R. Leijenaar

Decoding tumour phenotype by noninvasive imaging using a quantitative radiomics approach.

Human cancers exhibit strong phenotypic differences that can be visualized noninvasively by medical imaging. Radiomics refers to the comprehensive quantification of tumour phenotypes by applying a large number of quantitative image features. Here we present a radiomic analysis of 440 features quantifying tumour image intensity, shape and texture, which are extracted from computed tomography data of 1,019 patients with lung or head-and-neck cancer. We find that a large number of radiomic features have prognostic power in independent data sets of lung and head-and-neck cancer patients, many of which were not identified as significant before. Radiogenomics analysis reveals that a prognostic radiomic signature, capturing intratumour heterogeneity, is associated with underlying gene-expression patterns. These data suggest that radiomics identifies a general prognostic phenotype existing in both lung and head-and-neck cancer. This may have a clinical impact as imaging is routinely used in clinical practice, providing an unprecedented opportunity to improve decision-support in cancer treatment at low cost.

Radiomics: Extracting more information from medical images using advanced feature analysis

Solid cancers are spatially and temporally heterogeneous. This limits the use of invasive biopsy based molecular assays but gives huge potential for medical imaging, which has the ability to capture intra-tumoural heterogeneity in a non-invasive way. During the past decades, medical imaging innovations with new hardware, new imaging agents and standardised protocols, allows the field to move towards quantitative imaging. Therefore, also the development of automated and reproducible analysis methodologies to extract more information from image-based features is a requirement. Radiomics--the high-throughput extraction of large amounts of image features from radiographic images--addresses this problem and is one of the approaches that hold great promises but need further validation in multi-centric settings and in the laboratory.

CT-based radiomic signature predicts distant metastasis in lung adenocarcinoma

BACKGROUND AND PURPOSE Radiomics provides opportunities to quantify the tumor phenotype non-invasively by applying a large number of quantitative imaging features. This study evaluates computed-tomography (CT) radiomic features for their capability to predict distant metastasis (DM) for lung adenocarcinoma patients. MATERIAL AND METHODS We included two datasets: 98 patients for discovery and 84 for validation. The phenotype of the primary tumor was quantified on pre-treatment CT-scans using 635 radiomic features. Univariate and multivariate analysis was performed to evaluate radiomics performance using the concordance index (CI). RESULTS Thirty-five radiomic features were found to be prognostic (CI>0.60, FDR<5%) for DM and twelve for survival. It is noteworthy that tumor volume was only moderately prognostic for DM (CI=0.55, p-value=2.77×10(-5)) in the discovery cohort. A radiomic-signature had strong power for predicting DM in the independent validation dataset (CI=0.61, p-value=1.79×10(-17)). Adding this radiomic-signature to a clinical model resulted in a significant improvement of predicting DM in the validation dataset (p-value=1.56×10(-11)). CONCLUSIONS Although only basic metrics are routinely quantified, this study shows that radiomic features capturing detailed information of the tumor phenotype can be used as a prognostic biomarker for clinically-relevant factors such as DM. Moreover, the radiomic-signature provided additional information to clinical data.

Stability of FDG-PET Radiomics features: an integrated analysis of test-retest and inter-observer variability.

Abstract Purpose. Besides basic measurements as maximum standardized uptake value (SUV)max or SUVmean derived from 18F-FDG positron emission tomography (PET) scans, more advanced quantitative imaging features (i.e. “Radiomics” features) are increasingly investigated for treatment monitoring, outcome prediction, or as potential biomarkers. With these prospected applications of Radiomics features, it is a requisite that they provide robust and reliable measurements. The aim of our study was therefore to perform an integrated stability analysis of a large number of PET-derived features in non-small cell lung carcinoma (NSCLC), based on both a test-retest and an inter-observer setup. Methods. Eleven NSCLC patients were included in the test-retest cohort. Patients underwent repeated PET imaging within a one day interval, before any treatment was delivered. Lesions were delineated by applying a threshold of 50% of the maximum uptake value within the tumor. Twenty-three NSCLC patients were included in the inter-observer cohort. Patients underwent a diagnostic whole body PET-computed tomography (CT). Lesions were manually delineated based on fused PET-CT, using a standardized clinical delineation protocol. Delineation was performed independently by five observers, blinded to each other. Fifteen first order statistics, 39 descriptors of intensity volume histograms, eight geometric features and 44 textural features were extracted. For every feature, test-retest and inter-observer stability was assessed with the intra-class correlation coefficient (ICC) and the coefficient of variability, normalized to mean and range. Similarity between test-retest and inter-observer stability rankings of features was assessed with Spearmans rank correlation coefficient. Results. Results showed that the majority of assessed features had both a high test-retest (71%) and inter-observer (91%) stability in terms of their ICC. Overall, features more stable in repeated PET imaging were also found to be more robust against inter-observer variability. Conclusion. Results suggest that further research of quantitative imaging features is warranted with respect to more advanced applications of PET imaging as being used for treatment monitoring, outcome prediction or imaging biomarkers.

Robust Radiomics Feature Quantification Using Semiautomatic Volumetric Segmentation

Due to advances in the acquisition and analysis of medical imaging, it is currently possible to quantify the tumor phenotype. The emerging field of Radiomics addresses this issue by converting medical images into minable data by extracting a large number of quantitative imaging features. One of the main challenges of Radiomics is tumor segmentation. Where manual delineation is time consuming and prone to inter-observer variability, it has been shown that semi-automated approaches are fast and reduce inter-observer variability. In this study, a semiautomatic region growing volumetric segmentation algorithm, implemented in the free and publicly available 3D-Slicer platform, was investigated in terms of its robustness for quantitative imaging feature extraction. Fifty-six 3D-radiomic features, quantifying phenotypic differences based on tumor intensity, shape and texture, were extracted from the computed tomography images of twenty lung cancer patients. These radiomic features were derived from the 3D-tumor volumes defined by three independent observers twice using 3D-Slicer, and compared to manual slice-by-slice delineations of five independent physicians in terms of intra-class correlation coefficient (ICC) and feature range. Radiomic features extracted from 3D-Slicer segmentations had significantly higher reproducibility (ICC = 0.85±0.15, p = 0.0009) compared to the features extracted from the manual segmentations (ICC = 0.77±0.17). Furthermore, we found that features extracted from 3D-Slicer segmentations were more robust, as the range was significantly smaller across observers (p = 3.819e-07), and overlapping with the feature ranges extracted from manual contouring (boundary lower: p = 0.007, higher: p = 5.863e-06). Our results show that 3D-Slicer segmented tumor volumes provide a better alternative to the manual delineation for feature quantification, as they yield more reproducible imaging descriptors. Therefore, 3D-Slicer can be employed for quantitative image feature extraction and image data mining research in large patient cohorts.

Radiomic feature clusters and Prognostic Signatures specific for Lung and Head & Neck cancer

Radiomics provides a comprehensive quantification of tumor phenotypes by extracting and mining large number of quantitative image features. To reduce the redundancy and compare the prognostic characteristics of radiomic features across cancer types, we investigated cancer-specific radiomic feature clusters in four independent Lung and Head & Neck (H∓N) cancer cohorts (in total 878 patients). Radiomic features were extracted from the pre-treatment computed tomography (CT) images. Consensus clustering resulted in eleven and thirteen stable radiomic feature clusters for Lung and H & N cancer, respectively. These clusters were validated in independent external validation cohorts using rand statistic (Lung RS = 0.92, p < 0.001, H & N RS = 0.92, p < 0.001). Our analysis indicated both common as well as cancer-specific clustering and clinical associations of radiomic features. Strongest associations with clinical parameters: Prognosis Lung CI = 0.60 ± 0.01, Prognosis H & N CI = 0.68 ± 0.01; Lung histology AUC = 0.56 ± 0.03, Lung stage AUC = 0.61 ± 0.01, H & N HPV AUC = 0.58 ± 0.03, H & N stage AUC = 0.77 ± 0.02. Full utilization of these cancer-specific characteristics of image features may further improve radiomic biomarkers, providing a non-invasive way of quantifying and monitoring tumor phenotypic characteristics in clinical practice.

‘Rapid Learning health care in oncology’ – An approach towards decision support systems enabling customised radiotherapy’ ☆ ☆☆

PURPOSE An overview of the Rapid Learning methodology, its results, and the potential impact on radiotherapy. MATERIAL AND RESULTS Rapid Learning methodology is divided into four phases. In the data phase, diverse data are collected about past patients, treatments used, and outcomes. Innovative information technologies that support semantic interoperability enable distributed learning and data sharing without additional burden on health care professionals and without the need for data to leave the hospital. In the knowledge phase, prediction models are developed for new data and treatment outcomes by applying machine learning methods to data. In the application phase, this knowledge is applied in clinical practice via novel decision support systems or via extensions of existing models such as Tumour Control Probability models. In the evaluation phase, the predictability of treatment outcomes allows the new knowledge to be evaluated by comparing predicted and actual outcomes. CONCLUSION Personalised or tailored cancer therapy ensures not only that patients receive an optimal treatment, but also that the right resources are being used for the right patients. Rapid Learning approaches combined with evidence based medicine are expected to improve the predictability of outcome and radiotherapy is the ideal field to study the value of Rapid Learning. The next step will be to include patient preferences in the decision making.

The effect of SUV discretization in quantitative FDG-PET Radiomics: the need for standardized methodology in tumor texture analysis

FDG-PET-derived textural features describing intra-tumor heterogeneity are increasingly investigated as imaging biomarkers. As part of the process of quantifying heterogeneity, image intensities (SUVs) are typically resampled into a reduced number of discrete bins. We focused on the implications of the manner in which this discretization is implemented. Two methods were evaluated: (1) RD, dividing the SUV range into D equally spaced bins, where the intensity resolution (i.e. bin size) varies per image; and (2) RB, maintaining a constant intensity resolution B. Clinical feasibility was assessed on 35 lung cancer patients, imaged before and in the second week of radiotherapy. Forty-four textural features were determined for different D and B for both imaging time points. Feature values depended on the intensity resolution and out of both assessed methods, RB was shown to allow for a meaningful inter- and intra-patient comparison of feature values. Overall, patients ranked differently according to feature values–which was used as a surrogate for textural feature interpretation–between both discretization methods. Our study shows that the manner of SUV discretization has a crucial effect on the resulting textural features and the interpretation thereof, emphasizing the importance of standardized methodology in tumor texture analysis.

Radiomics: the bridge between medical imaging and personalized medicine

Radiomics, the high-throughput mining of quantitative image features from standard-of-care medical imaging that enables data to be extracted and applied within clinical-decision support systems to improve diagnostic, prognostic, and predictive accuracy, is gaining importance in cancer research. Radiomic analysis exploits sophisticated image analysis tools and the rapid development and validation of medical imaging data that uses image-based signatures for precision diagnosis and treatment, providing a powerful tool in modern medicine. Herein, we describe the process of radiomics, its pitfalls, challenges, opportunities, and its capacity to improve clinical decision making, emphasizing the utility for patients with cancer. Currently, the field of radiomics lacks standardized evaluation of both the scientific integrity and the clinical relevance of the numerous published radiomics investigations resulting from the rapid growth of this area. Rigorous evaluation criteria and reporting guidelines need to be established in order for radiomics to mature as a discipline. Herein, we provide guidance for investigations to meet this urgent need in the field of radiomics.

External validation of a prognostic CT-based radiomic signature in oropharyngeal squamous cell carcinoma

ABSTRACT Background. Oropharyngeal squamous cell carcinoma (OPSCC) is one of the fastest growing disease sites of head and neck cancers. A recently described radiomic signature, based exclusively on pre-treatment computed tomography (CT) imaging of the primary tumor volume, was found to be prognostic in independent cohorts of lung and head and neck cancer patients treated in the Netherlands. Here, we further validate this signature in a large and independent North American cohort of OPSCC patients, also considering CT artifacts. Methods. A total of 542 OPSCC patients were included for which we determined the prognostic index (PI) of the radiomic signature. We tested the signature model fit in a Cox regression and assessed model discrimination with Harrells c-index. Kaplan-Meier survival curves between high and low signature predictions were compared with a log-rank test. Validation was performed in the complete cohort (PMH1) and in the subset of patients without (PMH2) and with (PMH3) visible CT artifacts within the delineated tumor region. Results. We identified 267 (49%) patients without and 275 (51%) with visible CT artifacts. The calibration slope (β) on the PI in a Cox proportional hazards model was 1.27 (H0: β = 1, p = 0.152) in the PMH1 (n = 542), 0.855 (H0: β = 1, p = 0.524) in the PMH2 (n = 267) and 1.99 (H0: β = 1, p = 0.002) in the PMH3 (n = 275) cohort. Harrells c-index was 0.628 (p = 2.72e-9), 0.634 (p = 2.7e-6) and 0.647 (p = 5.35e-6) for the PMH1, PMH2 and PMH3 cohort, respectively. Kaplan-Meier survival curves were significantly different (p < 0.05) between high and low radiomic signature model predictions for all cohorts. Conclusion. Overall, the signature validated well using all CT images as-is, demonstrating a good model fit and preservation of discrimination. Even though CT artifacts were shown to be of influence, the signature had significant prognostic power regardless if patients with CT artifacts were included.