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      Treatment outcome analysis of bevacizumab combined with cyclophosphamide and oxaliplatin in advanced pseudomyxoma peritonei

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          Abstract

          BACKGROUND

          Pseudomyxoma peritonei (PMP) is a rare peritoneal malignant tumor syndrome. Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy is its standard treatment. However, there are few studies and insufficient evidence regarding systemic chemotherapy of advanced PMP. Regimens for colorectal cancer are often used clinically, but there is no uniform standard for late-stage treatment.

          AIM

          To determine if bevacizumab combined with cyclophosphamide and oxaliplatin (Bev+CTX+OXA) is effective for treatment of advanced PMP. The primary study endpoint was progression-free survival (PFS).

          METHODS

          Retrospective analysis was conducted on the clinical data of patients with advanced PMP who received Bev+CTX+OXA regimen (bevacizumab 7.5 mg/kg ivgtt d1, oxaliplatin 130 mg/m 2 ivgtt d1 and cyclophosphamide 500 mg/m 2 ivgtt d1, q3w) in our center from December 2015 to December 2020. Objective response rate (ORR), disease control rate (DCR) and incidence of adverse events were evaluated. PFS was followed up. Kaplan-Meier method was used to draw survival curve, and log-rank test was used for comparison between groups. Multivariate Cox proportional hazards regression model was used to analyze the independent influencing factors of PFS.

          RESULTS

          A total of 32 patients were enrolled. After 2 cycles, the ORR and DCR were 3.1% and 93.7%, respectively. The median follow-up time was 7.5 mo. During the follow-up period, 14 patients (43.8%) had disease progression, and the median PFS was 8.9 mo. Stratified analysis showed that the PFS of patients with a preoperative increase in CA125 (8.9 vs 2.1, P = 0.022) and a completeness of cytoreduction score of 2-3 (8.9 vs 5.0, P = 0.043) was significantly longer than that of the control group. Multivariate analysis showed that a preoperative increase in CA125 was an independent prognostic factor for PFS (HR = 0.245, 95%CI: 0.066-0.904, P = 0.035).

          CONCLUSION

          Our retrospective assessment confirmed that the Bev+CTX+OXA regimen is effective in second- or posterior-line treatment of advanced PMP and that adverse reactions can be tolerated. A preoperative increase in CA125 is an independent prognostic factor of PFS.

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          Most cited references17

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          Appendiceal tumours and pseudomyxoma peritonei: Literature review with PSOGI/EURACAN Clinical Practice Guidelines for diagnosis and treatment

          Pseudomyxoma Peritonei (PMP) is a rare peritoneal malignancy, most commonly originating from a perforated epithelial tumour of the appendix. Given its rarity, randomized controlled trials on treatment strategies are lacking, nor likely to be performed in the foreseeable future. However, many questions regarding the management of appendiceal tumours, especially when accompanied by PMP, remain unanswered. This consensus statement was initiated by members of the Peritoneal Surface Oncology Group International (PSOGI) Executive Committee as part of a global advisory role in the management of uncommon peritoneal malignancies. The manuscript concerns an overview and analysis of the literature on mucinous appendiceal tumours with, or without, PMP. Recommendations are provided based on three Delphi voting rounds with GRADE-based questions amongst a panel of 80 worldwide PMP experts.
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            Pseudomyxoma peritonei: natural history and treatment.

            Pseudomyxoma peritonei (PMP) is an uncommon disease characterised by mucinous ascites, classically originating from a ruptured low grade mucinous neoplasm of the appendix. The natural history of PMP revolves around the "redistribution phenomenon", whereby mucinous tumour cells accumulate at specific sites with relative sparing of the motile small bowel and to a lesser extent other parts of the gastrointestinal tract. Peritoneal tumour accumulates due to gravity and at the sites of peritoneal fluid absorption, namely, the greater and lesser omentum and the under-surface of the diaphragm, particularly on the right. The optimal treatment is complete macroscopic tumour excision termed cytoreductive surgery (CRS) combined with Hyperthermic Intra-Peritoneal Chemotherapy (HIPEC). Total operating time for complete CRS and HIPEC for extensive PMP is around 10 h and generally involves bilateral parietal and diaphragmatic peritonectomies, right hemicolectomy, radical greater omentectomy with splenectomy, cholecystectomy and liver capsulectomy, a pelvic peritonectomy with, or without, rectosigmoid resection and bilateral salpingo-oophorectomy with hysterectomy in females. A unique feature of low grade PMP, which differs from other peritoneal malignancies, includes slow disease progression, which may be asymptomatic until advanced stages. Additionally, very extensive disease with a high "PCI" (Peritoneal Carcinomatosis Index) may still be amenable to complete excision and cure. In cases where complete tumour removal is not feasible, maximum tumour debulking can still result in long-term survival in PMP. PMP is challenging, complex but nevertheless the most rewarding peritoneal malignancy amenable to cure by CRS and HIPEC.
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              Chinese expert consensus on cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal malignancies.

              Locoregional spread of abdominopelvic malignant tumors frequently results in peritoneal carcinomatosis (PC). The prognosis of PC patients treated by conventional systemic chemotherapy is poor, with a median survival of < 6 mo. However, over the past three decades, an integrated treatment strategy of cytoreductive surgery (CRS) + hyperthermic intraperitoneal chemotherapy (HIPEC) has been developed by the pioneering oncologists, with proved efficacy and safety in selected patients. Supported by several lines of clinical evidence from phases I, II and III clinical trials, CRS + HIPEC has been regarded as the standard treatment for selected patients with PC in many established cancer centers worldwide. In China, an expert consensus on CRS + HIPEC has been reached by the leading surgical and medical oncologists, under the framework of the China Anti-Cancer Association. This expert consensus has summarized the progress in PC clinical studies and systematically evaluated the CRS + HIPEC procedures in China as well as across the world, so as to lay the foundation for formulating PC treatment guidelines specific to the national conditions of China.
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                Author and article information

                Contributors
                Journal
                World J Gastrointest Surg
                WJGS
                World Journal of Gastrointestinal Surgery
                Baishideng Publishing Group Inc
                1948-9366
                27 June 2023
                27 June 2023
                : 15
                : 6
                : 1149-1158
                Affiliations
                Department of Peritoneal Cancer Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China
                Department of Peritoneal Cancer Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China
                Department of Peritoneal Cancer Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China
                Department of Peritoneal Cancer Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China
                Department of Peritoneal Cancer Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China. liyansd2@ 123456mail.ccmu.edu.cn
                Author notes

                Author contributions: Zhao X and Gao C collected the data; Zhang Y and Lin LY performed the data analysis; Zhang Y wrote the original draft preparation; Zhang Y and Li Y wrote the review and editing; Li Y contributed to the supervision.

                Supported by Beijing Municipal Administration of Hospitals’ Ascent Plan, No. DFL20180701; and Beijing Municipal Grant for Medical Talents Group on Peritoneal Surface Oncology, No. 2017400003235J007.

                Corresponding author: Yan Li, MD, PhD, Doctor, Surgical Oncologist, Department of Peritoneal Cancer Surgery, Beijing Shijitan Hospital, Capital Medical University, No. 10 Tieyi Road, Yangfangdian Street, Haidian District, Beijing 100038, China. liyansd2@ 123456mail.ccmu.edu.cn

                Article
                jWJGS.v15.i6.pg1149
                10.4240/wjgs.v15.i6.1149
                10315110
                37405093
                de0bc2cd-efba-43d1-8fb8-6bdd2aefff01
                ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.

                This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/

                History
                : 8 March 2023
                : 18 March 2023
                : 14 April 2023
                Categories
                Retrospective Study

                pseudomyxoma peritonei,bevacizumab,oxaliplatin,cyclophosphamide

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