Bhatt, A.

Glehen, O.

Hubner, M.

Kusamura, S.

Van Der Speeten, K.

English

Serveur académique lausannois

ASO AUTHOR REFLECTIONSASO Author Reflections: Standardizing HIPEC Methodologyand Regimens: a Prelude to the PSOGI Expert ConsensusAditi Bhatt, MS, MCh1, Kurt Van Der Speeten, MD, PhD2, Martin Hubner, MD, PhD3, Shigeki Kusamura, MD,PhD4, and Olivier Glehen, MD, PhD51Department of Surgical Oncology, Zydus Hospital, Ahmedabad, India; 2Department of Surgical Oncology, ZeikenhuisOost-Limberg, Genk, Belgium; 3Department of Visceral Surgery, Lausanne University Hospital CHUV, Lausanne,Switzerland; 4Department of Surgical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy;5Department of Surgical Oncology, Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon, Lyon, Pierre Bénite, FrancePASTHyperthermic intraperitoneal chemotherapy (HIPEC)was developed in combination with cytoreductive surgery(CRS) for the treatment of peritoneal metastases (PMs)from different primary tumors in an era when hyperthermiawas being used extensively in the treatment of differentmalignancies. Systemic chemotherapy (SC) produced dis-mal results for most tumors. The understanding of thebiology of PMs has grown, along with the experience withHIPEC, which has moved rapidly from the bench to thebedside.1 The initial decades were spent in developingcenters of expertise to reduce the proportion of incompleteresections and the morbidity and mortality from the pro-cedure. Due to gaps in the preclinical data and clinicalexperience, parameters for evaluating efficacy were poorlydefined and efficacy was evaluated for the combination ofCRS and HIPEC. During this period, surgeons developed amultitude of HIPEC regimens using different drug com-binations with multiple variations in the methodology andelements vital to the procedure.2 Some recent randomizedtrials have not shown a benefit of HIPEC over CRS aloneand the question has been raised as to whether a differentregimen would produce a favorable outcome.PRESENTThe use of newer SC regimens and targeted therapieshas improved the survival in patients with PMs treated withsystemic therapies alone, and SC is an essential adjunct toCRS and HIPEC for most tumors. At the same time, amultitude of clinical trials are being conducted to evaluatethe benefit of HIPEC for different indications. It isimportant to determine which regimens are best suited forevaluation in clinical trials and which regimens should beused for indications where there are no data from ran-domized trials. There is a need for peritoneal malignancycenters across the world to adopt a limited number ofregimens. This will increase the collective experience witheach regimen, make comparisons between studies moremeaningful, and lead to a greater acceptance of the resultsof randomized trials.Based on a critical review of the literature, we found thatthe preclinical/clinical data for most HIPEC regimens waslimited and studies comparing different regimens werescarce.3 Many regimens were neither supported by pre-clinical rationale data nor validated by a dose escalatingformal phase I trial. All regimens were based on pharma-cokinetic data and did not take chemosensitivity of PMsinto account.FUTUREMore research comprising of preclinical and phase I/IIstudies and studies on biological mechanisms underlyingthe drug–heat interaction and cytotoxicity of chemothera-peutic agents needs to be conducted. However, not allparameters can be tested in randomized trials and the Society of Surgical Oncology 2021First Received: 10 May 2021Accepted: 10 May 2021;Published Online: 4 June 2021O. Glehen, MD, PhDe-mail: olivier.glehen@chu-lyon.frAnn Surg Oncol (2021) 28:9114–9115https://doi.org/10.1245/s10434-021-10205-9methodology and regimens need to be standardized untilbetter evidence is available. The best way to minimize theheterogeneity is by carrying out an expert consensus thataims to identify and define a limited number of regimensfor each indication and primary site. The Grading ofRecommendations Assessment, Development, and Evalu-ation (GRADE) system for rating quality of evidenceshould be used to rate the evidence for such a consensus,especially since the evidence is limited.4 Regimens notsupported by preclinical rationale data and not validated bya dose-escalating formal phase I trial should be eliminated.The choice of regimen can then be tailored to the patientprofile and expected toxicity, as well as the methodologyaccording to regional factors.Surgeons should focus on methodological accuracy, aswell as on the three key elements, i.e. adequate drug dos-ing, maintenance of hyperthermia, and adequate perfusion.Personalized medicine approaches such as patient tumororganoids are being developed to determine the best regi-men for each patient, but clinical validation is likely to bechallenging.5FUNDING The authors received no funding for this study.DISCLOSURES Olivier Glehen has received honoraria fromGamida Tech. Aditi Bhatt, Kurt Van Der Speeten, Martin Hubner,and Shigeki Kusamura have no disclosures to declare.REFERENCES1. Stein MK, Williard FW, Xiu J, Tsao MW, Martin MG, DeschnerBW, et al. Comprehensive tumor profiling reveals unique molec-ular differences between peritoneal metastases and primarycolorectal adenocarcinoma. J Surg Oncol. 2020;121(8):1320–8. https://doi.org/10.1002/jso.25899.2. Lemoine L, Sugarbaker P, Van der Speeten K. Drugs, doses, anddurations of intraperitoneal chemotherapy: standardising HIPECand EPIC for colorectal, appendiceal, gastric, ovarian peritonealsurface malignancies and peritoneal mesothelioma. Int J Hyperth.2017;33(5):582–92. https://doi.org/10.1080/02656736.2017.1291999.3. Bhatt A, de Hingh I, Van Der Speeten K, Hubner M, Deraco M,Bakrin N, et al. HIPEC methodology and regimens: the need for anexpert consensus. Ann. Surg. Oncol. 2021. https://doi.org/10.1245/s10434-021-10193-w.4. Atkins D, Best D, Briss PA, Eccles M, Falck-Ytter Y, Flottorp S,et al. Grading quality of evidence and strength of recommenda-tions. BMJ. 2004;328(7454):1490. https://doi.org/10.1136/bmj.328.7454.1490.5. Votanopoulos KI, Mazzocchi A, Sivakumar H, et al. Appendicealcancer patient-specific tumor organoid model for predictingchemotherapy efficacy prior to initiation of treatment: a feasibilitystudy. Ann Surg Oncol. 2019;26:139–47. https://doi.org/10.1245/s10434-018-7008-2.Publisher’s Note Springer Nature remains neutral with regard tojurisdictional claims in published maps and institutional affiliations.Standardizing HIPEC Methodology and Regimens 9115

ASO Author Reflections: Standardizing HIPEC Methodology and Regimens: a Prelude to the PSOGI Expert Consensus.

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ASO Author Reflections: Standardizing HIPEC Methodology and Regimens: a Prelude to the PSOGI Expert Consensus.

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