An eHealth App (CAPABLE) Providing Symptom Monitoring, Well-Being Interventions, and Educational Material for Patients With Melanoma Treated With Immune Checkpoint Inhibitors: Protocol for an Exploratory Intervention Trial.

BACKGROUND: Since treatment with immune checkpoint inhibitors (ICIs) is becoming standard therapy for patients with high-risk and advanced melanoma, an increasing number of patients experience treatment-related adverse events such as fatigue. Until now, studies have demonstrated the benefits of using eHealth tools to provide either symptom monitoring or interventions to reduce treatment-related symptoms such as fatigue. However, an eHealth tool that facilitates the combination of both symptom monitoring and symptom management in patients with melanoma treated with ICIs is still needed. OBJECTIVE: In this pilot study, we will explore the use of the CAPABLE (Cancer Patients Better Life Experience) app in providing symptom monitoring, education, and well-being interventions on health-related quality of life (HRQoL) outcomes such as fatigue and physical functioning, as well as patients' acceptance and usability of using CAPABLE. METHODS: This prospective, exploratory pilot study will examine changes in fatigue over time in 36 patients with stage III or IV melanoma during treatment with ICI using CAPABLE (a smartphone app and multisensory smartwatch). This cohort will be compared to a prospectively collected cohort of patients with melanoma treated with standard ICI therapy. CAPABLE will be used for a minimum of 3 and a maximum of 6 months. The primary endpoint in this study is the change in fatigue between baseline and 3 and 6 months after the start of treatment. Secondary end points include HRQoL outcomes, usability, and feasibility parameters. RESULTS: Study inclusion started in April 2023 and is currently ongoing. CONCLUSIONS: This pilot study will explore the effect, usability, and feasibility of CAPABLE in patients with melanoma during treatment with ICI. Adding the CAPABLE system to active treatment is hypothesized to decrease fatigue in patients with high-risk and advanced melanoma during treatment with ICIs compared to a control group receiving standard care. The Medical Ethics Committee NedMec (Amsterdam, The Netherlands) granted ethical approval for this study (reference number 22-981/NL81970.000.22). TRIAL REGISTRATION: ClinicalTrials.gov NCT05827289; https://clinicaltrials.gov/study/NCT05827289. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/49252.

Artificial intelligence-based prediction of overall survival in metastatic renal cell carcinoma.

Background and objectives: Investigations of the prognosis are vital for better patient management and decision-making in patients with advanced metastatic renal cell carcinoma (mRCC). The purpose of this study is to evaluate the capacity of emerging Artificial Intelligence (AI) technologies to predict three- and five-year overall survival (OS) for mRCC patients starting their first-line of systemic treatment. Patients and methods: The retrospective study included 322 Italian patients with mRCC who underwent systemic treatment between 2004 and 2019. Statistical analysis included the univariate and multivariate Cox proportional-hazard model and the Kaplan-Meier analysis for the prognostic factors' investigation. The patients were split into a training cohort to establish the predictive models and a hold-out cohort to validate the results. The models were evaluated by the area under the receiver operating characteristic curve (AUC), sensitivity, and specificity. We assessed the clinical benefit of the models using decision curve analysis (DCA). Then, the proposed AI models were compared with well-known pre-existing prognostic systems. Results: The median age of patients in the study was 56.7 years at RCC diagnosis and 78% of participants were male. The median survival time from the start of systemic treatment was 29.2 months; 95% of the patients died during the follow-up that finished by the end of 2019. The proposed predictive model, which was constructed as an ensemble of three individual predictive models, outperformed all well-known prognostic models to which it was compared. It also demonstrated better usability in supporting clinical decisions for 3- and 5-year OS. The model achieved (0.786 and 0.771) AUC and (0.675 and 0.558) specificity at sensitivity 0.90 for 3 and 5 years, respectively. We also applied explainability methods to identify the important clinical features that were found to be partially matched with the prognostic factors identified in the Kaplan-Meier and Cox analyses. Conclusions: Our AI models provide best predictive accuracy and clinical net benefits over well-known prognostic models. As a result, they can potentially be used in clinical practice for providing better management for mRCC patients starting their first-line of systemic treatment. Larger studies would be needed to validate the developed model.

A Competition, Benchmark, Code, and Data for Using Artificial Intelligence to Detect Lesions in Digital Breast Tomosynthesis.

Importance: An accurate and robust artificial intelligence (AI) algorithm for detecting cancer in digital breast tomosynthesis (DBT) could significantly improve detection accuracy and reduce health care costs worldwide. Objectives: To make training and evaluation data for the development of AI algorithms for DBT analysis available, to develop well-defined benchmarks, and to create publicly available code for existing methods. Design, Setting, and Participants: This diagnostic study is based on a multi-institutional international grand challenge in which research teams developed algorithms to detect lesions in DBT. A data set of 22 032 reconstructed DBT volumes was made available to research teams. Phase 1, in which teams were provided 700 scans from the training set, 120 from the validation set, and 180 from the test set, took place from December 2020 to January 2021, and phase 2, in which teams were given the full data set, took place from May to July 2021. Main Outcomes and Measures: The overall performance was evaluated by mean sensitivity for biopsied lesions using only DBT volumes with biopsied lesions; ties were broken by including all DBT volumes. Results: A total of 8 teams participated in the challenge. The team with the highest mean sensitivity for biopsied lesions was the NYU B-Team, with 0.957 (95% CI, 0.924-0.984), and the second-place team, ZeDuS, had a mean sensitivity of 0.926 (95% CI, 0.881-0.964). When the results were aggregated, the mean sensitivity for all submitted algorithms was 0.879; for only those who participated in phase 2, it was 0.926. Conclusions and Relevance: In this diagnostic study, an international competition produced algorithms with high sensitivity for using AI to detect lesions on DBT images. A standardized performance benchmark for the detection task using publicly available clinical imaging data was released, with detailed descriptions and analyses of submitted algorithms accompanied by a public release of their predictions and code for selected methods. These resources will serve as a foundation for future research on computer-assisted diagnosis methods for DBT, significantly lowering the barrier of entry for new researchers.

Virtual Biopsy by Using Artificial Intelligence-based Multimodal Modeling of Binational Mammography Data.

Background Computational models based on artificial intelligence (AI) are increasingly used to diagnose malignant breast lesions. However, assessment from radiologic images of the specific pathologic lesion subtypes, as detailed in the results of biopsy procedures, remains a challenge. Purpose To develop an AI-based model to identify breast lesion subtypes with mammograms and linked electronic health records labeled with histopathologic information. Materials and Methods In this retrospective study, 26 569 images were collected in 9234 women who underwent digital mammography to pretrain the algorithms. The training data included individuals who had at least 1 year of clinical and imaging history followed by biopsy-based histopathologic diagnosis from March 2013 to November 2018. A model that combined convolutional neural networks with supervised learning algorithms was independently trained to make breast lesion predictions with data from 2120 women in Israel and 1642 women in the United States. Results were reported using the area under the receiver operating characteristic curve (AUC) with the 95% DeLong approach to estimate CIs. Significance was tested with bootstrapping. Results The Israeli model was validated in 456 women and tested in 441 women (mean age, 51 years ± 11 [SD]). The U.S. model was validated in 350 women and tested in 344 women (mean age, 60 years ± 12). For predicting malignancy in the test sets (consisting of 220 Israeli patient examinations and 126 U.S. patient examinations with ductal carcinoma in situ or invasive cancer), the algorithms obtained an AUC of 0.88 (95% CI: 0.85, 0.91) and 0.80 (95% CI: 0.74, 0.85) for Israeli and U.S. patients, respectively (P = .006). These results may not hold for other cohorts of patients, and generalizability across populations should be further investigated. Conclusion The results offer supporting evidence that artificial intelligence applied to clinical and mammographic images can identify breast lesion subtypes when the data are sufficiently large, which may help assess diagnostic workflow and reduce biopsy sampling errors. Published under a CC BY 4.0 license. Online supplemental material is available for this article.

Artificial Intelligence for Reducing Workload in Breast Cancer Screening with Digital Breast Tomosynthesis.

Background Digital breast tomosynthesis (DBT) has higher diagnostic accuracy than digital mammography, but interpretation time is substantially longer. Artificial intelligence (AI) could improve reading efficiency. Purpose To evaluate the use of AI to reduce workload by filtering out normal DBT screens. Materials and Methods The retrospective study included 13 306 DBT examinations from 9919 women performed between June 2013 and November 2018 from two health care networks. The cohort was split into training, validation, and test sets (3948, 1661, and 4310 women, respectively). A workflow was simulated in which the AI model classified cancer-free examinations that could be dismissed from the screening worklist and used the original radiologists' interpretations on the rest of the worklist examinations. The AI system was also evaluated with a reader study of five breast radiologists reading the DBT mammograms of 205 women. The area under the receiver operating characteristic curve (AUC), sensitivity, specificity, and recall rate were evaluated in both studies. Statistics were computed across 10 000 bootstrap samples to assess 95% CIs, noninferiority, and superiority tests. Results The model was tested on 4310 screened women (mean age, 60 years ± 11 [standard deviation]; 5182 DBT examinations). Compared with the radiologists' performance (417 of 459 detected cancers [90.8%], 477 recalls in 5182 examinations [9.2%]), the use of AI to automatically filter out cases would result in 39.6% less workload, noninferior sensitivity (413 of 459 detected cancers; 90.0%; P = .002), and 25% lower recall rate (358 recalls in 5182 examinations; 6.9%; P = .002). In the reader study, AUC was higher in the standalone AI compared with the mean reader (0.84 vs 0.81; P = .002). Conclusion The artificial intelligence model was able to identify normal digital breast tomosynthesis screening examinations, which decreased the number of examinations that required radiologist interpretation in a simulated clinical workflow. Published under a CC BY 4.0 license. Online supplemental material is available for this article. See also the editorial by Philpotts in this issue.

Leveraging Comprehensive Health Records for Breast Cancer Risk Prediction: A Binational Assessment.

Breast cancer (BC) risk models based on electronic health records (EHR) can assist physicians in estimating the probability of an individual with certain risk factors to develop BC in the future. In this retrospective study, we used clinical data combined with machine learning tools to assess the utility of a personalized BC risk model on 13,786 Israeli and 1,695 American women who underwent screening mammography in the years 2012-2018 and 2008-2018, respectively. Clinical features were extracted from EHR, personal questionnaires, and past radiologists' reports. Using a set of 1,547 features, the predictive ability for BC within 12 months was measured in both datasets and in sub-cohorts of interest. Our results highlight the improved performance of our model over previous established BC risk models, their ultimate potential for risk-based screening policies on first time patients and novel clinically relevant risk factors that can compensate for the absence of imaging history information.

Predicting Breast Cancer by Applying Deep Learning to Linked Health Records and Mammograms.

Background Computational models on the basis of deep neural networks are increasingly used to analyze health care data. However, the efficacy of traditional computational models in radiology is a matter of debate. Purpose To evaluate the accuracy and efficiency of a combined machine and deep learning approach for early breast cancer detection applied to a linked set of digital mammography images and electronic health records. Materials and Methods In this retrospective study, 52 936 images were collected in 13 234 women who underwent at least one mammogram between 2013 and 2017, and who had health records for at least 1 year before undergoing mammography. The algorithm was trained on 9611 mammograms and health records of women to make two breast cancer predictions: to predict biopsy malignancy and to differentiate normal from abnormal screening examinations. The study estimated the association of features with outcomes by using t test and Fisher exact test. The model comparisons were performed with a 95% confidence interval (CI) or by using the DeLong test. Results The resulting algorithm was validated in 1055 women and tested in 2548 women (mean age, 55 years ± 10 [standard deviation]). In the test set, the algorithm identified 34 of 71 (48%) false-negative findings on mammograms. For the malignancy prediction objective, the algorithm obtained an area under the receiver operating characteristic curve (AUC) of 0.91 (95% CI: 0.89, 0.93), with specificity of 77.3% (95% CI: 69.2%, 85.4%) at a sensitivity of 87%. When trained on clinical data alone, the model performed significantly better than the Gail model (AUC, 0.78 vs 0.54, respectively; P < .004). Conclusion The algorithm, which combined machine-learning and deep-learning approaches, can be applied to assess breast cancer at a level comparable to radiologists and has the potential to substantially reduce missed diagnoses of breast cancer. © RSNA, 2019 Online supplemental material is available for this article.