Miguel Romariz

Abstract
Abstract Background. Breast cancer treatment has improved overall survival rates, with different locoregional approaches offering patients similar locoregional control but variable aesthetic outcomes that may lead to disappointment and poor quality of life (QoL). There are no standardized methods for informing patients of the different therapies prior to intervention, nor validated tools for evaluation of aesthetics and patients' expectations. The CINDERELLA Project is based on years of research and developments of new healthcare technologies by various partners, aimed to provide an artificial intelligence (AI) tool to aid shared decision-making by showing breast cancer patients the predicted aesthetic outcomes of their locoregional treatment. The clinical trial will evaluate the use of this tool within an AI cloud-based platform approach (CINDERELLA App) versus a standard approach. We anticipate that the CINDERELLA App will lead to improved satisfaction, psychosocial well-being and health-related QoL while maintaining the quality of care and providing environmental and economic benefits. Trial design. CINDERELLA is an international multicentric interventional randomized controlled open-label clinical trial. Using the CINDERELLA App, the AI and Digital Health arm will provide patients with complete information about the proposed types of locoregional treatments and photographs of similar patients previously treated with the same techniques. The Control arm will follow the standard approach of each clinical site. Randomization will be conducted online using the digital health platform CANKADO, ensuring a balanced distribution of participants between the two groups. CANKADO is the underlying platform through which physicians control the patients' app content and conduct all data collection. Privacy, data protection and ethical principles in AI usage were taken into account. Eligibility criteria. Patients diagnosed with primary breast cancer without evidence of systemic disease. All patients must sign an informed consent and be able to use a web-based app autonomously or with home-based support. Specific aims. Primary objective: to assess the levels of agreement among patients' expectations regarding the aesthetic outcome before and 12 months after locoregional treatment. The trial will also evaluate the aesthetic outcome level of agreement between the AI evaluation tool and self-evaluation. Secondary objectives: health-related QoL (EQ-5D-5L and BREAST-Q ICHOM questionnaires) and resource consumption (e.g., time spent in the hospital, out-of-pocket expenses). The questionnaires and photographs will be applied prior to any treatment, at wound healing, at 6 and 12 months following the completion of locoregional therapy. Statistical methods. Wilcoxon signed rank test will be used to assess the intervention's impact on the agreement level between expectations and obtained results. Weighted Cohen's kappa will be calculated to measure the improvement in classifying aesthetic results with intervention. Statistical tests and/or bootstrap techniques will compare results between arms. A similarity measure will be calculated between self-evaluation and outcome obtained with the AI tool for each participant, and a beta regression model will be used to analyze the intervention's effect. Secondary objectives will be evaluated by scoring questionnaires based on provided guidelines. Target accrual. The clinical trial, led by Champalimaud Clinical Centre, will enroll a minimum of 515 patients in each arm between July 2023 and January 2025. Recruitment is currently open at five study sites in Germany, Israel, Italy, Poland and Portugal. The clinical trial is still open for further international study sites. Funding. European Union grant HORIZON-HLTH-2021-DISEASE-04-04 Agreement No. 101057389. Citation Format: Eduard-Alexandru Bonci, Orit Kaidar-Person, Marília Antunes, Oriana Ciani, Helena Cruz, Rosa Di Micco, Oreste Davide Gentilini, Nicole Rotmensz, Pedro Gouveia, Jörg Heil, Pawel Kabata, Nuno Freitas, Tiago Gonçalves, Miguel Romariz, Helena Montenegro, Hélder P. Oliveira, Jaime S. Cardoso, Henrique Martins, Daniela Lopes, Marta Martinho, Ludovica Borsoi, Elisabetta Listorti, Carlos Mavioso, Martin Mika, André Pfob, Timo Schinköthe, Giovani Silva, Maria-Joao Cardoso. CINDERELLA Clinical Trial (NCT05196269): using artificial intelligence-driven healthcare to enhance breast cancer locoregional treatment decisions [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-19-11.

Abstract

Abstract
TPS621 Background: Breast cancer treatments often pose challenges in balancing efficacy with quality of life. The CINDERELLA Project pioneers an artificial intelligence (AI)-driven approach (CINDERELLA APP) for shared decision-making process, aiming to harmonise locoregional therapeutic interventions with breast cancer patients' expectations about aesthetic outcomes. The CINDERELLA clinical trial aims to establish a new standard in patient-centred care by bridging the gap between clinical treatment options and patient expectations through innovative technology. The trial focuses on evaluating the effectiveness of the CINDERELLA APP in improving patient satisfaction regarding locoregional treatment aesthetic outcomes, aligning patient expectations with real-world results, and assessing its impact on overall quality of life and psychological well-being. Methods: Trial design and statistical methods: This international multicentric interventional randomised controlled open-label clinical trial will recruit and randomise patients into two groups: one receiving standard treatment information and the other using the AI-powered CINDERELLA APP. The primary objective is to assess the levels of agreement among patients' expectations regarding the aesthetic outcome before and 12 months after locoregional treatment. The trial will also evaluate the aesthetic outcome level of agreement between the AI evaluation tool and self-evaluation. The impact of the intervention on aligning expectations with outcomes will be evaluated using the Wilcoxon signed-rank test. The improvement in classification of aesthetic results post-intervention will be measured by calculating the Weighted Cohen's kappa. Outcomes across different groups will be compared using statistical tests and bootstrap methods. CANKADO functions as the base system, allowing doctors to supervise APP content for patients and handle data gathering, while upholding principles of privacy, data security, and ethical AI practices. Intervention planned: Using the CINDERELLA APP, the patient will have access to supervised medical information approved by breast cancer experts, and the AI system will match patient's information to pictures showing the potential aesthetic outcome (spectrum of good-poor) according to different locoregional approach. Major eligibility criteria: Non-metastatic breast cancer patients eligible for either breast-conserving surgery or mastectomy with immediate reconstruction. Current enrollment: Recruitment is currently open at six study sites. The recruitment started on 8 August 2023, aiming to enroll at least 515 patients/arm. As of January 26, 2024, clinical study sites have successfully randomised 177 patients. Clinical trial information: NCT05196269 .

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