Ovarian cancer remains one of the most lethal gynecological cancers in the world despite extensive progress in the areas of chemotherapy and surgery. Many studies have postulated that this is because ...of the profound heterogeneity that underpins response to therapy and prognosis. Standard imaging evaluation using CT or MRI does not take into account this tumoral heterogeneity especially in advanced stages with peritoneal carcinomatosis. As such, newly emergent fields in the assessment of tumor heterogeneity have been proposed using radiomics to evaluate the whole tumor burden heterogeneity as opposed to single biopsy sampling. This review provides an overview of radiomics, radiogenomics, and proteomics and examines the use of these newly emergent fields in assessing tumor heterogeneity and its implications in ovarian cancer.
High grade serous ovarian carcinoma (HGSOC) is a highly heterogeneous disease that typically presents at an advanced, metastatic state. The multi-scale complexity of HGSOC is a major obstacle to ...predicting response to neoadjuvant chemotherapy (NACT) and understanding critical determinants of response. Here we present a framework to predict the response of HGSOC patients to NACT integrating baseline clinical, blood-based, and radiomic biomarkers extracted from all primary and metastatic lesions. We use an ensemble machine learning model trained to predict the change in total disease volume using data obtained at diagnosis (n = 72). The model is validated in an internal hold-out cohort (n = 20) and an independent external patient cohort (n = 42). In the external cohort the integrated radiomics model reduces the prediction error by 8% with respect to the clinical model, achieving an AUC of 0.78 for RECIST 1.1 classification compared to 0.47 for the clinical model. Our results emphasize the value of including radiomics data in integrative models of treatment response and provide methods for developing new biomarker-based clinical trials of NACT in HGSOC.
Clinical trials for oncology drug development have long relied on surrogate outcome biomarkers that assess changes in tumor burden to accelerate drug registration (i.e., Response Evaluation Criteria ...in Solid Tumors version 1.1 (RECIST v1.1) criteria). Drug-induced reduction in tumor size represents an imperfect surrogate marker for drug activity and yet a radiologically determined objective response rate is a widely used endpoint for Phase 2 trials. With the addition of therapies targeting complex biological systems such as immune system and DNA damage repair pathways, incorporation of integrative response and outcome biomarkers may add more predictive value. We performed a review of the relevant literature in four representative tumor types (breast cancer, rectal cancer, lung cancer and glioblastoma) to assess the preparedness of volumetric and radiomics metrics as clinical trial endpoints. We identified three key areas—segmentation, validation and data sharing strategies—where concerted efforts are required to enable progress of volumetric- and radiomics-based clinical trial endpoints for wider clinical implementation.
Pathological response to neoadjuvant treatment for patients with high-grade serous ovarian carcinoma (HGSOC) is assessed using the chemotherapy response score (CRS) for omental tumor deposits. The ...main limitation of CRS is that it requires surgical sampling after initial neoadjuvant chemotherapy (NACT) treatment. Earlier and non-invasive response predictors could improve patient stratification. We developed computed tomography (CT) radiomic measures to predict neoadjuvant response before NACT using CRS as a gold standard.
Omental CT-based radiomics models, yielding a simplified fully interpretable radiomic signature, were developed using Elastic Net logistic regression and compared to predictions based on omental tumor volume alone. Models were developed on a single institution cohort of neoadjuvant-treated HGSOC (
= 61; 41% complete response to NCT) and tested on an external test cohort (
= 48; 21% complete response).
The performance of the comprehensive radiomics models and the fully interpretable radiomics model was significantly higher than volume-based predictions of response in both the discovery and external test sets when assessed using G-mean (geometric mean of sensitivity and specificity) and NPV, indicating high generalizability and reliability in identifying non-responders when using radiomics. The performance of a fully interpretable model was similar to that of comprehensive radiomics models.
CT-based radiomics allows for predicting response to NACT in a timely manner and without the need for abdominal surgery. Adding pre-NACT radiomics to volumetry improved model performance for predictions of response to NACT in HGSOC and was robust to external testing. A radiomic signature based on five robust predictive features provides improved clinical interpretability and may thus facilitate clinical acceptance and application.
High-Grade Serous Ovarian Carcinoma (HGSOC) is the most prevalent and lethal subtype of ovarian cancer, but has a paucity of clinically-actionable biomarkers due to high degrees of multi-level ...heterogeneity. Radiogenomics markers have the potential to improve prediction of patient outcome and treatment response, but require accurate multimodal spatial registration between radiological imaging and histopathological tissue samples. Previously published co-registration work has not taken into account the anatomical, biological and clinical diversity of ovarian tumours.
In this work, we developed a research pathway and an automated computational pipeline to produce lesion-specific three-dimensional (3D) printed moulds based on preoperative cross-sectional CT or MRI of pelvic lesions. Moulds were designed to allow tumour slicing in the anatomical axial plane to facilitate detailed spatial correlation of imaging and tissue-derived data. Code and design adaptations were made following each pilot case through an iterative refinement process.
Five patients with confirmed or suspected HGSOC who underwent debulking surgery between April and December 2021 were included in this prospective study. Tumour moulds were designed and 3D-printed for seven pelvic lesions, covering a range of tumour volumes (7 to 133 cm
) and compositions (cystic and solid proportions). The pilot cases informed innovations to improve specimen and subsequent slice orientation, through the use of 3D-printed tumour replicas and incorporation of a slice orientation slit in the mould design, respectively. The overall research pathway was compatible with implementation within the clinically determined timeframe and treatment pathway for each case, involving multidisciplinary clinical professionals from Radiology, Surgery, Oncology and Histopathology Departments.
We developed and refined a computational pipeline that can model lesion-specific 3D-printed moulds from preoperative imaging for a variety of pelvic tumours. This framework can be used to guide comprehensive multi-sampling of tumour resection specimens.
Renal cancer is responsible for over 100,000 yearly deaths and is principally discovered in computed tomography (CT) scans of the abdomen. CT screening would likely increase the rate of early renal ...cancer detection, and improve general survival rates, but it is expected to have a prohibitively high financial cost. Given recent advances in artificial intelligence (AI), it may be possible to reduce the cost of CT analysis and enable CT screening by automating the radiological tasks that constitute the early renal cancer detection pipeline. This review seeks to facilitate further interdisciplinary research in early renal cancer detection by summarising our current knowledge across AI, radiology, and oncology and suggesting useful directions for future novel work. Initially, this review discusses existing approaches in automated renal cancer diagnosis, and methods across broader AI research, to summarise the existing state of AI cancer analysis. Then, this review matches these methods to the unique constraints of early renal cancer detection and proposes promising directions for future research that may enable AI-based early renal cancer detection via CT screening. The primary targets of this review are clinicians with an interest in AI and data scientists with an interest in the early detection of cancer.
Artificial intelligence (AI) methods applied to healthcare problems have shown enormous potential to alleviate the burden of health services worldwide and to improve the accuracy and reproducibility ...of predictions. In particular, developments in computer vision are creating a paradigm shift in the analysis of radiological images, where AI tools are already capable of automatically detecting and precisely delineating tumours. However, such tools are generally developed in technical departments that continue to be siloed from where the real benefit would be achieved with their usage. Significant effort still needs to be made to make these advancements available, first in academic clinical research and ultimately in the clinical setting. In this paper, we demonstrate a prototype pipeline based entirely on open-source software and free of cost to bridge this gap, simplifying the integration of tools and models developed within the AI community into the clinical research setting, ensuring an accessible platform with visualisation applications that allow end-users such as radiologists to view and interact with the outcome of these AI tools.
Machine learning methods offer great promise for fast and accurate detection and prognostication of coronavirus disease 2019 (COVID-19) from standard-of-care chest radiographs (CXR) and chest ...computed tomography (CT) images. Many articles have been published in 2020 describing new machine learning-based models for both of these tasks, but it is unclear which are of potential clinical utility. In this systematic review, we consider all published papers and preprints, for the period from 1 January 2020 to 3 October 2020, which describe new machine learning models for the diagnosis or prognosis of COVID-19 from CXR or CT images. All manuscripts uploaded to bioRxiv, medRxiv and arXiv along with all entries in EMBASE and MEDLINE in this timeframe are considered. Our search identified 2,212 studies, of which 415 were included after initial screening and, after quality screening, 62 studies were included in this systematic review. Our review finds that none of the models identified are of potential clinical use due to methodological flaws and/or underlying biases. This is a major weakness, given the urgency with which validated COVID-19 models are needed. To address this, we give many recommendations which, if followed, will solve these issues and lead to higher-quality model development and well-documented manuscripts.Many machine learning-based approaches have been developed for the prognosis and diagnosis of COVID-19 from medical images and this Analysis identifies over 2,200 relevant published papers and preprints in this area. After initial screening, 62 studies are analysed and the authors find they all have methodological flaws standing in the way of clinical utility. The authors have several recommendations to address these issues.
Uncertainty quantification in automated image analysis is highly desired in many applications. Typically, machine learning models in classification or segmentation are only developed to provide ...binary answers; however, quantifying the uncertainty of the models can play a critical role for example in active learning or machine human interaction. Uncertainty quantification is especially difficult when using deep learning-based models, which are the state-of-the-art in many imaging applications. The current uncertainty quantification approaches do not scale well in high-dimensional real-world problems. Scalable solutions often rely on classical techniques, such as dropout, during inference or training ensembles of identical models with different random seeds to obtain a posterior distribution. In this paper, we present the following contributions. First, we show that the classical approaches fail to approximate the classification probability. Second, we propose a scalable and intuitive framework for uncertainty quantification in medical image segmentation that yields measurements that approximate the classification probability. Third, we suggest the usage of k-fold cross-validation to overcome the need for held out calibration data. Lastly, we motivate the adoption of our method in active learning, creating pseudo-labels to learn from unlabeled images and human–machine collaboration.
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•Existing approaches fail to approximate the classification probability.•Ensembles of models with differing sensitivity/precision express uncertainty.•Calibrated ensembles can approximate classification probability on unseen data.•Uncertainty quantification (UQ) might be used to better process or use unlabeled data.•Novel UQ method for pixel-wise probability heatmaps in 3D medical segmentation.
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