Statistical analysis plan for the PRO B study: open-label, superiority randomised controlled trial of alarm-based patient-reported outcome monitoring in patients with metastatic breast cancer.

BACKGROUND: With an increasing collection of patient-reported outcomes (PROs) to measure health-related quality of life (HRQoL) in oncological patients, there is still a lack of standardised strategies on how to interpret and use these data in patient care. Prior research has shown support for the use of digital PRO monitoring together with alarm systems to notify clinicians when the PRO values are deteriorating. This system has demonstrated advantages in improving HRQoL and increasing survival rates among oncology patients. Hence, we designed the PRO B study, a superiority multi-centre randomised controlled trial, to investigate the effects of alarm-based monitoring in metastatic breast cancer patients in Germany. The study protocol for the PRO B study was published in September 2021, and this manuscript describes a formal statistical analysis plan (SAP) for the PRO B study to improve the transparency and quality of this trial. METHODS AND DESIGN: The trial aimed to recruit 1000 patients with metastatic breast cancer. However, as of the completion of recruitment on June 15, 2023, we have successfully enrolled 924 patients from 52 breast cancer centres. Patients were 1:1 stratified randomised to the intervention and control groups. App-based PRO questionnaires are sent weekly to the intervention group and every 3 months to the control group. Only patients in the intervention group trigger an alarm if their PRO scores deteriorate, and they are subsequently contacted by the local care team within 48 h. The primary outcome is the fatigue score at 6 months, and secondary outcomes are other HRQoL and overall survival. Evaluation of the superiority of the intervention will be done using a linear mixed model with random intercepts for study centres. CONCLUSION: This detailed SAP defines the main components of the statistical analysis for the PRO B study to assist the statistician and prevent bias in selecting analysis and reporting findings. Version 1 of the SAP was finalised on January 18, 2024. TRIAL REGISTRATION: DRKS (German Clinical Trials Register) DRKS00024015 . Registered on February 15, 2021.

Association of body mass index with clinicopathological features and survival in patients with primary invasive lobular breast cancer.

PURPOSE: Invasive lobular carcinoma (ILC) represents up to 15% of all breast carcinomas. While the proportion of women with overweight and obesity increases globally, the impact of body mass index (BMI) at primary diagnosis on clinicopathological features of ILC and the prognosis of the patients has not been investigated yet. PATIENTS AND METHODS: We performed a multicentric retrospective study including patients diagnosed with non-metastatic pure ILC. The association of BMI at diagnosis with clinicopathological variables was assessed using linear or multinomial logistic regression. Univariable and multivariable survival analyses were performed to evaluate the association of BMI with disease-free survival (DFS), distant recurrence-free survival (DRFS), and overall survival (OS). RESULTS: The data of 2856 patients with ILC and available BMI at diagnosis were collected, of which 2570/2856 (90.0%) had oestrogen receptor (ER)-positive and human epidermal growth factor receptor (HER2) not amplified/overexpressed (ER+/HER2-) ILC. Of these 2570 patients, 80 were underweight (3.1%), 1410 were lean (54.9%), 712 were overweight (27.7%), and 368 were obese (14.3%). Older age at diagnosis, a higher tumour grade, a larger tumour size, a nodal involvement, and multifocality were associated with a higher BMI. In univariable models, higher BMI was associated with worse outcomes for all end-points (DFS: hazard ratio (HR) 1.21, 95CI 1.12-1.31, p value<0.01; DRFS: HR 1.25, 95CI 1.12-1.40, p value<0.01; OS: HR 1.25, 95CI 1.13-1.37, p value<0.01). This association was not statistically significant in multivariable analyses (DFS: HR 1.09, 95CI 0.99-1.20, p value 0.08; DRFS: HR 1.03, 95CI 0.89-1.20, p value 0.67; OS: HR 1.11, 95CI 0.99-1.24, p value 0.08), whereas grade, tumour size, and nodal involvement were still prognostic for all end-points. CONCLUSION: Worse prognostic factors such as higher grade, larger tumour size, and nodal involvement are associated with higher BMI in ER+/HER2- ILC, while there was no statistical evidence for an independent prognostic role for BMI. Therefore, we hypothesise that the effect of BMI on survival could be mediated through its association with these clinicopathological variables.

Data of real-world reference scores for EORTC QLQ-C30 and QLQ-BR23 at baseline in women with early breast cancer and other breast diseases.

Patient-reported outcomes are information about health status and health-related quality of life collected directly from patients. The data in this publication contain the first assessment of patient-reported outcomes (PROs) from real-life measurements in the breast cancer center at Charité - Universitätsmedizin Berlin between November 2016 and March 2021. At baseline (before the start of treatment), 1727 ambulatory patients with early breast cancer, ductal carcinoma in situ (DCIS), fibroadenoma, and other breast diseases were registered in the digital PRO-system as part of clinical routine. Patients' sociodemographic data, medical history, clinical variables, and raw scores of the EORTC QLQ-C30 and EORTC QLQ-BR23 are provided in this publication. This dataset can be used as a reference for PROs in a clinical care setting or in clinical studies with breast diseases and contribute to the discussion about the interpretation of score values. Furthermore, the association between patients' sociodemographic data, clinical variables, and PRO data at baseline can be analysed further.