Abstract
BackgroundTo evaluate proton-density fat-fraction (PDFF) and intravoxel incoherent motion (IVIM) techniques, and human 25-hydroxyvitamin D3 (25OH-VitD3) levels, as potential biomarkers in patients with colorectal cancer with liver metastasis (CRCLM). Changes were compared with those related to chemotherapy-associated steatohepatitis (CASH) and sinusoidal obstruction syndrome (SOS).Methods63 patients with pathologically confirmed colorectal adenocarcinoma received 4–6 courses of NC before liver resection and underwent magnetic resonance imaging (MRI) with iterative decomposition of water and fat with echo asymmetry and least-squares estimation quantification and IVIM sequences. Blood samples were analyzed using CTCAE. Pathological changes of liver tissues outside the metastases were assessed as the gold standard, and receiver operating characteristic (ROC) curves were analyzed.Results16 cases had CASH liver injury, 14 cases had SOS changes, and 4 cases had CASH and SOS, and 7 showed no significant changes. Consistency between biochemical indices and pathological findings was poor (kappa = 0.246, p = 0.005). The areas under the ROC curve (AUCs) of ALT, AST, ALP, GGT, and TBIL were 0.571–0.691. AUCs of D, FF, and 25OH-VitD3 exceeded 0.8; when considering these markers together, sensitivity was 85.29% and specificity was 93.13%. ANOVA showed statistically significant differences among D, FF, and 25OH-VitD3 for different grades of liver injury (F = 4.64–26.5, p = 0.000–0.016).ConclusionsD, FF, and 25OH-VitD3 are biomarkers for accurate prediction of NC-induced liver injury in patients with CRCLM, while FF and 25OH-VitD3 might be beneficial to distinguish liver injury grades.Trial registrationCurrent Trials was retrospectively registered as ChiCTR1800015242 at Chinese Clinical Trial Registry on March 16, 2018.
Highlights
To evaluate proton-density fat-fraction (PDFF) and intravoxel incoherent motion (IVIM) techniques, and human 25-hydroxyvitamin D3 (25OH-VitD3) levels, as potential biomarkers in patients with colorectal cancer with liver metastasis (CRCLM)
Extensive use of multiple chemotherapeutic agents has resulted in consensus regarding distinct hepatotoxicity patterns, including chemotherapy-associated steatohepatitis (CASH) and sinusoidal obstruction syndrome (SOS), which are associated with specific drugs [7,8,9]. 5-Fluorouracil (5-FU) is a fluoropyrimidine antimetabolite, and it induces impaired-oxidation and accumulation of fatty acids and causes hepatic steatosis [10, 11]
63 subjects diagnosed with CRCLM were included
Summary
To evaluate proton-density fat-fraction (PDFF) and intravoxel incoherent motion (IVIM) techniques, and human 25-hydroxyvitamin D3 (25OH-VitD3) levels, as potential biomarkers in patients with colorectal cancer with liver metastasis (CRCLM). Changes were compared with those related to chemotherapy-associated steatohepatitis (CASH) and sinusoidal obstruction syndrome (SOS). Colorectal cancer (CRC) is a leading cause of cancerrelated mortality in the world, with over 1.2 million new cases diagnosed each year [1]. Neoadjuvant chemotherapy (NC) provides an opportunity for cure with hepatic resection in selected patients with CLM. Extensive use of multiple chemotherapeutic agents has resulted in consensus regarding distinct hepatotoxicity patterns, including CASH and SOS, which are associated with specific drugs [7,8,9]. The related antibody-drug, including cetuximab and bevacizumab, were reported to cause no recognized hepatotoxicity in recent clinical trials [10, 13,14,15]
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