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Goetze T, Chevallay M, Dosch M, Marcelis J, Al-Batran SE, Mönig SP. Oligometastatic disease - a renaissance for surgery? Innov Surg Sci 2025; 10:51-59. [PMID: 40144786 PMCID: PMC11934942 DOI: 10.1515/iss-2023-0044] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2023] [Accepted: 06/28/2024] [Indexed: 03/28/2025] Open
Abstract
Half of the patients with esophageal cancer, cancer of the gastro-esophageal junction and gastric cancer present metastasis at the time of diagnosis. In addition, even patients originally thought to be free of metastasis will present metachronous metastasis in the course of the disease. These patients are considered incurable and current standard of care for metastatic esophageal, gastro-esophageal junction and gastric cancers is a systemic therapy without curative intention. However, patients presenting only a low metastatic load are now defined as oligometastatic disease and should benefit from an aggressive, multimodal therapy. We present here a review of recent publications investigating multimodal therapies for oligometastatic disease and showing that a systemic therapy combined with a resection of the primary tumor together with metastasis is associated with a better prognosis than a systemic therapy alone. We also give a precise focus on esophageal squamous cell carcinomas and adenocarcinomas of the gastro-esophageal junction and of the stomach. Interestingly, patients with oligometastatic cancer of the esophago-gastric junction can even be treated in curative intention with such a multimodal therapy as we present here in a short case report. In conclusion, new therapeutic strategies including multimodal approaches for oligometastatic disease have shown promising results in the last years and ongoing randomized prospective trials will provide us the evidence to include them in future European guidelines.
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Affiliation(s)
- Thorsten Goetze
- Institute for Clinical Cancer Research IKF, Frankfurt, Germany
- UCT-University Cancer Center, Krankenhaus Nordwest, Frankfurt, Germany
| | - Mickael Chevallay
- Division of Digestive Surgery, University Hospitals of Geneva, Geneva, Switzerland
- Oesophagogastric Surgery, Guy’s and St. Thomas Hospital, London, UK
| | - Michel Dosch
- Division of Digestive Surgery, University Hospitals of Geneva, Geneva, Switzerland
| | - Jordan Marcelis
- Division of Digestive Surgery, University Hospitals of Geneva, Geneva, Switzerland
| | - Salah-Eddin Al-Batran
- Institute for Clinical Cancer Research IKF, Frankfurt, Germany
- UCT-University Cancer Center, Krankenhaus Nordwest, Frankfurt, Germany
| | - Stefan Paul Mönig
- Division of Digestive Surgery, University Hospitals of Geneva, Geneva, Switzerland
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Sun W, Li X. Surgical Resection Enhances Survival in Patients With Liver Metastases From Gastric Cancer: A Population-Based, Case-Control Study. Health Sci Rep 2024; 7:e70220. [PMID: 39669188 PMCID: PMC11635178 DOI: 10.1002/hsr2.70220] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2024] [Revised: 10/25/2024] [Accepted: 11/04/2024] [Indexed: 12/14/2024] Open
Abstract
Background and Aims Gastric cancer with liver metastases (GCLM) is a challenging condition that significantly reduces long-term survival rates, but recent advancements in surgical techniques have shown promise. This study aims to comprehensively evaluate the impact of surgical resection on survival rates in GCLM patients. Methods We conducted a population-based analysis utilizing the SEER database for patients diagnosed with GCLM between 2010 and 2015. Overall survival (OS) was compared between patients who underwent cancer-directed surgery (CDS) and those who did not. The overlap weighting method based on lasso regression with penalty factors was employed to minimize selection bias. Survival outcomes were compared using Kaplan-Meier curves and Cox proportional hazards models, with subgroup analyses to further explore the effects of surgery among patients. Results A total of 3694 patients with GCLM were identified. Of those, 354 (9.58%) patients underwent CDS. After propensity score adjustment, The median OS was significantly higher in the surgical resection group (12 months, 95% confidence interval (CI) 11-16) compared to the nonresection group (6 months, 95% CI: 5-6). Cox regression analysis revealed a substantial improvement in OS for the surgical resection group, with a hazard ratio (HR) of 0.562 (95% CI: 0.482-0.656), including patients with adverse conditions. Conclusions The analysis demonstrated a clear association between surgical resection and enhanced OS in GCLM patients. Nevertheless, further research endeavors should be undertaken to identify specific prognostic factors that aid in the selection of optimal candidates for surgical resection.
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Affiliation(s)
- Wuhui Sun
- Department of Thyroid SurgerySecond Affiliated Hospital, Zhejiang University School of MedicineHangzhouChina
| | - Xiawei Li
- Department of SurgerySecond Affiliated Hospital, Zhejiang University School of MedicineHangzhouChina
- Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Cancer InstituteSecond Affiliated Hospital, Zhejiang University School of MedicineHangzhouChina
- Cancer CenterZhejiang UniversityHangzhouChina
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Hsu JT, Lin YN, Chen YF, Kou HW, Wang SY, Chou WC, Wu TR, Yeh TS. A comprehensive overview of gastric cancer management from a surgical point of view. Biomed J 2024:100817. [PMID: 39566657 DOI: 10.1016/j.bj.2024.100817] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2024] [Revised: 10/22/2024] [Accepted: 11/13/2024] [Indexed: 11/22/2024] Open
Abstract
Despite advancements in medical care, surgical technologies, and the development of novel treatments over the past decade, the prognosis for patients with gastric cancer (GC) has only modestly improved. This is primarily due to the fact that the majority of patients are diagnosed at advanced stages or present with metastatic disease. Radical resection remains the cornerstone of potentially curative treatment, yet the overall 5-year survival rate remains below 35%. The management of GC varies globally, influenced by factors such as geographical disparities, patient comorbidities and performance status, surgical approaches, and available medical resources. Multidisciplinary collaboration and a multimodal treatment approach are essential for optimizing patient outcomes. Surgeons must stay updated on emerging surgical concepts and make informed decisions regarding patient selection, timing of intervention, and the adoption of appropriate surgical techniques to improve both quality of life and prognosis. This review aims to provide a surgical perspective on the management of GC across all stages, highlighting the importance of a comprehensive treatment approach. Endoscopic resection may be a viable option for early GC in patients with minimal risk of lymph node metastasis, particularly in elderly patients with high surgical risk or severe comorbidities. For advanced GC, neoadjuvant therapy followed by surgery could be a promising strategy to improve patient outcomes. Conversion surgery offers a potential survival benefit for patients who respond to treatment with tumor downstaging. The treatment of peritoneal carcinomatosis remains challenging; however, hyperthermic intraperitoneal chemotherapy combined with complete cytoreductive surgery or pressurized intraperitoneal aerosolized chemotherapy may prolong survival or improve quality of life in highly selected patients.
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Affiliation(s)
- Jun-Te Hsu
- Department of General Surgery, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan.
| | - Yu-Ning Lin
- Department of General Surgery, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan
| | - Yi-Fu Chen
- Department of General Surgery, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan
| | - Hao-Wei Kou
- Department of General Surgery, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan
| | - Shan-Yu Wang
- Department of General Surgery, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan
| | - Wen-Chi Chou
- Department of Hematology-Oncology, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan
| | - Ting-Rong Wu
- Department of General Surgery, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan
| | - Ta-Sen Yeh
- Department of General Surgery, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan
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Takeno A, Motoori M, Kishi K, Omori T, Hirao M, Masuzawa T, Fujitani K, Yamamato K, Kurokawa Y, Doki Y. Prognostic factors of conversion surgery for stage IV gastric cancer: A multi-institutional retrospective analysis. Ann Gastroenterol Surg 2024; 8:431-442. [PMID: 38707233 PMCID: PMC11066490 DOI: 10.1002/ags3.12778] [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: 09/28/2023] [Revised: 01/06/2024] [Accepted: 01/13/2024] [Indexed: 05/07/2024] Open
Abstract
Background Conversion surgery (CS) is a highly anticipated strategy for stage IV advanced gastric cancer (AGC) with a good response to chemotherapy. However, prognostic factors limiting R0 resection remain unclear. In this multi-institutional study, we investigated the clinical outcomes of CS for stage IV AGC and the prognostic factors of CS-limiting R0 resection and analyzed them according to metastatic patterns. Methods Clinical data on 210 patients who underwent CS for stage IV AGC at six institutions between 2007 and 2017 were retrospectively retrieved. The patient background, preoperative treatment, operative outcomes, and survival times were recorded. Prognostic factors for overall and recurrence-free survival were investigated using univariate and multivariate analyses for patients who underwent R0 resection. Results R0 resection was achieved in 146 (70%) patients. The median survival time was 32 months, and the 3-year survival rate was 45%. Patients who achieved R0 resection had significantly longer survival than those with R1/2 resection (median survival time: 41.5 months vs. 20.7 months). Multivariate analysis identified pathological N positivity for overall and relapse-free survival and pathological T4 for relapse-free survival as significant independent poor prognostic factors of R0 resected patients. There was no significant difference in survival among the peritoneum, liver, and lymph node groups regarding the initial metastatic sites. Conclusions CS with R0 resection for patients with stage IV AGC can lead to longer survival. Patients with pathological T4 and pathological N positivity were eligible for intensive adjuvant therapy after CS with R0 resection.
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Affiliation(s)
- Atsushi Takeno
- Department of Surgery, National Hospital OrganizationOsaka National HospitalOsakaJapan
| | | | - Kentaro Kishi
- Department of SurgeryOsaka Police HospitalOsakaJapan
| | - Takeshi Omori
- Department of Gastroenterological SurgeryOsaka International Cancer InstituteOsakaJapan
| | - Motohiro Hirao
- Department of Surgery, National Hospital OrganizationOsaka National HospitalOsakaJapan
| | - Toru Masuzawa
- Department of SurgeryKansai Rosai HospitalAmagasakiHyogoJapan
| | | | - Kazuyoshi Yamamato
- Department of Gastroenterological Surgery, Graduate School of MedicineOsaka UniversitySuitaOsakaJapan
| | - Yukinori Kurokawa
- Department of Gastroenterological Surgery, Graduate School of MedicineOsaka UniversitySuitaOsakaJapan
| | - Yuichiro Doki
- Department of Gastroenterological Surgery, Graduate School of MedicineOsaka UniversitySuitaOsakaJapan
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Ministrini S, Bencivenga M, Filippini F, Mura G, Milandri C, Mazzei MA, Bagnacci G, Berselli M, Monti M, Morgagni P, Solaini L, Marrelli D, Piccioni S, De Pascale S, Graziosi L, Reddavid R, Rosa F, Belluco C, Tiberio G. A pragmatic approach improves the clinical management of stage IV gastric cancer: Comparison between the Meta-Gastro results and the GIRCG's retrospective series. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2024; 50:107275. [PMID: 37995604 DOI: 10.1016/j.ejso.2023.107275] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2023] [Revised: 10/29/2023] [Accepted: 11/10/2023] [Indexed: 11/25/2023]
Abstract
INTRODUCTION The Italian Research Group for Gastric Cancer developed a prospective database about stage IV gastric cancer, to evaluate how a pragmatic attitude impacts the management of these patients. MATERIALS AND METHODS We prospectively collected data about metastatic gastric cancer patients thanks to cooperation between radiologists, oncologists and surgeons and we analyzed survival and prognostic factors, comparing the results to those obtained in our retrospective study. RESULTS Three-hundred and eighty-three patients were enrolled from 2018 to September 2022. We observed a higher percentage of laparoscopic exploration with peritoneal lavage in the prospective cohort. In the registry only 3.6 % of patients was submitted to surgery without associated chemotherapy, while in the retrospective population 44.3 % of patients were operated on without any chemotherapy. At univariate and multivariate analyses, the different metastatic sites did not show any survival differences among each other (OS 20.0 vs 16.10 vs 16.7 months for lymphnodal, peritoneal and hepatic metastases, respectively), while the number of metastatic sites and the type of treatment showed a statistical significance (OS 16,7 vs 13,0 vs 4,5 months for 1, 2 and 3 different metastatic sites respectively, p < 0.001; 24,2 vs 12,0 vs 2,5 months for surgery with/without chemotherapy, chemotherapy alone and best supportive treatment respectively, p < 0.001). CONCLUSIONS Our data highlight that the different metastatic sites did not show different survivals, but survival is worse in case of multiple localization. In patients where a curative resection can be achieved, acceptable survival rates are possible. A better diagnostic workup and a more accurate staging impact favorably upon survival.
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Affiliation(s)
- Silvia Ministrini
- Surgical Unit, Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, ASST Spedali Civili of Brescia, 25123, Brescia, Italy.
| | - Maria Bencivenga
- General and Upper GI Surgery Division, Department of Surgery, University of Verona, Verona, Italy
| | - Federica Filippini
- General and Upper GI Surgery Division, Department of Surgery, University of Verona, Verona, Italy
| | - Gianni Mura
- Department of Surgery, San Donato Hospital, Arezzo, Italy
| | - Carlo Milandri
- Department of Oncology, San Donato Hospital, 52100, Arezzo, Italy
| | - Maria Antonietta Mazzei
- Unit of Diagnostic Imaging, Department of Medical, Surgical and Neuro Sciences and of Radiological Sciences, University of Siena, Azienda Ospedaliero-Universitaria Senese, 53100, Siena, Italy
| | - Giulio Bagnacci
- Unit of Diagnostic Imaging, Department of Medical, Surgical and Neuro Sciences and of Radiological Sciences, University of Siena, Azienda Ospedaliero-Universitaria Senese, 53100, Siena, Italy
| | - Mattia Berselli
- General Surgical Unit I, Department of Surgery, ASST Settelaghi-Varese, Italy
| | - Manlio Monti
- Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, Italy
| | - Paolo Morgagni
- General and Oncologic Surgery, "Morgagni-Pierantoni" Hospital, Forlì, Italy
| | - Leonardo Solaini
- General and Oncologic Surgery, "Morgagni-Pierantoni" Hospital, Forlì, Italy
| | - Daniele Marrelli
- Unit of General Surgery and Surgical Oncology, Department of Medicine, Surgery and Neurosciences, University of Siena, Strada delle Scotte, 4, 53100, Siena, Italy
| | - Stefania Piccioni
- Unit of General Surgery and Surgical Oncology, Department of Medicine, Surgery and Neurosciences, University of Siena, Strada delle Scotte, 4, 53100, Siena, Italy
| | - Stefano De Pascale
- Digestive Surgery Unit, European Institute of Oncology IRCCS, 20141, Milan, Italy
| | - Luigina Graziosi
- SC di Chirurgia Generale e d'Urgenza, Azienda Ospedaliera di Perugia, Perugia, Italy
| | - Rossella Reddavid
- University of Turin, Department of Oncology, Division of Surgical Oncology and Digestive Surgery, San Luigi University Hospital, Orbassano, Turin, Italy
| | - Fausto Rosa
- Department of Digestive Surgery, Catholic University, A. Gemelli Hospital, Rome, Italy
| | - Claudio Belluco
- Department of Surgical Oncology, Surgical Oncology Unit, National Cancer institute-Centro di Riferimento Oncologico IRCCS, Aviano, PN, Italy
| | - Guido Tiberio
- Surgical Unit, Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, ASST Spedali Civili of Brescia, 25123, Brescia, Italy
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Lin G, Liu Z, Shang‐Guan Z, Zeng G, Lin J, Wu J, Chen Q, Xie J, Li P, Huang C, Zheng C. Comparison of the efficacy between immunochemotherapy and chemotherapy in gastric cancer accompanied with synchronous liver metastases: A real-world retrospective study. Cancer Med 2023; 12:12221-12233. [PMID: 37062073 PMCID: PMC10278523 DOI: 10.1002/cam4.5917] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2022] [Revised: 03/20/2023] [Accepted: 03/27/2023] [Indexed: 04/17/2023] Open
Abstract
BACKGROUND Few studies have investigated the efficacy of comprehensive therapies, including immunotherapy, for gastric cancer with synchronous liver metastases (GCLM). We retrospectively compared the effect of immunochemotherapy and chemotherapy alone as conversion therapies on the oncological outcomes of patients with GCLM. METHODS The clinicopathological data of 100 patients with GCLM from February 2017 to October 2021 at our institution were retrospectively analyzed. Patients were divided into immunochemotherapy (n = 33) and chemotherapy-alone (n = 67) groups. RESULTS Baseline clinicopathological data did not differ significantly between the two groups. The immunochemotherapy group had a higher overall response rate (59.4% vs. 44.0%, p = 0.029) and disease control rate (71.9% vs. 49.2%, p = 0.036) than the chemotherapy group. The immunochemotherapy group showed better tumor regression in the gastric mass, metastatic lymph nodes, and liver lesions than the chemotherapy group. Ten (30.3%) patients in the immunochemotherapy group and 13 (19.4%) patients in the chemotherapy group underwent surgery after conversion therapy. However, the difference was not statistically significant. The overall survival (OS) and progression-free survival (PFS) rates were better in the immunochemotherapy group than in the chemotherapy group. Treatment-related adverse events occurred in 24 (72.7%) and 47 (70.1%) patients in the immunochemotherapy and chemotherapy groups, respectively. CONCLUSIONS As a conversion therapy for GCLM, immunotherapy yielded better primary and metastatic tumor regression and survival benefits, with no increase in adverse events compared to chemotherapy.
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Affiliation(s)
- Guang‐Tan Lin
- Department of Gastric SurgeryFujian Medical University Union HospitalFuzhouChina
- Department of General SurgeryFujian Medical University Union HospitalFuzhouChina
| | - Zhi‐Yu Liu
- Department of Gastric SurgeryFujian Medical University Union HospitalFuzhouChina
- Department of General SurgeryFujian Medical University Union HospitalFuzhouChina
| | - Zhi‐Xin Shang‐Guan
- Department of Gastric SurgeryFujian Medical University Union HospitalFuzhouChina
- Department of General SurgeryFujian Medical University Union HospitalFuzhouChina
| | - Gui‐Rong Zeng
- Fujian Medical University Diagnostic Pathology CenterFujian Medical UniversityFuzhouChina
| | - Jian‐Xian Lin
- Department of Gastric SurgeryFujian Medical University Union HospitalFuzhouChina
- Department of General SurgeryFujian Medical University Union HospitalFuzhouChina
- Key Laboratory of Ministry of Education of Gastrointestinal CancerFujian Medical UniversityFuzhouChina
| | - Ju Wu
- Department of General SurgeryAffiliated Zhongshan Hospital of Dalian UniversityDalianChina
| | - Qi‐Yue Chen
- Department of Gastric SurgeryFujian Medical University Union HospitalFuzhouChina
- Department of General SurgeryFujian Medical University Union HospitalFuzhouChina
| | - Jian‐Wei Xie
- Department of Gastric SurgeryFujian Medical University Union HospitalFuzhouChina
- Department of General SurgeryFujian Medical University Union HospitalFuzhouChina
| | - Ping Li
- Department of Gastric SurgeryFujian Medical University Union HospitalFuzhouChina
- Department of General SurgeryFujian Medical University Union HospitalFuzhouChina
- Key Laboratory of Ministry of Education of Gastrointestinal CancerFujian Medical UniversityFuzhouChina
| | - Chang‐Ming Huang
- Department of Gastric SurgeryFujian Medical University Union HospitalFuzhouChina
- Department of General SurgeryFujian Medical University Union HospitalFuzhouChina
- Key Laboratory of Ministry of Education of Gastrointestinal CancerFujian Medical UniversityFuzhouChina
| | - Chao‐Hui Zheng
- Department of Gastric SurgeryFujian Medical University Union HospitalFuzhouChina
- Department of General SurgeryFujian Medical University Union HospitalFuzhouChina
- Key Laboratory of Ministry of Education of Gastrointestinal CancerFujian Medical UniversityFuzhouChina
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7
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Jun C, Yamauchi S, Yube Y, Egawa H, Yoshimoto Y, Kubota A, Tsuda K, Kaji S, Orita H, Oka S, Mine S, Fukunaga T. Pathological complete response with nivolumab for recurrence of liver metastasis after gastrectomy of gastric cancer. Surg Case Rep 2023; 9:86. [PMID: 37204618 DOI: 10.1186/s40792-023-01668-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2023] [Accepted: 05/11/2023] [Indexed: 05/20/2023] Open
Abstract
BACKGROUND Advanced gastric cancer has an unfavorable prognosis and poor curability. Immune checkpoint inhibitors, such as nivolumab, have recently emerged as a potential solution for this aggressive disease. However, there is a lack of established evidence on the clinical efficacy of these agents, particularly in the perioperative period for advanced gastric cancer patients who are unresectable, recurrent, or preoperative. Despite the limited data available, there have been rare cases of dramatic therapeutic effects. In this study, we present a successful case of nivolumab treatment along with surgery. CASE PRESENTATION A 69-year-old female presented with pericardial discomfort and was diagnosed with advanced gastric cancer following upper gastrointestinal endoscopy. Laparoscopic distal gastrectomy with D2 lymph node dissection was performed, resulting in a final pathological diagnosis of Stage IIIA. The patient received postoperative adjuvant chemotherapy with oral S-1 therapy, but was found to have multiple liver metastases at 8 months postsurgery. Weekly paclitaxel and ramucirumab therapy was initiated, but the patient experienced adverse side effects, leading to the discontinuation of treatment. Nivolumab monotherapy was then administered for 18 cycles, resulting in a partial therapeutic response and PET-CT revealed a complete metabolic response. However, the patient developed a Grade 3 pemphigoid as an immune-related adverse event, leading to the cessation of nivolumab. The patient underwent laparoscopic partial hepatectomy. Postoperative pathology showed no residual tumor cells, indicating a complete response. At present, 25 months after surgery, the patient was alive without recurrence. CONCLUSION In this report, we present a case of gastric cancer with liver metastatic recurrence, in which a complete pathological response was achieved with nivolumab treatment. Although determining whether surgical intervention is necessary following successful drug treatment can be challenging, PET-CT imaging may be useful in decision-making regarding surgical treatment.
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Affiliation(s)
- Chen Jun
- Department of Esophageal and Gastroenterological Surgery, Juntendo University Hospital, 3-1-3 Hongo, Bunkyo-Ku, Tokyo, 113-8431, Japan
- Department of Surgery, Koshigaya Municipal Hospital, 10-32 Higasikoshigaya, Koshigaya, Saitama, 343-8577, Japan
| | - Suguru Yamauchi
- Department of Esophageal and Gastroenterological Surgery, Juntendo University Hospital, 3-1-3 Hongo, Bunkyo-Ku, Tokyo, 113-8431, Japan.
- Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
| | - Yukinori Yube
- Department of Esophageal and Gastroenterological Surgery, Juntendo University Hospital, 3-1-3 Hongo, Bunkyo-Ku, Tokyo, 113-8431, Japan
| | - Hiroki Egawa
- Department of Esophageal and Gastroenterological Surgery, Juntendo University Hospital, 3-1-3 Hongo, Bunkyo-Ku, Tokyo, 113-8431, Japan
| | - Yutaro Yoshimoto
- Department of Esophageal and Gastroenterological Surgery, Juntendo University Hospital, 3-1-3 Hongo, Bunkyo-Ku, Tokyo, 113-8431, Japan
| | - Akira Kubota
- Department of Esophageal and Gastroenterological Surgery, Juntendo University Hospital, 3-1-3 Hongo, Bunkyo-Ku, Tokyo, 113-8431, Japan
| | - Kenki Tsuda
- Department of Esophageal and Gastroenterological Surgery, Juntendo University Hospital, 3-1-3 Hongo, Bunkyo-Ku, Tokyo, 113-8431, Japan
| | - Sanae Kaji
- Department of Esophageal and Gastroenterological Surgery, Juntendo University Hospital, 3-1-3 Hongo, Bunkyo-Ku, Tokyo, 113-8431, Japan
| | - Hajime Orita
- Department of Esophageal and Gastroenterological Surgery, Juntendo University Hospital, 3-1-3 Hongo, Bunkyo-Ku, Tokyo, 113-8431, Japan
| | - Shinichi Oka
- Department of Esophageal and Gastroenterological Surgery, Juntendo University Hospital, 3-1-3 Hongo, Bunkyo-Ku, Tokyo, 113-8431, Japan
| | - Shinji Mine
- Department of Esophageal and Gastroenterological Surgery, Juntendo University Hospital, 3-1-3 Hongo, Bunkyo-Ku, Tokyo, 113-8431, Japan
| | - Tetsu Fukunaga
- Department of Esophageal and Gastroenterological Surgery, Juntendo University Hospital, 3-1-3 Hongo, Bunkyo-Ku, Tokyo, 113-8431, Japan
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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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9
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Goetze TO, Al-Batran SE. Perspectives on the Management of Oligometastatic Disease in Esophago-Gastric Cancer. Cancers (Basel) 2022; 14:5200. [PMID: 36358619 PMCID: PMC9658190 DOI: 10.3390/cancers14215200] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2022] [Revised: 10/17/2022] [Accepted: 10/21/2022] [Indexed: 09/22/2023] Open
Abstract
Gastric adenocarcinoma and esophageal cancer are the fifth and seventh most common cancer types worldwide. At the time of initial diagnosis, up to 50% of esophagogastric cancers present with distant metastatic lesions and are candidates for chemotherapy. Curative surgery in this stage is still an experimental approach. Only a small number of these metastatic patients show an oligometastatic disease with no uniform definition of what oligometastatic means in gastric cancer. Nevertheless, the question remains unanswered as to whether these patients are still candidates for curative concepts. Some studies have attempted to answer this question but have not been adequately designed to address the role of a curative-intended multimodal therapy in this setting. The current FLOT-5 is designed to potentially provide a definitive answer to the question of whether curatively intended surgery plays a role or is a disadvantage in this setting.
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Affiliation(s)
- Thorsten Oliver Goetze
- Krankenhaus Nordwest gGmbH, Institut of Clinical Cancer Research, UCT—University Cancer Center Frankfurt-Marburg, Steinbacher Hohl 2-26, 60488 Frankfurt, Germany
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Huang RY, Kou HW, Le PH, Kuo CJ, Chen TH, Wang SY, Chen JS, Yeh TS, Hsu JT. Outcomes of Conversion Surgery for Metastatic Gastric Cancer Compared with In-Front Surgery Plus Palliative Chemotherapy or In-Front Surgery Alone. J Pers Med 2022; 12:555. [PMID: 35455672 PMCID: PMC9026725 DOI: 10.3390/jpm12040555] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2022] [Revised: 03/27/2022] [Accepted: 03/30/2022] [Indexed: 12/27/2022] Open
Abstract
The survival benefits of conversion surgery in patients with metastatic gastric cancer (mGC) remain unclear. Thus, this study aimed to determine the outcomes of conversion surgery compared to in-front surgery plus palliative chemotherapy (PCT) or in-front surgery alone for mGC. We recruited 182 consecutive patients with mGC who underwent gastrectomy, including conversion surgery, in-front surgery plus PCT, and in-front surgery alone at Linkou Chang Gung Memorial Hospital from 2011 to 2019. The tumor was staged according to the 8th edition of the American Joint Committee on Cancer. Patient demographics and clinicopathological factors were assessed. Overall survival (OS) was evaluated using the Kaplan−Meier curve and compared among groups. Conversion surgery showed a significantly longer median OS than in-front surgery plus PCT or in-front surgery alone (23.4 vs. 13.7 vs. 5.6 months; log rank p < 0.0001). The median OS of patients with downstaging (pathological stage I−III) was longer than that of patients without downstaging (stage IV) (30.9 vs. 18.0 months; p = 0.016). Our study shows that conversion surgery is associated with survival benefits compared to in-front surgery plus PCT or in-front surgery alone in patients with mGC. Patients who underwent conversion surgery with downstaging had a better prognosis than those without downstaging.
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Affiliation(s)
- Ruo-Yi Huang
- Department of General Surgery, Chang Gung Memorial Hospital at Linkou, College of Medicine, Chang Gung University, Taoyuan 33305, Taiwan; (R.-Y.H.); (H.-W.K.); (S.-Y.W.); (T.-S.Y.)
| | - Hao-Wei Kou
- Department of General Surgery, Chang Gung Memorial Hospital at Linkou, College of Medicine, Chang Gung University, Taoyuan 33305, Taiwan; (R.-Y.H.); (H.-W.K.); (S.-Y.W.); (T.-S.Y.)
| | - Puo-Hsien Le
- Department of Gastroenterology, Chang Gung Memorial Hospital at Linkou, College of Medicine, Chang Gung University, Taoyuan 33305, Taiwan; (P.-H.L.); (C.-J.K.); (T.-H.C.)
| | - Chia-Jung Kuo
- Department of Gastroenterology, Chang Gung Memorial Hospital at Linkou, College of Medicine, Chang Gung University, Taoyuan 33305, Taiwan; (P.-H.L.); (C.-J.K.); (T.-H.C.)
| | - Tsung-Hsing Chen
- Department of Gastroenterology, Chang Gung Memorial Hospital at Linkou, College of Medicine, Chang Gung University, Taoyuan 33305, Taiwan; (P.-H.L.); (C.-J.K.); (T.-H.C.)
| | - Shang-Yu Wang
- Department of General Surgery, Chang Gung Memorial Hospital at Linkou, College of Medicine, Chang Gung University, Taoyuan 33305, Taiwan; (R.-Y.H.); (H.-W.K.); (S.-Y.W.); (T.-S.Y.)
| | - Jen-Shi Chen
- Department of Hematology-Oncology, Chang Gung Memorial Hospital at Linkou, College of Medicine, Chang Gung University, Taoyuan 33305, Taiwan;
| | - Ta-Sen Yeh
- Department of General Surgery, Chang Gung Memorial Hospital at Linkou, College of Medicine, Chang Gung University, Taoyuan 33305, Taiwan; (R.-Y.H.); (H.-W.K.); (S.-Y.W.); (T.-S.Y.)
| | - Jun-Te Hsu
- Department of General Surgery, Chang Gung Memorial Hospital at Linkou, College of Medicine, Chang Gung University, Taoyuan 33305, Taiwan; (R.-Y.H.); (H.-W.K.); (S.-Y.W.); (T.-S.Y.)
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11
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Yoshida K, Yasufuku I, Terashima M, Young Rha S, Moon Bae J, Li G, Katai H, Watanabe M, Seto Y, Hoon Noh S, Kwang Yang H, Ji J, Baba H, Kitagawa Y, Morita S, Nishiyama M, Kodera Y, CONVO‐GC‐1 Study Group, Federation of Asian Clinical Oncology (FACO). International Retrospective Cohort Study of Conversion Therapy for Stage IV Gastric Cancer 1 (CONVO-GC-1). Ann Gastroenterol Surg 2022; 6:227-240. [PMID: 35261948 PMCID: PMC8889854 DOI: 10.1002/ags3.12515] [Citation(s) in RCA: 69] [Impact Index Per Article: 23.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2021] [Revised: 09/21/2021] [Accepted: 09/24/2021] [Indexed: 12/23/2022] Open
Abstract
Aim Much attention has been paid to conversion therapy for stage IV gastric cancer, however, its operative comorbidities and survival benefit have not yet been clarified. CONVO-GC-1, an international retrospective cohort study, was designed to investigate the role of conversion surgery in Japan, Korea, and China. Methods The rate of operative complications was the primary endpoint and the overall survival (OS), according to the four-category criteria previously published (Gastric Cancer:19; 2016), was analyzed as the secondary endpoint. Results A total of 1206 patients underwent surgery after chemotherapy with curative intent. Operative complications were observed in 290 (24.0%) patients in all grades, including pancreatic fistula and surgical site infection. The median survival time (MST) of all resected patients was 36.7 mo (M) and those of R0, R1, and R2 resection were 56.6 M, 25.8 M, and 21.7 M, respectively. Moreover, the MST of R0 patients were 47.8 M, 116.7 M, 44.8 M in categories 1, 2, and 3, respectively, and not reached in category 4. Interestingly, the MST of P1 patients was as favorable as that of P0CY1 patients if R0 resection was achieved. The MST of patients with liver metastasis was also favorable regardless of the number of lesions, and the MST of patients with para-aortic lymph node (LN) No 16a1/b2 metastasis was not inferior to that of patients with para-aortic LN No 16a2/b1 metastasis. Conclusion Conversion therapy for stage IV gastric cancer is safe and could be a new therapeutic strategy to improve the survival of patients, especially those with R0 resection.
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Affiliation(s)
- Kazuhiro Yoshida
- Department of Surgical OncologySchool of MedicineGifu UniversityGifuJapan
| | - Itaru Yasufuku
- Department of Surgical OncologySchool of MedicineGifu UniversityGifuJapan
| | | | - Sun Young Rha
- Department of Medical OncologyYonsei UniversitySeoulKorea
| | - Jae Moon Bae
- Department of SurgerySamsung Medical CenterSungkyunkwan University School of MedicineSeoulKorea
| | - Guoxin Li
- Department of General SurgerySouthern Medical UniversityGuangzhouChina
| | - Hitoshi Katai
- Department of Gastric SurgeryNational Cancer CenterTokyoJapan
| | - Masahiko Watanabe
- Department of SurgeryKitasato University Kitasato Institute HospitalTokyoJapan
| | - Yasuyuki Seto
- Department of Gastrointestinal SurgeryThe University of TokyoTokyoJapan
| | | | | | - Jiafu Ji
- Department of SurgeryPeking University Cancer HospitalBeijingChina
| | - Hideo Baba
- Department of Gastrointestinal SurgeryKumamoto UniversityKumamotoJapan
| | - Yuko Kitagawa
- Department of Gastrointestinal SurgeryKeio UniversityTokyoJapan
| | - Satoshi Morita
- Department of Biomedical Statistics and BioinformaticsKyoto UniversityKyotoJapan
| | | | - Yasuhiro Kodera
- Department of Gastroenterological SurgeryNagoya UniversityJapan
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12
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Abstract
The prognosis of advanced gastric cancer (AGC) is extremely poor, and the therapeutic effect of traditional palliative chemotherapy is far from satisfactory. To overcome this bottleneck, palliative surgery resection, perioperative chemotherapy combined with surgical resection, hyperthermic intraperitoneal chemotherapy (HIPEC), pressurized intraperitoneal aerosol chemotherapy (PIPAC), radiation therapy, molecular-targeted therapy have been explored in AGC. Although considerable progress has been achieved, there is still no overwhelming therapeutic method. Due to the high heterogeneity of AGC, it is particularly vital to reshaped the paradigm of gastric cancer therapy according to the characteristics of clinical classifications and molecular subtypes.
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Affiliation(s)
- Tao Li
- Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Yufang He
- The First Clinical Medical School, Southern Medical University, Guangzhou, Guangdong, China
| | - Qinglei Zhong
- The First Clinical Medical School, Southern Medical University, Guangzhou, Guangdong, China
| | - Jiang Yu
- Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Xinhua Chen
- Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China
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13
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Liao PW, Cheng SB, Chou CW, Lin HC, Lin CH, Chen TC, Hsu CY, Jerry Teng CL, Shih YH. Chemotherapy for Metastatic Gastric Cancer: Does Age Matter? A Single-Center, Retrospective, Real-World Study. CLINICAL MEDICINE INSIGHTS: ONCOLOGY 2022; 16:11795549221123617. [PMID: 36134036 PMCID: PMC9483662 DOI: 10.1177/11795549221123617] [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: 04/07/2022] [Accepted: 08/10/2022] [Indexed: 11/26/2022] Open
Abstract
Background: Palliative chemotherapy is the preferred standard of care for patients with metastatic gastric cancer (mGC). It remains uncertain whether older patients with mGC would benefit from palliative chemotherapy. This study aimed to investigate the clinical impact of palliative chemotherapy in older patients with mGC. Methods: This single-institute, retrospective, and real-world study included 428 patients with mGC between January 2009 and December 2019. Among them, 306 who received palliative chemotherapy were further stratified into 2 groups according to age: ≤70 (n = 236) and >70 (n = 70) years. The clinical demographics, outcomes, and hematologic toxicities of chemotherapy were compared between the 2 groups. Prognostic factors were determined using the Cox proportional hazards model. Results: Of the screened 428 patients, older patients had worse overall survival (OS) than younger patients. Among patients who received chemotherapy (n = 306), patients aged >70 and ⩽70 years had comparable progression-free survival (PFS) and OS. The incidence of severe hematologic toxicity was similar between the 2 groups. The Eastern Cooperative Oncology Group performance status of 2 or more metastatic sites, elevated carbohydrate antigen 19-9 level, high neutrophil-to-lymphocyte ratio (NLR), and undergoing palliative gastrectomy were independent prognostic factors for OS. Notably, age >70 years was not a significant factor for poor OS. Conclusions: Older age of >70 years might not be considered an obstacle to administering palliative chemotherapy to patients with mGC.
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Affiliation(s)
- Po-Wei Liao
- Division of Hematology/Medical Oncology, Department of Medicine, Taichung Veterans General Hospital, Taichung
| | - Shao-Bin Cheng
- Division of General Surgery, Department of Surgery, Taichung Veterans General Hospital, Taichung
- School of Medicine, Chung Shan Medical University, Taichung
| | - Cheng-Wei Chou
- Division of Hematology/Medical Oncology, Department of Medicine, Taichung Veterans General Hospital, Taichung
- Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung
| | - Hsin-Chen Lin
- Division of Hematology/Medical Oncology, Department of Medicine, Taichung Veterans General Hospital, Taichung
| | - Cheng-Hsien Lin
- Division of Hematology/Medical Oncology, Department of Medicine, Taichung Veterans General Hospital, Taichung
| | - Tsung-Chih Chen
- Division of Hematology/Medical Oncology, Department of Medicine, Taichung Veterans General Hospital, Taichung
- Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei
| | - Chiann-Yi Hsu
- Biostatistics Task Force, Taichung Veterans General Hospital, Taichung
| | - Chieh-Lin Jerry Teng
- Division of Hematology/Medical Oncology, Department of Medicine, Taichung Veterans General Hospital, Taichung
- School of Medicine, Chung Shan Medical University, Taichung
- Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung
- Department of Life Science, Tunghai University, Taichung
| | - Yu-Hsuan Shih
- Division of Hematology/Medical Oncology, Department of Medicine, Taichung Veterans General Hospital, Taichung
- School of Medicine, Chung Shan Medical University, Taichung
- Institute of Medicine, Chung Shan Medical University, Taichung
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14
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Survival outcomes of management in metastatic gastric adenocarcinoma patients. Sci Rep 2021; 11:23142. [PMID: 34848751 PMCID: PMC8633380 DOI: 10.1038/s41598-021-02391-z] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2021] [Accepted: 11/09/2021] [Indexed: 12/27/2022] Open
Abstract
Chemotherapy is generally considered as the main treatment for metastatic gastric adenocarcinoma. The role of gastrectomy for metastatic gastric cancer without obvious symptoms is controversial. The objective of this study is to investigate survival outcomes of treatment modalities using a real-world data setting. A retrospective cohort study was designed using the Taiwan Cancer Registry database. We identified the treatment modalities and used Kaplan–Meier estimates and Cox regressions to compare patient survival outcomes. From 2008 to 2015, 5599 gastric adenocarcinoma patients were diagnosed with metastatic disease (M1). The median overall survival (OS) of patients with surgery plus chemotherapy had the longest survival of 14.2 months. The median OS of the patients who received chemotherapy alone or surgery alone was 7.0 and 3.9, respectively. Age at diagnosis, year of diagnosis, tumor grade, and treatment modalities are prognostic factors for survival. The hazard ratios for patients who received surgery plus chemotherapy, surgery alone, and supportive care were 0.47 (95% CI 0.44–0.51), 1.22 (95% CI 1.1–1.36), and 3.23 (95% CI 3.01–3.46), respectively, by multivariable Cox regression analysis when using chemotherapy alone as a referent. Chemotherapy plus surgery may have a survival benefit for some selected gastric adenocarcinoma patients with metastatic disease.
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15
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Matsumoto C, Iwatsuki M, Morinaga T, Yamashita K, Nakamura K, Kurashige J, Eto K, Iwagami S, Baba Y, Yoshida N, Miyamoto Y, Baba H. Long-term survival after multidisciplinary treatments for advanced esophagogastric junction cancer. Int Cancer Conf J 2021; 10:207-211. [PMID: 34221833 PMCID: PMC8206417 DOI: 10.1007/s13691-021-00480-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2020] [Accepted: 03/27/2021] [Indexed: 10/21/2022] Open
Abstract
Stage IV Gastric/Esophagogastric junction cancer (G/EGJ) has an unfavorable prognosis and poor curability. In this study, we report the case of long-term survival after multidisciplinary treatments for advanced esophagogastric junction cancer. A 53-year-old male patient was diagnosed with HER2 positive advanced esophagogastric junction cancer and mediastinal and paraaortic lymph node metastasis. After systemic chemotherapy for 1 year, minimally invasive esophagectomy was conducted as conversion surgery. However, peritoneal and liver metastasis was observed on 3 months after curative surgery. 2 years after operation, solitary brain metastasis was detected and stereotactic radiosurgery (SRS) using a gamma knife was underwent. After 1 year, despite the continuous administration of Nivolumab, the paraaortic lymph node increased in size again and radiation therapy was conducted. Currently, he is alive and undergoing chemotherapy.
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Affiliation(s)
- Chihiro Matsumoto
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto-City, 860-8556 Japan
| | - Masaaki Iwatsuki
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto-City, 860-8556 Japan
| | - Takeshi Morinaga
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto-City, 860-8556 Japan
| | - Kohei Yamashita
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto-City, 860-8556 Japan
| | - Kenichi Nakamura
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto-City, 860-8556 Japan
| | - Junji Kurashige
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto-City, 860-8556 Japan
| | - Kojiro Eto
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto-City, 860-8556 Japan
| | - Shiro Iwagami
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto-City, 860-8556 Japan
| | - Yoshifumi Baba
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto-City, 860-8556 Japan
| | - Naoya Yoshida
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto-City, 860-8556 Japan
| | - Yuji Miyamoto
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto-City, 860-8556 Japan
| | - Hideo Baba
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto-City, 860-8556 Japan
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16
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Ohnuma H, Sato Y, Onoyama N, Hamaguchi K, Hayasaka N, Sato M, Murase K, Takada K, Miyanishi K, Murakami T, Ito T, Nobuoka T, Takemasa I, Kato J. Survival benefit of conversion surgery after intensive chemotherapy for unresectable metastatic gastric cancer: a propensity score-matching analysis. J Cancer Res Clin Oncol 2021; 147:2385-2396. [PMID: 33534051 DOI: 10.1007/s00432-021-03516-7] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2020] [Accepted: 01/09/2021] [Indexed: 12/23/2022]
Abstract
PURPOSE The clinical benefit of conversion surgery (CS) for unresectable gastric cancer (GC), whereby unresectable GC responds to chemotherapy and subsequently receives curative-intent surgery, remains unclear. Here, we aimed to clarify the clinical value of CS. METHODS In this retrospective cohort study, we analyzed 175 unresectable GC, who received triple combined chemotherapy between 2004 and 2019. We divided patients into two groups: those who underwent CS and those receiving chemotherapy only (CS and C groups, respectively). Propensity score matching was used to minimize confounding bias. RESULTS Of 175 cases, 61 (34.9%) underwent CS. R0 resection was obtained in 85.2%. After matching, 44 pairs were selected; there were no significant differences in baseline covariants. Group CS had a significantly better median overall survival (OS) (18.8 vs. 46.0 months, p < 0.001), and prolonged progression-free survival (7.4 vs. 25.8 months, p < 0.001). Subgroup analysis of OS showed a favorable trend for CS for almost all subgroups. Multivariate analysis revealed that good ECOG performance status and CS were associated with a longer OS. CONCLUSION The survival benefit of CS was consistently demonstrated in the univariate and multivariate analysis, even in the matched cohort. Additional large-scale trials are needed for further validation.
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Affiliation(s)
- Hiroyuki Ohnuma
- Department of Medical Oncology, Sapporo Medical University School of Medicine, South 1, West 16, Chuo-ku, Sapporo, Hokkaido, 060-0061, Japan
| | - Yasushi Sato
- Department of Community Medicine for Gastroenterology and Oncology, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan
| | - Naoki Onoyama
- Department of Medical Oncology, Sapporo Medical University School of Medicine, South 1, West 16, Chuo-ku, Sapporo, Hokkaido, 060-0061, Japan
| | - Kota Hamaguchi
- Department of Medical Oncology, Sapporo Medical University School of Medicine, South 1, West 16, Chuo-ku, Sapporo, Hokkaido, 060-0061, Japan
| | - Naotaka Hayasaka
- Department of Medical Oncology, Sapporo Medical University School of Medicine, South 1, West 16, Chuo-ku, Sapporo, Hokkaido, 060-0061, Japan
| | - Masanori Sato
- Department of Medical Oncology, Sapporo Medical University School of Medicine, South 1, West 16, Chuo-ku, Sapporo, Hokkaido, 060-0061, Japan
| | - Kazuyuki Murase
- Department of Medical Oncology, Sapporo Medical University School of Medicine, South 1, West 16, Chuo-ku, Sapporo, Hokkaido, 060-0061, Japan
| | - Kohichi Takada
- Department of Medical Oncology, Sapporo Medical University School of Medicine, South 1, West 16, Chuo-ku, Sapporo, Hokkaido, 060-0061, Japan
| | - Koji Miyanishi
- Department of Medical Oncology, Sapporo Medical University School of Medicine, South 1, West 16, Chuo-ku, Sapporo, Hokkaido, 060-0061, Japan
| | - Takeshi Murakami
- Department of Surgery, Surgical Oncology and Science, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Tatsuya Ito
- Department of Surgery, Surgical Oncology and Science, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Takayuki Nobuoka
- Department of Surgery, Surgical Oncology and Science, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Ichiro Takemasa
- Department of Surgery, Surgical Oncology and Science, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Junji Kato
- Department of Medical Oncology, Sapporo Medical University School of Medicine, South 1, West 16, Chuo-ku, Sapporo, Hokkaido, 060-0061, Japan.
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17
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Kinoshita J, Yamaguchi T, Moriyama H, Fushida S. Current status of conversion surgery for stage IV gastric cancer. Surg Today 2021; 51:1736-1754. [PMID: 33486610 DOI: 10.1007/s00595-020-02222-0] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2020] [Accepted: 11/02/2020] [Indexed: 12/23/2022]
Abstract
Palliative chemotherapy with best supportive care is a mainstay for patients with gastric cancer (GC) and distant metastasis. However, with advances in GC chemotherapy, multimodal treatment, including perioperative chemotherapy plus conversion surgery, has attracted attention as a new strategy to improve the outcome of patients with stage IV disease. Conversion surgery is defined as surgical treatment aimed at R0 resection after a good response to induction chemotherapy for tumors originally considered unresectable or marginally resectable for technical and/or oncological reasons. Various biological characteristics differ, depending on each metastatic condition in stage IV GC. The main metastatic pathways of GC can be divided into three categories: lymphatic, hematogenous, and peritoneal. In each category, considerable historical data on conversion surgery have demonstrated the benefits of individualized approaches. However, owing to the diversity of these conditions, a common definition, including the choice of induction chemotherapy, optimal timing of resection, and eligibility for conversion surgery, has not been established among surgical oncologists. Thus, we explore the current and future treatment options by reviewing the literature on this controversial topic comprehensively.
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Affiliation(s)
- Jun Kinoshita
- Department of Gastroenterological Surgery, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, 13-1 Takara-machi, Kanazawa, Ishikawa, 920-8641, Japan
| | - Takahisa Yamaguchi
- Department of Gastroenterological Surgery, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, 13-1 Takara-machi, Kanazawa, Ishikawa, 920-8641, Japan
| | - Hideki Moriyama
- Department of Gastroenterological Surgery, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, 13-1 Takara-machi, Kanazawa, Ishikawa, 920-8641, Japan
| | - Sachio Fushida
- Department of Gastroenterological Surgery, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, 13-1 Takara-machi, Kanazawa, Ishikawa, 920-8641, Japan.
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18
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Zhang N, Deng J, Sun Y, Xiao J, Li H, Liang H. An unresectable gastric cancer with bulky lymph node metastases treated with SOX chemotherapy plus apatinib followed by D3 radical gastrectomy: a case report. Transl Cancer Res 2021; 10:537-545. [PMID: 35116283 PMCID: PMC8798783 DOI: 10.21037/tcr-20-1400] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2020] [Accepted: 12/04/2020] [Indexed: 11/16/2022]
Abstract
Conversion therapy for gastric cancer (GC) has been the subject of much recent attention. GC patients with bulky lymph node metastases were usually considered oncologically unresectable and surgery could be challenging and tumor shrinkage may serve to facilitate resection. Previous studies reported satisfactory survival data were obtained in the series of neoadjuvant studies with bulky N disease. However, the evidence of combining neoadjuvant chemotherapy with targeted therapy for patients with bulky N disease is inadequate. We report a 52-year-old man who was diagnosed with unresectable GC with bulky lymph node metastases after endoscopic biopsy and abdominal enhanced computed tomography (CT) examination. Histopathology confirmed poorly differentiated adenocarcinoma at the junction of the antrum and the body of the stomach. Abdominal enhanced CT showed marked thickening of more than two-thirds of the stomach wall and multiple enlarged and coalesced perigastric and extragastric lymph nodes. The clinical staging was cT4aN3M0. The patient was administered two cycles of S-1 and oxaliplatin (SOX regimen) plus apatinib. Repeat abdominal enhanced CT demonstrated decrease in stomach wall thickness and in the sizes of all perigastric and extragastric lymph nodes (<1.0 cm). D2 gastrectomy with para-aortic lymph node dissection was performed after 5 weeks. Pathological examination of resected specimen revealed a ypT4bN0M0 poorly differentiated adenocarcinoma. All 140 lymph nodes that were examined were negative. SOX chemotherapy regime was advised after surgery, but had to be discontinued after two cycles because of severe side effects. The patient has been followed up regularly for more than 2 years with enhanced abdominal CT and the examination of tumor markers. No recurrence or metastasis has been identified till the time of submission of this article. Our treatment experience might provide a reference for the treatment of GC patients with bulky lymph node metastases.
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Affiliation(s)
- Nannan Zhang
- Department of Gastroenterology, Tianjin Medical University Cancer Hospital, City Key Laboratory of Tianjin Cancer Center and National Clinical Research Center for Cancer, Tianjin, China
| | - Jingyu Deng
- Department of Gastroenterology, Tianjin Medical University Cancer Hospital, City Key Laboratory of Tianjin Cancer Center and National Clinical Research Center for Cancer, Tianjin, China
| | - Yan Sun
- Department of Pathology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China
- Tianjin’s Clinical Research Center for Cancer, Tianjin Medical University, Ministry of Education, Tianjin, China
| | - Jianyu Xiao
- Tianjin’s Clinical Research Center for Cancer, Tianjin Medical University, Ministry of Education, Tianjin, China
- Department of Radiology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China
| | - Hongli Li
- Tianjin’s Clinical Research Center for Cancer, Tianjin Medical University, Ministry of Education, Tianjin, China
- Department of Gastrointestinal Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China
| | - Han Liang
- Department of Gastroenterology, Tianjin Medical University Cancer Hospital, City Key Laboratory of Tianjin Cancer Center and National Clinical Research Center for Cancer, Tianjin, China
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19
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Jiang D, Xu Y, Chen Y, Jiang J, Wang M, Yang M, Chen Z, Yang L. Apatinib Combined With SOX Regimen in Conversion Treatment of Advanced Gastric Cancer: A Case Series and Literature Review. Front Pharmacol 2020; 11:1027. [PMID: 32765260 PMCID: PMC7381218 DOI: 10.3389/fphar.2020.01027] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2020] [Accepted: 06/24/2020] [Indexed: 12/30/2022] Open
Abstract
Gastric cancer is a common digestive tract tumor and the second most prevalent cancer. The prognosis of advanced gastric cancer is poor. Conversion therapy can reduce tumor burden, downgrade tumor, and increase the possibility of complete resection, thus prolonging the survival time of patients with gastric cancer. In conversion therapy, chemotherapy and targeted therapy are the main methods of medical treatment, which can control tumor growth and recurrence. As an antiangiogenic targeted drug, apatinib is widely used in the third-line treatment of advanced gastric cancer. Recent studies have shown that it may be of great help in rapid reduction of tumor stage and improvement of prognosis in conversion therapy. This study reported three cases of gastric cancer complicated with multiple abdominal and retroperitoneal lymph node metastases. After receiving apatinib combined with SOX regimen for four cycles, computed tomography showed that the focus and lymph node metastasis were reduced after treatment, and primary tumors were resected. Postoperative pathology result showed that the patients got R0 resection. After radical surgery, the maintenance therapy including apatinib was given. The progression-free survival time was more than 10 months. Apatinib combined with SOX regimen as a conversion therapy for advanced gastric adenocarcinoma increases the possibility of successful surgical resection, which might prolong the survival time of patients.
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Affiliation(s)
- Dingyi Jiang
- Department of Medical Oncology, The Qingdao University Medical College, Qingdao, China
| | - Yunyun Xu
- Department of Medical Oncology, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, China
| | - Yunwang Chen
- Department of Medical Oncology, The Qingdao University Medical College, Qingdao, China
| | - Jiahong Jiang
- Department of Medical Oncology, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, China
| | - Mingxing Wang
- Department of Medical Oncology, Bengbu Medical College, Bengbu, China
| | - Min Yang
- Department of Medical Oncology, The Qingdao University Medical College, Qingdao, China
| | - Zheling Chen
- Department of Medical Oncology, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, China
| | - Liu Yang
- Department of Medical Oncology, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, China
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20
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Chen GM, Yuan SQ, Nie RC, Luo TQ, Jiang KM, Liang CC, Li YF, Zhang DY, Yu JH, Hou F, Wang Y, Chen YB. Surgical Outcome and Long-Term Survival of Conversion Surgery for Advanced Gastric Cancer. Ann Surg Oncol 2020; 27:4250-4260. [PMID: 32506192 DOI: 10.1245/s10434-020-08559-7] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2019] [Indexed: 12/13/2022]
Abstract
BACKGROUND The present study aims to report the surgical outcome and long-term survival of conversion surgery and clarify its role in advanced gastric cancer. PATIENTS AND METHODS A total of 95 primary advanced gastric adenocarcinoma patients who underwent systemic chemotherapy and conversion surgery were reviewed retrospectively. The survival of conversion surgery was analyzed by Cox regression and the Kaplan-Meier method. Surgical outcomes were analyzed according to the Clavien-Dindo classification. RESULTS The median survival time (MST) of the 95 patients was 26.8 months, and the postoperative MST was 19.3 months. The MSTs of the patients in categories 1, 2, 3, and 4 were 28.8, 25.5, 43.6, and 11.3 months, respectively. The MSTs of the patients who underwent R0 resection (47 cases) and R1/2 resection (48 cases) were 49.3 months and 21.9 months, respectively. The MST of patients treated with total gastrectomy was shorter (21.9 months) than that of patients who underwent proximal (55.0 months) or distal (46.3 months) gastrectomy. Patients who received more than 6 cycles of induction chemotherapy had a longer MST than patients who received 3-5 cycles or 1-2 cycles (MST: 55.0 months versus 21.1 months versus 21.7 months). The incident postoperative complications and postoperative mortality rates were 10.5% and 1.1%, respectively. CONCLUSIONS Advanced gastric cancer patients may obtain a survival benefit from conversion surgery, except category 4. Performing a sufficient number of cycles of induction chemotherapy (usually ≥ 6 cycles) is recommended. Surgical oncologists should perform R0 resection and avoid total gastrectomy.
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Affiliation(s)
- Guo-Ming Chen
- State Key Laboratory of Oncology in South China, Department of Gastric Surgery, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Shu-Qiang Yuan
- State Key Laboratory of Oncology in South China, Department of Gastric Surgery, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Run-Cong Nie
- State Key Laboratory of Oncology in South China, Department of Gastric Surgery, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Tian-Qi Luo
- State Key Laboratory of Oncology in South China, Department of Gastric Surgery, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Kai-Ming Jiang
- State Key Laboratory of Oncology in South China, Department of Gastric Surgery, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Cheng-Cai Liang
- State Key Laboratory of Oncology in South China, Department of Gastric Surgery, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Yuan-Fang Li
- State Key Laboratory of Oncology in South China, Department of Gastric Surgery, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - De-Yao Zhang
- State Key Laboratory of Oncology in South China, Department of Gastric Surgery, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Jie-Hai Yu
- State Key Laboratory of Oncology in South China, Department of Gynecology, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Fan Hou
- Penn Graduate School of Education, University of Pennsylvania, Philadelphia, PA, USA
| | - Yun Wang
- State Key Laboratory of Oncology in South China, Department of Hematological Oncology, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.
| | - Ying-Bo Chen
- State Key Laboratory of Oncology in South China, Department of Gastric Surgery, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.
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21
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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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22
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Suh Y, Lee J, Woo H, Shin D, Kong S, Lee H, Shin A, Yang H. National cancer screening program for gastric cancer in Korea: Nationwide treatment benefit and cost. Cancer 2020; 126:1929-1939. [DOI: 10.1002/cncr.32753] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2019] [Revised: 12/25/2019] [Accepted: 12/28/2019] [Indexed: 12/24/2022]
Affiliation(s)
- Yun‐Suhk Suh
- Department of Surgery Seoul National University College of Medicine Seoul Korea
- Department of Surgery Seoul National University Hospital Seoul Korea
- Department of Surgery Seoul National University Bundang Hospital Seongnam Korea
| | - Joonki Lee
- Department of Preventive Medicine Seoul National University College of Medicine Seoul Korea
| | - Hyeongtaek Woo
- Department of Preventive Medicine Seoul National University College of Medicine Seoul Korea
| | - Dongwook Shin
- Department of Family Medicine, Samsung Medical Center Sungkyunkwan University School of Medicine Seoul Korea
| | - Seong‐Ho Kong
- Department of Surgery Seoul National University College of Medicine Seoul Korea
| | - Hyuk‐Joon Lee
- Department of Surgery Seoul National University College of Medicine Seoul Korea
- Cancer Research Institute Seoul National University College of Medicine Seoul Korea
| | - Aesun Shin
- Department of Preventive Medicine Seoul National University College of Medicine Seoul Korea
- Cancer Research Institute Seoul National University College of Medicine Seoul Korea
| | - Han‐Kwang Yang
- Department of Surgery Seoul National University College of Medicine Seoul Korea
- Cancer Research Institute Seoul National University College of Medicine Seoul Korea
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23
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Jung JO, Nienhüser H, Schleussner N, Schmidt T. Oligometastatic Gastroesophageal Adenocarcinoma: Molecular Pathophysiology and Current Therapeutic Approach. Int J Mol Sci 2020; 21:E951. [PMID: 32023907 PMCID: PMC7038165 DOI: 10.3390/ijms21030951] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2019] [Revised: 01/20/2020] [Accepted: 01/29/2020] [Indexed: 12/15/2022] Open
Abstract
Gastric and esophageal cancers are dreaded malignancies, with a majority of patients presenting in either a locally advanced or metastatic state. Global incidences are rising and the overall prognosis remains poor. The concept of oligometastasis has been established for other tumor entities and is also proposed for upper gastrointestinal tract cancers. This review article explores metastasis mechanisms on the molecular level, specific to esophageal and gastric adenocarcinoma. Existing data and recent studies that deal with upper gastrointestinal tumors in the oligometastatic state are reviewed. Furthermore, current therapeutic targets in gastroesophageal cancers are presented and discussed. Finally, a perspective about future diagnostic and therapeutic strategies is given.
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Affiliation(s)
| | | | | | - Thomas Schmidt
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany; (J.-O.J.); (H.N.); (N.S.)
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24
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Wang Z, Chen JQ, Liu JL, Tian L. Issues on peritoneal metastasis of gastric cancer: an update. World J Surg Oncol 2019; 17:215. [PMID: 31829265 PMCID: PMC6907197 DOI: 10.1186/s12957-019-1761-y] [Citation(s) in RCA: 50] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2019] [Accepted: 11/26/2019] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND Peritoneal metastasis (PM) is one of the most common forms of metastasis with a very poor prognosis in patients with gastric cancer (GC). The mechanisms, diagnosis, and management of PM remain controversial. MAIN BODY Stephen Paget's "seed-and-soil" hypothesis gives us an illustration of the mechanisms of PM. Recently, hematogenous metastasis and exosomes from GC are identified as novel mechanisms for PM. Diagnostic accuracy of conventional imaging modalities for PM is not satisfactory, but texture analysis may be a useful adjunct for the prediction of PM. Biological markers in peritoneal washings are helpful in identifying patients at high risk of PM, but many limitations remain to be overcome. Response of PM from systemic chemotherapy alone is very limited. However, conversion therapy is confirmed to be safe and able to prolong the survival of GC patients with PM. As an important part of conversion therapy, intraperitoneal chemotherapy with taxanes has become an ideal approach with several advantages. Additionally, gastrectomy should be considered in patients who would tolerate surgery if a remarkable response to chemotherapy was observed. CONCLUSION Texture analysis is a reliable adjunct for the prediction of PM, and conversion therapy provides a new choice for GC patients with PM. The underlying mechanisms and new biological markers for GC patients with PM should be the direction of future studies. Furthermore, significant aspects of conversion therapy, such as timing and method of the operation, and the indications remain to be clarified.
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Affiliation(s)
- Zhen Wang
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning, 530021, Guangxi Zhuang Autonomous Region, China.
| | - Jun-Qiang Chen
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning, 530021, Guangxi Zhuang Autonomous Region, China.
| | - Jin-Lu Liu
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning, 530021, Guangxi Zhuang Autonomous Region, China
| | - Lei Tian
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning, 530021, Guangxi Zhuang Autonomous Region, China
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25
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Zhang F, Huang X, Song Y, Gao P, Zhou C, Guo Z, Shi J, Wu Z, Wang Z. Conversion Surgery for Stage IV Gastric Cancer. Front Oncol 2019; 9:1158. [PMID: 31788445 PMCID: PMC6854003 DOI: 10.3389/fonc.2019.01158] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2019] [Accepted: 10/17/2019] [Indexed: 12/24/2022] Open
Abstract
The prognosis of stage IV gastric cancer (GC) is poor, with palliative chemotherapy remaining the main therapeutic option. Studies increasingly indicate that patients with unresectable stage IV GC, who undergo gastrectomy with radical intention after responding to several regimens of combined chemotherapy, can achieve good survival outcomes. Thus, surgery aiming at radical resection for unresectable stage IV GC after combined chemotherapy has received increasing attention in recent years. This novel therapeutic strategy was defined as conversion surgery in patients with unresectable stage IV GC and it can associate with significant improved survival when R0 resection can be achieved. Despite the recent advances in conversion surgery for patients with unresectable stage IV GC, selection criteria for combination chemotherapy regimens, indications for conversion surgery, optimal timing to surgery, and postoperative chemotherapy all remain controversial. This article reviews the current state of conversion surgery for unresectable stage IV GC.
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Affiliation(s)
- Fei Zhang
- Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, Department of Surgical Oncology and General Surgery, The First Affiliated Hospital of China Medical University, Shenyang, China
| | - Xuanzhang Huang
- Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, Department of Surgical Oncology and General Surgery, The First Affiliated Hospital of China Medical University, Shenyang, China
| | - Yongxi Song
- Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, Department of Surgical Oncology and General Surgery, The First Affiliated Hospital of China Medical University, Shenyang, China
| | - Peng Gao
- Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, Department of Surgical Oncology and General Surgery, The First Affiliated Hospital of China Medical University, Shenyang, China
| | - Cen Zhou
- Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, Department of Surgical Oncology and General Surgery, The First Affiliated Hospital of China Medical University, Shenyang, China
| | - Zhexu Guo
- Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, Department of Surgical Oncology and General Surgery, The First Affiliated Hospital of China Medical University, Shenyang, China
| | - Jinxin Shi
- Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, Department of Surgical Oncology and General Surgery, The First Affiliated Hospital of China Medical University, Shenyang, China
| | - Zhonghua Wu
- Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, Department of Surgical Oncology and General Surgery, The First Affiliated Hospital of China Medical University, Shenyang, China
| | - Zhenning Wang
- Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, Department of Surgical Oncology and General Surgery, The First Affiliated Hospital of China Medical University, Shenyang, China
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Solaini L, Ministrini S, Bencivenga M, D'Ignazio A, Marino E, Cipollari C, Molteni B, Mura G, Marrelli D, Graziosi L, Roviello F, De Manzoni G, Tiberio GAM, Morgagni P. Conversion gastrectomy for stage IV unresectable gastric cancer: a GIRCG retrospective cohort study. Gastric Cancer 2019; 22:1285-1293. [PMID: 31065878 DOI: 10.1007/s10120-019-00968-2] [Citation(s) in RCA: 46] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/21/2018] [Accepted: 04/25/2019] [Indexed: 02/07/2023]
Abstract
BACKGROUND The aim of this study is to report the experience with conversion surgery from six Gruppo Italiano Ricerca Cancro Gastrico (GIRCG) centers, focusing our analysis on factors affecting survival and the risk of recurrence. METHODS A retrospective, multicenter cohort study was performed in patients who had undergone conversion gastrectomy between 2005 and 2017. Data were extracted from a GIRCG database including all metastatic gastric cancer patients submitted to surgery. Only stage IV unresectable tumors/metastases which became resectable after chemotherapy were included in this analysis. RESULTS Forty-five resected M1 patients were included in the analysis. Reasons for being deemed unresectable at diagnosis were peritoneal involvement (PCI > 6) (n = 38, 84.4%), distant metastatic nodes (n = 3, 6.6%) and extensive liver involvement (n = 4, 8.8%). Median follow-up was 25 months (IQR 9-50). Median overall survival from surgery was 15 months and 1-, 3- and 5-year survivals were 57.2, 36.1 and 24%, respectively. Median progression-free survival was 12 months with 1- and 3-year survival of 46.4 and 33.9%, respectively. At cox regression analysis the only independent prognostic factor for OS was the presence of more than one type of metastasis (HR 4.41, 95% CI 1.72-11.3, p = 0.002). A positive microscopic resection margin was the only risk factor for recurrence (HR 5.72, 95% CI 1.04-31.4, p = 0.045). CONCLUSIONS Unresectable stage IV GC patients could benefit from radical surgery after chemotherapy and achieve long survivals. The main prognostic factor for these patients was the presence of more than one type of extra-gastric metastatic involvement.
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Affiliation(s)
- Leonardo Solaini
- General and Oncologic Surgery, Department of Surgery, Morgagni-Pierantoni Hospital, Via Forlanini 34, Forlì, Italy
| | - Silvia Ministrini
- Department of Experimental and Clinical Sciences, University of Brescia, Brescia, Italy
| | - Maria Bencivenga
- General and Upper GI Surgery Division, University of Verona, Verona, Italy
| | - Alessia D'Ignazio
- Department of Surgery, Policlinico le Scotte- University of Siena, Siena, Italy
| | - Elisabetta Marino
- Department of Surgery, Santa Maria della Misericordia Hospital University of Perugia, Perugia, Italy
| | - Chiara Cipollari
- General and Upper GI Surgery Division, University of Verona, Verona, Italy
| | - Beatrice Molteni
- Department of Experimental and Clinical Sciences, University of Brescia, Brescia, Italy
| | - Gianni Mura
- Department of Surgery, Azienda USl Toscana SudEst- Arezzo, Arezzo, Italy
| | - Daniele Marrelli
- Department of Surgery, Policlinico le Scotte- University of Siena, Siena, Italy
| | - Luigina Graziosi
- Department of Surgery, Santa Maria della Misericordia Hospital University of Perugia, Perugia, Italy
| | - Franco Roviello
- Department of Surgery, Policlinico le Scotte- University of Siena, Siena, Italy
| | | | - Guido A M Tiberio
- Department of Experimental and Clinical Sciences, University of Brescia, Brescia, Italy
| | - Paolo Morgagni
- General and Oncologic Surgery, Department of Surgery, Morgagni-Pierantoni Hospital, Via Forlanini 34, Forlì, Italy.
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Nie R, Yuan S, Li Y, Chen S, Li S, Yang L, Yang L, Chen Y, Zhou Z. Risk-stratification model to select conversion surgery for advanced gastric cancer patients. Chin J Cancer Res 2019; 31:178-187. [PMID: 30996576 PMCID: PMC6433581 DOI: 10.21147/j.issn.1000-9604.2019.01.13] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open
Abstract
Objective Conversion surgery is a surgery with a purpose of R0 resection in primary advanced gastric cancer (GC) that responded well to systemic chemotherapy. This study aimed to explore the efficacy of conversion surgery for advanced GC. Methods A total of 618 advanced GC patients receiving systemic chemotherapy were stratified into low-, moderate- and high-risk groups based on a nomogram-predicted probability of overall survival. The survival of conversion surgery and chemotherapy alone groups was compared using the log-rank test and Cox regression analysis after propensity score matching (PSM). Results A nomogram with good discrimination (concordance index: 0.65) and accurate calibration was constructed. After PSM, the median survival time (MST) of conversion surgery was 26.80 months, compared with 16.60 months of chemotherapy alone (P<0.001). Conversion surgery was associated with a longer MST for patients in the low-risk group (30.40 monthsvs. 20.90 months, P=0.013), whereas it was not associated with prolonged survival in the moderate- and high-risk groups (P=0.221 and P=0.131, respectively).
Conclusions Conversion surgery was associated with longer survival, especially for low-risk population.
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Affiliation(s)
- Runcong Nie
- Department of Gastric Surgery, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China
| | - Shuqiang Yuan
- Department of Gastric Surgery, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China
| | - Yuanfang Li
- Department of Gastric Surgery, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China
| | - Shi Chen
- Department of Gastric Surgery, The 6th Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, China
| | - Shuman Li
- Department of Experimental Research (Cancer Institute), Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China
| | - Lirong Yang
- Department of Gastric Surgery, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China
| | - Lifang Yang
- Department of Gastric Surgery, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China
| | - Yingbo Chen
- Department of Gastric Surgery, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China
| | - Zhiwei Zhou
- Department of Gastric Surgery, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China
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28
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Beom SH, Choi YY, Baek SE, Li SX, Lim JS, Son T, Kim HI, Cheong JH, Hyung WJ, Choi SH, Jung M, Kim HS, Jeung HC, Chung HC, Rha SY, Noh SH. Multidisciplinary treatment for patients with stage IV gastric cancer: the role of conversion surgery following chemotherapy. BMC Cancer 2018; 18:1116. [PMID: 30442107 PMCID: PMC6238319 DOI: 10.1186/s12885-018-4998-x] [Citation(s) in RCA: 49] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2018] [Accepted: 10/28/2018] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND With advances in gastric cancer chemotherapy, conversion surgery has drawn attention as a new strategy to improve the outcome of stage IV disease. We investigated the efficacy of conversion surgery following chemotherapy for patients with stage IV gastric cancer. METHODS We retrospectively reviewed clinico-pathologic variables and oncologic outcomes for 101 patients with stage IV gastric cancer who were treated with systemic chemotherapy followed by gastrectomy with intension of curative resection from January 2005 to December 2012. RESULTS In terms of the best response from palliative chemotherapy, complete or partial response were observed in 65 patients (64.4%) in overall. Complete response of metastatic site were observed in 72 (71.3%) and 66 (65.3%) patients as best and pre-operative response, respectively. The overall complete macroscopic resection, rate was 56.4%. Eleven patients (10.9%) received combined metastasectomy. There was no postoperative surgery-related mortality for 1 month. The median overall survival time was 26.0 months. Multivariable analysis identified complete macroscopic resection, chemotherapy response (complete response/partial response) of metastatic sites, and change in CEA level as independent prognostic factors contributing to overall survival. CONCLUSIONS Patients with stage IV gastric cancer who exhibit a good clinical response to chemotherapy might obtain greater survival benefit from gastrectomy following chemotherapy compared with patients who exhibit a poor response to chemotherapy. Prospective, randomized trials are required to determine the best strategy for combining initial chemotherapy with subsequent gastrectomy.
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Affiliation(s)
- Seung-Hoon Beom
- Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, Republic of Korea
| | - Yoon Young Choi
- Department of Surgery, Yonsei Cancer Center, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, Republic of Korea
| | - Song-Ee Baek
- Department of Radiology, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, Republic of Korea
| | - Shuang-Xi Li
- Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Surgery, Peking University Cancer Hospital & Institute, Beijing, 100142, China
| | - Joon Seok Lim
- Department of Radiology, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, Republic of Korea
| | - Taeil Son
- Department of Surgery, Yonsei Cancer Center, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, Republic of Korea
| | - Hyoung-Il Kim
- Department of Surgery, Yonsei Cancer Center, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, Republic of Korea
| | - Jae-Ho Cheong
- Department of Surgery, Yonsei Cancer Center, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, Republic of Korea
| | - Woo Jin Hyung
- Department of Surgery, Yonsei Cancer Center, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, Republic of Korea
| | - Seung Ho Choi
- Department of Surgery, Yonsei Cancer Center, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, Republic of Korea
| | - Minkyu Jung
- Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, Republic of Korea
| | - Hyo Song Kim
- Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, Republic of Korea
| | - Hei-Cheul Jeung
- Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, Republic of Korea
| | - Hyun Cheol Chung
- Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, Republic of Korea
| | - Sun Young Rha
- Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, Republic of Korea.
| | - Sung Hoon Noh
- Department of Surgery, Yonsei Cancer Center, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, Republic of Korea.
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Zurleni T, Gjoni E, Altomare M, Rausei S. Conversion surgery for gastric cancer patients: A review. World J Gastrointest Oncol 2018; 10:398-409. [PMID: 30487951 PMCID: PMC6247102 DOI: 10.4251/wjgo.v10.i11.398] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/27/2018] [Revised: 09/25/2018] [Accepted: 10/07/2018] [Indexed: 02/05/2023] Open
Abstract
Gastric cancer (GC) is the third most common cancer-related cause of death worldwide. In locally advanced tumors, neoadjuvant chemotherapy has recently been introduced in most international Western guidelines. For metastatic and unresectable disease, there is still debate regarding correct management and the role of surgery. The standard approach for stage IV GC is palliative chemotherapy. Over the last decade, an increasing number of M1 patients who responded to palliative regimens of induction chemotherapy have been subsequently undergone surgery with curative intent. The objective of the present review is to analyze the literature regarding this approach, known as “conversion surgery”, which has become one of the most commonly adopted therapeutic options. It is defined as a treatment aiming at an R0 resection after chemotherapy in initially unresectable tumors. The 13 retrospective studies analyzed, with a total of 411 patients treated with conversion therapy, clearly show that even if standardization of unresectable and metastatic criteria, post-chemotherapy resectability evaluation and timing of surgery has not yet been established, an R0 surgery after induction chemotherapy with partial or complete response seems to offer superior survival results than chemotherapy alone. Additional larger sample-size randomized control trials are needed to identify subgroups of well-stratified patients who could benefit from this multimodal approach.
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Affiliation(s)
- Tommaso Zurleni
- Department of Surgery, ASST Valle Olona, Busto Arsizio 21052, Italy
| | - Elson Gjoni
- Department of Surgery, ASST Valle Olona, Busto Arsizio 21052, Italy
| | - Michele Altomare
- Department of Surgery, ASST Valle Olona, Busto Arsizio 21052, Italy
| | - Stefano Rausei
- Department of Surgery, ASST Valle Olona, Gallarate. 21013, Italy
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Xiao SM, Xu R, Tang XL, Ding Z, Li JM, Zhou X. Conversion therapy for advanced gastric cancer with trastuzumab combined with chemotherapy: A case report. Oncol Lett 2018; 16:2085-2090. [PMID: 30008904 PMCID: PMC6036458 DOI: 10.3892/ol.2018.8942] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2016] [Accepted: 07/14/2017] [Indexed: 12/23/2022] Open
Abstract
Gastric cancer is a common cancer of the gastrointestinal tract and the second most prevalent cause of cancer-associated mortality globally. Gastric cancer-associated mortality is increased in China compared with that in other countries. Key contributors to the poor prognosis of gastric cancer include late clinical presentation and genetic heterogeneity. Treatment based on the subtype of gastric cancer is important for effective therapy. The overexpression of the erb-b2 receptor tyrosine kinase 2 (ERBB2) gene and protein is associated with gastric cancer in humans. Chemotherapy and targeted therapy may control tumor growth and recurrence, which is an important function of conversion surgery. The present study reported a patient diagnosed with gastric cancer with multiple abdominal cavity and retroperitoneal lymph node metastases. ERBB2 amplification and overexpression were identified in both case reports presented. The patients were treated with four cycles of oxaliplatin, capecitabine and trastuzumab. Computed tomography revealed the lymph node metastases decreased in size following treatment, and surgical resection was performed. The four cycles of oxaliplatin, capecitabine and trastuzumab were continued subsequent to surgical resection at the administered dose. No recurrence was observed for >1 year after surgery. Trastuzumab combined with oxaliplatin and capecitabine as a conversion therapy regime for ERBB2-overexpressing advanced gastric adenocarcinoma increased the likelihood of successful surgical resection, and prolonged progression-free survival.
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Affiliation(s)
- Shuo-Meng Xiao
- Department of Gastrointestinal Surgery, Sichuan Cancer Hospital, Chengdu, Sichuan 610041, P.R. China
| | - Rui Xu
- Department of Gastrointestinal Surgery, Sichuan Cancer Hospital, Chengdu, Sichuan 610041, P.R. China
| | - Xiao-Li Tang
- Department of Gastrointestinal Surgery, Sichuan Cancer Hospital, Chengdu, Sichuan 610041, P.R. China
| | - Zhi Ding
- Department of Gastrointestinal Surgery, Sichuan Cancer Hospital, Chengdu, Sichuan 610041, P.R. China
| | - Ji-Man Li
- Department of Pathology, Sichuan Cancer Hospital, Chengdu, Sichuan 610041, P.R. China
| | - Xiang Zhou
- Department of Gastrointestinal Surgery, Sichuan Cancer Hospital, Chengdu, Sichuan 610041, P.R. China
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31
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Morgagni P, Solaini L, Framarini M, Vittimberga G, Gardini A, Tringali D, Valgiusti M, Monti M, Ercolani G. Conversion surgery for gastric cancer: A cohort study from a western center. Int J Surg 2018; 53:360-365. [PMID: 29654967 DOI: 10.1016/j.ijsu.2018.04.016] [Citation(s) in RCA: 42] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2018] [Revised: 03/15/2018] [Accepted: 04/08/2018] [Indexed: 02/06/2023]
Abstract
BACKGROUND Advanced unresectable gastric cancer has a dismal prognosis. The aim of this study was to evaluate the short- and long-term outcomes of patients who underwent induction chemotherapy ± gastrectomy for advanced gastric cancer. MATERIAL AND METHODS All patients referred to our center with a clinical diagnosis of unresectable locally advanced or stage IV gastric adenocarcinoma between April 2005 and August 2016 were included in the study. Cox regression was performed to find independent prognostic factor among the considered variable. RESULTS The cohort included 73 patients: 16 had best supportive care, 35 chemotherapy alone and 22 chemotherapy plus radical surgery. Thirty-three patients underwent surgery after chemotherapy. Twenty-two patients had R0 surgery, while the remaining 11 had only an exploratory procedure. Nine patients (40.9%) underwent gastrectomy plus hyperthermic intraperitoneal chemotherapy. Three patients out of 22 developed postoperative complications with a Clavien-Dindo grade above 2. Median survival was 50 months for patients who had chemotherapy plus surgery while it was 14 and 3 for those who had chemotherapy alone and best supportive care, respectively (p < 0.0001). Cox regression analysis performed on the whole cohort identified only radical conversion surgery as an independent factor positively associated with survival (HR 0.12, 95% CI 0.05-0.29, p < 0.0001). CONCLUSION Conversion gastrectomy, when R0 could be achieved, is associated with long survivals and it is the most important prognostic factor in patients with advanced gastric cancer. Further studies are needed to define the ideal patient who can really benefit from this treatment.
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Affiliation(s)
- Paolo Morgagni
- General and Oncologic Surgery, Morgagni-Pierantoni Hospital, AUSL Romagna, Forlì, Italy
| | - Leonardo Solaini
- General and Oncologic Surgery, Morgagni-Pierantoni Hospital, AUSL Romagna, Forlì, Italy; Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.
| | - Massimo Framarini
- General and Oncologic Surgery, Morgagni-Pierantoni Hospital, AUSL Romagna, Forlì, Italy
| | - Giovanni Vittimberga
- General and Oncologic Surgery, Morgagni-Pierantoni Hospital, AUSL Romagna, Forlì, Italy
| | - Andrea Gardini
- General and Oncologic Surgery, Morgagni-Pierantoni Hospital, AUSL Romagna, Forlì, Italy
| | - Domenico Tringali
- General and Oncologic Surgery, Morgagni-Pierantoni Hospital, AUSL Romagna, Forlì, Italy
| | - Martina Valgiusti
- Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e Cura dei Tumori (IRST) IRCCS, Meldola, Italy
| | - Manlio Monti
- Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e Cura dei Tumori (IRST) IRCCS, Meldola, Italy
| | - Giorgio Ercolani
- General and Oncologic Surgery, Morgagni-Pierantoni Hospital, AUSL Romagna, Forlì, Italy; Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
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32
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Polom K, Böger C, Smyth E, Marrelli D, Behrens HM, Marano L, Becker T, Lordick F, Röcken C, Roviello F. Synchronous metastatic gastric cancer-molecular background and clinical implications with special attention to mismatch repair deficiency. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2018; 44:626-631. [PMID: 29545085 DOI: 10.1016/j.ejso.2018.02.208] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2017] [Revised: 02/06/2018] [Accepted: 02/15/2018] [Indexed: 12/21/2022]
Abstract
BACKGROUND Current guidelines recommend that metastatic gastric cancer should not be treated with surgery unless this is required for symptom control. We hypothesized that patients with mismatch repair deficiency (MMRd) gastric cancer and metastatic disease detected at the timepoint of surgical resection would have superior survival compared to patients with MMRd cancers in the same setting. METHODS Clinicopathological details and survival data were collected from prospective databases at two large European centers on patients who had undergone surgery and were diagnosed with synchronous stage IV gastric cancer (distant lymph nodes, positive peritoneal cytology, peritoneal, and distant metastases) at the timepoint of surgery. Resection specimens were tested for the presence of microsatellite instability using a standard 5 mononucleotide repeat panel. RESULTS One hundred and seventy six patients with resected stage IV gastric cancer were identified. 14/176 (8.0%) had MSI-H (high) disease. There was no significant difference between the clinical and pathological characteristics of MSI and microsatellite stable (MSS) patients. No differences in the type of metastases were observed between MSI and MSS groups. Patients who were MSI-H had superior OS compared to MSS patients (median OS 15.9 vs. 8 months, p = 0.023). However, in Cox regression multivariate analysis only liver and peritoneal metastases were independent predictors of survival. CONCLUSIONS Surgically treated patients with MSI-H stage IV gastric cancer have a better survival than patients with MSS gastric cancer. Further analysis of the role of surgery in MSI stage IV GC is required.
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Affiliation(s)
- Karol Polom
- General Surgery and Surgical Oncology Department, University of Siena, Italy viale Bracci 16, 53100, Siena, Italy; Department of Surgical Oncology, Medical University of Gdansk, Gdansk, Poland.
| | - Christine Böger
- Department of Pathology, Christian-Albrechts-University, Kiel, Germany
| | - Elizabeth Smyth
- Department of Gastrointestinal Oncology and Lymphoma, Royal Marsden Hospital, London and Sutton, United Kingdom
| | - Daniele Marrelli
- General Surgery and Surgical Oncology Department, University of Siena, Italy viale Bracci 16, 53100, Siena, Italy
| | | | - Luigi Marano
- General, Minimally Invasive and Robotic Surgery, Department of Surgery, "San Matteo degli Infermi Hospital"-ASL Umbria 2, 06049, Spoleto, Italy
| | - Thomas Becker
- Department of General, Visceral, Thoracic, Transplant and Pediatric Surgery, Christian-Albrechts-University, Kiel, Germany
| | - Florian Lordick
- University Cancer Center Leipzig (UCCL), University Medicine Leipzig, 04103 Leipzig, Germany
| | - Christoph Röcken
- Department of Pathology, Christian-Albrechts-University, Kiel, Germany
| | - Franco Roviello
- General Surgery and Surgical Oncology Department, University of Siena, Italy viale Bracci 16, 53100, Siena, Italy
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Al-Batran SE, Goetze TO, Mueller DW, Vogel A, Winkler M, Lorenzen S, Novotny A, Pauligk C, Homann N, Jungbluth T, Reissfelder C, Caca K, Retter S, Horndasch E, Gumpp J, Bolling C, Fuchs KH, Blau W, Padberg W, Pohl M, Wunsch A, Michl P, Mannes F, Schwarzbach M, Schmalenberg H, Hohaus M, Scholz C, Benckert C, Knorrenschild JR, Kanngießer V, Zander T, Alakus H, Hofheinz RD, Roedel C, Shah MA, Sasako M, Lorenz D, Izbicki J, Bechstein WO, Lang H, Moenig SP. The RENAISSANCE (AIO-FLOT5) trial: effect of chemotherapy alone vs. chemotherapy followed by surgical resection on survival and quality of life in patients with limited-metastatic adenocarcinoma of the stomach or esophagogastric junction - a phase III trial of the German AIO/CAO-V/CAOGI. BMC Cancer 2017; 17:893. [PMID: 29282088 PMCID: PMC5745860 DOI: 10.1186/s12885-017-3918-9] [Citation(s) in RCA: 143] [Impact Index Per Article: 17.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2017] [Accepted: 12/14/2017] [Indexed: 12/13/2022] Open
Abstract
Background Historical data indicate that surgical resection may benefit select patients with metastatic gastric and gastroesophageal junction cancer. However, randomized clinical trials are lacking. The current RENAISSANCE trial addresses the potential benefits of surgical intervention in gastric and gastroesophageal junction cancer with limited metastases. Methods This is a prospective, multicenter, randomized, investigator-initiated phase III trial. Previously untreated patients with limited metastatic stage (retroperitoneal lymph node metastases only or a maximum of one incurable organ site that is potentially resectable or locally controllable with or without retroperitoneal lymph nodes) receive 4 cycles of FLOT chemotherapy alone or with trastuzumab if Her2+. Patients without disease progression after 4 cycles are randomized 1:1 to receive additional chemotherapy cycles or surgical resection of primary and metastases followed by subsequent chemotherapy. 271 patients are to be allocated to the trial, of which at least 176 patients will proceed to randomization. The primary endpoint is overall survival; main secondary endpoints are quality of life assessed by EORTC-QLQ-C30 questionnaire, progression free survival and surgical morbidity and mortality. Recruitment has already started; currently (Feb 2017) 22 patients have been enrolled. Discussion If the RENAISSANCE concept proves to be effective, this could potentially lead to a new standard of therapy. On the contrary, if the outcome is negative, patients with gastric or GEJ cancer and metastases will no longer be considered candidates for surgical intervention. Trial registration The article reports of a health care intervention on human participants and is registered on October 12, 2015 under ClinicalTrials.gov Identifier: NCT02578368; EudraCT: 2014–002665-30.
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Affiliation(s)
- Salah-Eddin Al-Batran
- Institute of Clinical Cancer Research (IKF) at Krankenhaus Nordwest, UCT-University Cancer Center, Krankenhaus Nordwest, Steinbacher Hohl 2-26, 60488, Frankfurt am Main, Germany.
| | - Thorsten O Goetze
- Institute of Clinical Cancer Research (IKF) at Krankenhaus Nordwest, UCT-University Cancer Center, Krankenhaus Nordwest, Steinbacher Hohl 2-26, 60488, Frankfurt am Main, Germany
| | - Daniel W Mueller
- Institute of Clinical Cancer Research (IKF) at Krankenhaus Nordwest, UCT-University Cancer Center, Krankenhaus Nordwest, Steinbacher Hohl 2-26, 60488, Frankfurt am Main, Germany
| | - Arndt Vogel
- Department of Internal Medicine, Hannover Medical School, 30625, Hannover, Germany
| | - Michael Winkler
- Department of Surgery, Hannover Medical School, 30625, Hannover, Germany
| | - Sylvie Lorenzen
- Department of Internal Medicine, Klinikum rechts der Isar der TU München, 81675, Munich, Germany
| | - Alexander Novotny
- Department of Surgery, Klinikum rechts der Isar der TU München, 81675, Munich, Germany
| | - Claudia Pauligk
- Institute of Clinical Cancer Research (IKF) at Krankenhaus Nordwest, UCT-University Cancer Center, Krankenhaus Nordwest, Steinbacher Hohl 2-26, 60488, Frankfurt am Main, Germany
| | - Nils Homann
- Department of Internal Medicine II, Academic Teaching Hospital Wolfsburg, 05361, Wolfsburg, Germany
| | - Thomas Jungbluth
- Department of Surgery, Academic Teaching Hospital Wolfsburg, 05361, Wolfsburg, Germany
| | - Christoph Reissfelder
- Department of Surgery, University Hospital Carl Gustav Carus Dresden, 01307, Dresden, Germany
| | - Karel Caca
- Department of Internal Medicine, Klinikum Ludwigsburg, 71640, Ludwigsburg, Germany
| | - Steffen Retter
- Department of Surgery, Klinikum Ludwigsburg, 71640, Ludwigsburg, Germany
| | - Eva Horndasch
- Department of Internal Medicine, Kliniken des Landkreises Neumarkt, 92318, Neumarkt, Germany
| | - Julia Gumpp
- Department of Surgery, Kliniken des Landkreises Neumarkt, 92318, Neumarkt, Germany
| | - Claus Bolling
- Department of Internal Medicine, Agaplesion Markus Krankenhaus Frankfurter, Diakonie Kliniken gGmbH, 60431, Frankfurt, Germany
| | - Karl-Hermann Fuchs
- Department of Surgery, Agaplesion Markus Krankenhaus Frankfurter Diakonie Kliniken gGmbH, 60431, Frankfurt, Germany
| | - Wolfgang Blau
- Department of Medical Oncology, Gießen University Hospital, 35392, Gießen, Germany
| | - Winfried Padberg
- Department of Surgery, Gießen University Hospital, 35392, Gießen, Germany
| | - Michael Pohl
- Department of Internal Medicine, Ruhr-University Bochum, 44801, Bochum, Germany
| | - Andreas Wunsch
- Department of Surgery, Ruhr-University Bochum, 44801, Bochum, Germany
| | - Patrick Michl
- Department of Medical Oncology, Halle University Hospital, 06120, Halle (Saale), Germany
| | - Frank Mannes
- Department of Internal Medicine, Halle University Hospital, (Saale), 06120, Halle, Germany
| | | | - Harald Schmalenberg
- Department of Internal Medicine IV, Städtisches Klinikum Dresden, 01067, Dresden, Germany
| | - Michael Hohaus
- Department of Surgery, Städtisches Klinikum Dresden, 01067, Dresden, Germany
| | - Christian Scholz
- Department of Medical Oncology, Vivantes Klinikum Am Urban Berlin, 10967, Berlin, Germany
| | - Christoph Benckert
- Department of Surgery, Vivantes Klinikum Am Urban Berlin, 10967, Berlin, Germany
| | | | - Veit Kanngießer
- Department of Surgery, Marburg University Hospital, 35043, Marburg, Germany
| | - Thomas Zander
- Department of Internal Medicine, University Hospital Köln, 50937, Köln, Germany
| | - Hakan Alakus
- Department of Surgery, University Hospital Köln, 50937, Köln, Germany
| | | | - Claus Roedel
- Department of Radiation- Oncology, Frankfurt University Hospital, 60590, Frankfurt, Germany
| | - Manish A Shah
- Department of Medicine Hematology and Oncology, Weill Cornell Medicine, New York, USA
| | - Mitsuru Sasako
- Department of Surgery, Hyogo College of Medicine, Mukogawa-cho, Nishinomiya, Hyogo, Japan
| | - Dietmar Lorenz
- Department of General and Visceral Surgery, Sana- Klinikum Offenbach, 63069 Offenbach, Hamburg, Germany
| | - Jakob Izbicki
- Department of Surgery, Hamburg University Hospital, 20246, Hamburg, Germany
| | - Wolf O Bechstein
- Department of Surgery, Frankfurt University Hospital, 60590 Frankfurt, Hamburg, Germany
| | - Hauke Lang
- Department of Surgery, Mainz University Hospital, 55131, Mainz, Germany
| | - Stefan P Moenig
- Hôpitaux Universitaires de Genève, Service de Chirurgie viscéral, 1205, Genève, Switzerland
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Al-Batran SE, Homann N, Pauligk C, Illerhaus G, Martens UM, Stoehlmacher J, Schmalenberg H, Luley KB, Prasnikar N, Egger M, Probst S, Messmann H, Moehler M, Fischbach W, Hartmann JT, Mayer F, Höffkes HG, Koenigsmann M, Arnold D, Kraus TW, Grimm K, Berkhoff S, Post S, Jäger E, Bechstein W, Ronellenfitsch U, Mönig S, Hofheinz RD. Effect of Neoadjuvant Chemotherapy Followed by Surgical Resection on Survival in Patients With Limited Metastatic Gastric or Gastroesophageal Junction Cancer: The AIO-FLOT3 Trial. JAMA Oncol 2017; 3:1237-1244. [PMID: 28448662 DOI: 10.1001/jamaoncol.2017.0515] [Citation(s) in RCA: 323] [Impact Index Per Article: 40.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Importance Surgical resection has a potential benefit for patients with metastatic adenocarcinoma of the stomach and gastroesophageal junction. Objective To evaluate outcome in patients with limited metastatic disease who receive chemotherapy first and proceed to surgical resection. Design, Setting, and Participants The AIO-FLOT3 (Arbeitsgemeinschaft Internistische Onkologie-fluorouracil, leucovorin, oxaliplatin, and docetaxel) trial is a prospective, phase 2 trial of 252 patients with resectable or metastatic gastric or gastroesophageal junction adenocarcinoma. Patients were enrolled from 52 cancer care centers in Germany between February 1, 2009, and January 31, 2010, and stratified to 1 of 3 groups: resectable (arm A), limited metastatic (arm B), or extensive metastatic (arm C). Data cutoff was January 2012, and the analysis was performed in March 2013. Interventions Patients in arm A received 4 preoperative cycles of fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) followed by surgery and 4 postoperative cycles. Patients in arm B received at least 4 cycles of neoadjuvant FLOT and proceeded to surgical resection if restaging (using computed tomography and magnetic resonance imaging) showed a chance of margin-free (R0) resection of the primary tumor and at least a macroscopic complete resection of the metastatic lesions. Patients in arm C were offered FLOT chemotherapy and surgery only if required for palliation. Patients received a median (range) of 8 (1-15) cycles of FLOT. Main Outcomes and Measures The primary end point was overall survival. Results In total, 238 of 252 patients (94.4%) were eligible to participate. The median (range) age of participants was 66 (36-79) years in arm A (n = 51), 63 (28-79) years in arm B (n = 60), and 65 (23-83) years in arm C (n = 127). Patients in arm B (n = 60) had only retroperitoneal lymph node involvement (27 patients [45%]), liver involvement (11 [18.3%]), lung involvement (10 [16.7%]), localized peritoneal involvement (4 [6.7%]), or other (8 [13.3%]) incurable sites. Median overall survival was 22.9 months (95% CI, 16.5 to upper level not achieved) for arm B, compared with 10.7 months (95% CI, 9.1-12.8) for arm C (hazard ratio, 0.37; 95% CI, 0.25-0.55) (P < .001). The response rate for arm B was 60% (complete, 10%; partial, 50%), which is higher than the 43.3% for arm C. In arm B, 36 of 60 patients (60%) proceeded to surgery. The median overall survival was 31.3 months (95% CI, 18.9-upper level not achieved) for patients who proceeded to surgery and 15.9 months (95% CI, 7.1-22.9) for the other patients. Conclusions and Relevance Patients with limited metastatic disease who received neoadjuvant chemotherapy and proceeded to surgery showed a favorable survival. The AIO-FLOT3 trial provides a rationale for further randomized clinical trials. Trial Registration clinicaltrials.gov identifier: NCT00849615.
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Affiliation(s)
- Salah-Eddin Al-Batran
- Institute of Clinical Cancer Research, Krankenhaus Nordwest, Universitären University Cancer Center, Frankfurt, Germany
| | - Nils Homann
- Medical Department II, Klinikum Wolfsburg, Wolfsburg, Germany
| | - Claudia Pauligk
- Institute of Clinical Cancer Research, Krankenhaus Nordwest, Universitären University Cancer Center, Frankfurt, Germany
| | - Gerald Illerhaus
- Medical Department I, Universitätsklinikum Freiburg, Freiburg, Germany.,now with Clinic for Hematology, Oncology, and Palliative Care, Klinikum Stuttgart, Kriegsbergstraße, Stuttgart, Germany
| | - Uwe M Martens
- Medical Department III, SLK-Kliniken GmbH, Heilbronn, Germany
| | - Jan Stoehlmacher
- Medical Clinic and Polyclinic, Universitätsklinikum Carl Gustav Carus, Dresden, Germany.,now with Institute for Clinical Genetics, Bonn, Germany
| | - Harald Schmalenberg
- Medical Department II, Universitätsklinikum Jena, Jena, Germany.,now with Medical Department IV, Krankenhaus Dresden-Friedrichstadt, Dresden, Germany
| | - Kim B Luley
- Medical Department I Hematology/Oncology, Universitätsklinikum Schleswig-Holstein, Lübeck, Germany
| | - Nicole Prasnikar
- Medical Department I, Klinikum Ludwigsburg, Ludwigsburg, Germany.,now with Medical Department II, Asklepios Klinik Altona, Hamburg, Germany
| | - Matthias Egger
- Medical Department, Ortenau Klinikum Lahr, Lahr, Germany
| | - Stephan Probst
- Department of Hematology and Oncology, Klinikum Bielefeld, Bielefeld, Germany
| | - Helmut Messmann
- Medical Department III, Zentralklinikum Augsburg, Augsburg, Germany
| | - Markus Moehler
- Medical Department I, Universitätsklinik Mainz, Mainz, Germany
| | | | - Jörg T Hartmann
- Medical Department II, Universitätsklinikum der Eberhard-Karl-Universität, Tübingen, Germany.,now with Clinic for Hematology, Oncology, and Immunology, Franziskus Hospital Bielefeld, Bielefeld, Germany
| | - Frank Mayer
- Medical Department II, Universitätsklinikum der Eberhard-Karl-Universität, Tübingen, Germany.,now with Gemeinschaftspraxis, Friedrichshafen, Germany
| | | | - Michael Koenigsmann
- MediProjekt, Gesellschaft für Medizinstatistik und Projektentwicklung, Hannover, Germany
| | - Dirk Arnold
- Clinic and Polyclinic for Internal Medicine IV, Universitätsklinikum Halle, Halle, Germany.,now with CUF Hospitals Cancer Centre, Lisboa, Portugal
| | - Thomas W Kraus
- Department of Surgery, Krankenhaus Nordwest, Frankfurt, Germany
| | - Kersten Grimm
- Department of Surgery, Krankenhaus Nordwest, Frankfurt, Germany
| | - Stefan Berkhoff
- Department of Surgery, Krankenhaus Nordwest, Frankfurt, Germany
| | - Stefan Post
- Medical Department, Universitätsmedizin Mannheim, Mannheim, Germany
| | - Elke Jäger
- Department of Oncology and Hematology, Krankenhaus Nordwest, Frankfurt, Germany
| | - Wolf Bechstein
- Department of General and Visceral Surgery, University Hospital Frankfurt, Frankfurt, Germany
| | | | - Stefan Mönig
- Department of General and Visceral Surgery, Universitätsklinik Köln, Köln, Germany
| | - Ralf D Hofheinz
- Medical Department, Universitätsmedizin Mannheim, Mannheim, Germany
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35
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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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Uemura N, Kikuchi S, Sato Y, Ohnuma H, Okamoto K, Miyamoto H, Hirakawa M, Sagawa T, Fujikawa K, Takahashi Y, Okuda T, Minami S, Takahashi M, Okamoto T, Takada K, Miyanisi K, Takayama T, Kato J. A phase II study of modified docetaxel, cisplatin, and S-1 (mDCS) chemotherapy for unresectable advanced gastric cancer. Cancer Chemother Pharmacol 2017; 80:707-713. [PMID: 28849257 DOI: 10.1007/s00280-017-3404-8] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2016] [Accepted: 07/24/2017] [Indexed: 02/06/2023]
Abstract
PURPOSE Triplet therapy using docetaxel, cisplatin, and S-1 (DCS) against unresectable gastric cancer as previously reported by us showed high clinical efficacy, with a 87.1% total response rate; however, it also showed a high incidence of grade 3/4 toxicity. With the aim of reducing toxicities, we conducted a phase II study of modified DCS (mDCS), using a reduced dose of docetaxel, and evaluated the clinical efficacy and adverse events of this regimen. METHODS Patients with unresectable gastric cancer received chemotherapy with S-1 (40 mg/m2 b.i.d) on days 1-14, and docetaxel (50 mg/m2) plus cisplatin (60 mg/m2) on day 8 every 3 weeks. The primary endpoint was the response rate (RR). Overall (OS) and progression-free survival (PFS), and toxicities were also evaluated. RESULTS Forty-nine patients were enrolled from November 2011 to April 2014, and 43 were eligible. The overall RR was 79.1%, including two cases of a complete response (4.7%), and 32 cases of a partial response (74.4%). Nine cases had stable disease (20.9%) but none showed progressive disease. Of the 43 cases, 15 cases (34.9%) underwent curative conversion surgery. The median PFS was 350 days (95% CI 240-416 days) and median OS was 722 days (95% CI 411 days-not reached). Grade 3/4 neutropenia developed in 79.1%, and febrile neutropenia in 34.9%, of patients. Non-hematological grade 3/4 adverse events were anorexia (25.6%), nausea (4.7%), and diarrhea (9.3%). CONCLUSION Modified DCS therapy showed high clinical efficacy sufficient enough to attempt conversion therapy against unresectable gastric cancer. Modified DCS showed fewer toxicities, but careful management of these is still essential.
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Affiliation(s)
- Naoki Uemura
- Department of Medical Oncology and Hematology, Sapporo Medical University School of Medicine, S-1, W-16, Chuo-Ku, Sapporo, 060-8543, Japan
| | - Shohei Kikuchi
- Department of Medical Oncology and Hematology, Sapporo Medical University School of Medicine, S-1, W-16, Chuo-Ku, Sapporo, 060-8543, Japan
| | - Yasushi Sato
- Department of Community Medicine for Gastroenterology and Oncology, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan
| | - Hiroyuki Ohnuma
- Department of Medical Oncology and Hematology, Sapporo Medical University School of Medicine, S-1, W-16, Chuo-Ku, Sapporo, 060-8543, Japan
| | - Koichi Okamoto
- Department of Community Medicine for Gastroenterology and Oncology, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan
| | - Hiroshi Miyamoto
- Department of Community Medicine for Gastroenterology and Oncology, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan
| | - Masahiro Hirakawa
- Department of Medical Oncology and Hematology, Sapporo Medical University School of Medicine, S-1, W-16, Chuo-Ku, Sapporo, 060-8543, Japan
| | - Tamotsu Sagawa
- Department of Gastroenterology, Hokkaido Cancer Center, Sapporo, Japan
| | - Koshi Fujikawa
- Department of Gastroenterology, Hokkaido Cancer Center, Sapporo, Japan
| | - Yasuo Takahashi
- Department of Gastroenterology, Hokkaido Cancer Center, Sapporo, Japan
| | - Toshinori Okuda
- Department of Gastroenterology, Oji General Hospital, Tomakomai, Japan
| | - Shinya Minami
- Department of Gastroenterology, Oji General Hospital, Tomakomai, Japan
| | - Minoru Takahashi
- Department of Gastroenterology, Sapporo Kyoritsu-Gorinbashi Hospital, Sapporo, Japan
| | - Tetsuro Okamoto
- Department of Gastroenterology, Kiyota Hospital, Sapporo, Japan
| | - Kohichi Takada
- Department of Medical Oncology and Hematology, Sapporo Medical University School of Medicine, S-1, W-16, Chuo-Ku, Sapporo, 060-8543, Japan
| | - Koji Miyanisi
- Department of Medical Oncology and Hematology, Sapporo Medical University School of Medicine, S-1, W-16, Chuo-Ku, Sapporo, 060-8543, Japan
| | - Tetsuji Takayama
- Department of Community Medicine for Gastroenterology and Oncology, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan
| | - Junji Kato
- Department of Medical Oncology and Hematology, Sapporo Medical University School of Medicine, S-1, W-16, Chuo-Ku, Sapporo, 060-8543, Japan.
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Yuan SQ, Nie RC, Chen S, Chen XJ, Chen YM, Xu LP, Yang LF, Zhou ZW, Peng JS, Chen YB. Selective Gastric Cancer Patients with Peritoneal Seeding Benefit from Gastrectomy after Palliative Chemotherapy: A Propensity Score Matching Analysis. J Cancer 2017; 8:2231-2237. [PMID: 28819425 PMCID: PMC5560140 DOI: 10.7150/jca.18932] [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: 12/26/2016] [Accepted: 04/30/2017] [Indexed: 12/26/2022] Open
Abstract
Background: The present study aimed to explore whether gastric cancer patients with peritoneal seeding after receiving palliative chemotherapy could benefit from gastrectomy and to identify patients with peritoneal seeding who should be selected to receive gastrectomy. Methods: A total of 201 gastric cancer patients were diagnosed with peritoneal seeding and received palliative chemotherapy. Propensity score matching (PSM) was performed to balance the selection bias. Results: After PSM, compared with non-gastrectomy group, gastrectomy group had a longer median overall survival (OS) (23.60 vs. 13.80 moths; P=0.034). Patients with R0 resection had a median OS of 43.60 months compared with 11.27 months in patients who underwent R1/2 resection (P<0.001). The median OS times between the R1/2 resection and non-gastrectomy groups were not different (P=0.139). Subgroup analysis revealed that only patients receiving more than 4 periods of first-line chemotherapy benefited from gastrectomy (P=0.018), whereas patients receiving 1-4 periods of first-line chemotherapy did not (P=0.275). Multivariate analysis showed that gastrectomy (P=0.012) and the period of first-line chemotherapy (P<0.001) were independent prognostic factors. The overall postoperative morbidity was 3.03% (1/33) in the gastrectomy group, and no treatment-related death was observed. Conclusions: The present study indicated that gastrectomy after palliative chemotherapy is a safe procedure and showed a survival benefit for gastric cancer patients with peritoneal seeding. Moreover, clinically curative R0 gastrectomy and more than 4 periods of palliative chemotherapy resulted in better clinical outcomes.
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Affiliation(s)
- Shu-Qiang Yuan
- Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Run-Cong Nie
- Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Shi Chen
- Department of Gastric Surgery, the 6th Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Xiao-Jiang Chen
- Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Yong-Ming Chen
- Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Li-Pu Xu
- Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Li-Fang Yang
- Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Zhi-Wei Zhou
- Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Jun-Sheng Peng
- Department of Gastric Surgery, the 6th Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Ying-Bo Chen
- Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
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Conversion therapy for inoperable advanced gastric cancer patients by docetaxel, cisplatin, and S-1 (DCS) chemotherapy: a multi-institutional retrospective study. Gastric Cancer 2017; 20:517-526. [PMID: 27553665 DOI: 10.1007/s10120-016-0633-1] [Citation(s) in RCA: 67] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2016] [Accepted: 08/08/2016] [Indexed: 02/07/2023]
Abstract
BACKGROUND Conversion therapy is an option for unresectable metastatic gastric cancer when distant metastases are controlled by chemotherapy; however, the feasibility and efficacy remain unclear. This study aimed to assess the feasibility and efficacy of conversion therapy in patients with initially unresectable gastric cancer treated with docetaxel, cisplatin, and S-1 (DCS) chemotherapy by evaluating clinical outcomes. METHODS One hundred unresectable metastatic gastric cancer patients, enrolled in three DCS chemotherapy clinical trials, were retrospectively evaluated. The patients received oral S-1 (40 mg/m2 b.i.d.) on days 1-14 and intravenous cisplatin (60 mg/m2) and docetaxel (50-60 mg/m2) on day 8 every 3 weeks. Conversion therapy was defined when the patients could undergo R0 resection post-DCS chemotherapy and were able to tolerate curative surgery. RESULTS Conversion therapy was achieved in 33/100 patients, with no perioperative mortality. Twenty-eight of the 33 patients (84.8 %) achieved R0 resection, and 78.8 % were defined as histological chemotherapeutic responders. The median overall survival (OS) of patients who underwent conversion therapy was 47.8 months (95 % CI 28.0-88.5 months). Patients who underwent R0 resection had significantly longer OS than those who underwent R1 and R2 resections (P = 0.0002). Of the patients with primarily unresectable metastases, 10 % lived >5 years. Among patients who underwent conversion therapy, multivariate analysis showed that the pathological response was a significant independent predictor for OS. CONCLUSIONS DCS safely induced a high conversion rate, with very high R0 and pathological response rates, and was associated with a good prognosis; these findings warrant further prospective investigations.
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Gao L, Hao J, Niu YY, Tian M, Yang X, Zhu CH, Ding XL, Liu XH, Zhang HR, Liu C, Qin XM, Wu XZ. Network pharmacology dissection of multiscale mechanisms of herbal medicines in stage IV gastric adenocarcinoma treatment. Medicine (Baltimore) 2016; 95:e4389. [PMID: 27583849 PMCID: PMC5008533 DOI: 10.1097/md.0000000000004389] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Increasing evidence has shown that Chinese Herbal Medicine (CHM) has efficient therapeutic effects for advanced gastric adenocarcinoma, while the therapeutic mechanisms underlying this treatment remain unclear.In this study, the Kaplan-Meier method and Cox regression analysis were used to evaluate the survival benefit of CHM treatment, and correlation analysis was applied to identify the most effective components in the formulas. A network pharmacological approach was developed to decipher the potential therapeutic mechanisms of CHM.CHM treatment was an independent protective factor. The hazard ratio was 0.364 (95% CI 0.245-0.540; P < 0.001). The median survival time was 18 months for patients who received CHM treatment, while for patients without CHM treatment was decreased to 9 months (P < 0.001). Thirteen out of the total 204 herbs were significantly correlated with favorable survival outcomes (P < 0.05), likely representing the most effective components in these formulas. Bioinformatics analyses suggested that the simultaneous manipulation of multiple targets in proliferation pathways (such as epidermal growth factor receptor, fibroblast growth factor receptor 2, human epidermal growth factor receptor 2, proliferating cell nuclear antigen, and insulin like growth factor 2) and the process of cancer metastasis (collagen families, fibronectin 1 and matrix metalloproteinases families) might largely account for the mechanisms of the 13 herbs against gastric adenocarcinoma.A network pharmacology method was introduced to decipher the underlying mechanisms of CHM, which provides a good foundation for herbal research based on clinical data.
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Affiliation(s)
- Li Gao
- Modern Research Center for Traditional Chinese Medicine, Shanxi University, Taiyuan
| | - Jian Hao
- Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin
| | - Yang-Yang Niu
- Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin
| | - Miao Tian
- College of Chemistry and Chemical Engineering, Shanxi University, Taiyuan, P.R. China
| | - Xue Yang
- Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin
| | - Cui-Hong Zhu
- Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin
| | - Xiu-Li Ding
- Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin
| | - Xiao-Hui Liu
- Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin
| | - Hao-Ran Zhang
- Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin
| | - Chang Liu
- Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin
| | - Xue-Mei Qin
- Modern Research Center for Traditional Chinese Medicine, Shanxi University, Taiyuan
| | - Xiong-Zhi Wu
- Modern Research Center for Traditional Chinese Medicine, Shanxi University, Taiyuan
- Correspondence: Xiong-Zhi Wu, Zhong-Shan-Men Inpatient Department, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Huan-Hu-Xi Road, Ti-Yuan-Bei, He-Xi District, Tianjin 300060, P.R. China (e-mail: )
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Conversion therapy for gastric cancer: who can make conversion as successful as Goromaru? Gastric Cancer 2016; 19:685-6. [PMID: 27055560 DOI: 10.1007/s10120-016-0609-1] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2016] [Accepted: 03/30/2016] [Indexed: 02/07/2023]
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Kinoshita J, Fushida S, Tsukada T, Oyama K, Okamoto K, Makino I, Nakamura K, Miyashita T, Tajima H, Takamura H, Ninomiya I, Ohta T. Efficacy of conversion gastrectomy following docetaxel, cisplatin, and S-1 therapy in potentially resectable stage IV gastric cancer. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2015; 41:1354-1360. [PMID: 26028256 DOI: 10.1016/j.ejso.2015.04.021] [Citation(s) in RCA: 55] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2015] [Revised: 04/21/2015] [Accepted: 04/24/2015] [Indexed: 12/31/2022]
Abstract
BACKGROUND Recent advances in gastric cancer chemotherapy have made macroscopic complete resection possible in some patients with stage IV disease. METHODS We retrospectively investigated the efficacy of multimodal therapy with combined docetaxel, cisplatin, and S-1 (DCS) and conversion gastrectomy in 57 patients with stage IV gastric cancer. RESULTS Of the 57 patients, 15 patients were categorized into potentially resectable case, which is defined as patients with single incurable factor including the upper abdominal para-aortic lymph node metastasis (16a2b1 PAN metastasis) or fewer than three peripheral liver metastases. The other 42 were categorized as initially unresectable. All of patients underwent DCS therapy, and then 34 patients underwent conversion gastrectomy. The 3-year overall survival (OS) rate among the patients who underwent conversion gastrectomy was 50.1% with MST of 29.9 months. They had significantly longer OS than patients who underwent DCS therapy alone (p < 0.01). Univariate analysis among the patents with conversion gastrectomy identified 16a2b1PAN metastasis, peritoneal metastasis, potential resectable case, R0 resection as significant prognostic factors. A 3-year OS in potential resectable cases was 92.9%. Multivariate analysis identified potential resectability as the only independent prognostic factor contributing to OS (HR 0.133, 95%CI 0.024-0. 744, p = 0.021). In contrast, clinical response was selected as the only independent prognostic factor in the subgroup of initially unresectable cases (HR 0.354, 95%CI 0.151-0.783, p = 0.021). CONCLUSION Patients with potentially resectable disease had a remarkably good prognosis among stage IV gastric cancer patients, and might be ideal candidates for conversion gastrectomy following DCS therapy.
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Affiliation(s)
- J Kinoshita
- Department of Gastroenterologic Surgery Division of Cancer Medicine, Graduate School of Medicine Science, Kanazawa University, 13-1 Takaramachi, Kanazawa, 920-8641, Japan
| | - S Fushida
- Department of Gastroenterologic Surgery Division of Cancer Medicine, Graduate School of Medicine Science, Kanazawa University, 13-1 Takaramachi, Kanazawa, 920-8641, Japan.
| | - T Tsukada
- Department of Gastroenterologic Surgery Division of Cancer Medicine, Graduate School of Medicine Science, Kanazawa University, 13-1 Takaramachi, Kanazawa, 920-8641, Japan
| | - K Oyama
- Department of Gastroenterologic Surgery Division of Cancer Medicine, Graduate School of Medicine Science, Kanazawa University, 13-1 Takaramachi, Kanazawa, 920-8641, Japan
| | - K Okamoto
- Department of Gastroenterologic Surgery Division of Cancer Medicine, Graduate School of Medicine Science, Kanazawa University, 13-1 Takaramachi, Kanazawa, 920-8641, Japan
| | - I Makino
- Department of Gastroenterologic Surgery Division of Cancer Medicine, Graduate School of Medicine Science, Kanazawa University, 13-1 Takaramachi, Kanazawa, 920-8641, Japan
| | - K Nakamura
- Department of Gastroenterologic Surgery Division of Cancer Medicine, Graduate School of Medicine Science, Kanazawa University, 13-1 Takaramachi, Kanazawa, 920-8641, Japan
| | - T Miyashita
- Department of Gastroenterologic Surgery Division of Cancer Medicine, Graduate School of Medicine Science, Kanazawa University, 13-1 Takaramachi, Kanazawa, 920-8641, Japan
| | - H Tajima
- Department of Gastroenterologic Surgery Division of Cancer Medicine, Graduate School of Medicine Science, Kanazawa University, 13-1 Takaramachi, Kanazawa, 920-8641, Japan
| | - H Takamura
- Department of Gastroenterologic Surgery Division of Cancer Medicine, Graduate School of Medicine Science, Kanazawa University, 13-1 Takaramachi, Kanazawa, 920-8641, Japan
| | - I Ninomiya
- Department of Gastroenterologic Surgery Division of Cancer Medicine, Graduate School of Medicine Science, Kanazawa University, 13-1 Takaramachi, Kanazawa, 920-8641, Japan
| | - T Ohta
- Department of Gastroenterologic Surgery Division of Cancer Medicine, Graduate School of Medicine Science, Kanazawa University, 13-1 Takaramachi, Kanazawa, 920-8641, Japan
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Marrelli D, Polom K, de Manzoni G, Morgagni P, Baiocchi GL, Roviello F. Multimodal treatment of gastric cancer in the west: Where are we going? World J Gastroenterol 2015; 21:7954-7969. [PMID: 26185368 PMCID: PMC4499339 DOI: 10.3748/wjg.v21.i26.7954] [Citation(s) in RCA: 58] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2015] [Revised: 03/25/2015] [Accepted: 05/02/2015] [Indexed: 02/06/2023] Open
Abstract
The incidence of gastric cancer (GC) is decreasing worldwide, especially for intestinal histotype of the distal third of the stomach. On the contrary, proximal location and diffuse Lauren histotype have been reported to be generally stable over time. In the west, no clear improvement in long-term results was observed in clinical and population-based studies. Results of treatment in these neoplasms are strictly dependent on tumor stage. Adequate surgery and extended lymphadenectomy are associated with good long-term outcome in early-stage cancer; however, results are still unsatisfactory for advanced stages (III and IV), for which additional treatments could provide a survival benefit. This implies a tailored approach to GC. The aim of this review was to summarize the main multimodal treatment options in advanced resectable GC. Perioperative or postoperative treatments, including chemotherapy, chemoradiotherapy, targeted therapies, and hyperthermic intraperitoneal chemotherapy have been reviewed, and the main ongoing and completed trials have been analyzed. An original tailored multimodal approach to non-cardia GC has been also proposed.
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Loss of HER2 Positivity after Trastuzumab in HER2-Positive Gastric Cancer: Is Change in HER2 Status Significantly Frequent? Case Rep Gastrointest Med 2015; 2015:132030. [PMID: 25893119 PMCID: PMC4393931 DOI: 10.1155/2015/132030] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/22/2014] [Accepted: 03/10/2015] [Indexed: 01/01/2023] Open
Abstract
Trastuzumab has recently been introduced as a treatment for HER2-positive metastatic and/or unresectable gastric cancer (MUGC); however, compared with breast cancer, some issues concerning HER2 and trastuzumab therapy for gastric cancer remain unclear. A 74-year-old woman received trastuzumab-containing chemotherapy for HER2-positive MUGC. She had a marked response to 8 months of chemotherapy, and gastrectomy and hepatic metastasectomy with curative intent were performed. The resected specimen showed complete loss of HER2 positivity in the residual tumor. For MUGC, a change in HER2 status during the course of the disease with or without chemotherapy has rarely been reported. However, in breast cancer, a significant frequency of change in HER2 status during the course of disease has been reported, and reevaluation of HER2 positivity in metastatic/recurrent sites is recommended. The choice of trastuzumab for MUGC is currently based on the HER2 status of the primary tumor at the time of initial diagnosis, without reassessment of HER2 status during the course of disease and/or in metastatic/recurrent sites, on the assumption that HER2 status is stable. However, our case casts doubt on the stability of HER2 in gastric cancer.
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Abstract
Adenocarcinoma of the stomach is often diagnosed in the late stages of the disease. Surgical resection of all gross and microscopic disease is essential for curative treatment. Complete resection is often not achievable when patients present with advanced stage IV cancer. In the absence of symptoms, chemotherapy without resection has been the standard of care in most major centers. With improvements in response to chemotherapy and less invasive surgical approaches, patients with metastatic gastric cancer have had better survival outcomes than in the past. The challenge today when treating these patients is in defining who will benefit from more aggressive interventions. Reviewing the literature for guidance is difficult because the goals of treatment are often not clearly defined. Finding the proper balance of aggressiveness needed to extend survival while preserving and maximizing quality of life is a decision that clinicians have to make with increasing frequency. This review will attempt to provide a framework to aid in determining what role, if any, gastrectomy has in the management of patients with stage IV gastric cancer.
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Affiliation(s)
- Martin S Karpeh
- Department of Surgery, Beth Israel Medical Center, Continuum Cancer Centers of New York, New York, N.Y., USA.
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Takemura N, Saiura A, Koga R, Arita J, Yoshioka R, Ono Y, Hiki N, Sano T, Yamamoto J, Kokudo N, Yamaguchi T. Long-term outcomes after surgical resection for gastric cancer liver metastasis: an analysis of 64 macroscopically complete resections. Langenbecks Arch Surg 2012; 397:951-957. [PMID: 22615045 DOI: 10.1007/s00423-012-0959-z] [Citation(s) in RCA: 99] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2012] [Accepted: 05/07/2012] [Indexed: 02/06/2023]
Abstract
PURPOSE The indication for hepatectomy in cases of gastric cancer liver metastases (GLM) remains unclear and it remains controversial whether surgical resection is beneficial for GLM. The objective of this retrospective study was to clarify the indications for and benefit of hepatectomy for GLM. METHODS Seventy-three patients underwent hepatectomies for GLM from January 1993 to January 2011. Macroscopically complete (R0 or R1) resection was achieved in 64 patients. Among them, 32 patients underwent synchronous hepatectomy with gastrectomy and the remaining 32 patients underwent metachronous hepatectomy. Repeat hepatectomy was done in 14 patients for resectable intrahepatic recurrences. Clinicopathological factors were evaluated by univariate and multivariate analyses among patients who received macroscopically complete resection for those affecting survival. RESULTS The overall 1-, 3-, and 5-year survival rates after macroscopically complete (R0 or R1) liver resection (n = 64) for GLM were 84, 50, and 37 %, respectively, with a median survival of 34 months. Univariate analysis identified serosal invasion of the primary gastric cancer and blood transfusions during surgery as poor prognosis indicators. By multivariate analysis, serosal invasion of the primary gastric cancer and larger hepatic tumor (>5 cm in diameter) were found to be independent indicators of poor prognosis. CONCLUSIONS GLM patients with the maximum diameter of hepatic tumors of <5 cm and without serosal invasion of the primary gastric cancer are the best candidate for hepatectomy.
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Affiliation(s)
- Nobuyuki Takemura
- Department of Gastroenterological Surgery, Cancer Institute Ariake Hospital, Japanese Foundation for Cancer Research, 3-10-6 Ariake, Koto-ku, Tokyo, Japan
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