Latent patterns of fatigue

Patterns of fatigue in patients with benign and malignant brain tumors [Seed Funding]

In a close collaboration, researchers from Tilburg University (departments of CNP and MTO) and Elisabeth-TweeSteden Hospital Tilburg investigate latent patterns in previously obtained data on fatigue in patients brain tumors before start of treatment, and their relationship with disease and patient characteristics. The aim is to 1) better understand the heterogeneity in the manifestation of fatigue in this population, and 2) provide a starting point for investigations into its longitudinal course and value in predicting functional and disease outcomes. This project is part of the Personalized Prevention and Care theme.

Brain tumors (BT) pose a great burden to health care due to their disruptive effects across cognitive, emotional, behavioral and physical functioning. Some symptoms, such as language and motor disorders, are relatively well understood, because they are closely linked to disease characteristics (e.g., tumor location). Other symptoms, such as fatigue, are more complex and remain hard to explain from patient and disease factors, despite efforts in clinical research. As a consequence, targeting appropriate interventions to alleviate them is difficult.

Fatigue is a multidimensional symptom that comprises several facets, e.g., physical, mental and activity-related. It is the most frequently reported symptom in the BT population, and affects patients’ lives across disease types and stages. For patients with a positive prognosis, fatigue can affect recovery towards regular daily functioning. In patients in the palliative phase, fatigue poses a threat to the main care priority, namely optimizing quality of life.

A key difficulty in finding effective interventions for fatigue is the vast heterogeneity in its nature and severity between individual BT patients. Published research mostly approaches fatigue as a unidimensional construct or studies its dimensions as separate outcomes. However, for an adequate understanding of the observed heterogeneity, it is essential to study fatigue as the multidimensional symptom it is. This means that the interdependency between its dimensions should be taken into account. Such an approach requires methodological expertise beyond that of most clinical researchers.

The goal is two-fold: 1) identify distinct pre-treatment “fatigue profiles”, and 2) relate fatigue profiles to disease and patient characteristics.

The identification of fatigue profiles, in which the complex nature of the symptom and individual differences and are taken into account, is an essential step towards the personalization of care. If fatigue profiles vary between different tumor types, this would warrant clinicians to tailor monitoring and intervention to (expected) diagnosis at an early stage. If profiles are similar across diagnoses, but differ as a function of patient characteristics, e.g., sex or age, a cross-diagnostic approach tailored to patient factors would be more appropriate. Furthermore, the results will provide a starting point for follow-up investigation in which we can study the longitudinal course of fatigue profiles. This would allow us to better understand the effects of treatment on the manifestation of fatigue.

This project is a key example of the importance of collaboration between different disciplines as well as between clinicians and scientists.

The project takes place at the intersection of neuro-oncology, (neuro-)psychology and, methodology, and aims to provide practical information for professionals involved in daily clinical care for brain tumor patients, but also provides a starting point for follow-up studies on the longitudinal course of fatigue profiles. The collaborating partners are affiliated with the department of Cognitive Neuropsychology of Tilburg School of Social and Behavior Sciences (TiU), the department of Neurosurgery at Elisabeth-Tweesteden Hospital (ETH) and the department of Methodology and Statistics (MTO) at Tilburg School of Social and Behavior Sciences (TiU). The departments CNP of TiU and Neurosurgery at ETH have a longstanding collaboration on projects regarding functional outcomes of patients with brain tumors. The MTO department has contributed its very specific methodological expertise in several of these collaborative studies.

The team

Elke Butterbrod is postdoctoral researcher at ETH’s department of Neurosurgery and at TiU’s department of Cognitive Neuropsychology. She focuses on prediction of cognitive outcomes in patients with primary brain tumors and the use of cognitive measures to predict survival.

Eline Verhaak is postdoctoral researcher at ETH’s Gamma Knife Center. Eline researches functional outcomes, a.o. fatigue, quality of life and cognition, in patients with brain metastases undergoing radiosurgical treatment.

Karin Gehring is senior researcher at TiU’s department of Cognitive Neuropsychology and at the ETH’s department of Neurosurgery, and has a proven track record in (international) research on cognitive functioning, and patient-reported outcomes including fatigue, and on cognitive rehabilitation, in patients with brain tumors.

Inga Schwabe is assistant professor at the department of Methodology and Statistics. She is an expert on Latent Class Analysis and (modelling of) genetic data and mood disorders.

Geert-Jan Rutten is neurosurgeon at ETH’s department of Neurosurgery. Alongside his clinical work, Geert-Jan’s research focuses on prediction of surgical and functional outcomes of patients with primary brain tumors and with a special interest in the use of neuroimaging modalities for this.

Margriet Sitskoorn is professor of Clinical Neuropsychology, program leader for TiU’s Impact-theme Enhancing Health & Wellbeing, and BIG-registered Clinical Neuropsychologist. Her research focus lies in (manifestations of) neural plasticity in healthy and (brain) diseased individuals. She also focuses on the translation of scientific neuroscientific knowledge for the general public, e.g., through her books.


Project duration: 2020 - 2021

Cross-cutting themes

The Herbert Simon Research Institute for Health, Well-being, and Adaptiveness is a research center devoted to carrying out excellent, state of the art research in order to contribute to healthy and resilient people. We have selected three themes, which involve the collaboration between various Departments  and address actual themes in need of both fundamental and applied research.