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Wong E, Kamarajah SK, Dahdaleh F, Naffouje S, Kunene V, Fackrell D, Griffiths EA. Adjuvant chemotherapy for node-negative gastric adenocarcinoma after neoadjuvant chemotherapy and gastrectomy: A propensity score matched analysis study. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2025; 51:109506. [PMID: 39756161 DOI: 10.1016/j.ejso.2024.109506] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2024] [Revised: 11/10/2024] [Accepted: 11/28/2024] [Indexed: 01/07/2025]
Abstract
INTRODUCTION The long term survival of patients undergoing curative resection for gastric cancer remains poor owing to high recurrence rates. The use of adjuvant chemotherapy in node positive gastric cancer to prolong survival and prevent recurrence is widely accepted. However, the role for adjuvant chemotherapy in node negative gastric cancer is less clear, particularly in the era of neoadjuvant chemotherapy. OBJECTIVE To determine the association of adjuvant chemotherapy with survival in patients undergoing pathologically node negative gastric cancer resection, following neoadjuvant chemotherapy. METHODS We examined a national cancer database containing patients who had undergone neoadjuvant chemotherapy and pathologically node negative curative gastrectomy. We divided these patients into those who had undergone adjuvant chemotherapy versus those who had not. Using a propensity score matched analysis, we analyzed the survival of these patients between the 2 groups. RESULTS 5309 patients who had undergone curative gastrectomy were identified from the database and 806 of these patients were given adjuvant chemotherapy. Following propensity score matched analysis, patients who had been given adjuvant chemotherapy had an increased median survival of 150 vs 125 months (5-year 68 % vs 62 %, p < 0.001). CONCLUSION There is a small, but statistically significant survival benefit for adjuvant chemotherapy in patients with node negative gastric cancer who had undergone neoadjuvant chemotherapy. Further studies are required to examine the role of adjuvant chemotherapy in this subset of patients.
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Affiliation(s)
- Enoch Wong
- Department of Upper Gastrointestinal Surgery, Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Trust, Birmingham, UK
| | - Sivesh K Kamarajah
- Department of Upper Gastrointestinal Surgery, Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Trust, Birmingham, UK; Institute of Cancer and Genomic Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK
| | - Fadi Dahdaleh
- Department of Surgical Oncology, Edward-Elmshurst Health, Naperville, IL, USA
| | - Samer Naffouje
- Department of General Surgery, Cleveland Clinic Main Campus, Cleveland, OH, USA
| | - Victoria Kunene
- Department of Oncology, Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Trust, Birmingham, UK
| | - David Fackrell
- Department of Oncology, Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Trust, Birmingham, UK
| | - Ewen A Griffiths
- Department of Upper Gastrointestinal Surgery, Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Trust, Birmingham, UK; Institute of Cancer and Genomic Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
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Plum PS, Pamuk A, Barutcu AG, Mallmann C, Niesen E, Berlth F, Zander T, Chon SH, Moenig SP, Quaas A, Bruns CJ, Hoelscher AH, Alakus H. Two decades of gastric and gastroesophageal junction cancer surgery. J Cancer Res Clin Oncol 2023; 149:7679-7688. [PMID: 37000260 PMCID: PMC10374756 DOI: 10.1007/s00432-023-04719-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2023] [Accepted: 03/20/2023] [Indexed: 04/01/2023]
Abstract
PURPOSE Diagnosis and treatment of gastric and gastroesophageal junction cancer have undergone many critical changes during the last two decades. We addressed the question of how clinical reality outside of clinical trials has changed for gastric and gastroesophageal junction cancer patients in a European center for upper gastrointestinal surgery. METHODS In this retrospective cohort study, patients undergoing (sub)total gastrectomy for gastric or gastroesophageal junction adenocarcinoma between 1996 and 2017 in a tertiary upper gastrointestinal center were included. The time was divided into a) before (1996-2006) (pre-CTx) and b) after (2006-2017) (CTx) the MAGIC trial. Data were comprehensively analyzed for demographics, tumor stage, perioperative treatment, surgery, histopathology, and survival rates (SR). RESULTS 737 patients (32% female) underwent gastrectomy, 255 patients in the pre-CTx era and 482 patients in the CTx era. The median age was 65 years and the median follow-up was 27.5 months for surviving patients. Around 16.9% of patients received neoadjuvant treatment in the pre-CTx era versus 46.3% in the CTx era. The 3-year survival rate (3-YSR) was 46.4% in the pre-CTx and 60.9% in the CTx era (p < 0.001). For pretreated patients, 3-YSR was 39.0% (pre-CTx) versus 55.3% (CTx) (p = 0.168). Survival rate (SR) for locally advanced tumor stages (cT3/cT4) was higher when neoadjuvant therapy was administered (3-YSR: 56.7% vs 40.6%; p = 0.022). There were no significant differences according to sex (p = 0.357), age (p = 0.379), pT category (p = 0.817), pN stage (p = 0.074), cM stage (p = 0.112), Laurén classification (p = 0.158), and SRs (3-YSR: 60.3% vs 59.4%; p = 0.898) between the MAGIC and FLOT regimens. CONCLUSIONS Survival rates have dramatically improved for gastric cancer patients during the last two decades. MAGIC and FLOT regimens showed similar results in the postsurgical follow-up.
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Affiliation(s)
- Patrick S Plum
- Department of General, Visceral, Cancer and Transplantation Surgery, University Hospital Cologne, Kerpener Str. 62, 50937, Cologne, Germany
- Department of Visceral, Transplant, Thoracic and Vascular Surgery, University Hospital Leipzig, Leipzig, Germany
| | - Aylin Pamuk
- Department of General, Visceral, Cancer and Transplantation Surgery, University Hospital Cologne, Kerpener Str. 62, 50937, Cologne, Germany
| | - Atakan G Barutcu
- Department of General, Visceral, Cancer and Transplantation Surgery, University Hospital Cologne, Kerpener Str. 62, 50937, Cologne, Germany
| | - Christoph Mallmann
- Department of General, Visceral, Cancer and Transplantation Surgery, University Hospital Cologne, Kerpener Str. 62, 50937, Cologne, Germany
| | - Emanuel Niesen
- Department I of Internal Medicine, Center for Integrated Oncology (CIO), University Hospital Cologne, Cologne, Germany
- Gastrointestinal Cancer Group Cologne (GCGC), Cologne, Germany
| | - Felix Berlth
- Department of General, Visceral and Transplant Surgery, University Medical Center, Mainz, Germany
| | - Thomas Zander
- Department I of Internal Medicine, Center for Integrated Oncology (CIO), University Hospital Cologne, Cologne, Germany
- Gastrointestinal Cancer Group Cologne (GCGC), Cologne, Germany
| | - Seung-Hun Chon
- Department of General, Visceral, Cancer and Transplantation Surgery, University Hospital Cologne, Kerpener Str. 62, 50937, Cologne, Germany
| | - Stefan P Moenig
- Service de Chirurgie Viscéral, Hôpitaux Universitaires de Genève, Geneva, Switzerland
| | - Alexander Quaas
- Institute of Pathology, University Hospital Cologne, Cologne, Germany
| | - Christiane J Bruns
- Department of General, Visceral, Cancer and Transplantation Surgery, University Hospital Cologne, Kerpener Str. 62, 50937, Cologne, Germany
- Gastrointestinal Cancer Group Cologne (GCGC), Cologne, Germany
| | | | - Hakan Alakus
- Department of General, Visceral, Cancer and Transplantation Surgery, University Hospital Cologne, Kerpener Str. 62, 50937, Cologne, Germany.
- Department I of Internal Medicine, Center for Integrated Oncology (CIO), University Hospital Cologne, Cologne, Germany.
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Tang XH, Wu XL, Gan XJ, Wang YD, Jia FZ, Wang YX, Zhang Y, Gao XY, Li ZY. Using Normalized Carcinoembryonic Antigen and Carbohydrate Antigen 19 to Predict and Monitor the Efficacy of Neoadjuvant Chemotherapy in Locally Advanced Gastric Cancer. Int J Mol Sci 2023; 24:12192. [PMID: 37569566 PMCID: PMC10418931 DOI: 10.3390/ijms241512192] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2023] [Revised: 07/23/2023] [Accepted: 07/24/2023] [Indexed: 08/13/2023] Open
Abstract
Carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) are established prognostic biomarkers for patients with gastric cancer. However, their potential as predictive markers for neoadjuvant chemotherapy (NACT) efficacy has not been fully elucidated. METHODS We conducted a retrospective analysis to determine values of CEA and CA19-9 prior to NACT (pre-NACT) and after NACT (post-NACT) in 399 patients with locally advanced gastric cancer (LAGC) who received intended NACT and surgery. RESULTS Among the 399 patients who underwent NACT plus surgery, 132 patients (33.1%) had elevated pre-NACT CEA/CA19-9 values. Furthermore, either pre-NACT or post-NACT CEA /CA19-9 levels were significantly associated with prognosis (p = 0.0023) compared to patients with non-elevated levels. Moreover, among the patients, a significant proportion (73/132, 55.3%) achieved normalized CEA/CA19-9 following NACT, which is a strong marker of a favorable treatment response and survival benefits. In addition, the patients with normalized CEA/CA19-9 also had a prolonged survival compared to those who underwent surgery first (p = 0.0140), which may be attributed to the clearance of micro-metastatic foci. Additionally, the magnitude of CEA/CA19-9 changes did not exhibit a statistically significant prognostic value. CONCLUSIONS Normalization of CEA/CA19-9 is a strong biomarker for the effectiveness of treatment, and can thus be exploited to prolong the long-term survival of patients with LAGC.
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Affiliation(s)
- Xiao-Huan Tang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gas-Trointestinal Cancer Center, Ward I, Peking University Cancer Hospital & Institute, Beijing 100142, China; (X.-H.T.); (X.-L.W.)
| | - Xiao-Long Wu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gas-Trointestinal Cancer Center, Ward I, Peking University Cancer Hospital & Institute, Beijing 100142, China; (X.-H.T.); (X.-L.W.)
| | - Xue-Jun Gan
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gas-Trointestinal Cancer Center, Ward I, Peking University Cancer Hospital & Institute, Beijing 100142, China; (X.-H.T.); (X.-L.W.)
| | - Yi-Ding Wang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gas-Trointestinal Cancer Center, Ward I, Peking University Cancer Hospital & Institute, Beijing 100142, China; (X.-H.T.); (X.-L.W.)
| | - Fang-Zhou Jia
- Biological Sample Bank, Peking University Cancer Hospital & Institute, Beijing 100142, China
| | - Yi-Xue Wang
- Biological Sample Bank, Peking University Cancer Hospital & Institute, Beijing 100142, China
| | - Yan Zhang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gas-Trointestinal Cancer Center, Ward I, Peking University Cancer Hospital & Institute, Beijing 100142, China; (X.-H.T.); (X.-L.W.)
| | - Xiang-Yu Gao
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gas-Trointestinal Cancer Center, Ward I, Peking University Cancer Hospital & Institute, Beijing 100142, China; (X.-H.T.); (X.-L.W.)
| | - Zi-Yu Li
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gas-Trointestinal Cancer Center, Ward I, Peking University Cancer Hospital & Institute, Beijing 100142, China; (X.-H.T.); (X.-L.W.)
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Yu Z, Tu H, Qiu S, Dong X, Zhang Y, Ma C, Li P. Multidisciplinary treatment for locally advanced gastric cancer: A systematic review and network meta-analysis. J Minim Access Surg 2023; 19:335-347. [PMID: 37282430 PMCID: PMC10449051 DOI: 10.4103/jmas.jmas_170_22] [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: 06/20/2022] [Revised: 01/10/2023] [Accepted: 03/27/2023] [Indexed: 06/08/2023] Open
Abstract
Introduction This study aimed to evaluate the efficacy of multidisciplinary treatment for patients with locally advanced gastric cancer (LAGC) who underwent radical gastrectomy. Patients and Methods Randomised controlled trials (RCTs) comparing the effectiveness of surgery alone, adjuvant chemotherapy (CT), adjuvant radiotherapy (RT), adjuvant chemoradiotherapy (CRT), neoadjuvant CT, neoadjuvant RT, neoadjuvant CRT, perioperative CT and hyperthermic intraperitoneal chemotherapy (HIPEC) for LAGC were searched. Overall survival (OS), disease-free survival (DFS), recurrence and metastasis, long-term mortality, adverse events (grade ≥3), operative complications and R0 resection rate were used as outcome indicators for meta-analysis. Results Forty-five RCTs with 10077 participants were finally analysed. Adjuvant CT had higher OS (hazard ratio [HR] = 0.74, 95% credible interval [CI] = 0.66-0.82) and DFS (HR = 0.67, 95% CI = 0.60-0.74) than surgery-alone group. Perioperative CT (odds ratio [OR] = 2.56, 95% CI = 1.19-5.50) and adjuvant CT (OR = 0.48, 95% CI = 0.27-0.86) both had more recurrence and metastasis than HIPEC + adjuvant CT, while adjuvant CRT tended to have less recurrence and metastasis than adjuvant CT (OR = 1.76, 95% CI = 1.29-2.42) and even adjuvant RT (OR = 1.83, 95% CI = 0.98-3.40). Moreover, the incidence of mortality in HIPEC + adjuvant CT was lower than that in adjuvant RT (OR = 0.28, 95% CI = 0.11-0.72), adjuvant CT (OR = 0.45, 95% CI = 0.23-0.86) and perioperative CT (OR = 2.39, 95% CI = 1.05-5.41). Analysis of adverse events (grade ≥3) showed no statistically significant difference between any two adjuvant therapy groups. Conclusion A combination of HIPEC with adjuvant CT seems to be the most effective adjuvant therapy, which contributes to reducing tumour recurrence, metastasis and mortality - without increasing surgical complications and adverse events related to toxicity. Compared with CT or RT alone, CRT can reduce recurrence, metastasis and mortality but increase adverse events. Moreover, neoadjuvant therapy can effectively improve the radical resection rate, but neoadjuvant CT tends to increase surgical complications.
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Affiliation(s)
- Zhiyuan Yu
- School of Medicine, Nankai University, Nankai District, Tianjin, China
- Medical School of Chinese PLA, Haidian District, Beijing, China
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Haidian District, Beijing, China
| | - Huaiyu Tu
- Medical School of Chinese PLA, Haidian District, Beijing, China
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Haidian District, Beijing, China
| | - Shuzhong Qiu
- Medical School of Chinese PLA, Haidian District, Beijing, China
| | - Xiaoyu Dong
- Medical School of Chinese PLA, Haidian District, Beijing, China
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Haidian District, Beijing, China
| | - Yonghui Zhang
- Medical School of Chinese PLA, Haidian District, Beijing, China
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Haidian District, Beijing, China
| | - Chao Ma
- Medical School of Chinese PLA, Haidian District, Beijing, China
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Haidian District, Beijing, China
| | - Peiyu Li
- School of Medicine, Nankai University, Nankai District, Tianjin, China
- Medical School of Chinese PLA, Haidian District, Beijing, China
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Haidian District, Beijing, China
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Wang T, Li C, Li X, Zhai J, Wang S, Shen L. The optimal neoadjuvant chemotherapy regimen for locally advanced gastric and gastroesophageal junction adenocarcinoma: a systematic review and Bayesian network meta-analysis. Eur J Med Res 2022; 27:239. [DOI: 10.1186/s40001-022-00878-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2022] [Accepted: 11/01/2022] [Indexed: 11/11/2022] Open
Abstract
Abstract
Background
Neoadjuvant chemotherapy (NAC) for locally advanced gastric and gastroesophageal junction adenocarcinoma (LAGC) has been recommended in several guidelines. However, there is no global consensus about the optimum of NAC regimens. We aimed to determine the optimal NAC regimen for LAGC.
Methods
A systematic review and Bayesian network meta-analysis was performed. The literature search was conducted from inception to June 2022. The odds ratio (OR) value and 95% confidence interval (95% CI) were used for assessment of R0 resection rate and pathological complete response rate (pCR) as primary outcomes. The hazard ratio (HR) value and 95% CI were interpreted for the assessment of overall survival (OS) and disease-free survival (DFS) as second outcomes. The risk ratio (RR) value and 95% CI were used for safety assessment.
Results
Twelve randomized controlled trials were identified with 3846 eligible participants. The network plots for R0 resectability, OS, and DFS constituted closed loops. The regimens of TPF (taxane and platinum plus fluoropyrimidine), ECF (epirubicin and cisplatin plus fluorouracil), and PF (platinum plus fluoropyrimidine) showed a meaningful improvement of R0 resectability, as well as OS and/or DFS, compared with surgery (including surgery-alone and surgery plus postoperative adjuvant chemotherapy). Importantly, among these regimens, TPF regimen showed significant superiority in R0 resection rate (versus ECF regimen), OS (versus ECF regimen), DFS (versus PF and ECF regimens), and pCR (versus PF regimen).
Conclusions
The taxane-based triplet regimen of TPF is likely the optimal neoadjuvant chemotherapy regimen for LAGC patients.
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Herng SC, Htet NH, Naing C. A comparison of neoadjuvant therapies for gastroesophageal and gastric cancer on tumour resection rate: A network meta-analysis. PLoS One 2022; 17:e0275186. [PMID: 36156598 PMCID: PMC9512180 DOI: 10.1371/journal.pone.0275186] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2021] [Accepted: 09/12/2022] [Indexed: 11/18/2022] Open
Abstract
Background
Gastric cancer is one of the most common malignancies around the world, and a variety of neoadjuvant chemotherapies with different drug combinations are available for the treatment. R0 resection refers to a microscopically negative margin on resection, where no gross or microscopic tumour remains in the primary tumour. We aimed to find evidence on the relative effectiveness of neoadjuvant therapies for patients with advanced gastroesophageal and gastric cancer on the R0 resection rate.
Methods
Relevant randomised controlled trials were searched using appropriate keywords in health-related databases. We performed network meta-analysis within a frequentist framework. The endpoint assessed was the R0 resection rate. We assessed consistency and transitivity assumptions that are necessary for network meta-analysis. This study only used data from published studies. The need for consent from participants was waived by the Ethics Review Committee of the International Medical University in Malaysia.
Results
Six randomised controlled trials involving 1700 patients were identified. A network plot was formed with five neoadjuvant regimens [DLX (pyrimidine analogue + platinum compounds + chemoradiotherapy), DELX (pyrimidine analogue + epipodophylllotoxins/etoposide + platinum compounds + chemoradiotherapy), ADL (anthracycline + pyrimidine analogue + platinum compounds), ADM (anthracycline+ pyrimidine analogue + anti-folate compounds) and LTX (platinum compounds + taxane + chemoradiotherapy)] and surgery alone for management of patients with advanced gastroesophageal and gastric cancer. Assumptions required for a network meta-analysis such as consistency ((global test: Chi2 (1): 3.71; p:0.054)), and the transitivity in accord to the characteristics of interventions considered in this review were not violated. In the network comparison, surgery alone has a lower R0 resection rate compared with LTX (OR 0.2, 95%CI:0.01, 0.38) or DLX (OR 0.48, 95%CI: 0.29, 0.79). LTX has higher resection rate compared with DLX (OR 2.47, 95%CI: 1.08 to 5.63), DELX (OR 106.0, 95%CI: 25.29 to 444.21), ADM (OR 5.41, 95%CI: 1.56 to 18.78) or ADL (OR 3.12, 95%CI: 1.27 to 7.67). There were wide or very wide CIs in many of these comparisons. Overall certainty of the evidence was low or very low. Further research in this field is very likely to have an important impact on our confidence in the R0 resection rates between LTX versus other neoadjuvant chemotherapy is likely to change the estimate.
Conclusions
Findings suggest that overall quality of evidence on the relative effectiveness of neoadjuvant chemotherapies was low to very low level. Therefore, we are very uncertain about the true effect of neoadjuvant therapies in the R0 resection rate in patients with gastroesophageal and gastric cancer. Future well-designed large trials are needed. To recruit large samples in this field, multicountry trials are recommended. Future trials also need to assess treatment-related adverse events, and patients-centered outcomes such as health‐related quality of life.
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Affiliation(s)
- Seow Chee Herng
- International Medical University, Kuala Lumpur, Malaysia
- University of New South Wales, Sydney, Australia
| | - Norah Htet Htet
- International Medical University, Kuala Lumpur, Malaysia
- * E-mail: (CN); (NHH)
| | - Cho Naing
- Division of Tropical Health and Medicine, James Cook University, Townsville, Queensland, Australia
- * E-mail: (CN); (NHH)
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Comparison of treatment strategies and survival of early-onset gastric cancer: a population-based study. Sci Rep 2022; 12:6288. [PMID: 35428811 PMCID: PMC9012810 DOI: 10.1038/s41598-022-10156-5] [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: 01/04/2022] [Accepted: 03/29/2022] [Indexed: 11/25/2022] Open
Abstract
Treatments for early-onset gastric cancer (EOGC) patients are rarely included in clinical trials, resulting in an unclear impact on survival. This study aimed to investigate the treatment patterns of EOGC patients and their impact on survival. Based on the Surveillance, Epidemiology, and End Results database, we conducted a retrospective analysis of 1639 EOGC patients (< 50 years) diagnosed between 2010 and 2018. Patients with larger tumours, distant metastasis, and AJCC TNM stage in IV were prone to receive nonsurgical treatment. Patients treated with surgery alone had a better prognosis than those receiving SROC or SCRT or nonsurgical treatment. However, analyses stratified by histological type, tumour size and TNM stage showed that patients did not benefit more from SROC and SCRT than from surgery alone. Similar results were observed in the stratified Cox regression risk analysis. Patients who received nonsurgical treatment had the highest risk of overall death [hazard ratio (HR) = 2.443, 95% confidence interval (CI) 1.865–3.200, P < 0.001]. This study indicated that additional radiotherapy, chemotherapy or chemoradiotherapy did not provide a coordinated survival benefit to EOGC patients.
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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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Du R, Ming J, Geng J, Zhu X, Zhang Y, Li S, Liu Z, Wang H, Wang Z, Tang L, Zhang X, Wu A, Bu Z, Yan Y, Li Z, Li Y, Li Z, Wang W. Establishment of prognostic models for adenocarcinoma of oesophagogastric junction patients with neoadjuvant chemoradiotherapy: a real-world study. Radiat Oncol 2022; 17:45. [PMID: 35241109 PMCID: PMC8896317 DOI: 10.1186/s13014-022-02016-3] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2022] [Accepted: 02/17/2022] [Indexed: 01/19/2023] Open
Abstract
BACKGROUND Multimodal therapies based on surgical resection have been recommended for the treatment of adenocarcinoma of the oesophagogastric junction (AEG). We aimed to evaluate prognostic factors in AEG patients receiving neoadjuvant chemoradiotherapy and to build predictive models. METHODS T3 - T4N + M0 AEG patients with resectable Siewert type II/III tumours were enrolled in this study. All patients underwent neoadjuvant chemoradiation, followed by radical surgery or systemic therapy according to clinical response. Survival analysis was performed using the Kaplan-Meier method; multivariate analysis using the Cox proportional hazards method was also conducted. The Harrell concordance index (C-index) was used to test the prognostic value of models involving prognostic factors, and consistency between actual and predicted survival rates was evaluated by calibration curves. RESULTS From February 2009 to February 2018, 79 patients were treated with neoadjuvant chemoradiotherapy; 60 patients of them underwent radical surgery. The R0 resection rate was 98.3%, and 46.7% of patients achieved a major pathologic response (MPR), namely, a residual tumour issue less than 10%. The 5-year overall survival (OS) rate was 63%, and the 5-year progression-free survival (PFS) rate was 48%. The incidence of grade 3 complications was 21.5%, and no grade 4 complications were reported. According to the results of univariate and multivariate analyses, we included the neutrophil-lymphocyte ratio (NLR), prognostic nutrition index (PNI), eosinophilic granulocyte (EOS) and postoperative pathologic stage in nomogram analysis to establish prediction models for OS and PFS; the C-index of each model was 0.814 and 0.722, respectively. Both the C-index and calibration curves generated to validate consistency between the actual and predicted survival indicated that the models were well calibrated and of good predictive value. CONCLUSIONS AEG patients achieved favourable downstaging and pathologic response after neoadjuvant chemoradiation, with acceptable adverse effects. Inflammation-based and nutrition-related factors and postoperative pathologic stage had a significant influence on OS and PFS, and the predictive value was verified through prognostic models.
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Affiliation(s)
- Rongxu Du
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiation Oncology, Peking University Cancer Hospital and Institute, Beijing, 100142, People's Republic of China
| | - Jiao Ming
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiation Oncology, Peking University Cancer Hospital and Institute, Beijing, 100142, People's Republic of China
| | - Jianhao Geng
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiation Oncology, Peking University Cancer Hospital and Institute, Beijing, 100142, People's Republic of China
| | - Xianggao Zhu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiation Oncology, Peking University Cancer Hospital and Institute, Beijing, 100142, People's Republic of China
| | - Yangzi Zhang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiation Oncology, Peking University Cancer Hospital and Institute, Beijing, 100142, People's Republic of China
| | - Shuai Li
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiation Oncology, Peking University Cancer Hospital and Institute, Beijing, 100142, People's Republic of China
| | - Zhiyan Liu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiation Oncology, Peking University Cancer Hospital and Institute, Beijing, 100142, People's Republic of China
| | - Hongzhi Wang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiation Oncology, Peking University Cancer Hospital and Institute, Beijing, 100142, People's Republic of China
| | - Zhilong Wang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Medical Imaging, Peking University Cancer Hospital and Institute, Beijing, 100142, People's Republic of China
| | - Lei Tang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Medical Imaging, Peking University Cancer Hospital and Institute, Beijing, 100142, People's Republic of China
| | - Xiaotian Zhang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Oncology, Peking University Cancer Hospital and Institute, Beijing, 100142, People's Republic of China
| | - Aiwen Wu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Surgery, Peking University Cancer Hospital and Institute, Beijing, 100142, People's Republic of China
| | - Zhaode Bu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Surgery, Peking University Cancer Hospital and Institute, Beijing, 100142, People's Republic of China
| | - Yan Yan
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Endoscopy Center, Peking University Cancer Hospital and Institute, Beijing, 100142, People's Republic of China
| | - Zhongwu Li
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Pathology, Peking University Cancer Hospital and Institute, Beijing, 100142, People's Republic of China
| | - Yongheng Li
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiation Oncology, Peking University Cancer Hospital and Institute, Beijing, 100142, People's Republic of China.
| | - Ziyu Li
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Surgery, Peking University Cancer Hospital and Institute, Beijing, 100142, People's Republic of China.
| | - Weihu Wang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiation Oncology, Peking University Cancer Hospital and Institute, Beijing, 100142, People's Republic of China.
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10
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Sugawara K, Kawaguchi Y, Seto Y, Vauthey JN. Multidisciplinary treatment strategy for locally advanced gastric cancer: A systematic review. Surg Oncol 2021; 38:101599. [PMID: 33991939 DOI: 10.1016/j.suronc.2021.101599] [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: 01/20/2021] [Accepted: 04/26/2021] [Indexed: 01/17/2023]
Abstract
BACKGROUND Multidisciplinary management of patients with locally advanced gastric cancer (LAGC) remains unstandardized worldwide. We performed a systemic review to summarize the advancements, regional differences, and current recommended multidisciplinary treatment strategies for LAGC. METHODS Eligible studies were identified through a comprehensive search of PubMed, Web of Science, Cochrane Library databases and Embase. Phase 3 randomized controlled trials which investigated survival of patients with LAGC who underwent gastrectomy with pre-/perioperative, postoperative chemotherapy, or chemoradiotherapy were included. RESULTS In total, we identified 11 studies of pre-/perioperative chemotherapy, 38 of postoperative chemotherapy, and 14 of chemoradiotherapy. In Europe and the USA, the current standard of care is perioperative chemotherapy for patients with LAGC using the regimen of 5-FU, folinic acid, oxaliplatin and docetaxel (FLOT). In Eastern Asia, upfront gastrectomy and postoperative chemotherapy is commonly used. The S-1 monotherapy or a regimen of capecitabine and oxaliplatin (CapOx) are used for patients with stage II disease, and the CapOx regimen or the S-1 plus docetaxel regimen are recommended for those with stage III Gastric cancer (GC). The addition of postoperative radiotherapy to peri- or postoperative chemotherapy is currently not recommended. Additionally, clinical trials testing targeted therapy and immunotherapy are increasingly performed worldwide. CONCLUSIONS Recent clinical trials showed a survival benefit of peri-over postoperative chemotherapy and chemoradiotherapy. As such, this strategy may have a potential as a global standard for patients with LAGC. Outcome of the ongoing clinical trials is expected to establish the global standard of multidisciplinary treatment strategy in patients with LAGC.
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Affiliation(s)
- Kotaro Sugawara
- Department of Gastrointestinal Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Yoshikuni Kawaguchi
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
| | - Yasuyuki Seto
- Department of Gastrointestinal Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Jean-Nicolas Vauthey
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
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11
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Wu F, Hong J, Du N, Wang Y, Chen J, He Y, Chen P. Long-Term Outcomes of Neoadjuvant Chemotherapy in Locally Advanced Gastric Cancer/Esophagogastric Junction Cancer: A Systematic Review and Meta-Analysis. Anticancer Agents Med Chem 2021; 22:143-151. [PMID: 33719964 DOI: 10.2174/1871520621666210315091932] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2020] [Revised: 01/31/2021] [Accepted: 02/01/2021] [Indexed: 11/22/2022]
Abstract
BACKGROUND Neoadjuvant chemotherapy (NAC) has been defined as any preoperative chemotherapy scheme aiming to reduce tumor staging and to control preoperative micrometastasis, which has been extensively used as a treatment for resectable gastric cancer. However, its effect on the long-term survival of patients with locally advanced gastric cancer (AGC) or esophagogastric junction cancer (EGC) remains unknown. OBJECTIVE This study aimed at investigating the long-term efficacy of NAC in locally AGC/EGC. METHODS The following databases were searched for articles published from their inception up to April 2020: PubMed, Web of Science, EBSCO, and Cochrane library. The primary outcomes were overall survival (OS) and progression-free survival (PFS). RESULTS A total of 19 articles were included in this meta-analysis, with a total of 4,446 patients. The results showed that NAC increased the patients' 3-year OS (HR, 0.56; 95%CI, 0.21-0.91; P<0.001), 3-year PFS (HR, 0.76; 95%CI, 0.66-0.87; P<0.001), 5-year OS (HR, 0.71; 95% CI, 0.64-0.78; P<0.001), and 5-year PFS (HR, 0.70; 95% CI, 0.61-0.79; P<0.001) respectively. Besides, subgroup analysis showed that Asian countries have benefited significantly from NAC (HR, 0.65; 95%CI, 0.55-0.74; P<0.001), and other countries have also benefited (HR, 0.79; 95%CI, 0.68-0.89; P<0.001). CONCLUSIONS Compared with adjuvant chemotherapy and surgery alone, NAC can improve the long-term survival outcomes (OS and PFS) of patients with resectable AGC or EGC.
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Affiliation(s)
- Feng Wu
- Department of General Surgery, HwaMei Hospital, University of Chinese Academy of Sciences, Ningbo, Zhejiang. China
| | - Jiaze Hong
- The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang. China
| | - Nannan Du
- The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang. China
| | - Yiran Wang
- The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang. China
| | - Juan Chen
- Basic Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang. China
| | - Yuanfang He
- Basic Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang. China
| | - Ping Chen
- Department of General Surgery, HwaMei Hospital, University of Chinese Academy of Sciences, Ningbo, Zhejiang. China
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12
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Griffin SM, Kamarajah SK, Navidi M, Wahed S, Immanuel A, Hayes N, Phillips AW. Evolution of gastrectomy for cancer over 30-years: Changes in presentation, management, and outcomes. Surgery 2021; 170:2-10. [PMID: 33674126 DOI: 10.1016/j.surg.2021.01.040] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2020] [Revised: 12/07/2020] [Accepted: 01/25/2021] [Indexed: 11/28/2022]
Abstract
BACKGROUND Gastric cancer has seen a considerable change in management, and outcomes for the past 30 years. Historically, the overall prognosis has been regarded as poor. However, the use of multimodal treatment, and integration of enhanced recovery pathways have improved short and long-term outcomes. The aim of this study was to evaluate the changing trends in presentation, management, and outcomes for patients undergoing surgical treatment for gastric cancers over 30 years. METHODS Data from consecutive patients undergoing gastrectomy with curative intent for gastric adenocarcinoma between 1989 and 2018 from a single-center, high-volume unit were reviewed. Presentation method, management strategies and outcomes were reviewed. Patients were grouped into successive 5-year cohorts for comparison and evaluation of changing trends. RESULTS Between 1989 and 2018, 1,162 patients underwent gastrectomy with curative intent for cancer. Median age was 71 years (interquartile range, 63-76 years) and 763 (66%) were male. Patient presentation changed with epigastric discomfort now the most common presentation (67%). An improvement in overall complications from 54% to 35% (P = .006) and mortality from 8% to 1% (P < .001) was seen over the time period and overall survival improved from 28 months to 53 months (P < .001). CONCLUSION Both short-term and long-term outcomes have significantly improved over the 30 years studied. The reasons for this are multifactorial and include the use of perioperative chemotherapy, the introduction of an enhanced recovery pathway, and improved preoperative assessment of patients through a multidisciplinary input.
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Affiliation(s)
- S Michael Griffin
- Northern Oesophagogastric Unit, Royal Victoria Infirmary, Newcastle upon Tyne NHS Foundation Trust, Newcastle-Upon-Tyne, UK. https://twitter.com/smgriffin3
| | - Sivesh K Kamarajah
- Northern Oesophagogastric Unit, Royal Victoria Infirmary, Newcastle upon Tyne NHS Foundation Trust, Newcastle-Upon-Tyne, UK; Institute of Cellular Medicine, Newcastle University, Newcastle-Upon-Tyne, UK. https://twitter.com/sivesh93
| | - Maziar Navidi
- Northern Oesophagogastric Unit, Royal Victoria Infirmary, Newcastle upon Tyne NHS Foundation Trust, Newcastle-Upon-Tyne, UK. https://twitter.com/Maz_surgery
| | - Shajahan Wahed
- Northern Oesophagogastric Unit, Royal Victoria Infirmary, Newcastle upon Tyne NHS Foundation Trust, Newcastle-Upon-Tyne, UK
| | - Arul Immanuel
- Northern Oesophagogastric Unit, Royal Victoria Infirmary, Newcastle upon Tyne NHS Foundation Trust, Newcastle-Upon-Tyne, UK. https://twitter.com/ArulImmanuel
| | - Nick Hayes
- Northern Oesophagogastric Unit, Royal Victoria Infirmary, Newcastle upon Tyne NHS Foundation Trust, Newcastle-Upon-Tyne, UK
| | - Alexander W Phillips
- Northern Oesophagogastric Unit, Royal Victoria Infirmary, Newcastle upon Tyne NHS Foundation Trust, Newcastle-Upon-Tyne, UK; School of Medical Education, Newcastle University, Newcastle upon Tyne.
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13
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Janarthinakani M, Kalaiselvi S, Priyadarshini R, Arun S, Shashidhar K, Krishnakumar R, Manjunath N, Roopa S, Raman SG. Does Neoadjuvant Chemotherapy Increase the Survival in Patients with Locally Advanced Gastric Cancer Patients? – A Real‑World Evidence. Indian J Med Paediatr Oncol 2020. [DOI: 10.4103/ijmpo.ijmpo_188_20] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
Abstract
Background: In locally advanced gastric cancer (LAGC), perioperative chemotherapy has shown to improve the survival to a larger extent compared to surgery alone. In India, the treatment followed for gastric carcinoma widely varies based on the type of health-care provider and treatment access. There is a paucity of data on the role of neoadjuvant chemotherapy on survival among LAGC patients in the Indian context. Aim: The aim of this study was to compare the disease-free survival (DFS) and overall survival (OS) between neoadjuvant and adjuvant chemotherapies among LAGC patients. Subjects and Methods: This was a retrospective cohort study involving clinical record review of LAGC patients enrolled between 2015 and 2017 from four tertiary cancer centers in South India. The date for the following events, namely diagnosis, recurrence, death, and last day of visit, was extracted in a mobile-based open-access tool. The median duration of OS and DFS between the neoadjuvant and adjuvant groups was compared using Kaplan–Meier survival curves. Results: Of the 137 patients, 70 (51%) had received neoadjuvant chemotherapy followed by surgery and 67 (49%) had adjuvant chemotherapy following the surgery. The mean (standard deviation) age of participants was 55.4 (11.4) years. Seventy-eight percent of the patients were diagnosed at Stage 3 or 4. Regional lymph nodes were involved in 83.9%. The median duration of follow-up was 15 months. The OS in the neoadjuvant and adjuvant groups was 18.6 months and 8.3 months, respectively. Nonregional lymph node involvement and adjacent organ involvement had independently increased the risk of death. Conclusion: Among LAGC patients, the neoadjuvant chemotherapy indicated a better median and DFS compared to the adjuvant group. However, these findings were statistically not significant. The current study has contributed an important finding to the existing evidences of clinical practice in an Indian setting. Further large-scale studies are required to validate the promising trend of using neoadjuvant chemotherapy in LAGC.
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Affiliation(s)
| | | | - Rajamani Priyadarshini
- Department of Research, Fenivi Research Solutions Private Limited, Chennai, Tamil Nadu, India
| | - Seshachalam Arun
- Department of Medical Oncology, GVN Cancer Institute, Trichy, Tamil Nadu, India
| | - K Shashidhar
- Vydehi Institute of Medical Sciences and Research Centre, Bengaluru, Karnataka, India
| | - R Krishnakumar
- Meenakshi Mission Hospital and Research Centre, Madurai, Tamil Nadu, India
| | - N Manjunath
- Vydehi Institute of Medical Sciences and Research Centre, Bengaluru, Karnataka, India
| | - Sirigeri Roopa
- Department of Oncology, Columbia Asia, Bengaluru, Karnataka, India
| | - SG Raman
- Department of Medical Oncology, Madras Cancer Care Foundation, Chennai, Tamil Nadu, India
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14
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Zhu Z, Li L, Xu J, Ye W, Zeng J, Chen B, Huang Z. Laparoscopic versus open approach in gastrectomy for advanced gastric cancer: a systematic review. World J Surg Oncol 2020; 18:126. [PMID: 32534587 PMCID: PMC7293787 DOI: 10.1186/s12957-020-01888-7] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2020] [Accepted: 05/19/2020] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Additional studies comparing laparoscopic gastrectomy (LG) versus open gastrectomy (OG) for advanced gastric cancer (AGC) have been published, and it is necessary to update the systematic review of this subject. OBJECTIVE We conducted the meta-analysis to find some proof for the use of LG in AGC and evaluate whether LG is an alternative treatment for AGC. METHOD Randomized controlled trials (RCT) and high-quality retrospective studies (NRCT) compared LG and OG for AGC, which were published in English between January 2010 and May 2019, were search in PubMed, Embase, and Web of Knowledge by three authors independently and thoroughly. Some primary endpoints were compared between the two groups, including intraoperative time, intraoperative blood loss, harvested lymph nodes, first flatus, first oral intake, first out of bed, post-operative hospital stay, postoperative morbidity and mortality, rate of disease recurrence, and 5-year over survival (5-y OS). Besides, considering for this 10-year dramatical surgical material development between 2010 and 2019, we furtherly make the same analysis based on recent studies published between 2016 and 2019. RESULT Thirty-six studies were enrolled in this systematic review and meta-analysis, including 5714 cases in LAG and 6094 cases in OG. LG showed longer intraoperative time, less intraoperative blood loss, and quicker recovery after operations. The number of harvested lymph nodes, hospital mortality, and tumor recurrence were similar. Postoperative morbidity and 5-y OS favored LG. Furthermore, the systemic analysis of recent studies published between 2016 and 2019 revealed similar result. CONCLUSION A positive trend was indicated towards LG. LG can be performed as an alternative to OG for AGC.
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Affiliation(s)
- Zhipeng Zhu
- Department of Gastrointestinal Surgery, Xiamen Cancer Center, The First Affiliated Hospital of Xiamen University, 55 Zhen Hai Road, Si Ming District, Xiamen, 361003, Fujian, People's Republic of China
| | - Lulu Li
- Department of Gastrointestinal Surgery, Xiamen Cancer Center, The First Affiliated Hospital of Xiamen University, 55 Zhen Hai Road, Si Ming District, Xiamen, 361003, Fujian, People's Republic of China
| | - Jiuhua Xu
- Department of Clinical Medicine, Fujian Medical University, Fuzhou, 350004, Fujian, People's Republic of China
| | - Weipeng Ye
- Department of Clinical Medicine, Fujian Medical University, Fuzhou, 350004, Fujian, People's Republic of China
| | - Junjie Zeng
- Department of Gastrointestinal Surgery, Xiamen Cancer Center, The First Affiliated Hospital of Xiamen University, 55 Zhen Hai Road, Si Ming District, Xiamen, 361003, Fujian, People's Republic of China
| | - Borong Chen
- Department of Gastrointestinal Surgery, Xiamen Cancer Center, The First Affiliated Hospital of Xiamen University, 55 Zhen Hai Road, Si Ming District, Xiamen, 361003, Fujian, People's Republic of China
| | - Zhengjie Huang
- Department of Gastrointestinal Surgery, Xiamen Cancer Center, The First Affiliated Hospital of Xiamen University, 55 Zhen Hai Road, Si Ming District, Xiamen, 361003, Fujian, People's Republic of China. .,Department of Clinical Medicine, Fujian Medical University, Fuzhou, 350004, Fujian, People's Republic of China.
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15
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Machlowska J, Baj J, Sitarz M, Maciejewski R, Sitarz R. Gastric Cancer: Epidemiology, Risk Factors, Classification, Genomic Characteristics and Treatment Strategies. Int J Mol Sci 2020; 21:E4012. [PMID: 32512697 PMCID: PMC7312039 DOI: 10.3390/ijms21114012] [Citation(s) in RCA: 774] [Impact Index Per Article: 154.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2020] [Revised: 05/31/2020] [Accepted: 06/01/2020] [Indexed: 02/06/2023] Open
Abstract
Gastric cancer (GC) is one of the most common malignancies worldwide and it is the fourth leading cause of cancer-related death. GC is a multifactorial disease, where both environmental and genetic factors can have an impact on its occurrence and development. The incidence rate of GC rises progressively with age; the median age at diagnosis is 70 years. However, approximately 10% of gastric carcinomas are detected at the age of 45 or younger. Early-onset gastric cancer is a good model to study genetic alterations related to the carcinogenesis process, as young patients are less exposed to environmental carcinogens. Carcinogenesis is a multistage disease process specified by the progressive development of mutations and epigenetic alterations in the expression of various genes, which are responsible for the occurrence of the disease.
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Affiliation(s)
- Julita Machlowska
- Center for Medical Genomics OMICRON, Jagiellonian University Medical College, 31-034 Kraków, Poland;
- Department of Human Anatomy, Medical University of Lublin, 20-090 Lublin, Poland; (J.B.); (R.M.)
| | - Jacek Baj
- Department of Human Anatomy, Medical University of Lublin, 20-090 Lublin, Poland; (J.B.); (R.M.)
| | - Monika Sitarz
- Department of Conservative Dentistry with Endodontics, Medical University of Lublin, 20-090 Lublin, Poland;
| | - Ryszard Maciejewski
- Department of Human Anatomy, Medical University of Lublin, 20-090 Lublin, Poland; (J.B.); (R.M.)
| | - Robert Sitarz
- Department of Human Anatomy, Medical University of Lublin, 20-090 Lublin, Poland; (J.B.); (R.M.)
- Department of Surgery, Center of Oncology of the Lublin Region St. Jana z Dukli, 20-090 Lublin, Poland
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16
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Bauer K, Manzini G, Henne-Bruns D, Buechler P. Perioperative chemotherapy for advanced gastric cancer - results from a tertiary-care hospital in Germany. World J Gastrointest Oncol 2020; 12:559-568. [PMID: 32461787 PMCID: PMC7235186 DOI: 10.4251/wjgo.v12.i5.559] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2019] [Revised: 03/18/2020] [Accepted: 04/09/2020] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Neoadjuvant/perioperative chemotherapy is the recommended treatment for advanced stages of gastric cancer (> T2, N+) before tumour resection in many European guidelines. However, there is no consensus as to whether perioperative chemotherapy is as effective in distal as in proximal tumours, in addition to a relevant uncertainty concerning appropriate treatment modalities for elderly patients.
AIM To investigate the role of perioperative chemotherapy in advanced gastric cancer in patients from a German tertiary clinic with respect to efficacy, localisation, and age.
METHODS We performed a retrospective analysis of 158 patients from our clinic with adenocarcinoma of the stomach or the gastroesophageal junction who underwent resection between 2008 and 2016. The data were evaluated particularly in relation to patient age, tumour site, and perioperative therapy.
RESULTS Administration of perioperative chemotherapy did not lead to a significant survival advantage in our study population. The 5-year survival rates were 40% for patients who received perioperative chemotherapy and 29% for the group without perioperative chemotherapy (P = 0.125). Our patients were on average distinctly older than patients in most of the published randomised controlled trials. Patients elder than 75 years received perioperative chemotherapy far less frequently. Patients with a proximal tumour received perioperative chemotherapy much more often.
CONCLUSION This analysis reconfirms our previous data concerning the effectiveness of perioperative chemotherapy for advanced gastric cancer. There is reasonable doubt that the quality of the existing randomized controlled trials is sufficient to generally justify perioperative chemotherapy in patients with advanced gastric cancer independent of tumour localization or age.
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Affiliation(s)
- Katrin Bauer
- Department for General, Visceral, Thoracic and Paediatric Surgery, Clinic of Kempten, Kempten 87439, Germany
| | - Giulia Manzini
- Department of General and Visceral Surgery, University Hospital of Ulm, Ulm 89081, Germany
| | - Doris Henne-Bruns
- Department of General and Visceral Surgery, University Hospital of Ulm, Ulm 89081, Germany
| | - Peter Buechler
- Department for General, Visceral, Thoracic and Paediatric Surgery, Clinic of Kempten, Kempten 87439, Germany
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17
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Li Z, Gao X, Peng X, May Chen MJ, Li Z, Wei B, Wen X, Wei B, Dong Y, Bu Z, Wu A, Wu Q, Tang L, Li Z, Liu Y, Zhang L, Jia S, Zhang L, Shan F, Zhang J, Wu X, Ji X, Ji K, Wu X, Shi J, Xing X, Wu J, Lv G, Shen L, Ji X, Liang H, Ji J. Multi-omics characterization of molecular features of gastric cancer correlated with response to neoadjuvant chemotherapy. SCIENCE ADVANCES 2020; 6:eaay4211. [PMID: 32133402 PMCID: PMC7043923 DOI: 10.1126/sciadv.aay4211] [Citation(s) in RCA: 62] [Impact Index Per Article: 12.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/17/2019] [Accepted: 12/06/2019] [Indexed: 05/05/2023]
Abstract
Neoadjuvant chemotherapy is a common treatment for patients with gastric cancer. Although its benefits have been demonstrated, neoadjuvant chemotherapy is underutilized in gastric cancer management, because of the lack of biomarkers for patient selection and a limited understanding of resistance mechanisms. Here, we performed whole-genome, whole-exome, and RNA sequencing on 84 clinical samples (including matched pre- and posttreatment tumors) from 35 patients whose responses to neoadjuvant chemotherapy were rigorously defined. We observed increased microsatellite instability and mutation burden in nonresponse tumors. Through comparisons of response versus nonresponse tumors and pre- versus posttreatment samples, we found that C10orf71 mutations were associated with treatment resistance, which was supported by drug response data and potentially through inhibition of cell cycle, and that MYC amplification correlated with treatment sensitivity, whereas MDM2 amplification showed the opposite pattern. Neoadjuvant chemotherapy also reshapes tumor-immune signaling and microenvironment. Our study provides a critical basis for developing precision neoadjuvant regimens.
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Affiliation(s)
- Ziyu Li
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Gastrointestinal Cancer Center, Peking University Cancer Hospital and Institute, Beijing 100142, China
| | - Xiangyu Gao
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Gastrointestinal Cancer Center, Peking University Cancer Hospital and Institute, Beijing 100142, China
| | - Xinxin Peng
- Precision Scientific (Beijing) Ltd., Beijing 100085, China
| | - Mei-Ju May Chen
- Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Zhe Li
- Precision Scientific (Beijing) Ltd., Beijing 100085, China
| | - Bin Wei
- Precision Scientific (Beijing) Ltd., Beijing 100085, China
| | - Xianzi Wen
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), GI Cancer Translation Research Lab, Peking University Cancer Hospital and Institute, Beijing 100142, China
| | - Baoye Wei
- Precision Scientific (Beijing) Ltd., Beijing 100085, China
| | - Yu Dong
- Precision Scientific (Beijing) Ltd., Beijing 100085, China
| | - Zhaode Bu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Gastrointestinal Cancer Center, Peking University Cancer Hospital and Institute, Beijing 100142, China
| | - Aiwen Wu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Gastrointestinal Cancer Center, Peking University Cancer Hospital and Institute, Beijing 100142, China
| | - Qi Wu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Endoscopy Center, Peking University Cancer Hospital and Institute, Beijing 100142, China
| | - Lei Tang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiology, Peking University Cancer Hospital and Institute, Beijing 100142, China
| | - Zhongwu Li
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Pathology, Peking University Cancer Hospital and Institute, Beijing 100142, China
| | - Yiqiang Liu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Pathology, Peking University Cancer Hospital and Institute, Beijing 100142, China
| | - Li Zhang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Pathology, Peking University Cancer Hospital and Institute, Beijing 100142, China
| | - Shuqin Jia
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Center for Molecular Diagnostics, Peking University Cancer Hospital and Institute, Beijing 100142, China
| | - Lianhai Zhang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Gastrointestinal Cancer Center, Peking University Cancer Hospital and Institute, Beijing 100142, China
| | - Fei Shan
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Gastrointestinal Cancer Center, Peking University Cancer Hospital and Institute, Beijing 100142, China
| | - Ji Zhang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Gastrointestinal Cancer Center, Peking University Cancer Hospital and Institute, Beijing 100142, China
| | - Xiaojiang Wu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Gastrointestinal Cancer Center, Peking University Cancer Hospital and Institute, Beijing 100142, China
| | - Xin Ji
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Gastrointestinal Cancer Center, Peking University Cancer Hospital and Institute, Beijing 100142, China
| | - Ke Ji
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Gastrointestinal Cancer Center, Peking University Cancer Hospital and Institute, Beijing 100142, China
| | - Xiaolong Wu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Gastrointestinal Cancer Center, Peking University Cancer Hospital and Institute, Beijing 100142, China
| | - Jinyao Shi
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), GI Cancer Translation Research Lab, Peking University Cancer Hospital and Institute, Beijing 100142, China
| | - Xiaofang Xing
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Center for Molecular Diagnostics, Peking University Cancer Hospital and Institute, Beijing 100142, China
| | - Jianmin Wu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Center for Cancer Bioinformatics, Peking University Cancer Hospital and Institute, Beijing 100142, China
| | - Guoqing Lv
- Department of Gastrointestinal Surgery, Peking University Shenzhen Hospital, Shenzhen 518036, China
| | - Lin Shen
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of GI Oncology, Peking University Cancer Hospital and Institute, Beijing 100142, China
| | - Xuwo Ji
- Precision Scientific (Beijing) Ltd., Beijing 100085, China
| | - Han Liang
- Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
- Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
- Corresponding author. (J.J.); (H.L.)
| | - Jiafu Ji
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Gastrointestinal Cancer Center, Peking University Cancer Hospital and Institute, Beijing 100142, China
- Corresponding author. (J.J.); (H.L.)
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18
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Aytaç E, Aslan F, Çicek B, Erdamar S, Gürses B, Güven K, Falay O, Karahasanoğlu T, Selçukbiricik F, Selek U, Atalar B, Balık E, Tözün N, Rozanes İ, Arıcan A, Hamzaoğlu İ, Baca B, Molinas Mandel N, Saruç M, Göksel S, Demir G, Ağaoğlu F, Yakıcıer C, Özbek U, Özben V, Özyar E, Güner AL, Er Ö, Kaban K, Bölükbaşı Y, Buğra D, Group Tİ. Dealing with the gray zones in the management of gastric cancer: The consensus statement of the İstanbul Group. TURKISH JOURNAL OF GASTROENTEROLOGY 2020; 30:584-598. [PMID: 30541724 DOI: 10.5152/tjg.2018.18737] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
The geographical location and differences in tumor biology significantly change the management of gastric cancer. The prevalence of gastric cancer ranks fifth and sixth among men and women, respectively, in Turkey. The international guidelines from the Eastern and Western countries fail to manage a considerable amount of inconclusive issues in the management of gastric cancer. The uncertainties lead to significant heterogeneities in clinical practice, lack of homogeneous data collection, and subsequently, diverse outcomes. The physicians who are professionally involved in the management of gastric cancer at two institutions in Istanbul, Turkey, organized a consensus meeting to address current problems and plan feasible, logical, measurable, and collective solutions in their clinical practice for this challenging disease. The evidence-based data and current guidelines were reviewed. The gray zones in the management of gastric cancer were determined in the first session of this consensus meeting. The second session was constructed to discuss, vote, and ratify the ultimate decisions. The identification of the T stage, the esophagogastric area, imaging algorithm for proper staging and follow-up, timing and patient selection for neoadjuvant treatment, and management of advanced and metastatic disease have been accepted as the major issues in the management of gastric cancer. The recommendations are presented with the percentage of supporting votes in the results section with related data.
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Affiliation(s)
- Erman Aytaç
- Acıbadem Mehmet Ali Aydınlar University School of Medicine, İstanbul, Turkey
| | - Fatih Aslan
- Koç University School of Medicine, İstanbul, Turkey
| | - Bahattin Çicek
- Acıbadem Mehmet Ali Aydınlar University School of Medicine, İstanbul, Turkey
| | - Sibel Erdamar
- Acıbadem Mehmet Ali Aydınlar University School of Medicine, İstanbul, Turkey
| | - Bengi Gürses
- Koç University School of Medicine, İstanbul, Turkey
| | - Koray Güven
- Acıbadem Mehmet Ali Aydınlar University School of Medicine, İstanbul, Turkey
| | - Okan Falay
- Koç University School of Medicine, İstanbul, Turkey
| | | | | | - Uğur Selek
- Koç University School of Medicine, İstanbul, Turkey
| | - Banu Atalar
- Acıbadem Mehmet Ali Aydınlar University School of Medicine, İstanbul, Turkey
| | - Emre Balık
- Koç University School of Medicine, İstanbul, Turkey
| | - Nurdan Tözün
- Acıbadem Mehmet Ali Aydınlar University School of Medicine, İstanbul, Turkey
| | | | - Ali Arıcan
- Acıbadem Mehmet Ali Aydınlar University School of Medicine, İstanbul, Turkey
| | - İsmail Hamzaoğlu
- Acıbadem Mehmet Ali Aydınlar University School of Medicine, İstanbul, Turkey
| | - Bilgi Baca
- Acıbadem Mehmet Ali Aydınlar University School of Medicine, İstanbul, Turkey
| | | | - Murat Saruç
- Acıbadem Mehmet Ali Aydınlar University School of Medicine, İstanbul, Turkey
| | - Süha Göksel
- Acıbadem Mehmet Ali Aydınlar University School of Medicine, İstanbul, Turkey
| | - Gökhan Demir
- Acıbadem Mehmet Ali Aydınlar University School of Medicine, İstanbul, Turkey
| | - Fulya Ağaoğlu
- Acıbadem Mehmet Ali Aydınlar University School of Medicine, İstanbul, Turkey
| | - Cengiz Yakıcıer
- Acıbadem Mehmet Ali Aydınlar University School of Medicine, İstanbul, Turkey
| | - Uğur Özbek
- Acıbadem Mehmet Ali Aydınlar University School of Medicine, İstanbul, Turkey
| | - Volkan Özben
- Acıbadem Mehmet Ali Aydınlar University School of Medicine, İstanbul, Turkey
| | - Enis Özyar
- Acıbadem Mehmet Ali Aydınlar University School of Medicine, İstanbul, Turkey
| | - Ahmet Levent Güner
- Acıbadem Mehmet Ali Aydınlar University School of Medicine, İstanbul, Turkey
| | - Özlem Er
- Acıbadem Mehmet Ali Aydınlar University School of Medicine, İstanbul, Turkey
| | - Kerim Kaban
- Koç University School of Medicine, İstanbul, Turkey
| | - Yasemin Bölükbaşı
- Acıbadem Mehmet Ali Aydınlar University School of Medicine, İstanbul, Turkey
| | - Dursun Buğra
- Koç University School of Medicine, İstanbul, Turkey
| | - The İstanbul Group
- Acıbadem Mehmet Ali Aydınlar University School of Medicine, İstanbul, Turkey
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Wang XZ, Zeng ZY, Ye X, Sun J, Zhang ZM, Kang WM. Interpretation of the development of neoadjuvant therapy for gastric cancer based on the vicissitudes of the NCCN guidelines. World J Gastrointest Oncol 2020; 12:37-53. [PMID: 31966912 PMCID: PMC6960069 DOI: 10.4251/wjgo.v12.i1.37] [Citation(s) in RCA: 38] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/03/2019] [Revised: 09/09/2019] [Accepted: 09/26/2019] [Indexed: 02/05/2023] Open
Abstract
Gastric cancer is one of the most common digestive system tumors in China, and locally advanced gastric cancer (LAGC) accounts for a high proportion of newly diagnosed cases. Although surgery is the main treatment for gastric cancer, surgical excision alone cannot achieve satisfactory outcomes in LAGC patients. Neoadjuvant therapy (NAT) has gradually become the standard treatment for patients with LAGC, and this treatment can not only achieve tumor downstaging and improve surgical rate and the R0 resection rate, but it also significantly improves the long-term prognosis of patients. Peri/preoperative neoadjuvant chemotherapy and preoperative chemoradiotherapy are both recommended according to a large number of studies, and the regimens have also been evolved in the past decades. Since the NCCN guidelines for gastric cancer are one of the most authoritative evidence-based guidelines worldwide, here, we demonstrate the development course and major breakthroughs of NAT for gastric cancer based on the vicissitudes of the NCCN guidelines from 2007 to 2019, and also discuss the future of NAT.
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Affiliation(s)
- Xian-Ze Wang
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100730, China
| | - Zi-Yang Zeng
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100730, China
| | - Xin Ye
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100730, China
| | - Juan Sun
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100730, China
| | - Zi-Mu Zhang
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100730, China
| | - Wei-Ming Kang
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100730, China
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20
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Disease-free survival as a surrogate for overall survival in neoadjuvant trials of gastroesophageal adenocarcinoma: Pooled analysis of individual patient data from randomised controlled trials. Eur J Cancer 2019; 123:101-111. [DOI: 10.1016/j.ejca.2019.10.001] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2019] [Revised: 09/25/2019] [Accepted: 10/01/2019] [Indexed: 01/05/2023]
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21
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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: 84] [Impact Index Per Article: 14.0] [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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22
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van den Ende T, Abe Nijenhuis FA, van den Boorn HG, Ter Veer E, Hulshof MCCM, Gisbertz SS, van Oijen MGH, van Laarhoven HWM. COMplot, A Graphical Presentation of Complication Profiles and Adverse Effects for the Curative Treatment of Gastric Cancer: A Systematic Review and Meta-Analysis. Front Oncol 2019; 9:684. [PMID: 31403035 PMCID: PMC6677173 DOI: 10.3389/fonc.2019.00684] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2019] [Accepted: 07/11/2019] [Indexed: 12/24/2022] Open
Abstract
Background: For the curative treatment of gastric cancer, several neoadjuvant, and adjuvant treatment-regimens are available which have shown to improve overall survival. No overview is available regarding toxicity and surgery related outcomes. Our aim was to construct a novel graphical method concerning adverse events (AEs) associated with multimodality treatment and perform a meta-analysis to compare different clinically relevant cytotoxic regimens with each other. Methods: The PubMed, EMBASE, CENTRAL, and ASCO/ESMO databases were searched up to May 2019 for randomized controlled trials investigating curative treatment regimens for gastric cancer. To construct single and bidirectional bar-charts (COMplots), grade 1–2 and grade 3–5 AEs were extracted per cytotoxic regimen. For surgery-related outcomes a pre-specified set of complications was used. Thereafter, treatment-arms comparing the same regimens were combined in a single-arm random-effects meta-analysis and pooled-proportions were calculated with 95% confidence-intervals. Comparative meta-analyses were performed based on clinical relevance and compound similarity. Results: In total 16 RCTs (n = 4,526 patients) were included investigating pre-operative-therapy and 39 RCTs investigating adjuvant-therapy (n = 13,732 patients). Pre-operative COMplots were created for among others; 5-fluorouracil/leucovorin-oxaliplatin-docetaxel (FLOT), epirubicin-cisplatin-fluoropyrimidine (ECF), cisplatin-fluoropyrimidine (CF), and oxaliplatin-fluoropyrimidine (FOx). Pre-operative FLOT showed a minor increase in grade 1–2 and grade 3–4 AEs compared to pre-operative ECF, CF, and FOx. A pooled analysis of patients who had received pre-operative therapy compared to patients who underwent direct surgery did not reveal any significant difference in surgery related morbidity/mortality. When we compared three commonly used adjuvant regimens; S-1 had the lowest amount of grade 3–4 AEs compared to capecitabine with oxaliplatin (CAPOX) and 5-FU with radiotherapy (5-FU+RT). Conclusion: COMplot provides a novel tool to visualize and compare treatment related AEs for gastric cancer. Based on our comparisons, pre-operative FLOT had a manageable toxicity profile compared to other pre-operative doublet or triplet regimens. We found no evidence indicating surgical outcomes might be hampered by pre-operative therapy. Adjuvant S-1 had a more favorable toxicity profile compared to CAPOX and 5-FU+RT.
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Affiliation(s)
- Tom van den Ende
- Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam University Medical Centers (UMC), University of Amsterdam, Amsterdam, Netherlands
| | - Frank A Abe Nijenhuis
- Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam University Medical Centers (UMC), University of Amsterdam, Amsterdam, Netherlands
| | - Héctor G van den Boorn
- Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam University Medical Centers (UMC), University of Amsterdam, Amsterdam, Netherlands
| | - Emil Ter Veer
- Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam University Medical Centers (UMC), University of Amsterdam, Amsterdam, Netherlands
| | - Maarten C C M Hulshof
- Department of Radiotherapy, Cancer Center Amsterdam, Amsterdam University Medical Centers (UMC), University of Amsterdam, Amsterdam, Netherlands
| | - Suzanne S Gisbertz
- Department of Surgery, Cancer Center Amsterdam, Amsterdam University Medical Centers (UMC), University of Amsterdam, Amsterdam, Netherlands
| | - Martijn G H van Oijen
- Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam University Medical Centers (UMC), University of Amsterdam, Amsterdam, Netherlands
| | - Hanneke W M van Laarhoven
- Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam University Medical Centers (UMC), University of Amsterdam, Amsterdam, Netherlands
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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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24
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Du R, Hu P, Liu Q, Zhang J. Conversion Surgery for Unresectable Advanced Gastric Cancer: A Systematic Review and Meta-Analysis. Cancer Invest 2019; 37:16-28. [PMID: 30632817 DOI: 10.1080/07357907.2018.1551898] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
For patients with unresectable advanced gastric cancer, induction chemotherapy could down-stage primary tumors, resulting in conversion surgery becoming possible. However, the feasibility and therapeutic benefit of conversion surgery remains controversial. Therefore, this meta-analysis aimed to systematically review and investigate the efficacy of conversion surgery followed by chemotherapy for unresectable AGC.
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Affiliation(s)
- Rui Du
- a Department of Oncology , Weifang Medical College , Weifang , China
| | - Pingping Hu
- c Department of Radiation Oncology , Qianfoshan Hospital Affiliated to Shandong University , Jinan , China
| | - Qiqi Liu
- b Department of Oncology , Shandong University School of Medicine , Jinan , China
| | - Jiandong Zhang
- c Department of Radiation Oncology , Qianfoshan Hospital Affiliated to Shandong University , Jinan , China
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25
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van den Ende T, Ter Veer E, Machiels M, Mali RMA, Abe Nijenhuis FA, de Waal L, Laarman M, Gisbertz SS, Hulshof MCCM, van Oijen MGH, van Laarhoven HWM. The Efficacy and Safety of (Neo)Adjuvant Therapy for Gastric Cancer: A Network Meta-analysis. Cancers (Basel) 2019; 11:E80. [PMID: 30641964 PMCID: PMC6356558 DOI: 10.3390/cancers11010080] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2018] [Revised: 01/05/2019] [Accepted: 01/05/2019] [Indexed: 12/21/2022] Open
Abstract
Background: Alternatives in treatment-strategies exist for resectable gastric cancer. Our aims were: (1) to assess the benefit of perioperative, neoadjuvant and adjuvant treatment-strategies and (2) to determine the optimal adjuvant regimen for gastric cancer treated with curative intent. Methods: PubMed, EMBASE, CENTRAL, and ASCO/ESMO conferences were searched up to August 2017 for randomized-controlled-trials on the curative treatment of resectable gastric cancer. We performed two network-meta-analyses (NMA). NMA-1 compared perioperative, neoadjuvant and adjuvant strategies only if there was a direct comparison. NMA-2 compared different adjuvant chemo(radio)therapy regimens, after curative resection. Overall-survival (OS) and disease-free-survival (DFS) were analyzed using random-effects NMA on the hazard ratio (HR)-scale and calculated as combined HRs and 95% credible intervals (95% CrIs). Results: NMA-1 consisted of 9 direct comparisons between strategies for OS (14 studies, n = 4187 patients). NMA-2 consisted of 16 direct comparisons between adjuvant chemotherapy/chemoradiotherapy regimens for OS (37 studies, n = 10,761) and 14 for DFS (30 studies, n = 9714 patients). Compared to taxane-based-perioperative-chemotherapy, surgery-alone (HR = 0.58, 95% CrI = 0.38⁻0.91) and perioperative-chemotherapy regimens without a taxane (HR = 0.79, 95% CrI = 0.58⁻1.15) were inferior in OS. After curative-resection, the doublet oxaliplatin-fluoropyrimidine (for one-year) was the most efficacious adjuvant regimen in OS (HR = 0.47, 95% CrI = 0.28⁻0.80). Conclusions: For resectable gastric cancer, (1) taxane-based perioperative-chemotherapy was the most promising treatment strategy; and (2) adjuvant oxaliplatin-fluoropyrimidine was the most promising regimen after curative resection. More research is warranted to confirm or reproach these findings.
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Affiliation(s)
- Tom van den Ende
- Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam University Medical Centers (UMC) location AMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.
| | - Emil Ter Veer
- Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam University Medical Centers (UMC) location AMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.
| | - Mélanie Machiels
- Department of Radiotherapy, Cancer Center Amsterdam, Amsterdam University Medical Centers (UMC) location AMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.
| | - Rosa M A Mali
- Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam University Medical Centers (UMC) location AMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.
| | - Frank A Abe Nijenhuis
- Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam University Medical Centers (UMC) location AMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.
| | - Laura de Waal
- Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam University Medical Centers (UMC) location AMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.
| | - Marety Laarman
- Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam University Medical Centers (UMC) location AMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.
| | - Suzanne S Gisbertz
- Department of Surgery, Cancer Center Amsterdam, Amsterdam University Medical Centers (UMC) location AMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.
| | - Maarten C C M Hulshof
- Department of Radiotherapy, Cancer Center Amsterdam, Amsterdam University Medical Centers (UMC) location AMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.
| | - Martijn G H van Oijen
- Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam University Medical Centers (UMC) location AMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.
| | - Hanneke W M van Laarhoven
- Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam University Medical Centers (UMC) location AMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.
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26
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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] [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. (www.actabiomedica.it)
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Affiliation(s)
- Federico Coccolini
- Emergency, General and Trauma Surgery dept., Bufalini hospital, Cesena, Italy.
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27
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Comprehensive Analysis of the Neutrophil-to-Lymphocyte Ratio for Preoperative Prognostic Prediction Nomogram in Gastric Cancer. World J Surg 2018; 42:2530-2541. [PMID: 29392430 DOI: 10.1007/s00268-018-4510-4] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
BACKGROUND The role of neutrophil-to-lymphocyte ratio (NLR) and preoperative prediction model in gastric cancer is controversial, while postoperative prognostic models are available. This study investigated NLR as a preoperative prognostic indicator in gastric cancer. METHODS We reviewed patients with primary gastric cancer who underwent surgery during 2007-2010. Preoperative clinicopathologic factors were analyzed with their interaction and used to develop a prognosis prediction nomogram. That preoperative prediction nomogram was compared to a nomogram using pTNM or a historical postoperative prediction nomogram. The contribution of NLR to a preoperative nomogram was evaluated with integrated discrimination improvement (IDI). RESULTS Using 2539 records, multivariable analysis revealed that NLR was one of the independent prognostic factors and had a significant interaction with only age among other preoperative factors (especially significant in patients < 50 years old). NLR was constantly significant between 1.1 and 3.1 without any distinctive cutoff value. Preoperative prediction nomogram using NLR showed a Harrell's C-index of 0.79 and an R2 of 25.2%, which was comparable to the C-index of 0.78 and 0.82 and R2 of 26.6 and 25.8% from nomogram using pTNM and a historical postoperative prediction nomogram, respectively. IDI of NLR to nomogram in the overall population was 0.65%, and that of patients < 50 years old was 2.72%. CONCLUSIONS NLR is an independent prognostic factor for gastric cancer, especially in patients < 50 years old. A preoperative prediction nomogram using NLR can predict prognosis of gastric cancer as effectively as pTNM and a historical postoperative prediction nomogram.
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28
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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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Cai Z, Yin Y, Shen C, Wang J, Yin X, Chen Z, Zhou Y, Zhang B. Comparative effectiveness of preoperative, postoperative and perioperative treatments for resectable gastric cancer: A network meta-analysis of the literature from the past 20 years. Surg Oncol 2018; 27:563-574. [PMID: 30217320 DOI: 10.1016/j.suronc.2018.07.011] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2018] [Revised: 06/14/2018] [Accepted: 07/15/2018] [Indexed: 02/08/2023]
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Cai Z, Yin Y, Zhao Z, Xin C, Cai Z, Yin Y, Shen C, Yin X, Wang J, Chen Z, Zhou Y, Zhang B. Comparative Effectiveness of Neoadjuvant Treatments for Resectable Gastroesophageal Cancer: A Network Meta-Analysis. Front Pharmacol 2018; 9:872. [PMID: 30127746 PMCID: PMC6087755 DOI: 10.3389/fphar.2018.00872] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2018] [Accepted: 07/19/2018] [Indexed: 02/05/2023] Open
Abstract
Background: Several neoadjuvant treatments are available for patients with resectable gastroesophageal cancer. We did a Bayesian network meta-analysis (NMA) to compare available treatments, summarizing the direct and indirect evidence. Method: We searched relevant databases for randomized controlled trials of neoadjuvant treatments for resectable gastroesophageal cancer which compared two or more of the following treatments: surgery alone, perioperative docetaxel, oxaliplatin, leucovorin, and fluorouracil (FLOT), and neoadjuvant treatments listed in National Comprehensive Cancer Network guideline. Then we performed a NMA to summarize the direct and indirect evidence to estimate the relative efficacy for outcomes including overall survival (OS), progression-free survival and R0 resection rate. We calculated odds ratio (OR) and hazard ratio (HR) with 95% credible intervals (CrI) for dichotomous data and time-to-event data, respectively. We also calculated the surface under the cumulative ranking curve (SUCRA) value of each intervention to obtain a hierarchy of treatments. Result: Eight eligible trials (2434 patients) were included in our NMA. The treatment with the highest probability of benefit on OS as compared with surgery alone was perioperative FLOT [HR = 0.58 with 95% CrI: (0.43, 0.78), SUCRA = 93%], followed by preoperative radiotherapy, paclitaxel, and carboplatin (RT/PC) [HR = 0.68 with 95% CrI: (0.53, 0.87), SUCRA = 72%], perioperative cisplatin with fluorouracil (CF) [HR = 0.70 with 95% CrI: (0.51, 0.95), SUCRA = 68%], and perioperative epirubicin, cisplatin, and fluorouracil or capecitabine (ECF/ECX) [HR = 0.75 with 95% CrI: (0.60, 0.94), SUCRA = 56%]. Conclusion: Compared with surgery alone, perioperative CF, perioperative ECF/ECX, perioperative FLOT, and preoperative RT/PC significantly improved survival. Perioperative FLOT is likely to be the most effective neoadjuvant treatment for the disease. Further clinical studies are needed and justified.
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Affiliation(s)
- Zhaolun Cai
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Yiqiong Yin
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Zhou Zhao
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Chunyu Xin
- West China College of Public Health, Sichuan University, Chengdu, China
| | - Zhaohui Cai
- Department of Infectious Disease, Jiangsu Province Hospital of Traditional Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
- The First College of Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Yuan Yin
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Chaoyong Shen
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Xiaonan Yin
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Jian Wang
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Zhixin Chen
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Ye Zhou
- Department of Gastric Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Bo Zhang
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China
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Neoadjuvant chemotherapy in advanced gastric and esophago-gastric cancer. Meta-analysis of randomized trials. Int J Surg 2018; 51:120-127. [PMID: 29413875 DOI: 10.1016/j.ijsu.2018.01.008] [Citation(s) in RCA: 99] [Impact Index Per Article: 14.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2017] [Accepted: 01/07/2018] [Indexed: 02/07/2023]
Abstract
INTRODUCTION Even in after curative surgery and adequate linfoadenectomy the survival of advanced gastric cancer (AGC) remains poor. At present some data have been published on the effects of NACT and perioperative chemotherapy on AGC and Esophago-gastric cancer (EGC) but not definitive ones. The present meta-analysis aims to evaluate the effects of neoadjuvant chemotherapy (NACT) on the AGC and EGC. MATERIAL AND METHODS A systematic review with meta-analysis of randomized controlled trials (RCTs) of NACT + surgery vs. Surgery in patients with AGC and EGC was performed. RESULTS 15 RCTs have been included (2001 patients: 977 into NACT + surgery arm and 1024 into control arm). NACT + Surgery reduces the overall mortality at 1, 3 and 5-year in cumulative analysis (RR = 0.78; 0.81; 0.88 respectively), at 1, 2, 3 and 5-years in EGC (RR = 0.79; 0.83; 0.84; 0.91 respectively) and at 3 and 5-years in AGC (RR = 0.74; 0.82 respectively). Morbidity and perioperative mortality rate are not influenced by NACT. Recurrence rate is reduced by NACT + surgery in EGC (RR = 0.80). CONCLUSIONS NACT reduces the mortality in gastric and esophago-gastric cancer. Morbidity and perioperative mortality are not influenced by NACT. The overall recurrence rate is reduced by NACT in esophago-gastric cancer.
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Miao ZF, Liu XY, Wang ZN, Zhao TT, Xu YY, Song YX, Huang JY, Xu H, Xu HM. Effect of neoadjuvant chemotherapy in patients with gastric cancer: a PRISMA-compliant systematic review and meta-analysis. BMC Cancer 2018; 18:118. [PMID: 29385994 PMCID: PMC5793339 DOI: 10.1186/s12885-018-4027-0] [Citation(s) in RCA: 59] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2016] [Accepted: 01/23/2018] [Indexed: 01/19/2023] Open
Abstract
BACKGROUND Neoadjuvant chemotherapy (NAC) is extensively used in the treatment of patients with gastric cancer (GC), particularly in high risk, advanced gastric cancer. Previous trials testing the efficacy of NAC have reported inconsistent results. METHODS This study compares the combined use of NAC and surgery with surgery alone for GC by using a meta-analytic approach. We performed an electronic search of PubMed, EmBase, and the Cochrane Library to identify randomized controlled trials (RCTs) on NAC published before Oct 2015. The primary outcome of the studies was data on survival rates for patients with GC. The summary results were pooled using the random-effects model. We included 12 prospective RCTs reporting data on 1538 GC patients. RESULTS Patients who received NAC were associated with significant improvement of OS (P = 0.001) and PFS (P < 0.001). Furthermore, NAC therapy significantly increased the incidence of 1-year survival rate (SR) (P = 0.020), 3-year SR (P = 0.011), and 4-year SR (P = 0.001). Similarly, NAC therapy was associated with a lower incidence of 1-year (P < 0.001), 2-year (P < 0.001), 3-year (P < 0.001), 4-year (P = 0.001), and 5-year recurrence rate (P = 0.002). Conversely, patients who received NAC also experienced a significantly increased risk of lymphocytopenia (P = 0.003), and hemoglobinopathy (P = 0.021). CONCLUSIONS The findings of this study suggested that NAC is associated with significant improvement in the outcomes of survival and disease progression for GC patients while also increasing some toxicity.
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Affiliation(s)
- Zhi-Feng Miao
- Department of Surgical Oncology, First Hospital of China Medical University, Shenyang, 110001 China
| | - Xing-Yu Liu
- Department of Surgical Oncology, First Hospital of China Medical University, Shenyang, 110001 China
| | - Zhen-Ning Wang
- Department of Surgical Oncology, First Hospital of China Medical University, Shenyang, 110001 China
| | - Ting-Ting Zhao
- Department of Breast Surgery, First Hospital of China Medical University, Shenyang, China
| | - Ying-Ying Xu
- Department of Breast Surgery, First Hospital of China Medical University, Shenyang, China
| | - Yong-Xi Song
- Department of Surgical Oncology, First Hospital of China Medical University, Shenyang, 110001 China
| | - Jin-Yu Huang
- Department of Surgical Oncology, First Hospital of China Medical University, Shenyang, 110001 China
| | - Hao Xu
- Department of Surgical Oncology, First Hospital of China Medical University, Shenyang, 110001 China
| | - Hui-Mian Xu
- Department of Surgical Oncology, First Hospital of China Medical University, Shenyang, 110001 China
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Reddavid R, Sofia S, Chiaro P, Colli F, Trapani R, Esposito L, Solej M, Degiuli M. Neoadjuvant chemotherapy for gastric cancer. Is it a must or a fake? World J Gastroenterol 2018; 24:274-289. [PMID: 29375213 PMCID: PMC5768946 DOI: 10.3748/wjg.v24.i2.274] [Citation(s) in RCA: 76] [Impact Index Per Article: 10.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2017] [Revised: 12/13/2017] [Accepted: 12/20/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate the neoadjuvant chemotherapy (NAC) effect on the survival of patients with proper stomach cancer submitted to D2 gastrectomy.
METHODS We proceeded to a review of the literature with PubMed, Embase, ASCO and ESMO meeting abstracts as well as computerized use of the Cochrane Library for randomized controlled trials (RCTs) comparing NAC followed by surgery (NAC + S) with surgery alone (SA) for gastric cancer (GC). The primary outcome was the overall survival rate. Secondary outcomes were the site of the primary tumor, extension of node dissection according to Japanese Gastric Cancer Association (JGCA) performed in both arms, disease-specific (DSS) and disease-free survival (DFS) rates, clinical and pathological response rates and resectability rates after perioperative treatment.
RESULTS We identified a total of 16 randomized controlled trials comparing NAC + S (n = 1089) with SA (n = 973) published in the period from January 1993 - March 2017. Only 6 of these studies were well-designed, structured trials in which the type of lymph node (LN) dissection performed or at least suggested in the trial protocol was reported. Two out of three of the RCTs with D2 lymphadenectomy performed in almost all cases failed to show survival benefit in the NAC arm. In the third RCT, the survival rate was not even reported, and the primary end points were the clinical outcomes of surgery with and without NAC. In the remaining three RCTs, D2 lymph node dissection was performed in less than 50% of cases or only recommended in the “Study Treatment” protocol without any description in the results of the procedure really perfomed. In one of the two studies, the benefit of NAC was evident only for esophagogastric junction (EGJ) cancers. In the second study, there was no overall survival benefit of NAC. In the last trial, which documented a survival benefit for the NAC arm, the chemotherapy effect was mostly evident for EGJ cancer, and more than one-fourth of patients did not have a proper stomach cancer. Additionally, several patients did not receive resectional surgery. Furthermore, the survival rates of international reference centers that provide adequate surgery for homogeneous stomach cancer patients’ populations are even higher than the survival rates reported after NAC followed by incomplete surgery.
CONCLUSION NAC for GC has been rapidly introduced in international western guidelines without an evidence-based medicine-related demonstration of its efficacy for a homogeneous population of patients with only stomach tumors submitted to adequate surgery following JGCA guidelines with extended (D2) LN dissection. Additional larger sample-size multicentre RCTs comparing the newer NAC regimens including molecular therapies followed by adequate extended surgery with surgery alone are needed.
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Affiliation(s)
- Rossella Reddavid
- Surgical Oncology and Digestive Surgery, Department of Oncology, University of Turin, San Luigi University Hospital, Orbassano, Turin 10049, Italy
| | - Silvia Sofia
- Surgical Oncology and Digestive Surgery, Department of Oncology, University of Turin, San Luigi University Hospital, Orbassano, Turin 10049, Italy
| | - Paolo Chiaro
- Department of Surgical Sciences, Digestive and Oncological Surgery, University of Turin, Molinette Hospital, Turin 10126, Italy
| | - Fabio Colli
- Department of Surgical Sciences, Digestive and Oncological Surgery, University of Turin, Molinette Hospital, Turin 10126, Italy
| | - Renza Trapani
- Surgical Oncology and Digestive Surgery, Department of Oncology, University of Turin, San Luigi University Hospital, Orbassano, Turin 10049, Italy
| | - Laura Esposito
- Surgical Oncology and Digestive Surgery, Department of Oncology, University of Turin, San Luigi University Hospital, Orbassano, Turin 10049, Italy
| | - Mario Solej
- Surgical Oncology and Digestive Surgery, Department of Oncology, University of Turin, San Luigi University Hospital, Orbassano, Turin 10049, Italy
| | - Maurizio Degiuli
- Surgical Oncology and Digestive Surgery, Department of Oncology, University of Turin, San Luigi University Hospital, Orbassano, Turin 10049, Italy
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Bringeland EA, Wasmuth HH, Grønbech JE. Perioperative chemotherapy for resectable gastric cancer - what is the evidence? Scand J Gastroenterol 2017; 52:647-653. [PMID: 28276825 DOI: 10.1080/00365521.2017.1293727] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
The UK MAGIC trial published in 2006 was the first RCT to identify improved long-term survival rates using preoperative chemotherapy for resectable gastric or gastroesophageal cancer. Overnight, the treatment regimen impacted European guidelines. However, the majority of patients underwent limited lymph node dissection, and analyses of the rates of curative resection, downsizing and downstaging were not by intention to treat, rightfully raising concerns about their validity. For the subset of true gastric cancers, meta-analyses may even question the claims of improved long-term survival rates by present-day regimens. A rhetorical question can be posed as to whether downstaging and improved survival rates by preoperative (radio)-chemotherapy for cancers of the distal esophagus or gastric cardia, has confounded our conclusions on the (lack of) effect of present-day regimens of perioperative chemotherapy for true gastric cancers, let alone in a situation with proper lymph node dissection. At present, a plea can be made to move one step back and revert to an RCT with a surgery alone arm. Inclusion criteria and analyses of future RCTs must stratify on tumor location and the Lauren type and embrace the newly developed scheme of sub-classification of gastric cancers based on extensive molecular profiling as reported in the seminal Cancer Genome Atlas Study.
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Affiliation(s)
- Erling A Bringeland
- a Department of Gastrointestinal Surgery , St. Olavs Hospital, Trondheim University Hospital , Trondheim , Norway
| | - Hans H Wasmuth
- a Department of Gastrointestinal Surgery , St. Olavs Hospital, Trondheim University Hospital , Trondheim , Norway
| | - Jon E Grønbech
- a Department of Gastrointestinal Surgery , St. Olavs Hospital, Trondheim University Hospital , Trondheim , Norway.,b Department of Cancer Research and Molecular Medicine , Norwegian University of Science and Technology , Trondheim , Norway
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Abstract
OPINION STATEMENT Two cycles of neoadjuvant cisplatin and fluoropyrimidine (CF) and 6 cycles of perioperative CF with or without epirubicin are an evidence-based approach in operable esophageal and esophagogastric junctional adenocarcinomas. Three-drug regimens with anthracycline or taxane are associated with significantly higher tumor regression rates, with an expected increase in toxicity. In order to achieve an R0 resection and consequently a survival advantage, in selected patients having a risk of a threatened margin or incomplete resection, chemotherapy might be continued beyond 2 cycles if a response has been demonstrated. In metastatic setting, multidrug combination regimens have demonstrated a significant survival benefit when compared to single-agent regimes. A three-drug regimen should be considered for fit patients and/or when a response is required for symptom control. The expected increase in toxicity needs to be carefully considered and discussed with patients. The choice to use a taxane in first-line setting may limit the options of second-line treatment to irinotecan-containing regimens and also precludes the use of anthracyclines in the first line. For this reason, we prefer to reserve taxane-based therapy for the second-line setting.
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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: 4] [Impact Index Per Article: 0.5] [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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Ronellenfitsch U, Schwarzbach M, Hofheinz R, Kienle P, Nowak K, Kieser M, Slanger TE, Burmeister B, Kelsen D, Niedzwiecki D, Schuhmacher C, Urba S, van de Velde C, Walsh TN, Ychou M, Jensen K. Predictors of overall and recurrence-free survival after neoadjuvant chemotherapy for gastroesophageal adenocarcinoma: Pooled analysis of individual patient data (IPD) from randomized controlled trials (RCTs). Eur J Surg Oncol 2017; 43:1550-1558. [PMID: 28551325 DOI: 10.1016/j.ejso.2017.05.005] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2017] [Accepted: 05/02/2017] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Neoadjuvant chemotherapy improves prognosis of patients with locally advanced gastroesophageal adenocarcinoma. The aim of this study was to identify predictors for postoperative survival following neoadjuvant therapy. These could be useful in deciding about postoperative continuation of chemotherapy. METHODS This meta-analysis used IPD from RCTs comparing neoadjuvant chemotherapy with surgery alone for gastroesophageal adenocarcinoma. Trials providing IPD on age, sex, performance status, pT/N stage, resection status, overall and recurrence-free survival were included. Survival was calculated in the entire study population and subgroups stratified by supposed predictors and compared using the log-rank test. Multivariable Cox models were used to identify independent survival predictors. RESULTS Four RCTs providing IPD from 553 patients fulfilled the inclusion criteria. (y)pT and (y)pN stage and resection status strongly predicted postoperative survival both after neoadjuvant therapy and surgery alone. Patients with R1 resection after neoadjuvant therapy survived longer than those with R1 resection after surgery alone. Patients with stage pN0 after surgery alone had better prognosis than those with ypN0 after neoadjuvant therapy. Patients with stage ypT3/4 after neoadjuvant therapy survived longer than those with stage pT3/4 after surgery alone. Multivariable regression identified resection status and (y)pN stage as predictors of survival in both groups. (y)pT stage predicted survival only after surgery alone. CONCLUSION After neoadjuvant therapy for gastroesophageal adenocarcinoma, survival is determined by the same factors as after surgery alone. However, ypT stage is not an independent predictor. These results can facilitate the decision about postoperative continuation of chemotherapy in pretreated patients.
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Affiliation(s)
- U Ronellenfitsch
- Department of Surgery, University Medical Center Mannheim, Medical Faculty Mannheim of the University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany.
| | - M Schwarzbach
- Department of General, Visceral, Vascular, and Thoracic Surgery, Klinikum Frankfurt Höchst, Gotenstraße 6-8, 65929 Frankfurt am Main, Germany.
| | - R Hofheinz
- Day Treatment Center (TTZ), Interdisciplinary Tumor Center Mannheim (ITM) & 3rd Department of Medicine, University Medical Centre Mannheim, Medical Faculty Mannheim of the University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany.
| | - P Kienle
- Department of Surgery, University Medical Center Mannheim, Medical Faculty Mannheim of the University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany.
| | - K Nowak
- Department of Surgery, University Medical Center Mannheim, Medical Faculty Mannheim of the University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany.
| | - M Kieser
- Institute of Medical Biometry and Informatics, University of Heidelberg, Im Neuenheimer Feld 130, 69120 Heidelberg, Germany.
| | - T E Slanger
- Department of Surgery, University Medical Center Mannheim, Medical Faculty Mannheim of the University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany.
| | - B Burmeister
- University of Queensland, Princess Alexandra Hospital, Brisbane, QLD 4102, Australia.
| | - D Kelsen
- Memorial Sloan-Kettering Cancer Center and Weill Cornell Medical College, New York, NY 10021, USA.
| | - D Niedzwiecki
- The Alliance for Clinical Trials in Oncology (Alliance) Statistics and Data Center, Duke University Medical Center, Hock Plaza, 2424 Erwin Rd, Room 8040, Durham, NC 27705, USA.
| | - C Schuhmacher
- Department of Surgery, Klinikum rechts der Isar, Technical University Munich, Ismaninger Str. 22, 81675 Munich, Germany.
| | - S Urba
- Division of Hematology/Oncology, University of Michigan Medical Center, 1500 E Medical Center Drive, C347, SPC 5848, Ann Arbor, MI 48109, USA.
| | - C van de Velde
- Department of Surgery, Leiden University Medical Center, K6-R, P.O. Box 9600, 2300 RC Leiden, The Netherlands.
| | - T N Walsh
- Department of Surgery, Connolly Hospital, Blanchardstown, Dublin 15, Ireland.
| | - M Ychou
- Centre Régional de Lutte Contre le Cancer, Val d'Aurelle, Montpellier Cedex 05, France.
| | - K Jensen
- Institute of Medical Biometry and Informatics, University of Heidelberg, Im Neuenheimer Feld 130, 69120 Heidelberg, Germany.
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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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Morita S, Fukagawa T, Fujiwara H, Katai H. Questionnaire survey regarding the current status of super-extended lymph node dissection in Japan. World J Gastrointest Oncol 2016; 8:707-714. [PMID: 27672429 PMCID: PMC5027026 DOI: 10.4251/wjgo.v8.i9.707] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2016] [Revised: 06/19/2016] [Accepted: 07/13/2016] [Indexed: 02/05/2023] Open
Abstract
AIM To verify the current status of super-extended lymph node dissection for advanced gastric cancer according to a questionnaire survey.
METHODS One-hundred and five institutions responded to the questionnaire. The survey included the following items: Number of experiences, whether performed prophylactically and/or therapeutically, whether preoperative chemotherapy was provided, number of preoperative chemotherapy rounds, and therapeutic options after chemotherapy.
RESULTS Eighty-seven of the 105 institutions (83%) had performed D3 gastrectomy in the past or continued to perform D3 gastrectomy at present. However, D3 gastrectomy was rarely performed prophylactically in clinical practice. Seventy-eight institutions (74%) indicated that preoperative chemotherapy with curative intent was required for patients suspected of having para-aortic node (PAN) metastases. After chemotherapy, a D3 gastrectomy was scheduled for patients with a complete or partial response, stable disease, and progressive disease at 36 (46%), 28 (36%), and 13 (17%) of the institutions, respectively.
CONCLUSION For patients with apparent PAN metastasis, a D3 gastrectomy is typically planned if a few courses of preoperative chemotherapy yield at least a stable disease condition.
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40
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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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den Dulk M, Verheij M, Cats A, Jansen EPM, Hartgrink HH, Van de Velde CJH. The Essentials of Locoregional Control in the Treatment of Gastric Cancer. Scand J Surg 2016; 95:236-42. [PMID: 17249271 DOI: 10.1177/145749690609500405] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Abstract
Gastric cancer is the fourth most frequent cancer in the world. For curative treatment and local control of gastric cancer, surgery is essential. The extent of the lymph node dissection is still under debate. Only one available trial showed significantly increased overall survival, whereas in all other randomised trials no significant difference could be found. As surgery alone often is not sufficient in the curative treatment in gastric cancer, different (neo)adjuvant treatment strategies have extensively been studied. The recently published MAGIC trial showed downstaging, downsizing and an improved overall survival for patients treated with perioperative chemotherapy, compared to surgery alone (difference 13%, p = 0.009). The INT 0116 trial on the other hand, demonstrated the benefit of postoperative chemoradiotherapy compared to surgery alone for patients with a curative resection of gastric cancer. However, the quality of resections in this trial was poor, illustrating the importance of standardisation by quality control. This could be done by the Maruyama index, which quantifies the likelihood of unresected disease. In the Netherlands, the CRITICS trial has recently been launched, which will be a quality controlled trial comparing postoperative chemoradiotherapy and chemotherapy on survival and/or locoregional control in patients who receive neoadjuvant chemotherapy followed by a D1+ gastric resection.
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Affiliation(s)
- M den Dulk
- Leiden University Medical Center, Department of Surgery, Leiden, The Netherlands
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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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Wu AW, Yuan P, Li ZY, Tang L, Bu ZD, Ren H, Ji JF. Capecitabine plus paclitaxel induction treatment in gastric cancer patients with liver metastasis: a prospective, uncontrolled, open-label Phase II clinical study. Future Oncol 2016; 12:2107-16. [PMID: 27256000 DOI: 10.2217/fon-2016-0145] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
AIM To determine the overall survival rate, radical resection rate, objective response rate and safety of capecitabine plus paclitaxel induction chemotherapy in gastric cancer patients with liver metastases. PATIENTS & METHODS A total of 30 patients (median age: 59.5 years) diagnosed as gastric adenocarcinoma with liver metastasis received ≥3 cycles of capecitabine and paclitaxel therapy followed by radical resection 4-6 weeks after termination of chemotherapy. RESULTS The median survival time was 11.4 months, and the objective response rate was 53.3%. The radical resection rate was 23.3% (95% CI: 9.9-42.3). Major toxicities included grade 3 neutropenia (10.0%) and grade 3 diarrhea (3.3%). CONCLUSION Capecitabine plus paclitaxel chemotherapy may be effective and safe to improve overall survival and the resection rate of gastric cancer patients with liver metastases. ClinicalTrials.gov identifier: NCT0116704.
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Affiliation(s)
- Ai-Wen Wu
- Department of Gastrointestinal Surgery, Key Laboratory of Carcinogenesis & Translational Research (Ministry of Education), Peking University Cancer Hospital, Beijing Cancer Hospital & Institute, Beijing 100142, China
| | - Peng Yuan
- Department of Endoscopy, Key Laboratory of Carcinogenesis & Translational Research (Ministry of Education), Peking University Cancer Hospital, Beijing Cancer Hospital & Institute, Beijing 100142, China
| | - Zi-Yu Li
- Department of Gastrointestinal Surgery, Key Laboratory of Carcinogenesis & Translational Research (Ministry of Education), Peking University Cancer Hospital, Beijing Cancer Hospital & Institute, Beijing 100142, China
| | - Lei Tang
- Department of Radiology, Key Laboratory of Carcinogenesis & Translational Research (Ministry of Education), Peking University Cancer Hospital, Beijing Cancer Hospital & Institute, Beijing 100142, China
| | - Zhao-De Bu
- Department of Gastrointestinal Surgery, Key Laboratory of Carcinogenesis & Translational Research (Ministry of Education), Peking University Cancer Hospital, Beijing Cancer Hospital & Institute, Beijing 100142, China
| | - Hui Ren
- Department of Gastrointestinal Surgery, Key Laboratory of Carcinogenesis & Translational Research (Ministry of Education), Peking University Cancer Hospital, Beijing Cancer Hospital & Institute, Beijing 100142, China
| | - Jia-Fu Ji
- Department of Gastrointestinal Surgery, Key Laboratory of Carcinogenesis & Translational Research (Ministry of Education), Peking University Cancer Hospital, Beijing Cancer Hospital & Institute, Beijing 100142, China
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Fazio N, Biffi R, Maibach R, Hayoz S, Thierstein S, Brauchli P, Bernhard J, Stupp R, Andreoni B, Renne G, Crosta C, Morant R, Chiappa A, Luca F, Zampino M, Huber O, Goldhirsch A, de Braud F, Roth A, Pace U, Cenciarelli S, Pozzi S, Bertani E, Mura S, Lorizzo K, Di Meglio G, Ravizza D, Boselli S, Matter M, Richter M, Monfardini S, Dittrich C, Häfner M, Clemens M. Preoperative versus postoperative docetaxel–cisplatin–fluorouracil (TCF) chemotherapy in locally advanced resectable gastric carcinoma: 10-year follow-up of the SAKK 43/99 phase III trial. Ann Oncol 2016; 27:668-673. [DOI: 10.1093/annonc/mdv620] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/29/2023] Open
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Kim JS, Kang SH, Moon HS, Sung JK, Jeong HY, Sul JY. Clinical Outcome of Doublet and Triplet Neoadjuvant Chemotherapy for Locally Advanced Gastric Cancer. THE KOREAN JOURNAL OF GASTROENTEROLOGY 2016; 68:245-252. [DOI: 10.4166/kjg.2016.68.5.245] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
Affiliation(s)
- Ju Seok Kim
- Division of Gastroenterology, Chungnam National University School of Medicine, Daejeon, Korea
| | - Sun Hyung Kang
- Division of Gastroenterology, Chungnam National University School of Medicine, Daejeon, Korea
| | - Hee Seok Moon
- Division of Gastroenterology, Chungnam National University School of Medicine, Daejeon, Korea
| | - Jae Kyu Sung
- Division of Gastroenterology, Chungnam National University School of Medicine, Daejeon, Korea
| | - Hyun Yong Jeong
- Division of Gastroenterology, Chungnam National University School of Medicine, Daejeon, Korea
| | - Ji Young Sul
- Department of Internal Medicine, Department of Surgery, Chungnam National University School of Medicine, Daejeon, Korea
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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: 33] [Impact Index Per Article: 3.3] [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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Adjuvant and neoadjuvant options in resectable gastric cancer: is there an optimal treatment approach? Curr Oncol Rep 2015; 17:18. [PMID: 25708803 DOI: 10.1007/s11912-015-0442-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
Gastric cancer is one of the most prevalent and deadliest forms of cancer worldwide. Even though neoadjuvant, perioperative, and adjuvant chemotherapy and/or radiation therapy may improve outcomes compared with surgery alone, the optimal combination of treatment modalities remains controversial. While European and North American trials established perioperative chemotherapy and adjuvant chemoradiation regimens for gastric cancer, Asian countries have focused on the use of adjuvant chemotherapy. This review summarizes results from contemporary randomized controlled trials and meta-analyses to elucidate the relative merits of each treatment approach.
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Surgical management of advanced gastric cancer: An evolving issue. Eur J Surg Oncol 2015; 42:18-27. [PMID: 26632080 DOI: 10.1016/j.ejso.2015.10.016] [Citation(s) in RCA: 63] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2015] [Accepted: 10/30/2015] [Indexed: 01/01/2023] Open
Abstract
Worldwide, gastric cancer represents the fifth most common cancer and the third leading cause of cancer deaths. Although the overall 5-year survival for resectable disease was more than 70% in Japan due to the implementation of screening programs resulting in detection of disease at earlier stages, in Western countries more than two thirds of gastric cancers are usually diagnosed in advanced stages reporting a 5-year survival rate of only 25.7%. Anyway surgical resection with extended lymph node dissection remains the only curative therapy for non-metastatic advanced gastric cancer, while neoadjuvant and adjuvant chemotherapies can improve the outcomes aimed at the reduction of recurrence and extension of survival. High-quality research and advances in technologies have contributed to well define the oncological outcomes and have stimulated many clinical studies testing multimodality managements in the advanced disease setting. This review article aims to outline and discuss open issues in current surgical management of advanced gastric cancer.
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Newton AD, Datta J, Loaiza-Bonilla A, Karakousis GC, Roses RE. Neoadjuvant therapy for gastric cancer: current evidence and future directions. J Gastrointest Oncol 2015; 6:534-43. [PMID: 26487948 DOI: 10.3978/j.issn.2078-6891.2015.047] [Citation(s) in RCA: 40] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
Although surgical resection remains the only potentially curative treatment for gastric cancer (GC), poor long-term outcomes with resection alone compel a multimodality approach to this disease. Multimodality strategies vary widely; while adjuvant approaches are typically favored in Asia and the United States (USA), a growing body of evidence supports neoadjuvant and/or perioperative strategies in locally advanced tumors. Neoadjuvant approaches are particularly attractive given the morbidity associated with surgical management of GC and the substantial risk of omission of adjuvant therapy. The specific advantages of chemoradiotherapy (CRT) compared to chemotherapy have not been well defined, particularly in the preoperative setting and trials aimed at determining the optimal elements and sequencing of therapy are underway. Future studies will also define the role of targeted and biologic therapies.
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Affiliation(s)
- Andrew D Newton
- 1 Department of Surgery, 2 Division of Hematology/Oncology, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA
| | - Jashodeep Datta
- 1 Department of Surgery, 2 Division of Hematology/Oncology, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA
| | - Arturo Loaiza-Bonilla
- 1 Department of Surgery, 2 Division of Hematology/Oncology, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA
| | - Giorgos C Karakousis
- 1 Department of Surgery, 2 Division of Hematology/Oncology, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA
| | - Robert E Roses
- 1 Department of Surgery, 2 Division of Hematology/Oncology, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA
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Tian SB, Yu JC, Kang WM, Ma ZQ, Ye X, Yan C, Huang YK. Effect of Neoadjuvant Chemotherapy Treatment on Prognosis of Patients with Advanced Gastric Cancer: a Retrospective Study. ACTA ACUST UNITED AC 2015; 30:84-9. [PMID: 26148998 DOI: 10.1016/s1001-9294(15)30017-1] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
OBJECTIVE To evaluate the prognostic effects of neoadjuvant chemotherapy (NAC) in patients with local advanced gastric cancer. METHODS We retrospectively analyzed prognosis in 191 patients with advanced gastric cancer, of whom 71 were treated with NAC and 120 received surgery only between February 2007 and July 2013. Postoperative complication rate was recorded. Survival by clinicopathological features, pathological T and N stages, and histopathological tumor regression was retrospectively compared between the two groups. RESULTS According to Response Evaluation Criteria in Solid Tumors, none of the 71 patients in the NAC followed by surgery group showed complete response, 36 showed partial response, 25 had stable disease, and 10 had progressive disease. The chemotherapy response rate was 50.7%; the disease control rate was 85.9%. Grade 3/4 adverse events were seen in less than 20% patients, with acceptable toxicities. No difference was found in the overall postoperative complication rates between the two groups (7 versus 22 cases, P=0.18). Median survival time was significantly different, at 54 months in the NAC combined with surgery group and 25 months in the surgery-only group (P=0.025). CONCLUSION In patients with operable gastric adenocarcinomas, NAC can significantly improve overall survival without increasing surgical complications.
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