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Effect of 5-Fluoro-Uracile + Oxaliplatin chemotherapy on the histological response of PEritoneal and hePatIc corectal metasTases in a mOuse model: PEPITO experimental study

Published:November 17, 2022DOI:https://doi.org/10.1016/j.ejso.2022.11.097

      Abstract

      Background

      The histological responses (HRs) after systemic chemotherapy should be used to determine the optimal management of patients with peritoneal and liver metastasis from colorectal cancer (cPM, cLM), in curative intent. We aimed to compare HRs of cPM and cLM in metastatic mice model after chemotherapy.

      Methods

      Colon carcinoma CT26-luc cells were transplanted into syngeneic BALB/c mice by intraperitoneal (leading to cPM), intrasplenic (leading to cLM), or intraperitoneal + intrasplenic (leading to cPM cLM) injections and follow up using bioluminescence during 21 days. Bi-chemotherapeutic treatment (5-fluorouracil at D11, D17, and D20, and oxaliplatin at D13 and D19) was administered. The peritoneal cancer index (PCI) and HRs using Peritoneal Regression Grading Score (PRGS) and Tumor Regression Grade (TRG) classifications were analyzed at day 21.

      Results

      Unlike bioluminescence rate, PCI was reduced after chemotherapy in all treated groups with cPM comparatively to controls (33 ± 9.5 vs. 19.8 ± 5, p = 0.002 for cPM groups; 37.7 ± 3.6 vs. 25.2 ± 10.8, p = 0.0003 for the cPM + cLM groups). The complete or major HR rates were higher in all treated groups compared to the non-treated mice (cPM, 2.29 ± 0.55 vs. 3.56 ± 1.01; cLM, 2.43 ± 1.89 vs. 4.86 ± 0.378; cPM + cLM, 2.73 ± 1.03 and 2.2 ± 0.65 vs. 3.79 ± 0.75 and 4.36 ± 0.43). The complete or major HR rates after chemotherapy were similar across the metastatic sites in 60% for cPM + cLM group.

      Conclusions

      The efficacy of chemotherapeutic treatment did not differ between the metastatic sites. Murine models are suitable in histological analyses to study tumor development and regression but clinical study will be performed to confirm these results.

      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.
        CA Cancer J Clin. 2018; 68: 394-424
        • de Cuba E.M.V.
        • Kwakman R.
        • Knol D.L.
        • Bonjer H.J.
        • Meijer G.A.
        • Te Velde E.A.
        Cytoreductive surgery and HIPEC for peritoneal metastases combined with curative treatment of colorectal liver metastases: systematic review of all literature and meta-analysis of observational studies.
        Cancer Treat Rev. 2013; 39: 321-327
        • Thomassen I.
        • van Gestel Y.R.
        • Lemmens V.E.
        • de Hingh I.H.
        Incidence, prognosis, and treatment options for patients with synchronous peritoneal carcinomatosis and liver metastases from colorectal origin.
        Dis Colon Rectum. 2013; 56: 1373-1380
        • Abdalla E.K.
        • Vauthey J.N.
        • Ellis L.M.
        • Ellis V.
        • Pollock R.
        • Broglio K.R.
        • et al.
        Recurrence and outcomes following hepatic resection, radiofrequency ablation, and combined resection/ablation for colorectal liver metastases.
        Ann Surg. 2004; 239 (; discussion 825-827): 818-825
        • Kianmanesh R.
        • Scaringi S.
        • Sabate J.M.
        • Castel B.
        • Pons-Kerjean N.
        • Coffin B.
        • et al.
        Iterative cytoreductive surgery associated with hyperthermic intraperitoneal chemotherapy for treatment of peritoneal carcinomatosis of colorectal origin with or without liver metastases.
        Ann Surg. 2007; 245: 597-603
        • Adileh M.
        • Mor E.
        • Assaf D.
        • Benvenisti H.
        • Laks S.
        • Ben-Yaacov A.
        • et al.
        Perioperative and oncological outcomes of combined hepatectomy with complete cytoreduction and hyperthermic intraperitoneal chemotherapy for metastatic colorectal cancer.
        Ann Surg Oncol. 2021; 28: 3320-3329
        • Lo Dico R.
        • Faron M.
        • Yonemura Y.
        • Glehen O.
        • Pocard M.
        • Sardi A.
        • et al.
        Combined liver resection and cytoreductive surgery with HIPEC for metastatic colorectal cancer: results of a worldwide analysis of 565 patients from the Peritoneal Surface Oncology Group International (PSOGI).
        Eur J Surg Oncol. 2021; 47: 89-100
        • Mandard A.M.
        • Dalibard F.
        • Mandard J.C.
        • Marnay J.
        • Henry-Amar M.
        • Petiot J.F.
        • et al.
        Pathologic assessment of tumor regression after preoperative chemoradiotherapy of esophageal carcinoma.
        Clinicopathologic correlations. Cancer. 1994; 73: 2680-2686
        • Rubbia-Brandt L.
        • Giostra E.
        • Brezault C.
        • Roth A.D.
        • Andres A.
        • Audard V.
        • et al.
        Importance of histological tumor response assessment in predicting the outcome in patients with colorectal liver metastases treated with neo-adjuvant chemotherapy followed by liver surgery.
        Ann Oncol. 2007; 18: 299-304
        • Solass W.
        • Sempoux C.
        • Detlefsen S.
        • Carr N.J.
        • Bibeau F.
        Peritoneal sampling and histological assessment of therapeutic response in peritoneal metastasis: proposal of the Peritoneal Regression Grading Score (PRGS).
        Pleura Peritoneum. 7 juin 2016; 1 ([cité 26 janv 2021]) (Disponible sur:): 99-107
        • Taibi A.
        • Lo Dico R.
        • Kaci R.
        • Naneix A.L.
        • Malgras B.
        • Mathonnet M.
        • et al.
        Evaluation of a new histological grading system for assessing the response to chemotherapy of peritoneal metastases from colorectal cancer: a mouse model study.
        Eur J Surg Oncol. 2020; 46: 160-165
        • Taibi A.
        • Lo Dico R.
        • Kaci R.
        • Naneix A.L.
        • Mathonnet M.
        • Pocard M.
        Impact of preoperative chemotherapy on the histological response of patients with peritoneal metastases from colorectal cancer according to peritoneal regression grading score (PRGS) and TRG Impact de la chimiothérapie préopératoire sur la réponse histologique des patients présentant des métastases péritonéales du cancer colorectal selon le score de gradation de régression péritonéale (PRGS) et TRG.
        Surg Oncol. 2020; 33: 158-163
        • Rubbia-Brandt L.
        • Giostra E.
        • Brezault C.
        • Roth A.D.
        • Andres A.
        • Audard V.
        • et al.
        Importance of histological tumor response assessment in predicting the outcome in patients with colorectal liver metastases treated with neo-adjuvant chemotherapy followed by liver surgery.
        Ann Oncol. 2007; 18: 299-304
        • Pocard M.
        • Mirshahi M.
        • Therwath A.
        The hallmarks of oligometastatic diseases: solution for the treatment dilemma.
        Surg Open Dig Adv Volume. June 2021; 2100012https://doi.org/10.1016/j.soda.2021.100012
        • Solass W.
        • Horvath P.
        • Struller F.
        • Königsrainer I.
        • Beckert S.
        • Königsrainer A.
        • et al.
        Functional vascular anatomy of the peritoneum in health and disease.
        Pleura Peritoneum. 2016; 1: 145-158
        • Sebagh M.
        • Allard M.A.
        • Bosselut N.
        • Dao M.
        • Vibert E.
        • Lewin M.
        • et al.
        Evidence of intermetastatic heterogeneity for pathological response and genetic mutations within colorectal liver metastases following preoperative chemotherapy.
        Oncotarget. 19 avr. 2016; 7: 21591-21600
        • Taibi A.
        • Albouys J.
        • Jacques J.
        • Perrin M.L.
        • Yardin C.
        • Durand Fontanier S.
        • et al.
        Comparison of implantation sites for the development of peritoneal metastasis in a colorectal cancer mouse model using non-invasive bioluminescence imaging.
        PLoS One. 2019; 14e0220360
        • Lim C.
        • Broqueres-You D.
        • Brouland J.P.
        • Merkulova-Rainon T.
        • Faussat A.M.
        • Hilal R.
        • et al.
        Hepatic ischemia-reperfusion increases circulating bone marrow-derived progenitor cells and tumor growth in a mouse model of colorectal liver metastases.
        J Surg Res. 2013; 184: 888-897
        • Taibi A.
        • Lo Dico R.
        • Kaci R.
        • Naneix A.L.
        • Malgras B.
        • Mathonnet M.
        • et al.
        Evaluation of a new histological grading system for assessing the response to chemotherapy of peritoneal metastases from colorectal cancer: a mouse model study.
        Eur J Surg Oncol. 2020; 46: 160-165
        • Khalil A.A.
        • Jameson M.J.
        • Broaddus W.C.
        • Lin P.S.
        • Dever S.M.
        • Golding S.E.
        • et al.
        The influence of hypoxia and pH on bioluminescence imaging of luciferase-transfected tumor cells and xenografts.
        Int J Mol Imag. 2013; 2013287697
        • Hoffman R.
        Green fluorescent protein imaging of tumour growth, metastasis, and angiogenesis in mouse models.
        Lancet Oncol. sept. 2002; 3: 546-556
        • Solass W.
        • Horvath P.
        • Struller F.
        • Königsrainer I.
        • Beckert S.
        • Königsrainer A.
        • et al.
        Functional vascular anatomy of the peritoneum in health and disease.
        Pleura Peritoneum. 2016; 1: 145-158
        • Passot G.
        • You B.
        • Boschetti G.
        • Fontaine J.
        • Isaac S.
        • Decullier E.
        • et al.
        Pathological response to neoadjuvant chemotherapy: a new prognosis tool for the curative management of peritoneal colorectal carcinomatosis.
        Ann Surg Oncol. 2014; 21: 2608-2614
        • Gervaz P.
        • Rubbia-Brandt L.
        • Andres A.
        • Majno P.
        • Roth A.
        • Morel P.
        • et al.
        Neoadjuvant chemotherapy in patients with stage IV colorectal cancer: a comparison of histological response in liver metastases, primary tumors, and regional lymph nodes.
        Ann Surg Oncol. 2010; 17: 2714-2719
        • Vigano L.
        • Corleone P.
        • Darwish S.S.
        • Turri N.
        • Famularo S.
        • Viggiani L.
        • et al.
        Hepatic and extrahepatic colorectal metastases have discordant responses to systemic therapy. Pathology data from patients undergoing simultaneous resection of multiple tumor sites.
        Cancers (Basel). 2021; 13: 464