CODAGLIO 2.0: Combining clinical trial datasets in glioma patients to answer clinically relevant questions about patients’ health related quality of life

The CODAGLIO 2.0 project, which started in October 2022, aims to update the original CODAGLIO database to a version 2.0 by adding new randomized controlled trials (RCTs) conducted in glioma (i.e., primary brain tumor) patients as well as the addition of clinical variables, including tumor molecular data and physician-reported adverse events data, to already existing trials in the original database. The project is a collaboration between the Quality of Life Group, the Brain Tumor Group, and the Quality of Life Department. We have included 17 RCTs conducted in about 5931 patients in the database. With this large database, we will be able to answer five clinically relevant questions, such as: ‘1) Is there a difference in HRQoL patterns between glioma patients with different molecular profiles (WHO 2021 criteria)?’, ‘2) Are HRQoL patterns in glioma patients related to sociodemographic characteristics (e.g., age or sex)?’, ‘3) Can we identify symptom(s) (clusters) that are predictive of radiological tumor progression in glioma patients?’, ‘4) Are physician-reported adverse events translated into a deterioration in HRQoL over time in glioma?’, and ‘5) Can HRQoL during the course of disease be accurately predicted using machine-learning models?’.

Since the approval of the study by the institutional review board of Leiden University Medical Center, we have obtained consent from the principal investigators or pharmaceutical companies to include the data collected in clinical trials into our database. We have also established the Data Sharing and Transfer Agreements. Ultimately, we have harmonized and cleaned all the data for statistical analysis and constructed detailed and coherent statistical analysis plans for all the research questions.

Research Question 1 and 2: Data is fully analyzed. The manuscript is in preparation.

Research Question 3: Statistical analysis is ongoing.

Research Questions 4 and 5: Not started yet.

Address Research Questions 4 and 5, complete the statistical analyses and write up the manuscripts.

Patients with a glioma, the most prevalent primary malignant brain tumor, demonstrate a high symptom burden including motor weakness, cognitive dysfunction, seizures, etc. Although patients are treated with surgery, radiotherapy, and chemotherapy, current treatment options are not curative. Therefore, the quality of survival is for these patients at least as important as the duration of survival. Collection of enough quality of survival data is crucial but challenging in patients with glioma, as glioma is a relatively rare disease, only a few trials included health-related quality of life (HRQOL) assessments, and patients’ compliance rates rapidly decline over time as a result of tumor progression, neurocognitive impairments, and treatment toxicity. To increase statistical power, combining different datasets is important in order to answer clinically relevant questions. For example, we will identify multiple concurrent symptoms that will be predictive of tumor progression. Also, we will use different models to assess clinical and sociodemographic variables that are related to worse HRQoL over time. Such information may help physicians in the early identification of subgroups of glioma patients prone to worse HRQoL as well as be relevant in clinical decision-making over offering timely and effective personalized supportive care. Effective supportive care strategies may eventually result in an improved HRQOL.