Abstract
Entropy is a promising quantitative imaging biomarker for characterizing cancer imaging phenotype. Entropy has been associated with tumor gene expression, tumor metabolism, tumor stage, patient prognosis, and treatment response. Our hypothesis states that tumor-specific biomarkers such as entropy should be correlated between synchronous metastases. Therefore, a significant proportion of the variance of entropy should be attributed to the malignant process. We analyzed 112 patients with matched/paired synchronous metastases (SM#1 and SM#2) prospectively enrolled in the MOSCATO-01 clinical trial. Imaging features were extracted from Regions Of Interest (ROI) delineated on CT-scan using TexRAD software. We showed that synchronous metastasis entropy was correlated across 5 Spatial Scale Filters: Spearman’s Rho ranged between 0.41 and 0.59 (P = 0.0001, Bonferroni correction). Multivariate linear analysis revealed that entropy in SM#1 is significantly associated with (i) primary tumor type; (ii) entropy in SM#2 (same malignant process); (iii) ROI area size; (iv) metastasis site; and (v) entropy in the psoas muscle (reference tissue). Entropy was a logarithmic function of ROI area in normal control tissues (aorta, psoas) and in mathematical models (P < 0.01). We concluded that entropy is a tumor-specific metric only if confounding factors are corrected.
Highlights
Tumors exhibit an extensive genetic and phenotypic variation
Our study proposed a methodology for exploration of the biological meaning of the entropy imaging feature as measured on clinical CT-scans
We demonstrated that entropy is specific to a given malignant process, but is influenced by confounding factors
Summary
Tumors exhibit an extensive genetic and phenotypic variation. This translates to a heterogeneity that can be observed at different scales: between patients, across metastases from the same primary tumor, or within a single metastasis. An increasing body of studies in the literature are proving the potential clinical value of Shannon’s entropy calculated after a Laplacian of Gaussian transformation using the settings included in the TexRAD software[11,12,13,14,15,16,17,18,19] These studies have depicted that entropy is associated with staging[11, 12], outcome[13,14,15,16], expression of molecular pathways such as tumor metabolism[11, 12], and treatment response[11,12,13,14,15, 17,18,19] in esophageal, lung, colorectal, and head and neck cancers. This need has arisen with the advent of precision medicine and new drugs associated with atypical patterns of response that get misclassified by conventional response criteria[20,21,22,23,24,25,26,27,28]
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