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Bausys A, Ümarik T, Dobrzhanskyi O, Luksta M, Kondratskyi Y, Reinsoo A, Vassiljev M, Bausys B, Bickaite K, Rauduvyte K, Luksaite-Lukste R, Bausys R, Strupas K. Neoadjuvant Chemotherapy Followed by Gastrectomy for Cytology-Positive Gastric Cancer without Any Other Non-Curative Factors in a Western Setting: An International Eastern European Cohort Study. Cancers (Basel) 2023; 15:5794. [PMID: 38136339 PMCID: PMC10741658 DOI: 10.3390/cancers15245794] [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: 10/18/2023] [Revised: 12/01/2023] [Accepted: 12/07/2023] [Indexed: 12/24/2023] Open
Abstract
The optimal approach for treating cytology-positive (Cy1) gastric cancer (GC) patients without additional non-curative factors remains uncertain. While neoadjuvant chemotherapy followed by gastrectomy shows promise, its suitability for Western patients is not well supported by existing data. To address this knowledge gap, a cohort study was conducted across four major GC treatment centers in Lithuania, Estonia, and Ukraine. Forty-three consecutive Cy1 GC patients who underwent neoadjuvant chemotherapy between 2016 and 2020 were enrolled. The study evaluated overall survival (OS), progression-free survival (PFS), cytology status conversion, and major pathological response rates, along with the factors influencing these outcomes. All patients underwent surgery post-neoadjuvant chemotherapy, with 53.5% experiencing cytological status conversion and 23.3% achieving a major pathological response. The median OS and PFS were 20 (95% CI: 16-25) and 19 (95% CI: 11-20) months, respectively. Conversion to negative cytology significantly reduced the relative risk of peritoneal progression (RR: 0.11; 95% CI: 0.03-0.47, p = 0.002). The study suggests that neoadjuvant chemotherapy followed by gastrectomy holds promise as a treatment option for Cy1 GC without additional non-curative factors, associating cytology status conversion with improved long-term outcomes and reduced peritoneal relapse risk.
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Affiliation(s)
- Augustinas Bausys
- Clinic of Gastroenterology, Nephrourology, and Surgery, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, 03101 Vilnius, Lithuania
- Centre for Visceral Medicine and Translational Research, Faculty of Medicine, Institute of Clinical Medicine, Vilnius University, 03101 Vilnius, Lithuania
| | - Toomas Ümarik
- Upper Gastrointestinal Tract Surgery Department, North Estonia Medical Centre, 13419 Tallinn, Estonia; (T.Ü.)
| | - Oleksii Dobrzhanskyi
- Upper Gastrointestinal Tumors Department, National Cancer Institute, 03022 Kyiv, Ukraine; (O.D.)
| | - Martynas Luksta
- Clinic of Gastroenterology, Nephrourology, and Surgery, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, 03101 Vilnius, Lithuania
| | - Yourii Kondratskyi
- Upper Gastrointestinal Tumors Department, National Cancer Institute, 03022 Kyiv, Ukraine; (O.D.)
| | - Arvo Reinsoo
- Upper Gastrointestinal Tract Surgery Department, North Estonia Medical Centre, 13419 Tallinn, Estonia; (T.Ü.)
| | - Mihhail Vassiljev
- Pathology Department, North Estonia Medical Centre, 13419 Tallinn, Estonia
| | - Bernardas Bausys
- Clinic of Gastroenterology, Nephrourology, and Surgery, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, 03101 Vilnius, Lithuania
| | - Klaudija Bickaite
- Clinic of Gastroenterology, Nephrourology, and Surgery, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, 03101 Vilnius, Lithuania
| | - Kornelija Rauduvyte
- Centre for Visceral Medicine and Translational Research, Faculty of Medicine, Institute of Clinical Medicine, Vilnius University, 03101 Vilnius, Lithuania
| | - Raminta Luksaite-Lukste
- Clinic of Gastroenterology, Nephrourology, and Surgery, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, 03101 Vilnius, Lithuania
- Centre for Visceral Medicine and Translational Research, Faculty of Medicine, Institute of Clinical Medicine, Vilnius University, 03101 Vilnius, Lithuania
| | - Rimantas Bausys
- Clinic of Gastroenterology, Nephrourology, and Surgery, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, 03101 Vilnius, Lithuania
- Department of Abdominal Surgery and Oncology, National Cancer Institute, 08406 Vilnius, Lithuania
| | - Kestutis Strupas
- Clinic of Gastroenterology, Nephrourology, and Surgery, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, 03101 Vilnius, Lithuania
- Centre for Visceral Medicine and Translational Research, Faculty of Medicine, Institute of Clinical Medicine, Vilnius University, 03101 Vilnius, Lithuania
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Lu S, Chen YG, Liu XW, Yang ZY, Shi M, Yuan H, Liu WT, Ni ZT, Yao XX, Hua ZC, Feng RH, He CY, Zheng YN, Wang ZQ, Sah BK, Chen MM, Zhu ZL, Li C, Zhang J, Yan M, Xia JZ, Zhu ZG, Yan C. A phase II study of perioperative treatment in gastric cancer with No.16a2/b1 lymph node metastasis: DRAGON-06 trial. Future Oncol 2022; 18:4239-4349. [PMID: 36651765 DOI: 10.2217/fon-2022-0718] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2022] [Accepted: 12/07/2022] [Indexed: 01/19/2023] Open
Abstract
Although gastric cancer with para-aortic lymph node (PAN) metastasis is commonly regarded as unresectable, surgeons have explored the optimal treatment for patients with PAN metastases limited to No.16a2/b1 in the past few decades. Preoperative systemic therapy combined with D2 gastrectomy plus PAN dissection may improve the prognosis of these patients. In this multicenter phase II trial, 29 gastric cancer patients with PAN metastasis limited to No.16a2/b1 will receive preoperative treatment with nab-paclitaxel, oxaliplatin, S-1 (nab-POS: nab-paclitaxel, oxaliplatin, S-1) and sintilimab followed by D2 gastrectomy plus PAN dissection; and postoperative treatment with oral S-1, intravenous sintilimab and intraperitoneal paclitaxel. The end points for the study are 3-year overall survival, 3-year disease-free survival, pathological response rate, incidence of postoperative complications and adverse events.
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Affiliation(s)
- Sheng Lu
- Department of General Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
| | - Yi-Gang Chen
- Department of General Surgery, Wuxi Second People's Hospital, Jiangsu Province, 214001,China
| | - Xiao-Wen Liu
- Department of Gastric Surgery, Fudan University ShanghaiCancer Center, Shanghai, 200032, China
| | - Zhong-Yin Yang
- Department of General Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
| | - Min Shi
- Department of Oncology, Ruijin Hospital,Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
| | - Hong Yuan
- Department of Oncology, Ruijin Hospital,Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
| | - Wen-Tao Liu
- Department of General Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
| | - Zhen-Tian Ni
- Department of General Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
| | - Xue-Xin Yao
- Department of General Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
| | - Zi-Chen Hua
- Department of General Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
| | - Run-Hua Feng
- Department of General Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
| | - Chang-Yu He
- Department of General Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
| | - Ya-Nan Zheng
- Department of General Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
| | - Zhen-Qiang Wang
- Department of General Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
| | - Birendra Kumar Sah
- Department of General Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
| | - Ming-Min Chen
- Department of General Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
| | - Zheng-Lun Zhu
- Department of General Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
| | - Chen Li
- Department of General Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
| | - Jun Zhang
- Department of Oncology, Ruijin Hospital,Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
| | - Min Yan
- Department of General Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
| | - Jia-Zeng Xia
- Department of General Surgery, Wuxi Second People's Hospital, Jiangsu Province, 214001,China
| | - Zheng-Gang Zhu
- Department of General Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
| | - Chao Yan
- Department of General Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
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Shinkai M, Imano M. The clinical effect of conversion surgery for advanced gastric cancer patients with peritoneal metastasis. J Gastrointest Oncol 2022; 13:2169-2177. [PMID: 36388679 PMCID: PMC9660049 DOI: 10.21037/jgo-21-431] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/19/2021] [Accepted: 04/15/2022] [Indexed: 12/02/2022] Open
Abstract
BACKGROUND The prognosis of gastric cancer (GC) patients with peritoneal metastasis (PM) is extremely poor. We developed a new promising regimen combining intraperitoneal (i.p.) paclitaxel (PTX) with systemic PTX and S-1 chemotherapy for GC patients with PM. However, the value of conversion surgery (CS) for GC patients with PM remains unclear. This study aimed to clarify the clinical effect of CS from our updated previous report. METHODS We retrospectively analyzed 50 GC patients, divided into chemotherapy alone (CTx; n=15) and conversion surgery intervention (CSI; n=35) groups. In the CTx group, chemotherapy was continued in responders, while in the CSI group, surgery was performed in chemotherapy-responders. The primary endpoint was overall survival (OS) of the two groups. The secondary endpoint was the safety of CS. RESULTS In the CTx group, 9 of 15 patients (60%) responded to chemotherapy. In the CSI group, PM disappeared in 22 of 35 patients (62.9%), all of whom underwent CS. Post-operative complications occurred in 2 patients (9%) who underwent CS. There were no treatment-related deaths. Regarding OS, there was no significant difference between the two groups [P=0.14; 95% confidence interval (CI), 0.3016-1.197], nor between chemotherapy-responders in the two groups (P=0.059; 95% CI, 0.1473-1.039). However, four patients in the CSI group have survived more than 5 years after CS. CONCLUSIONS CS may be a promising treatment strategy for some GC patients with PM who have responded to chemotherapy.
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Affiliation(s)
- Masayuki Shinkai
- Department of Surgery, Faculty of Medicine, Kindai University, Osaka, Japan
| | - Motohiro Imano
- Department of Surgery, Faculty of Medicine, Kindai University, Osaka, Japan
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Prabhu A, Mishra D, Brandl A, Yonemura Y. Gastric Cancer With Peritoneal Metastasis-A Comprehensive Review of Current Intraperitoneal Treatment Modalities. Front Oncol 2022; 12:864647. [PMID: 35719946 PMCID: PMC9204320 DOI: 10.3389/fonc.2022.864647] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2022] [Accepted: 04/22/2022] [Indexed: 12/24/2022] Open
Abstract
The treatment of patients with peritoneal metastasis from gastric cancer continues to evolve. With various forms of intraperitoneal drug delivery available, it is now possible to reach the sites of peritoneal metastases, which were otherwise sub-optimally covered by systemic chemotherapy, owing to the blood peritoneal barrier. We conducted a narrative review based on an extensive literature research, highlighting the current available intraperitoneal treatment options, which resulted in improved survival in well-selected patients of peritoneally metastasized gastric cancer. Intraperitoneal chemotherapy showed promising results in four different treatment modalities: prophylactic, neoadjuvant, adjuvant, and palliative. It is now possible to choose the type of intraperitoneal treatment/s in combination with systemic treatment/s, depending on patients' general condition and peritoneal disease burden, thus providing individualized treatment to these patients. Randomized controlled trials for the different treatment modalities were mainly conducted in Asia and lack further validation in the other parts of the world. Most recent application tools, such as pressurized intraperitoneal aerosol chemotherapy, seem promising and need to pass the ongoing clinical trials.
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Affiliation(s)
- Aruna Prabhu
- Department of Surgical Oncology, Thangam Cancer Center, Namakkal, India
| | - Deepti Mishra
- Department of Surgical Oncology, Thangam Cancer Center, Namakkal, India
| | - Andreas Brandl
- Digestive Unit, Champalimaud Foundation, Lisbon, Portugal
- Department of Surgery, Campus Virchow-Klinikum, Charité-Universitätsmedizin Berlin, Berlin, Germany
| | - Yutaka Yonemura
- Department of Regional Cancer therapy, Peritoneal Surface Malignancy Centee, Kishiwada Tokushukai Hospital, Kishiwada, Japan
- Japanese/Asian School of Peritoneal Surface Oncology, Osaka, Japan
- Department of Regional Cancer therapy, Peritoneal Surface Malignancy Center, Kusatsu General Hospital, Shiga, Japan
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5
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Bausys A, Gricius Z, Aniukstyte L, Luksta M, Bickaite K, Bausys R, Strupas K. Current treatment strategies for patients with only peritoneal cytology positive stage IV gastric cancer. World J Clin Cases 2021; 9:9711-9721. [PMID: 34877310 PMCID: PMC8610919 DOI: 10.12998/wjcc.v9.i32.9711] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2021] [Revised: 07/28/2021] [Accepted: 09/16/2021] [Indexed: 02/06/2023] Open
Abstract
Gastric cancer (GC) is one of the most common malignancies worldwide and surgery remains the only potentially curative treatment option for it. Although a significant proportion of GC patients are found with distant metastases already at the initial diagnosis. Peritoneal dissemination is the most common site of metastases. Positive peritoneal cytology (Cy1) is associated with poor long-term outcomes; thus, these patients are considered as stage IV even if macroscopic carcinomatosis is absent. Currently, there is no clear evidence for the most optimal treatment for this distinct subpopulation of the stage IV cohort. Available strategies vary from palliative chemotherapy to upfront gastrectomy. This comprehensive review summarized current evidence of different treatment strategies for Cy1 GC including roles of surgery, systemic and intraperitoneal chemotherapy.
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Affiliation(s)
- Augustinas Bausys
- Department of Abdominal Surgery and Oncology, National Cancer Institute, Vilnius 08406, Lithuania
- Clinic of Gastroenterology, Nephrourology and Surgery, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, Vilnius 03101, Lithuania
| | - Zilvinas Gricius
- Faculty of Medicine, Vilnius University, Vilnius 08406, Lithuania
| | - Laura Aniukstyte
- Faculty of Medicine, Vilnius University, Vilnius 08406, Lithuania
| | - Martynas Luksta
- Clinic of Gastroenterology, Nephrourology and Surgery, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, Vilnius 03101, Lithuania
| | | | - Rimantas Bausys
- Department of Abdominal Surgery and Oncology, National Cancer Institute, Vilnius 08406, Lithuania
| | - Kestutis Strupas
- Clinic of Gastroenterology, Nephrourology and Surgery, Institute of Clinical Medicine, Vilnius University, Vilnius 03101, Lithuania
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Parray A, Gupta V, Chaudhari VA, Shrikhande SV, Bhandare MS. Role of intraperitoneal chemotherapy in gastric cancer. SURGERY IN PRACTICE AND SCIENCE 2021. [DOI: 10.1016/j.sipas.2020.100025] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
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Yonemura Y, Iahibashi H, Sako S, Mizumoto A, Takao N, Ichinose M, Motoi S, Liu Y, Wakama S, Kamada Y, Nishihara K. Advances with pharmacotherapy for peritoneal metastasis. Expert Opin Pharmacother 2020; 21:2057-2066. [PMID: 32783786 DOI: 10.1080/14656566.2020.1793957] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
INTRODUCTION A new treatment strategy involving cytoreductive surgery (CRS) combined with perioperative intraperitoneal (IP) chemotherapy was proposed in 1999 by the Peritoneal Surface Oncology Group International, and the strategy is now justified as a state-of-the-art treatment to improve the long-term survival of patients with peritoneal metastasis (PM). To achieve cure in the patients with PM, complete removal of macroscopic tumors and eradication of micrometastasis on the peritoneum, left after CRS are essential. Systemic chemotherapy is not indicated for the treatment of PM. In contrast, intraperitoneal (IP) chemotherapy brings about significantly higher locoregional dose intensity in the peritoneal cavity and subperitoneal tissues. In combination with anticancer drugs, hyperthermia enhances cytotoxicity against cancer cells. AREA COVERED This article provides a systematic overview of PM from various cancers including gastric, colorectal, small bowel, appendiceal cancer, and mesothelioma. It also includes all the essential aspects of therapy. EXPERT OPINION CRS plus perioperative intraperitoneal chemotherapy is safe with acceptable morbidity and mortality. It is justified as a standard treatment to improve the long-term survival of patients with PM and is now performed with curative intent for PM from various malignancies.
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Affiliation(s)
- Yutaka Yonemura
- Department of Regional Cancer Therapies, Peritoneal Surface Malignancy Treatment Center, Kishiwada Tokushukai Hospital , Kishiwada City, Oosaka-Fu, Japan.,Department of Peritoneal Surface Malignancy Treatment, Kusatsu General Hospital , Kusatsu City, Shiga, Japan
| | - Haruaki Iahibashi
- Department of Regional Cancer Therapies, Peritoneal Surface Malignancy Treatment Center, Kishiwada Tokushukai Hospital , Kishiwada City, Oosaka-Fu, Japan
| | - Shouzou Sako
- Department of Regional Cancer Therapies, Peritoneal Surface Malignancy Treatment Center, Kishiwada Tokushukai Hospital , Kishiwada City, Oosaka-Fu, Japan
| | - Akiyoshi Mizumoto
- Department of Peritoneal Surface Malignancy Treatment, Kusatsu General Hospital , Kusatsu City, Shiga, Japan
| | - Nobuyuki Takao
- Department of Peritoneal Surface Malignancy Treatment, Kusatsu General Hospital , Kusatsu City, Shiga, Japan
| | - Masumi Ichinose
- Department of Peritoneal Surface Malignancy Treatment, Kusatsu General Hospital , Kusatsu City, Shiga, Japan
| | - Shunsuke Motoi
- Department of Peritoneal Surface Malignancy Treatment, Kusatsu General Hospital , Kusatsu City, Shiga, Japan
| | - Yang Liu
- Department of Regional Cancer Therapies, Peritoneal Surface Malignancy Treatment Center, Kishiwada Tokushukai Hospital , Kishiwada City, Oosaka-Fu, Japan
| | - Satoshi Wakama
- Department of Regional Cancer Therapies, Peritoneal Surface Malignancy Treatment Center, Kishiwada Tokushukai Hospital , Kishiwada City, Oosaka-Fu, Japan
| | - Yasuyuki Kamada
- Department of Regional Cancer Therapies, Peritoneal Surface Malignancy Treatment Center, Kishiwada Tokushukai Hospital , Kishiwada City, Oosaka-Fu, Japan
| | - Kazurou Nishihara
- Department of Regional Cancer Therapies, Peritoneal Surface Malignancy Treatment Center, Kishiwada Tokushukai Hospital , Kishiwada City, Oosaka-Fu, Japan
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Lo Dico R, Gornet JM, Guglielmo N, Zaanan A, Taieb J, Pocard M. Bidirectional chemotherapy combining intraperitoneal docetaxel with intravenous 5-fluorouracil and oxaliplatin for patients with unresectable peritoneal metastasis from gastric cancer: the first study in Western countries. Pleura Peritoneum 2020; 5:20190035. [PMID: 32566725 PMCID: PMC7292234 DOI: 10.1515/pp-2019-0035] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2019] [Accepted: 03/03/2020] [Indexed: 12/18/2022] Open
Abstract
Background A new treatment using bidirectional intraperitoneal (IP) and intravenous (IV) chemotherapy developed by Asiatic surgeons improves outcomes in patients with synchronous peritoneal metastasis (PM) from gastric cancer (GC). Methods We enrolled six consecutive patients with unresectable PM from GC who underwent bidirectional chemotherapy using IP docetaxel and IV FOLFOX or LV5FU2. In one course, IP docetaxel 30 mg/m2 was administrated on days 1, 8 and 15, and IV FOLFOX or LV5FU2 was administered on days 1 and 15, followed by 7 days of rest. Before and after a complete bidirectional cycle of three courses, the peritoneal cancer index (PCI) was evaluated by laparoscopy. The primary endpoint was to evaluate the feasibility and safety of bidirectional chemotherapy. Secondary endpoints were overall survival (OS), and the success of the therapeutic strategy was reflected by a decrease of 25% of the initial PCI. Results All patients completed one bidirectional cycle. The regimen was well tolerated. The median OS was 13 months [range 5–18], and the 1-year OS rate was 67%. After the first bidirectional cycle, the PCI decrease ≥25% of the initial value in four patients. A major histological response was observed in four patients. Conclusions This is the first Western study and confirms the feasibility and safety of bidirectional treatment using IP and IV chemotherapy for patients with unresectable PM from GC, resulting in a 13-month median OS with limited morbidity. The decrease in PCI after one bidirectional cycle is promising.
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Affiliation(s)
- Rea Lo Dico
- University of Paris, UMR 1275 CAP Paris-Tech, Department of Digestive Surgery, Lariboisière Hospital, AP-HP, F-75010Paris, France
| | - Jean Marc Gornet
- Department of Hepatology, Gastroenterology and Digestive Oncology, Saint-Louis Hospital, AP-HP, Paris, France
| | - Nicola Guglielmo
- Department of Digestive Surgery, Lariboisiere Hospital, AP-HP, Paris, France
| | - Aziz Zaanan
- Department of Hepatology, Gastroenterology and Digestive Oncology, Georges Pompiodou European Hospital, AP-HP, Paris, University of Paris, France
| | - Julien Taieb
- Department of Hepatology, Gastroenterology and Digestive Oncology, Georges Pompiodou European Hospital, AP-HP, Paris, University of Paris, France
| | - Marc Pocard
- University of Paris, UMR 1275 CAP Paris-Tech, Department of Digestive Surgery, Lariboisière Hospital, AP-HP, F-75010Paris, France
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Shinkai M, Imano M, Chiba Y, Iwama M, Shiraisi O, Yasuda A, Tsubaki M, Nishida S, Kimura Y, Yasuda T. Phase II trial of neoadjuvant chemotherapy with intraperitoneal paclitaxel, S-1, and intravenous cisplatin and paclitaxel for stage IIIA or IIIB gastric cancer. J Surg Oncol 2018; 119:56-63. [PMID: 30444009 DOI: 10.1002/jso.25295] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2018] [Accepted: 10/23/2018] [Indexed: 12/25/2022]
Abstract
BACKGROUND We carried out a phase II trial to evaluate the feasibility and efficacy of neoadjuvant chemotherapy comprising a single intraperitoneal administration of paclitaxel, followed by intravenous administrations of paclitaxel and cisplatin with S-1 for clinical stage III gastric cancer. METHODS Patients with potentially resectable gastric cancer were eligible. A laparoscopic survey was performed to confirm CY0 and P0. Intraperitoneal paclitaxel (60 mg/m 2 ) was administered, followed by systemic chemotherapy. Surgery was performed after two cycles of chemotherapy. The primary endpoint was the response rate of chemotherapy. Secondary endpoints were adverse events, pathological response rate, and overall survival rate. RESULTS Twenty patients were enrolled. Planned cycles were completed in all patients. Grade 3/4 leukopenia and grade 3/4 neutropenia were observed in four (20%) and seven (35%) patients, respectively. The overall response rate was 70% (partial response: 14, stable disease: 5, progressive disease: 1). All patients underwent R0 gastrectomy with D2 lymph-node dissection, with no surgery-related deaths. The pathological response rate was 65% (13 of 20). The 3- and 5-year overall survival rates were 90.0% and 77.1%, respectively. CONCLUSIONS Neoadjuvant chemotherapy including intraperitoneal paclitaxel followed by sequential intravenous paclitaxel and cisplatin with S-1 for resectable advanced gastric cancer is feasible and effective.
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Affiliation(s)
- Masayuki Shinkai
- Department of Surgery, Faculty of Medicine, Kindai University, Osakasayama, Japan
| | - Motohiro Imano
- Department of Surgery, Faculty of Medicine, Kindai University, Osakasayama, Japan
| | - Yasutaka Chiba
- Clinical Research Center, Kindai University Hospital, Osakasayama, Japan
| | - Mitsuru Iwama
- Department of Surgery, Faculty of Medicine, Kindai University, Osakasayama, Japan
| | - Osamu Shiraisi
- Department of Surgery, Faculty of Medicine, Kindai University, Osakasayama, Japan
| | - Atsushi Yasuda
- Department of Surgery, Faculty of Medicine, Kindai University, Osakasayama, Japan
| | - Masanobu Tsubaki
- Division of Pharmacotherapy, Faculty of Pharmacy, Kindai University, Higashiosaka, Japan
| | - Shozo Nishida
- Division of Pharmacotherapy, Faculty of Pharmacy, Kindai University, Higashiosaka, Japan
| | - Yutaka Kimura
- Department of Surgery, Faculty of Medicine, Kindai University, Osakasayama, Japan
| | - Takushi Yasuda
- Department of Surgery, Faculty of Medicine, Kindai University, Osakasayama, Japan
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10
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Ilhan E, Alemdar A, Ureyen O, Bas K. The Importance of Extensive Intraoperative Peritoneal Lavage as a Promising Method in Patients with Gastric Cancer Showing Positive Peritoneal Cytology Without Overt Peritoneal Metastasis and Other Therapeutic Approaches. J INVEST SURG 2017; 30:318-324. [PMID: 27806214 DOI: 10.1080/08941939.2016.1247930] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Peritoneal invasion is more common and has a worse prognosis in gastric cancer than most of other intestinal cancers. Advanced gastric cancers have a poor course in terms of the development of peritoneal carcinomatosis and prognosis, even if the curative resection has been performed. Patients usually die within the first 2 years of the postoperative period mainly due to peritoneal metastasis. It is, therefore, essential to eradicate intraperitoneal free cancer cells to prevent peritoneal recurrences. A standard therapy has not been developed yet for patients with gastric cancer with a positive peritoneal cytology or a gross peritoneal metastasis. Curative resection following neoadjuvant chemotherapy, postoperative oral S-1 chemotherapy, intraoperative intraperitoneal chemotherapy (IPC), and extensive intraoperative peritoneal lavage (EIPL)-IPC are recommended as therapeutic approaches. Although there is a limited number of studies on EIPL, which is a promising and exciting method in this patient population, unexpected results of survival have been demonstrated. We consider that the results of ongoing and further studies would lead to an extensive use of EIPL, which is a simple and easy method which can be applied anywhere and anytime, in patients with advanced gastic cancer and/or peritoneal cytology positive but peritoneal metastasis negative (CY+/P0) gastric cancer.
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Affiliation(s)
- Enver Ilhan
- a Izmir Bozyaka Training and Research Hospital, The Division of General Surgery-A , Karabaglar , 35170 Turkey
| | - Ali Alemdar
- b Okmeydani Training and Research Hospital, The Division of General Surgery , Okmeydani , 34384 Turkey
| | - Orhan Ureyen
- a Izmir Bozyaka Training and Research Hospital, The Division of General Surgery-A , Karabaglar , 35170 Turkey
| | - Koray Bas
- a Izmir Bozyaka Training and Research Hospital, The Division of General Surgery-A , Karabaglar , 35170 Turkey
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11
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Prognostic significance, diagnosis and treatment in patients with gastric cancer and positive peritoneal washings. A review of the literature. Rep Pract Oncol Radiother 2017; 22:434-440. [PMID: 28883764 DOI: 10.1016/j.rpor.2017.08.004] [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: 08/21/2016] [Revised: 03/17/2017] [Accepted: 08/03/2017] [Indexed: 12/17/2022] Open
Abstract
Peritoneal dissemination is a common consequence of a relapse following a radical surgical treatment of gastric cancer. The development of the disease in the peritoneum depends not only on its stage, but also on free cancer cells exfoliated from the tumor mass or from involved lymph nodes, and which are capable of being implanted in the peritoneum. According to the latest TNM (7 edition; 2010) classification, patients with free cancer cells in the peritoneal washings qualify for stage IV of the disease. Patients in whom free cancer cells were found during the operation - have a recurrence of gastric cancer - mainly in the peritoneum, and the majority of them die within two years of the diagnosis. To properly assess the prognosis, it is vital to determine the stage of cancer by additionally assessing the washings for the presence of free cancer cells before taking a therapeutic decision. This also allows identifying those patients who require different medical procedures to obtain the best treatment results possible. Medical literature describes various methods of examining peritoneal washings aimed at detecting free cancer cells. The methods apply different cancer cell detection rates, sensitivity and specificity in prediction of a peritoneal relapse. Oncological Departments performing the evaluation of the washings employ non-standard methods of treatment in this group of patients and the results presented are promising.
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12
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Kobayashi D, Kodera Y. Intraperitoneal chemotherapy for gastric cancer with peritoneal metastasis. Gastric Cancer 2017; 20:111-121. [PMID: 27803990 DOI: 10.1007/s10120-016-0662-9] [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: 08/30/2016] [Accepted: 10/15/2016] [Indexed: 02/07/2023]
Abstract
Peritoneal metastasis is the most frequent pattern of gastric cancer recurrence or metastasis and is a definitive determinant of prognosis. However, an effective means of treating peritoneal disease has not yet been established. Systemic chemotherapy has only a limited effect on peritoneal metastasis, although some progress has been shown in terms of median survival time, especially among patients with a minimal or moderate disease burden. Clinical research related to intraperitoneal administration of anticancer drugs is currently underway. An advantage of intraperitoneal chemotherapy is the ability to achieve high concentrations of anticancer drugs in the peritoneal cavity and the direct exposure of peritoneal deposits and free cancer cells to those drugs. In addition, pharmacokinetic studies with taxanes have shown that these high intraperitoneal drug concentrations are sustained for a considerable length of time, allowing prolonged exposure. As taxanes are the most appropriate drugs for intraperitoneal administration, the development of repeated intraperitoneal chemotherapy using taxanes for gastric cancer peritoneal metastasis-either alone or in combination with systemic chemotherapy-has taken place over the past decade, mostly in Japan. Several phase II trials and a phase III trial have recently demonstrated the efficacy of this therapy, including median survival times of 14.4-24.6 months and one-year overall survival rates of 67-91%. These results may lead to the approval of intraperitoneal taxanes, especially paclitaxel, for official insurance coverage in the near future.
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Affiliation(s)
- Daisuke Kobayashi
- Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan.
| | - Yasuhiro Kodera
- Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan
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13
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Conversion Surgery Post-Intraperitoneal Paclitaxel and Systemic Chemotherapy for Gastric Cancer Carcinomatosis Peritonei. Are We Ready? J Gastrointest Surg 2017; 21:425-433. [PMID: 27981493 DOI: 10.1007/s11605-016-3336-3] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/27/2016] [Accepted: 11/23/2016] [Indexed: 01/31/2023]
Abstract
Peritoneal metastasis is common in gastric cancer. It is difficult to treat and carries a poor prognosis. Intraperitoneal (IP) delivery of chemotherapy can attain a higher drug exposure in the peritoneal cavity but with reduced systemic toxicity. Therefore, we hypothesized that IP paclitaxel with systemic chemotherapy would be clinically beneficial for gastric cancer with peritoneal metastases. Patients with unresectable and/or recurrent gastric adenocarcinoma with peritoneal dissemination and/or positive peritoneal washing cytology were recruited. They underwent eight cycles of IP paclitaxel and systemic XELOX. The primary endpoint was 1-year overall survival rate and secondary endpoints were safety, response rate, and peritoneal cytological response. Patients who subsequently had no distant metastases and two consecutive negative peritoneal cytologies underwent conversion gastrectomy if there was no macroscopic evidence of peritoneal disease at diagnostic laparoscopy. Twenty-two patients were enrolled, receiving at least one cycle of IP paclitaxel at the time of reporting (data cutoff-March 11, 2016). The median number of cycles was 7.5. The median overall survival was 18.8 months, and the 1-year survival rate was 72.2%. One patient died of neutropenic sepsis. Of 19 evaluable patients with measurable disease, 7 (36.8%) achieved PR, 8 (42.1%) achieved SD, and 4 (21.1%) experienced PD. Peritoneal cytology turned negative in 11 of 17 (64.7%) patients. Six patients underwent conversion gastrectomy (4 R0, 2 R1) with a median survival of 21.6 months (range = 8.7-29.9 months). XELOX and IP paclitaxel appears to be an effective regimen in gastric cancer with peritoneal metastases. Conversion gastrectomy may be considered in patients with a favorable response.
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14
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Dong Y, Ma S, Yang S, Luo F, Wang Z, Guo F. Non-curative surgery for patients with gastric cancer with local peritoneal metastasis: A retrospective cohort study. Medicine (Baltimore) 2016; 95:e5607. [PMID: 27930586 PMCID: PMC5266058 DOI: 10.1097/md.0000000000005607] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Abstract
The role of non-curative surgery for patients with M1 gastric cancer (GC) is controversial. This study aimed to evaluate the efficacy of non-curative resectional surgery for patients with GC with local peritoneal metastasis.We reviewed the medical records of 47 patients with GC with local peritoneal metastasis, which was found by laparotomy or laparoscopy. The patients were divided into 2 groups: those who underwent gastric resection (n = 29), and a non-resection group who did not (n = 18). The clinical characteristics, postoperative complications, mortality, palliative intervention, and long-term outcomes of the 2 groups were compared.Complications occurred more frequently in the resection group than in non-resection group (P = 0.017). There was no postoperative mortality or reoperation in either group. Palliative intervention was performed in 9 (31%) patients in resection group and 16 (88.9%) patients in non-resection group (P < 0.001). The intervention interval and hospital-free time were significant longer in resection group than in non-resection group (P < 0.001, P < 0.001). The Kaplan-Meier survival curves revealed that resection group had longer survival than non-resection group (P < 0.001).Non-curative resectional surgery helps prolong survival time and improve the quality of life for patients with GC with local peritoneal metastasis.
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Affiliation(s)
| | - Shulan Ma
- Department of Gynecology, Huashan North Hospital
- Central Laboratory, Huashan North Hospital
| | - Shuo Yang
- Department of General Surgery, Huashan Hospital
| | - Fen Luo
- Department of General Surgery, Huashan Hospital
- Surgical Laboratory, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
| | - Zhiming Wang
- Department of General Surgery, Huashan Hospital
- Central Laboratory, Huashan North Hospital
- Surgical Laboratory, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
| | - Fenghua Guo
- Department of General Surgery, Huashan Hospital
- Surgical Laboratory, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
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15
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Ji ZH, Peng KW, Li Y. Intraperitoneal free cancer cells in gastric cancer: pathology of peritoneal carcinomatosis and rationale for intraperitoneal chemotherapy/hyperthermic intraperitoneal chemotherapy in gastric cancer. Transl Gastroenterol Hepatol 2016; 1:69. [PMID: 28138635 DOI: 10.21037/tgh.2016.08.03] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2016] [Accepted: 08/15/2016] [Indexed: 12/19/2022] Open
Abstract
Peritoneal carcinomatosis (PC) is one of the most common causes of death in gastric cancer patients. Intraperitoneal free cancer cells (IFCCs) play a very important role in forming PC, but the administration of intraperitoneal chemotherapy (IPC) and/or hyperthermic intraperitoneal chemotherapy (HIPEC) could be an effective treatment for IFCCs. This review focuses on the origin of IFCCs, the mechanism of PC formatting, the rationale of IPC/HIPEC, and the current clinical trials on IPC/HIPEC to treat advanced gastric cancer patients.
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Affiliation(s)
- Zhong-He Ji
- Department of Peritoneal Cancer Surgery, Cancer Center of Beijing Shijitan Hospital affiliated to the Capital Medical University, Beijing 100038, China
| | - Kai-Wen Peng
- Department of Peritoneal Cancer Surgery, Cancer Center of Beijing Shijitan Hospital affiliated to the Capital Medical University, Beijing 100038, China
| | - Yan Li
- Department of Peritoneal Cancer Surgery, Cancer Center of Beijing Shijitan Hospital affiliated to the Capital Medical University, Beijing 100038, China
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16
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Peng YF, Imano M, Itoh T, Satoh T, Chiba Y, Imamoto H, Tsubaki M, Nishida S, Yasuda T, Furukawa H. A phase II trial of perioperative chemotherapy involving a single intraperitoneal administration of paclitaxel followed by sequential S-1 plus intravenous paclitaxel for serosa-positive gastric cancer. J Surg Oncol 2015; 111:1041-6. [PMID: 26060133 DOI: 10.1002/jso.23928] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2015] [Accepted: 04/06/2015] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND OBJECTIVES We carried out a phase II trial to evaluate the feasibility, efficacy, and tolerability of perioperative chemotherapy including single intraperitoneal(IP) administration of paclitaxel(PTX) followed by intravenous(IV) administrations of PTX with S-1 in a neoadjuvant setting for serosa-positive gastric cancer. METHODS Patients with cT4a gastric cancer were enrolled. A laparoscopic survey was performed before study inclusion for the confirmation of serosal invasion, negative lavage cytology, and negative peritoneal metastasis. IP PTX (80 mg/m(2)) was administered, followed by systemic chemotherapy. Surgery was performed after the completion of chemotherapy. The primary endpoint was the treatment completion rate. RESULTS 37 patients were recruited. The treatment completion rate was 67.6% (25/37; 90% CI, 52.8-80.1%), which was significantly higher than 50%; we set this as a threshold value (P = 2.4% [one-sided]). 14 patients had target lesions; of these, 10 showed a partial response (71.4%), three had stable disease (21.4%), and one had progressive disease(7.2%). The response rate was 71.4% (10/14). All patients underwent gastrectomy with D2 lymph node dissection. The 3- and 5-year OS rates were 78.0 and 74.9%, respectively. CONCLUSIONS Perioperative chemotherapy including neoadjuvant IP PTX followed by sequential IV PTX with S-1 for serosa-positive gastric cancer is feasible, safe, and efficient.
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Affiliation(s)
- Ying-Feng Peng
- Department of Surgery, Kinki University, Faculty of Medicine, Osaka-sayama, Osaka, Japan
| | - Motohiro Imano
- Department of Surgery, Kinki University, Faculty of Medicine, Osaka-sayama, Osaka, Japan
| | - Tatsuki Itoh
- Department of Pathology, Kinki University, Faculty of Medicine, Osaka-sayama, Osaka, Japan
| | - Takao Satoh
- Department of Pathology, Kinki University, Faculty of Medicine, Osaka-sayama, Osaka, Japan
| | - Yasutaka Chiba
- Clinical Research Center, Kinki University Hospital, Osaka-sayama, Osaka, Japan
| | - Haruhiko Imamoto
- Department of Surgery, Kinki University, Faculty of Medicine, Osaka-sayama, Osaka, Japan
| | - Masahiro Tsubaki
- Division of Pharmacotherapy, Kinki University, Faculty of Pharmacy, Higashi-osaka, Osaka, Japan
| | - Shozo Nishida
- Division of Pharmacotherapy, Kinki University, Faculty of Pharmacy, Higashi-osaka, Osaka, Japan
| | - Takushi Yasuda
- Department of Surgery, Kinki University, Faculty of Medicine, Osaka-sayama, Osaka, Japan
| | - Hiroshi Furukawa
- Department of Surgery, Kinki University, Faculty of Medicine, Osaka-sayama, Osaka, Japan
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17
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Cabalag CS, Chan STF, Kaneko Y, Duong CP. A systematic review and meta-analysis of gastric cancer treatment in patients with positive peritoneal cytology. Gastric Cancer 2015; 18:11-22. [PMID: 24890254 DOI: 10.1007/s10120-014-0388-5] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/13/2013] [Accepted: 05/02/2014] [Indexed: 02/07/2023]
Abstract
Gastric cancer patients with positive peritoneal cytology as the only marker of metastatic disease have poor prognoses. There is no universal consensus on the most appropriate treatment regimen for this particular patient group. We reviewed and analyzed published data to determine the optimal treatment regimen for patients with peritoneal cytology-positive gastric adenocarcinomas. Six electronic databases were explored [PubMed, Cochrane (Systematic Reviews and Controlled Trials), PROSPERO, DARE, and EMBASE]. The primary outcome was overall survival with secondary outcomes including patterns of recurrence and treatment-related morbidity. Six studies were included for data extraction. There was no significant heterogeneity between studies. The use of S1 monotherapy was associated with a significant survival benefit (HR 0.48; 95% CI 0.32-0.70; p = 0.0002). Intraoperative intraperitoneal chemotherapy (IIPC) with adjuvant chemotherapy showed a trend toward improvement in overall survival (HR 0.70; 9 % CI 0.47-1.04; p = 0.08). A recent randomized controlled trial examining extensive intraperitoneal lavage (EIPL) with IIPC showed a significant improvement in overall survival (5-year overall survival, 43.8% for EIPL-IPC group compared with 4.6% for IPC group). However, these promising results need to be validated in larger prospective randomized trials.
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Affiliation(s)
- Carlos Suhady Cabalag
- Department of Surgical Oncology, Peter MacCallum Cancer Centre, 7 St. Andrews Place, East Melbourne, VIC, 3002, Australia,
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18
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Kwon OK, Chung HY, Yu W. Early postoperative intraperitoneal chemotherapy for macroscopically serosa-invading gastric cancer patients. Cancer Res Treat 2014; 46:270-9. [PMID: 25038762 PMCID: PMC4132443 DOI: 10.4143/crt.2014.46.3.270] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2013] [Accepted: 10/04/2013] [Indexed: 12/11/2022] Open
Abstract
PURPOSE Peritoneal recurrence is one of the most common patterns of recurrence after gastric cancer surgery and it has a poor prognosis despite all efforts. The aim of this study is to evaluate the prognostic impact of early postoperative intraperitoneal chemotherapy (EPIC) after surgery with curative intent for macroscopically serosa-invading gastric cancer patients. MATERIALS AND METHODS The records of 245 patients under the age of 70 were reviewed. These patients were suffering from macroscopically seroa-invading gastric cancer and they underwent curative surgery from 1995 to 2004 at the Kyungpook National University Hospital, Daegu, Korea. The overall survival, gastric cancer-specific survival, complications, and patterns of recurrence were compared between the patients who were treated with EPIC and those who were not. RESULTS EPIC was administered to 65 patients, and the remaining 180 patients did not receive this treatment. The 5-year overall and gastric cancer-specific survival rates for the EPIC group were 47.4% and 53.1%, respectively, and those for the non-EPIC group were 26.7% and 29.7%, respectively (p=0.012 for overall survival and p=0.011 for gastric cancer-specific survival). The rates of peritoneal recurrence for the EPIC group and the non-EPIC group were 18.5% and 32.2%, respectively (p=0.038). There were no significant differences in the morbidity or mortality between the two groups. Based on a multivariate analysis of the factors with prognostic significance in univariate analyses, EPIC, pathological lymph node metastasis, differentiation, and the extent of gastric resection were independent prognostic factors. CONCLUSION The use of EPIC to treat gastric cancer patients with macroscopic serosal invasions resulted in better survival rate by reducing the risk of peritoneal recurrence.
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Affiliation(s)
- Oh Kyoung Kwon
- Gastric Cancer Center, Kyungpook National University Medical Center, Daegu, Korea
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19
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Kitayama J, Ishigami H, Yamaguchi H, Emoto S, Watanabe T. Intraperitoneal Paclitaxel is useful as adjuvant chemotherapy for advanced gastric cancer with serosal exposure. Case Rep Oncol 2014; 7:58-64. [PMID: 24575018 PMCID: PMC3934609 DOI: 10.1159/000358379] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
BACKGROUND Intraperitoneal administration of paclitaxel (PTX) can elicit a marked clinical response in peritoneal metastases of gastric cancer. METHODS In this study, we retrospectively analyzed the clinical outcome of 17 patients who underwent R0 resection with D2 dissection for advanced gastric cancer with macroscopic serosal exposure and received intraperitoneal PTX as adjuvant therapy. RESULTS A pathological study revealed that the depth of invasion of the primary tumor was pT4a or pT4b in 10 cases, and that the pN stage was more than pN2 in 8 cases. Genetic analysis of peritoneal lavage fluid was performed in 14 cases, all of which were positive for carcinoembryonic antigen mRNA. In these patients, PTX was intraperitoneally administered at 20-60 mg/m(2) with oral S-1 for 3-36 months after surgery. In a median follow-up period of 66 months, recurrence occurred in the liver and peritoneum in 2 (11.7%) and 1 (5.9%) patients, respectively, and no nodal recurrence was observed. Five-year overall survival and disease-free survival were 88.2 and 82.3%, respectively. CONCLUSION Since these patients are considered to be a high-risk group for peritoneal recurrence, this result strongly suggests that adjuvant chemotherapy including intraperitoneal PTX is a promising protocol to improve the outcome of patients with advanced gastric cancer with serosal exposure.
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Affiliation(s)
- Joji Kitayama
- Department of Surgical Oncology, University of Tokyo, Tokyo, Japan
| | | | | | - Shigenobu Emoto
- Department of Surgical Oncology, University of Tokyo, Tokyo, Japan
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20
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Shimizu T, Murata S, Sonoda H, Mekata E, Ohta H, Takebayashi K, Miyake T, Tani T. Hyperthermic intraperitoneal chemotherapy with mitomycin C and 5-fluorouracil in patients at high risk of peritoneal metastasis from colorectal cancer: A preliminary clinical study. Mol Clin Oncol 2014; 2:399-404. [PMID: 24772307 DOI: 10.3892/mco.2014.244] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2013] [Accepted: 12/18/2013] [Indexed: 01/29/2023] Open
Abstract
Although hyperthermic intraperitoneal chemotherapy (HIPEC) has been extensively used to treat patients with peritoneal metastases (PM) from colorectal cancer (CRC), a standard protocol has not yet been established. The aim of this preliminary clinical study was to confirm in vitro the efficacy of mitomycin C combined with 5-fluorouracil (MMC-5FU) under hyperthermic conditions in CRC and investigate the pharmacokinetics and feasibility of HIPEC with MMC-5FU for patients at high risk of PM from CRC. To simulate HIPEC in vitro, we used the collagen gel droplet-embedded culture drug sensitivity test with the HCT166 colorectal cell line to assess the antitumor efficacy of MMC and 5FU as single-agent and combination treatments following incubation with HCT116 cells for 30 min at either 37 or 42°C. In addition, five patients at high risk of PM from CRC underwent surgical tumor resection followed by HIPEC with MMC-5FU. Our results demonstrated that the combined administration of MMC-5FU suppressed tumor cell proliferation more efficiently compared to either agent used alone. In addition, hyperthermia at 42°C significantly enhanced drug sensitivity. During the clinical application of HIPEC with MMC-5FU, no grade 4 hematological toxicities or surgical adverse events were recorded. In addition, there was no evidence of peritoneal recurrence during a median observational period of 38 months. Of note, two patients with positive intraoperative peritoneal cytology at the first surgery developed no peritoneal recurrence and exhibited negative peritoneal cytology at the second surgery. In conclusion, HIPEC using MMC-5FU was shown to be a feasible therapeutic option, with an acceptable toxicity profile, for patients at high risk of PM from CRC. Therefore, HIPEC with MMC-5FU may be a promising novel therapeutic option for such patients, which merits further verification of its safety and efficacy in large-scale clinical trials.
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Affiliation(s)
- Tomoharu Shimizu
- Department of Surgery, Shiga University of Medical Science, Otsu, Shiga 520-2192, Japan
| | - Satoshi Murata
- Department of Surgery, Shiga University of Medical Science, Otsu, Shiga 520-2192, Japan
| | - Hiromichi Sonoda
- Department of Surgery, Shiga University of Medical Science, Otsu, Shiga 520-2192, Japan
| | - Eiji Mekata
- Department of Surgery, Shiga University of Medical Science, Otsu, Shiga 520-2192, Japan
| | - Hiroyuki Ohta
- Department of Surgery, Shiga University of Medical Science, Otsu, Shiga 520-2192, Japan
| | - Katsushi Takebayashi
- Department of Surgery, Shiga University of Medical Science, Otsu, Shiga 520-2192, Japan
| | - Tohru Miyake
- Department of Surgery, Shiga University of Medical Science, Otsu, Shiga 520-2192, Japan
| | - Tohru Tani
- Department of Surgery, Shiga University of Medical Science, Otsu, Shiga 520-2192, Japan
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