Abstract
Breast cancer locoregional treatment causes alterations to the physical aspect of the breast, often negatively impacting the self-esteem of patients unaware of the possible aesthetic outcomes of those treatments. To improve patients' self-esteem and enable a more informed choice of treatment when multiple options are available, the possibility to predict how the patient might look like after surgery would be of invaluable help. However, no work has been proposed to predict the aesthetic outcomes of breast cancer treatment. As a first step, we compare traditional computer vision and deep learning approaches to reproduce asymmetries of post-operative patients on pre-operative breast images. The results suggest that the traditional approach is better at altering the contour of the breast. In contrast, the deep learning approach succeeds in realistically altering the position and direction of the nipple.

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
Breast cancer locoregional treatment can cause significant and long-lasting alterations to a patient's body. As various surgical options may be available to a patient and considering the impact that the aesthetic outcome may have on the patient's self-esteem, it is critical for the patient to be adequately informed of the possible outcomes of each treatment when deciding on the treatment plan. With the purpose of simulating how a patient may look like after treatment, we propose a deep generative model to transfer asymmetries caused by treatment from post-operative breast patients into pre-operative images, taking advantage of the inherent symmetry of breast images. Furthermore, we disentangle asymmetries related with the breast shape from the nipple within the latent space of the network, enabling higher control over the alterations to the breasts. Finally, we show the proposed model's wide applicability in medical imaging, by applying it to generate counterfactual explanations for cardiomegaly and pleural effusion prediction in chest radiographs.

Abstract
With the growing adoption of Deep Learning for imaging tasks in biometrics and healthcare, it becomes increasingly important to ensure privacy when using and sharing images of people. Several works enable privacy-preserving image sharing by anonymizing the images so that the corresponding individuals are no longer recognizable. Most works average images or their embeddings as an anonymization technique, relying on the assumption that the average operation is irreversible. Recently, cold diffusion models, based on the popular denoising diffusion probabilistic models, have succeeded in reversing deterministic transformations on images. In this work, we leverage cold diffusion to decompose superimposed images, empirically demonstrating that it is possible to obtain two or more identically-distributed images given their average. We propose novel sampling strategies for this task and show their efficacy on three datasets. Our findings highlight the risks of averaging images as an anonymization technique and argue for the use of alternative anonymization strategies.

Abstract
Breast cancer patients often face difficulties when choosing among diverse surgeries. To aid patients, this paper proposes ACID-GAN (Anatomically and Clinically Informed Deep Generative Adversarial Network), a conditional generative model for predicting post-operative breast cancer outcomes using deep learning. Built on Pix2Pix, the model incorporates clinical metadata, such as surgery type and cancer laterality, by introducing a dedicated encoder for semantic supervision. Further improvements include colour preservation and anatomically informed losses, as well as clinical supervision via segmentation and classification modules. Experiments on a private dataset demonstrate that the model produces realistic, context-aware predictions. The results demonstrate that the model presents a meaningful trade-off between generating precise, anatomically defined results and maintaining patient-specific appearance, such as skin tone and shape. © 2025 Elsevier B.V., All rights reserved.

Abstract
Breast cancer locoregional treatment includes a wide variety of procedures with diverse aesthetic outcomes. The aesthetic assessment of such procedures is typically subjective, hindering the fair comparison between their outcomes, and consequently restricting evidence-based improvements. Most objective evaluation tools were developed for conservative surgery, focusing on asymmetries while ignoring other relevant traits. To overcome these limitations, we propose SiameseOrdinalCLIP, an ordinal classification network based on image-text matching and pairwise ranking optimisation for the aesthetic evaluation of breast cancer treatment. Furthermore, we integrate a concept bottleneck module into the network for increased explainability. Experiments on a private dataset show that the proposed model surpasses the state-of-the-art aesthetic evaluation and ordinal classification networks. © 2025 Elsevier B.V., All rights reserved.