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14 september 2022: Bron ESMO 2022

Op ESMO 2022 werden de resultaten gepresenteerd van de HYPTEC4 studie. Een fase III studie die de veiligheid en werkzaamheid van hyperthermische intraperitoneale chemotherapie (HIPEC) met mitomycine C onderzoekt als deze wordt toegepast tijdens de operatie van patiënten met lokaal gevorderde darmkanker stadium IIIc en IV. 
Op 3-jaars meting werd een duidelijk verschil gezien in zoals de onderzoekers dat noemen locale controle tussen de patiënten uit de Hypecgroep en de controlegroep. 97% vs. 87% (p = 0.025).

Recent is ook een reviewstudie gepresenteerd van belangrijke studies met Hypec en daaruit blijkt dat het wel belangrijk is om van te voren een goede selectie te maken van welke patiënten voor een hypec in aanmerking komen.

Zie deze studie (abstract staat verderop in dit artikel): 

Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Colorectal Peritoneal Metastases: A Summary of Key Clinical Trials


Uit het abstract van de op ESMO 2022 gepresenteerde studie: 

314O - Adjuvant hyperthermic intraperitoneal chemotherapy in locally advanced colon cancer (HIPECT4): A randomized phase III study



We deden een open-label, gerandomiseerde fase III-studie in 17 ziekenhuizen in Spanje. In aanmerking komende patiënten waren 18-75 jaar oud en waren preoperatief met lokaal gevorderde primaire darmkanker gediagnosticeerd (cT4NxM0).
Patiënten werden willekeurig (1:1) toegewezen aan chirurgie of chirurgie plus HIPEC (mitomycine C 30 mg/m2 gedurende 60 minuten), beide gevolgd door systemische adjuvante chemotherapie.
Randomisatie gebeurde via een webgebaseerd systeem, met stratificatie naar behandelcentrum en geslacht. Het primaire doel was 3 jaar locoregionale controle, gedefinieerd als de tijd van behandeling tot herhaling van peritoneale ziekte of overlijden door welke oorzaak dan ook, geanalyseerd door intentie om te behandelen (ITT). Ziektevrije tijd en overall overleving waren secundaire einddoelen.

Resultaten

Tussen november 2015 en januari 2021 werden 184 patiënten gerekruteerd en gerandomiseerd ingedeeld (89 patiënten voor de Hypecgroep versus 95 patiënten in de controlegroep).

  • De mediane studie follow-up was 36 maanden (IQR 27-36).
  • Demografische kenmerken, tumorkenmerken, chirurgische behandeling en definitieve pathologierapporten waren vergelijkbaar tussen beide groepen.
  • De loco-regionale controle (LC) was verbeterd in de Hypecgroep (35,3 ± 0,4 vs. 33,2 ± 0,8 maanden) met een 3 jaar LC-percentage van 97% vs. 87% (p = 0,025).
  • Er werden geen verschillen waargenomen in ziektevrije tijd en overall overleving.
  • De pT4-subgroep vertoonde een duidelijk voordeel van loco-regionale controle (LC) in de HIPEC groep.
  • Er werden geen verschillen in morbiditeit waargenomen tussen groepen.

Conclusie:

De toevoeging van hyperthermische intraperitoneale chemotherapie met mitomycine C aan een complete chirurgische resectie voor lokaal gevorderde darmkanker verbetert de loco-regionale controlegraad. Dit voordeel wordt duidelijker in de subgroep van patiënten met pT4-darmkanker.

Date

11 Sep 2022

Session

Proffered Paper session 1: GI, lower digestive

Presenters

Alvaro Arjona-Sanchez

Citation

Annals of Oncology (2022) 33 (suppl_7): S136-S196. 10.1016/annonc/annonc1048

Authors

A. Arjona-Sanchez1, M.T. Cano-Osuna2, A. Gutierrez3, J.J. Segura4, E. Perez5, V. concepcion6, S. Sanchez7, A. Garcia8, I. Prieto9, P. Barrios Sanchez10, J. Torres11, M. Ramirez12, A. Prada13, J. Carrasco14, M. Artiles15, P. Villarejo16, G. Ortega17, E. Boldo18, E. Aranda19, S. Rufian1

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Abstract 314O

Background

Peritoneal metastasis in locally advanced colon cancer (T4 stage) is estimated around 25% at 3 years from surgical resection with a poor prognosis. There is controversy about the results using prophylactic hyperthermic intraperitoneal chemotherapy (HIPEC) in this group of patients. We led a randomized controlled trial to determine the efficacy and safety of adjuvant HIPEC in patients with locally advanced colon cancer.

Methods

We did an open-label, randomized phase III study in 17 hospitals in Spain. Eligible patients were aged 18-75 years and had locally advanced primary colorectal cancer diagnosed preoperatively (cT4NxM0). Patients were randomly assigned (1:1) to surgery or surgery plus HIPEC (mitomycin C 30 mg/m2 during 60 minutes), both followed by systemic adjuvant chemotherapy. Randomisation was done via a web-based system, with stratification by treatment centre and gender. The primary outcome was 3 years loco-regional control rate, defined as the time from treatment to peritoneal disease recurrence or death form any cause, analysed by intention to treat (ITT). DFS and OS were secondary endpoints.

Results

Between November 2015 and January 2021 184 patients were recruited and randomized (89 experimental vs. 95 control). The median of follow-up was 36 (IQR 27-36) months. Demographic, tumour features, surgical management and final pathology reports were similar between both groups. The loco-regional control (LC) was improved in the experimental arm (35,3 ± 0.4 vs. 33.2 ± 0.8 months) with a 3 years LC rate of 97% vs. 87% (p = 0.025). No differences were observed in DFS and OS. The pT4 subgroup showed a clear benefit of LC in the HIPEC arm. No differences in morbidity were observed between groups.

Conclusions

The addition of hyperthermic intraperitoneal chemotherapy with mitomycin C to a complete surgical resection for locally advanced colon cancer improves the loco-regional control rate. This benefit becomes more evident in the subgroup of patients with pT4 colon cancer.

Clinical trial identification

NCT02614534.

Editorial acknowledgement

Legal entity responsible for the study

IMIBIC Maimonides Biomedical research Institute cordoba, Spain. Universitary Hospital Reina Sofia, Cordoba, Spain.

Funding

FIBICO (Biomedical Research Foundation, Cordoba) and Spanish Surgeon's Association (AEC).

Disclosure

All authors have declared no conflicts of interest.

Review
 
2022 Jun 14;11(12):3406.
 doi: 10.3390/jcm11123406.

Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Colorectal Peritoneal Metastases: A Summary of Key Clinical Trials

Affiliations 
Free PMC article

Abstract

The peritoneal cavity is a common site of metastatic spread from colorectal cancer (CRC). Patients with peritoneal metastases (PM) often have aggressive underlying tumor biology and poor survival. While only a minority of patients with CRC have potentially resectable disease, the high overall incidence of CRC makes management of PM a common clinical problem. In this population, cytoreductive surgery (CRS)-hyperthermic intraperitoneal chemotherapy (HIPEC) is the only effective therapy for appropriately selected patients. In this narrative review, we summarize the existing literature on CRS-HIPEC in colorectal PM. Recent prospective clinical trials have shown conflicting evidence regarding the benefit of HIPEC perfusion in addition to CRS. Current strategies to prevent PM in those at high-risk have been shown to be ineffective. Herein we will provide a framework for clinicians to understand and apply these data to treat this complex disease presentation.

Keywords: colorectal peritoneal carcinomatosis; cytoreductive surgery; hyperthermic intraperitoneal chemotherapy (HIPEC).

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
 
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5. Conclusions

Colorectal PM is a clinical problem commonly encountered in practice, which requires evaluation and management at specialized centers by experienced clinicians. Attention to proper patient selection, in line with recommendations established in the Chicago consensus, is paramount to success []. The studies described in this review show that adjuvant HIPEC and delayed second-look surgery using 30 min of intraperitoneal oxaliplatin are ineffective strategies to reduce PM/recurrence and improve survival in patients with CRC PM. Although early data supported CRS-HIPEC, results from the recent PRODIGE 7 study question the added benefit of HIPEC for this treatment strategy. These studies confirm the benefit of CRS, which should be considered the standard of care. Although many methodological critiques of PRODIGE 7 exist, the onus now appears to be on HIPEC enthusiasts to develop future trials required to resolve criticisms of the study and demonstrate any potential survival benefit of HIPEC for CRC PM.

Abbreviations

Colorectal cancer (CRC); peritoneal metastases (PM); cytoreductive surgery (CRS); hyperthermic intraperitoneal chemotherapy (HIPEC); completeness of cytoreduction (CCR); mitomycin C (MMC); randomized control trial (RCT); 5-fluorouracil (5-FU); overall survival (OS); peritoneal carcinomatosis index (PCI); circulating tumor DNA (ctDNA).

Funding Statement

This research received no external funding.

Author Contributions

Conceptualization, K.M.T. and S.H.P.; methodology, K.M.T. and S.H.P.; software, K.M.T.; resources, K.M.T. and M.C.M.; writing—original draft preparation, K.M.T., M.C.M. and S.H.P.; writing—review & editing, K.M.T., M.C.M., D.S., J.J.S., G.C.W., S.A.A. and S.H.P.; visualization, K.M.T.; supervision, S.A.A. and S.H.P.; project administration, K.M.T. and S.H.P. All authors have read and agreed to the published version of the manuscript.

Informed Consent Statement

Patient consent was waived as a review of existing publicly available literature.

Conflicts of Interest

The authors declare no conflict of interest.

Footnotes

Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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