Combining Deep Learning and Handcrafted Radiomics for Classification of Suspicious Lesions on Contrast-enhanced Mammograms.

Background Handcrafted radiomics and deep learning (DL) models individually achieve good performance in lesion classification (benign vs malignant) on contrast-enhanced mammography (CEM) images. Purpose To develop a comprehensive machine learning tool able to fully automatically identify, segment, and classify breast lesions on the basis of CEM images in recall patients. Materials and Methods CEM images and clinical data were retrospectively collected between 2013 and 2018 for 1601 recall patients at Maastricht UMC+ and 283 patients at Gustave Roussy Institute for external validation. Lesions with a known status (malignant or benign) were delineated by a research assistant overseen by an expert breast radiologist. Preprocessed low-energy and recombined images were used to train a DL model for automatic lesion identification, segmentation, and classification. A handcrafted radiomics model was also trained to classify both human- and DL-segmented lesions. Sensitivity for identification and the area under the receiver operating characteristic curve (AUC) for classification were compared between individual and combined models at the image and patient levels. Results After the exclusion of patients without suspicious lesions, the total number of patients included in the training, test, and validation data sets were 850 (mean age, 63 years ± 8 [SD]), 212 (62 years ± 8), and 279 (55 years ± 12), respectively. In the external data set, lesion identification sensitivity was 90% and 99% at the image and patient level, respectively, and the mean Dice coefficient was 0.71 and 0.80 at the image and patient level, respectively. Using manual segmentations, the combined DL and handcrafted radiomics classification model achieved the highest AUC (0.88 [95% CI: 0.86, 0.91]) (P < .05 except compared with DL, handcrafted radiomics, and clinical features model, where P = .90). Using DL-generated segmentations, the combined DL and handcrafted radiomics model showed the highest AUC (0.95 [95% CI: 0.94, 0.96]) (P < .05). Conclusion The DL model accurately identified and delineated suspicious lesions on CEM images, and the combined output of the DL and handcrafted radiomics models achieved good diagnostic performance. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Bahl and Do in this issue.

Development of an isotoxic decision support system integrating genetic markers of toxicity for the implantation of a rectum spacer.

INTRODUCTION: Previous studies revealed that dose escalated radiotherapy for prostate cancer patients leads to higher tumor control probabilities (TCP) but also to higher rectal toxicities. An isotoxic model was developed to maximize the given dose while controlling the toxicity level. This was applied to analyze the effect of an implantable rectum spacer (IRS) and extended with a genetic test of normal tissue radio-sensitivity. A virtual IRS (V-IRS) was tested using this method. We hypothesized that the patients with increased risk of toxicity would benefit more from an IRS. MATERIAL AND METHODS: Sixteen localized prostate cancer patients implanted with an IRS were included in the study. Treatment planning was performed on computed tomography (CT) images before and after the placement of the IRS and with a V-IRS. The normal tissue complication probability (NTCP) was calculated using a QUANTEC reviewed model for Grade > =2 late rectal bleeding and the number of fractions of the plans were adjusted until the NTCP value was under 5%. The resulting treatment plans were used to calculate the TCP before and after placement of an IRS. This was extended by adding the effect of two published genetic single nucleotide polymorphisms (SNP's) for late rectal bleeding. RESULTS: The median TCP resulting from the optimized plans in patients before the IRS was 75.1% [32.6-90.5%]. With IRS, the median TCP is significantly higher: 98.9% [80.8-99.9%] (p < .01). The difference in TCP between the V-IRS and the real IRS was 1.8% [0.0-18.0%]. Placing an IRS in the patients with SNP's improved the TCP from 49.0% [16.1-80.8%] and 48.9% [16.0-72.8%] to 96.3% [67.0-99.5%] and 90.1% [49.0-99.5%] (p < .01) respectively for either SNP. CONCLUSION: This study was a proof-of-concept for an isotoxic model with genetic biomarkers with a V-IRS as a multifactorial decision support system for the decision of a placement of an IRS.

Open Source Repository and Online Calculator of Prediction Models for Diagnosis and Prognosis in Oncology.

(1) Background: The main aim was to develop a prototype application that would serve as an open-source repository for a curated subset of predictive and prognostic models regarding oncology, and provide a user-friendly interface for the included models to allow online calculation. The focus of the application is on providing physicians and health professionals with patient-specific information regarding treatment plans, survival rates, and side effects for different expected treatments. (2) Methods: The primarily used models were the ones developed by our research group in the past. This selection was completed by a number of models, addressing the same cancer types but focusing on other outcomes that were selected based on a literature search in PubMed and Medline databases. All selected models were publicly available and had been validated TRIPOD (Transparent Reporting of studies on prediction models for Individual Prognosis Or Diagnosis) type 3 or 2b. (3) Results: The open source repository currently incorporates 18 models from different research groups, evaluated on datasets from different countries. Model types included logistic regression, Cox regression, and recursive partition analysis (decision trees). (4) Conclusions: An application was developed to enable physicians to complement their clinical judgment with user-friendly patient-specific predictions using models that have received internal/external validation. Additionally, this platform enables researchers to display their work, enhancing the use and exposure of their models.

Modeling-Based Decision Support System for Radical Prostatectomy Versus External Beam Radiotherapy for Prostate Cancer Incorporating an In Silico Clinical Trial and a Cost-Utility Study.

The aim of this study is to build a decision support system (DSS) to select radical prostatectomy (RP) or external beam radiotherapy (EBRT) for low- to intermediate-risk prostate cancer patients. We used an individual state-transition model based on predictive models for estimating tumor control and toxicity probabilities. We performed analyses on a synthetically generated dataset of 1000 patients with realistic clinical parameters, externally validated by comparison to randomized clinical trials, and set up an in silico clinical trial for elderly patients. We assessed the cost-effectiveness (CE) of the DSS for treatment selection by comparing it to randomized treatment allotment. Using the DSS, 47.8% of synthetic patients were selected for RP and 52.2% for EBRT. During validation, differences with the simulations of late toxicity and biochemical failure never exceeded 2%. The in silico trial showed that for elderly patients, toxicity has more influence on the decision than TCP, and the predicted QoL depends on the initial erectile function. The DSS is estimated to result in cost savings (EUR 323 (95% CI: EUR 213-433)) and more quality-adjusted life years (QALYs; 0.11 years, 95% CI: 0.00-0.22) than randomized treatment selection.

Decision Support Systems in Oncology.

Precision medicine is the future of health care: please watch the animation at https://vimeo.com/241154708 . As a technology-intensive and -dependent medical discipline, oncology will be at the vanguard of this impending change. However, to bring about precision medicine, a fundamental conundrum must be solved: Human cognitive capacity, typically constrained to five variables for decision making in the context of the increasing number of available biomarkers and therapeutic options, is a limiting factor to the realization of precision medicine. Given this level of complexity and the restriction of human decision making, current methods are untenable. A solution to this challenge is multifactorial decision support systems (DSSs), continuously learning artificial intelligence platforms that integrate all available data-clinical, imaging, biologic, genetic, cost-to produce validated predictive models. DSSs compare the personalized probable outcomes-toxicity, tumor control, quality of life, cost effectiveness-of various care pathway decisions to ensure optimal efficacy and economy. DSSs can be integrated into the workflows both strategically (at the multidisciplinary tumor board level to support treatment choice, eg, surgery or radiotherapy) and tactically (at the specialist level to support treatment technique, eg, prostate spacer or not). In some countries, the reimbursement of certain treatments, such as proton therapy, is already conditional on the basis that a DSS is used. DSSs have many stakeholders-clinicians, medical directors, medical insurers, patient advocacy groups-and are a natural consequence of big data in health care. Here, we provide an overview of DSSs, their challenges, opportunities, and capacity to improve clinical decision making, with an emphasis on the utility in oncology.

Towards a Clinical Decision Support System for External Beam Radiation Oncology Prostate Cancer Patients: Proton vs. Photon Radiotherapy? A Radiobiological Study of Robustness and Stability.

We present a methodology which can be utilized to select proton or photon radiotherapy in prostate cancer patients. Four state-of-the-art competing treatment modalities were compared (by way of an in silico trial) for a cohort of 25 prostate cancer patients, with and without correction strategies for prostate displacements. Metrics measured from clinical image guidance systems were used. Three correction strategies were investigated; no-correction, extended-no-action-limit, and online-correction. Clinical efficacy was estimated via radiobiological models incorporating robustness (how probable a given treatment plan was delivered) and stability (the consistency between the probable best and worst delivered treatments at the 95% confidence limit). The results obtained at the cohort level enabled the determination of a threshold for likely clinical benefit at the individual level. Depending on the imaging system and correction strategy; 24%, 32% and 44% of patients were identified as suitable candidates for proton therapy. For the constraints of this study: Intensity-modulated proton therapy with online-correction was on average the most effective modality. Irrespective of the imaging system, each treatment modality is similar in terms of robustness, with and without the correction strategies. Conversely, there is substantial variation in stability between the treatment modalities, which is greatly reduced by correction strategies. This study provides a 'proof-of-concept' methodology to enable the prospective identification of individual patients that will most likely (above a certain threshold) benefit from proton therapy.

Big Data in radiation therapy: challenges and opportunities.

Data collected and generated by radiation oncology can be classified by the Volume, Variety, Velocity and Veracity (4Vs) of Big Data because they are spread across different care providers and not easily shared owing to patient privacy protection. The magnitude of the 4Vs is substantial in oncology, especially owing to imaging modalities and unclear data definitions. To create useful models ideally all data of all care providers are understood and learned from; however, this presents challenges in the guise of poor data quality, patient privacy concerns, geographical spread, interoperability and large volume. In radiation oncology, there are many efforts to collect data for research and innovation purposes. Clinical trials are the gold standard when proving any hypothesis that directly affects the patient. Collecting data in registries with strict predefined rules is also a common approach to find answers. A third approach is to develop data stores that can be used by modern machine learning techniques to provide new insights or answer hypotheses. We believe all three approaches have their strengths and weaknesses, but they should all strive to create Findable, Accessible, Interoperable, Reusable (FAIR) data. To learn from these data, we need distributed learning techniques, sending machine learning algorithms to FAIR data stores around the world, learning from trial data, registries and routine clinical data rather than trying to centralize all data. To improve and personalize medicine, rapid learning platforms must be able to process FAIR "Big Data" to evaluate current clinical practice and to guide further innovation.

Development of a virtual spacer to support the decision for the placement of an implantable rectum spacer for prostate cancer radiotherapy: Comparison of dose, toxicity and cost-effectiveness.

INTRODUCTION: Previous studies have shown that the implantable rectum spacer (IRS) is not beneficial for all patients. A virtual IRS (V-IRS) was constructed to help identify the patients for whom it is cost-effective to implant an IRS, and its viability as a tool to tailor the decision of an IRS implantation to be beneficial for the specified patient was assessed. Please watch animation: (https://www.youtube.com/watch?v=tDlagSXMKqw) MATERIALS AND METHODS: The V-IRS was tested on 16 patients: 8 with a rectal balloon implant (RBI) and 8 with a hydrogel spacer. A V-IRS was developed using 7 computed tomography (CT) scans of patients with a RBI. To examine the V-IRS, CT scans before and after the implantation of an IRS were used. IMRT plans were made based on CT scans before the IRS, after IRS and with the V-IRS, prescribing 70 Gray (Gy) to the planning target volume. Toxicity was accessed using externally validated normal tissue complication probability (NTCP) models, and the Cost-effectiveness was analyzed using a published Markov model. RESULTS: The rectum volume receiving 75Gy (V75) were improved by both the IRS and the V-IRS with on average 4.2% and 4.3% respectively. The largest NTCP reduction resulting from the IRS and the V-IRS was 4.0% and 3.9% respectively. The RBI was cost-effective for 1 out of 8 patients, and the hydrogel was effective for 2 out of 8 patients, and close to effective for a third patient. The classification accuracy of the model, regarding cost-effectiveness, was 100%. CONCLUSION: The V-IRS approach in combination with a toxicity prediction model and a cost-effectiveness analyses is a promising basis for a decision support tool for the implantation of either a hydrogel spacer or a rectum balloon implant.

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.