Hepatotoxicities Induced by Neoadjuvant Chemotherapy in Colorectal Cancer Liver Metastases: Distinguishing the True From the False

Marie Desjardin; Benjamin Bonhomme; Brigitte Le Bail; Serge Evrard; Véronique Brouste; Gregoire Desolneux; Marianne Fonck; Yves Bécouarn; Dominique Béchade

doi:10.1177/1179554918825450

Hepatotoxicities Induced by Neoadjuvant Chemotherapy in Colorectal Cancer Liver Metastases: Distinguishing the True From the False

Clin Med Insights Oncol. 2019 Jan 22:13:1179554918825450. doi: 10.1177/1179554918825450. eCollection 2019.

Authors

Marie Desjardin¹, Benjamin Bonhomme², Brigitte Le Bail³, Serge Evrard¹, Véronique Brouste⁴, Gregoire Desolneux¹, Marianne Fonck¹, Yves Bécouarn¹, Dominique Béchade¹

Affiliations

¹ Digestive Tumours Unit, Institut Bergonié, Bordeaux, France.
² Department of Anatomopathology, Institut Bergonié, Bordeaux, France.
³ Department of Anatomopathology, University Hospital, Bordeaux, France.
⁴ Clinical and Epidemiological Research Unit, Institut Bergonié, Bordeaux, France.

Abstract

Background: Pre-operative chemotherapy for colorectal liver metastasis (CRLM) is thought to be the cause of hepatotoxicity of non-tumoural parenchyma. Studies on hepatotoxicity are contradictory. We investigated the impact of a single-line pre-operative chemotherapy on non-tumoural liver analysed by an expert hepatico-pancreatico-biliary pathologist, and the consequences on surgical outcomes.

Patients and methods: Patients operated for CRLM, after a pure first-line pre-operative chemotherapy, were retrospectively included. Two comparative histopathological analyses were performed for vascular toxicity and steatohepatitis.

Results: Between 2003 and 2015, 147 patients were included. Chemotherapy was based on oxaliplatin (40.1%), irinotecan (55.8%), or both (4.1%). The expert pathologist described 38.8% of vascular lesions including dilation, nodular regeneration, and peliosis. In multivariate analysis, vascular lesions correlated to male sex (P = .01), pre-operative platelets <150 g/L (P = .04), and aspartate aminotransferase to platelet ratio index (APRI) score >0.36 (P = .02). Steatohepatitis was observed in 15 patients (10.2%), more frequently after irinotecan (14.8% vs 3.4%, P = .01; odds ratio [OR] = 7.3; 95% confidence interval [CI] = [1.5-34.7]), and for patients with body mass index (BMI) >25 kg/m² (P = .004; OR = 10.0; 95% CI = [2.1-47.5]). A total of 29 patients (19.7%) developed major complications with 2 risk factors: portal vein obstruction (PVO) and septic surgery. Reproducibility assessment of steatohepatitis and dilated lesions by 2 pathologists showed moderate agreement (Kappa score 0.53 and 0.54, respectively).

Conclusions: There is a probable association between non-alcoholic steatohepatitis (NASH) and irinotecan. Oxaliplatin seems to lead to higher vascular lesions. Except in the presence of pre-existent comorbidities, liver toxicities should not restrain the use of pre-operative chemotherapy prior to parenchymal-sparing surgery.

Keywords: colorectal cancer; hepatic metastasis; hepatotoxicity; neoadjuvant chemotherapy; steatohepatitis; vascular toxicity.