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Hyperthermic intraperitoneal chemotherapy for epithelial ovarian cancer: A meta-analysis

  • Author Footnotes
    1 These two authors contributed equally as the first authors.
    Se Ik Kim
    Footnotes
    1 These two authors contributed equally as the first authors.
    Affiliations
    Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Republic of Korea
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  • Author Footnotes
    1 These two authors contributed equally as the first authors.
    Ji Hyun Kim
    Footnotes
    1 These two authors contributed equally as the first authors.
    Affiliations
    Center for Gynecologic Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Republic of Korea
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  • Sanghee Lee
    Affiliations
    Department of Cancer Control and Population Health, National Cancer Center Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Republic of Korea
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  • Hyunsoon Cho
    Affiliations
    Department of Cancer Control and Population Health, National Cancer Center Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Republic of Korea
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  • Willemien J. van Driel
    Affiliations
    Department of Medical Oncology, the Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, the Netherlands
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  • Gabe S. Sonke
    Affiliations
    Department of Gynecology, the Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, the Netherlands
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  • Robert E. Bristow
    Affiliations
    Division of Gynecologic Oncology, Obstetrics and Gynecology, Irvine Medical Center, University of California, California, USA
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  • Sang-Yoon Park
    Affiliations
    Center for Gynecologic Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Republic of Korea
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  • Author Footnotes
    2 These two authors have equally contributed to this study as cosenior authors.
    Christina Fotopoulou
    Footnotes
    2 These two authors have equally contributed to this study as cosenior authors.
    Affiliations
    Department of Surgery and Cancer, Gynaecologic Oncology, Imperial College London, London, UK
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  • Author Footnotes
    2 These two authors have equally contributed to this study as cosenior authors.
    Myong Cheol Lim
    Correspondence
    Corresponding author at: Division of Rare and Refractory Cancer, Center for Gynecologic Cancer, and Center for Clinical Trial, Research Institute and Hospital, Department of Cancer Control and Policy, Graduate School of Cancer Science and Policy, National Cancer Center, 323, Ilsan-ro, Ilsandong-gu, Goyang-si, Gyeonggi-do 10408, Republic of Korea.
    Footnotes
    2 These two authors have equally contributed to this study as cosenior authors.
    Affiliations
    Center for Gynecologic Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Republic of Korea

    Department of Cancer Control and Policy, National Cancer Center Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Republic of Korea

    Rare & Pediatric Cancer Branch and Immuno-oncology Branch, Division of Rare and Refractory Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Republic of Korea

    Center for Clinical Trial, Research Institute and Hospital, National Cancer Center, Goyang, Republic of Korea
    Search for articles by this author
  • Author Footnotes
    1 These two authors contributed equally as the first authors.
    2 These two authors have equally contributed to this study as cosenior authors.
Published:October 20, 2022DOI:https://doi.org/10.1016/j.ygyno.2022.10.010

      Highlights

      • The value of HIPEC at cytoreductive surgery for ovarian cancer remains controversial in most guidelines.
      • A total of 15 studies of 1861 patients contributed data for meta-analysis.
      • In the study, the value of HIPEC appears to depend on the timing of the last systemic chemotherapy exposure.

      Abstract

      Background

      The value of hyperthermic intraperitoneal chemotherapy (HIPEC) at the time of cytoreductive surgery (CRS) for epithelial ovarian cancer (EOC) is controversial and its use remains experimental in most national and international guidelines. We wished to systematically evaluate all available evidence.

      Methods

      A comprehensive review of data from MEDLINE, EMBASE, and Cochrane Library databases was conducted from the first report on HIPEC in EOC till April 3, 2022. Progression-free survival (PFS) and overall survival (OS) were compared between the HIPEC and control groups. This meta-analysis was registered with PROSPERO (CRD42021265810).

      Results

      Fifteen studies (10 case-control studies and 5 randomized controlled trials [RCTs]) were included in the present meta-analysis. Based on the time interval between the last systemic chemotherapy exposure and timing of CRS +/− HIPEC, all studies and patients' cohorts we classified into recent (<6 months; n = 9 studies/patients cohorts) and non-recent (≥6 months, n = 8 studies/patients cohorts) chemotherapy exposure groups. In the recent chemotherapy exposure group, HIPEC was associated with improvement of both PFS (HR, 0.585; 95% CI, 0.422–0.811) and OS (HR, 0.519; 95% CI, 0.346–0.777). On the contrary, in the non-recent chemotherapy exposure group, HIPEC failed to significantly affect PFS (HR, 1.037; 95% CI, 0.684–1.571) or OS (HR, 0.932; 95% CI, 0.607–1.430). Consistent results were observed in subsequent sensitivity analyses.

      Conclusion

      Our present meta-analysis demonstrates that the value of HIPEC at CRS for EOC appears to depend on the timing of the last systemic chemotherapy exposure. Future trials are awaited to define the role of HIPEC in EOC.

      Keywords

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      References

        • Sung H.
        • Ferlay J.
        • Siegel R.L.
        • Laversanne M.
        • Soerjomataram I.
        • Jemal A.
        • et al.
        Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.
        CA Cancer J. Clin. 2021; 71: 209-249
        • Ha H.I.
        • Chang H.K.
        • Park S.J.
        • Lim J.
        • Won Y.J.
        • Lim M.C.
        The incidence and survival of cervical, ovarian, and endometrial cancer in Korea, 1999-2017: Korea central Cancer registry.
        Obstet. Gynecol. Sci. 2021; 64: 444-453
        • Kang M.J.
        • Won Y.J.
        • Lee J.J.
        • Jung K.W.
        • Kim H.J.
        • Kong H.J.
        • et al.
        Cancer statistics in Korea: incidence, mortality, survival, and prevalence in 2019.
        Cancer Res. Treat. 2022; 54: 330-344
        • Webb P.M.
        • Jordan S.J.
        Epidemiology of epithelial ovarian cancer.
        Best Practice Res. Cli. Obstetrics Gynaecol. 2017; 41: 3-14
        • Ledermann J.A.
        • Raja F.A.
        • Fotopoulou C.
        • Gonzalez-Martin A.
        • Colombo N.
        • Sessa C.
        Newly diagnosed and relapsed epithelial ovarian carcinoma: ESMO clinical practice guidelines for diagnosis, treatment and follow-up.
        Ann. Oncol. 2013; 24 (vi24-32)
        • Monk B.J.
        • Parkinson C.
        • Lim M.C.
        • O’Malley D.M.
        • Oaknin A.
        • Wilson M.K.
        • et al.
        A Randomized, Phase III Trial to Evaluate Rucaparib Monotherapy as Maintenance Treatment in Patients With Newly Diagnosed Ovarian Cancer (ATHENA-MONO/GOG-3020/ENGOT-ov45).
        J. Clin. Oncol. 2022; : JCO2201003
        • Ray-Coquard I.
        • Pautier P.
        • Pignata S.
        • Perol D.
        • Gonzalez-Martin A.
        • Berger R.
        • et al.
        Olaparib plus bevacizumab as first-line maintenance in ovarian Cancer.
        N. Engl. J. Med. 2019; 381: 2416-2428
        • Moore K.
        • Colombo N.
        • Scambia G.
        • Kim B.G.
        • Oaknin A.
        • Friedlander M.
        • et al.
        Maintenance Olaparib in patients with newly diagnosed advanced ovarian Cancer.
        N. Engl. J. Med. 2018; 379: 2495-2505
        • Gonzalez-Martin A.
        • Pothuri B.
        • Vergote I.
        • DePont Christensen R.
        • Graybill W.
        • Mirza M.R.
        • et al.
        Niraparib in patients with newly diagnosed advanced ovarian Cancer.
        N. Engl. J. Med. 2019; 381: 2391-2402
        • Coleman R.L.
        • Fleming G.F.
        • Brady M.F.
        • Swisher E.M.
        • Steffensen K.D.
        • Friedlander M.
        • et al.
        Veliparib with first-line chemotherapy and as maintenance therapy in ovarian Cancer.
        N. Engl. J. Med. 2019; 381: 2403-2415
        • Perren T.J.
        • Swart A.M.
        • Pfisterer J.
        • Ledermann J.A.
        • Pujade-Lauraine E.
        • Kristensen G.
        • et al.
        A phase 3 trial of bevacizumab in ovarian cancer.
        N. Engl. J. Med. 2011; 365: 2484-2496
        • van Driel W.J.
        • Koole S.N.
        • Sikorska K.
        • Schagen van Leeuwen J.H.
        • Schreuder H.W.R.
        • Hermans R.H.M.
        • et al.
        Hyperthermic intraperitoneal chemotherapy in ovarian cancer.
        N. Engl. J. Med. 2018; 378: 230-240
        • Quenet F.
        • Elias D.
        • Roca L.
        • Goere D.
        • Ghouti L.
        • Pocard M.
        • et al.
        Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy versus cytoreductive surgery alone for colorectal peritoneal metastases (PRODIGE 7): a multicentre, randomised, open-label, phase 3 trial.
        Lancet Oncol. 2021; 22: 256-266
        • Zivanovic O.
        • Chi D.S.
        • Zhou Q.
        • Iasonos A.
        • Konner J.A.
        • Makker V.
        • et al.
        Secondary Cytoreduction and carboplatin Hyperthermic intraperitoneal chemotherapy for platinum-sensitive recurrent ovarian Cancer: an MSK team ovary phase II study.
        J. Clin. Oncol. 2021; : JCO2100605
        • Lim M.C.
        • Chang S.J.
        • Park B.
        • Yoo H.J.
        • Yoo C.W.
        • Nam B.H.
        • et al.
        Survival after Hyperthermic intraperitoneal chemotherapy and primary or interval Cytoreductive surgery in ovarian Cancer: a randomized clinical trial.
        JAMA Surg. 2022; 157: 374-383
        • Spiliotis J.
        • Halkia E.
        • Lianos E.
        • Kalantzi N.
        • Grivas A.
        • Efstathiou E.
        • et al.
        Cytoreductive surgery and HIPEC in recurrent epithelial ovarian cancer: a prospective randomized phase III study.
        Ann. Surg. Oncol. 2015; 22: 1570-1575
        • Goere D.
        • Glehen O.
        • Quenet F.
        • Guilloit J.M.
        • Bereder J.M.
        • Lorimier G.
        • et al.
        Second-look surgery plus hyperthermic intraperitoneal chemotherapy versus surveillance in patients at high risk of developing colorectal peritoneal metastases (PROPHYLOCHIP-PRODIGE 15): a randomised, phase 3 study.
        Lancet Oncol. 2020; 21: 1147-1154
        • Arjona-Sanchez A.
        • Barrios P.
        • Boldo-Roda E.
        • Camps B.
        • Carrasco-Campos J.
        • Concepcion Martin V.
        • et al.
        HIPECT4: multicentre, randomized clinical trial to evaluate safety and efficacy of Hyperthermic intra-peritoneal chemotherapy (HIPEC) with Mitomycin C used during surgery for treatment of locally advanced colorectal carcinoma.
        BMC Cancer. 2018; 18: 183
        • Rovers K.P.
        • Bakkers C.
        • Simkens G.
        • Burger J.W.A.
        • Nienhuijs S.W.
        • Creemers G.M.
        • et al.
        Perioperative systemic therapy and cytoreductive surgery with HIPEC versus upfront cytoreductive surgery with HIPEC alone for isolated resectable colorectal peritoneal metastases: protocol of a multicentre, open-label, parallel-group, phase II-III, randomised, superiority study (CAIRO6).
        BMC Cancer. 2019; 19: 390
        • Antonio C.C.P
        • Alida G.G.
        • Elena G.G.
        • Rocío G.S.
        • Jerónimo M.G.
        • Luis A.R.J.
        • Aníbal N.D.
        • Francisco B.V.
        • Jesús G.R.Á.
        • Pablo R.R.
        • José G.M.
        • et al.
        Cytoreductive Surgery With or Without HIPEC After Neoadjuvant Chemotherapy in Ovarian Cancer: A Phase 3 Clinical Trial.
        Ann. Surg. Oncol. 2022; 29: 2617-2625
        • Lei Z.
        • Wang Y.
        • Wang J.
        • Wang K.
        • Tian J.
        • Zhao Y.
        • et al.
        Evaluation of Cytoreductive surgery with or without Hyperthermic intraperitoneal chemotherapy for stage III epithelial ovarian Cancer.
        JAMA Netw. Open. 2020; 3e2013940
        • Safra T.
        • Grisaru D.
        • Inbar M.
        • Abu-Abeid S.
        • Dayan D.
        • Matceyevsky D.
        • et al.
        Cytoreduction surgery with hyperthermic intraperitoneal chemotherapy in recurrent ovarian cancer improves progression-free survival, especially in BRCA-positive patients- a case-control study.
        J. Surg. Oncol. 2014; 110: 661-665
        • Ryu K.S.
        • Kim J.H.
        • Ko H.S.
        • Kim J.W.
        • Ahn W.S.
        • Park Y.G.
        • et al.
        Effects of intraperitoneal hyperthermic chemotherapy in ovarian cancer.
        Gynecol. Oncol. 2004; 94: 325-332
        • Liberati A.
        • Altman D.G.
        • Tetzlaff J.
        • Mulrow C.
        • Gøtzsche P.C.
        • Ioannidis J.P.
        • et al.
        The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration.
        PLoS Med. 2009; 6e1000100
        • Fagotti A.
        • Costantini B.
        • Petrillo M.
        • Vizzielli G.
        • Fanfani F.
        • Margariti P.A.
        • et al.
        Cytoreductive surgery plus HIPEC in platinum-sensitive recurrent ovarian cancer patients: a case-control study on survival in patients with two year follow-up.
        Gynecol. Oncol. 2012; 127: 502-505
        • Cascales-Campos P.A.
        • Gil J.
        • Gil E.
        • Feliciangeli E.
        • González-Gil A.
        • Parrilla J.J.
        • et al.
        Treatment of microscopic disease with hyperthermic intraoperative intraperitoneal chemotherapy after complete cytoreduction improves disease-free survival in patients with stage IIIC/IV ovarian cancer.
        Ann. Surg. Oncol. 2014; 21: 2383-2389
        • Warschkow R.
        • Tarantino I.
        • Lange J.
        • Müller S.A.
        • Schmied B.M.
        • Zünd M.
        • et al.
        Does hyperthermic intraoperative chemotherapy lead to improved outcomes in patients with ovarian cancer? A single center cohort study in 111 consecutive patients.
        Patient Safety Surg. 2012; 6: 12
        • Muñoz-Casares F.C.
        • Rufián S.
        • Rubio M.J.
        • Díaz C.J.
        • Díaz R.
        • Casado A.
        • et al.
        The role of hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) in the treatment of peritoneal carcinomatosis in recurrent ovarian cancer.
        Clin. Transl. Oncol. 2009; 11: 753-759
        • Gori J.
        • Castaño R.
        • Toziano M.
        • Häbich D.
        • Staringer J.
        • De Quirós D.G.
        • et al.
        Intraperitoneal hyperthermic chemotherapy in ovarian cancer.
        Int. J. Gynecol. Cancer. 2005; 15: 233-239
        • Kim J.H.
        • Lee J.M.
        • Ryu K.S.
        • Lee Y.S.
        • Park Y.G.
        • Hur S.Y.
        • et al.
        Consolidation hyperthermic intraperitoneal chemotherapy using paclitaxel in patients with epithelial ovarian cancer.
        J. Surg. Oncol. 2010; 101: 149-155
        • Le Brun J.F.
        • Campion L.
        • Berton-Rigaud D.
        • Lorimier G.
        • Marchal F.
        • Ferron G.
        • et al.
        Survival benefit of hyperthermic intraperitoneal chemotherapy for recurrent ovarian cancer: a multi-institutional case control study.
        Ann. Surg. Oncol. 2014; 21: 3621-3627
        • Cascales-Campos P.A.
        • Gil J.
        • Feliciangeli E.
        • Gil E.
        • González-Gil A.
        • López V.
        • et al.
        The role of hyperthermic intraperitoneal chemotherapy using paclitaxel in platinum-sensitive recurrent epithelial ovarian cancer patients with microscopic residual disease after cytoreduction.
        Ann. Surg. Oncol. 2015; 22: 987-993
        • Baiocchi G.
        • Ferreira F.O.
        • Mantoan H.
        • da Costa A.A.
        • Faloppa C.C.
        • Kumagai L.Y.
        • et al.
        Hyperthermic intraperitoneal chemotherapy after secondary cytoreduction in epithelial ovarian cancer: a single-center comparative analysis.
        Ann. Surg. Oncol. 2016; 23: 1294-1301
        • Marocco F.
        • Vaira M.
        • Milani A.
        • Genta S.
        • Maggiorotto F.
        • Magistris A.
        • et al.
        Secondary cytoreductive surgery, hyperthermic intraperitoneal intraoperative chemotherapy, and chemotherapy alone: a retrospective comparison of alternative approaches in relapsed platinum sensitive ovarian cancer.
        Eur. J. Gynaecol. Oncol. 2016; 37: 638-643
        • Mendivil A.A.
        • Rettenmaier M.A.
        • Abaid L.N.
        • Brown 3rd, J.V.
        • Mori K.M.
        • Lopez K.L.
        • et al.
        Consolidation hyperthermic intraperitoneal chemotherapy for the treatment of advanced stage ovarian carcinoma: a 3 year experience.
        Cancer Chemother. Pharmacol. 2017; 80: 405-410
        • Ceresoli M.
        • Verrengia A.
        • Montori G.
        • Busci L.
        • Coccolini F.
        • Ansaloni L.
        • et al.
        Effect of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy on relapse pattern in primary epithelial ovarian cancer: a propensity score based case-control study.
        J. Gynecol. Oncol. 2018; 29e53
        • Tierney J.F.
        • Stewart L.A.
        • Ghersi D.
        • Burdett S.
        • Sydes M.R.
        Practical methods for incorporating summary time-to-event data into meta-analysis.
        Trials. 2007; 8: 16
        • Stang A.
        Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses.
        Eur. J. Epidemiol. 2010; 25: 603-605
        • Higgins J.P.
        • Thompson S.G.
        • Deeks J.J.
        • Altman D.G.
        Measuring inconsistency in meta-analyses.
        BMJ (Clinical research ed). 2003; 327: 557-560
        • Sedgwick P.
        Meta-analyses: what is heterogeneity?.
        BMJ. 2015; 350h1435
        • DerSimonian R.
        • Laird N.
        Meta-analysis in clinical trials.
        Control. Clin. Trials. 1986; 7: 177-188
        • Mantel N.
        • Haenszel W.
        Statistical aspects of the analysis of data from retrospective studies of disease.
        J. Natl. Cancer Inst. 1959; 22: 719-748
        • Huo Y.R.
        • Richards A.
        • Liauw W.
        • Morris D.L.
        Hyperthermic intraperitoneal chemotherapy (HIPEC) and cytoreductive surgery (CRS) in ovarian cancer: a systematic review and meta-analysis.
        Eur. J. Surg. Oncol. 2015; 41: 1578-1589
        • Zhang G.
        • Zhu Y.
        • Liu C.
        • Chao G.
        • Cui R.
        • Zhang Z.
        The prognosis impact of hyperthermic intraperitoneal chemotherapy (HIPEC) plus cytoreductive surgery (CRS) in advanced ovarian cancer: the meta-analysis.
        J. Ovarian Res. 2019; 12: 33
        • Kim S.I.
        • Cho J.
        • Lee E.J.
        • Park S.
        • Park S.J.
        • Seol A.
        • et al.
        Selection of patients with ovarian cancer who may show survival benefit from hyperthermic intraperitoneal chemotherapy: a systematic review and meta-analysis.
        Medicine. 2019; 98e18355
        • Wang Y.
        • Ren F.
        • Chen P.
        • Liu S.
        • Song Z.
        • Ma X.
        Effects of CytoReductive surgery plus hyperthermic IntraPEritoneal chemotherapy (HIPEC) versus CytoReductive surgery for ovarian cancer patients: a systematic review and meta-analysis.
        Eur. J. Surg. Oncol. 2019; 45: 301-309
        • Colombo N.
        • Sessa C.
        • du Bois A.
        • Ledermann J.
        • McCluggage W.G.
        • McNeish I.
        • et al.
        ESMO-ESGO consensus conference recommendations on ovarian cancer: pathology and molecular biology, early and advanced stages, borderline tumours and recurrent disease†.
        Ann. Oncol. 2019; 30: 672-705
        • National Comprehensive Cancer Network
        NCCN Clinical Practice Guidelines in Oncology. Ovarian cancer including fallopian tube cancer and primary peritoneal cancer. Version 1.
        (Available at:)
        • Alter R.
        • Turaga K.
        • Lengyel E.
        Are we ready for Hyperthermic intraperitoneal chemotherapy in the upfront treatment of ovarian Cancer?.
        JAMA Netw. Open. 2020; 3e2014184
        • Vergote I.
        • Harter P.
        • Chiva L.
        Is There a Role for Intraperitoneal Chemotherapy, Including HIPEC, in the Management of Ovarian Cancer?.
        J. Clin. Oncol. 2019; 37: 2420-2423https://doi.org/10.1200/JCO.19.00091
        • Kim J.H.
        • Lee D.E.
        • Lee Y.
        • Ha H.I.
        • Chang Y.J.
        • Chang S.J.
        • et al.
        Quality of life outcomes from the randomized trial of hyperthermic intraperitoneal chemotherapy following cytoreductive surgery for primary ovarian cancer (KOV-HIPEC-01).
        J. Gynecol. Oncol. 2022; 33e54
        • Koole S.
        • van Stein R.
        • Sikorska K.
        • Barton D.
        • Perrin L.
        • Brennan D.
        • et al.
        Primary cytoreductive surgery with or without hyperthermic intraperitoneal chemotherapy (HIPEC) for FIGO stage III epithelial ovarian cancer: OVHIPEC-2, a phase III randomized clinical trial.
        Int. J. Gynecol. Cancer. 2020; 30: 888-892
      1. HIPEC for Platinum-Resistant Recurrent Ovarian Cancer (KOV-HIPEC-02). 2022. ClinicalTrials.gov Identifier: NCT05316181.

        • Zunino B.
        • Ricci J.E.
        Hyperthermic intra-peritoneal chemotherapy and anticancer immune response.
        Oncoimmunology. 2016; 5e1060392
        • Steg A.D.
        • Bevis K.S.
        • Katre A.A.
        • Ziebarth A.
        • Dobbin Z.C.
        • Alvarez R.D.
        • et al.
        Stem cell pathways contribute to clinical chemoresistance in ovarian cancer.
        Clin. Cancer Res. 2012; 18: 869-881
        • Lim M.C.
        • Song Y.J.
        • Seo S.S.
        • Yoo C.W.
        • Kang S.
        • Park S.Y.
        Residual cancer stem cells after interval cytoreductive surgery following neoadjuvant chemotherapy could result in poor treatment outcomes for ovarian cancer.
        Onkologie. 2010; 33: 324-330
        • Maymon R.
        • Bar-Shira Maymon B.
        • Holzinger M.
        • Tartakovsky B.
        • Leibovici J.
        Augmentative effects of intracellular chemotherapy penetration combined with hyperthermia in human ovarian cancer cells lines.
        Gynecol. Oncol. 1994; 55: 265-270
        • Hettinga J.V.
        • Konings A.W.
        • Kampinga H.H.
        Reduction of cellular cisplatin resistance by hyperthermia--a review.
        Int. J. Hyperth. 1997; 13: 439-457
        • Oei A.L.
        • Vriend L.E.M.
        • Krawczyk P.M.
        • Horsman M.R.
        • Franken N.A.P.
        • Crezee J.
        Targeting therapy-resistant cancer stem cells by hyperthermia.
        Int. J. Hyperth. 2017; 33: 419-427
        • Krawczyk P.M.
        • Eppink B.
        • Essers J.
        • Stap J.
        • Rodermond H.
        • Odijk H.
        • et al.
        Mild hyperthermia inhibits homologous recombination, induces BRCA2 degradation, and sensitizes cancer cells to poly (ADP-ribose) polymerase-1 inhibition.
        Proc. Natl. Acad. Sci. U. S. A. 2011; 108: 9851-9856
        • Yagawa Y.
        • Tanigawa K.
        • Kobayashi Y.
        • Yamamoto M.
        Cancer immunity and therapy using hyperthermia with immunotherapy, radiotherapy, chemotherapy, and surgery.
        J. Cancer Metastasis Treat. 2017; 3: 218-230
        • Adkins I.
        • Sadilkova L.
        • Hradilova N.
        • Tomala J.
        • Kovar M.
        • Spisek R.
        Severe, but not mild heat-shock treatment induces immunogenic cell death in cancer cells.
        Oncoimmunology. 2017; 6e1311433
        • Song C.W.
        • Kang M.S.
        • Rhee J.G.
        • Levitt S.H.
        The effect of hyperthermia on vascular function, pH, and cell survival.
        Radiology. 1980; 137: 795-803
        • Vaupel P.W.
        • Kelleher D.K.
        Pathophysiological and vascular characteristics of tumours and their importance for hyperthermia: heterogeneity is the key issue.
        Int. J. Hyperthermia. 2010; 26: 211-223
        • González-Moreno S.
        • González-Bayón L.A.
        • Ortega-Pérez G.
        Hyperthermic intraperitoneal chemotherapy: rationale and technique.
        World J. Gastrointestinal Oncol. 2010; 2: 68-75
        • Kim S.I.
        • Kim J.W.
        Role of surgery and hyperthermic intraperitoneal chemotherapy in ovarian cancer.
        ESMO Open. 2021; 6100149
        • Fotopoulou C.
        • Sehouli J.
        • Aletti G.
        • Harter P.
        • Mahner S.
        • Querleu D.
        • et al.
        Value of neoadjuvant chemotherapy for newly diagnosed advanced ovarian Cancer: a European perspective.
        J. Clin. Oncol. 2017; 35: 587-590
        • Vergote I.
        • Trope C.G.
        • Amant F.
        • Kristensen G.B.
        • Ehlen T.
        • Johnson N.
        • et al.
        Neoadjuvant chemotherapy or primary surgery in stage IIIC or IV ovarian cancer.
        N. Engl. J. Med. 2010; 363: 943-953
        • Kehoe S.
        • Hook J.
        • Nankivell M.
        • Jayson G.C.
        • Kitchener H.
        • Lopes T.
        • et al.
        Primary chemotherapy versus primary surgery for newly diagnosed advanced ovarian cancer (CHORUS): an open-label, randomised, controlled, non-inferiority trial.
        Lancet. 2015; 386: 249-257
        • Vergote I.
        • Coens C.
        • Nankivell M.
        • Kristensen G.B.
        • Parmar M.K.B.
        • Ehlen T.
        • et al.
        Neoadjuvant chemotherapy versus debulking surgery in advanced tubo-ovarian cancers: pooled analysis of individual patient data from the EORTC 55971 and CHORUS trials.
        Lancet Oncol. 2018; 19: 1680-1687
        • Reuss A.
        • du Bois A.
        • Harter P.
        • Fotopoulou C.
        • Sehouli J.
        • Aletti G.
        • et al.
        TRUST: trial of radical upfront surgical therapy in advanced ovarian cancer (ENGOT ov33/AGO-OVAR OP7).
        Int. J. Gynecol. Cancer. 2019; 29: 1327-1331
        • Koole S.
        • van Stein R.
        • Sikorska K.
        • Barton D.
        • Perrin L.
        • Brennan D.
        • et al.
        Primary cytoreductive surgery with or without hyperthermic intraperitoneal chemotherapy (HIPEC) for FIGO stage III epithelial ovarian cancer: OVHIPEC-2, a phase III randomized clinical trial.
        Int. J. Gynecol. Cancer. 2020; 30: 888-892
        • Baek M.H.
        • Park E.Y.
        • Ha H.I.
        • Park S.Y.
        • Lim M.C.
        • Fotopoulou C.
        • et al.
        Secondary Cytoreductive surgery in platinum-sensitive recurrent ovarian Cancer: a Meta-analysis.
        J. Clin. Oncol. 2022; 40: 1659-1670
        • Harter P.
        • Sehouli J.
        • Vergote I.
        • Ferron G.
        • Reuss A.
        • Meier W.
        • et al.
        Randomized trial of Cytoreductive surgery for relapsed ovarian Cancer.
        N. Engl. J. Med. 2021; 385: 2123-2131
        • Chiva L.
        • Harter P.
        • Boria F.
        • Ramirez P.
        A comment on a recent failed HIPEC trial.
        Ann. Surg. Oncol. 2022; 29: 3359-3360
        • Schwameis R.
        • Chiva L.
        • Harter P.
        There is no role for hyperthermic intraperitoneal chemotherapy (HIPEC) in ovarian cancer.
        Int. J. Gynecol. Cancer. 2022; 32: 578
        • Vergote I.
        • Harter P.
        • Chiva L.
        Hyperthermic intraperitoneal chemotherapy does not improve survival in advanced ovarian cancer.
        Cancer. 2019; 125: 4594-4597
        • Harter P.
        • du Bois A.
        • Sehouli J.
        • Mahner S.
        • Vergote I.
        • Chiva L.
        • et al.
        Is there a role for HIPEC in ovarian cancer?.
        Arch. Gynecol. Obstet. 2018; 298: 859-860
        • Fotopoulou C.
        • Sehouli J.
        • Mahner S.
        • Harter P.
        • Van Nieuwenhuysen E.
        • Gonzalez-Martin A.
        • et al.
        HIPEC: HOPE or HYPE in the fight against advanced ovarian cancer?.
        Ann. Oncol. 2018; 29: 1610-1613
        • Harter P.
        • Reuss A.
        • Sehouli J.
        • Chiva L.
        • du Bois A.
        Brief Report About the Role of Hyperthermic Intraperitoneal Chemotherapy in a Prospective Randomized Phase 3 Study in Recurrent Ovarian Cancer From Spiliotis et al..
        Int. J. Gynecol. Cancer. 2017; 27: 246-247