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Wang HT, Chiu CF, Yang HR, Jeng LB, Bai EJ, Chen TH, Yeh CC, Chu CL, Bai LY. Adjuvant chemotherapy for stage II and III gastric adenocarcinoma: A retrospective analysis with long-term follow-up. J Formos Med Assoc 2025; 124:311-319. [PMID: 38719675 DOI: 10.1016/j.jfma.2024.04.020] [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: 05/21/2023] [Revised: 01/16/2024] [Accepted: 04/30/2024] [Indexed: 04/02/2025] Open
Abstract
BACKGROUND Whether adjuvant chemotherapy should be different for patients with stage II and III gastric cancer is unknown. METHODS We retrospectively analyzed the effects of adjuvant chemotherapy on the outcomes of 140 and 256 patients with stage II and III gastric cancer, respectively, between January 2008 and December 2018. Chemotherapies were stratified as fluoropyrimidine plus platinum versus fluoropyrimidine alone, tegafur/gimeracil/octeracil (S-1)-containing versus non-S-1-containing regimens, and S-1 plus cisplatin versus S-1 alone. RESULTS The median age of patients was 67.0 (range 24.6-98.8) years. With a median follow-up of 105 months, recurrence occurred in 32 (22.9%) and 130 (50.8%) patients with stage II and III disease, respectively. Adjuvant chemotherapy was administered as fluoropyrimidine monotherapy to 68 (48.6%) and 73 (28.5%) patients, fluoropyrimidine plus platinum to 9 (6.4%) and 104 (40.6%) patients, and none to 63 (45.0%) and 79 (30.9%) patients with stage II and III gastric cancer, respectively. Doublet chemotherapy was associated with longer disease-free survival (DFS) (26.5 vs. 15.2 months, P = 0.001) and overall survival (OS) (41.2 vs. 22.0 months, P < 0.001) than fluoropyrimidine monotherapy for stage IIIB-IIIC disease. Furthermore, S-1-containing regimens prolonged DFS (57.4 vs. 21.9 months, P = 0.044) and OS (81.4 vs. 28.6 months, P = 0.023) compared with non-S-1-containing chemotherapy in stage III disease. CONCLUSION Although fluoropyrimidine monotherapy is feasible for stage II-IIIA disease, doublet chemotherapy is significantly associated with longer survival than monotherapy for stage IIIB-IIIC disease. S-1-containing regimens might lead to longer survival than non-S-1-containing chemotherapy in stage III gastric cancer.
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Affiliation(s)
- Hsiu-Tzu Wang
- Division of Hematology and Oncology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Chang-Fang Chiu
- Division of Hematology and Oncology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan; College of Medicine, School of Medicine, China Medical University, Taichung, Taiwan; Cancer Center, China Medical University Hospital, Taichung, Taiwan
| | - Horng-Ren Yang
- College of Medicine, School of Medicine, China Medical University, Taichung, Taiwan; Department of Surgery, China Medical University Hospital, Taichung, Taiwan
| | - Long-Bin Jeng
- Department of Surgery, China Medical University Hospital, Taichung, Taiwan
| | - En-Jia Bai
- Bachelor of Science in Kinesiology, Exercise Science, The University of Texas at Austin, TX, 78712, USA
| | - Te-Hong Chen
- College of Medicine, School of Medicine, China Medical University, Taichung, Taiwan; Department of Surgery, China Medical University Hospital, Taichung, Taiwan
| | - Chun-Chieh Yeh
- College of Medicine, School of Medicine, China Medical University, Taichung, Taiwan; Department of Surgery, China Medical University Hospital, Taichung, Taiwan
| | - Chien-Lun Chu
- Cancer Center, China Medical University Hospital, Taichung, Taiwan
| | - Li-Yuan Bai
- Division of Hematology and Oncology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan; College of Medicine, School of Medicine, China Medical University, Taichung, Taiwan.
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Hasegawa K, Nishio S, Yamamoto K, Fujiwara H, Itagaki H, Nagai T, Takano H, Yamaguchi S, Kudoh A, Suzuki Y, Nakamoto T, Kurosaki A, Kamio M, Kato K, Nakamura K, Takehara K, Yahata H, Kobayashi H, Saito M, Fujiwara K. Tegafur-uracil maintenance chemotherapy post-chemoradiotherapy for cervical cancer: Randomized trial. Eur J Cancer 2025; 219:115304. [PMID: 40010135 DOI: 10.1016/j.ejca.2025.115304] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2024] [Revised: 01/31/2025] [Accepted: 02/01/2025] [Indexed: 02/28/2025]
Abstract
AIM Concurrent chemoradiotherapy (CCRT) is the standard treatment for locally advanced cervical cancer (LACC), but recurrence rates remain high. This multicenter phase-3 randomized trial (GOTIC-002) evaluated the efficacy of low-dose oral tegafur-uracil (UFT) as maintenance chemotherapy following curative CCRT for LACC. METHODS Between 2010 and 2018, 351 patients with stage Ib2-IVa cervical cancer were enrolled. After achieving complete or partial remission post-CCRT, patients were randomized 1:1 into observation (arm O) or UFT maintenance therapy (arm UFT). UFT doses were 300-400 mg/day based on body surface area for 2 years, disease progression or adverse effects occurred. The primary endpoint was progression-free survival (PFS), with overall survival (OS) and safety as secondary endpoints. RESULTS Patient characteristics were similar between the groups (n = 178 in arm O, n = 173 in arm UFT). During a median follow-up of 3 years, median PFS was not reached in either group. 5-year PFS rates were similar between them (arm O: 61.3 %, arm UFT: 62.0 %, hazard ratio: 0.92, P = .634). 5-year OS rates were also comparable (77.6 % vs 76.1 %, hazard ratio: 1.04, P = .869). Compliance with UFT ranged from 87.8 % to 98.8 %. Although adverse events were more frequent in arm UFT (93.5 % vs 73.9 %, odds ratio: 5.05), most were mild or moderate. Despite its tolerability, UFT did not improve PFS or OS. CONCLUSIONS These findings suggest the need to reconsider maintenance therapy strategies after CCRT for potentially shifting away from cytotoxic chemotherapy towards alternative methods to enhance survival outcomes in patients with LACC.
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Affiliation(s)
- Kosei Hasegawa
- Department of Gynecologic Oncology, Saitama Medical University International Medical Center, Japan.
| | - Shin Nishio
- Department of Obstetrics and Gynecology, Kurume University, Japan
| | - Kouji Yamamoto
- Department of Biostatistics, Yokohama City University, Japan
| | - Hiroyuki Fujiwara
- Department of Obstetrics and Gynecology, Jichi Medical University, Japan
| | - Hiroya Itagaki
- Department of Obstetrics and Gynecology, University of Tsukuba, Japan
| | - Tomonori Nagai
- Department of Obstetrics and Gynecology, Saitama Medical Center, Saitama Medical University, Japan
| | - Hirokuni Takano
- Department of Obstetrics and Gynecology, Jikei University Kashiwa Hospital, Japan
| | | | - Akiko Kudoh
- Department of Obstetrics and Gynecology, Tottori University, Japan
| | - Yurina Suzuki
- Department of Gynecology, Saitama Cancer Center, Japan
| | - Tomoko Nakamoto
- Department of Obstetrics and Gynecology, The University of the Ryukyus, Japan
| | - Akira Kurosaki
- Department of Gynecologic Oncology, Saitama Medical University International Medical Center, Japan
| | - Masaaki Kamio
- Department of Gynecologic Oncology, Kagoshima Medical Center, Japan
| | - Kazuyoshi Kato
- Department of Obstetrics and Gynecology, Kitasato University, Japan
| | - Kazuto Nakamura
- Department of Gynecologic Oncology, Gunma Prefectural Cancer Center, Japan
| | - Kazuhiro Takehara
- Department of Gynecologic Oncology, NHO Shikoku Cancer Center, Japan
| | - Hideaki Yahata
- Department of Obstetrics and Gynecology, Kyushu University, Japan
| | | | - Motoaki Saito
- Department of Obstetrics and Gynecology, The Jikei University School of Medicine, Japan
| | - Keiichi Fujiwara
- Department of Gynecologic Oncology, Saitama Medical University International Medical Center, Japan
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Su C, Lin Z, Ye Z, Liang J, Yu R, Wan Z, Hou J. Development of a prognostic model for early-stage gastric cancer-related DNA methylation-driven genes and analysis of immune landscape. Front Mol Biosci 2024; 11:1455890. [PMID: 39575189 PMCID: PMC11579923 DOI: 10.3389/fmolb.2024.1455890] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2024] [Accepted: 09/13/2024] [Indexed: 11/24/2024] Open
Abstract
Background and Aims This study aimed to develop a prognostic model based on DNA methylation-driven genes for patients with early-stage gastric cancer and to examine immune infiltration and function across varying risk levels. Methods We analyzed data from stage I/II gastric cancer patients in The Cancer Genome Atlas which included clinical details, mRNA expression profiles, and level 3 DNA methylation array data. Using the empirical Bayes method of the limma package, we identified differentially expressed genes (DEGs), and the MethylMix package facilitated the identification of DNA methylation-driven genes (DMGs). Univariate Cox regression and LASSO (least absolute shrinkage and selector operation) analyses were utilized to pinpoint critical genes. A risk score prediction model was formulated using two genes that demonstrated the most significant hazard ratios (HRs). Model performance was evaluated within the initial cohort and verified in the GSE84437 cohort; a nomogram was also constructed based on these genes. We further examined 50 methylation sites associated with three CpG islands in C1orf35 and 14 methylation sites linked to one CpG island in FAAH. The CIBERSORT package was employed to identify immune cell clusters in the prediction model. Results A total of 176 DNA methylation-driven genes were refined down to a four-gene signature (ZC3H12A was hypermethylated; GATA3, C1orf35, and FAAH were hypomethylated), which exhibited a significant correlation with overall survival (OS), as evidenced by p-values below 0.05 following univariate Cox regression and LASSO analysis. Specifically, for the risk score prediction model, C1orf35, which had the highest hazard ratio (HR = 2.035, p = 0.028), and FAAH, with the lowest hazard ratio (HR = 0.656, p = 0.012), were selected. The Kaplan-Meier analysis demonstrated distinct survival outcomes between the high-risk and low-risk score groups. The model's predictive accuracy was confirmed with an area under the curve (AUC) of 0.611 for 3-year survival and 0.564 for 5-year survival. Notably, the hypomethylation of the three CpG islands in C1orf35 and the single CpG island in FAAH was significantly different in stage I/II gastric cancer patients compared to normal tissues. Additionally, the high-risk score group showed a notable association with resting CD4 memory T cells. Conclusion Promoter hypomethylation of C1orf35 and FAAH in early-stage gastric cancer underscores their potential as biomarkers for accurate diagnosis and treatment. The developed predictive model employing genes affected by DNA methylation serves as a crucial independent prognostic factor in early-stage gastric cancer.
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Affiliation(s)
- Chen Su
- The School of Clinical Medical, Fujian Medical University, Fuzhou, Fujian, China
- Department of Gastrointestinal Surgery, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China
- Institute of Gastrointestinal Oncology, School of Medicine, Xiamen University, Xiamen, China
| | - Zeyang Lin
- Department of Pathology, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China
| | - Zhijian Ye
- Department of Gastrointestinal Surgery, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China
- Institute of Gastrointestinal Oncology, School of Medicine, Xiamen University, Xiamen, China
| | - Jing Liang
- Department of Pathology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Rong Yu
- Department of Gastrointestinal Surgery, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China
- Institute of Gastrointestinal Oncology, School of Medicine, Xiamen University, Xiamen, China
| | - Zheng Wan
- Department of Minimally Invasive and Interventional Therapy for Cancer, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen, China
| | - Jingjing Hou
- The School of Clinical Medical, Fujian Medical University, Fuzhou, Fujian, China
- Department of Gastrointestinal Surgery, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China
- Institute of Gastrointestinal Oncology, School of Medicine, Xiamen University, Xiamen, China
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Zhong Q, Liu ZY, Shang-Guan ZX, Li YF, Li Y, Wu J, Huang Q, Li P, Xie JW, Chen QY, Huang CM, Zheng CH. Impact of chemotherapy delay on long-term prognosis of laparoscopic radical surgery for locally advanced gastric cancer: a pooled analysis of four randomized controlled trials. Gastric Cancer 2024; 27:1100-1113. [PMID: 38809487 DOI: 10.1007/s10120-024-01513-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2024] [Accepted: 05/17/2024] [Indexed: 05/30/2024]
Abstract
BACKGROUND Adjuvant chemotherapy following curative surgery for locally advanced gastric cancer (AGC) significantly improves long-term patient prognosis. However, delayed chemotherapy (DC), in which patients are unable to receive timely treatment, is a common phenomenon in clinical practice for various reasons. This study aimed to investigate the impact of DC on the prognosis of patients with stage II-III locally AGC and explore the associated risk factors. METHODS Data from four prospective studies were included in the pooled analysis. The planned chemotherapy (PC) group was defined as the time interval between surgery and the first chemotherapy ≤ 49 d, while the DC group was defined as the time interval between surgery and chemotherapy > 49 d. The prognosis, recurrence, and risk factors were compared, and a nomogram for predicting DC was established. RESULTS In total, 596 patients were included, of whom 531 (89.1%) had PC and 65 (10.9%) had DC. Survival analysis revealed that the 5-year overall survival (OS) and disease-free survival (DFS) were significantly lower in the DC group than those in the PC group (log-rank P < 0.001). Cox univariable and multivariable analyses showed that DC was an independent risk factor for OS and DFS in stage II-III patients (P < 0.05). Based on the significant factors for DC, a prediction model was established that had a good fit, high accuracy (AUC = 0.780), and clinical applicability in both the training and validation sets. CONCLUSION Delayed chemotherapy after gastrectomy is associated with poor long-term prognosis in patients with locally advanced stage II-III GC disease. But standardized, full-cycle adjuvant chemotherapy after surgery may play a remedial role, and can to a certain extent compensate the poor effects caused by delayed chemotherapy.
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Affiliation(s)
- Qing Zhong
- Department of Gastric Surgery, Fujian Medical University Union Hospital, No. 29 Xinquan Road, Fuzhou, 350001, Fujian Province, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China
| | - Zhi-Yu Liu
- Department of Gastric Surgery, Fujian Medical University Union Hospital, No. 29 Xinquan Road, Fuzhou, 350001, Fujian Province, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China
| | - Zhi-Xin Shang-Guan
- Department of Gastric Surgery, Fujian Medical University Union Hospital, No. 29 Xinquan Road, Fuzhou, 350001, Fujian Province, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China
| | - Yi-Fan Li
- Department of Gastric Surgery, Fujian Medical University Union Hospital, No. 29 Xinquan Road, Fuzhou, 350001, Fujian Province, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
| | - Yi Li
- Department of Gastric Surgery, Fujian Medical University Union Hospital, No. 29 Xinquan Road, Fuzhou, 350001, Fujian Province, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
| | - Ju Wu
- Department of General Surgery, Affiliated Zhongshan Hospital of Dalian University, Dalian, China
| | - Qiang Huang
- Department of Gastric Surgery, Fujian Medical University Union Hospital, No. 29 Xinquan Road, Fuzhou, 350001, Fujian Province, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
| | - Ping Li
- Department of Gastric Surgery, Fujian Medical University Union Hospital, No. 29 Xinquan Road, Fuzhou, 350001, Fujian Province, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
| | - Jian-Wei Xie
- Department of Gastric Surgery, Fujian Medical University Union Hospital, No. 29 Xinquan Road, Fuzhou, 350001, Fujian Province, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China
| | - Qi-Yue Chen
- Department of Gastric Surgery, Fujian Medical University Union Hospital, No. 29 Xinquan Road, Fuzhou, 350001, Fujian Province, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
| | - Chang-Ming Huang
- Department of Gastric Surgery, Fujian Medical University Union Hospital, No. 29 Xinquan Road, Fuzhou, 350001, Fujian Province, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
| | - Chao-Hui Zheng
- Department of Gastric Surgery, Fujian Medical University Union Hospital, No. 29 Xinquan Road, Fuzhou, 350001, Fujian Province, China.
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China.
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China.
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Chen CH, Chen CJ, Huang YC, Huang PS, Chi HC, Chuang HC, Lin MH, Huang TH, Hsu JT, Chen CY. Secreted Frizzled-Related Protein 4 Induces Gastric Cancer Progression and Resistance to Cisplatin and Oxaliplatin via β-Catenin Dysregulation. Chemotherapy 2023; 69:150-164. [PMID: 38071975 DOI: 10.1159/000533767] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2023] [Accepted: 08/18/2023] [Indexed: 09/05/2024]
Abstract
INTRODUCTION Gastric cancer is the fifth most common cancer and third leading cause of cancer-related death worldwide. There are three main ways to treat gastric cancer: surgical resection, radiation therapy, and drug therapy. Furthermore, combinations of two to three regimens can improve survival. However, the survival outcomes of chemotherapy in advanced gastric cancer patients are still unsatisfactory. Unfortunately, no widely useful biomarkers have been verified to predict the efficacy of chemotherapy for locally advanced gastric cancer. METHODS An MTT assay was used to determine the cell viability after cisplatin or oxaliplatin treatment. Western blotting and immunohistochemistry were utilized to examine the secreted frizzled-related protein 4 (sFRP4) level and associated signaling pathways. Immunofluorescence staining was utilized to analyze the location of β-catenin. Colony formation and Transwell assays were used to analyze the functions related with cisplatin, oxaliplatin, and sFRP4. RESULTS We have found that gastric cancer patients treated with combinations of 5-fluorouracil (5-FU) and cisplatin regimens have better survival rates than those treated with 5-FU-based chemotherapy alone. sFRP4 was selected as a potential target from stringent analysis and intersection of 5-FU and cisplatin resistance-related gene sets. sFRP4 was shown to be overexpressed in clinical gastric tumor tissues and positively correlated with a worse survival rate. In addition, sFRP4 and β-catenin were upregulated in cisplatin- and oxaliplatin-resistant gastric cancer cells compared to parental cells. Immunofluorescence staining and nuclear fractionation showed that β-catenin was translocated from the cytosol into the nucleus. Moreover, sFRP4 was detected in the conditioned medium of these resistant cells, which indicates that sFRP4 might have an extracellular role in chemotherapy resistance. Increased migration capacity and dysregulation of epithelial-mesenchymal transition-related markers, which might result from the dysregulation of sFRP4, were observed in cisplatin- and oxaliplatin-resistant gastric cancer cells. DISCUSSION/CONCLUSION In summary, sFRP4 might play a critical role in resistance to cisplatin and oxaliplatin, cell metastasis, and poor prognosis in gastric cancer via the Wnt-β-catenin pathway. Investigations of the molecular mechanism underlying sFRP4-modulated cancer progression and chemotherapeutic outcomes can provide additional therapeutic strategies for gastric cancer.
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Affiliation(s)
- Chun-Han Chen
- Division of General Surgery, Department of Surgery, Chang Gung Memorial Hospital, Chiayi, Taiwan
| | - Chih-Jung Chen
- Department of Pathology and Laboratory Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
- School of Medicine, Chung Shan Medical University, Taichung, Taiwan
- Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan
| | - Yi-Ching Huang
- Department of Cell Biology and Anatomy, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Po-Shuan Huang
- Department of Biochemistry, College of Medicine, Chang Gung University, Taoyuan, Taiwan
- Graduate Institute of Biochemical and Biomedical Engineering, Chang Gung University, Taoyuan, Taiwan
| | - Hsiang-Cheng Chi
- Graduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan
- Chinese Medicine Research Center, China Medical University, Taichung, Taiwan
| | - Huei-Chieh Chuang
- Department of Anatomic Pathology, Chang Gung Memorial Hospital, Chiayi, Taiwan
- Chang Gung University College of Medicine, Taoyuan, Taiwan
| | - Meng-Hung Lin
- Health Information and Epidemiology Laboratory, Chang Gung Memorial Hospital, Chiayi Branch, Taiwan
| | - Tzu-Hao Huang
- Division of General Surgery, Department of Surgery, Chang Gung Memorial Hospital, Chiayi, Taiwan
| | - Jun-Te Hsu
- Chang Gung University College of Medicine, Taoyuan, Taiwan
- Department of General Surgery, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan
| | - Cheng-Yi Chen
- Department of Cell Biology and Anatomy, College of Medicine, National Cheng Kung University, Tainan, Taiwan
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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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Fang J, Zhang F, Lu J, Deng Z, Li X, Chen X, Huang C, Chen Y, Lian L, Peng J, Chen S. Prognostic factors and the necessity of chemotherapy for stage II gastric cancer: a model based on multicenter retrospective study. Discov Oncol 2023; 14:58. [PMID: 37154867 PMCID: PMC10167061 DOI: 10.1007/s12672-023-00663-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/11/2023] [Accepted: 04/17/2023] [Indexed: 05/10/2023] Open
Abstract
BACKGROUND This study aimed to construct a prognostic model for prognosis prediction and assess the response to adjuvant chemotherapy (ACT) of stage II gastric cancer (GC) patients on high and low survival risk stratifications. METHODS We retrospectively reviewed 547 stage II gastric cancer patients who underwent D2 radical gastrectomy from January 2009 to May 2017 in Sixth Affiliated Hospital of Sun Yat-Sen University (SAH-SYSU), the Fujian Medical University Union Hospital (FJUUH), and the Sun Yat-Sen University Cancer Center (SYSUCC).The propensity score matching (PSM) of all variables was performed to balance selective bias between ACT and surgery alone (SA) groups. Kaplan-Meier survival and multivariate Cox regression analyses were carried out to identify independent prognostic factors. Independent factors selected by the Cox regression were integrated into the nomogram. The nomogram points stratified patients into high-risk and low-risk groups by the optimal cut-off value. RESULTS 278 patients were selected after PSM. Age, tumor site, T stage and lymph-nodes-examined (LNE) selected by Cox regression as independent prognostic factors were integrated into the nomogram. The nomogram performed well with a C-index of 0.76 and with C-indexes of 0.73 in and 0.71 in two validate cohorts. AUCs of the 3 year and 5 year ROC curves were 0.81 and 0.78. High- and low-risk groups stratified by the cut-off value demonstrated different responses to ACT. CONCLUSIONS The nomogram performed well in prognosis prediction. Patients in high- and low-risk groups demonstrated different responses to ACT, and high-risk patients might need ACT.
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Affiliation(s)
- Jiaming Fang
- Department of Gastric Surgery, Department of General Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, No 26, YuanCun ErHeng Road, TianHe District, Guangzhou, 510655, People's Republic of China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, China
| | - Feiyang Zhang
- Department of Gastric Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Jun Lu
- Department of Gastric Surgery, Fujian Medical University Union Hospital, No. 29 Xinquan Road, Fuzhou, 350001, China
| | - Zijian Deng
- Department of Gastric Surgery, Department of General Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, No 26, YuanCun ErHeng Road, TianHe District, Guangzhou, 510655, People's Republic of China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, China
| | - Xianzhe Li
- Department of Gastric Surgery, Department of General Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, No 26, YuanCun ErHeng Road, TianHe District, Guangzhou, 510655, People's Republic of China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, China
| | - Xijie Chen
- Department of Gastric Surgery, Department of General Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, No 26, YuanCun ErHeng Road, TianHe District, Guangzhou, 510655, People's Republic of China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, China
| | - Changming Huang
- Department of Gastric Surgery, Fujian Medical University Union Hospital, No. 29 Xinquan Road, Fuzhou, 350001, China
| | - Yingbo Chen
- Department of Gastric Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Lei Lian
- Department of Gastric Surgery, Department of General Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, No 26, YuanCun ErHeng Road, TianHe District, Guangzhou, 510655, People's Republic of China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, China
| | - Junsheng Peng
- Department of Gastric Surgery, Department of General Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, No 26, YuanCun ErHeng Road, TianHe District, Guangzhou, 510655, People's Republic of China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, China
| | - Shi Chen
- Department of Gastric Surgery, Department of General Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, No 26, YuanCun ErHeng Road, TianHe District, Guangzhou, 510655, People's Republic of China.
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, China.
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8
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Ishii T, Watanabe T, Higashi T. Differences in the performance of adjuvant chemotherapy between hemodialysis and nonhemodialysis patients. Cancer Med 2023; 12:4033-4041. [PMID: 36128898 PMCID: PMC9972071 DOI: 10.1002/cam4.5258] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2022] [Revised: 09/01/2022] [Accepted: 09/07/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND The survival of hemodialysis (HD) patients with cancer is poor, which may be caused by undertreatment due to renal dysfunction. Particularly, adjuvant chemotherapy after surgery may be considered optional because of its preventive nature. This study investigated the current frequency of administration of adjuvant chemotherapy to HD patients compared with non-HD patients in Japan. METHODS We used data from the Hospital-Based Cancer Registries national database linked to health services utilization data to analyze cases of newly diagnosed colon cancer, gastric cancer, breast cancer, and non-small cell lung cancer (NSCLC) at the stages where adjuvant chemotherapy is generally required. We compared the performance rate of adjuvant chemotherapy and the adjuvant chemotherapy regimens between HD and non-HD patients from October 2011 to December 2017. RESULTS Of the 99,761 patients who underwent curative surgery, 1207 (1%) were HD patients. HD patients received adjuvant chemotherapy less frequently than non-HD patients (24% vs. 63%, p < 0.001). After adjusting for potential confounders, HD remained negatively related to adjuvant chemotherapy administration for all four cancer types. Among all patients who received adjuvant chemotherapy 0(N = 61,873), HD patients were less likely to receive standard regimens and chemotherapy requiring dose adjustment than non-HD patients (88% vs. 95%, p < 0.001 and 92% vs. 98%, p < 0.001, respectively). This trend was particularly pronounced among patients with gastric cancer. CONCLUSIONS HD patients were less likely to receive adjuvant chemotherapy with standard regimens than non-HD patients.
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Affiliation(s)
- Taisuke Ishii
- Division of Health Services Research, National Cancer Center, Tokyo, Japan
| | - Tomone Watanabe
- Division of Health Services Research, National Cancer Center, Tokyo, Japan
| | - Takahiro Higashi
- Division of Health Services Research, National Cancer Center, Tokyo, Japan
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9
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Huang PW, Lin CY, Lee LY, Hsieh CH, Hsu CL, Liau CT, Fan KH, Huang SF, Liao CT, Chang TC, Wang HM. Maintenance tegafur-plus-uracil after adjuvant concurrent chemoradiotherapy may improve outcome for resected oral cavity squamous cell carcinoma with extranodal extension. Front Oncol 2022; 12:866890. [PMID: 36249049 PMCID: PMC9554642 DOI: 10.3389/fonc.2022.866890] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2022] [Accepted: 08/30/2022] [Indexed: 12/24/2022] Open
Abstract
Objectives To evaluate whether tegafur-uracil maintenance (UFTm) following postoperation adjuvant cisplatin-based concurrent chemoradiotherapy (CCRT) may reduce distant metastasis in patients with resected oral cavity squamous cell carcinoma (OSCC) with pathologic extranodal extension (pENE+). Methods A retrospective comparison was conducted between two cohorts of patients with resected pENE+ OSCC who completed adjuvant CCRT between March 2015 and December 2017, including one cohort of a phase II trial using UFTm and a trial-eligible but off-protocol cohort without using UFTm (non-UFTm) after their adjuvant CCRT. The UFTm trial enrolled patients without relapse within 2 months after the end of adjuvant CCRT and administered UFT 400 mg/day for 1 year. Kaplan-Meier methods estimated the actuarial rate of distant metastasis-free (DMF), locoregional control (LRC), event-free survival (EFS), and overall survival (OS). Results A total of 103 patients were included in this study, 64 patients in UFTm and 39 patients in non-UFTm. Severe adverse events in UFTm included grade 3 anemia (n = 1, 1.6%) and grade 3 mucositis (n = 1, 1.6%). A total of 40 (62.5%) patients completed the full course of UFTm, while the remaining terminated UFTm earlier due to disease relapse (n = 14, 21.8%), poor compliance (n = 9, 14.1%), and adverse event (n = 1, 1.6%). The median (range) follow-up time of surviving patients was 43 (22-65) months. The outcomes compared between UFTm and non-UFTm were OS (hazard ratio [HR] 0.31 [95% CI: 0.17-0.57], p < 0·001), EFS (0.45 [0.25-0.82], 0.009), LRC (0.45 [0.19-1.05], 0.067), and DMF (0.47 [0.24-0.95], 0.035). Multivariable analysis, adjusted for UFTm, Charlson comorbidity index score 1-3, site of tongue, and number of ENE+ LN ≧4, confirmed better OS (0.29 [0.16-0.54], <0.001) and EFS (0.47 [0.26-0.85], 0.012) in favor of UFTm over non-UFTm. The 2-year DM rate was 25.8% in UFTm and 44.2% in non-UFTm. For relapsed patients in UFTm vs. non-UFTm, the rate of metastasectomy for oligometastasis was 53% vs. 6%, and the OS was 21.0 (95% CI: 17.8-24.1) months vs. 11.0 (9.1-12.8) months (p < 0.001), respectively. Conclusions UFTm may improve the dismal outcomes of the resected pENE+ OSCC. Further investigations are needed to confirm our observations.
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Affiliation(s)
- Pei-Wei Huang
- Division of Medical Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan
| | - Chien-Yu Lin
- Departments of Radiation Oncology, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan
- College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Li-Yu Lee
- College of Medicine, Chang Gung University, Taoyuan, Taiwan
- Department of Pathology, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan
| | - Chia-Hsun Hsieh
- Division of Medical Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan
- College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Cheng-Lung Hsu
- Division of Medical Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan
- College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Chi-Ting Liau
- Division of Medical Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan
| | - Kang-Hsing Fan
- Departments of Radiation Oncology, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan
- College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Shiang-Fu Huang
- College of Medicine, Chang Gung University, Taoyuan, Taiwan
- Section of Head and Neck Surgery, Department of Otorhinolaryngology, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan
| | - Chun-Ta Liao
- College of Medicine, Chang Gung University, Taoyuan, Taiwan
- Section of Head and Neck Surgery, Department of Otorhinolaryngology, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan
| | - Tung-Chieh Chang
- Departments of Radiation Oncology, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan
- College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Hung-Ming Wang
- Division of Medical Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan
- College of Medicine, Chang Gung University, Taoyuan, Taiwan
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10
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Choi M, Ishizawa S, Kraemer D, Sasson A, Feinberg E. Perioperative chemotherapy versus adjuvant chemotherapy strategies in resectable gastric and gastroesophageal cancer: A Markov decision analysis. Eur J Surg Oncol 2021; 48:403-410. [PMID: 34446344 DOI: 10.1016/j.ejso.2021.08.012] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2021] [Revised: 07/22/2021] [Accepted: 08/09/2021] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND Perioperative chemotherapy has been shown to improve overall survival (OS) for operable gastric and gastroesophageal cancer. However, optimal sequence of surgery and chemotherapy has not been clearly identified. Markov models are useful for analyzing the outcomes of different treatment strategies in the absence of adequately powered randomized clinical trials. In this study, we use Markov decision analysis models to compare median OS (mOS), quality-adjusted mOS, life expectancy (LE), and quality-adjusted life expectancy (QALE) of perioperative chemotherapy with adjuvant chemotherapy strategies in resectable gastric and gastroesophageal cancer patients. METHODS Markov models are constructed to compare two strategies: adjuvant chemotherapy after surgery and preoperative chemotherapy followed by cancer resection and postoperative chemotherapy. LE and QALE are calculated analytically, and mOS are obtained by simulation. Parameters used in the models are computed from prospective clinical trial data published in PUBMED from January 2000 to July 2020. RESULTS Total of 8088 patients from 25 prospective studies were included in this analysis. Regardless of R0 resection ratio, the analyses of the models show a higher mOS for patients in the perioperative therapy arm compared to adjuvant chemotherapy. For R0 resected patients, the perioperative therapy arm provided an additional 11.0 mOS months (61.3 months vs. 50.3 months). For R1 resected patients, the perioperative therapy arm had mOS of 17.0 months vs. 10.7 months in adjuvant therapy. CONCLUSIONS The Markov models indicate that perioperative chemotherapy improves mOS, quality-adjusted mOS, LE, and QALE for resectable gastric and gastroesophageal cancer patients compared to adjuvant chemotherapy strategies.
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Affiliation(s)
- Minsig Choi
- Department of Medicine, Stony Brook University, USA.
| | - Sayaka Ishizawa
- Department of Applied Mathematics and Statistics, Stony Brook University, USA
| | - David Kraemer
- Department of Applied Mathematics and Statistics, Stony Brook University, USA
| | - Aaron Sasson
- Department of Surgery, Stony Brook University, Stony Brook, NY, 11794-3600, USA
| | - Eugene Feinberg
- Department of Applied Mathematics and Statistics, Stony Brook University, USA
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11
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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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12
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Yen HH, Chen CN, Yeh CC, Lai IR. Adjuvant tegafur-uracil (UFT) or S-1 monotherapy for advanced gastric cancer: a single center experience. World J Surg Oncol 2021; 19:124. [PMID: 33865416 PMCID: PMC8053033 DOI: 10.1186/s12957-021-02233-2] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2021] [Accepted: 04/06/2021] [Indexed: 12/24/2022] Open
Abstract
Background Adjuvant tegafur-gimeracil-oteracil (S-1) is commonly used for gastric cancer in Asia, and tegafur-uracil (UFT) is another oral fluoropyrimidine when S-1 is unavailable. The real-world data of adjuvant UFT has less been investigated. Methods Patients with pathological stage II-IIIB (except T1) gastric cancer receiving adjuvant UFT or S-1 monotherapy after D2 gastrectomy were included. Usage of UFT or S-1 was based on reimbursement policy of the Taiwanese healthcare system. The characteristics, chemotherapy completion rates, and 5-year recurrence-free survival (RFS) and overall survival (OS), were compared between these two groups. Results From 2005 to 2016, 86 eligible patients were included. Most tumor characteristics were similar between the UFT group (n = 37; age 59.1 ± 13.9 years) and S-1 group (n = 49; age 56.3 ± 10.7 years), except there were significantly more Borrmann type III/IV (86.5% versus 67.3%; p = 0.047) and T4 (56.8% versus 10.2%; p < 0.001) lesions in the UFT group than in the S-1 group. The chemotherapy complete rates were similar in the two groups. The 5-year RFS was 56.1% in the UFT group and 59.6% in the S-1 group (p = 0.71), and the 5-year OS was 78.3% in the UFT group and 73.1% in the S-1 group (p = 0.48). The hazard ratio of adjuvant chemotherapy (S-1 versus UFT) on RFS was 1.25 (95% confidence interval = 0.53-2.94) when Borrmann type and T and N stages were adjusted. Conclusions This small cohort study showed adjuvant UFT, and S-1 monotherapy had a comparable long-term outcome for pathological stage II-IIIB gastric cancer following D2 gastrectomy. Supplementary Information The online version contains supplementary material available at 10.1186/s12957-021-02233-2.
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Affiliation(s)
- Hung-Hsuan Yen
- Department of Surgery, National Taiwan University Biomedical Park Hospital, Hsinchu County, Taiwan.,Department of Surgery, National Taiwan University Hospital, No. 7 Chung-Shan South Rd, Zhongzheng District, Taipei, 10002, Taiwan
| | - Chiung-Nien Chen
- Department of Surgery, National Taiwan University Hospital, No. 7 Chung-Shan South Rd, Zhongzheng District, Taipei, 10002, Taiwan
| | - Chi-Chuan Yeh
- Department of Surgery, National Taiwan University Hospital, No. 7 Chung-Shan South Rd, Zhongzheng District, Taipei, 10002, Taiwan.,Department of Medical Education, National Taiwan University Hospital, Taipei, Taiwan
| | - I-Rue Lai
- Department of Surgery, National Taiwan University Hospital, No. 7 Chung-Shan South Rd, Zhongzheng District, Taipei, 10002, Taiwan. .,Graduate Institute of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, Taiwan.
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13
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Khachfe HH, Salhab HA, Fares MY, Chahrour MA, Jamali FR. Landscape of interventional clinical trials involving gastrectomy for gastric cancer. Ecancermedicalscience 2021; 15:1218. [PMID: 34158822 PMCID: PMC8183643 DOI: 10.3332/ecancer.2021.1218] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2020] [Indexed: 01/14/2023] Open
Abstract
Background Gastric cancer (GC) is the third most common cause of malignancy associated mortality globally. The cornerstone of curative treatment involves surgical gastrectomy. In this study, we explore clinical trials involving gastrectomy for GC, highlighting inadequacies and underlining promising surgical interventions and strategies. Materials and methods On 1 May 2020, ClinicalTrials.gov was explored for interventional trials related to gastrectomy for GC, without adding limitations for location or date. All data pertaining to the trials were collected. Characteristics such as phase, duration, enrolment size, location, treatment allocation, masking and primary endpoint were analysed. Results One hundred thirty-eight clinical trials met the search criteria. Clinical trials were performed in only 14 countries; most of them occurring in China. Most trials (33%) were still in the recruiting phase. On average, the length of trials was 3.9 years. Most trials had parallel assignment, were randomised and masked. The primary endpoint which was mostly commonly studied was overall survival (33%). The most common intervention studied is laparoscopic gastrectomy in 43 (31%) trials. Conclusions Our study exposed a small number of trials, publication rate, absence of geographic variety in clinical trials involving gastrectomy for GC. Adequate management of trial design can help decrease duration and increase validity of results. More trials comparing different surgical techniques are needed to update the surgical practice of gastrectomy for GC.
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Affiliation(s)
- Hussein H Khachfe
- Faculty of Medicine, American University of Beirut Medical Center, Beirut 00000, Lebanon.,Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA 15260, USA.,Division of GI Surgical Oncology, UPMC Pancreatic Cancer Center, University of Pittsburgh Medical Center, UPMC Cancer Pavilion, Pittsburgh, PA 15260, USA
| | - Hamza A Salhab
- Faculty of Medicine, American University of Beirut Medical Center, Beirut 00000, Lebanon.,Neuroscience Research Center, Faculty of Medical Sciences, Lebanese University, Beirut 00000, Lebanon
| | - Mohamad Y Fares
- Faculty of Medicine, American University of Beirut Medical Center, Beirut 00000, Lebanon.,Neuroscience Research Center, Faculty of Medical Sciences, Lebanese University, Beirut 00000, Lebanon
| | - Mohamad A Chahrour
- Faculty of Medicine, American University of Beirut Medical Center, Beirut 00000, Lebanon
| | - Faek R Jamali
- Division of General Surgery, Department of Surgery, Sheikh Shakhbout Medical City, Abu Dhabi 11001, UAE
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14
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Tokunaga M, Sato Y, Nakagawa M, Aburatani T, Matsuyama T, Nakajima Y, Kinugasa Y. Perioperative chemotherapy for locally advanced gastric cancer in Japan: current and future perspectives. Surg Today 2020; 50:30-37. [PMID: 31612329 PMCID: PMC6954129 DOI: 10.1007/s00595-019-01896-5] [Citation(s) in RCA: 55] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2019] [Accepted: 09/20/2019] [Indexed: 12/24/2022]
Abstract
The standard treatment for locally advanced gastric cancer differs across the world. In western countries, perioperative chemotherapy or postoperative adjuvant chemoradiotherapy are the preferred treatment options, whereas in Asia, D2 gastrectomy followed by postoperative adjuvant chemotherapy is standard. In Japan, adjuvant chemotherapy with S-1 is the standard treatment for pStage II gastric cancer, whereas adjuvant chemotherapy with a doublet regimen is preferred for pStage III gastric cancer. The efficacy of preoperative neoadjuvant chemotherapy using S-1 plus cisplatin, has been investigated in selected patients with expected poor survival outcomes. To expand the indications for neoadjuvant chemotherapy, a clinical trial investigating the efficacy of preoperative S-1 plus oxaliplatin in patients with cStage III (cT3-4N1-3) gastric cancer (JCOG1509) is ongoing in Japan. The addition of immune checkpoint inhibitors to cytotoxic chemotherapy also seems promising and is being investigated in international randomized clinical trials. Although we have to await the final results of these studies, preoperative neoadjuvant chemotherapy is a promising treatment strategy and likely to become standard treatment for locally advanced gastric cancer in Japan.
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Affiliation(s)
- Masanori Tokunaga
- Department of Gastrointestinal Surgery, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, Japan.
| | - Yuya Sato
- Department of Gastrointestinal Surgery, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, Japan
| | - Masatoshi Nakagawa
- Department of Gastrointestinal Surgery, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, Japan
| | - Tomoki Aburatani
- Department of Gastrointestinal Surgery, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, Japan
| | - Takatoshi Matsuyama
- Department of Gastrointestinal Surgery, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, Japan
| | - Yasuaki Nakajima
- Department of Gastrointestinal Surgery, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, Japan
| | - Yusuke Kinugasa
- Department of Gastrointestinal Surgery, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, Japan
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15
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Sasako M. Progress in the treatment of gastric cancer in Japan over the last 50 years. Ann Gastroenterol Surg 2020; 4:21-29. [PMID: 32021955 PMCID: PMC6992673 DOI: 10.1002/ags3.12306] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2019] [Revised: 11/27/2019] [Accepted: 12/02/2019] [Indexed: 12/16/2022] Open
Abstract
There have been remarkable changes in gastric cancer treatments in Japan, resulting in superb improvement of prognosis in patients with this disease. In this paper, the last 50 years have been divided into three eras: before 1990; the 1990s; and the era of evidence, which means after 2000. Changes of treatments and prognosis were analyzed by several factors, such as surgery, chemotherapy, informed consent, clinical trials, and others, as improvement of prognosis is not due to one factor but several ones influencing each other.
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Affiliation(s)
- Mitsuru Sasako
- Yodogawa Christian HospitalOsakaJapan
- Hyogo College of MedicineHyogoJapan
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16
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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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The prognostic significance of the comprehensive complication index in patients with gastric cancer. Surg Today 2019; 49:913-920. [PMID: 31147763 DOI: 10.1007/s00595-019-01828-3] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2019] [Accepted: 05/06/2019] [Indexed: 02/06/2023]
Abstract
PURPOSE Postoperative complications worsen the prognosis of gastric cancer patients. The Clavien-Dindo classification is used to evaluate postoperative complications. The prognostic significance of the comprehensive complication index (CCI), a new tool for evaluating postoperative complications, remains unclear. METHODS This study included 452 gastric adenocarcinoma patients who underwent curative surgery. RESULTS The CCI values were significantly higher in older patients ( ≥ 70 years; P < 0.0001), male patients (P < 0.0001), those with lymphatic invasion (P = 0.039), and those with vascular invasion (P = 0.037). The five-year overall survival (OS) and disease-specific survival (DSS) rates were significantly higher in patients without postoperative complications and those with Clavien-Dindo grade 1 complications in comparison to those with Clavien-Dindo grade 2-4 complications (80.4% vs. 66.2%, P = 0.0011; 89.7% vs. 82.3%; P = 0.045, respectively). Among patients with Clavien-Dindo grade 2-4 complications, the 5-year OS and DSS rates in the CCIHigh group ( ≥ 32.15) were significantly lower than those in the CCILow group ( < 32.15; 47.5% vs. 74.9%, P = 0.0086; 63.1% vs. 90.0%, P = 0.0003). A multivariate analysis identified the CCI as an independent prognostic indicator in patients with Clavien-Dindo grade 2-4 complications. CONCLUSIONS The CCI was closely associated with the prognosis of patients with Clavien-Dindo grade 2-4 complications and may be a prognostic indicator.
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18
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Late start and insufficient S-1 dose in adjuvant chemotherapy can lead to poor prognosis in stage II/III gastric cancer. Int J Clin Oncol 2019; 24:1190-1196. [DOI: 10.1007/s10147-019-01468-0] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2019] [Accepted: 05/07/2019] [Indexed: 12/19/2022]
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19
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van den Ende T, Ter Veer E, Mali RMA, van Berge Henegouwen MI, Hulshof MCCM, van Oijen MGH, van Laarhoven HWM. Prognostic and Predictive Factors for the Curative Treatment of Esophageal and Gastric Cancer in Randomized Controlled Trials: A Systematic Review and Meta-Analysis. Cancers (Basel) 2019; 11:E530. [PMID: 31013858 PMCID: PMC6521055 DOI: 10.3390/cancers11040530] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2019] [Revised: 04/05/2019] [Accepted: 04/09/2019] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND An overview of promising prognostic variables and predictive subgroups concerning the curative treatment of esophageal and gastric cancer from randomized controlled trials (RCTs) is lacking. Therefore, we conducted a systematic review and meta-analysis. METHODS PubMed, EMBASE, CENTRAL, and ASCO/ESMO conferences were searched up to March 2019 for RCTs on the curative treatment of esophageal or gastric cancer with data on prognostic and/or predictive factors for overall survival. Prognostic factors were deemed potentially clinically relevant according to the following criteria; (1) statistically significant (p < 0.05) in a multivariate analysis, (2) reported in at least 250 patients, and (3) p < 0.05, in ≥ 33% of the total number of patients in RCTs reporting this factor. Predictive factors were potentially clinically-relevant if (1) the p-value for interaction between subgroups was <0.20 and (2) the hazard ratio in one of the subgroups was significant (p < 0.05). RESULTS For gastric cancer, 39 RCTs were identified (n = 13,530 patients) and, for esophageal cancer, 33 RCTs were identified (n = 8618 patients). In total, we identified 23 potentially clinically relevant prognostic factors for gastric cancer and 16 for esophageal cancer. There were 15 potentially clinically relevant predictive factors for gastric cancer and 10 for esophageal cancer. CONCLUSION The identified prognostic and predictive factors can be included and analyzed in future RCTs and be of guidance for nomograms. Further validation should be performed in large patient cohorts.
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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.
| | - 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.
| | - Mark I van Berge Henegouwen
- 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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20
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Kamio H, Uchiyama T, Kanno H, Onoe Y, Saito K, Kameoka S, Kamio T, Okamoto T. Association between SLCO1B1 rs4149056 and tegafur-uracil-induced hepatic dysfunction in breast cancer. Pharmacogenomics 2019; 20:353-365. [PMID: 30734632 DOI: 10.2217/pgs-2018-0100] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023] Open
Abstract
Aim: The aim of this study was to identify pharmacogenomic biomarkers to predict tegafur-uracil (UFT)-induced liver dysfunction. Patients & methods: A total of 68 patients, who were administered UFT, were evaluated using a two-step pharmacogenomics analysis. Results: The first screening revealed the association between five SNPs and UFT-induced hepatic dysfunction. In the second step, SLCO1B1 (rs4149056) was found to be the only SNP associated with UFT treatment-related elevation of aspartate aminotransferase (odds ratio: C/C vs T/T = 7.8, C/T vs T/T = 5.7; p = 0.037) and alanine transaminase (odds ratio: C/C vs T/T = 12.2, C/T vs T/T = 4.1; p = 0.034) levels. Conclusion: The SLCO1B1 polymorphisms are possible predictors of UFT treatment-related hepatic dysfunction.
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Affiliation(s)
- Hidenori Kamio
- Department of Surgery II, School of Medicine, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan
| | - Toshitaka Uchiyama
- Institute of Medical Genetics, School of Medicine, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan
| | - Hitoshi Kanno
- Institute of Medical Genetics, School of Medicine, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan
| | - Yoshiko Onoe
- Department of Obstetrics & Gynecology, School of Medicine, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan
| | - Kayoko Saito
- Institute of Medical Genetics, School of Medicine, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan
| | - Shingo Kameoka
- Department of Surgery II, School of Medicine, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan
| | - Takako Kamio
- Department of Surgery II, School of Medicine, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan
| | - Takahiro Okamoto
- Department of Surgery II, School of Medicine, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan
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21
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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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22
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Huang SM, Chen YC, Chen WY, Yang LY, Tsan DL, Tsang NM, Yap WK, Tsai CS, Leung WM, Hong JH, Chang JTC, Yeh TS, Wu TH, Chen YC, Lin YH, Huang BS. Optimal Timing for Postsurgical Adjuvant Therapy in Patients with Gastric Cancer: A Propensity Score Matching Study. J Cancer 2019; 10:332-340. [PMID: 30719127 PMCID: PMC6360315 DOI: 10.7150/jca.27753] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2018] [Accepted: 10/03/2018] [Indexed: 12/20/2022] Open
Abstract
Background:In clinical trials, adjuvant therapy (AT) has been shown to improve the prognosis in patients with gastric adenocarcinoma who undergo curative gastrectomy and adequate lymph node dissection. However, the optimal timing for initiating AT is still unclear. Method:We collected data from 538 patients with stage II-III gastric cancer who underwent curative gastrectomy and AT in two tertiary hospitals from 2006 to 2013. Patients were divided into the early group (≤8 weeks, n=393) and the late group (>8 weeks, n=145), based on the interval between gastrectomy and initiation of AT. Propensity score matching was applied according to baseline characteristics. Results:After 1:1 propensity score matching, an even distribution of characteristics in both groups (143:143) was achieved. The 5-year overall survival (OS) rates were 56.6% and 40.2% in the matched early and late groups, respectively (p=0.062), while the corresponding 5-year recurrence-free survival (RFS) rates were 57.6% and 46.4%, respectively (p=0.028). The time to AT initiation was correlated with RFS and had a positive association with OS. The 5-year distant metastasis-free survival was also significantly better (HR 0.682, 95% CI 0.472-0.985, p=0.040), suggesting an early AT results in a better outcome in patients. Conclusion:We observed that initiation of AT within 8 weeks of curative gastrectomy produces better disease control and may contribute to better overall survival.
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Affiliation(s)
- Shih-Ming Huang
- Department of Radiation Oncology, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan
| | - Yen-Chao Chen
- Department of Radiation Oncology, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan
| | - Wan-Yu Chen
- Division of Radiation Oncology, Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan.,Cancer Research Center, National Taiwan University College of Medicine, Taipei, Taiwan.,Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Lan-Yan Yang
- Clinical Trial Center, Chang Gung Memorial Hospital, Linkou, Taiwan
| | - Din-Li Tsan
- Department of Radiation Oncology, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan
| | - Ngan-Ming Tsang
- Department of Radiation Oncology, Proton and radiation therapy center, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan
| | - Wing-Keen Yap
- Department of Radiation Oncology, Proton and radiation therapy center, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan
| | - Chien-Sheng Tsai
- Department of Radiation Oncology, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan
| | - Wai-Man Leung
- Department of Radiation Oncology, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan
| | - Ji-Hong Hong
- Department of Radiation Oncology, Proton and radiation therapy center, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan
| | - Joseph Tung-Chieh Chang
- Department of Radiation Oncology, Proton and radiation therapy center, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan
| | - Ta-Sen Yeh
- Department of Surgery, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan
| | - Tsung-Han Wu
- Division of Hematology and Oncology, Department of Internal Medicine, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan.,College of Medicine, Chang Gung University, Taoyuan, Taiwan.,Department of Food Science, National Taiwan Ocean University, Keelung, Taiwan
| | - Yi-Chan Chen
- Division of general surgery, Department of surgery, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan
| | - Yun-Hsuan Lin
- Department of Ophthalmology, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan
| | - Bing-Shen Huang
- Department of Radiation Oncology, Proton and radiation therapy center, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan.,Graduate Institute of Clinical Medical Science, Chang Gung University, Taoyuan, Taiwan
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23
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Cai Z, Yin Y, Yin Y, Shen C, Wang J, Yin X, Chen Z, Zhou Y, Zhang B. Comparative effectiveness of adjuvant treatments for resected gastric cancer: a network meta-analysis. Gastric Cancer 2018; 21:1031-1040. [PMID: 29728791 DOI: 10.1007/s10120-018-0831-0] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2018] [Accepted: 04/27/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND Different adjuvant treatments are available for patients with gastric cancer, but conventional meta-analyses performing direct comparisons between two alternative treatments did not have enough power to compare all the adjuvant treatments. Thus, we did a network meta-analysis summarizing the direct and indirect comparisons to identify the optimum treatment. METHODS We systematically searched for RCTs of adjuvant treatments for gastric cancer comparing two or more of the following treatments: surgery alone, radiotherapy with fluoropyrimidine, S-1-based regimens, and XELOX. The treatments offering available indirect evidence to investigate the comparative effectiveness of adjuvant treatments mentioned above were also included. Then we performed a Bayesian network meta-analysis to summarize the direct and indirect comparisons. We estimated hazard ratios with 95% credible intervals (CrI) for OS and DFS. RESULTS 11 eligible RCTs (5620 patients) were included in the network meta-analysis. Radiotherapy with fluorouracil (5-FU/RT), S-1-based regimens, and XELOX significantly improved OS as compared with surgery alone [(HR = 0.75 with 95% CrI: 0.63-0.89), (HR = 0.63 with 95% CrI: 0.52-0.76), and (HR = 0.66 with 95% CrI: 0.51-0.85), respectively]. No treatment was clearly superior to others; however, S-1-based regimes and XELOX showed a statistically non-significant trend to better survival as compared with 5-FU/RT. CONCLUSIONS S-1-based chemotherapy and XELOX are likely to be the most effective adjuvant treatments for patients with resected gastric cancer. 5-FU alone provided little survival benefits as compared with surgery alone. Further clinical trials may be required to investigate S-1-based and XELOX-based adjuvant treatment strategies.
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Affiliation(s)
- Zhaolun Cai
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China
| | - Yiqiong Yin
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China
| | - Yuan Yin
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China
| | - Chaoyong Shen
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China
| | - Jian Wang
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China
| | - Xiaonan Yin
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China
| | - Zhixin Chen
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China
| | - Ye Zhou
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China
| | - Bo Zhang
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.
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24
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Chen JS, Hung CY, Liu KH, Tsai CY, Kuo YC, Hsu JT, Chou WC. Factors related to patient propensity to receive adjuvant chemotherapy and outcomes in stage III gastric cancer cases after D2 surgery. Asian J Surg 2018; 42:604-612. [PMID: 30249414 DOI: 10.1016/j.asjsur.2018.08.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2018] [Revised: 07/25/2018] [Accepted: 08/06/2018] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Radical gastrectomy and extended lymph node (D2) dissection followed by adjuvant chemotherapy is the optimal treatment for patients with stage III gastric cancer in Asian population. The clinical factors associated with patient propensity to receive adjuvant chemotherapy and outcomes were analyzed. METHODS In total, 509 patients with stage III gastric cancer who had undergone D2 surgery between 2007 and 2017 at a single medical center in Taiwan were analyzed. The patients' preoperative clinical characteristics relevant to adjuvant chemotherapy adherence were analyzed using multivariate regression. Significant variables were analyzed using recursive partitioning analysis (RPA) for identifying specific patient groups with the lowest and highest probabilities of adjuvant chemotherapy adherence. RESULTS After surgery, 361 (70.9%) patients in the cohort had received adjuvant chemotherapy. All patients were categorized into five probability groups with adherence to adjuvant chemotherapy according to age, Eastern Cooperative Oncology Group (ECOG) performance status grade, and American Society of Anesthesiologists (ASA) class, which were discovered to be independent factors in the RPA-based probability prediction. In general, adjuvant chemotherapy improved survival across broad categories of stage III gastric cancer patients (overall survival hazard ratio: 0.53-0.75 and disease-free survival hazard ratio: 0.47-0.76). CONCLUSIONS Our study identified that age, ECOG grade, and ASA class were independent clinical factors associated with patient propensity to receive adjuvant chemotherapy in stage III gastric cancer. Knowledge of the clinical factors of patients may help clinicians identify and encourage specific patients to receive the adjuvant chemotherapy.
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Affiliation(s)
- Jen-Shi Chen
- Division of Hematology-Oncology, Department of Internal Medicine, Linkou Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taoyuan, Taiwan
| | - Chia-Yen Hung
- Division of Hematology-Oncology, Department of Internal Medicine, Linkou Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taoyuan, Taiwan; Department of Hematoloy-Oncology, Division of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan
| | - Keng-Hao Liu
- Division of General Surgery, Department of Surgery, Linkou Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taoyuan, Taiwan
| | - Chun-Yi Tsai
- Division of General Surgery, Department of Surgery, Linkou Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taoyuan, Taiwan
| | - Yung-Chia Kuo
- Division of Hematology-Oncology, Department of Internal Medicine, Linkou Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taoyuan, Taiwan
| | - Jun-Te Hsu
- Division of General Surgery, Department of Surgery, Linkou Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taoyuan, Taiwan
| | - Wen-Chi Chou
- Division of Hematology-Oncology, Department of Internal Medicine, Linkou Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taoyuan, Taiwan.
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25
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Slagter AE, Jansen EPM, van Laarhoven HWM, van Sandick JW, van Grieken NCT, Sikorska K, Cats A, Muller-Timmermans P, Hulshof MCCM, Boot H, Los M, Beerepoot LV, Peters FPJ, Hospers GAP, van Etten B, Hartgrink HH, van Berge Henegouwen MI, Nieuwenhuijzen GAP, van Hillegersberg R, van der Peet DL, Grabsch HI, Verheij M. CRITICS-II: a multicentre randomised phase II trial of neo-adjuvant chemotherapy followed by surgery versus neo-adjuvant chemotherapy and subsequent chemoradiotherapy followed by surgery versus neo-adjuvant chemoradiotherapy followed by surgery in resectable gastric cancer. BMC Cancer 2018; 18:877. [PMID: 30200910 PMCID: PMC6131797 DOI: 10.1186/s12885-018-4770-2] [Citation(s) in RCA: 100] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2018] [Accepted: 08/22/2018] [Indexed: 12/21/2022] Open
Abstract
Background Although radical surgery remains the cornerstone of cure in resectable gastric cancer, survival remains poor. Current evidence-based (neo)adjuvant strategies have shown to improve outcome, including perioperative chemotherapy, postoperative chemoradiotherapy and postoperative chemotherapy. However, these regimens suffer from poor patient compliance, particularly in the postoperative phase of treatment. The CRITICS-II trial aims to optimize preoperative treatment by comparing three treatment regimens: (1) chemotherapy, (2) chemotherapy followed by chemoradiotherapy and (3) chemoradiotherapy. Methods In this multicentre phase II non-comparative study, patients with clinical stage IB-IIIC (TNM 8th edition) resectable gastric adenocarcinoma are randomised between: (1) 4 cycles of docetaxel+oxaliplatin+capecitabine (DOC), (2) 2 cycles of DOC followed by chemoradiotherapy (45Gy in combination with weekly paclitaxel and carboplatin) or (3) chemoradiotherapy. Primary endpoint is event-free survival, 1 year after randomisation (events are local and/or regional recurrence or progression, distant recurrence, or death from any cause). Secondary endpoints include: toxicity, surgical outcomes, percentage radical (R0) resections, pathological tumour response, disease recurrence, overall survival, and health related quality of life. Exploratory endpoints include translational studies on predictive and prognostic biomarkers. Discussion The aim of this study is to select the most promising among three preoperative treatment arms in patients with resectable gastric adenocarcinoma. This treatment regimen will subsequently be compared with the standard therapy in a phase III trial. Trial registration clinicaltrials.gov NCT02931890; registered 13 October 2016. Date of first enrolment: 21 December 2017.
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Affiliation(s)
- Astrid E Slagter
- Department of Radiation Oncology, Netherlands Cancer Institute - Antoni van Leeuwenhoek, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands
| | - Edwin P M Jansen
- Department of Radiation Oncology, Netherlands Cancer Institute - Antoni van Leeuwenhoek, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands
| | - Hanneke W M van Laarhoven
- Department of Medical Oncology, Academic Medical Center Amsterdam, Meibergdreef 9, 1106 AZ, Amsterdam, The Netherlands
| | - Johanna W van Sandick
- Department of Surgery, Netherlands Cancer Institute - Antoni van Leeuwenhoek, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands
| | - Nicole C T van Grieken
- Department of Pathology, VU University Medical Center, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands
| | - Karolina Sikorska
- Statistical Department, Netherlands Cancer Institute - Antoni van Leeuwenhoek, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands
| | - Annemieke Cats
- Department of Gastroenterology, Netherlands Cancer Institute - Antoni van Leeuwenhoek, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands
| | - Pietje Muller-Timmermans
- Department of Radiation Oncology, Netherlands Cancer Institute - Antoni van Leeuwenhoek, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands
| | - Maarten C C M Hulshof
- Department of Radiation Oncology, Academic Medical Center Amsterdam, Meibergdreef 9, 1106 AZ, Amsterdam, The Netherlands
| | - Henk Boot
- Department of Gastroenterology, Netherlands Cancer Institute - Antoni van Leeuwenhoek, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands
| | - Maartje Los
- Department of Medical Oncology, St. Antonius Hospital, Koekoekslaan 1, 3435 CM, Nieuwegein, The Netherlands
| | - Laurens V Beerepoot
- Department of Medical Oncology, St. Elisabeth Hospital, Hilvarenbeekse Weg 60, 5022 GC, Tilburg, The Netherlands
| | - Frank P J Peters
- Department of Medical Oncology, Zuyderland Sittard-Geleen, Dr. H. van der Hoffplein 1, 6162 BG, Sittard-Geleen, The Netherlands
| | - Geke A P Hospers
- Department of Medical Oncology, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands
| | - Boudewijn van Etten
- Department of Surgery, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands
| | - Henk H Hartgrink
- Department of Surgery, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands
| | - Mark I van Berge Henegouwen
- Department of Surgery, Academic Medical Center Amsterdam, Meibergdreef 9, 1106 AZ, Amsterdam, The Netherlands
| | - Grard A P Nieuwenhuijzen
- Department of Surgery, Catharina Hospital Eindhoven, Michelangelolaan 2, 5623 EJ, Eindhoven, The Netherlands
| | - Richard van Hillegersberg
- Department of Surgery, University Medical Center Utrecht, Heidelberglaan 100, 3484 CX, Utrecht, The Netherlands
| | - Donald L van der Peet
- Department of Surgery, VU University Medical Center, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands
| | - Heike I Grabsch
- Department of Pathology, GROW - School for Oncology and Developmental Biology, Maastricht University Medical Center, P Debyelaan 25, 6229 HX, Maastricht, The Netherlands.,Department of Pathology & Tumour Biology, Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, UK
| | - Marcel Verheij
- Department of Radiation Oncology, Netherlands Cancer Institute - Antoni van Leeuwenhoek, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands.
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26
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Gastric Cancer Patients Receiving Maintenance Hemodialysis After Surgery With and Without Postoperative Chemotherapy: A Case Series of 6. Int Surg 2018. [DOI: 10.9738/intsurg-d-16-00127.1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Background:
The management of gastric cancer patients who received gastrectomy and/or postoperative chemotherapy is of high importance. However, the safety and efficacy of chemotherapy in hemodialysis patients have not been established. In this study, we report 6 cases of hemodialysis patients who underwent gastrectomy for gastric cancer.
Case Presentation:
The presented cases included 5 men and 1 woman, with a mean age of 66.3 years (range, 59–74 years). All patients underwent standard laparotomy, with 3 of 6 patients (50%) experiencing postoperative complications. Three patients who did not experience any postoperative complications could receive subsequent chemotherapy. S-1 chemotherapy regimen and uracil and tegafur chemotherapy regimen were administered to 1 and 2 patients, respectively. These 3 patients did not experience any chemotherapy-related side effects. Among the 4 patients who received a diagnosis of pathologic stages II to III, 2 patients treated with postoperative chemotherapy achieved better prognoses than those who did not receive chemotherapy (mean, 25.5 versus 5.0 months).
Discussion and Conclusion:
Hemodialysis patients with gastric cancer who received gastrectomy exhibited a high morbidity rate. Postoperative chemotherapy can be performed immediately after surgery in patients who do not experience postoperative complications. S-1 regimen and uracil and tegafur regimen could be administered safely in hemodialysis patients. Postoperative chemotherapy may lead to a good prognosis in gastric cancer patients receiving hemodialysis.
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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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Chang SC, Liu KH, Hung CY, Tsai CY, Hsu JT, Yeh TS, Chen JS, Kuo YC, Hung YS, Chou WC. Adjuvant Chemotherapy Improves Survival in Stage III Gastric Cancer after D2 Surgery. J Cancer 2018; 9:81-91. [PMID: 29290772 PMCID: PMC5743714 DOI: 10.7150/jca.21989] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2017] [Accepted: 10/09/2017] [Indexed: 12/13/2022] Open
Abstract
Background: Stage III gastric cancer is characterized by locally advanced disease with varying anatomic extent as measured by the 7th edition of the American Joint Committee on Cancer (AJCC) staging system. There are no prognostic factors specifically identified in patients with stage III gastric cancer following extended lymph node dissection (D2) surgery. Materials and Methods: From 2007 to 2014, 534 patients with stage III gastric cancer underwent radical gastrectomy and D2 dissection at the Chang Gung Memorial Hospital. Patients' characteristics and the impact of adjuvant chemotherapy were analyzed using univariate and multivariate analyses to identify variables associated with overall survival (OS) and disease-free survival (DFS). Results: There were 320 deaths (60.0%) and 284 recurrences (53.2%) by the end of the study. The median OS and DFS were 30.7 months (95% confidence interval [CI]: 27.5-33.9) and 26.4 months (95% CI: 21.2-31.6), respectively. The multivariate analysis identified 7 variables that were independent prognostic factors both for OS and DFS including ratio of metastatic lymph nodes to total resection lymph nodes, carcinoembryonic antigen level, Eastern Cooperative Oncology Group performance status, gastrectomy method, vascular invasion, surgical margin, and adjuvant chemotherapy. Patients with stage IIIA-IIIC disease who received adjuvant chemotherapy had better OS and DFS outcomes than those who did not. Conclusions: Our study identified several independent prognostic factors that might help determine the appropriate counseling patients following surgical treatment. D2 surgery alone was inadequate to achieve long-term survival. As the only correctable independent prognostic factor, postoperative adjuvant chemotherapy should be recommended for eligible patients with stage III gastric cancer.
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Affiliation(s)
- Shin-Chun Chang
- Department of Surgery, Chang Gung Memorial Hospital at Linkou, 5 Fu-Hsing Street, Kwei-Shan Shiang, Taoyuan, Taiwan
| | - Keng-Hao Liu
- Department of Surgery, Chang Gung Memorial Hospital at Linkou, 5 Fu-Hsing Street, Kwei-Shan Shiang, Taoyuan, Taiwan
| | - Chia-Yen Hung
- Department of Hematology and Oncology, Chang Gung Memorial Hospital at Linkou, 5 Fu-Hsing Street, Kwei-Shan Shiang, Taoyuan, Taiwan.,Department of Hema-Oncology, Division of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan
| | - Chun-Yi Tsai
- Department of Surgery, Chang Gung Memorial Hospital at Linkou, 5 Fu-Hsing Street, Kwei-Shan Shiang, Taoyuan, Taiwan
| | - Jun-Te Hsu
- Department of Surgery, Chang Gung Memorial Hospital at Linkou, 5 Fu-Hsing Street, Kwei-Shan Shiang, Taoyuan, Taiwan
| | - Ta-Sen Yeh
- Department of Surgery, Chang Gung Memorial Hospital at Linkou, 5 Fu-Hsing Street, Kwei-Shan Shiang, Taoyuan, Taiwan
| | - Jen-Shi Chen
- Department of Hematology and Oncology, Chang Gung Memorial Hospital at Linkou, 5 Fu-Hsing Street, Kwei-Shan Shiang, Taoyuan, Taiwan
| | - Yung-Chia Kuo
- Department of Hematology and Oncology, Chang Gung Memorial Hospital at Linkou, 5 Fu-Hsing Street, Kwei-Shan Shiang, Taoyuan, Taiwan
| | - Yu-Shin Hung
- Department of Hematology and Oncology, Chang Gung Memorial Hospital at Linkou, 5 Fu-Hsing Street, Kwei-Shan Shiang, Taoyuan, Taiwan
| | - Wen-Chi Chou
- Department of Hematology and Oncology, Chang Gung Memorial Hospital at Linkou, 5 Fu-Hsing Street, Kwei-Shan Shiang, Taoyuan, Taiwan.,Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan
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Hashimoto T, Kurokawa Y, Mori M, Doki Y. Update on the Treatment of Gastric Cancer. JMA J 2018; 1:40-49. [PMID: 33748521 PMCID: PMC7969864 DOI: 10.31662/jmaj.2018-0006] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2018] [Accepted: 08/17/2018] [Indexed: 12/12/2022] Open
Abstract
Gastric cancer remains a major health concern worldwide, particularly in Asia. Surgery is the only curative treatment, and D2 gastrectomy is the standard therapy for resectable cases. Several clinical trials have been conducted in Japan to achieve higher cure rates via extended surgery; however, despite higher morbidity, none demonstrated prolonged survival. Against this background, minimally invasive surgical approaches that preserve gastric function and improve postoperative quality of life have been developed in recent years. For early gastric cancer, endoscopic resection and laparoscopic gastrectomy have achieved remarkable success even for later-stage cases. Long-term outcomes have been investigated in large-scale, randomized controlled trials. In addition, robot-assisted gastrectomy is now more common in clinical practice. S-1, an anti-tumor drug, is a key agent for treating gastric cancer and has resulted in dramatic improvements in survival. For locally advanced gastric cancer, patients are usually treated with surgery and adjuvant or neoadjuvant chemotherapy, and the efficacies of various regimens have been examined in many clinical trials. For unresectable or recurrent gastric cancer, new agents such as molecular-targeted agents and immune checkpoint inhibitors have emerged as notable treatments and are now being tested in numerous clinical trials. This review provides an update on gastric cancer treatment, highlighting current individualized strategies and future perspectives.
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Affiliation(s)
- Tadayoshi Hashimoto
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Yukinori Kurokawa
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Masaki Mori
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Yuichiro Doki
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Osaka, Japan
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30
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Hung YS, Chang SC, Liu KH, Hung CY, Kuo YC, Tsai CY, Hsu JT, Yeh TS, Chen JS, Chou WC. A prognostic model based on lymph node metastatic ratio for predicting survival outcome in gastric cancer patients with N3b subclassification. Asian J Surg 2017; 42:85-92. [PMID: 29248301 DOI: 10.1016/j.asjsur.2017.10.001] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2017] [Revised: 09/28/2017] [Accepted: 10/11/2017] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Determining the survival outcome for gastric cancer patients with metastases to more than 15 regional lymph nodes is difficult. This study aims to develop a lymph node metastatic ratio (LNR)-based prognostic model to predict the survival outcome after D2 surgery in such patient groups. METHODS Our study retrospectively enrolled 139 gastric cancer patients with metastases to more than 15 regional lymph nodes who underwent D2 surgery between 2007 and 2014. Clinicopathologic variables to predict overall survival (OS) using multivariate Cox regression were selected to create a prognostic model. RESULTS The prognostic model for predicting OS was developed based on five independent factors, namely, T-classification (T2 or T3 vs. T4), LNR (<0.80 vs. ≥0.80), carcinoembryonic antigen level (<5 vs. ≥5 ng/ml), Eastern Cooperative Oncology Group performance scale (scale 0-1 vs. ≥2), and adjuvant chemotherapy (yes vs. no). Using the prognostic score, patients were stratified into good, intermediate, and poor prognostic groups. The median OS in the good, intermediate, and poor prognostic risk groups was 32.0 months (95% confidence interval [CI]: 22.3-41.7), 12.4 months (95% CI: 8.5-16.3), and 5.4 months (95% CI: 2.1-8.7), respectively. The c-index of the prognostic model was 0.79 (95% CI: 0.71-0.87). CONCLUSION This study developed an accurate LNR-based prognostic model for predicting the survival outcome after D2 surgery in gastric cancer patients with metastasis to more than 15 regional lymph nodes. This model might assist clinicians in prognostic stratification of such patients and convince eligible patients to receive adjuvant chemotherapy.
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Affiliation(s)
- Yu-Shin Hung
- Department of Hematology-Oncology, Chang Gung Memorial Hospital at Linkou, Taiwan
| | - Shin-Chun Chang
- Department of Surgery, Chang Gung Memorial Hospital at Linkou, Taiwan
| | - Keng-Hao Liu
- Department of Surgery, Chang Gung Memorial Hospital at Linkou, Taiwan
| | - Chia-Yen Hung
- Department of Hematology-Oncology, Chang Gung Memorial Hospital at Linkou, Taiwan; Department of Hema-Oncology, Division of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan
| | - Yung-Chia Kuo
- Department of Hematology-Oncology, Chang Gung Memorial Hospital at Linkou, Taiwan
| | - Chun-Yi Tsai
- Department of Surgery, Chang Gung Memorial Hospital at Linkou, Taiwan
| | - Jun-Te Hsu
- Department of Surgery, Chang Gung Memorial Hospital at Linkou, Taiwan
| | - Ta-Sen Yeh
- Department of Surgery, Chang Gung Memorial Hospital at Linkou, Taiwan
| | - Jen-Shi Chen
- Department of Hematology-Oncology, Chang Gung Memorial Hospital at Linkou, Taiwan
| | - Wen-Chi Chou
- Department of Hematology-Oncology, Chang Gung Memorial Hospital at Linkou, Taiwan; Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
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31
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Irino T, Takeuchi H, Terashima M, Wakai T, Kitagawa Y. Gastric Cancer in Asia: Unique Features and Management. Am Soc Clin Oncol Educ Book 2017; 37:279-291. [PMID: 28561675 DOI: 10.1200/edbk_175228] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Gastric cancer (GC) poses a burden to patients across the globe as the third leading cause of cancer deaths worldwide. Incidence of GC is particularly high in Asian countries, which is attributed to the prevalence of Helicobacter pylori (H. pylori) infection and has prompted the establishment of unique treatment strategies. D2 gastrectomy, which was established in the 1950s in Japan, has served as a gold standard for locally advanced GC for over half a century. Since the beginning of the 21st century, endoscopic resection (ER) techniques and minimally invasive laparoscopic surgery have greatly changed the treatment of patients with early GC. S-1, which showed a striking survival benefit in a large randomized trial in Japan, has been used as adjuvant therapy for the last decade. Likewise, S-1-based chemotherapy regimens are currently the standard of care for the treatment of unresectable/metastatic GC in Asia. Along with the development of standardized therapy, novel techniques and new drugs have been rapidly brought into clinical practice. State-of-the-art sentinel node (SN) navigation surgery enables clinicians to perform truly minimally invasive surgery for early GC, and appropriate chemotherapy regimens are now determined by a tumor's molecular expression. New classifications based on gene signatures are proposed and may replace conventional clinical classifications. Such highly individualized treatment has the potential to alter our clinical practice in GC in the near future. The best practice in each geographic region should be shared and integrated, resulting in the best practice without borders.
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Affiliation(s)
- Tomoyuki Irino
- From the Division of Gastric Surgery, Shizuoka Cancer Center, Shizuoka, Japan; Department of Surgery, Keio University School of Medicine, Tokyo, Japan; Division of Gastric Surgery, Shizuoka Cancer Center, Shizuoka, Japan; Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Science, Niigata, Japan; Department of Surgery, Keio University School of Medicine, Tokyo, Japan
| | - Hiroya Takeuchi
- From the Division of Gastric Surgery, Shizuoka Cancer Center, Shizuoka, Japan; Department of Surgery, Keio University School of Medicine, Tokyo, Japan; Division of Gastric Surgery, Shizuoka Cancer Center, Shizuoka, Japan; Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Science, Niigata, Japan; Department of Surgery, Keio University School of Medicine, Tokyo, Japan
| | - Masanori Terashima
- From the Division of Gastric Surgery, Shizuoka Cancer Center, Shizuoka, Japan; Department of Surgery, Keio University School of Medicine, Tokyo, Japan; Division of Gastric Surgery, Shizuoka Cancer Center, Shizuoka, Japan; Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Science, Niigata, Japan; Department of Surgery, Keio University School of Medicine, Tokyo, Japan
| | - Toshifumi Wakai
- From the Division of Gastric Surgery, Shizuoka Cancer Center, Shizuoka, Japan; Department of Surgery, Keio University School of Medicine, Tokyo, Japan; Division of Gastric Surgery, Shizuoka Cancer Center, Shizuoka, Japan; Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Science, Niigata, Japan; Department of Surgery, Keio University School of Medicine, Tokyo, Japan
| | - Yuko Kitagawa
- From the Division of Gastric Surgery, Shizuoka Cancer Center, Shizuoka, Japan; Department of Surgery, Keio University School of Medicine, Tokyo, Japan; Division of Gastric Surgery, Shizuoka Cancer Center, Shizuoka, Japan; Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Science, Niigata, Japan; Department of Surgery, Keio University School of Medicine, Tokyo, Japan
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Wang C, Xi W, Jiang J, Ji J, Yu Y, Zhu Z, Zhang J. Metronomic chemotherapy remodel cancer-associated fibroblasts to decrease chemoresistance of gastric cancer in nude mice. Oncol Lett 2017; 14:7903-7909. [PMID: 29344235 DOI: 10.3892/ol.2017.7197] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2016] [Accepted: 09/13/2017] [Indexed: 12/26/2022] Open
Abstract
The present study aimed to evaluate whether capecitabine or 5-fluorouracil (5-Fu) chemotherapy with the metronomic pattern may cause significant chemoresistance compared with the traditional pattern, and whether CAFs are involved in drug resistance. SGC-7901 cells were subcutaneously injected into the nude mice, and the mice were divided into five groups: The control group, intraperitoneally injected with normal saline; the 5-Fu conventional dose group [5-Fu maximum tolerated dose (MTD) group], intraperitoneally injected with 50 mg/kg, twice per week for 2 weeks, with an 1-week discontinuation for 6 weeks; the capecitabine conventional dose group (capecitabine MTD group), intragastric 500 mg/kg, twice per week for 2 weeks, with a 1-week discontinuation for 6 weeks; the 5-Fu metronomic group [5-Fu low-dose metronomic (LDM) group], intraperitoneally injected with 15 mg/kg, twice a week for 6 weeks; and the capecitabine metronomic group (capecitabine LDM group), intragastric administration at 200 mg/kg, twice a week for 6 weeks. The chemotherapy resistance markers [glutathione transferase Pi (GSTP) and multidrug resistance protein 1 (MDR1)] were detected by immunohistochemical staining (IHC), and the association of the expression of these markers with the chemotherapy administration patterns was analyzed. Vascular endothelial growth factor (VEGF) and the cancer-associated fibroblast (CAF) marker α-smooth muscle actin were also examined by IHC to illustrate the possible mechanism of chemoresistance. The expression of GSTP and MDR1 in the MTD groups was significantly higher compared with those of the LDM groups (P<0.01). Furthermore, the number of CAFs and the level of VEGF in the MTD groups were significantly higher compared with those of the LDM groups (P<0.05). The low dose metronomic chemotherapy did not increase the risk of chemoresistance compared with the conventional dose traditional chemotherapy in terms of capecitabine or 5-Fu, the increasing amount of CAFs in the microenvironment of cancer cell following therapy may protect cell from capecitabine or 5-Fu via producing VEGF to increase vascularization.
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Affiliation(s)
- Chao Wang
- Department of Oncology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P.R. China
| | - Wenqi Xi
- Department of Oncology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P.R. China
| | - Jinling Jiang
- Department of Oncology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P.R. China
| | - Jun Ji
- Department of Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P.R. China
| | - Yingyan Yu
- Department of Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P.R. China
| | - Zhenggang Zhu
- Department of Oncology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P.R. China.,Department of Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P.R. China
| | - Jun Zhang
- Department of Oncology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P.R. China
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Manzini G, Henne-Bruns D, Kremer M. Validity of studies suggesting postsurgical chemotherapy for resectable gastric cancer: critical appraisal of randomised trials. BMJ Open Gastroenterol 2017; 4:e000138. [PMID: 29177062 PMCID: PMC5689483 DOI: 10.1136/bmjgast-2017-000138] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2017] [Revised: 07/03/2017] [Accepted: 07/17/2017] [Indexed: 12/12/2022] Open
Abstract
Background and aim In 2013, Diaz-Nieto et al published a Cochrane review to summarise the impact of postsurgical chemotherapy versus surgery alone on survival for resectable gastric cancer. The authors concluded that postsurgical chemotherapy showed an improvement in overall survival. The aim of this article was to assess the validity of four studies included in the Cochrane review and to investigate the impact of an exclusion of these four studies on the result of the meta-analysis. Methods Overall survival was selected as endpoint of interest. Among the 34 included papers which analysed this endpoint, we identified the four publications which have the highest weights to influence the final result. The validity of these papers was analysed using the CONSORT (Consolidated Standards of Reporting Trials) checklist for randomised controlled trials. We performed a new meta-analysis without the four studies in order to assess their impact on the general result of the original meta-analysis. Results The analysed four studies revealed several inconsistencies: inappropriate answers were found in up to 77% of the items of the CONSORT checklist. Unclear or inadequate randomisation, missing blinded set-up, conflict of interest and lacking intention-to-treat analysis were the most common findings. When performing a meta-analysis excluding the four criticised studies, postsurgical chemotherapy still showed a significant improvement in overall survival. Even when excluding all single studies with a statistically significant outcome by themselves and performing a meta-analysis on the remaining 26 studies, the result remains statistically significant. Conclusion The four most powerful publications in the Cochrane review show substantial deficits. We suggest a more critical appraisal regarding the validity of single studies. However, after the exclusion of these four studies, the result of the meta-analysis did not change.
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Affiliation(s)
- Giulia Manzini
- Department of General and Visceral Surgery, Universitat Ulm, Ulm, Germany
| | - Doris Henne-Bruns
- Department of General and Visceral Surgery, Universitat Ulm, Ulm, Germany
| | - Michael Kremer
- Department of General and Visceral Surgery, Universitat Ulm, Ulm, Germany
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Jiang Y, Li T, Liang X, Hu Y, Huang L, Liao Z, Zhao L, Han Z, Zhu S, Wang M, Xu Y, Qi X, Liu H, Yang Y, Yu J, Liu W, Cai S, Li G. Association of Adjuvant Chemotherapy With Survival in Patients With Stage II or III Gastric Cancer. JAMA Surg 2017; 152:e171087. [PMID: 28538950 DOI: 10.1001/jamasurg.2017.1087] [Citation(s) in RCA: 102] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Importance The current staging system of gastric cancer is not adequate for defining a prognosis and predicting the patients most likely to benefit from chemotherapy. Objective To construct a survival prediction model based on specific tumor and patient characteristics that enables individualized predictions of the net survival benefit of adjuvant chemotherapy for patients with stage II or stage III gastric cancer. Design, Setting, and Participants In this multicenter retrospective analysis, a survival prediction model was constructed using data from a training cohort of 746 patients with stage II or stage III gastric cancer who satisfied the study's inclusion criteria and underwent surgery between January 1, 2004, and December 31, 2012, at Nanfang Hospital in Guangzhou, China. Patient and tumor characteristics were included as covariates, and their association with overall survival and disease-free survival with and without adjuvant chemotherapy was assessed. The model was internally validated for discrimination and calibration using bootstrap resampling. To externally validate the model, data were included from a validation cohort of 973 patients with stage II or stage III gastric cancer who met the inclusion criteria and underwent surgery at First Affiliated Hospital in Guangzhou, China, and at West China Hospital of Sichuan Hospital in Chendu, China, between January 1, 2000, and June 30, 2009. Data were analyzed from July 10, 2016, to September 1, 2016. Main Outcomes and Measures Concordance index and decision curve analysis for each measure associated with postoperative overall survival and disease-free survival. Results Of the 1719 patients analyzed, 1183 (68.8%) were men and 536 (31.2%) were women and the median (interquartile range) age was 57 (49-66) years. Age, location, differentiation, carcinoembryonic antigen, cancer antigen 19-9, depth of invasion, lymph node metastasis, and adjuvant chemotherapy were significantly associated with overall survival and disease-free survival, with P < .05. The survival prediction model demonstrated good calibration and discrimination, with relatively high bootstrap-corrected concordance indexes in the training and validation cohorts. In the validation cohort, the concordance index for overall survival was 0.693 (95% CI, 0.671-0.715) and for disease-free survival was 0.704 (95% CI, 0.681-0.728). Two nomograms and a calculating tool were built on the basis of specific input variables to estimate an individual's net survival gain attributable to adjuvant chemotherapy. Conclusions and Relevance The survival prediction model can be used to make individualized predictions of the expected survival benefit from the addition of adjuvant chemotherapy for patients with stage II or stage III gastric cancer.
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Affiliation(s)
- Yuming Jiang
- Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China2Guangdong Key Laboratory of Liver Disease Research, Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Tuanjie Li
- Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China2Guangdong Key Laboratory of Liver Disease Research, Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Xiaoling Liang
- Department of Pharmacy, Nanfang Hospital, Southern Medical University, Guangzhou, China4School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, China
| | - Yanfeng Hu
- Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Lei Huang
- German Cancer Research Center (Deutsches Krebsforschungszentrum), Heidelberg, Germany
| | - Zhenchen Liao
- Department of Biomedical Engineering, Southern Medical University, Guangzhou, China
| | - Liying Zhao
- Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Zhen Han
- Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Shuguang Zhu
- Guangdong Key Laboratory of Liver Disease Research, Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China7Department of Hepatic Surgery, Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Menglan Wang
- Guangdong Key Laboratory of Liver Disease Research, Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China8Department of Infectious Disease, Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Yangwei Xu
- Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China
| | - Xiaolong Qi
- Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Hao Liu
- Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Yang Yang
- Guangdong Key Laboratory of Liver Disease Research, Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China7Department of Hepatic Surgery, Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Jiang Yu
- Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Wei Liu
- Guangdong Key Laboratory of Liver Disease Research, Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China7Department of Hepatic Surgery, Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Shirong Cai
- Department of Gastrointestinal Surgery, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Guoxin Li
- Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China
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Evolution in the surgical management of gastric cancer: is extended lymph node dissection back in vogue in the USA? World J Surg Oncol 2017; 15:135. [PMID: 28716043 PMCID: PMC5514466 DOI: 10.1186/s12957-017-1204-6] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2016] [Accepted: 07/08/2017] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Gastric cancer remains a formidable treatment challenge. For decades, treatment consisted mostly of surgical intervention for this deadly disease. With improvements in the multi-disciplinary management of solid organ malignancies, the approach to this disease is being stepwise refined. MAIN BODY One of the prevalent controversies in the surgical management of gastric cancer rests on the need for adequate harvesting of lymph nodes. For decades, lymph node dissection is regarded as a staging technique useful in only upstaging the disease. The adoption of D2 lymphadenectomy has been particularly slow to mature. But with prevailing data from Asia consistently demonstrating a survival benefit from lymphadenectomy, it calls into question the notion of lymphadenectomy as being solely a staging procedure. CONCLUSIONS As gastric resection techniques are being better defined in western countries and surgical morbidities lowered on its execution, D2 lymphadenectomy is becoming more accepted as the new standard in the management of gastric cancer.
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Kurokawa Y, Sasako M. The Asian Perspective on the Surgical and Adjuvant Management of Esophagogastric Cancer. Surg Oncol Clin N Am 2017; 26:213-224. [PMID: 28279465 DOI: 10.1016/j.soc.2016.10.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
In East Asia, D2 dissection has been routine surgical procedure for curable advanced gastric cancer. More extended surgery than D2 is reserved for borderline resectable disease with extended nodal metastasis. The addition of radiation therapy to adjuvant chemotherapy failed to improve the outcome after D2 dissection. Because many patients are diagnosed in East Asia with early-stage disease, postoperative adjuvant chemotherapy is preferred, and S-1 monotherapy or capecitabine-oxaliplatin is standard care. Neoadjuvant chemotherapy may be preferred for stage III tumors; for borderline resectable tumors, preoperative chemotherapy is under study given the limitations of postoperative adjuvant chemotherapy in high-risk patients.
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Affiliation(s)
- Yukinori Kurokawa
- Department of Gastrointestinal Surgery, Osaka University Graduate School of Medicine, 2-2, Yamadagaoka, Suita, Osaka Prefecture 565-0871, Japan
| | - Mitsuru Sasako
- Department of Multidisciplinary Surgical Oncology, Hyogo College of Medicine, 1-1, Mukogawacho, Nishinomiya, Hyogo Prefecture 663-8501, Japan.
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Qu J, Qu X. The predictors of response to neoadjuvant chemotherapy in patients with locally advanced gastric cancer. Cancer Biomark 2017; 17:49-54. [PMID: 27314292 DOI: 10.3233/cbm-160616] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
Abstract
BACKGROUND Chemotherapy-sensitivity test is crucial to screen out patients who are insensitive to the treatment and to avoid unnecessary preoperative chemotherapy. OBJECTIVE To investigate the predictors for the response to mFOLFOX7 neoadjuvant chemotherapy (NACT) in advanced gastric cancer. METHODS The expression of C-met, EGFR, HER2, Ki-67, MMP7, P53 and TOPOII in tumor tissue from 53 locally advanced gastric cancer patients (AGC) was detected by immunohistochemistry. The relationship between tumor marker expression and the efficacy of NACT was determined by chi-square test and multivariate logistic regression analysis. The relationship between the combined expression of HER2 and P53 and the efficacy of NACT was further analyzed by chi-square test. RESULTS The overall response rate was 52.8% (28/53). There were no significant differences of tumor markers' expression before and after chemotherapy (P> 0.05). The response rate in HER2-positive patients (83.33%) was significantly higher than that in HER2-negative patients (43.90%, P= 0.016), whereas the response rate in P53-positive patients (35.71%) was significantly lower than that in P53-negative patients (72.0%, P= 0.008). Moreover, the response rate was the highest in the patients who were positive for HER2 but negative for P53. CONCLUSION HER2 and P53 were identified as independent predictors for the response to mFOLFOX7 NACT in AGC.
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Affiliation(s)
- Jianjun Qu
- Department of oncology, Weifang People's Hospital, Weifang, Shandong, China
| | - Xiangyang Qu
- Department of medicine, Weifang Second People's Hospital, Weifang, Shandong, China
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Hu X, Chen L, Du Y, Fan B, Bu Z, Wang X, Ye Y, Zhang Z, Xiao G, Li F, He Q, Li G, Shen X, Xiong B, Zhu L, Liu J, Liu L, Wu T, Zhou J, Zhang J, Zhao G, Wang X, Liang P, Wang X, Zhang Y, Wu X, Zhang J, Ji X, Zong X, Fu T, Jia Z, Ji J. Postoperative chemotherapy with S-1 plus oxaliplatin versus S-1 alone in locally advanced gastric cancer (RESCUE-GC study): a protocol for a phase III randomized controlled trial. Chin J Cancer Res 2017; 29:144-148. [PMID: 28536493 PMCID: PMC5422416 DOI: 10.21147/j.issn.1000-9604.2017.02.07] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
BACKGROUND The ACTS-GC study had shown postoperative adjuvant therapy with S-1 improved survival of patients with locally advanced gastric cancer. Addition of oxaliplatin to S-1 is considered to be acceptable as one of the treatment options for gastric cancer patients after radical gastrectomy with D2 lymph node excision. METHODS We have commenced a randomized phase III trial in December 2016 to evaluate S-1 plus oxaliplatin compared with S-1 alone in the adjuvant setting for locally advanced gastric cancer. A total of 564 patients will be accrued from 13 Chinese institutions in two years. The primary endpoint is 3-year relapse-free survival. The secondary endpoints are 5-year overall survival, proportion of patients who complete the postoperative chemotherapy and incidence of adverse events. ETHIC AND DISSEMINATION The trial has been approved by the institutional review board of each participating institution and it was activated on December, 2016. The enrollment will be finished in December, 2018. Patient's follow-up will be ended until December, 2023. TRIAL REGISTRATION ClinicalTrials.gov, identifier: NCT02867839. Registered on August 4, 2016.
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Affiliation(s)
- Xiang Hu
- Department of Gastrointestinal Surgery, the First Affiliated Hospital of Dalian Medical University, Dalian 116011, China
| | - Lin Chen
- Department of Gastrointestinal Surgery, the First Affiliated Hospital of Dalian Medical University, Dalian 116011, China
| | - Yian Du
- Department of Gastrointestinal Surgery, the First Affiliated Hospital of Dalian Medical University, Dalian 116011, China
| | - Biao Fan
- Department of Gastrointestinal Surgery, the First Affiliated Hospital of Dalian Medical University, Dalian 116011, China
| | - Zhaode Bu
- Department of Gastrointestinal Surgery, the First Affiliated Hospital of Dalian Medical University, Dalian 116011, China
| | - Xin Wang
- Department of Gastrointestinal Surgery, the First Affiliated Hospital of Dalian Medical University, Dalian 116011, China
| | - Yingjiang Ye
- Department of Gastrointestinal Surgery, the First Affiliated Hospital of Dalian Medical University, Dalian 116011, China
| | - Zhongtao Zhang
- Department of Gastrointestinal Surgery, the First Affiliated Hospital of Dalian Medical University, Dalian 116011, China
| | - Gang Xiao
- Department of Gastrointestinal Surgery, the First Affiliated Hospital of Dalian Medical University, Dalian 116011, China
| | - Fei Li
- Department of Gastrointestinal Surgery, the First Affiliated Hospital of Dalian Medical University, Dalian 116011, China
| | - Qingsi He
- Department of Gastrointestinal Surgery, the First Affiliated Hospital of Dalian Medical University, Dalian 116011, China
| | - Guoli Li
- Department of Gastrointestinal Surgery, the First Affiliated Hospital of Dalian Medical University, Dalian 116011, China
| | - Xian Shen
- Department of Gastrointestinal Surgery, the First Affiliated Hospital of Dalian Medical University, Dalian 116011, China
| | - Bin Xiong
- Department of Gastrointestinal Surgery, the First Affiliated Hospital of Dalian Medical University, Dalian 116011, China
| | - Liming Zhu
- Department of Gastrointestinal Surgery, the First Affiliated Hospital of Dalian Medical University, Dalian 116011, China
| | - Jiwei Liu
- Department of Gastrointestinal Surgery, the First Affiliated Hospital of Dalian Medical University, Dalian 116011, China
| | - Lian Liu
- Department of Gastrointestinal Surgery, the First Affiliated Hospital of Dalian Medical University, Dalian 116011, China
| | - Tao Wu
- Department of Gastrointestinal Surgery, the First Affiliated Hospital of Dalian Medical University, Dalian 116011, China
| | - Jing Zhou
- Department of Gastrointestinal Surgery, the First Affiliated Hospital of Dalian Medical University, Dalian 116011, China
| | - Jun Zhang
- Department of Gastrointestinal Surgery, the First Affiliated Hospital of Dalian Medical University, Dalian 116011, China
| | - Gang Zhao
- Department of Gastrointestinal Surgery, the First Affiliated Hospital of Dalian Medical University, Dalian 116011, China
| | - Xulin Wang
- Department of Gastrointestinal Surgery, the First Affiliated Hospital of Dalian Medical University, Dalian 116011, China
| | - Pin Liang
- Department of Gastrointestinal Surgery, the First Affiliated Hospital of Dalian Medical University, Dalian 116011, China
| | - Xinxin Wang
- Department of Gastrointestinal Surgery, the First Affiliated Hospital of Dalian Medical University, Dalian 116011, China
| | - Yan Zhang
- Department of Gastrointestinal Surgery, the First Affiliated Hospital of Dalian Medical University, Dalian 116011, China
| | - Xiaojiang Wu
- Department of Gastrointestinal Surgery, the First Affiliated Hospital of Dalian Medical University, Dalian 116011, China
| | - Ji Zhang
- Department of Gastrointestinal Surgery, the First Affiliated Hospital of Dalian Medical University, Dalian 116011, China
| | - Xin Ji
- Department of Gastrointestinal Surgery, the First Affiliated Hospital of Dalian Medical University, Dalian 116011, China
| | - Xianglong Zong
- Department of Gastrointestinal Surgery, the First Affiliated Hospital of Dalian Medical University, Dalian 116011, China
| | - Tao Fu
- Department of Gastrointestinal Surgery, the First Affiliated Hospital of Dalian Medical University, Dalian 116011, China
| | - Ziyu Jia
- Department of Gastrointestinal Surgery, the First Affiliated Hospital of Dalian Medical University, Dalian 116011, China
| | - Jiafu Ji
- Department of Gastrointestinal Surgery, the First Affiliated Hospital of Dalian Medical University, Dalian 116011, China
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Shida M, Yasuda M, Fujita M, Miyazawa M, Kajiwara H, Hirasawa T, Ikeda M, Matsui N, Muramatsu T, Mikami M. Possible role of thymidine phosphorylase in gynecological tumors as an individualized treatment strategy. Oncol Lett 2016; 12:3215-3223. [PMID: 27899985 PMCID: PMC5103922 DOI: 10.3892/ol.2016.5082] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2015] [Accepted: 04/01/2016] [Indexed: 11/30/2022] Open
Abstract
Thymidine phosphorylase (TP) is structurally similar to platelet-derived endothelial cell growth factor, and it activates 5-fluorouracil (5-FU) prodrugs and also promotes angiogenesis. In the present study, the possibility of using TP expression as a biomarker for 5-FU prodrugs, and the significance of TP as an angiogenic factor, were investigated in patients with gynecological tumors. The subjects enrolled in the study were 188 patients with gynecological tumors who provided informed consent and underwent tumor resection at the Department of Obstetrics and Gynecology of Tokai University Hospital between February 2002 and January 2010. Measurement of the enzymatic activity of TP and dihydropyrimidine dehydrogenase (DPD) was performed by enzyme-linked immunosorbent assay. In addition, immunohistochemistry (IHC) analysis of microvessels by monochrome imaging, western blotting and reverse transcription-polymerase chain reaction were performed. The mean TP activity and the TP/DPD ratio were increased in squamous cell carcinoma of the cervix (306.9 and 2.2 U/mg protein, respectively) and adenosquamous carcinoma (317.6 and 1.4 U/mg protein, respectively) compared with benign tumors and other malignancies, including endometrial (uterine) carcinoma, ovarian serous adenocarcinoma and ovarian mucinous adenocarcinoma. However, these parameters were also elevated in other histological types of cancer such as clear cell adenocarcinoma of the ovary (115.2 and 2.1 U/mg protein, respectively), in which the microvessel area was the largest of all the histological types analyzed. Since high TP expression and a high TP/DPD ratio were identified in other tumors besides cervical cancer, it is possible that patients for whom 5-FU prodrugs are indicated could be selected appropriately if their TP activity is determined and their TP expression is analyzed by IHC prior to initiation of the treatment.
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Affiliation(s)
- Masako Shida
- Department of Obstetrics and Gynecology, Tokai University School of Medicine, Isehara, Kanagawa 259-1193, Japan
| | - Masanori Yasuda
- Department of Pathology, Saitama Medical University International Medical Center, Hidaka, Saitama 350-1298, Japan
| | - Mariko Fujita
- Department of Obstetrics and Gynecology, Tokai University School of Medicine, Isehara, Kanagawa 259-1193, Japan
| | - Masaki Miyazawa
- Department of Obstetrics and Gynecology, Tokai University School of Medicine, Isehara, Kanagawa 259-1193, Japan
| | - Hiroshi Kajiwara
- Department of Pathology, Tokai University School of Medicine, Isehara, Kanagawa 259-1193, Japan
| | - Takeshi Hirasawa
- Department of Obstetrics and Gynecology, Tokai University School of Medicine, Isehara, Kanagawa 259-1193, Japan
| | - Masae Ikeda
- Department of Obstetrics and Gynecology, Tokai University School of Medicine, Isehara, Kanagawa 259-1193, Japan
| | - Naruaki Matsui
- Department of Pathology, Tokai University Oiso Hospital, Oiso, Kanagawa 259-0198, Japan
| | - Toshinari Muramatsu
- Department of Obstetrics and Gynecology, Tokai University Hachioji Hospital, Hachioji, Tokyo 192-0032, Japan
| | - Mikio Mikami
- Department of Obstetrics and Gynecology, Tokai University School of Medicine, Isehara, Kanagawa 259-1193, Japan
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Mahlberg R, Lorenzen S, Thuss-Patience P, Heinemann V, Pfeiffer P, Möhler M. New Perspectives in the Treatment of Advanced Gastric Cancer: S-1 as a Novel Oral 5-FU Therapy in Combination with Cisplatin. Chemotherapy 2016; 62:62-70. [PMID: 27643822 DOI: 10.1159/000443984] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2015] [Accepted: 01/12/2016] [Indexed: 11/19/2022]
Abstract
Oral fluoropyrimidines have been available for more than 10 years. Capecitabine is well established in treating solid tumors in Europe. S-1 (Teysuno®), an oral formulation containing the 5-fluorouracil (5-FU) prodrug tegafur and the two enzyme modulators gimeracil and oteracil, has not been available in non-Asia countries until recently. In Japan, S-1 in combination with cisplatin is the recommended first-line treatment in patients with gastric cancer. In Europe, the first trials with S-1 were disappointing due to high unacceptable incidences of adverse events. Pharmacokinetic studies showed differences in Asian and Caucasian patients; therefore, a new non-Asian study program was initiated, which led to the pivotal phase 3 trial First-Line Advanced Gastric Cancer Study (FLAGS). In FLAGS, 1,053 patients with advanced gastric cancer from 24 non-Asian countries were enrolled. S-1 plus cisplatin showed no overall survival (OS) benefit when compared to 5-FU plus cisplatin. The primary endpoint superior OS was not met but better tolerability was shown. A post hoc noninferiority OS and safety analysis showed that S-1 plus cisplatin has the same efficacy as 5-FU plus cisplatin but a more favorable safety profile. This led to the approval of S-1 in combination with cisplatin in gastric cancer in Europe in 2011. This article reviews the mode of action of S-1, pivotal study results from an EU point of view, and future perspectives.
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Affiliation(s)
- Rolf Mahlberg
- First Department of Medicine, Mutterhaus der Borromäerinnen, Trier, Germany
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Abstract
Gastric cancer is one of the main causes of cancer-related deaths worldwide. Even when diagnosed as a localized disease and resected with the intent to cure, recurrences frequently arise due to undetected or invisible micrometastases. Importantly, several proposed multimodal strategies to eliminate micrometastases have met some clinical success. However, while pivotal Phase III clinical trials comparing adjuvant therapies with surgery alone have confirmed the overall benefit of adjunctive treatments in patients with locally advanced gastric cancer, further improvement in postoperative outcomes is required, particularly in stage III disease. This review presents the current status of multimodal treatment strategies, with a particular focus on unresolved issues, based on updated literature searches and analysis of clinical trial databases.
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Affiliation(s)
- Mitsuro Kanda
- a 1 Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan
| | - Yasuhiro Kodera
- a 1 Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan
| | - Junichi Sakamoto
- b 2 Tokai Central Hospital, 4-6-2 Sohara Higashijima-cho, Kakamigahara, Gifu 504-8601, Japan
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42
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Lichthardt S, Kerscher A, Dietz UA, Jurowich C, Kunzmann V, von Rahden BHA, Germer CT, Wiegering A. Original article: role of adjuvant chemotherapy in a perioperative chemotherapy regimen for gastric cancer. BMC Cancer 2016; 16:650. [PMID: 27538392 PMCID: PMC4991066 DOI: 10.1186/s12885-016-2708-0] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2016] [Accepted: 08/11/2016] [Indexed: 11/17/2022] Open
Abstract
Background Multimodal treatment strategies – perioperative chemotherapy (CTx) and radical surgery – are currently accepted as treatment standard for locally advanced gastric cancer. However, the role of adjuvant postoperative CTx (postCTx) in addition to neoadjuvant preoperative CTx (preCTx) in this setting remains controversial. Methods Between 4/2006 and 12/2013, 116 patients with locally advanced gastric cancer were treated with preCTx. 72 patients (62 %), in whom complete tumor resection (R0, subtotal/total gastrectomy with D2-lymphadenectomy) was achieved, were divided into two groups, one of which receiving adjuvant therapy (n = 52) and one without (n = 20). These groups were analyzed with regard to survival and exclusion criteria for adjuvant therapy. Results Postoperative complications, as well as their severity grade, did not correlate with fewer postCTx cycles administered (p = n.s.). Long-term survival was shorter in patients receiving postCTx in comparison to patients without postCTx, but did not show statistical significance. In per protocol analysis by excluding two patients with perioperative death, a shorter 3-year survival rate was observed in patients receiving postCTx compared to patients without postCTx (3-year survival: 71.2 % postCTx group vs. 90.0 % non-postCTx group; p = 0.038). Conclusion These results appear contradicting to the anticipated outcome. While speculative, they question the value of post-CTx. Prospectively randomized studies are needed to elucidate the role of postCTx.
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Affiliation(s)
- Sven Lichthardt
- Department of General, Visceral, Vascular and Pediatric Surgery, University Hospital, University of Wuerzburg, Oberduerrbacherstr.6, 97080, Wuerzburg, Germany
| | - Alexander Kerscher
- Comprehensive Cancer Centre Mainfranken, University Hospital, University of Wuerzburg, Josef-Schneiderstr. 6, 97080, Wuerzburg, Germany
| | - Ulrich A Dietz
- Department of General, Visceral, Vascular and Pediatric Surgery, University Hospital, University of Wuerzburg, Oberduerrbacherstr.6, 97080, Wuerzburg, Germany
| | - Christian Jurowich
- Department of General, Visceral, Vascular and Pediatric Surgery, University Hospital, University of Wuerzburg, Oberduerrbacherstr.6, 97080, Wuerzburg, Germany
| | - Volker Kunzmann
- Comprehensive Cancer Centre Mainfranken, University Hospital, University of Wuerzburg, Josef-Schneiderstr. 6, 97080, Wuerzburg, Germany.,Department of Internal Medicine II, University of Wuerzburg Medical Center, Oberduerrbacherstr.2, 97080, Wuerzburg, Germany
| | - Burkhard H A von Rahden
- Department of General, Visceral, Vascular and Pediatric Surgery, University Hospital, University of Wuerzburg, Oberduerrbacherstr.6, 97080, Wuerzburg, Germany
| | - Christoph-Thomas Germer
- Department of General, Visceral, Vascular and Pediatric Surgery, University Hospital, University of Wuerzburg, Oberduerrbacherstr.6, 97080, Wuerzburg, Germany.,Comprehensive Cancer Centre Mainfranken, University Hospital, University of Wuerzburg, Josef-Schneiderstr. 6, 97080, Wuerzburg, Germany
| | - Armin Wiegering
- Department of General, Visceral, Vascular and Pediatric Surgery, University Hospital, University of Wuerzburg, Oberduerrbacherstr.6, 97080, Wuerzburg, Germany. .,Department of Biochemistry and Molecular Biology, University of Wuerzburg, Am Hubland, 97074, Wuerzburg, Germany.
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Predictive factors for recurrence in T2N0 and T3N0 gastric cancer patients. Langenbecks Arch Surg 2016; 401:823-8. [PMID: 27460840 DOI: 10.1007/s00423-016-1480-6] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2015] [Accepted: 07/12/2016] [Indexed: 12/12/2022]
Abstract
PURPOSE Adjuvant chemotherapy is an indispensable component of treatment for preventing recurrence in advanced gastric cancer patients after macroscopically complete tumor resection (R0). However, the efficacy of this treatment for patients with T2N0 and T3N0 gastric cancer is not well characterized. METHODS This study examined 1019 T1, 126 T2N0, and 67 T3N0 gastric adenocarcinoma patients who underwent gastrectomies at our institution between 1975 and 2005 to determine the predictive factors for recurrence in T2N0 and T3N0 gastric cancer patients. RESULTS Among 193 T2N0 and T3N0 patients, 14 patients (7.3 %) have recurred. The prevalence of ly2/3 and v2/3 was significantly higher in patients with recurrence compared with those without recurrence. The prognosis for either T2N0 or T3N0 gastric cancer patients was significantly worse than that for T1 gastric cancer patients. Multivariate analysis indicated that lymphatic and blood vessel invasion were independent prognostic indicators in T2N0 and T3N0 gastric cancer patients. Ten-year survival rates for T2N0 and T3N0 gastric cancer patients with both ly2/3 and v2/3, with either ly2/3 or v2/3, and without ly2/3 and v2/3 were 42.9, 86.1, and 96.7 %, respectively. T2N0 and T3N0 gastric cancer patients with both ly2/3 and v2/3 had a significantly worse prognosis than that of patients with either ly2/3 or v2/3 and those without ly2/3 and v2/3. CONCLUSIONS Our data indicate that T2N0 and T3N0 patients with both ly2/3 and v2/3 have a high risk of recurrence. Therefore, adjuvant chemotherapy should be administered to these patients.
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Chang SH, Kim SN, Choi HJ, Park M, Kim RB, Go SI, Lee WS. Adjuvant Chemotherapy for Advanced Gastric Cancer in Elderly and Non-elderly Patients: Meta-Analysis of Randomized Controlled Trials. Cancer Res Treat 2016; 49:263-273. [PMID: 27384158 PMCID: PMC5266393 DOI: 10.4143/crt.2016.054] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2016] [Accepted: 05/27/2016] [Indexed: 02/07/2023] Open
Abstract
PURPOSE This study evaluated the benefits of adjuvant chemotherapy on elderly patients with advanced gastric cancer (AGC) using meta-analysis of well-designed randomized controlled clinical studies. MATERIALS AND METHODS PubMed, Embase, and Cochrane were searched to retrieve clinical studies evaluating the benefits of adjuvant chemotherapy in the elderly with AGC. Hazards ratios (HRs) with 95% confidence intervals (CIs) were pooled across studies using a fixed-effects model. RESULTS Two studies were included in this meta-analysis to estimate HR for the overall survival (OS), and relapse-free survival (RFS) between adjuvant chemotherapy and surgery in elderly and non-elderly patients. HR for OS in the elderly and non-elderly was 0.745 (95% CI, 0.552 to 1.006, p=0.055) and 0.636 (95% CI, 0.522 to 0.776; p < 0.001), respectively, which showed no heterogeneity regarding HR between the two groups (pinteraction=0.389). HR for RFS in the elderly and non-elderly was 0.613 (95% CI, 0.466 to 0.806; p < 0.001) and 0.633 (95% CI, 0.533 to 0.753; p < 0.001), respectively (pinteraction=0.846). CONCLUSION Meta-analysis suggests that the benefit of adjuvant chemotherapy to the elderly is not big enough to reach statistical significance while the HR for OS is less than 1 (0.745) and no heterogeneity are observed regarding the HR between the elderly and non-elderly patients.
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Affiliation(s)
- Seong-Hwan Chang
- Department of Surgery, Konkuk University School of Medicine, Seoul, Korea
| | - Soo-Nyung Kim
- Department of Obstetrics and Gynecology, Konkuk University School of Medicine, Seoul, Korea
| | - Hye Jung Choi
- Department of Internal Medicine, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju, Korea
| | - Misuk Park
- Medical Library, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju, Korea
| | - Rock Bum Kim
- Department of Preventive Medicine and Environmental Health, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju, Korea
| | - Se-Il Go
- Department of Internal Medicine, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju, Korea
| | - Won Sup Lee
- Department of Internal Medicine, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju, Korea
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Chiu CF, Yang HR, Yang MD, Jeng LB, Sargeant AM, Yeh SP, Bai LY. The role of adjuvant chemotherapy for patients with stage II and stage III gastric adenocarcinoma after surgery plus D2 lymph node dissection: a real-world observation. SPRINGERPLUS 2016; 5:728. [PMID: 27375997 PMCID: PMC4909665 DOI: 10.1186/s40064-016-2552-3] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/06/2016] [Accepted: 06/09/2016] [Indexed: 12/23/2022]
Abstract
Background The influence of adjuvant chemotherapy on the survival of gastric adenocarcinoma patients in a stage-specific manner is controversial. Methods To further explore this topic, we retrospectively analyzed the impact of adjuvant chemotherapy on the clinical outcomes of 77 stage II and 117 stage III patients diagnosed between January 2008 and December 2012. Results All 194 patients underwent radical operation plus D2 dissection, and were followed a median time of 23.3 (range 0.4–80.2) months. Median patient age was 67.7 (range 33.9–97.5) years. Adjuvant chemotherapy prolonged the relapse-free survival [22.9 (95 % confidence interval 9.4–36.4) vs. 14.2 (95 % CI 8.6–19.8) months, P = 0.009] and overall survival [32.3 (95 % CI 22.6–42.0) vs. 13.4 (95 % CI 9.5–17.2) months, P < 0.001] for patients with stage III, but not stage II, disease. Higher overall survival from adjuvant chemotherapy in stage II patients with node involvement did not reach the level of statistical significance (P = 0.102). To reduce the selection bias, 142 patients aged <75 years were included in a subgroup analysis in which the benefit of adjuvant chemotherapy on relapse-free survival and overall survival were demonstrated for patients with stage III disease. Conclusions Adjuvant chemotherapy prolongs relapse-free and overall survival for patients with stage III gastric cancer in a real-world situation. Tailoring therapy based on different characteristics for patients with stage II gastric cancer may produce better outcomes.
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Affiliation(s)
- Chang-Fang Chiu
- Division of Hematology and Oncology, Department of Internal Medicine, China Medical University Hospital, 2, Yude Road, Taichung, 40402 Taiwan ; Cancer Center, China Medical University Hospital, Taichung, 40402 Taiwan ; College of Medicine, School of Medicine, China Medical University, Taichung, 40402 Taiwan
| | - Horng-Ren Yang
- Department of Surgery, China Medical University Hospital, Taichung, 40402 Taiwan
| | - Mei-Due Yang
- Department of Surgery, China Medical University Hospital, Taichung, 40402 Taiwan
| | - Long-Bin Jeng
- Department of Surgery, China Medical University Hospital, Taichung, 40402 Taiwan
| | - Aaron M Sargeant
- Charles River Laboratories, Preclinical Services, Spencerville, OH 45887 USA
| | - Su-Peng Yeh
- Division of Hematology and Oncology, Department of Internal Medicine, China Medical University Hospital, 2, Yude Road, Taichung, 40402 Taiwan ; College of Medicine, School of Medicine, China Medical University, Taichung, 40402 Taiwan
| | - Li-Yuan Bai
- Division of Hematology and Oncology, Department of Internal Medicine, China Medical University Hospital, 2, Yude Road, Taichung, 40402 Taiwan ; College of Medicine, School of Medicine, China Medical University, Taichung, 40402 Taiwan
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Borrmann type IV gastric cancer should be classified as pT4b disease. J Surg Res 2016; 203:258-67. [PMID: 27363630 DOI: 10.1016/j.jss.2016.04.026] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2016] [Revised: 03/26/2016] [Accepted: 04/14/2016] [Indexed: 02/06/2023]
Abstract
BACKGROUND The impact of macroscopic pathologic features of primary tumor that could be obtained preoperatively on pT classification has not been reported so far. The aim of this study was to investigate the feasibility of incorporation of Borrmann type IV gastric cancer into the pT classification. MATERIALS AND METHODS Clinicopathologic and prognostic data of 1622 patients with advanced gastric cancer who underwent radical surgery were retrospectively studied. RESULTS Of 1622 patients, 135 (8.32%) patients were classified as having Borrmann type IV gastric cancer. We first confirmed that Borrmann type IV gastric cancer was one of the independent prognostic factors for patients with advanced gastric cancer who underwent radical surgery. Interestingly, we found that overall survival of patients with Borrmann type IV gastric cancer could be clearly distinguished by pN classification and pathological TNM stage but not by pT classification. Importantly, further analysis demonstrated that the prognosis of Borrmann type IV gastric cancers was homogeneous with that of pT4b cancers but poorer than pT2, pT3, pT4a cancers. Therefore, we proposed a novel pT classification in which pT4b disease was defined as cancers that were Borrmann type IV or those that had invaded adjacent structures. Two-step multivariate analysis demonstrated that the novel pT classification was more suitable for prognostic assessment than the original classification. CONCLUSIONS Classifying Borrmann type IV gastric cancer as pT4b disease improves pT classification prediction of prognosis in patients with advanced gastric cancer after radical surgery.
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Lin JS, Cheng CY, Liu CJ. Oral uracil and tegafur as postoperative adjuvant metronomic chemotherapy in patients with advanced oral squamous cell carcinoma. J Dent Sci 2015. [DOI: 10.1016/j.jds.2015.03.004] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
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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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Sakaguchi I, Motohara T, Saito F, Takaishi K, Fukumatsu Y, Tohya T, Shibata S, Mimori H, Tashiro H, Katabuchi H. High-dose oral tegafur-uracil maintenance therapy in patients with uterine cervical cancer. J Gynecol Oncol 2015; 26:193-200. [PMID: 25686399 PMCID: PMC4510335 DOI: 10.3802/jgo.2015.26.3.193] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2014] [Revised: 01/08/2015] [Accepted: 01/22/2015] [Indexed: 11/30/2022] Open
Abstract
Objective The aim of this study was to determine the efficacy and toxicity of oral administration of tegafur-uracil (UFT) at a high dose, 600 mg/day, based on the tegafur dose, against uterine cervical cancer. Methods This study consisted of a retrospective analysis. From April 1986 to March 1997, 309 patients with uterine cervical cancer were registered. Oral UFT was administered to 162 patients for maintenance therapy after an initial treatment (the UFT group). The other 147 patients were not treated with UFT (the control group). The survival rate was calculated for both groups and statistically analyzed using the log-rank test. Adverse events were compared between the UFT and control groups. Results In the UFT group, 103 patients (63.6%) received UFT for ≥90 days. The drug dose was 600 mg/day for 137 patients (84.6%) and 300 to 400 mg/day for the remainder. The overall survival rate was significantly higher in the UFT group than in the control group (p<0.05). The prognosis was particularly favorable in stage III cases, in cases of squamous cell carcinoma, and in cases that were treated by radiotherapy. The most frequent side effects were nausea/vomiting (12.2%), appetite loss (10.1%), and leukopenia/neutropenia (5.8%). Conclusion High-dose oral UFT maintenance treatment prolonged the disease-free survival and overall survival of patients with uterine cervical cancer, particularly of those with advanced disease.
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Affiliation(s)
- Isao Sakaguchi
- Department of Obstetrics and Gynecology, Kumamoto University Faculty of Life Sciences, Kumamoto, Japan.
| | - Takeshi Motohara
- Department of Obstetrics and Gynecology, Kumamoto University Faculty of Life Sciences, Kumamoto, Japan
| | - Fumitaka Saito
- Department of Obstetrics and Gynecology, Kumamoto University Faculty of Life Sciences, Kumamoto, Japan
| | - Kiyomi Takaishi
- Department of Obstetrics and Gynecology, Kumamoto University Faculty of Life Sciences, Kumamoto, Japan
| | - Yukitoshi Fukumatsu
- Department of Obstetrics and Gynecology, Japanese Red Cross Kumamoto Hospital, Kumamoto, Japan
| | - Toshimitsu Tohya
- Department of Obstetrics and Gynecology, Kumamoto Rosai Hospital, Yatsushiro, Japan
| | - Saburo Shibata
- Department of Obstetrics and Gynecology, Arao Municipal Hospital, Arao, Japan
| | - Hiroyuki Mimori
- Department of Obstetrics and Gynecology, National Hospital Organization Kumamoto Medical Center, Kumamoto, Japan
| | - Hironori Tashiro
- School & Graduate School of Health Sciences, Kumamoto University Faculty of Life Sciences, Kumamoto, Japan
| | - Hidetaka Katabuchi
- Department of Obstetrics and Gynecology, Kumamoto University Faculty of Life Sciences, Kumamoto, Japan
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