5-Fluorouracil induced liver toxicity in patients with colorectal cancer: role of computed tomography texture analysis as a potential biomarker
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To assess if CT texture analysis (TA) can serve as a biomarker of liver toxicity in patients with colorectal cancer treated with 5-fluorouracil (5-FU)-based chemotherapy.
In this IRB-approved, HIPAA-compliant retrospective study, patients with colorectal cancer treated with 5-FU-based regimens during 2008–2010 were identified from institutional electronic database. Total 43 patients (23 women; mean age 56 years) with normal baseline liver function tests (LFTs), availability of baseline (pre-chemotherapy) and first follow-up CT (median 1.7 months, interquartile range (IQR) 1.5–2.5) performed during chemotherapy were included. Two single-slice ROI of right and left liver lobe were obtained on baseline and first follow-up CT for TA. Texture features [mean, entropy, kurtosis, skewness, mean of positive pixel, standard deviation (SD)] were extracted using a commercially available software (TexRAD; Feedback Medical Ltd, Cambridge, UK). Changes in texture parameters between baseline and follow-up CT were evaluated with Wilcoxon signed-rank test for patients with and without LFT elevation during chemotherapy.
Patients with LFT elevation (n = 34; 79%) showed significantly different mean, entropy, skewness, and SD (p values range 0.007–0.047) between baseline and first follow-up CT. No significant changes in features were observed in patients without LFT elevation (n = 9; 21%). In 19 patients (56%), first follow-up CT was performed before elevation of LFTs was observed.
This proof-of-concept study shows that there are early changes in liver texture on first follow-up CT in patients with LFT elevation during 5-FU-based chemotherapy for colorectal cancer. In more than 50% of cases, these changes occur before LFT elevation becomes evident on blood tests.
KeywordsTomography X-ray computed Chemotherapy Liver Drug-induced liver injury
Compliance with ethical standards
Conflict of interest
Francesco Alessandrino, Sonia Sahu, Gisele Cruz, Lei Qin, Michael H. Rosenthal and Jeffrey A. Meyerhardt, no related financial relationships to disclose. Atul B. Shinagare Consultant, Arog Pharmaceuticals; research funding, GTx Inc.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
For this type of study formal consent is not required.
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