Co-occurrence of symptoms after radiochemotherapy in locally advanced cervix cancer patients: a cluster analysis

BACKGROUND: State of the art combined radiochemotherapy and image-guided brachytherapy for locally advanced cervical cancer (LACC) has shown improved disease control and survival as well as a significant reduction of organ related morbidity. However, LACC cancer survivors are still experiencing a spectrum of symptoms. The aim of this study was to identify co-occurring symptoms in cervix cancer survivors by using patient-reported outcome and physician assessed morbidity. MATERIALS AND METHOD: EMBRACE I is a multicenter prospective observational study with 1416 LACC patients (2008-2015). Information on physician-assessed morbidity and patient-reported outcome was assessed at baseline and at regular follow-ups up with the CTCAE v.3 and EORTC-C30/CX24, respectively. Patients with at least 2 years of follow-up were included and data from 3 months to 2 years was used in the analysis. Factor analysis was used on both EORTC and CTCAE data with symptoms and follow-ups as observations. The extracted factors represent clusters of symptoms. Subsequently, regression models were built to investigate associations between the symptom clusters and QOL. RESULTS: The analysis included 742 patients. Despite the differences in the definition of physician-assessed and patient-reported symptoms, similar clusters are identified by the two assessment methods. Three main organ-related clusters are recognized for urinary, gastro-intestinal and vaginal morbidity. Furthermore, a general symptoms cluster where fatigue, pain, insomnia, neuropathy, and hot flashes have large weights is found. Lastly, a cluster with nausea, vomit and lack of appetite is also identified. The general, gastrointestinal and nausea clusters show significant associations with general QOL. CONCLUSIONS: This analysis on both PRO and physician-assessed morbidity found a cluster associated with general symptoms and organ-related symptom clusters (urinary, gastrointestinal, vaginal). This shows that LACC survivors experience a variety of co-occurring symptoms. Our analysis also shows that the cluster of general symptoms is associated with a decrease in QOL.