Abstract

e15086 Background: Metastatic Colorectal cancer (mCRC) is the 2nd cause of cancer death worldwide. Repeated cycles of therapies, combined with surgery in oligo-metastatic cases, are the therapeutic standard in mCRC. However, this strategy is seldom resolutive. Different lesions in in the same patient could have different responses to systemic therapy. Recently, CT texture analysis (CTTA) had been shown to potentially provide with prognostic and predictive markers, overcoming the limitations of biopsy sampling in defining tumor heterogeneity. The aim of this study is to use CT texture analysis (CTTA) to identify imaging biomarkers of HER2+ mCRC able to predict lesion response to therapy. Methods: The dataset is composed of 39 extended RAS wild type patients with amplified HER2 mCRC enrolled in the HERACLES trial (NCT03225937) that received either a lapatinib+trastuzumab treatment (n = 23) or a pertuzumab+ trastuzumab-emtansine treatment (n = 16). All patients underwent CT examination every 8 weeks, until disease progression. All mCRC on baseline CT were semi-automatically segmented and quantitative features extracted: size, mean, percentiles, 28 texture features. A logistic regression model was created using: (i) the whole dataset of mCRC as training and test set and (ii) 100 randomly generated training sets (with 70% of responder (R+) mCRC and an equal number of non-responder (R-) mCRC), and 100 test sets including the remaining mCRC. A mCRC was classified as R+ if size decreased (-10%) or was stable (±10%); as R- if size increased (+10%), during subsequent CT scans. Results: A total of 199 metastases were included (75R+ and 124R-). The training set was composed of 53R+ and 53R- mCRC and the test set of 22R+ and 71R- mCRC. Using the whole dataset, the model reached an AUC = 0.82 (sensitivity = 84%, specificity = 70%), while it reached a mean AUC of 0.70 (sensitivity = 68%, specificity = 67%) within the 100 repetitions. Conclusions: CTTA might help in stratifying different behaviors of mCRC, opening the way for lesion-specific therapies, with conceivable cost and life savings. Further extended analysis is needed to better characterize and validate predictive value of these biomarkers.

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