Abstract

Simple SummaryIn locally advanced rectal cancer (LARC), a minority of patients presents a pathological complete response (pCR) after neoadjuvant chemoradiotherapy (CRT). In this sub-population, organ preservation could be proposed without compromising overall survival. Using a robust neural network based statistical approach, correction of imbalanced data and inter-center variability, a radiomics-based model was externally validated with a balanced accuracy of 85.5%. This model efficiently predicted the patients with a pCR in an external cohort and could be used to select the patients eligible for organ preservation.Objective: Our objective was to develop a radiomics model based on magnetic resonance imaging (MRI) and contrast-enhanced computed tomography (CE-CT) to predict pathological complete response (pCR) to neoadjuvant treatment in locally advanced rectal cancer (LARC). Material: All patients treated for a LARC with neoadjuvant CRT and subsequent surgery in two separate institutions between 2012 and 2019 were considered. Both pre-CRT pelvic MRI and CE-CT were mandatory for inclusion. The tumor was manually segmented on the T2-weighted and diffusion axial MRI sequences and on CE-CT. In total, 88 radiomic parameters were extracted from each sequence using the Miras© software, with a total of 822 features by patient. The cohort was split into training (Institution 1) and testing (Institution 2) sets. The ComBat and Synthetic Minority Over-sampling Technique (SMOTE) approaches were used to account for inter-institution heterogeneity and imbalanced data, respectively. We selected the most predictive characteristics using Spearman’s rank correlation and the Area Under the ROC Curve (AUC). Five pCR prediction models (clinical, radiomics before and after ComBat, and combined before and after ComBat) were then developed on the training set with a neural network approach and a bootstrap internal validation (n = 1000 replications). A cut-off maximizing the model’s performance was defined on the training set. Each model was then evaluated on the testing set using sensitivity, specificity, balanced accuracy (Bacc) with the predefined cut-off. Results: Out of the 124 included patients, 14 had pCR (11.3%). After ComBat harmonization, the radiomic and the combined models obtained a Bacc of 68.2% and 85.5%, respectively, while the clinical model and the pre-ComBat combined achieved respective Baccs of 60.0% and 75.5%. Conclusions: After correction of inter-site variability and imbalanced data, addition of radiomic features enhances the prediction of pCR after neoadjuvant CRT in LARC.

Highlights

  • Colorectal cancer is one of the most common cancers worldwide, with breast and lung cancer, and is frequent in the Western population: in Europe alone, for the year 2020, the estimated incidence of rectal cancer was 113,684 new cases [1]

  • The clinical model achieved a balanced accuracy (Bacc) of 60.0% with 88.0% of false positives among patients classified at high chance of pathological complete response (pCR)

  • We evaluated several pCR prediction models in patients treated with neoadjuvant CRT for a locally advanced rectal cancer (LARC)

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Summary

Introduction

Colorectal cancer is one of the most common cancers worldwide, with breast and lung cancer, and is frequent in the Western population: in Europe alone, for the year 2020, the estimated incidence of rectal cancer was 113,684 new cases [1]. The five years overall survival reaches approximately 55%, and colorectal represents the second leading cause of cancer death worldwide. It is hypothesized that patients with a complete response after neoadjuvant CRT could benefit from a wait-and-see strategy and avoid the morbidity of surgery [6,7] without compromising survival outcomes [8–10]. Predicting this complete response to neo-adjuvant treatment is an unmet need in the management of LARC

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