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Radiomics strategies for risk assessment of tumour failure in head-and-neck cancer

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 Added by Martin Valli\\`eres
 Publication date 2017
and research's language is English




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Quantitative extraction of high-dimensional mineable data from medical images is a process known as radiomics. Radiomics is foreseen as an essential prognostic tool for cancer risk assessment and the quantification of intratumoural heterogeneity. In this work, 1615 radiomic features (quantifying tumour image intensity, shape, texture) extracted from pre-treatment FDG-PET and CT images of 300 patients from four different cohorts were analyzed for the risk assessment of locoregional recurrences (LR) and distant metastases (DM) in head-and-neck cancer. Prediction models combining radiomic and clinical variables were constructed via random forests and imbalance-adjustment strategies using two of the four cohorts. Independent validation of the prediction and prognostic performance of the models was carried out on the other two cohorts (LR: AUC = 0.69 and CI = 0.67; DM: AUC = 0.86 and CI = 0.88). Furthermore, the results obtained via Kaplan-Meier analysis demonstrated the potential of radiomics for assessing the risk of specific tumour outcomes using multiple stratification groups. This could have important clinical impact, notably by allowing for a better personalization of chemo-radiation treatments for head-and-neck cancer patients from different risk groups.

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OAR segmentation is a critical step in radiotherapy of head and neck (H&N) cancer, where inconsistencies across radiation oncologists and prohibitive labor costs motivate automated approaches. However, leading methods using standard fully convolutional network workflows that are challenged when the number of OARs becomes large, e.g. > 40. For such scenarios, insights can be gained from the stratification approaches seen in manual clinical OAR delineation. This is the goal of our work, where we introduce stratified organ at risk segmentation (SOARS), an approach that stratifies OARs into anchor, mid-level, and small & hard (S&H) categories. SOARS stratifies across two dimensions. The first dimension is that distinct processing pipelines are used for each OAR category. In particular, inspired by clinical practices, anchor OARs are used to guide the mid-level and S&H categories. The second dimension is that distinct network architectures are used to manage the significant contrast, size, and anatomy variations between different OARs. We use differentiable neural architecture search (NAS), allowing the network to choose among 2D, 3D or Pseudo-3D convolutions. Extensive 4-fold cross-validation on 142 H&N cancer patients with 42 manually labeled OARs, the most comprehensive OAR dataset to date, demonstrates that both pipeline- and NAS-stratification significantly improves quantitative performance over the state-of-the-art (from 69.52% to 73.68% in absolute Dice scores). Thus, SOARS provides a powerful and principled means to manage the highly complex segmentation space of OARs.
A 3D deep learning model (OARnet) is developed and used to delineate 28 H&N OARs on CT images. OARnet utilizes a densely connected network to detect the OAR bounding-box, then delineates the OAR within the box. It reuses information from any layer to subsequent layers and uses skip connections to combine information from different dense block levels to progressively improve delineation accuracy. Training uses up to 28 expert manual delineated (MD) OARs from 165 CTs. Dice similarity coefficient (DSC) and the 95th percentile Hausdorff distance (HD95) with respect to MD is assessed for 70 other CTs. Mean, maximum, and root-mean-square dose differences with respect to MD are assessed for 56 of the 70 CTs. OARnet is compared with UaNet, AnatomyNet, and Multi-Atlas Segmentation (MAS). Wilcoxon signed-rank tests using 95% confidence intervals are used to assess significance. Wilcoxon signed ranked tests show that, compared with UaNet, OARnet improves (p<0.05) the DSC (23/28 OARs) and HD95 (17/28). OARnet outperforms both AnatomyNet and MAS for DSC (28/28) and HD95 (27/28). Compared with UaNet, OARnet improves median DSC up to 0.05 and HD95 up to 1.5mm. Compared with AnatomyNet and MAS, OARnet improves median (DSC, HD95) by up to (0.08, 2.7mm) and (0.17, 6.3mm). Dosimetrically, OARnet outperforms UaNet (Dmax 7/28; Dmean 10/28), AnatomyNet (Dmax 21/28; Dmean 24/28), and MAS (Dmax 22/28; Dmean 21/28). The DenseNet architecture is optimized using a hybrid approach that performs OAR-specific bounding box detection followed by feature recognition. Compared with other auto-delineation methods, OARnet is better than or equal to UaNet for all but one geometric (Temporal Lobe L, HD95) and one dosimetric (Eye L, mean dose) endpoint for the 28 H&N OARs, and is better than or equal to both AnatomyNet and MAS for all OARs.
In medical imaging, radiological scans of different modalities serve to enhance different sets of features for clinical diagnosis and treatment planning. This variety enriches the source information that could be used for outcome prediction. Deep learning methods are particularly well-suited for feature extraction from high-dimensional inputs such as images. In this work, we apply a CNN classification network augmented with a FCN preprocessor sub-network to a public TCIA head and neck cancer dataset. The training goal is survival prediction of radiotherapy cases based on pre-treatment FDG PET-CT scans, acquired across 4 different hospitals. We show that the preprocessor sub-network in conjunction with aggregated residual connection leads to improvements over state-of-the-art results when combining both CT and PET input images.
Importance: Lung cancer is the leading cause of cancer mortality in the US, responsible for more deaths than breast, prostate, colon and pancreas cancer combined and it has been recently demonstrated that low-dose computed tomography (CT) screening of the chest can significantly reduce this death rate. Objective: To compare the performance of a deep learning model to state-of-the-art automated algorithms and radiologists as well as assessing the robustness of the algorithm in heterogeneous datasets. Design, Setting, and Participants: Three low-dose CT lung cancer screening datasets from heterogeneous sources were used, including National Lung Screening Trial (NLST, n=3410), Lahey Hospital and Medical Center (LHMC, n=3174) data, Kaggle competition data (from both stages, n=1595+505) and the University of Chicago data (UCM, a subset of NLST, annotated by radiologists, n=197). Relevant works on automated methods for Lung Cancer malignancy estimation have used significantly less data in size and diversity. At the first stage, our framework employs a nodule detector; while in the second stage, we use both the image area around the nodules and nodule features as inputs to a neural network that estimates the malignancy risk for the entire CT scan. We trained our two-stage algorithm on a part of the NLST dataset, and validated it on the other datasets. Results, Conclusions, and Relevance: The proposed deep learning model: (a) generalizes well across all three data sets, achieving AUC between 86% to 94%; (b) has better performance than the widely accepted PanCan Risk Model, achieving 11% better AUC score; (c) has improved performance compared to the state-of-the-art represented by the winners of the Kaggle Data Science Bowl 2017 competition on lung cancer screening; (d) has comparable performance to radiologists in estimating cancer risk at a patient level.
Over half a million individuals are diagnosed with head and neck cancer each year worldwide. Radiotherapy is an important curative treatment for this disease, but it requires manual time consuming delineation of radio-sensitive organs at risk (OARs). This planning process can delay treatment, while also introducing inter-operator variability with resulting downstream radiation dose differences. While auto-segmentation algorithms offer a potentially time-saving solution, the challenges in defining, quantifying and achieving expert performance remain. Adopting a deep learning approach, we demonstrate a 3D U-Net architecture that achieves expert-level performance in delineating 21 distinct head and neck OARs commonly segmented in clinical practice. The model was trained on a dataset of 663 deidentified computed tomography (CT) scans acquired in routine clinical practice and with both segmentations taken from clinical practice and segmentations created by experienced radiographers as part of this research, all in accordance with consensus OAR definitions. We demonstrate the models clinical applicability by assessing its performance on a test set of 21 CT scans from clinical practice, each with the 21 OARs segmented by two independent experts. We also introduce surface Dice similarity coefficient (surface DSC), a new metric for the comparison of organ delineation, to quantify deviation between OAR surface contours rather than volumes, better reflecting the clinical task of correcting errors in the automated organ segmentations. The models generalisability is then demonstrated on two distinct open source datasets, reflecting different centres and countries to model training. With appropriate validation studies and regulatory approvals, this system could improve the efficiency, consistency, and safety of radiotherapy pathways.
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