Dataset Information

Identifying Genetic Mutation Status in Patients with Colorectal Cancer Liver Metastases Using Radiomics-Based Machine-Learning Models.

ABSTRACT: For patients with colorectal cancer liver metastases (CRLM), the genetic mutation status is important in treatment selection and prognostication for survival outcomes. This study aims to investigate the relationship between radiomics imaging features and the genetic mutation status (KRAS mutation versus no mutation) in a large multicenter dataset of patients with CRLM and validate these findings in an external dataset. Patients with initially unresectable CRLM treated with systemic therapy of the randomized controlled CAIRO5 trial (NCT02162563) were included. All CRLM were semi-automatically segmented in pre-treatment CT scans and radiomics features were calculated from these segmentations. Additionally, data from the Netherlands Cancer Institute (NKI) were used for external validation. A total of 255 patients from the CAIRO5 trial were included. Random Forest, Gradient Boosting, Gradient Boosting + LightGBM, and Ensemble machine-learning classifiers showed AUC scores of 0.77 (95%CI 0.62-0.92), 0.77 (95%CI 0.64-0.90), 0.72 (95%CI 0.57-0.87), and 0.86 (95%CI 0.76-0.95) in the internal test set. Validation of the models on the external dataset with 129 patients resulted in AUC scores of 0.47-0.56. Machine-learning models incorporating CT imaging features could identify the genetic mutation status in patients with CRLM with a good accuracy in the internal test set. However, in the external validation set, the models performed poorly. External validation of machine-learning models is crucial for the assessment of clinical applicability and should be mandatory in all future studies in the field of radiomics.

SUBMITTER: Wesdorp N

PROVIDER: S-EPMC10705206 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature

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Identifying Genetic Mutation Status in Patients with Colorectal Cancer Liver Metastases Using Radiomics-Based Machine-Learning Models.

Wesdorp Nina N Zeeuw Michiel M van der Meulen Delanie D van 't Erve Iris I Bodalal Zuhir Z Roor Joran J van Waesberghe Jan Hein JH Moos Shira S van den Bergh Janneke J Nota Irene I van Dieren Susan S Stoker Jaap J Meijer Gerrit G Swijnenburg Rutger-Jan RJ Punt Cornelis C Huiskens Joost J Beets-Tan Regina R Fijneman Remond R Marquering Henk H Kazemier Geert G On Behalf Of The Dutch Colorectal Cancer Group Liver Expert Panel

Cancers 20231129 23

For patients with colorectal cancer liver metastases (CRLM), the genetic mutation status is important in treatment selection and prognostication for survival outcomes. This study aims to investigate the relationship between radiomics imaging features and the genetic mutation status (KRAS mutation versus no mutation) in a large multicenter dataset of patients with CRLM and validate these findings in an external dataset. Patients with initially unresectable CRLM treated with systemic therapy of th ...[more]

PMID: 38067353

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Project description:BackgroundMetastatic complications are a major cause of cancer-related morbidity, with up to 40% of cancer patients experiencing at least one brain metastasis. Earlier detection may significantly improve patient outcomes and overall survival. We investigated machine learning (ML) models for early detection of brain metastases based on diffusion weighted imaging (DWI) radiomics.MethodsLongitudinal diffusion imaging from 116 patients previously treated with stereotactic radiosurgery (SRS) for brain metastases were retrospectively analyzed. Clinical contours from 600 metastases were extracted from radiosurgery planning computed tomography, and rigidly registered to corresponding contrast enhanced-T1 and apparent diffusion coefficient (ADC) maps. Contralateral contours located in healthy brain tissue were used as control. The dataset consisted of (I) radiomic features using ADC maps, (II) radiomic feature change calculated using timepoints before the metastasis manifested on contrast enhanced-T1, (III) primary cancer, and (IV) anatomical location. The dataset was divided into training and internal validation sets using an 80/20 split with stratification. Four classification algorithms [Linear Support Vector Machine (SVM), Random Forest (RF), AdaBoost, and XGBoost] underwent supervised classification training, with contours labeled either 'control' or 'metastasis'. Hyperparameters were optimized towards balanced accuracy. Various model metrics (receiver operating characteristic curve area scores, accuracy, recall, and precision) were calculated to gauge performance.ResultsThe radiomic and clinical data set, feature engineering, and ML models developed were able to identify metastases with an accuracy of up to 87.7% on the training set, and 85.8% on an unseen test set. XGBoost and RF showed superior accuracy (XGBoost: 0.877±0.021 and 0.833±0.47, RF: 0.823±0.024 and 0.858±0.045) for training and validation sets, respectively. XGBoost and RF also showed strong area under the receiver operating characteristic curve (AUC) performance on the validation set (0.910±0.037 and 0.922±0.034, respectively). AdaBoost performed slightly lower in all metrics. SVM model generalized poorly with the internal validation set. Important features involved changes in radiomics months before manifesting on contrast enhanced-T1.ConclusionsThe proposed models using diffusion-based radiomics showed encouraging results in differentiating healthy brain tissue from metastases using clinical imaging data. These findings suggest that longitudinal diffusion imaging and ML may help improve patient care through earlier diagnosis and increased patient monitoring/follow-up. Future work aims to improve model classification metrics, robustness, user-interface, and clinical applicability.

Project description:Abstract Background Early diagnosis of liver metastasis is of great importance for enhancing the survival of colorectal adenocarcinoma (CAD) patients, and the combined use of a single biomarker in a classier model has shown great improvement in predicting the metastasis of several types of cancers. However, it is little reported for CAD. This study therefore aimed to screen an optimal classier model of CAD with liver metastasis and explore the metastatic mechanisms of genes when applying this classier model. Methods The differentially expressed genes between primary CAD samples and CAD with metastasis samples were screened from the Moffitt Cancer Center (MCC) dataset GSE131418. The classification performances of six selected algorithms, namely, LR, RF, SVM, GBDT, NN, and CatBoost, for classification of CAD with liver metastasis samples were compared using the MCC dataset GSE131418 by detecting their classification test accuracy. In addition, the consortium datasets of GSE131418 and GSE81558 were used as internal and external validation sets to screen the optimal method. Subsequently, functional analyses and a drug‐targeted network construction of the feature genes when applying the optimal method were conducted. Results The optimal CatBoost model with the highest accuracy of 99%, and an area under the curve of 1, was screened, which consisted of 33 feature genes. A functional analysis showed that the feature genes were closely associated with a “steroid metabolic process” and “lipoprotein particle receptor binding” (eg APOB and APOC3). In addition, the feature genes were significantly enriched in the “complement and coagulation cascade” pathways (eg FGA, F2, and F9). In a drug‐target interaction network, F2 and F9 were predicted as targets of menadione. Conclusion The CatBoost model constructed using 33 feature genes showed the optimal classification performance for identifying CAD with liver metastasis. APOB, APOC3, FGA, F2, F9, and NKX2‐3 were potential biomarkers for classification of CAD with liver metastasis. Menadione might be a promising anti‐metastatic drug of CAD cells through functioning its role at sites of F2 and F9. CatBoost model constructed by 33 feature genes showed the optimal classification performance for identifying CAD liver metastasis.

Dataset Information

Identifying Genetic Mutation Status in Patients with Colorectal Cancer Liver Metastases Using Radiomics-Based Machine-Learning Models.

Publications

Identifying Genetic Mutation Status in Patients with Colorectal Cancer Liver Metastases Using Radiomics-Based Machine-Learning Models.

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