Abstract

BackgroundThe liver is one of the most frequent sites of metastases in rectal cancer. This study aimed to evaluate how the development of synchronous or metachronous liver metastasis and overall survival are impacted by baseline liver steatosis and chemotherapy-induced liver damage in rectal cancer patients.MethodsPatients diagnosed with stage II to IV rectal cancer between 2010 and 2016 in our province with suitable baseline CT scan were included. Data on cancer diagnosis, staging, therapy, outcomes and liver function were collected. CT scans were retrospectively reviewed to assess baseline steatosis (liver density < 48 HU and/or liver-to-spleen ratio < 1.1). Among patients without baseline steatosis and treated with neoadjuvant chemotherapy, chemotherapy-induced liver damage was defined as steatosis appearance, ≥ 10% liver volume increase, or significant increase in liver function tests.ResultsWe included 283 stage II to IV rectal cancer patients with suitable CT scan (41% females; mean age 68 ± 14 years). Steatosis was present at baseline in 90 (31.8%) patients, synchronous liver metastasis in 42 (15%) patients and metachronous liver metastasis in 26 (11%); 152 (54%) deaths were registered. The prevalence of synchronous liver metastasis was higher in patients with steatosis (19% vs 13%), while the incidence of metachronous liver metastasis was similar. After correcting for age, sex, stage, and year of diagnosis, steatosis was not associated with metachronous liver metastasis nor with overall survival. In a small analysis of 63 patients without baseline steatosis and treated with neoadjuvant chemotherapy, chemotherapy-induced liver damage was associated with higher incidence of metachronous liver metastasis and worse survival, results which need to be confirmed by larger studies.ConclusionsOur data suggest that rectal cancer patients with steatosis had a similar occurrence of metastases during follow-up, even if the burden of liver metastases at diagnosis was slightly higher, compatible with chance.

Highlights

  • The liver is one of the most frequent sites of metastases in rectal cancer

  • Since non-alcoholic fatty liver disease and metabolic syndrome are associated with increased incidence of colorectal cancer (CRC) [2, 3], the expected prevalence of liver steatosis in CRC patients is at least similar or possibly higher than that estimated in the general population

  • This liver side effect is described in patients with metastatic CRC [4, 5], who develop steatosis in 30–47% cases and steatohepatitis in about 20% of those cases treated with irinotecan [6, 7]

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Summary

Introduction

The liver is one of the most frequent sites of metastases in rectal cancer. This study aimed to evaluate how the development of synchronous or metachronous liver metastasis and overall survival are impacted by baseline liver steatosis and chemotherapy-induced liver damage in rectal cancer patients. Cancer patients have a strong risk of developing liver steatosis and steatohepatitis as a consequence of anticancer therapies, especially chemotherapy drugs such as 5-Fluorouracil, an anti-metabolite (anti-pyrimidine), and irinotecan, a cytotoxic anti-tumour molecule of the DNA topoisomerase inhibitor class. This liver side effect is described in patients with metastatic CRC [4, 5], who develop steatosis in 30–47% cases and steatohepatitis in about 20% of those cases treated with irinotecan [6, 7]. Personalized biomarkers to correctly stratify the risk of liver recurrence could be useful to improving the management of those patients

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