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Du XY, Xia RJ, Shen LW, Ma JG, Yao WQ, Xu W, Lin ZP, Ma LB, Niu GQ, Fan RF, Xu SM, Yan L. Quadruple therapy with immunotherapy and chemotherapy as first-line conversion treatment for unresectable advanced gastric adenocarcinoma: A case report. World J Gastrointest Oncol 2025; 17:102258. [PMID: 40235902 PMCID: PMC11995329 DOI: 10.4251/wjgo.v17.i4.102258] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/13/2024] [Revised: 01/20/2025] [Accepted: 02/24/2025] [Indexed: 03/25/2025] Open
Abstract
BACKGROUND The treatment of gastric cancer remains highly challenging, particularly in cases of unresectable locally advanced or metastatic disease. Although chemotherapy and immunotherapy have shown some efficacy in such patients, significant limitations persist in extending survival and enhancing safety. To address these challenges, we designed an innovative first-line quadruple conversion therapy regimen that integrates a programmed cell death protein 1 (PD-1) inhibitor with chemotherapy, and we successfully implemented this therapy regimen in the treatment of a patient with unresectable locally advanced gastric adenocarcinoma. CASE SUMMARY We report the case of a 55-year-old male who was diagnosed with unresectable locally advanced gastric adenocarcinoma and presented with intermittent epigastric pain and multiple lymph node metastases in the abdominal cavity, with the metastasis being notably large in size. The tumor tissue was negative for human epidermal growth factor receptor 2 by immunohistochemistry. Considering the patient's status, the multidisciplinary team decided to administer sintilimab in combination with albumin-bound paclitaxel (nab-paclitaxel), S-1, and oxaliplatin as a quadruple drug conversion therapy. After 4 cycles of conversion therapy, the patient's epigastric pain was significantly alleviated, his stool color normalized, the volume of the primary tumor and lymph node metastases was markedly reduced, and the tumor marker levels decreased to within the normal range. The patient subsequently underwent laparoscopic total gastrectomy with abdominal lymph node dissection, and postoperative pathological biopsy revealed a pathological complete response and R0 resection, after which the patient recovered to an excellent physical status. CONCLUSION To the best of our knowledge, this is the first reported case of unresectable locally advanced gastric adenocarcinoma successfully treated with quadruple therapy with a PD-1 inhibitor and chemotherapy as a first-line conversion regimen. This first-line conversion therapy with the quadruple regimen may be effective and safe for unresectable locally advanced gastric adenocarcinoma.
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Affiliation(s)
- Xiao-Yu Du
- Department of Hepatobiliary Surgery and General Surgery, The 940th Hospital of Joint Logistic Support Force of Chinese People’s Liberation Army, Lanzhou 730050, Gansu Province, China
- Department of Medicine, Northwest Minzu University, Lanzhou 730050, Gansu Province, China
| | - Ren-Jie Xia
- Department of Hepatobiliary Surgery and General Surgery, The 940th Hospital of Joint Logistic Support Force of Chinese People’s Liberation Army, Lanzhou 730050, Gansu Province, China
- Department of Medicine, Northwest Minzu University, Lanzhou 730050, Gansu Province, China
| | - Li-Wen Shen
- Department of Medical Support Center, The 940th Hospital of Joint Logistic Support Force of Chinese People’s Liberation Army, Lanzhou 730050, Gansu Province, China
| | - Jian-Guo Ma
- Department of Hepatobiliary Surgery and General Surgery, The 940th Hospital of Joint Logistic Support Force of Chinese People’s Liberation Army, Lanzhou 730050, Gansu Province, China
- First School of Clinical Medicine, Gansu University of Chinese Medicine, Lanzhou 730030, Gansu Province, China
| | - Wei-Qing Yao
- Department of Hepatobiliary Surgery and General Surgery, The 940th Hospital of Joint Logistic Support Force of Chinese People’s Liberation Army, Lanzhou 730050, Gansu Province, China
- Department of Medicine, Northwest Minzu University, Lanzhou 730050, Gansu Province, China
| | - Wei Xu
- Department of Hepatobiliary Surgery and General Surgery, The 940th Hospital of Joint Logistic Support Force of Chinese People’s Liberation Army, Lanzhou 730050, Gansu Province, China
| | - Zhi-Peng Lin
- Department of Hepatobiliary Surgery and General Surgery, The 940th Hospital of Joint Logistic Support Force of Chinese People’s Liberation Army, Lanzhou 730050, Gansu Province, China
| | - Liang-Bin Ma
- Department of Hepatobiliary Surgery and General Surgery, The 940th Hospital of Joint Logistic Support Force of Chinese People’s Liberation Army, Lanzhou 730050, Gansu Province, China
| | - Guo-Qiang Niu
- Department of Hepatobiliary Surgery and General Surgery, The 940th Hospital of Joint Logistic Support Force of Chinese People’s Liberation Army, Lanzhou 730050, Gansu Province, China
| | - Rui-Fang Fan
- Department of Hepatobiliary Surgery and General Surgery, The 940th Hospital of Joint Logistic Support Force of Chinese People’s Liberation Army, Lanzhou 730050, Gansu Province, China
| | - Shu-Mei Xu
- Department of Hepatobiliary Surgery and General Surgery, The 940th Hospital of Joint Logistic Support Force of Chinese People’s Liberation Army, Lanzhou 730050, Gansu Province, China
| | - Long Yan
- Department of Hepatobiliary Surgery and General Surgery, The 940th Hospital of Joint Logistic Support Force of Chinese People’s Liberation Army, Lanzhou 730050, Gansu Province, China
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Liang H, Yan X, Li Z, Chen X, Qiu Y, Li F, Wang M, Huang Z, Huang K, Xie Q, Zhang H, Zhong R, Zhao Z, Zou Y, Yu J, Hu Y, Liu H, Li G, Zhao L. Clinical outcomes of conversion surgery following immune checkpoint inhibitors and chemotherapy in stage IV gastric cancer. Int J Surg 2023; 109:4162-4172. [PMID: 37720943 PMCID: PMC10720795 DOI: 10.1097/js9.0000000000000738] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2023] [Accepted: 08/24/2023] [Indexed: 09/19/2023]
Abstract
BACKGROUND The clinical benefit of conversion surgery following immunochemotherapy in patients with stage IV gastric cancer (GC) remains uncertain. This study aims to clarify the clinical outcomes of conversion surgery for such patients. METHODS This retrospective cohort study enroled consecutive patients with stage IV GC treated with a combination of immune checkpoint inhibitors and chemotherapy and/or anti-human epidermal growth factor receptor-2 targeted therapy as first-line therapy. Cumulative survival curves were estimated using Kaplan-Meier method. Logistic regression and Cox regression analyses were conducted to identify factors associated with conversion surgery and survival, respectively. RESULTS Among the 136 patients included in the study. The disease control rate was 72.1% (98/136), with objective response rate in 58.8% (80/136) and complete response rate in 5.9% (8/136). Among 98 patients with disease control, 56 patients underwent palliative immunochemotherapy with median progression-free survival (PFS) and overall survival at 9.2 and 16.2 months, respectively; the remaining 42 patients underwent conversion surgery, yielding an unreached median PFS over a 19.0-month median follow-up, accompanied by 1-year overall survival and PFS rates of 96.6% and 89.1%, respectively. The R0 resection rate reached 90.5% (38/42). 7 out of 42 patients achieved pathological complete response, of whom three patients demonstrated human epidermal growth factor receptor-2 positivity. No serious complications leading to death were observed during the perioperative period. Multivariate analysis indicated that programmed death ligand 1 combined positive score greater than or equal to 5 (odds ratio, 0.22; 95% CI, 0.08-0.57; P =0.002) favored successful conversion surgery, while signet ring cell carcinoma (hazard ratio, 6.29; 95% CI, 1.56-25.36; P =0.010) was the poor prognostic factor associated with survival in patients who underwent conversion surgery. CONCLUSIONS Conversion surgery holds the potential for significant survival benefits in stage IV GC patients who have achieved a favourable clinical response to immunochemotherapy. Individuals with signet ring cell carcinoma may experience increased post-conversion surgery recurrence.
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Affiliation(s)
- Huayuan Liang
- Department of General Surgery and Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University
| | - Xiao Yan
- Department of General Surgery and Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University
| | - Zhiwei Li
- Department of General Surgery and Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University
| | - Xinhua Chen
- Department of General Surgery and Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University
| | - Yaopeng Qiu
- Department of General Surgery and Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University
| | - Fengping Li
- Department of General Surgery and Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University
| | - Minghao Wang
- Department of General Surgery and Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University
| | - Zhicheng Huang
- Department of General Surgery and Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University
| | - Kaihua Huang
- Department of General Surgery and Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University
| | - Qing Xie
- Department of General Surgery and Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University
| | - Huimin Zhang
- Department of General Surgery and Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University
| | - Rou Zhong
- Department of General Surgery and Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University
| | - Zhuoyang Zhao
- Department of Pathology, Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, China
| | - Yuan Zou
- Department of Pathology, Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, China
| | - Jiang Yu
- Department of General Surgery and Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University
- Multidisciplinary Team of Gastric Tumor , Nanfang Hospital, Southern Medical University
| | - Yanfeng Hu
- Department of General Surgery and Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University
- Multidisciplinary Team of Gastric Tumor , Nanfang Hospital, Southern Medical University
| | - Hao Liu
- Department of General Surgery and Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University
- Multidisciplinary Team of Gastric Tumor , Nanfang Hospital, Southern Medical University
| | - Guoxin Li
- Department of General Surgery and Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University
- Multidisciplinary Team of Gastric Tumor , Nanfang Hospital, Southern Medical University
| | - Liying Zhao
- Department of General Surgery and Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University
- Multidisciplinary Team of Gastric Tumor , Nanfang Hospital, Southern Medical University
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Kano Y, Ichikawa H, Hanyu T, Muneoka Y, Ishikawa T, Aizawa M, Matsuki A, Yabusaki H, Bamba T, Nakagawa S, Kobayashi K, Kuwabara S, Makino S, Kawachi Y, Naito T, Tani T, Hirukawa H, Tada T, Shimada Y, Sakata J, Wakai T. Conversion surgery for stage IV gastric cancer: a multicenter retrospective study. BMC Surg 2022; 22:428. [PMCID: PMC9749226 DOI: 10.1186/s12893-022-01874-8] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2022] [Accepted: 12/02/2022] [Indexed: 12/15/2022] Open
Abstract
Abstract
Background
Recent improvements in systemic chemotherapy have provided an opportunity for patients with stage IV gastric cancer (GC) to undergo conversion surgery (CS). The aim of this study was to evaluate the long-term outcomes of patients who underwent CS and to elucidate the prognostic factors for CS in stage IV GC.
Methods
A total of 79 patients who underwent CS with the aim of R0 resection for stage IV GC at six institutions from January 2008 to July 2019 were enrolled. We retrospectively reviewed the clinicopathological data and prognosis.
Results
Of the 79 patients, 23 (31.1%) had initially resectable disease (IR) before chemotherapy, defined as positive for cancer on peritoneal cytology (CY1), resectable hepatic metastasis, or para-aortic lymph node No. 16a2/b1 metastasis. Of the 56 remaining patients with primary unresectable disease, 39 had peritoneal dissemination. R0 resection was accomplished in 63 patients (79.7%). The 3-year OS rates for patients with IR and unresectable disease were 78.3% and 44.5%, respectively. Multivariate analysis showed that IR (P = 0.014) and R0 (P = 0.014) were statistically significant independent prognostic factors for favorable OS. Among patients with peritoneal dissemination alone, OS was significantly better for patients with R0 resection than for patients with R1/2 resection, with the 3-year OS rates of 65.5% and 23.1%, respectively (P = 0.011).
Conclusions
CS is a treatment option for selected patients with stage IV GC. Patients with IR and patients who achieve R0 resection may obtain a survival benefit from CS.
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Yu D, Wang Z, He T, Yang L. Neoadjuvant Bevacizumab Plus Docetaxel/Cisplatin/Capecitabine Chemotherapy in Locally Advanced Gastric Cancer Patients: A Pilot Study. Front Surg 2022; 9:842828. [PMID: 35647008 PMCID: PMC9130594 DOI: 10.3389/fsurg.2022.842828] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2021] [Accepted: 01/26/2022] [Indexed: 02/03/2023] Open
Abstract
BackgroundBevacizumab (BEV) plus chemotherapy as a neoadjuvant regimen presents good efficacy in patients with locally advanced cancer. However, its role in patients with locally advanced gastric cancer (LAGC) is not clear. Thus, the study aimed to assess the efficacy and safety of neoadjuvant BEV plus chemotherapy in patients with LAGC.MethodsTwenty resectable patients with LAGC who received BEV plus docetaxel/cisplatin/capecitabine (DCC) chemotherapy for 3 cycles with 21 days as one cycle as neoadjuvant regimen were involved. Besides, their treatment response, survival profiles, and adverse events were assessed.ResultsIn total, two (10.0%), 9 (45.0%), 8 (40.0%), and 1 (5.0%) patients achieved complete remission, partial remission, stable disease, and progressive disease (PD) according to imaging evaluation, which resulted in 55.0% of objective response rate and 95.0% of disease control rate, respectively. Moreover, the number of patients with pathological response grades 1, 2, and 3 was 8 (40.0%), 8 (40.0%), and 3 (15.0%); while 1 (5.0%) patient did not receive surgery due to PD, thus the data of this patient was not assessable. Meanwhile, 18 (90.0%) patients achieved R0 resection. Regarding survival profile, the median disease-free survival or overall survival were both not reached. The 1-year, 2-, and 3-year disease-free survival rates were 88.8, 80.7, and 67.3%. Meanwhile, the 1-, 2-, and 3-year overall survival rates were 100.0%, 75.8%, and 75.8%, respectively. Additionally, the main adverse events were anemia (90.0%), alopecia (90.0%), leukopenia (70.0%), and anorexia (65.0%). Indeed, most adverse events were of grade 1 or 2 and were manageable.ConclusionNeoadjuvant BEV plus DCC chemotherapy presents a favorable pathological response and survival profile with acceptable safety in patients with LAGC.
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Affiliation(s)
- Deguo Yu
- Department of Emergency Surgery, The Second People's Hospital of Liaocheng, Linqing, China
| | - Zhenfeng Wang
- Department of General Surgery, The Second People's Hospital of Liaocheng, Linqing, China
| | - Tingbang He
- Department of General Surgery, The People's Hospital of XiaJin Affiliated to Shandong First Medical University, Xiajin, China
- *Correspondence: Tingbang He
| | - Lijun Yang
- Department of Emergency, The Second People's Hospital of Liaocheng, Linqing, China
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Short-term survival and safety of apatinib combined with oxaliplatin and S-1 in the conversion therapy of unresectable gastric cancer. BMC Cancer 2021; 21:702. [PMID: 34126957 PMCID: PMC8204414 DOI: 10.1186/s12885-021-08459-3] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2021] [Accepted: 06/07/2021] [Indexed: 02/03/2023] Open
Abstract
Background We conducted a single-arm phase II trial to investigate the short-term efficacy and safety of apatinib combined with oxaliplatin and S-1 in the treatment of unresectable gastric cancer. Patients and methods Previously untreated patients with unresectable HER-2-negative advanced gastric cancer were selected. All the patients received six cycles of S-1 and oxaliplatin and five cycles of apatinib, which were administered at intervals of three weeks. The surgery was performed after six cycles of drug treatment. The primary endpoints were radical resection (R0) rate and safety. This study was registered with the China Trial Register, number ChiCTR-ONC-17010430 (01/12/2016–01/12/2022). Results A total of 39 patients were enrolled. Efficacy evaluation was feasible for 37 patients. One patient achieved complete response (CR, 2.7%), 26 patients achieved partial response (PR, 70.3%), three patients had stable disease (SD, 8.1%) and seven patients had progressive disease (PD, 18.9%). The objective response rate (ORR) was 73.0% and the disease control rate (DCR) was 81.1%. 22 patients underwent surgery, among which 14 patients underwent radical resection (R0), with a R0 resection rate of 63.6%. The 1-year survival rate of the surgical group (22 patients) was 71.1% and the 2-year survival rate was 41.1%. The median survival time was 21 months. The incidence of adverse events (AEs) was 100%. Leucopenia (65.3%) and granulocytopenia (69.2%) were the most common hematological AEs. The most common non-hematological AEs were fatigue (51.3%) and oral mucositis (35.9%). Conclusion Apatinib combined with oxaliplatin and S-1 showed good short-term survival and acceptable safety in the conversion therapy of unresectable gastric cancer.
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Yeh YS, Huang MY, Ma CJ, Huang CW, Tsai HL, Chen YC, Li CC, Yu FJ, Shih HY, Wang JY. Observational Study Comparing Efficacy and Safety between Neoadjuvant Concurrent Chemoradiotherapy and Chemotherapy for Patients with Unresectable Locally Advanced or Metastatic Gastric Cancer. JOURNAL OF ONCOLOGY 2020; 2020:6931317. [PMID: 32963531 PMCID: PMC7492932 DOI: 10.1155/2020/6931317] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/27/2020] [Revised: 07/07/2020] [Accepted: 07/15/2020] [Indexed: 02/08/2023]
Abstract
OBJECTIVE Dismal outcomes in patients with locally advanced or metastatic gastric cancer (GC) highlight the need for effective systemic neoadjuvant treatment strategies to improve clinical results. Neoadjuvant multimodality strategies vary widely. This study compared the efficacy, safety, and clinical outcomes of neoadjuvant CCRT and chemotherapy for such patients. MATERIALS AND METHODS Sixty-five patients with histologically confirmed locally advanced or metastatic GC following neoadjuvant CCRT or computed tomography (CT) were retrospectively enrolled between January 2010 and April 2019. Clinical outcomes included response, progression-free survival (PFS), and overall survival (OS), and toxicity was compared between the two groups. RESULTS Of the 65 patients, 18 (27.7%) were in the response group (2 patients with a complete response and 16 with a partial response) and 47 (72.3%) in the nonresponse group (29 patients with a stable disease and 18 with a progressive disease). Multivariate analysis revealed no independent response predictor between CCRT and chemotherapy groups (all P > 0.05). Furthermore, results revealed no statistical differences in toxicity between the two groups (all P > 0.05). With a follow-up median of 12 months (ranging 6-48 months), 12-month OS and PFS were 39.7% and 20.4% in the CCRT group and 30.3% and 13.2% in the chemotherapy group, respectively. The median OS and PFS were 14.0 months (95% CI 9.661-18.339) and 9.0 months (95% CI 6.805-11.195) in the CCRT group and 10.0 months (95% CI 6.523-13.477) and 8.0 months (95% CI 6.927-9.073) in the chemotherapy group, respectively. Both OS (P=0.011) and PFS (P=0.008) in patients with CCRT were significantly better than those in patients with chemotherapy alone. CONCLUSION Neoadjuvant CCRT achieved more favorable OS and PFS than did neoadjuvant chemotherapy alone, without significant increases of toxicity in patients. However, prospective randomized trials comparing treatment modalities are necessary to confirm the potential advantages of neoadjuvant CCRT.
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Affiliation(s)
- Yung-Sung Yeh
- Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Division of Trauma and Surgical Critical Care, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ming-Yii Huang
- Department of Radiation Oncology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Radiation Oncology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Cheng-Jen Ma
- Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Division of General and Digestive Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ching-Wen Huang
- Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Surgery, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Hsiang-Lin Tsai
- Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Surgery, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Yen-Cheng Chen
- Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ching-Chun Li
- Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Fang-Jung Yu
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Department of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Hsiang-Yao Shih
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Department of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Jaw-Yuan Wang
- Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Surgery, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Clinical Pharmacogenomics and Pharmacoproteinomics, College of Pharmacy, Taipei Medical University, Taipei, Taiwan
- Drug Development and Value Creation Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan
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Huang C, Hu C, Zhu J, Zhang W, Huang J, Zhu Z. Establishment of Decision Rules and Risk Assessment Model for Preoperative Prediction of Lymph Node Metastasis in Gastric Cancer. Front Oncol 2020; 10:1638. [PMID: 32984033 PMCID: PMC7492596 DOI: 10.3389/fonc.2020.01638] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2020] [Accepted: 07/27/2020] [Indexed: 12/26/2022] Open
Abstract
Background: Preoperative accurate prediction of lymph node status is especially important for the formulation of treatment plans for patients with gastric cancer (GC). The purpose of this study was to establish decision rules and a risk assessment model for lymph node metastasis (LNM) in GC using preoperative indicators. Methods: The clinical data of 554 patients who underwent gastrectomy with D2 lymphadenectomy were collected. A 1:1 propensity score matching (PSM) system was used, and the clinical data of the matched 466 patients were further analyzed. The important risk factors for LNM were extracted by the random forest algorithm, and decision rules and nomogram models for LNM were constructed with a classification tree and the "rms" package of R software, respectively. Results: Tumor size (OR: 2.058; P = 0.000), computed tomography (CT) findings (OR: 1.969; P = 0.001), grade (OR: 0.479; P = 0.000), hemoglobin (Hb) (OR: 1.211; P = 0.005), CEA (OR: 1.111; P = 0.017), and CA19-9 (OR: 1.040; P = 0.033) were independent risk factors for LNM in GC. Tumor size did rank first in the ranking of important factors for LNM in GC and was the first-level segmentation of the two initial branches of the classification tree. The accuracy, sensitivity, specificity, and positive predictive value of the decision rules in diagnosing preoperative LNM in GC were 75.6, 85.7, 73.9, 73.5, and 79.3%, respectively. The accuracy, sensitivity, and specificity of the risk assessment model in predicting preoperative LNM in GC were 79.3, 80.3, and 79.4%, respectively. Conclusion: Tumor size was the most important factor for evaluating LNM in GC. This decision rules and nomogram model constructed to take into account tumor size, CT findings, grade, hemoglobin, CEA, and CA19-9 effectively predicted the incidence of LNM in preoperative GC.
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Affiliation(s)
| | | | | | | | | | - Zhengming Zhu
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, China
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Jeong GS, Lee IS, Park YS, Kim BS, Yoo MW, Yook JH, Kim BS. Advantages of ypTNM Staging in Post-surgical Prognosis for Initially Unresectable or Stage IV Gastric Cancers. J Gastric Cancer 2020; 20:233-244. [PMID: 33024580 PMCID: PMC7521980 DOI: 10.5230/jgc.2020.20.e20] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/01/2020] [Revised: 04/16/2020] [Accepted: 05/01/2020] [Indexed: 11/29/2022] Open
Abstract
Purpose For unresectable or initially metastatic gastric cancer, conversion surgery (CVS), after systemic chemotherapy, has received attention as a treatment strategy. This study evaluated the prognostic value of ypTNM stage and the oncologic outcomes in patients receiving CVS. Materials and Methods A retrospective review of clinicopathologic findings and oncologic outcomes of 116 patients who underwent CVS with curative intent, after combination chemotherapy, between January 2000 and December 2015, has been reported here. Results Twenty-six patients (22.4%) underwent combined resection of another organ and 12 patients received para-aortic lymphadenectomy (10.3%). Pathologic complete remission (CR) was confirmed in 11 cases (9.5%). The median overall survival (OS) and disease-free survival (DFS) times were 35.0 and 21.3 months, respectively. In multivariate analysis, ypTNM stage was the sole independent prognostic factor for DFS (P=0.042). Tumors invading an adjacent organ or involving distant lymph nodes showed better survival than those with peritoneal seeding or solid organ metastasis (P=0.084). Kaplan-Meier curves showed that the 3-year OS rate of patients with pathologic CR and those with CR of the primary tumor but residual node metastasis was 81.8% and 80.0%, respectively. OS was 65.8% for stage 1 patients, 49.8% for those at stage 2, and 36.3% for those at stage 3. Conclusions The ypTNM staging is a significant prognostic factor in patients who underwent CVS for localized unresectable or stage IV gastric cancers. Patients with locally advanced but unresectable lesions or with tumors with distant nodal metastasis may be good candidates for CVS.
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Affiliation(s)
- Gyu-Seong Jeong
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - In-Seob Lee
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Young-Soo Park
- Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Beom-Su Kim
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Moon-Won Yoo
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Jeong-Hwan Yook
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Byung-Sik Kim
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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Park JH, Yang JY, Park YH, Lee WK. The long-term prognostic difference between gastrectomy with and without preoperative chemotherapy in patients with clinical stage IV gastric cancer. Asian J Surg 2019; 42:922-929. [PMID: 30685146 DOI: 10.1016/j.asjsur.2019.01.006] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2018] [Revised: 12/28/2018] [Accepted: 01/08/2019] [Indexed: 01/23/2023] Open
Abstract
BACKGROUND/OBJECTIVE The role of gastrectomy for stage IV gastric cancer (GC) has not yet been established. Thus, we aimed to compare the prognoses of patients with clinical stage IV GC who underwent gastrectomy with and without preoperative chemotherapy after precise recategorization of patients. METHODS We retrospectively reviewed a total of 92 clinical stage IV GC patients who underwent gastrectomy with or without preoperative chemotherapy between 2010 and 2016 at a single institution. Yoshida's classification was used to categorize the patients into the following categories: 1, technically resectable metastasis; 2, marginally resectable metastasis; 3, unresectable peritoneal dissemination; and 4, incurable peritoneal dissemination with distant organ metastasis. Two-year disease-specific survival (DSS) rates were compared between patients who underwent primary surgery and preoperative chemotherapy for each category. RESULTS The two-year DSS rates of primary surgery vs. preoperative chemotherapy in Categories 1, 2, 3, and 4 (n = 35, 39, 14, and 4, respectively) were 48.6% vs. 41.7% (p = 0.829), 52.6% vs. 40.0% (p = 0.855), 50.0% vs. 75.0% (p = 0.027), and 0% vs. 66.7% (p = 0.083), respectively. Patients in Categories 1 and 2 who underwent preoperative chemotherapy tended to have lower two-year DSS rates (p = 0.911), whereas patients in Categories 3 and 4 had significantly higher two-year DSS rates than those who underwent primary surgery (p = 0.014). CONCLUSIONS Primary surgery may be performed in patients without peritoneal dissemination when GC is technically resectable. However, if peritoneal dissemination is suspected, chemotherapy should be prioritized.
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Affiliation(s)
- Ji-Hyeon Park
- Department of Surgery, Gachon University Gil Medical Center, 21 Namdong-daero 774 Beon-gil, Namdong-gu, Incheon, 21565, Republic of Korea
| | - Jun-Young Yang
- Department of Surgery, Gachon University College of Medicine, Hambacwero 191, Yeonsu-gu, Incheon, 21936, Republic of Korea.
| | - Yeon-Ho Park
- Department of Surgery, Gachon University College of Medicine, Hambacwero 191, Yeonsu-gu, Incheon, 21936, Republic of Korea
| | - Woon-Kee Lee
- Department of Surgery, Gachon University College of Medicine, Hambacwero 191, Yeonsu-gu, Incheon, 21936, Republic of Korea.
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10
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Maeda O, Ando Y. Recent progress of chemotherapy and biomarkers for gastroesophageal cancer. World J Gastrointest Oncol 2019; 11:518-526. [PMID: 31367271 PMCID: PMC6657220 DOI: 10.4251/wjgo.v11.i7.518] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2019] [Revised: 04/17/2019] [Accepted: 05/29/2019] [Indexed: 02/05/2023] Open
Abstract
Key cytotoxic drugs of chemotherapy for gastroesophageal cancer include fluoropyrimidine, platinum, taxanes and irinotecan. Concurrent chemoradiotherapy is one of the main treatment strategies, especially for esophageal cancer. As molecular target agents, the anti-HER2 antibody trastuzumab for HER2-positive gastric cancer and the anti-angiogenesis agent ramucirumab combined with paclitaxel have been proven to improve the survival of gastric cancer patients. Recently, anti-PD-1 antibodies have become available as second- or later-line chemotherapy. Microsatellite instability is also useful as a biomarker to select patients suitable for immunotherapy. Furthermore, genome-wide analysis has improved our understanding of the biological features and molecular mechanisms of gastroesophageal cancer and will provide optimized treatment selection.
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Affiliation(s)
- Osamu Maeda
- Department of Clinical Oncology and Chemotherapy, Nagoya University Hospital, Nagoya 466-8560, Japan
| | - Yuichi Ando
- Department of Clinical Oncology and Chemotherapy, Nagoya University Hospital, Nagoya 466-8560, Japan
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11
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Su Z, Shu K, Kang M, Wang G. Pathological complete response from oral chemotherapy combined with trans-arterial chemotherapy and embolization in an unresectable gastric cancer patient: A case report. Medicine (Baltimore) 2019; 98:e16075. [PMID: 31232946 PMCID: PMC6636947 DOI: 10.1097/md.0000000000016075] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Abstract
RATIONALE Gastric cancer is still one of the most common cancer in East Asia. More than 70% gastric cancer patients are diagnosed at an advanced stage in China. Moreover, about 10% cases are unresectable which usually suffer a poor prognosis with a median survival time of 5 to 12 months. In recent years, some clinical studies found that many unresectable gastric cancer cases could get opportunity for surgery after treatment that improve prognosis significantly PATIENT CONCERNS:: 64-year-old male patient was admitted with upper abdominal pain. Upper gastrointestinal endoscopy showed a large ulcerated tumor located from the cardia to the anterior wall of the upper gastric body. Histopathological examination showed it was moderately differentiated adenocarcinoma. Computed tomography (CT) scan image showed a large bulging mass with internal ulcer at the lesser curvature wall, left gastric artery and coeliac trunk were surrounded by fused lymph nodes. DIAGNOSES Based on the histopathological examination and imaging findings, patient was diagnosed advanced gastric cancer and hardly to resect radically. INTERVENTION Oral chemotherapy combined with trans-arterial chemotherapy and embolization (TACE) was initiated. Eight weeks after initial therapy, radical laparoscopy-assisted total gastrectomy with D2 lymph node dissection and Roux-en-Y anastomosis were performed successfully. OUTCOMES Patient was discharged on postoperative day 11 without complications. Histological analysis of the specimen and resected 31 lymph nodes revealed no malignancy. The patient experienced a pathological complete response (pCR). LESSONS In this case, oral chemotherapy combined with TACE which was rarely reported in the treatment of unresectable gastric cancer achieves a great therapeutic benefit. Although further clinical studies will be needed to establish, it may be a potent strategy for degrading stage and supplying a new chance for surgery.
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Affiliation(s)
- Zhaoran Su
- Department of Gastrointestinal Surgery
- Department of Digestive Endoscopy
| | - Kuanshan Shu
- Department of Gastrointestinal Surgery
- Department of Digestive Endoscopy
| | - Min Kang
- Department of Pathology, People's Hospital of Tongling City, Tongling, Anhui, People's Republic of China
| | - Guihe Wang
- Department of Gastrointestinal Surgery
- Department of Digestive Endoscopy
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12
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Wang Y, Zhuang RY, Yu YY, Yu S, Hou J, Ji Y, Sun YH, Shen KT, Shen ZB, Liu FL, Zhao NQ, Liu TS. Efficacy of preoperative chemotherapy regimens in patients with initially unresectable locally advanced gastric adenocarcinoma: capecitabine and oxaliplatin (XELOX) or with epirubicin (EOX). Oncotarget 2018; 7:76298-76307. [PMID: 27602586 PMCID: PMC5342815 DOI: 10.18632/oncotarget.11818] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2016] [Accepted: 08/25/2016] [Indexed: 01/16/2023] Open
Abstract
Purpose We assessed the effectiveness of EOX (capecitabine, oxaliplatin and epirubicin) compared with XELOX (capecitabine and oxaliplatin) as preoperative chemotherapy for initially unresectable locally advanced gastric cancer.Methods This is a prospective observational study. Patients with unresectable locally advanced gastric cancer were performed EOX regimen or XELOX regimen at the discretion of the investigators. They were assessed for response every 2 cycles by CT (computed tomography) scan. A multidisciplinary team reassessed resectability after 4 cycles. The primary endpoint was the response rate. Secondary end points included the R0 resection rate, survival and adverse events.Results From November 2008 to May 2015, 242 patients were enrolled; 112 of them were assigned to EOX regimen and 130 to XELOX regimen. The response rates were 33.0% and 33.8% respectively in EOX group and XELOX group (P = 0.997). After 4 cycles of chemotherapy, 63 patients (56.3%) in EOX group and 81 patients (62.3%) in XELOX group received radical operation (P = 0.408). There was no significant difference in progress-free survival (PFS, 12.0m vs. 15.4m, P = 0.925) and overall survival (OS, 25.7m vs. 29.0m, P = 0.783) in two groups. In addition, more adverse effects occurred in EOX group, such as more leucopenia (22.3% vs. 10.0%, P = 0.014), neutropenia (23.2% vs. 11.5%, P = 0.025), fatigue (11.6% vs. 3.8%, P = 0.041) and vomiting (10.7% vs. 2.3%, P = 0.015).Conclusions For unresectable locally advanced gastric cancer patients, XELOX regimen showed similar effects in response rate, radical resection rate and survival benefits, but with less toxicity effects.
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Affiliation(s)
- Yan Wang
- Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Rong-Yuan Zhuang
- Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yi-Yi Yu
- Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Shan Yu
- Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Jun Hou
- Department of Pathology, Fudan University, Zhongshan Hospital, Shanghai, China
| | - Yuan Ji
- Department of Pathology, Fudan University, Zhongshan Hospital, Shanghai, China
| | - Yi-Hong Sun
- Department of General Surgery, Fudan University, Zhongshan Hospital, Shanghai, China
| | - Kun-Tang Shen
- Department of General Surgery, Fudan University, Zhongshan Hospital, Shanghai, China
| | - Zhen-Bin Shen
- Department of General Surgery, Fudan University, Zhongshan Hospital, Shanghai, China
| | - Feng-Lin Liu
- Department of General Surgery, Fudan University, Zhongshan Hospital, Shanghai, China
| | - Nai-Qing Zhao
- Department of Biostatistics and Social Medicine, School of Public Health, Fudan University, Shanghai, China
| | - Tian-Shu Liu
- Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai, China.,Center of Evidence-Based Medicine, Fudan University, Shanghai, China
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13
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Park K, Jang G, Baek S, Song H. Usefulness of Combined PET/CT to Assess Regional Lymph Node Involvement in Gastric Cancer. TUMORI JOURNAL 2018; 100:201-6. [DOI: 10.1177/030089161410000214] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Aims and Background The aim of this study was to evaluate the value of positron emission tomography/computed tomography (PET/CT) for preoperative staging of gastric cancer and to compare the diagnostic performance of PET/CT with that of contrast-enhanced computed tomography (CECT). Methods We retrospectively reviewed 74 gastric cancer patients who underwent preoperative PET/CT and CECT, and subsequent curative surgical resection between April 2007 and July 2011. Preoperative PET/CT and CECT images for primary tumors of the stomach and lymph node metastases were reviewed retrospectively. The final diagnoses of primary tumors and LN metastases were based on histopathological specimens in all patients. Results Advanced gastric cancer was present in 65% of patients (n = 48), and the remaining patients had early gastric cancer (n = 26). Sixteen patients (22%) showed signet-ring-cell histology. For the detection of the primary tumor, the sensitivity of PET/CT was significantly higher than that of CECT (67% vs 55%, respectively; P = 0.049). For the evaluation of regional lymph node metastasis, the sensitivity, specificity, and accuracy of PET/CT and CECT were 34% and 51% (P = 0.065), 88% and 79% (P = 0.687), and 58% and 64% (P = 0.332), respectively. Neither PET/CT nor CECT detected regional lymph node metastases in early gastric cancer patients. Signet-ringcell histology showed trends of non-FDG-avid lymph node metastases (odds ratio = 0.15, 95% confidence interval 0.17–1.37, P = 0.093) Conclusions The accuracy of PET/CT is low and it is not a useful tool in the staging of gastric cancer overall in early gastric cancer and in signet-ring-cell carcinoma. Furthermore, the sensitivity of PET/CT could be inferior to that of CECT in the diagnosis of regional lymph node metastasis.
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Affiliation(s)
- Kwonoh Park
- Department of Hemato-Oncology, KEPCO Medical Center, Seoul
| | - Geundoo Jang
- Department of Internal Medicine, Kangdong Sacred Heart Hospital, University of Hallym College of Medicine, Seoul, Korea
| | - Sora Baek
- Department of Nuclear Medicine, Kangdong Sacred Heart Hospital, University of Hallym College of Medicine, Seoul, Korea
| | - Hunho Song
- Department of Internal Medicine, Kangdong Sacred Heart Hospital, University of Hallym College of Medicine, Seoul, Korea
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14
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Preoperative tumor restaging and resectability assessment of gastric cancers after chemotherapy: diagnostic accuracy of MDCT using new staging criteria. Abdom Radiol (NY) 2017. [PMID: 28643135 DOI: 10.1007/s00261-017-1224-2] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
PURPOSE To evaluate the diagnostic performance of preoperative MDCT for tumor restaging and determination of resectability in gastric cancers after chemotherapy using new staging criteria. METHODS This retrospective study was approved by our institutional review board and the requirement for informed consent was waived. Thirty-seven patients with initially unresectable gastric cancers who had received chemotherapy followed by surgery were included. Two independent radiologists reviewed preoperative MDCT images to determine the TNM staging and rate the overall likelihood of resectability using a 5-point scale (5: definitely unresectable, 1: definitely resectable). New post-chemotherapy MDCT criteria do not use non-enhancing perigastric infiltrations, non-enhancing lymph nodes (LNs), and subtle remaining infiltrations after marked decrease in the size of distant metastases for T, N, and M upstaging, respectively. Discrepancies in TNM staging were resolved by a third reviewer. The diagnostic performances of MDCT were assessed using pathologic results or operation records as reference standards. RESULTS For predicting resectability, the areas under the ROC curve were 0.885 and 0.882 (95% CIs 0.737-0.966 and 0.733-0.964) in reviewers 1 and 2, respectively, with substantial inter-reader agreement (weighted κ = 0.689). Sensitivities and specificities of MDCT for tumor restaging on a consensus review were 80.0% (4/5) and 100% (29/29) for T4b, 35.3% (6/17) and 81.3% (13/16) for N-positive, and 63.6% (7/11) and 100% (26/26) for M1, respectively. CONCLUSIONS For gastric cancers after chemotherapy, new MDCT criteria demonstrated high specificities for T4b and M-staging and good performances to predict resectability before conversion surgery.
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15
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Jung YJ, Seo HS, Kim JH, Park CH, Lee HH. Cross-Sectional Location of Gastric Cancer Affects the Long-Term Survival of Patients as Tumor Invasion Deepens. Ann Surg Oncol 2017; 24:3947-3953. [PMID: 28980179 DOI: 10.1245/s10434-017-6101-2] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2017] [Indexed: 12/20/2022]
Abstract
BACKGROUND The prognosis of gastric cancer is generally determined by tumor depth and lymph node metastasis, while the effect of cross-sectional tumor location on prognosis remains unclear. METHODS This study recruited patients who had been diagnosed with gastric cancer and who underwent gastrectomy from 1989 to 2012. The cross-sectional locations of the gastric cancers were classified into four regions: the lesser (LC) and greater curvatures (GC), and anterior (AW) and posterior walls (PW). RESULTS Overall, 4820 patients were enrolled in this study. The most common site of gastric cancer among the four cross-sectional locations was the LC (46.4%), while the proportions of PW (19.9%), AW (18.4%), and GC (15.4%) were similar. Overall survival differed statistically (p = 0.013) according to the cross-sectional location, and the 5-year overall survival of those with tumors with a GC location was significantly worse (p = 0.003) than for the other three locations. In subgroup multivariate analysis, GC location was an independent prognostic indicator for a worse clinical outcome at T stage 3-4b (hazard ratio 1.365, 95% confidence interval 1.150-1.620, p < 0.001). In addition, a GC gastric cancer had a higher recurrence rate in terms of peritoneal seeding compared with other locations. CONCLUSIONS The cross-sectional location of gastric cancer is associated with long-term survival. A GC location predicts a worse prognosis, especially in gastric cancer patients with deeper T stages.
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Affiliation(s)
- Yoon Ju Jung
- Division of Gastrointestinal Surgery, Department of Surgery, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea
| | - Ho Seok Seo
- Division of Gastrointestinal Surgery, Department of Surgery, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea
| | - Ji Hyun Kim
- Division of Gastrointestinal Surgery, Department of Surgery, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea
| | - Cho Hyun Park
- Division of Gastrointestinal Surgery, Department of Surgery, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea
| | - Han Hong Lee
- Division of Gastrointestinal Surgery, Department of Surgery, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea. .,Catholic Cancer Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Korea.
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16
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Will molecular target agents enable the multidisciplinary treatment in stage IV gastric cancer? Eur J Surg Oncol 2017; 43:1835-1845. [PMID: 28888797 DOI: 10.1016/j.ejso.2017.08.006] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2017] [Revised: 08/02/2017] [Accepted: 08/10/2017] [Indexed: 02/06/2023] Open
Abstract
A detailed molecular characterization of gastric cancer has been revealed by global initiatives and a number of new molecular agents are under investigation. Currently only trastuzumab, a monoclonal antibody for human epidermal growth factor receptor 2 (HER2), is clinically used for HER2 positive advanced gastric cancer patients and ramucirumab, a monoclonal antibody directed against the extracellular ligand-binding domain of vascular endothelial growth factor receptor (VEGFR)2, can be used in second line. However, despite the progress in gastric cancer treatment, the prognosis of stage IV gastric cancer patients remains dismal. To achieve a remarkable improvement in the prognosis of patients, a multidisciplinary treatment approach with the help of effective molecular target agents should be considered. So far the role of multidisciplinary treatment for stage IV gastric cancer is still uncertain due to limited available data and absence of long-lasting tumor control with systemic therapy. Herein, an overview of the latest developments of molecular targeted agents for gastric cancer in advanced stages, in the perioperative setting and in oligometastatic disease is provided. The possibility of a multidisciplinary strategy using molecular target agents and surgery for stage IV gastric cancer is also assessed.
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17
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Li Y, Chen J, He Q, Ji X, Wang X, Fan C, Li G. Clinical efficacy of neoadjuvant chemotherapy regimens FLEEOX vs. XELOX in patients with initially unresectable advanced gastric cancer: a propensity score analysis. Oncotarget 2017; 8:86886-86896. [PMID: 29156843 PMCID: PMC5689733 DOI: 10.18632/oncotarget.19004] [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: 02/23/2017] [Accepted: 05/15/2017] [Indexed: 02/06/2023] Open
Abstract
Purpose This study was designed to assess the effectiveness of FLEEOX (5-Fu, leucovorin, etoposide, oxaliplatin, and epirubicin) compared with XELOX (capecitabine and oxaliplatin) as neoadjuvant chemotherapy (NAC) for initially unresectable advanced gastric cancer (AGC). Methods This study reviewed patients who underwent FLEEOX or XELOX for initially unresectable AGC. To reduce the bias in patient selection, we conducted propensity score match (PSM) with 1:1 ratio. Tumor and pathological response, surgical characteristics, chemotherapy-related toxicity and overall survival (OS) were analyzed. Results From January 2004 to December 2012, 436 patients were enrolled; 99 pairs of patients were generated after PSM. The tumor response rates were 80.8% and 68.7% in FLEEOX and XELOX (P=0.018). 80 patients (80.8%) in FLEEOX and 63 (63.6%) in XELOX received radical resection (P<0.001). The pathological complete response rate and R0 rate were 11.1% and 69.7% in FLEEOX, respectively, while 4.8% and 38.4% in XELOX (P<0.001). Median OS time was longer in FLEEOX (30.0 vs. 25.1 months, P<0.001). In addition, more toxicities occurred in FLEEOX, including leukocytopenia (17.2% vs. 7.1%, P=0.024), nausea (17.2% vs. 6.1%, P=0.012) and vomiting (22.2% vs. 10.1%, P=0.016). The overall toxicity rate was higher in FLEEOX (71.7% vs. 35.4%, P<0.001). Conclusion The FLEEOX regimen as NAC for patients with initially unresectable AGC can improve tumor response rate, radical resection rate, R0 rate, and OS as compared to XELOX regimen. More chemotherapy-related toxicity was observed in FLEEOX group, although no chemotherapy-related deaths and aborting were observed. Further randomized clinical trials on the FLEEOX regimen are necessary.
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Affiliation(s)
- Yang Li
- Division of Digestive Surgery, Xijing Hospital, Fourth Military Medical University, 710032, Xi'an, Shaanxi, China.,Research Institute of General Surgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing 210002, China
| | - Jun Chen
- Research Institute of General Surgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing 210002, China
| | - Qi He
- Research Institute of General Surgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing 210002, China
| | - Xiang Ji
- Research Institute of General Surgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing 210002, China
| | - Xulin Wang
- Research Institute of General Surgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing 210002, China
| | - Chaogang Fan
- Research Institute of General Surgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing 210002, China
| | - Guoli Li
- Research Institute of General Surgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing 210002, China
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Kim JH, Park SR, Ryu MH, Ryoo BY, Kim KP, Kim BS, Yoo MW, Yook JH, Kim BS, Kim J, Byeon SJ, Kang YK. Phase II Study of Induction Chemotherapy with Docetaxel, Capecitabine, and Cisplatin Plus Bevacizumab for Initially Unresectable Gastric Cancer with Invasion of Adjacent Organs or Paraaortic Lymph Node Metastasis. Cancer Res Treat 2017; 50:518-529. [PMID: 28546521 PMCID: PMC5912143 DOI: 10.4143/crt.2017.005] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2017] [Accepted: 05/22/2017] [Indexed: 12/19/2022] Open
Abstract
Purpose The purpose of this study was to evaluate the efficacy and safety of induction chemotherapy with docetaxel, capecitabine, and cisplatin (DXP) plus bevacizumab (BEV) on initially unresectable locally advanced gastric cancer (LAGC) or paraaortic lymph node (PAN) metastatic gastric cancer (GC). Materials and Methods Patients with LAGC or unresectable PAN metastatic GC received six induction chemotherapy cycles (60 mg/m2 docetaxel intravenously on day 1, 937.5 mg/m2 capecitabine orally twice daily on days 1-14, 60 mg/m2 cisplatin intravenously on day 1, and 7.5 mg/kg BEV intravenously on day 1 every 3 weeks), followed by conversion surgery. The primary endpoint was R0 resection rate. Results Thirty-one patients with invasion to adjacent organs but without PAN metastasis (n=14, LAGC group) or with PAN metastasis regardless of invasion (n=17, PAN group) were enrolled between July 2010 and December 2014. Twenty-seven patients (87.1%) completed six chemotherapy cycles. The most common grade ≥ 3 toxicities were neutropenia (71%), neutropenia with fever/infection (22.6%/3.2%), and stomatitis (16.1%). The clinical response and R0 resection rates were 64.3% (95% confidence interval [CI], 46.6 to 82.0) and 64.5% (LAGC group, 71.4%; PAN group, 58.8%), respectively. The pathological complete regression rate was 12.9%. After a median follow-up of 44.5 months (range, 39.4 to 49.7 months), the median progression-free survival and overall survival were 13.1 months (95% CI, 8.9 to 17.3) and 38.6 months (95% CI, 22.0 to 55.1), respectively. Conclusion Induction chemotherapy with DXP+BEV displayed antitumor activities with encouraging R0 resection rate and manageable toxicity profiles on patients with LAGC or PAN metastatic GC.
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Affiliation(s)
- Jwa Hoon Kim
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Sook Ryun Park
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Min-Hee Ryu
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Baek-Yeol Ryoo
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Kyu-Pyo Kim
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Beom Su Kim
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Moon-Won Yoo
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Jeong Hwan Yook
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Byung Sik Kim
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Jihun Kim
- Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Sun-Ju Byeon
- Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Yoon-Koo Kang
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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Mieno H, Yamashita K, Hosoda K, Moriya H, Higuchi K, Azuma M, Komori S, Yoshida T, Tanabe S, Koizumi W, Katada N, Watanabe M. Conversion surgery after combination chemotherapy of docetaxel, cisplatin and S-1 (DCS) for far-advanced gastric cancer. Surg Today 2017; 47:1249-1258. [PMID: 28365892 DOI: 10.1007/s00595-017-1512-z] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2016] [Accepted: 02/13/2017] [Indexed: 02/06/2023]
Abstract
PURPOSE A triplet regimen of docetaxel, cisplatin, and S-1(DCS) is highly effective against metastatic gastric cancer. We performed this study to clarify the safety and efficacy of surgical resection in patients with initially unresectable gastric cancer, after down-staging or disease control was achieved by DCS chemotherapy. METHODS The subjects of this retrospective study were 31 consecutive patients with initially unresectable gastric cancer, who underwent surgical resection between October, 2006 and December, 2012, after down-staging or disease control was achieved by DCS chemotherapy. We evaluated the clinicopathological factors and clinical outcomes and assessed radiographic response based on the RECIST criteria, not by central review. RESULT Before DCS chemotherapy, 18 patients had extra-regional lymph node metastasis, 5 had liver metastasis, 8 had macroscopic peritoneal metastasis, and 8 had pancreatic head invasion. Twenty-three (74.2%) of the 31 patients underwent R0 resection. Postoperative morbidity and mortality rates were 16.1 and 0%. During chemotherapy, grade 3/4 toxicities included neutropenia (54.8%), leukopenia (32.3%), and anemia (16.1%). Median progression-free survival and median overall survival (OS) were 42.1 and 56.1 months, respectively. These results were similar for all patients, except those with locally advanced disease alone. In the multivariate analysis for OS, ypN remained an independent negative prognostic factor (p = 0.018). CONCLUSION Surgical resection after DCS chemotherapy for initially unresectable gastric cancer was safe and provided a reasonable R0 resection rate and good mid-term survival.
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Affiliation(s)
- Hiroaki Mieno
- Department of Surgery, Kitasato University School of Medicine, Kitasato 1-15-1, Minami-ku, Sagamihara, Kanagawa, 252-0374, Japan.
| | - Keishi Yamashita
- Department of Surgery, Kitasato University School of Medicine, Kitasato 1-15-1, Minami-ku, Sagamihara, Kanagawa, 252-0374, Japan
| | - Kei Hosoda
- Department of Surgery, Kitasato University School of Medicine, Kitasato 1-15-1, Minami-ku, Sagamihara, Kanagawa, 252-0374, Japan
| | - Hiromitsu Moriya
- Department of Surgery, Kitasato University School of Medicine, Kitasato 1-15-1, Minami-ku, Sagamihara, Kanagawa, 252-0374, Japan
| | - Katsuhiko Higuchi
- Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Japan
| | - Mizutomo Azuma
- Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Japan
| | - Shouko Komori
- Department of Radiology and Radiation Oncology, Kitasato University School of Medicine, Sagamihara, Japan
| | - Tsutomu Yoshida
- Department of Pathology, Kitasato University School of Medicine, Sagamihara, Japan
| | - Satoshi Tanabe
- Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Japan
| | - Wasaburo Koizumi
- Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Japan
| | - Natsuya Katada
- Department of Surgery, Kitasato University School of Medicine, Kitasato 1-15-1, Minami-ku, Sagamihara, Kanagawa, 252-0374, Japan
| | - Masahiko Watanabe
- Department of Surgery, Kitasato University School of Medicine, Kitasato 1-15-1, Minami-ku, Sagamihara, Kanagawa, 252-0374, Japan
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Maeda O, Matsuoka A, Miyahara R, Funasaka K, Hirooka Y, Fukaya M, Nagino M, Kodera Y, Goto H, Ando Y. Modified docetaxel, cisplatin and capecitabine for stage IV gastric cancer in Japanese patients: A feasibility study. World J Gastroenterol 2017; 23:1090-1097. [PMID: 28246483 PMCID: PMC5311098 DOI: 10.3748/wjg.v23.i6.1090] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/20/2016] [Revised: 12/30/2016] [Accepted: 01/17/2017] [Indexed: 02/07/2023] Open
Abstract
AIM
To evaluate the feasibility of chemotherapy including fluoropyrimidine, platinum and taxane with modified dosages for unresectable gastric cancer in Japanese patients.
METHODS
We performed a feasibility study of a modified docetaxel, cisplatin and capecitabine (DCX) regimen for stage IV gastric cancer. In particular, 30 or 40 mg/m2 of docetaxel on day 1, 60 mg/m2 of cisplatin on day 1, and 2000 mg/m2 of capecitabine for 2 wk were administered every three weeks.
RESULTS
Three patients were treated with modified DCX (mDCX) with 30 mg/m2 docetaxel, and five patients were treated with this regimen with 40 mg/m2 docetaxel. Grade 3 or 4 neutropenia was observed in six of the eight patients; no patients exhibited febrile neutropenia. Partial response was achieved in four of the eight patients. Three patients underwent gastrectomy, which achieved R0 resection without residual tumors in dissected lymph nodes. In one of these three patients, resected specimens revealed pathological complete response in the primary lesion and in lymph nodes.
CONCLUSION
mDCX was well tolerated by Japanese patients with stage IV gastric cancer. This regimen might be useful for allowing gastric cancer patients with distant lymph node metastasis to undergo conversion surgery.
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Phase 2 study of adjuvant chemotherapy with docetaxel, capecitabine, and cisplatin in patients with curatively resected stage IIIB-IV gastric cancer. Gastric Cancer 2017; 20:182-189. [PMID: 26661592 DOI: 10.1007/s10120-015-0580-2] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2015] [Accepted: 11/17/2015] [Indexed: 02/07/2023]
Abstract
OBJECTIVE Postoperative chemotherapy with S-1 or capecitabine plus oxaliplatin is a standard treatment for resectable gastric cancer (GC). However, survival outcomes of stage IIIB-IV (M0) GC cases are still poor. We investigated the efficacy and safety of docetaxel, capecitabine, and cisplatin (DXP) in patients with stage IIIB-IV GC. METHODS This was a single-arm phase 2 study that included patients with stage IIIB-IV GC who underwent D2 gastrectomy. Patients received six cycles of docetaxel [60 mg/m2 on day 1 (D1)], capecitabine (1,875 mg/m2/day on D1-14), and cisplatin (60 mg/m2 on D1) every 3 weeks. The primary end-point was recurrence-free survival (RFS). RESULTS A total of 46 GC patients between January 2007 and August 2008 were included. After a median follow-up of 56.1 months (range 52.2-64.1), the median RFS and overall survival (OS) were 26.9 months (95 % CI 7.5-46.4) and 43.9 months (95 % CI 29.2-58.7), respectively. The 5-year RFS and OS rates were 39.1 and 41.3 %, respectively. The most common grade 3/4 toxicities were neutropenia (40 %), anorexia (22 %), and febrile neutropenia (15 %). CONCLUSIONS Adjuvant DXP is feasible and effective for patients with stage IIIB-IV GC. A phase 3 study comparing triplet and doublet regimens for these patients is ongoing.
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Dassen AE, Bernards N, Lemmens VEPP, Wouw YAJVD, Bosscha K, Creemers GJ, Pruijt HJFM. Phase II study of docetaxel, cisplatin and capecitabine as preoperative chemotherapy in resectable gastric cancer. World J Gastrointest Surg 2016; 8:706-712. [PMID: 27830043 PMCID: PMC5081553 DOI: 10.4240/wjgs.v8.i10.706] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/18/2016] [Revised: 07/06/2016] [Accepted: 08/08/2016] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate the feasibility of preoperative docetaxel, cisplatin and capecitabine (DCC) in patients with resectable gastric cancer.
METHODS Patients with resectable gastric cancer fulfilling the inclusion criteria, were treated with 4 cycles of docetaxel (60 mg/m2), cisplatin (60 mg/m2) and capecitabine (1.875 mg/m2 orally on day 1-14, two daily doses) repeated every three weeks, followed by surgery. Primary end point was the feasibility and toxicity/safety profile of DCC, secondary endpoints were pathological complete resection rate and pathological complete response (pCR) rate.
RESULTS All of the patients (51) were assessable for the feasibility and safety of the regimen. The entire preoperative regimen was completed by 68.6% of the patients. Grade III/IV febrile neutropenia occurred in 10% of all courses. Three patients died due to treatment related toxicity (5.9%), one of them (also) because of refusing further treatment for toxicity. Of the 45 patients who were evaluable for secondary endpoints, four developed metastatic disease and 76.5% received a curative resection. In 3 patients a pCR was seen (5.9%), two patients underwent a R1 resection (3.9%).
CONCLUSION Four courses of DCC as a preoperative regimen for patients with primarily resectable gastric cancer is highly demanding. The high occurrence of febrile neutropenia is of concern. To decrease the occurrence of febrile neutropenia the prophylactic use of granulocyte colony-stimulating factor (G-CSF) should be explored. A curative resection rate of 76.5% is acceptable. The use of DCC without G-CSF support as preoperative regimen in resectable gastric cancer is debatable.
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Abstract
Unresectable gastric cancer cases are often diagnosed at a far advanced stage, which are hard to resect radically and suffer a poor prognosis. Therefore, palliative chemotherapy is recommended as the main treatment by the current clinical guidelines for gastric cancer. Fortunately, in recent years some clinical studies revealed that after treatment with chemotherapy, radiotherapy, targeted therapy, interventional therapy, hyperthermic intraperitoneal chemotherapy (HIPEC) and so on, and multidisciplinary assessment, many unresectable gastric cancer cases could be converted into resectable cases, which consequently prolongs their survival time and improves their quality of life significantly. In the present review, we summarize the status and progress of treatment for unresectable gastric cancer, as well as the strategy and case selection for conversion therapy.
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Kinoshita O, Ichikawa D, Ichijo Y, Komatsu S, Okamoto K, Kishimoto M, Yanagisawa A, Otsuji E. Histological evaluation for chemotherapeutic responses of metastatic lymph nodes in gastric cancer. World J Gastroenterol 2015; 21:13500-13506. [PMID: 26730161 PMCID: PMC4690179 DOI: 10.3748/wjg.v21.i48.13500] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/03/2015] [Revised: 09/22/2015] [Accepted: 10/20/2015] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the effect of preoperative chemotherapy (pre-CTx) for metastatic lymph nodes (MLNs) of gastric cancer (GC).
METHODS: A retrospective cohort of patients with advanced GC, who underwent pre-CTx followed by gastrectomy, was reviewed. The histological tumor regression grade (TRG), which considered the percentage of residual cancer in the visible tumor bed, was applied to primary tumors and individual MLNs: G1a (complete response), G1b (< 10%), G2 (10%-50%) and G3 (> 50%). The clinical response to pre-CTx was retrospectively evaluated using only MLNs information, and we compared the histological and clinical evaluations of MLNs.
RESULTS: Twenty-eight patients were enrolled. A total of 438 MLNs were retrieved, and 22 (5%), 48 (11%), 63 (14%) and 305 (70%) LNs were assigned as G1a, G1b, G2 and G3, respectively. Stratification of the residual MLNs based on the TRGs was as follows: 28 G1b MLNs (9%), 48 G2 MLNs (15%), and 253 G3 MLNs (76%) in the D1 region; 20 (23%), 15 (17%), and 52 (60%) in the D2 region, respectively. However, no significant correlation was found between TRGs in MLNs and clinical response in the subgroup for which evaluation of clinical response was available.
CONCLUSION: Pre-CTx does not provide any outstanding histological benefit for MLNs, and an appropriate D2 lymphadenectomy should routinely be performed to offer the chance of curative resection.
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Ma J, Yao S, Li XS, Kang HR, Yao FF, Du N. Neoadjuvant Therapy of DOF Regimen Plus Bevacizumab Can Increase Surgical Resection Ratein Locally Advanced Gastric Cancer: A Randomized, Controlled Study. Medicine (Baltimore) 2015; 94:e1489. [PMID: 26496252 PMCID: PMC4620807 DOI: 10.1097/md.0000000000001489] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2015] [Revised: 07/14/2015] [Accepted: 08/10/2015] [Indexed: 12/17/2022] Open
Abstract
Locally advanced gastric cancer (LAGC) is best treated with surgical resection. Bevacizumab in combination with chemotherapy has shown promising results in treating advanced gastric cancer. This study aimed to investigate the efficacy of neoadjuvant chemotherapy using the docetaxel/oxaliplatin/5-FU (DOF) regimen and bevacizumab in LAGC patients.Eighty LAGC patients were randomized to receive DOF alone (n = 40) or DOF plus bevacizumab (n = 40) as neoadjuvant therapy before surgery. The lesions were evaluated at baseline and during treatment. Circulating tumor cells (CTCs) were counted using the FISH test. Patients were followed up for 3 years to analyze the disease-free survival (DFS) and overall survival (OS).The total response rate was significantly higher in the DOF plus bevacizumab group than the DOF group (65% vs 42.5%, P = 0.0436). The addition of bevacizumab significantly increased the surgical resection rate and the R0 resection rate (P < 0.05). The DOF plus bevacizumab group showed significantly greater reduction in CTC counts after neoadjuvant therapy in comparison with the DOF group (P = 0.0335). Although the DOF plus bevacizumab group had significantly improved DFS than the DOF group (15.2 months vs 12.3 months, P = 0.013), the 2 groups did not differ significantly in OS (17.6 ± 1.8 months vs 16.4 ± 1.9 months, P = 0.776. Cox proportional model analysis showed that number of metastatic lymph nodes, CTC reduction, R0 resection, and neoadjuvant therapy are independent prognostic factors for patients with LAGC.Neoadjuvant of DOF regimen plus bevacizumab can improve the R0 resection rate and DFS in LAGC. These beneficial effects might be associated with the reduction in CTC counts.
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Affiliation(s)
- Junxun Ma
- From the Department of Medical Oncology, First Affiliated Hospital, Chinese PLA General Hospital, Beijing, China
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Koo DH, Ryu MH, Ryoo BY, Seo J, Lee MY, Chang HM, Lee JL, Lee SS, Kim TW, Kang YK. Improving trends in survival of patients who receive chemotherapy for metastatic or recurrent gastric cancer: 12 years of experience at a single institution. Gastric Cancer 2015; 18:346-53. [PMID: 24832201 DOI: 10.1007/s10120-014-0385-8] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2014] [Accepted: 04/23/2014] [Indexed: 02/06/2023]
Abstract
BACKGROUND The aim of this retrospective study was to evaluate the changes in clinical features and treatment outcomes of the patients with metastatic or recurrent gastric cancer (MRGC) treated in the past 12 years. METHODS A total of 3888 patients who received chemotherapy for MRGC between January 2000 and December 2011 were analyzed via a prospectively collected registry. The analysis focused on the comparison among three periods: 2000-2003 (period 1), 2004-2007 (period 2) and 2008-2011 (period 3). RESULTS There were 880 patients (23%) in period 1, 1573 (40%) in period 2 and 1435 (37%) in period 3. The most commonly used first-line chemotherapy regimen was fluoropyrimidine with/without platinum (72%) for all periods. The use of second- and third-line chemotherapy was slightly but significantly more common in the two recent periods: 46 and 19 % in period 1, 54 and 26% in period 2, and 53 and 27% in period 3, respectively. Overall, 3494 patients (89.9%) died with a median overall survival (OS) of 10.6 months (95% CI 10.2-11.0). The OS was statistically significantly improved over the study period: 9.6 months (95% CI 9.0-10.2) in period 1, 10.3 months (95% CI 9.8-10.9) in period 2 and 11.7 months (95% CI 11.0-12.4) in period 3 (p for trend <0.001). Multivariate analysis including eight prognostic factors (performance, gastrectomy, peritoneal/bone/lung metastasis, abnormal alkaline phosphatase/albumin/total bilirubin) showed that the more recent treatment period was an independent favorable prognostic factor for OS (p < 0.001). CONCLUSION The OS of patients who receive chemotherapy for MRGC has been shown to improve over time.
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Affiliation(s)
- Dong Hoe Koo
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 138-736, Korea
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Phua VCE, Wong WQ, Tan PL, Bustam AZ, Saad M, Alip A, Ishak WZW. Capecitabine Pattern of Usage, Rate of Febrile Neutropaenia and Treatment Related Death in Asian Cancer Patients in Clinical Practice. Asian Pac J Cancer Prev 2015; 16:1449-53. [DOI: 10.7314/apjcp.2015.16.4.1449] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open
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Bilici A, Selcukbiricik F, Demir N, Ustaalioglu BBO, Dikilitas M, Yildiz O. Modified Docetaxel and Cisplatin in Combination with Capecitabine (DCX) as a First-Line Treatment in HER2-Negative Advanced Gastric Cancer. Asian Pac J Cancer Prev 2014; 15:8661-6. [DOI: 10.7314/apjcp.2014.15.20.8661] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
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Ozdemir N, Abali H, Vural M, Yalcin S, Oksuzoglu B, Civelek B, Oguz D, Bostanci B, Yalcin B, Zengin N. Docetaxel, cisplatin, and fluorouracil combination in neoadjuvant setting in the treatment of locally advanced gastric adenocarcinoma: Phase II NEOTAX study. Cancer Chemother Pharmacol 2014; 74:1139-47. [DOI: 10.1007/s00280-014-2586-6] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2014] [Accepted: 09/02/2014] [Indexed: 01/28/2023]
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Wei ZW, Li JL, Wu Y, Xia GK, Schwarz RE, He YL, Zhang CH. Impact of pre-existing type-2 diabetes on patient outcomes after radical resection for gastric cancer: a retrospective cohort study. Dig Dis Sci 2014; 59:1017-24. [PMID: 24318804 DOI: 10.1007/s10620-013-2965-6] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/12/2013] [Accepted: 11/15/2013] [Indexed: 12/29/2022]
Abstract
BACKGROUND The aim of this study was to evaluate the impact of pre-existing type-2 diabetes on postoperative recovery and prognosis in gastric cancer (GC) patients who underwent radical gastrectomy. RESEARCH DESIGN AND METHODS From June 2001 to June 2011, a total of 1,014 eligible patients were enrolled. Among them, 67 patients were diagnosed with type-2 diabetes. The clinicopathologic features and prognostic data were compared between patients with type-2 diabetes (the DM group) and without diabetes (the non-DM group). RESULTS Median survival was 68.3 months. The 5-year overall survival in the DM group was similar to that in the non-DM group (52.1 vs. 53.0 %, p = 0.411). Propensity score matching analysis demonstrated that the hazard ratio of death in the DM group was 1.191 (95 % confidential index 0.693-2.072; p = 0.531) compared to the-non DM group. Incidence of postoperative complications was higher in the DM group than in the non-DM group (17.9 vs. 8.1 %, p = 0.006). The DM remission rate was 46 % among patients who received Roux-en-Y reconstruction, and 13 % among patients who received Billroth II anastomosis (p = 0.009). The 5-year overall survival rate was 62.1 % for patients with cured or improved DM and 23.4 % for patients with worse or same DM status (p = 0.003). CONCLUSION Type-2 diabetes can be cured by radical gastrectomy plus Roux-en-Y reconstruction in some GC patients. Pre-existing diabetes is associated with increased postoperative complications and decreased survival when it becomes worse after curative dissection for GC.
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Affiliation(s)
- Zhe-Wei Wei
- Department of Gastrointestinopancreatic Surgery, The First Affiliated Hospital, Sun Yat-sen University, 58 Zhongshan 2nd Road, Guangzhou, 510080, Guangdong, China
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Shen L, Shan YS, Hu HM, Price TJ, Sirohi B, Yeh KH, Yang YH, Sano T, Yang HK, Zhang X, Park SR, Fujii M, Kang YK, Chen LT. Management of gastric cancer in Asia: resource-stratified guidelines. Lancet Oncol 2013; 14:e535-47. [PMID: 24176572 DOI: 10.1016/s1470-2045(13)70436-4] [Citation(s) in RCA: 378] [Impact Index Per Article: 31.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Gastric cancer is the fourth most common cancer globally, and is the second most common cause of death from cancer worldwide. About three-quarters of newly diagnosed cases in 2008 were from Asian countries. With a high mortality-to-incidence ratio, management of gastric cancer is challenging. We discuss evidence for optimum management of gastric cancer in aspects of screening and early detection, diagnosis, and staging; endoscopic and surgical intervention; and the concepts of perioperative, postoperative, and palliative chemotherapy and use of molecularly targeted therapy. Recommendations are formulated on the basis of the framework provided by the Breast Health Global Initiative, using the categories of basic, limited, enhanced, and maximum level. We aim to provide a stepwise strategy for management of gastric cancer applicable to different levels of health-care resources in Asian countries.
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Affiliation(s)
- Lin Shen
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Oncology, Peking University Cancer Hospital and Institute, Beijing, China
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Abstract
This review presents the current status of adjuvant and neoadjuvant treatment options for primary resectable gastric cancer in the East, with updated data from recent studies. Marked disparities between the East and the West in standard surgical procedures (D2 vs. D1/0 lymphadenectomy) and their outcomes result in significant geographical variation in preferred adjuvant treatments. Currently, oral fluoropyrimidine-based postoperative adjuvant chemotherapy, 1 year of S-1 chemotherapy, or capecitabine plus oxaliplatin for 6 months are the standards of care after curative resection with D2 lymphadenectomy for stage II/III gastric cancer in the East, though there is still some room for improvement. The role of postoperative adjuvant chemoradiotherapy (CRT) following curative D2 gastrectomy has long been debated in the East. However, the first prospective randomized controlled trial comparing CRT with chemotherapy alone failed to demonstrate a survival benefit, thus further studies are required. Chemotherapy has been pursued as a neoadjuvant approach in East Asia because of a rare locoregional recurrence after curative D2 gastrectomy. Locally advanced, marginally resectable gastric cancer with poor prognosis, such as large type 3 or 4 tumors, para-aortic and/or bulky nodal disease, and serosa-positive gastric cancer, is the main target of neoadjuvant chemotherapy. Promising efficacy has been demonstrated in several phase II studies with the safe use of D2 or more extended surgery following neoadjuvant chemotherapy. Although the results of ongoing phase III trials are awaited, Asian findings could be relevant and generalizable to other regions when D2 surgery is performed by experienced surgeons.
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Affiliation(s)
- Kazumasa Fujitani
- Department of Surgery, Osaka National Hospital, Osaka 540-006, Japan.
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An JY, Kim HI, Cheong JH, Hyung WJ, Kim CB, Noh SH. Pathologic and oncologic outcomes in locally advanced gastric cancer with neoadjuvant chemotherapy or chemoradiotherapy. Yonsei Med J 2013; 54:888-94. [PMID: 23709422 PMCID: PMC3663211 DOI: 10.3349/ymj.2013.54.4.888] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
PURPOSE Although neoadjuvant therapy has been accepted as a treatment option in locally-advanced gastric cancer, its prognostic value has been difficult to evaluate. MATERIALS AND METHODS Seventy-four gastric cancer patients who underwent gastrectomy after neoadjuvant treatment were divided into two groups according to the pathologic response: favorable (ypT0) and others (ypT1-4). The clinicopathologic characteristics, predictive factors for pathologic response, and oncologic outcome were evaluated. RESULTS Eleven patients (14.8%) demonstrated ypT0 and the remaining 63 patients (85.2%) were ypT1-4. Chemoradiotherapy (CCRTx) rather than chemotherapy (CTx) was the only predictive factor for a favorable pathologic response. Chemotherapeutic factors and tumor marker levels did not predict pathologic response. The 1-, 2-, and 3-year disease-free survivals were 83.4%, 70%, and 52.2%. The 1-, 3-, 5-year overall survivals were 88.5%, 67.5%, and 51.2%, respectively. Although a complete pathologic response (ypT0N0M0) was achieved in 7 patients, 28.6% of them demonstrated recurrence of the tumor within 6 months after curative surgery. CONCLUSION CCRTx rather than CTx appears to be more effective for achieving good pathologic response. Although favorable pathologic response has been achieved after neoadjuvant treatment, the survival benefit remains controversial.
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Affiliation(s)
- Ji Yeong An
- Department of Surgery, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752, Korea.
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Liao Y, Yang ZL, Peng JS, Xiang J, Wang JP. Neoadjuvant chemotherapy for gastric cancer: a meta-analysis of randomized, controlled trials. J Gastroenterol Hepatol 2013; 28:777-82. [PMID: 23425049 DOI: 10.1111/jgh.12152] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 01/11/2013] [Indexed: 12/27/2022]
Abstract
BACKGROUND AND AIM Although the effect of neoadjuvant chemotherapy in gastric cancer has been extensively studied, the data of survival benefit are still controversial. The purpose of this work was to assess the effectiveness of neoadjuvant chemotherapy followed by surgery in patients with gastric cancer. METHODS We searched systematically electronic through the databases of PUBMED, EMBASE, China Biological Medicine, and China National Knowledge Infrastructure Whole Article for studies published from 1975. Two reviewers independently evaluated the relevant reports and searched manually reference from these reports for additional trials. Outcomes assessed by meta-analysis included overall survival rate, progression-free survival rate, R0 resection rate, downstaging effect, postoperative complications, and perioperative mortality. RESULTS Six randomized, controlled trials with 781 patients were included in the meta-analysis. Odds ratio (95% confidence interval; P-value), expressed as neoadjuvant chemotherapy and surgery versus surgery alone, was 1.16 (0.85-1.58; P = 0.36) for overall survival, 1.24 (0.78-1.96; P = 0.36) for R0 resection, 1.25 (0.75-2.09; P = 0.39) for postoperative complications, and 3.60 (0.59-22.45; P = 0.17) for perioperative mortality. CONCLUSIONS Compared with surgery alone, neoadjuvant chemotherapy followed by surgery was not associated with a higher rate of overall survival or complete resection (R0 resection). It does not increase treatment-related morbidity and mortality. This meta-analysis did not demonstrate a survival benefit for the combination of neoadjuvant chemotherapy and surgery.
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Affiliation(s)
- Yi Liao
- Department of Gastrointestinal Surgery, the Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
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Son SY, Lee CM, Lee JH, Ahn SH, Kim JW, Lee KU, Park DJ, Kim HH. Laparoscopy-assisted gastrectomy with para-aortic lymphadenectomy after palliative chemotherapy for advanced gastric cancer with isolated para-aortic lymph node metastasis. JOURNAL OF THE KOREAN SURGICAL SOCIETY 2013; 84:304-8. [PMID: 23646317 PMCID: PMC3641371 DOI: 10.4174/jkss.2013.84.5.304] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/17/2012] [Revised: 01/26/2013] [Accepted: 02/12/2013] [Indexed: 01/13/2023]
Abstract
Prophylactic para-aortic lymphadenectomy is not recommended in curable advanced gastric cancer. However, there are few reports on therapeutic para-aortic lymphadenectomy after palliative chemotherapy in far advanced gastric cancer. We report three cases of laparoscopy-assisted gastrectomy with para-aortic lymphadenectomy after palliative chemotherapy for the first time in Korea. Three gastric cancer patients with isolated para-aortic lymph node (PAN) metastasis showed partial response to capecitabine-based chemotherapy, and laparoscopy-assisted gastrectomy with para-aortic lymphadenectomy was performed with curative intent. The mean total operation time was 365 minutes (range, 310 to 415 minutes), and the mean estimated blood loss was 158 mL (range, 125 to 200 mL). The mean number of retrieved PAN was 9 (range, 8 to 11), and all pathologic results showed no metastasis of para-aortic region. All patients recovered and were discharged without any significant complications.
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Affiliation(s)
- Sang-Yong Son
- Department of Surgery, Seoul National University Bundang Hospital, Seongnam, Korea
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Han DS, Suh YS, Kong SH, Lee HJ, Im SA, Bang YJ, Kim WH, Yang HK. Outcomes of surgery aiming at curative resection in good responder to induction chemotherapy for gastric cancer with distant metastases. J Surg Oncol 2013; 107:511-516. [PMID: 23090791 DOI: 10.1002/jso.23284] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2011] [Accepted: 09/30/2012] [Indexed: 01/30/2023]
Abstract
BACKGROUND The aim of this study is to analyze the outcome of surgery with curative intent in good responder to induction chemotherapy for gastric cancer with distant metastases (M1 gastric cancer). MATERIALS AND METHODS We reviewed M1 gastric cancer patients in whom radiologic evaluation suggests disappearance of metastatic lesion after chemotherapy and received operation from January 2000 to December 2009. Clinicopathologic variables and oncologic outcomes were evaluated. RESULTS Of the 34 patients who underwent surgery with curative intent after chemotherapy, overall R0 resection rate was 76.5% (26/34). R0 resection rate was 88.0% (22/25) in initial one metastatic site and 44.4% (4/9) in two metastatic sites (P = 0.017). Postoperative morbidity and mortality rate were 14.7% and 0%. Recurrence rate was 61.5% (16/26) after R0 resection. Median survival was 22.9 and 7.8 months according to R0 versus non-R0 resection (P = 0.033). After R0 resection, 3-year overall survival was 51.7% in ypN0-2 stage group. CONCLUSION The present study provides evidence that in patients with M1 gastric cancer which confined to one site who respond well to induction chemotherapy, a higher rate of R0 resection and longer survival can be expected. A multicenter cohort study is needed to explore this concept further.
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Affiliation(s)
- Dong-Seok Han
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
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Lorenzen S, Pauligk C, Homann N, Schmalenberg H, Jäger E, Al-Batran SE. Feasibility of perioperative chemotherapy with infusional 5-FU, leucovorin, and oxaliplatin with (FLOT) or without (FLO) docetaxel in elderly patients with locally advanced esophagogastric cancer. Br J Cancer 2013; 108:519-26. [PMID: 23322206 PMCID: PMC3593547 DOI: 10.1038/bjc.2012.588] [Citation(s) in RCA: 77] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND The aim of this exploratory subgroup analysis of the fluorouracil, oxaliplatin, docetaxel (FLOT)65+ trial was to determine tolerability and feasibility of perioperative chemotherapy in elderly, potentially operable esophagogastric cancer patients. METHODS Patients aged ≥65 with locally advanced esophagogastric adenocarcinoma were randomized to perioperative chemotherapy consisting of four pre- and four postoperative cycles of infusional 5-FU, leucovorin, and oxaliplatin (FLO) without or with docetaxel 50 mg m(-)(2) (FLOT), every 2 weeks. RESULTS Forty-four patients with a median age of 70 years were randomized and 43 patients started preoperative chemotherapy (FLO, 22; FLOT, 21). Thirty-eight (86.4%) patients completed four cycles of preoperative chemotherapy and 32 (74.4%) proceeded to surgery, with 67.4% R0 resections on intent-to-treat analysis (90.1% of the 32 patients who underwent resection). Median overall survival was not reached and median progression-free survival (PFS) was 17.3 months. Compared with the FLO group, the FLOT group showed a trend towards an improved median PFS (21.1 vs 12.0 months; P=0.09), however, associated with increased chemotherapy related toxicity. No perioperative mortality was observed. Postoperative morbidity was observed in 46.9% of patients (FLO, 35.3%; FLOT, 60%). CONCLUSION Neoadjuvant FLO or FLOT may offer a reasonable chance of curative surgery in elderly patients with locally advanced resectable gastroesophageal cancer. However, the increase in side effects with the FLOT regimen and postoperative morbidity should be carefully considered when an intensive chemotherapy regimen is planned.
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Affiliation(s)
- S Lorenzen
- Third Department of Internal Medicine (Hematology/Medical Oncology), Klinikum rechts der Isar, Technische Universität München, Munich, Germany
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Thuss-Patience PC, Hofheinz RD, Arnold D, Florschütz A, Daum S, Kretzschmar A, Mantovani-Löffler L, Bichev D, Breithaupt K, Kneba M, Schumacher G, Glanemann M, Schlattmann P, Reichardt P, Gahn B. Perioperative chemotherapy with docetaxel, cisplatin and capecitabine (DCX) in gastro-oesophageal adenocarcinoma: a phase II study of the Arbeitsgemeinschaft Internistische Onkologie (AIO){dagger}. Ann Oncol 2012; 23:2827-2834. [PMID: 22734012 DOI: 10.1093/annonc/mds129] [Citation(s) in RCA: 58] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND This prospective multicentre phase II trial assessed the feasibility and efficacy of perioperative chemotherapy with docetaxel, cisplatin and capecitabine (DCX) in patients with gastro-oesophageal adenocarcinoma. METHODS Patients with curatively resectable adenocarcinoma of the stomach, the gastro-oesophageal junction or the lower third of the oesophagus were enrolled. Patients received docetaxel 75 mg/m(2) plus cisplatin 60 mg/m(2) (day 1), followed by oral capecitabine 1875 mg/m(2) divided into two doses (days 1-14) every 3 weeks. There were three cycles preoperatively and three cycles postoperatively. The primary end point was the R0 resection rate. RESULTS Fifty-one patients were recruited and assessed for feasibility and efficacy. 94.1% of patients received all three planned cycles preoperatively, and 52.9% received three cycles postoperatively. The R0 resection rate was 90.2%. 13.7% of patients showed complete pathological remission (pCR). Toxicity was acceptably tolerable. Without prophylactic granulocyte colony-stimulating factor administration, neutropenic fever developed in 21.5% of patients preoperatively (grade 3 or 4) and in 11.1% of patients postoperatively. CONCLUSIONS DCX is a safe and feasible perioperative regimen in the treatment of gastro-oesophageal adenocarcinoma with a high percentage of cycles delivered pre- and postoperatively, compared with standard practice. The high efficacy in terms of R0 resection rate and pCR is very promising.
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Affiliation(s)
- P C Thuss-Patience
- Department of Haematology, Oncology and Tumorimmunology, Campus Virchow-Klinikum, Charité - University Medicine Berlin, Berlin.
| | - R D Hofheinz
- 3rd Medical Clinic, University Medicine Mannheim, Mannheim
| | - D Arnold
- Hubertus Wald Tumour Center, University Cancer Center Hamburg (UCCH), University Medical Center Hamburg-Eppendorf, Hamburg
| | - A Florschütz
- Department of Haematology and Oncology, Städtisches Klinikum Dessau, Dessau
| | - S Daum
- Department of Gastroenterology, Infectious Diseases and Rheumatology, Campus Benjamin-Franklin, Charité - University Medicine Berlin, Berlin
| | - A Kretzschmar
- Department of Haematology, Oncology and Tumorimmunology, HELIOS-Klinikum Berlin-Buch, Berlin; Department of Medical Oncology and Haematology, St George's Hospital, Leipzig
| | - L Mantovani-Löffler
- Department of Medical Oncology and Haematology, St George's Hospital, Leipzig
| | - D Bichev
- Department of Haematology, Oncology and Tumorimmunology, Campus Virchow-Klinikum, Charité - University Medicine Berlin, Berlin
| | - K Breithaupt
- Department of Haematology, Oncology and Tumorimmunology, Campus Virchow-Klinikum, Charité - University Medicine Berlin, Berlin
| | - M Kneba
- 2nd Department of Medicine, University Medical Center Schleswig-Holstein, Kiel
| | - G Schumacher
- Department of Surgery, Städtisches Klinikum Braunschweig, Braunschweig; Department of General, Visceral and Transplant Surgery, Campus Virchow-Klinikum, Charité - University Medicine Berlin, Berlin
| | - M Glanemann
- Department of General, Visceral and Transplant Surgery, Campus Virchow-Klinikum, Charité - University Medicine Berlin, Berlin
| | - P Schlattmann
- Department of Medical Statistics, Informatics and Documentation, University Hospital of Friedrich-Schiller University Jena, Jena
| | - P Reichardt
- Department of Haematology, Oncology, Palliative Medicine, HELIOS-Klinikum Bad Saarow, Bad Saarow, Germany
| | - B Gahn
- 2nd Department of Medicine, University Medical Center Schleswig-Holstein, Kiel
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An JY, Kim KM, Kim YM, Cheong JH, Hyung WJ, Noh SH. Surgical complications in gastric cancer patients preoperatively treated with chemotherapy: their risk factors and clinical relevance. Ann Surg Oncol 2012; 19:2452-8. [PMID: 22395984 DOI: 10.1245/s10434-012-2267-9] [Citation(s) in RCA: 50] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2011] [Indexed: 12/27/2022]
Abstract
BACKGROUND This study was designed to identify risk factors and oncological value for the development of postoperative complications after gastrectomy in gastric cancer patients with preoperative chemotherapy. METHODS A total of 123 gastric cancer patients who underwent gastrectomy after chemotherapy were enrolled in this study. The incidence, type, risk factors, and prognostic value of surgical complications were evaluated. RESULTS The postoperative complication rate was 29.3% and mortality rate was 1.6%. The development of postoperative complications was associated with operation time (>200 min) and transfusion during surgery. The resection extent, preoperative chemotherapy cycles and regimens, tumor stage, and patients' nutritional status were not predictive factors for the development of surgical complications. In the multivariate analysis, operation time was an independent risk factor for the development of postoperative complications (odds ratio, 3.813; P = 0.011). The median follow-up after surgery was 19 months. The 3-year, disease-free survival was 57.1% in patients without complications and 25.7% in patients with complications (P = 0.004). Multivariable analysis demonstrated postoperative complications were a significant prognostic factor for disease-free survival (hazard ratio, 2.676; P = 0.024). CONCLUSIONS The incidence of surgical complications was high in gastric cancer patients who received preoperative chemotherapy. Long operation time was a risk factor for surgical complications, and the development of postoperative complication was predictive of patients' prognoses.
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Affiliation(s)
- Ji Yeong An
- Department of Surgery, Yonsei University College of Medicine, Seoul, Korea
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A prognostic model in patients who receive chemotherapy for metastatic or recurrent gastric cancer: validation and comparison with previous models. Cancer Chemother Pharmacol 2011; 68:913-21. [PMID: 21290247 DOI: 10.1007/s00280-011-1561-8] [Citation(s) in RCA: 58] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2010] [Accepted: 01/16/2011] [Indexed: 10/18/2022]
Abstract
PURPOSE To make up for the limitations of previous prognostic models, we developed and validated a model in patients with metastatic or recurrent gastric adenocarcinoma (AGC), and to compare with previous models. METHODS A total of 2,805 patients received chemotherapy for AGC in Asan Medical Center between January 2000 and December 2008 and were randomly split into training and validation sets of 1,870 and 935 patients, respectively. A prognostic model was developed from the training set. RESULTS The median follow-up duration was 26.5 months (range, 10.8-116.3), during which time 2,495 patients (88.9%) died. Eight factors associated with poor prognosis were identified by multivariate analysis: ECOG performance status ≥2 (2 points), no gastrectomy, peritoneal metastasis, bone metastasis (2 points), lung metastasis, alkaline phosphatase > 120 IU/l, albumin < 3.3 g/dL, and total bilirubin > 1.2 mg/dL. A prognostic model was developed by dividing patients into good (0-1 points), moderate (2-3), and poor (≥4) risk groups. The overall survival (OS) curves for three risk groups differed significantly for both the training and the validation sets (P < 0.001 each). In the training set, the median OS for the three risk groups was 14.0, 9.4, and 5.1 months, respectively. Application of three previous prognostic models to our validation set showed that the four models, including ours, had similar ability to predict survival outcomes (c-statistics, 0.5520-0.5836). CONCLUSION Validation and comparison of prognostic models indicated that our model was as effective as the previous models to stratify the patients with AGC.
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Kang YK, Ryu MH, Yoo C, Chang HM, Yook JH, Oh ST, Kim BS, Kim TW. Phase I/II study of a combination of docetaxel, capecitabine, and cisplatin (DXP) as first-line chemotherapy in patients with advanced gastric cancer. Cancer Chemother Pharmacol 2010; 67:1435-43. [PMID: 20811894 DOI: 10.1007/s00280-010-1444-4] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2010] [Accepted: 08/20/2010] [Indexed: 12/12/2022]
Abstract
BACKGROUND This study was conducted to determine the optimal dosage of the docetaxel-capecitabine-cisplatin (DXP) regimen and to evaluate its efficacy and safety in patients with advanced gastric cancer. METHODS Patients with advanced gastric or esophagogastric junctional adenocarcinoma received capecitabine (days 1-14) and intravenous docetaxel and cisplatin (day 1) every 3 weeks. RESULTS In the phase I study, 15 patients were treated with 4 different dose levels. Asthenia and neutropenic fever were the dose-limiting toxicities. For the phase II study, 1,125 mg/m(2) of capecitabine was initially recommended with 60 mg/m(2) docetaxel and 60 mg/m(2) cisplatin. However, frequent dose modifications at this dose level resulted in a final optimal dose of 937.5 mg/m(2) capecitabine. Among the 40 patients enrolled in the phase II study, 4 complete and 23 partial responses were observed, presenting objective response rate of 68%. Ten patients achieving good response with complete disappearance of distant metastases underwent surgery, and 4 pathologic complete responses were identified. After the median follow-up of 83.7 months (range, 20.2-86.5) in surviving patients, the median overall survival was 14.4 months and median progression-free survival was 7.6 months. The most frequent grade 3/4 adverse events were neutropenia (62.5%) and asthenia (37.5%). Ten per cent of the patients experienced neutropenic fever, with one case of sepsis-induced death. CONCLUSION DXP displays considerable antitumor activity, and may thus present effective first-line treatment for advanced gastric cancer. Further investigation of the efficacy and safety of this regimen in both first-line and neoadjuvant settings is warranted.
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Affiliation(s)
- Yoon-Koo Kang
- Department of Oncology, Asan Medical Center, 86 Asanbyeongwon-gil, Songpa-gu, Seoul 138-736, South Korea.
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Phase II study of S-1, docetaxel and cisplatin combination chemotherapy in patients with unresectable metastatic gastric cancer. Cancer Chemother Pharmacol 2009; 66:721-8. [PMID: 20041328 DOI: 10.1007/s00280-009-1215-2] [Citation(s) in RCA: 57] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2009] [Accepted: 12/09/2009] [Indexed: 12/11/2022]
Abstract
PURPOSE We evaluated the activity and toxicity of docetaxel, cisplatin, and S-1 (DCS) combination chemotherapy in patients with unresectable metastatic gastric cancer. METHODS Patients with histologically proven, unresectable metastatic gastric adenocarcinoma, performance status (PS) 0-2, and no prior chemotherapy were eligible. Patients received oral S-1 (40 mg/m(2) b.i.d.) on days 1-14 and intravenous cisplatin (60 mg/m(2)) and docetaxel (60 mg/m(2)) on day 8 every 3 weeks. RESULTS Thirty-four patients were enrolled between March 2005 and April 2007. Three patients were considered ineligible and did not receive the DSC therapy. Clinical characteristics were as follows: median age, 63 years (range, 44-77); PS, 0/1/2: 23/8/0; women/men, 8/23; and well-differentiated/undifferentiated adenocarcinoma, 10/21. The objective response rate was 87.1% with 1 complete response (3.2%) and 26 partial responses (83.9%) in 31 assessable patients. Four had stable disease (12.9%) but none had progressive disease. Of these 27 responders, 8 (25.8%) achieved downstaging and 7 (22.6%) underwent curative surgery. The median survival time and progression-free survival were 687 days [confidence interval (95% CI), 600.0-1,138.1] and 226 days (95% CI, 182.5-379.3), respectively. Most common grade 3/4 hematologic toxicity was neutropenia (77.4%). Most common grade 3 nonhematologic toxicities included anorexia (35.5%) and nausea (32.3%). All treatment-related toxicities resolved, and no toxic deaths were observed. CONCLUSIONS DCS combination chemotherapy is highly active against unresectable metastatic gastric cancer and can be given safely with proper management of adverse events. Further studies of this combination are warranted.
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