CINDERELLA: Comparing Decision on Aesthetics After Breast Cancer Locoregional Treatment.

Sponsor

Fundacao Champalimaud (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05196269

Collaborator

(none)

1,030

Enrollment

Locations

Arms

Anticipated Duration (Months)

257.5

Patients Per Site

6.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Breast cancer is the most commonly diagnosed cancer, with an estimated 2.3 million new cases per year globally. Approximately 90% of these patients will undergo breast surgery with/without radiation (locoregional treatment). Different surgical techniques can be offered to the patient, each leading to completely different aesthetic outcomes. Moreover, for different patients, undergoing the same surgery, the aesthetic outcome could be completely different based on individual patient's factors (e.g, age, body habitus). In the CINDERELLA trial the investigators will be using the (Breast Locoregional (BreLO) AI system (an artificial intelligence-based tool for classification of aesthetic outcomes and matching data and photographs) integrated in CANKADO (a cloud-based healthcare platform) to create an easy-to-use application that can be used on any electronic device, to simulate visually to the patient the aesthetic outcome of a certain surgery or radiation treatment. In the CINDERELLA trial the investigators plan to compare if the application helped to fulfil the expectations and lead to better quality of life compared with the classical approach. In the classical approach (control arm) doctors usually propose a locoregional treatment and explain theoretically how the result will be. Nurses help by explaining further details about surgery and possible outcomes. In the majority of centers no photographic evaluation is done and expectations are not measured. The CINDERELLA trial will help to overcome any miscommunication and potential boundaries in patient's or physician's understanding of the potential outcomes of locoregional treatment of breast cancer.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Device: Artificial Intelligence and Digital Health Arm	N/A

Detailed Description

The CINDERELLA clinical trial will be an open prospective randomized trial that will be coordinated by Champalimaud Foundation. Five clinical centers agreed to participate in the trial. The trial will be designed and reported according to the latest SPIRIT-AI and CONSORT-AI guidelines.

The randomization will be made adopting a dynamical approach following the Minimization Method. Assignment of the recruited patients to the study arms will take into account stratification of the participants (younger and older than 50 /breast conserving treatment or mastectomy /mastectomy with or without radiotherapy), aiming to reduce bias and confounding by assuring the balance of the group. This procedure will be centralized at CF using R package 'randPack' - Randomization routines for Clinical Trials - to implement the assignment routine.

After being proposed to the trial and checked that for all the eligibility criteria, patients' will be given the complete patient information before signing the informed consent.

For the 5 centres, a minimum of 515 patients should be enrolled in each arm of the study.

After randomization the patient will either follow

- The intervention arm with the CINDERELLA APProach (Fig. 7) with the introduction an access to the CANKADO with the BreLO AI system. Expectation's questionnaire and standard PROMs Q-5D, EORTC QLQ C-30 and EORTC BR-23/ EORTC QLQ BR-45 and BREAST Q ICHOM all be filled electronically. Standard photographic capture will be taken at this point. After the photographic capture the BreLO AI will match the patient biometrics and images with the more identical case existent in the BreLO repository and already classified by the BCCT.core into excellent, good, fair and poor. The new patient can then visualize the results.

In case of doubts query's will be answered through the app or if needed with phone call or booking of another appointment.

Questionnaires and Photographs will be repeated after healing is complete and six months and one year after the end of treatment (surgery or radiotherapy if radiotherapy was done). The Harris scale will also be completed by patients at the same time points and photographs will also be captured on the same moments.

- The control arm with the Conventional approach (Fig. 4) with a theoretical explanation by the doctor/nurse of the proposed locoregional treatment and possible outcomes. Expectation's questionnaire and standard PROMs Q-5D, EORTC QLQ C-30 and EORTC BR-23/ EORTC QLQ BR-45 and BREAST Q ICHOM all be filled in the paper version. Standard photographic capture will be taken at this point.

In case of doubts the patient will book of another appointment, with the doctor/nurse as usually done in routine practice.

DATA COLLECTION PATIENT RELATED FACTORS

Date of birth, Weight / Height /BMI, Thoracic perimeter, Bra size-Cup
Education degree, Profession, Hobbies
Marital status, Pregnancies and offspring
Breast-feeding, Menopausal status
Smoking, Diabetes, Alcohol
Connective tissue diseases
Confirmed Pathogenic Germline Variant TUMOUR RELATED FACTORS
Unilateral (unifocal, multifocal, multicentric) Bilateral
Histological type according to WHO classification (e.g., invasive ductal carcinoma, lobular carcinoma) (size in mm) staging ER, PR, Her2 and Ki67 . cTNM - pTNM /ypTNM TREATMENT RELATED FACTORS *Type of Surgery/ Type of Reconstruction: (data collection regarding surgery should include also ADM if used - type and placement) TYPE OF SURGERY C1- Conservative surgery - unilateral C2 - Conservative surgery - bilateral C2 - Conservative surgery with bilateral reduction (uni or bilateral) C3 - Conservative surgery with LD or LICAP / TDAP C4 - Conservative surgery with bilateral breast augmentation M1 -Mastectomy with unilateral reconstruction with implant M2 -Mastectomy with unilateral reconstruction with autologous flap M3 -Mastectomy with bilateral reconstruction with implants M4- Mastectomy with bilateral reconstruction with autologous flaps M5-Mastectomy with unilateral reconstruction with implant and contralateral symmetrisation with implant (augmentation).

M6-Mastectomy with unilateral reconstruction with implant and contralateral symmetrisation with reduction.

M7-Mastectomy with unilateral reconstrution with autologous flap and contralateral symmetrisation with reduction M8-Mastectomy with unilateral reconstruction with autologous flap and contralateral symmetrisation with implant (augmentation) Digital Photography (same protocol for all participating centers)

Before treatment in standard position for all patients
After healing is complete or prior to radiotherapy if planned
6 months after the end of locoregional treatment*
12 months after the end of locoregional treatment* A similar protocol for image capture will exist for all centers. The standalone photography with an automatic robot will be progressively implemented (photorobot.com)

*In case of adjuvant radiotherapy, consider the end of radiotherapy as the end of locoregional treatment Questionnaires

Expectations (before treatment and 6 and 12 months after treatment) no reference questionnaire exists.

(the developed questionnaire for the CINDERELLA study will be translated and validated in all languages before the start of the trial) according to standard validating procedures for expectations questionnaires.

Harris Scale (6 and 12 months after treatment) standard validated questionnaire for aesthetic outcome
EQ-5D, EORTC QLQ C-30 and EORTC BR-23/ EORTC QLQ BR-45 and BREAST Q ICHOM (at baseline 6 and 12 months after treatment) (all the questionnaires are validated for all languages except for the Portuguese version of the ICHOM questionnaire post-op. Cooperation and instructions for translation and validation have been already obtained from the Q -Portfolio Team)

STATISTICAL ANALYSIS An extensive descriptive analysis will be performed aiming to characterize the groups in detail as well as the outcomes of the study at baseline as well as in the following points of data collection.

Concerning the primary objectives, models of the class of generalized linear mixed models (in particular, multinomial regression models for ordinal data) will be estimated to evaluate the effect of the training and the women's characteristics on their evaluation of the aesthetic results of the surgery at each time and along time through longitudinal analysis. The Wilcoxon signed rank test for pairs will also be used to evaluate the effect of training in the level of agreement of the expectations and the final result. In order to assess the improvement in the ability to classify the aesthetic result of their surgery provided by training, Weighted Cohen's k will be calculated for both groups (train and control) and compared using a statistical test and/or bootstrap techniques. A measure of similarity between self-evaluation and the BCCT.core will be computed for each participant and a beta regression model will be estimated to assess the effect of training, controlling by variables that can play as confounders such as women's and disease's characteristics at each time point and in a longitudinal perspective.

Concerning the secondary objectives, the patient-reported outcome measures administered will be scored according to the official guidelines provided by the developers of the instruments. Utility values will be derived from the preference-based EQ-5D-5L questionnaire, based on the value set recently derived from a representative sample of the Italian population. Besides the descriptive statistics, the outcomes will be compared between groups using the adequate statistical tests. Again, models of the class of the general linear mixed models will be used.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

1030 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Prospective randomized open trial with parallel groupsProspective randomized open trial with parallel groups

Masking:

None (Open Label)

Primary Purpose:

Other

Official Title:

Comparing Decision on Match of Expectations and Aesthetics Using a Conventional Versus a Cloud Based Healthcare Platform Based Approach in Breast Cancer Patients Proposed for Locoregional Treatment: A Prospective Randomized Trial

Anticipated Study Start Date :

Jun 1, 2022

Anticipated Primary Completion Date :

Aug 1, 2024

Anticipated Study Completion Date :

Dec 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Artificial Intelligence and Digital Health Arm Using an Artificial Intelligence approach integrated in a cloud-based healthcare platform CANKADO to give the patient complete information about the proposed type of locoregional treatment and access to photographs and data of patients with similar characteristics previously treated with the same technique (using AI). All interaction will be through the CANKADO Platform	Device: Artificial Intelligence and Digital Health Arm A previous large database repository of images having thousands of pre and post operative photographs of breast cancer patients proposed for locoregional treatment with clinical and biometric data will be matched using artificial intelligence within the CANKADO platform. Patients proposed for breast cancer locoregional treatment will have the access to the software installed and they will have access to all the information about the type of treatment they will receive. All the question and questionnaires will be filled online and they can vusalize the expected outcome from excellent to poor. Other Names: Artificial Intellienge and cloud based digital health platform
Other: Control Comparator The standard approach of proposing patients for locoregional treatment with or without printed or digital materials and hypothetic visualization of results	Device: Artificial Intelligence and Digital Health Arm A previous large database repository of images having thousands of pre and post operative photographs of breast cancer patients proposed for locoregional treatment with clinical and biometric data will be matched using artificial intelligence within the CANKADO platform. Patients proposed for breast cancer locoregional treatment will have the access to the software installed and they will have access to all the information about the type of treatment they will receive. All the question and questionnaires will be filled online and they can vusalize the expected outcome from excellent to poor. Other Names: Artificial Intellienge and cloud based digital health platform

Arm

Intervention/Treatment

Experimental: Artificial Intelligence and Digital Health Arm

Using an Artificial Intelligence approach integrated in a cloud-based healthcare platform CANKADO to give the patient complete information about the proposed type of locoregional treatment and access to photographs and data of patients with similar characteristics previously treated with the same technique (using AI). All interaction will be through the CANKADO Platform

Device: Artificial Intelligence and Digital Health Arm

A previous large database repository of images having thousands of pre and post operative photographs of breast cancer patients proposed for locoregional treatment with clinical and biometric data will be matched using artificial intelligence within the CANKADO platform. Patients proposed for breast cancer locoregional treatment will have the access to the software installed and they will have access to all the information about the type of treatment they will receive. All the question and questionnaires will be filled online and they can vusalize the expected outcome from excellent to poor.

Other Names:

Artificial Intellienge and cloud based digital health platform

Other: Control Comparator

The standard approach of proposing patients for locoregional treatment with or without printed or digital materials and hypothetic visualization of results

Device: Artificial Intelligence and Digital Health Arm

Other Names:

Artificial Intellienge and cloud based digital health platform

Outcome Measures

Primary Outcome Measures

Agreement between patients expectations before and after treatment in both the intervention and the control arm. [12 months after locoregional treatment (surgery or radiotherapy in case adjuvant radiotherapy is done)]
Agreement between patient's expectations about the aesthetic outcome measured before and after treatment, evaluated at 12 months after treatment (Cohen's Kappa and weighted Kappa Statistics) both the intervention and the control arm.
Agreement about the aesthetic outcome between the objective evaluation and self- evaluation measured after treatment in both the intervention and the control arm [12 months after locoregional treatment (surgery or radiotherapy in case adjuvant radiotherapy is done)]
Agreement about the aesthetic outcome between the AI evaluation tool (BCT.core software) and self- evaluation after treatment (Cohen's Kappa and weighted Kappa Statistics) in both the intervention and the control arm.

Secondary Outcome Measures

Patient's body image satisfaction after surgery measured through the BREAST Q- International Consortium for Health Outcomes Measurement ( ICHOM ) questionnaire. [12 months after locoregional treatment (surgery or radiotherapy in case adjuvant radiotherapy is done)]
Body image perception and satisfaction using the BREAST Q- ICHOM questionnaire The scale scores from 0 lowest to 100 highest (body image satisfaction) in both the intervention and the control arm .
Resource consumption a) time spent in hospital, b) number of appointments, c) duration until treatment, d) out of pocket expenditure, additional care sought by patients [12 months after locoregional treatment (surgery or radiotherapy in case adjuvant radiotherapy is done]
Resource consumption ( cost per patient evaluated by the amount of appointments between the surgical proposal by the surgeon and the end of the trial) in both the intervention and control arm
Patient's satisfaction with their professional life evaluated in both the intervention and control arm with the EORTC QLQ C-30 (Quality of Life of Cancer Patients) and BR23 (Breast 23 items ) [12 months after locoregional treatment (surgery or radiotherapy in case adjuvant radiotherapy is done)]
How results impact in patients professional life measured through the EORTC QLQ C-30 and BR23 that is a companion questionnaire for the C-30 specific to breast with 23 items. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a high / healthy level of functioning.
Patient's sexual life satisfaction evaluated in both the intervention and control arm with with the EORTC QLQ C-30 (Quality of Life of Cancer Patients) and BR23 (Breast 23 items ) [12 months after locoregional treatment (surgery or radiotherapy in case adjuvant radiotherapy is done)]
How results impact in patients professional life measured through the EORTC QLQ C-30 and BR23 that is a companion questionnaire for the C-30 specific to breast with 23 items. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a high / healthy level of functioning.
Patient's general health-related quality of life evaluated in both the intervention and control arm with the EQ-5D-5L (Euro-Quality Group 5 dimensions /5 levels and EORTC QLQ C-30 questionnaires. [12 months after locoregional treatment (surgery or radiotherapy in case adjuvant radiotherapy is done)]
How results impact in patients general quality of life evaluated in both the intervention and control arm with the EQ-5D-5L and EORTC QLQ C-30 questionnaires. Both score from 0 -100. A high scale score represents a high / healthy level of functioning.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion :

More than 18 years old
Written informed consent
Primary breast cancer in situ or invasive without evidence of systemic disease - non Stage IV or locally advanced non-operable breast cancer.
ECOG performance status 0 or 1
Uni or Bilateral surgery even if prophylactic in one side
Capacity to use a web-based app autonomously or with home-based support

Exclusion:

Mastectomy without reconstruction
Pregnancy or lactation
Previous radiation to breast/chest (e.g., lymphoma)
Previous ipsilateral breast surgery due to malignant disease.
Other neoplasm in the last 5 years (excluding basal cell carcinoma of the skin and adequately treated carcinoma in situ of the cervix)
Severe skin disease that will contra-indicate the use of radiotherapy
Prophylactic surgery

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Universitätsklinikum Heidelberg	Heidelberg	Germany	69120
2	Medical Research Infrastructure Development and Health Services Fund by the Sheba Medical Center	Ramat Gan	Israel	52621
3	Ospedale San Raffaele Srl	Milano	Italy	20132
4	Gdanski Uniwersytet Medyczny	Gdańsk	Poland	80210