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

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: Chemotherapy; Colorectal cancer; Liver metastases; PRGS; Peritoneal metastases; TRG.