RADCURE: An open-source head and neck cancer CT dataset for clinical radiation therapy insights.

PURPOSE: This manuscript presents RADCURE, one of the most extensive head and neck cancer (HNC) imaging datasets accessible to the public. Initially collected for clinical radiation therapy (RT) treatment planning, this dataset has been retrospectively reconstructed for use in imaging research. ACQUISITION AND VALIDATION METHODS: RADCURE encompasses data from 3346 patients, featuring computed tomography (CT) RT simulation images with corresponding target and organ-at-risk contours. These CT scans were collected using systems from three different manufacturers. Standard clinical imaging protocols were followed, and contours were manually generated and reviewed at weekly RT quality assurance rounds. RADCURE imaging and structure set data was extracted from our institution's radiation treatment planning and oncology information systems using a custom-built data mining and processing system. Furthermore, images were linked to our clinical anthology of outcomes data for each patient and includes demographic, clinical and treatment information based on the 7th edition TNM staging system (Tumor-Node-Metastasis Classification System of Malignant Tumors). The median patient age is 63, with the final dataset including 80% males. Half of the cohort is diagnosed with oropharyngeal cancer, while laryngeal, nasopharyngeal, and hypopharyngeal cancers account for 25%, 12%, and 5% of cases, respectively. The median duration of follow-up is five years, with 60% of the cohort surviving until the last follow-up point. DATA FORMAT AND USAGE NOTES: The dataset provides images and contours in DICOM CT and RT-STRUCT formats, respectively. We have standardized the nomenclature for individual contours-such as the gross primary tumor, gross nodal volumes, and 19 organs-at-risk-to enhance the RT-STRUCT files' utility. Accompanying demographic, clinical, and treatment data are supplied in a comma-separated values (CSV) file format. This comprehensive dataset is publicly accessible via The Cancer Imaging Archive. POTENTIAL APPLICATIONS: RADCURE's amalgamation of imaging, clinical, demographic, and treatment data renders it an invaluable resource for a broad spectrum of radiomics image analysis research endeavors. Researchers can utilize this dataset to advance routine clinical procedures using machine learning or artificial intelligence, to identify new non-invasive biomarkers, or to forge prognostic models.

Multi-institutional Prognostic Modeling in Head and Neck Cancer: Evaluating Impact and Generalizability of Deep Learning and Radiomics.

Artificial intelligence (AI) and machine learning (ML) are becoming critical in developing and deploying personalized medicine and targeted clinical trials. Recent advances in ML have enabled the integration of wider ranges of data including both medical records and imaging (radiomics). However, the development of prognostic models is complex as no modeling strategy is universally superior to others and validation of developed models requires large and diverse datasets to demonstrate that prognostic models developed (regardless of method) from one dataset are applicable to other datasets both internally and externally. Using a retrospective dataset of 2,552 patients from a single institution and a strict evaluation framework that included external validation on three external patient cohorts (873 patients), we crowdsourced the development of ML models to predict overall survival in head and neck cancer (HNC) using electronic medical records (EMR) and pretreatment radiological images. To assess the relative contributions of radiomics in predicting HNC prognosis, we compared 12 different models using imaging and/or EMR data. The model with the highest accuracy used multitask learning on clinical data and tumor volume, achieving high prognostic accuracy for 2-year and lifetime survival prediction, outperforming models relying on clinical data only, engineered radiomics, or complex deep neural network architecture. However, when we attempted to extend the best performing models from this large training dataset to other institutions, we observed significant reductions in the performance of the model in those datasets, highlighting the importance of detailed population-based reporting for AI/ML model utility and stronger validation frameworks. We have developed highly prognostic models for overall survival in HNC using EMRs and pretreatment radiological images based on a large, retrospective dataset of 2,552 patients from our institution.Diverse ML approaches were used by independent investigators. The model with the highest accuracy used multitask learning on clinical data and tumor volume.External validation of the top three performing models on three datasets (873 patients) with significant differences in the distributions of clinical and demographic variables demonstrated significant decreases in model performance. Significance: ML combined with simple prognostic factors outperformed multiple advanced CT radiomics and deep learning methods. ML models provided diverse solutions for prognosis of patients with HNC but their prognostic value is affected by differences in patient populations and require extensive validation.

Effect of Radiation Therapy Quality Assurance on Nasopharyngeal Carcinoma: Usage of a Novel, Web-Based Quality Assurance Application.

PURPOSE: We used a new web application for rapid review of radiation therapy (RT) target volumes to evaluate the relationship between target delineation compliance with the international guidelines and outcomes of definitive RT for nasopharyngeal carcinoma (NPC). METHODS AND MATERIALS: The data set consisted of computed tomography simulation scans, RT structures, and clinical data of 354 patients with pathology-confirmed NPC treated with intensity modulated RT between 2005 and 2017. Target volumes were peer-reviewed in RT quality assurance rounds, and target contours were revised, if recommended, before treatment. We imported the contours of intermediate-risk clinical target volumes of the primary tumor (CTVp) of 332 patients into the application. Inclusion of anatomic sites within intermediate-risk CTVp was determined in accordance with 2018 international guidelines for CTV delineation for NPC and correlated with time to local failure (TTLF) using Cox regression. RESULTS: In the peer-review quality assurance analysis, local and distant control and overall survival rates were similar between peer-reviewed and nonreviewed cases and between cases with and without target contour changes. In the CTV compliance analysis, with a median follow-up of 5.6 years, 5-year TTLF and overall survival rates were 93.1% and 85.9%, respectively. The most frequently non-guideline-compliant anatomic sites were sphenoid sinus (n = 69, 20.8%), followed by cavernous sinus (n = 38, 19.3%), left and right petrous apices (n = 37 and 32, 11.1% and 9.6%), and clivus (n = 14, 4.2%). Among 23 patients with a local failure (6.9%), the number of noncompliant cases was 8 for sphenoid sinus, 7 cavernous sinus, 4 left and 3 right petrous apices, and 2 clivus. Cavernous sinus-conforming cases showed higher TTLF in comparison with nonconforming cases (93.6% vs 89.1%, P = .013). Multivariable analysis confirmed that cavernous sinus noncompliance was prognostic for TTLF. CONCLUSIONS: Our application allowed rapid quantitative review of CTVp in a large NPC cohort. Although compliance with the international guidelines was high, undercoverage of the cavernous sinus was correlated with TTLF.

Prediction of Incomplete Response of Primary Tumour Based on Clinical and Radiomics Features in Inoperable Head and Neck Cancers after Definitive Treatment.

Radical treatment of patients diagnosed with inoperable and locally advanced head and neck cancers (LAHNC) is still a challenge for clinicians. Prediction of incomplete response (IR) of primary tumour would be of value to the treatment optimization for patients with LAHNC. Aim of this study was to develop and evaluate models based on clinical and radiomics features for prediction of IR in patients diagnosed with LAHNC and treated with definitive chemoradiation or radiotherapy. Clinical and imaging data of 290 patients were included into this retrospective study. Clinical model was built based on tumour and patient related features. Radiomics features were extracted based on imaging data, consisting of contrast- and non-contrast-enhanced pre-treatment CT images, obtained in process of diagnosis and radiotherapy planning. Performance of clinical and combined models were evaluated with area under the ROC curve (AUROC). Classification performance was evaluated using 5-fold cross validation. Model based on selected clinical features including ECOG performance, tumour stage T3/4, primary site: oral cavity and tumour volume were significantly predictive for IR, with AUROC of 0.78. Combining clinical and radiomics features did not improve model's performance, achieving AUROC 0.77 and 0.68 for non-contrast enhanced and contrast-enhanced images respectively. The model based on clinical features showed good performance in IR prediction. Combined model performance suggests that real-world imaging data might not yet be ready for use in predictive models.

Automated detection of dental artifacts for large-scale radiomic analysis in radiation oncology.

BACKGROUND AND PURPOSE: Computed tomography (CT) is one of the most common medical imaging modalities in radiation oncology and radiomics research, the computational voxel-level analysis of medical images. Radiomics is vulnerable to the effects of dental artifacts (DA) caused by metal implants or fillings and can hamper future reproducibility on new datasets. In this study we seek to better understand the robustness of quantitative radiomic features to DAs. Furthermore, we propose a novel method of detecting DAs in order to safeguard radiomic studies and improve reproducibility. MATERIALS AND METHODS: We analyzed the correlations between radiomic features and the location of dental artifacts in a new dataset containing 3D CT scans from 3211 patients. We then combined conventional image processing techniques with a pre-trained convolutional neural network to create a three-class patient-level DA classifier and slice-level DA locator. Finally, we demonstrated its utility in reducing the correlations between the location of DAs and certain radiomic features. RESULTS: We found that when strong DAs were present, the proximity of the tumour to the mouth was highly correlated with 36 radiomic features. We predicted the correct DA magnitude yielding a Matthews correlation coefficient of 0.73 and location of DAs achieving the same level of agreement as human labellers. CONCLUSIONS: Removing radiomic features or CT slices containing DAs could reduce the unwanted correlations between the location of DAs and radiomic features. Automated DA detection can be used to improve the reproducibility of radiomic studies; an important step towards creating effective radiomic models for use in clinical radiation oncology.

Machine learning helps identifying volume-confounding effects in radiomics.

PURPOSE: Highlighting the risk of biases in radiomics-based models will help improve their quality and increase usage as decision support systems in the clinic. In this study we use machine learning-based methods to identify the presence of volume-confounding effects in radiomics features. Methods 841 radiomics features were extracted from two retrospective publicly available datasets of lung and head neck cancers using open source software. Unsupervised hierarchical clustering and principal component analysis (PCA) identified relations between radiomics and clinical outcomes (overall survival). Bootstrapping techniques with logistic regression verified features' prognostic power and robustness. Results Over 80% of the features had large pairwise correlations. Nearly 30% of the features presented strong correlations with tumor volume. Using volume-independent features for clustering and PCA did not allow risk stratification of patients. Clinical predictors outperformed radiomics features in bootstrapping and logistic regression. Conclusions The adoption of safeguards in radiomics is imperative to improve the quality of radiomics studies. We proposed machine learning (ML) - based methods for robust radiomics signatures development.

Sensitivity of radiomic features to inter-observer variability and image pre-processing in Apparent Diffusion Coefficient (ADC) maps of cervix cancer patients.

PURPOSE: The aims of this study are to evaluate the stability of radiomic features from Apparent Diffusion Coefficient (ADC) maps of cervical cancer with respect to: (1) reproducibility in inter-observer delineation, and (2) image pre-processing (normalization/quantization) prior to feature extraction. MATERIALS AND METHODS: Two observers manually delineated the tumor on ADC maps derived from pre-treatment diffusion-weighted Magnetic Resonance imaging of 81 patients with FIGO stage IB-IVA cervical cancer. First-order, shape, and texture features were extracted from the original and filtered images considering 5 different normalizations (four taken from the available literature, and one based on urine ADC) and two different quantization techniques (fixed-bin widths from 0.05 to 25, and fixed-bin count). Stability of radiomic features was assessed using intraclass correlation coefficient (ICC): poor (ICC < 0.75); good (0.75 ≤ ICC ≤ 0.89), and excellent (ICC ≥ 0.90). Dependencies of the features with tumor volume were assessed using Spearman's correlation coefficient (ρ). RESULTS: The approach using urine-normalized values together with a smaller bin width (0.05) was the most reproducible (428/552, 78% features with ICC ≥ 0.75); the fixed-bin count approach was the least (215/552, 39% with ICC ≥ 0.75). Without normalization, using a fixed bin width of 25, 348/552 (63%) of features had an ICC ≥ 0.75. Overall, 26% (range 25-30%) of the features were volume-dependent (ρ ≥ 0.6). None of the volume-independent shape features were found to be reproducible. CONCLUSION: Applying normalization prior to features extraction increases the reproducibility of ADC-based radiomics features. When normalization is applied, a fixed-bin width approach with smaller widths is suggested.

Stability of radiomic features of apparent diffusion coefficient (ADC) maps for locally advanced rectal cancer in response to image pre-processing.

Quantitative imaging features (radiomics) extracted from apparent diffusion coefficient (ADC) maps of rectal cancer patients can provide additional information to support treatment decision. Most available radiomic computational packages allow extraction of hundreds to thousands of features. However, two major factors can influence the reproducibility of radiomic features: interobserver variability, and imaging filtering applied prior to features extraction. In this exploratory study we seek to determine to what extent various commonly-used features are reproducible with regards to the mentioned factors using ADC maps from two different clinics (56 patients). Features derived from intensity distribution histograms are less sensitive to manual tumour delineation differences, noise in ADC images, pixel size resampling and intensity discretization. Shape features appear to be strongly affected by delineation quality. On the whole, textural features appear to be poorly or moderately reproducible with respect to the image pre-processing perturbations we reproduced.