad G, Frumovitz M, Meyer J, Mittra E, Myrehaug S, Nakakura E, Raj N, Soares HP, Untch B, Vijayvergia N, Chan JA. Expert Consensus Practice Recommendations of the North American Neuroendocrine Tumor Society for the management of high grade gastroenteropancreatic and gynecologic neuroendocrine neoplasms. Endocr Relat Cancer 2023; 30:e220206. [PMID: 37184955 PMCID: PMC10388681 DOI: 10.1530/erc-22-0206] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/05/2023] [Accepted: 05/15/2023] [Indexed: 05/16/2023]
Abstract
High-grade neuroendocrine neoplasms are a rare disease entity and account for approximately 10% of all neuroendocrine neoplasms. Because of their rarity, there is an overall lack of prospectively collected data available to advise practitioners as to how best to manage these patients. As a result, best practices are largely based on expert opinion. Recently, a distinction was made between well-differentiated high-grade (G3) neuroendocrine tumors and poorly differentiated neuroendocrine carcinomas, and with this, pathologic details, appropriate imaging practices and treatment have become more complex. In an effort to provide practitioners with the best guidance for the management of patients with high-grade neuroendocrine neoplasms of the gastrointestinal tract, pancreas, and gynecologic system, the North American Neuroendocrine Tumor Society convened a panel of experts to develop a set of recommendations and a treatment algorithm that may be used by practitioners for the care of these patients. Here, we provide consensus recommendations from the panel on pathology, imaging practices, management of localized disease, management of metastatic disease and surveillance and draw key distinctions as to the approach that should be utilized in patients with well-differentiated G3 neuroendocrine tumors vs poorly differentiated neuroendocrine carcinomas.
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Affiliation(s)
- Jennifer R Eads
- Division of Hematology and Oncology, Abramson Cancer Center, University of Pennsylvania, Pennsylvania, USA
| | | | - Tim Asmis
- Division of Medical Oncology, University of Ottawa, Ottawa, Ontario, Canada
| | - Andrew M Bellizzi
- Department of Pathology, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA
| | - Emily K Bergsland
- Department of Medicine, University of California, San Francisco, California, USA
| | - Arvind Dasari
- Division of Gastrointestinal Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Ghassan El-Haddad
- Department of Diagnostic Imaging and Interventional Radiology, Moffitt Cancer Center and Research Institute, Tampa, Florida, USA
| | - Michael Frumovitz
- Division of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Joshua Meyer
- Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA
| | - Erik Mittra
- Division of Molecular Imaging and Therapy, Oregon Health & Science University, Portland, Oregon, USA
| | - Sten Myrehaug
- Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
| | - Eric Nakakura
- Department of Surgery, University of California, San Francisco, California, USA
| | - Nitya Raj
- Department of Medicine, Gastrointestinal Oncology Service, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - Heloisa P Soares
- Division of Oncology, Huntsman Cancer Institute, University of Utah, Salt Lake City, Salt Lake City, Utah, USA
| | - Brian Untch
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - Namrata Vijayvergia
- Department of Hematology and Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA
| | - Jennifer A Chan
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA
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Shen J, Zhu X, Du Y, Zhu Y, Yu P, Yang L, Xu Z, Huang L, Zhang Y, Zhang Y, Liu L, Cheng X. Adjuvant SOX chemotherapy versus concurrent chemoradiotherapy after D2 radical resection of locally advanced esophagogastric junction (EGJ) adenocarcinoma: study protocol for a randomized phase III trial (ARTEG). Trials 2021; 22:753. [PMID: 34717717 PMCID: PMC8556914 DOI: 10.1186/s13063-021-05617-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2020] [Accepted: 09/13/2021] [Indexed: 12/23/2022] Open
Abstract
BACKGROUND Survival benefit of adjuvant radiotherapy for locally advanced gastric cancer following gastrectomy plus D2 lymphadenectomy has always been controversial. Esophagogastric junction (EGJ) adenocarcinoma, which is usually classified as gastric cancer in East Asia, often has a higher locoregional recurrence rate after operation because of its special anatomical characteristics. The aim of this study is to determine whether adjuvant radiotherapy can improve survival of locally advanced EGJ adenocarcinoma after D2 radical resection. METHODS In this phase III, randomized, open label, controlled trial, we plan to recruit 378 patients with Siewert type II and III adenocarcinoma of EGJ, who had undergone transabdominal radical surgery and D2 lymphadenectomy, and were divided into pathological stage IIB to IIIC. All patients will be randomized 1:1 to receive either adjuvant chemotherapy alone (control group) or adjuvant chemotherapy plus chemoradiotherapy (experimental group). Patients allocated to control group will receive eight cycles of S-1 plus oxaliplatin (SOX), while the experimental group will receive two cycles of SOX followed by 45-Gy RT combined with S-1 and four additional cycles of SOX. The primary endpoint is 3-year disease-free survival rate (DFS). The secondary endpoints are 3-year overall survival rate (OS), 3-year locoregional recurrence-free survival rate (LRFS), 3-year distant metastasis-free survival rate (DMFS), and quality of life (QoL). DISCUSSION In the past, the adjuvant treatment of EGJ adenocarcinoma needs to draw on the experience of esophageal adenocarcinoma or gastric adenocarcinoma. In this study, EGJ adenocarcinoma is considered as an independent disease, and the conclusion will provide evidence for optimal adjuvant therapy of locally advanced EGJ adenocarcinoma after D2 radical resection. TRIAL REGISTRATION ClinicalTrials.gov NCT03973008 . Registered on 1 June 2019 (retrospectively registered), URL: https://clinicaltrials.gov/ct2/show/NCT03973008?term=NCT03973008&draw=2&rank=1.
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Affiliation(s)
- Jinwen Shen
- Department of Abdominal Radiotherapy, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), 1 East Banshan Road, Hangzhou, 310022 P.R. China
- Zhejiang Provincial Research Center for Cancer of Upper Gastrointestinal Tract, 1 East Banshan Road, Hangzhou, 310022 P.R. China
| | - Xiu Zhu
- Department of Pathology, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), 1 East Banshan Road, Hangzhou, 310022 P.R. China
| | - Yian Du
- Zhejiang Provincial Research Center for Cancer of Upper Gastrointestinal Tract, 1 East Banshan Road, Hangzhou, 310022 P.R. China
- Department of Abdominal Surgery, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), 1 East Banshan Road, Hangzhou, 310022 P.R. China
| | - Yuan Zhu
- Department of Abdominal Radiotherapy, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), 1 East Banshan Road, Hangzhou, 310022 P.R. China
- Zhejiang Provincial Research Center for Cancer of Upper Gastrointestinal Tract, 1 East Banshan Road, Hangzhou, 310022 P.R. China
| | - Pengfei Yu
- Zhejiang Provincial Research Center for Cancer of Upper Gastrointestinal Tract, 1 East Banshan Road, Hangzhou, 310022 P.R. China
- Department of Abdominal Surgery, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), 1 East Banshan Road, Hangzhou, 310022 P.R. China
| | - Litao Yang
- Zhejiang Provincial Research Center for Cancer of Upper Gastrointestinal Tract, 1 East Banshan Road, Hangzhou, 310022 P.R. China
- Department of Abdominal Surgery, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), 1 East Banshan Road, Hangzhou, 310022 P.R. China
| | - Zhiyuan Xu
- Zhejiang Provincial Research Center for Cancer of Upper Gastrointestinal Tract, 1 East Banshan Road, Hangzhou, 310022 P.R. China
- Department of Abdominal Surgery, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), 1 East Banshan Road, Hangzhou, 310022 P.R. China
| | - Ling Huang
- Zhejiang Provincial Research Center for Cancer of Upper Gastrointestinal Tract, 1 East Banshan Road, Hangzhou, 310022 P.R. China
- Department of Abdominal Surgery, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), 1 East Banshan Road, Hangzhou, 310022 P.R. China
| | - Yunli Zhang
- Zhejiang Provincial Research Center for Cancer of Upper Gastrointestinal Tract, 1 East Banshan Road, Hangzhou, 310022 P.R. China
- Department of Abdominal Surgery, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), 1 East Banshan Road, Hangzhou, 310022 P.R. China
| | - Yanqiang Zhang
- Zhejiang Provincial Research Center for Cancer of Upper Gastrointestinal Tract, 1 East Banshan Road, Hangzhou, 310022 P.R. China
- Department of Abdominal Surgery, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), 1 East Banshan Road, Hangzhou, 310022 P.R. China
| | - Luying Liu
- Department of Abdominal Radiotherapy, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), 1 East Banshan Road, Hangzhou, 310022 P.R. China
- Zhejiang Provincial Research Center for Cancer of Upper Gastrointestinal Tract, 1 East Banshan Road, Hangzhou, 310022 P.R. China
| | - Xiangdong Cheng
- Zhejiang Provincial Research Center for Cancer of Upper Gastrointestinal Tract, 1 East Banshan Road, Hangzhou, 310022 P.R. China
- Department of Abdominal Surgery, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), 1 East Banshan Road, Hangzhou, 310022 P.R. China
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Trumbull DA, Lemini R, Díaz Vico T, Jorgensen MS, Attwood K, Ji W, Brady M, Gabriel E, Kukar M. Prognostic Significance of Complete Pathologic Response Obtained with Chemotherapy Versus Chemoradiotherapy in Gastric Cancer. Ann Surg Oncol 2020; 28:766-773. [PMID: 32737698 DOI: 10.1245/s10434-020-08921-9] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2019] [Accepted: 07/04/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND Few studies have compared the survival advantage of complete pathologic response (cPR) achieved through neoadjuvant chemotherapy (nCT) versus neoadjuvant chemoradiotherapy (nCRT) in gastric adenocarcinoma. Our study utilizes a large national cancer database to address this question. PATIENTS AND METHODS This is a retrospective review of patients with clinical stage I to III gastric adenocarcinoma from 2004 to 2013 who received nCT or nCRT. Patients who achieved cPR were selected. Associations were evaluated using Mann-Whitney U and Fisher's exact tests. Survival information was summarized using standard Kaplan-Meier methods, where estimates of the median and 5-year survival rates were estimated with 95% confidence intervals. RESULTS A total of 413 patients who had cPR were identified. Eighty-four patients received nCT and 329 patients received nCRT. Patients in the nCRT group had higher clinical stage (88.4% vs. 75.0%) and more proximal location of tumors (95.4% vs. 45.2%). The nCT group (n = 84) had a 94% 5-year survival rate, while the nCRT group's (n = 329) rate was 60% (p < 0.001). On Cox regression modeling using a propensity-weighted approach, nCT treatment was an independent predictor of improved overall survival (nCRT vs. nCT; HR 10.44, p < 0.001). CONCLUSIONS The use of nCT leads to a significant increase in overall survival in patients when compared with nCRT for those who achieved cPR in gastric adenocarcinoma. While this study is limited in identifying the cause for this difference in overall survival, this important finding nonetheless requires further investigation and should be considered in the development of future gastric cancer trials.
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Affiliation(s)
| | | | | | | | - Kristopher Attwood
- Department of Biostatistics, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA
| | - Wenyan Ji
- Department of Biostatistics, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA
| | - Maureen Brady
- Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA
| | | | - Moshim Kukar
- Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA.
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Global updates in the treatment of gastric cancer: a systematic review. Part 2: perioperative management, multimodal therapies, new technologies, standardization of the surgical treatment and educational aspects. Updates Surg 2020; 72:355-378. [PMID: 32306277 DOI: 10.1007/s13304-020-00771-0] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2020] [Accepted: 04/11/2020] [Indexed: 12/24/2022]
Abstract
Gastric cancer is the fifth malignancy and the third cause of cancer death worldwide, according to the global cancer statistics presented in 2018. Its definition and staging have been revised in the eight edition of the AJCC/TNM classification, which took effect in 2018. Novel molecular classifications for GC have been recently established and the process of translating these classifications into clinical practice is ongoing. The cornerstone of GC treatment is surgical, in a context of multimodal therapy. Surgical treatment is being standardized, and is evolving according to new anatomical concepts and to the recent technological developments. This is leading to a massive improvement in the use of mini-invasive techniques. Mini-invasive techniques aim to be equivalent to open surgery from an oncologic point of view, with better short-term outcomes. The persecution of better short-term outcomes also includes the optimization of the perioperative management, which is being implemented on large scale according to the enhanced recovery after surgery principles. In the era of precision medicine, multimodal treatment is also evolving. The long-time-awaited results of many trials investigating the role for preoperative and postoperative management have been published, changing the clinical practice. Novel investigations focused both on traditional chemotherapeutic regimens and targeted therapies are currently ongoing. Modern platforms increase the possibility for further standardization of the different treatments, promote the use of big data and open new possibilities for surgical learning. This systematic review in two parts assesses all the current updates in GC treatment.
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8
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Agnes A, Biondi A, Laurino A, Persiani R, D'Ugo D. Global updates in the treatment of gastric cancer: a systematic review. Part 1: staging, classification and surgical treatment. Updates Surg 2020; 72:341-353. [PMID: 32157635 DOI: 10.1007/s13304-020-00736-3] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2020] [Accepted: 02/25/2020] [Indexed: 02/07/2023]
Abstract
Gastric cancer (GC) is the fifth malignancy and the third cause of cancer death worldwide, according to the global cancer statistics presented in 2018. Its definition and staging have been revised in the eight edition of the AJCC/TNM classification, which took effect in 2018. Novel molecular classifications for GC have been recently established and the process of translating these classifications into clinical practice is ongoing. The cornerstone of GC treatment is surgical, in a context of multimodal therapy. Surgical treatment is being standardized, and is evolving according to new anatomical concepts and to the recent technological developments. This is leading to a massive improvement in the use of mini-invasive techniques. Mini-invasive techniques aim to be equivalent to open surgery from an oncologic point of view, with better short-term outcomes. The persecution of better short-term outcomes also includes the optimization of the perioperative management, which is being implemented on large scale according to the enhanced recovery after surgery principles. In the era of precision medicine, multimodal treatment is also evolving. The long-time-awaited results of many trials investigating the role for preoperative and postoperative management have been published, changing the clinical practice. Novel investigations focused both on traditional chemotherapeutic regimens and targeted therapies are currently ongoing. Modern platforms increase the possibility for further standardization of the different treatments, promote the use of big data, and open new possibilities for surgical learning. This systematic review in two parts assesses all the current updates in GC treatment.
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Affiliation(s)
- Annamaria Agnes
- Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario Agostino Gemelli, Largo A. Gemelli n. 8, 00168, Rome, Italy
| | - Alberto Biondi
- General Surgery Unit, Abdominal Surgery Area, Dipartimento Di Scienze Gastroenterologiche, Nefrourologiche Ed Endocrinometaboliche, IRCSS Fondazione Policlinico Universitario Agostino Gemelli, Largo A. Gemelli n. 8, 00168, Rome, Italy. .,Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario Agostino Gemelli, Largo A. Gemelli n. 8, 00168, Rome, Italy. .,General Surgery Unit, Abdominal Surgery Area, Dipartimento Di Scienze Gastroenterologiche, Nefro-Urologiche Ed Endocrinometaboliche, IRCSS Fondazione Policlinico Universitario Agostino Gemelli, Largo Francesco Vito n. 1, 00168, Rome, Italy.
| | - Antonio Laurino
- Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario Agostino Gemelli, Largo A. Gemelli n. 8, 00168, Rome, Italy
| | - Roberto Persiani
- General Surgery Unit, Abdominal Surgery Area, Dipartimento Di Scienze Gastroenterologiche, Nefrourologiche Ed Endocrinometaboliche, IRCSS Fondazione Policlinico Universitario Agostino Gemelli, Largo A. Gemelli n. 8, 00168, Rome, Italy.,Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario Agostino Gemelli, Largo A. Gemelli n. 8, 00168, Rome, Italy
| | - Domenico D'Ugo
- General Surgery Unit, Abdominal Surgery Area, Dipartimento Di Scienze Gastroenterologiche, Nefrourologiche Ed Endocrinometaboliche, IRCSS Fondazione Policlinico Universitario Agostino Gemelli, Largo A. Gemelli n. 8, 00168, Rome, Italy.,Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario Agostino Gemelli, Largo A. Gemelli n. 8, 00168, Rome, Italy
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Hayashi S, Kanda M, Ito S, Mochizuki Y, Teramoto H, Ishigure K, Murai T, Asada T, Ishiyama A, Matsushita H, Tanaka C, Kobayashi D, Fujiwara M, Murotani K, Kodera Y. Number of retrieved lymph nodes is an independent prognostic factor after total gastrectomy for patients with stage III gastric cancer: propensity score matching analysis of a multi-institution dataset. Gastric Cancer 2019; 22:853-863. [PMID: 30483985 DOI: 10.1007/s10120-018-0902-2] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2018] [Accepted: 11/20/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND The prognostic significance of the number of retrieved lymph nodes (RLNs) in gastric cancer remains controversial. Therefore, we designed a multicenter collaborative database to investigate the correlation between the number of RLNs and prognosis of patients with advanced gastric cancer after curative resection. METHODS We retrospectively analyzed 1103 patients who underwent gastrectomy for stage II/III gastric cancer between 2010 and 2014. Lymph nodes, which were retrieved by surgeons from surgically resected specimens, were validated by pathologists. A target population and the optimal cutoff were determined using receiver operating characteristic (ROC) curve analysis. After propensity score matching of eight variables, including splenectomy and adjuvant chemotherapy, the prognostic significance of RLNs was evaluated. RESULTS According to ROC curve analysis, the optimum cutoff score for predicting postoperative survival was 40. After matching, the backgrounds of patients in the RLN < 40 and RLN ≥ 40 groups (n = 87 each) became well-balanced. The RLN < 40 group experienced significantly shorter relapse-free and overall survival. The prevalence of peritoneal recurrence was significantly increased in the RLN < 40 group. RLN < 40 was an independent prognostic factor in multivariable analysis, although pathological N status was not. A forest plot revealed that the RLN < 40 group was at greater risk of recurrence in most subgroups. CONCLUSIONS RLN < 40 was associated with an adverse prognosis of patients with stage III gastric cancer who underwent total gastrectomy.
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Affiliation(s)
- Shogo Hayashi
- Department of Surgery, Tosei General Hospital, Seto, Japan
| | - Mitsuro Kanda
- Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan.
| | - Seiji Ito
- Department of Gastroenterological Surgery, Aichi Cancer Center, Nagoya, Japan
| | | | - Hitoshi Teramoto
- Department of Surgery, Yokkaichi Municipal Hospital, Yokkaichi, Japan
| | | | - Toshifumi Murai
- Department of Surgery, Ichinomiya Municipal Hospital, Ichinomiya, Japan
| | - Takahiro Asada
- Department of Surgery, Gifu Prefectural Tajimi Hospital, Tajimi, Japan
| | | | | | - Chie Tanaka
- Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan
| | - Daisuke Kobayashi
- Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan
| | - Michitaka Fujiwara
- Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan
| | - Kenta Murotani
- Biostatistics Center, Graduate School of Medicine, Kurume University, Kurume, Japan
| | - Yasuhiro Kodera
- Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan
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Suenaga Y, Kanda M, Ito S, Mochizuki Y, Teramoto H, Ishigure K, Murai T, Asada T, Ishiyama A, Matsushita H, Tanaka C, Kobayashi D, Fujiwara M, Murotani K, Kodera Y. Prognostic significance of perioperative tumor marker levels in stage II/III gastric cancer. World J Gastrointest Oncol 2019; 11:17-27. [PMID: 30984347 PMCID: PMC6451928 DOI: 10.4251/wjgo.v11.i1.17] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2018] [Revised: 11/20/2018] [Accepted: 12/05/2018] [Indexed: 02/05/2023] Open
Abstract
AIM To evaluate the prognostic significance of perioperative carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) levels in stage II/III gastric cancer.
METHODS From a multi-institutional retrospective database compiled by integrating clinical data from nine institutions, data of 998 patients who underwent curative resection for stage II/III gastric cancer between 2010 and 2014 were retrieved and analyzed. The prognostic impact of the preoperative and postoperative levels and chronological changes in CEA, CA19-9 and their combination were evaluated. To test whether postoperative adjuvant chemotherapy alters the prognostic impact of perioperative CEA and CA19-9 levels, the hazard ratios for mortality were compared between patients who underwent surgery alone and patients who underwent surgery followed by adjuvant chemotherapy.
RESULTS The prognostic impact of postoperative CEA and CA19-9 was superior to that of the preoperative levels. Multivariable analysis identified high postoperative CEA and CA19-9 levels as independent prognostic factors for overall survival. Disease-free survival rates clearly decreased in a stepwise manner in association with postoperative CEA and CA19-9 levels, and patients with high levels of both markers showed significantly poorer prognosis than other patient groups. When we analyzed perioperative changes in serum CEA and CA19-9 levels, patients with high levels before and after surgery had the worst disease-free survival rates among all patient groups. Patients with normalized CEA levels after surgery had a significantly lower disease-free survival rate than those with normal perioperative levels, whereas patients with normalized CA19-9 levels after surgery had equivalent survival to those with normal perioperative levels. The prognostic impact of high CEA levels was observably smaller in patients who underwent adjuvant chemotherapy than in patients who underwent surgery alone, whereas that of high CA19-9 was greater in patients who underwent adjuvant chemotherapy. High postoperative CEA levels were significantly associated with an increased prevalence of liver, lung and bone recurrences, and high postoperative CA19-9 levels were significantly associated with increased frequencies of lymph node and liver recurrences.
CONCLUSION The evaluation of serum CEA and CA 19-9 levels both before and after surgery provides useful information for precise risk stratification after curative gastrectomy.
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Affiliation(s)
- Yasuhito Suenaga
- Department of Surgery, Yokkaichi Municipal Hospital, Yokkaichi 510-8567, Japan
- Department of Gastroenterological Surgery, Aichi Cancer Center, Nagoya 464-8681, Japan
| | - Mitsuro Kanda
- Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan
| | - Seiji Ito
- Department of Gastroenterological Surgery, Aichi Cancer Center, Nagoya 464-8681, Japan
| | | | - Hitoshi Teramoto
- Department of Surgery, Yokkaichi Municipal Hospital, Yokkaichi 510-8567, Japan
| | - Kiyoshi Ishigure
- Department of Surgery, Konan Kosei Hospital, Konan 483-8704, Japan
| | - Toshifumi Murai
- Department of Surgery, Ichinomiya Municipal Hospital, Ichinomiya 491-8558, Japan
| | - Takahiro Asada
- Department of Surgery, Gifu Prefectural Tajimi Hospital, Tajimi 507-8522, Japan
| | - Akiharu Ishiyama
- Department of Surgery, Okazaki City Hospital, Okazaki 444-8553, Japan
| | | | - Chie Tanaka
- Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan
| | - Daisuke Kobayashi
- Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan
| | - Michitaka Fujiwara
- Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan
| | - Kenta Murotani
- Biostatistics Center, Graduate School of Medicine, Kurume University, Kurume 830-0011, Japan
| | - Yasuhiro Kodera
- Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan
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11
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Nakagawa N, Kanda M, Ito S, Mochizuki Y, Teramoto H, Ishigure K, Murai T, Asada T, Ishiyama A, Matsushita H, Tanaka C, Kobayashi D, Fujiwara M, Murotani K, Kodera Y. Pathological tumor infiltrative pattern and sites of initial recurrence in stage II/III gastric cancer: Propensity score matching analysis of a multi-institutional dataset. Cancer Med 2018; 7:6020-6029. [PMID: 30411544 PMCID: PMC6308072 DOI: 10.1002/cam4.1868] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2018] [Revised: 09/27/2018] [Accepted: 10/22/2018] [Indexed: 12/23/2022] Open
Abstract
Background Advanced gastric cancer frequently recurs even after radical resection followed by adjuvant chemotherapy. The aim of this study was to evaluate the relationship between pathological infiltrative pattern (INF) and initial recurrence patterns in patients with stage II/III gastric cancer using a large multicenter database. Methods We retrospectively analyzed 1098 eligible patients who underwent curative gastrectomy for stage II/III gastric cancer at nine institutions between 2010 and 2014. Patients were categorized into the INF‐a/b and INF‐c groups and adjusted using propensity score matching. Results After propensity score matching, 686 patients (343 for each) were classified in the INF‐a/b and INF‐c groups. There were no significant differences in overall and disease‐free survival between the two groups. In the INF‐a/b group, frequencies of recurrence at the peritoneum, lymph node, and liver were equivalent. In contrast, the peritoneum was the most frequent site and accounted for 60% of the total recurrences in the INF‐c group. The cumulative peritoneal recurrence rate was significantly higher in the INF‐c group than in the INF‐a/b group (hazard ratio 2.47). INF‐c was a significant risk factor for peritoneal recurrences in most subgroups including age, sex, macroscopic type, tumor differentiation, and disease stage, and whether the postoperative treatment was given. Multivariate analysis identified INF‐c as an independent risk factor for peritoneal recurrences. The cumulative liver recurrence rate was significantly higher in the INF‐a/b group than in the INF‐c group (hazard ratio 3.44). Conclusions INF may represent an important predictor of recurrence patterns after curative resection of stage II/III gastric cancer.
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Affiliation(s)
- Nobuhiko Nakagawa
- Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Mitsuro Kanda
- Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Seiji Ito
- Department of Gastroenterological Surgery, Aichi Cancer Center, Nagoya, Japan
| | | | - Hitoshi Teramoto
- Department of Surgery, Yokkaichi Municipal Hospital, Yokkaichi, Japan
| | | | - Toshifumi Murai
- Department of Surgery, Ichinomiya Municipal Hospital, Ichinomiya, Japan
| | - Takahiro Asada
- Department of Surgery, Gifu Prefectural Tajimi Hospital, Tajimi, Japan
| | | | | | - Chie Tanaka
- Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Daisuke Kobayashi
- Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Michitaka Fujiwara
- Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Kenta Murotani
- Biostatistics Center, Graduate School of Medicine, Kurume University, Kurume, Japan
| | - Yasuhiro Kodera
- Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan
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