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Mortality of patients with metastatic colorectal cancer who received elective or emergent operation after exposure to bevacizumab: A nationwide database study

  • Yu-Hsun Chen
    Affiliations
    Division of Colorectal Surgery, Department of Surgery, Kaohsiung Veterans General Hospital, No. 386, Dazhong 1st Rd, Zuoying District, Kaohsiung, 813414, Taiwan
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  • Yi-Chia Su
    Affiliations
    Department of Pharmacy, Kaohsiung Veterans General Hospital, No. 386, Dazhong 1st Rd, Zuoying District, Kaohsiung, 813414, Taiwan

    Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng-Kung University, No. 1, University Rd, East District, Tainan City 701, Taiwan

    Department of Nursing, Shu-Zen Junior College of Medicine and Management, No. 452, Huanqiu Rd, Luzhu District, Kaohsiung, 821, Taiwan
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  • Chao-Wen Hsu
    Affiliations
    Division of Colorectal Surgery, Department of Surgery, Kaohsiung Veterans General Hospital, No. 386, Dazhong 1st Rd, Zuoying District, Kaohsiung, 813414, Taiwan

    Department of Surgery, School of Medicine, National Yang Ming Chiao Tung University, No. 155, Sec. 2, Linong Street, Taipei, 112, Taiwan
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  • Meng-Che Hsieh
    Affiliations
    Department of Hematology and Oncology, E-Da Cancer Hospital, No.1, Yida Road, Jiaosu Village, Yanchao District, Kaohsiung, 824005, Taiwan

    College of Medicine, I-Shou University, No. 1, Section 1, Xuecheng Rd, Dashu District, Kaohsiung, 84001, Taiwan
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  • Yung-Chang Wang
    Affiliations
    Division of Colorectal Surgery, Department of Surgery, Kaohsiung Veterans General Hospital, No. 386, Dazhong 1st Rd, Zuoying District, Kaohsiung, 813414, Taiwan
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  • Ming-Hung Lee
    Affiliations
    Division of Colorectal Surgery, Department of Surgery, Kaohsiung Veterans General Hospital, No. 386, Dazhong 1st Rd, Zuoying District, Kaohsiung, 813414, Taiwan
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  • Chien-Yuan Lin
    Affiliations
    Division of Colorectal Surgery, Department of Surgery, Kaohsiung Veterans General Hospital, No. 386, Dazhong 1st Rd, Zuoying District, Kaohsiung, 813414, Taiwan
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  • Yu-Ching Chang
    Affiliations
    Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng-Kung University, No. 1, University Rd, East District, Tainan City 701, Taiwan
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  • Chih-Chien Wu
    Correspondence
    Corresponding author. Division of Colorectal Surgery, Department of Surgery, Kaohsiung Veterans General Hospital, No. 386, Dazhong 1st Rd., Zuoying Dist., Kaohsiung City, 813414, Taiwan.
    Affiliations
    Division of Colorectal Surgery, Department of Surgery, Kaohsiung Veterans General Hospital, No. 386, Dazhong 1st Rd, Zuoying District, Kaohsiung, 813414, Taiwan

    Department of Surgery, School of Medicine, National Yang Ming Chiao Tung University, No. 155, Sec. 2, Linong Street, Taipei, 112, Taiwan
    Search for articles by this author
Published:October 01, 2022DOI:https://doi.org/10.1016/j.ejso.2022.09.018

      Abstract

      Introduction

      Treatment guidelines for colorectal cancer (CRC) indicate that surgical intervention within 4 weeks or 8 weeks after bevacizumab therapy might increase the risk of postoperative complications and mortality, especially in patients who received emergent operation. Therefore, we aimed to assess the association between different surgical timings, emergent or elective surgery, and the risk of postoperative mortality.

      Materials and methods

      Using the Taiwan National Health Insurance Database and Taiwan Cancer Registry, we identified patients with metastatic colorectal cancer (mCRC) who underwent surgery within 1 year of receiving bevacizumab between January 2010 and December 2017. The primary outcomes were 30-day, 60-day, and in-hospital mortality; the secondary outcomes were hospital stay, 30-day readmission rate, and surgical complications. Multivariate analysis was used to adjust for confounders.

      Results

      This study included 2,047 patients. In the multivariate analysis, patients who underwent emergent operation and had higher Charlson scores had a significantly higher mortality rate. Patients with a longer interval to surgery, more cycles of bevacizumab treatment, and distal metastectomy had the opposite result. In subgroup analysis, patients who received emergent operation within 28 days had the highest surgical mortality.

      Conclusions

      The interval to operation among mCRC patients who receive bevacizumab treatment should exceed 4 weeks to avoid additional risk of mortality whether patients receiving elective or emergent operation. Patients who received emergent operation within 28 days of bevcizumab infusion had the highest risk of mortality.

      Keywords

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      References

        • Bray F.
        • Ferlay J.
        • Soerjomataram I.
        • Siegel R.L.
        • Torre L.A.
        • Jemal A.
        Global Cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.
        C.A. Cancer J. Clin. 2018; 68: 394-424https://doi.org/10.3322/caac.21492
        • Vatandoust S.
        • Price T.J.
        • Karapetis C.S.
        Colorectal cancer: metastases to a single organ.
        World J Gastroenterol. 2015; 21: 11767-11776https://doi.org/10.3748/wjg.v21.i41.11767
      1. National Comprehensive Cancer Network; Cancer, C., 1.2021 version. https://www.nccn.org/professionals/physician_gls/pdf/colon.pdf, (accessed 19 May 2021).

        • Onaitis M.W.
        • Petersen R.P.
        • Haney J.C.
        • et al.
        Prognostic factors for recurrence after pulmonary resection of colorectal cancer metastases.
        Ann Thorac Surg. 2009; 87: 1684-1688https://doi.org/10.1016/j.athoracsur.2009.03.034
        • Faron M.
        • Pignon J.P.
        • Malka D.
        • et al.
        Is primary tumour resection associated with survival improvement in patients with colorectal cancer and unresectable synchronous metastases? A pooled analysis of individual data from four randomised trials.
        Eur J Cancer. 2015; 51: 166-176https://doi.org/10.1016/j.ejca.2014.10.023
        • Shida D.
        • Boku N.
        • Tanabe T.
        • et al.
        Primary tumor resection for stage IV colorectal cancer in the era of targeted chemotherapy.
        J Gastrointest Surg. 2019; 23: 2144-2150https://doi.org/10.1007/s11605-018-4044-y
        • Kubicka S.
        • Greil R.
        • André T.
        • et al.
        Bevacizumab plus chemotherapy continued beyond first progression in patients with metastatic colorectal cancer previously treated with bevacizumab plus chemotherapy: ML18147 study KRAS subgroup findings.
        Ann Oncol. 2013; 24: 2342-2349https://doi.org/10.1093/annonc/mdt231
        • Sharma K.
        • Marcus J.R.
        Bevacizumab and wound-healing complications: mechanisms of action, clinical evidence, and management recommendations for the plastic surgeon.
        Ann Plast Surg. 2013; 71: 434-440https://doi.org/10.1097/SAP.0b013e31824e5e57
        • Kim S.A.
        • Kim J.W.
        • Suh K.J.
        • et al.
        Conversion surgery after cetuximab or bevacizumab plus FOLFIRI chemotherapy in colorectal cancer patients with liver- and/or lung-limited metastases.
        J Cancer Res Clin Oncol. 2020; 146: 2399-2410https://doi.org/10.1007/s00432-020-03233-7
        • Scappaticci F.A.
        • Fehrenbacher L.
        • Cartwright T.
        • et al.
        Surgical wound healing complications in metastatic colorectal cancer patients treated with bevacizumab.
        J Surg Oncol. 2005; 91: 173-180https://doi.org/10.1002/jso.20301
        • D'Angelica M.
        • Kornprat P.
        • Gonen M.
        • et al.
        Lack of evidence for increased operative morbidity after hepatectomy with perioperative use of bevacizumab: a matched case-control study.
        Ann Surg Oncol. 2007; 14: 759-765https://doi.org/10.1245/s10434-006-9074-0
        • Kesmodel S.B.
        • M Ellis L.
        • Lin E.
        • et al.
        Preoperative bevacizumab does not significantly increase postoperative complication rates in patients undergoing hepatic surgery for colorectal cancer liver metastases.
        J Clin Oncol. 2008; 26: 5254-5260https://doi.org/10.1200/JCO.2008.17.7857
        • Utsumi H.
        • Honma Y.
        • Nagashima K.
        • et al.
        Bevacizumab and postoperative wound complications in patients with liver metastases of colorectal cancer.
        Anticancer Res. 2015; 35: 2255-2261
        • Lubezky N.
        • Winograd E.
        • Papoulas M.
        • et al.
        Perioperative complications after neoadjuvant chemotherapy with and without bevacizumab for colorectal liver metastases.
        J Gastrointest Surg. 2013; 17: 527-532https://doi.org/10.1007/s11605-012-2108-y
        • Constantinidou A.
        • Cunningham D.
        • Shurmahi F.
        • et al.
        Perioperative chemotherapy with or without bevacizumab in patients with metastatic colorectal cancer undergoing liver resection.
        Clin Colorectal Cancer. 2013; 12: 15-22https://doi.org/10.1016/j.clcc.2012.07.002
        • Bose D.
        • Meric-Bernstam F.
        • Hofstetter W.
        • Reardon D.A.
        • Flaherty K.T.
        • Ellis L.M.
        Vascular endothelial growth factor targeted therapy in the perioperative setting: implications for patient care.
        Lancet Oncol. 2010; 11: 373-382https://doi.org/10.1016/S1470-2045(09)70341-9
        • Barnett A.
        • Cedar A.
        • Siddiqui F.
        • Herzig D.
        • Fowlkes E.
        • Thomas Jr., C.R.
        Colorectal cancer emergencies.
        J Gastrointest Cancer. 2013; 44: 132-142https://doi.org/10.1007/s12029-012-9468-0
        • Gunnarsson H.
        • Holm T.
        • Ekholm A.
        • Olsson L.I.
        Emergency presentation of colon cancer is most frequent during summer.
        Colorectal Dis. 2011; 13: 663-668https://doi.org/10.1111/j.1463-1318.2010.02270.x
      2. Bureau of National Health Insurance in Taiwan. The Drugs Payment Guideline for Anti-Neoplastic Agents. https://www.nhi.gov.tw/DL.aspx?sitessn=292&u=LzAwMS9VcGxvYWQvMjkyL3JlbGZpbGUvMC82MTM3L2NoYXA5XzExMDExLnBkZg%3d%3d&n=Y2hhcDlfMTEwMTEucGRm&ico%20=.pdf, (accessed 24 Dec 2020).

        • National Health Insurance Research Database
        http://nhird.nhri.org.tw/en/index.htm
        Date accessed: December 24, 2020
        ([Health and Welfare Data Science Center, Ministry of Health and Welfare, Taiwan])
        • Hsieh C.Y.
        • Su C.C.
        • Shao S.C.
        • et al.
        Taiwan's national Health insurance research database: past and future.
        Clin Epidemiol. 2019; 11: 349-358https://doi.org/10.2147/CLEP.S196293
        • Chiang C.J.
        • You S.L.
        • Chen C.J.
        • Yang Y.W.
        • Lo W.C.
        • Lai M.S.
        Quality assessment and improvement of nationwide cancer registration system in Taiwan: a review.
        Jpn J Clin Oncol. 2015; 45: 291-296https://doi.org/10.1093/jjco/hyu211
        • Charlson M.E.
        • Charlson R.E.
        • Peterson J.C.
        • Marinopoulos S.S.
        • Briggs W.M.
        • Hollenberg J.P.
        The Charlson comorbidity index is adapted to predict costs of chronic disease in primary care patients.
        J Clin Epidemiol. 2008; 61: 1234-1240https://doi.org/10.1016/j.jclinepi.2008.01.006
        • Deyo R.A.
        • Cherkin D.C.
        • Ciol M.A.
        Adapting a clinical comorbidity index for use with ICD-9-CM administrative databases.
        J Clin Epidemiol. 1992; 45: 613-619https://doi.org/10.1016/0895-4356(92)90133-8
        • Thornton A.D.
        • Ravn P.
        • Winslet M.
        • Chester K.
        Angiogenesis inhibition with bevacizumab and the surgical management of colorectal cancer.
        Br J Surg. 2006; 93: 1456-1463https://doi.org/10.1002/bjs.5624
        • Bao P.
        • Kodra A.
        • Tomic-Canic M.
        • Golinko M.S.
        • Ehrlich H.P.
        • Brem H.
        The role of vascular endothelial growth factor in wound healing.
        J Surg Res. 2009; 153: 347-358https://doi.org/10.1016/j.jss.2008.04.023
        • Starlinger P.
        • Alidzanovic L.
        • Schauer D.
        • et al.
        Neoadjuvant bevacizumab persistently inactivates VEGF at the time of surgery despite preoperative cessation.
        Br J Cancer. 2012; 107: 961-966https://doi.org/10.1038/bjc.2012.342
        • Gordon M.S.
        • Margolin K.
        • Talpaz M.
        • et al.
        Phase I safety and pharmacokinetic study of recombinant human anti-vascular endothelial growth factor in patients with advanced cancer.
        J Clin Oncol. 2001; 19: 843-850https://doi.org/10.1200/JCO.2001.19.3.843
        • Kundes F.
        • Kement M.
        • Cetin K.
        • et al.
        Evaluation of the patients with colorectal cancer undergoing emergent curative surgery.
        SpringerPlus. 2016; 5: 2024https://doi.org/10.1186/s40064-016-3725-9
        • Jansson Timan T.
        • Hagberg G.
        • Sernert N.
        • Karlsson O.
        • Prytz M.
        Mortality following emergency laparotomy: a Swedish cohort study.
        BMC Surg. 2021; 21: 322https://doi.org/10.1186/s12893-021-01319-8
        • Kim J.W.
        • Mannalithara A.
        • Sehgal M.
        • Mithal A.
        • Singh G.
        • Ladabaum U.
        A nationwide analysis of readmission rates after colorectal cancer surgery in the US in the Era of the Addordable Care Act.
        Am J Surg. 2020; 220: 1015-1022https://doi.org/10.1016/j.amjsurg.2020.04.013
        • Baxter N.N.
        • Fischer H.D.
        • Richardson D.P.
        • et al.
        A population-based study of complications after colorectal surgery in patients who have received bevacizumab.
        Dis Colon Rectum. 2018; 61: 306-313https://doi.org/10.1097/DCR.0000000000000966
        • Hompes D.
        • Ruers T.
        Review: incidence and clinical significance of bevacizumab-related non-surgical and surgical serious adverse events in metastatic colorectal cancer.
        Eur J Surg Oncol. 2011; 37: 737-746https://doi.org/10.1016/j.ejso.2011.06.004
        • Kozloff M.
        • Yood M.U.
        • Berlin J.
        • et al.
        Clinical outcomes associated with bevacizumab-containing treatment of metastatic colorectal cancer: the BRiTE observational cohort study.
        Oncol. 2009; 14: 862-870https://doi.org/10.1634/theoncologist.2009-0071
        • Van Cutsem E.
        • Rivera F.
        • Berry S.
        • et al.
        Safety and efficacy of first-line bevacizumab with FOLFOX, XELOX, FOLFIRI and fluoropyrimidines in metastatic colorectal cancer: the BEAT study.
        Ann Oncol. 2009; 20: 1842-1847https://doi.org/10.1093/annonc/mdp233
        • Wicherts D.A.
        • de Haas R.J.
        • Sebagh M.
        • et al.
        Impact of bevacizumab on functional recovery and histology of the liver after resection of colorectal metastases.
        Br J Surg. 2011; 98: 399-407https://doi.org/10.1002/bjs.7368
        • Shubert C.R.
        • Habermann E.B.
        • Bergquist J.R.
        • et al.
        A NSQIP review of major morbidity and mortality of synchronous liver resection for colorectal metastasis stratified by extent of liver resection and type of colorectal resection.
        J Gastrointest Surg. 2015; 19: 1982-1994https://doi.org/10.1007/s11605-015-2895-z