The GLOW study explored whether Whole Genome Sequencing could help identify additional treatment options for people with recurrent glioblastoma. While the study demonstrated the value of complete genome profiling in clinical practice, it also highlighted the challenges of translating scientific insights into patient care.
For people with recurrent glioblastoma, treatment options are often limited. The GLOW study set out to explore whether Whole Genome Sequencing (WGS) could help identify additional treatment options by providing a more complete understanding of each patient's tumour.
Conducted under the scientific leadership of Edwin Cuppen (Oncode Institute Alumnus, UMCU Utrecht and Hartwig Medical Foundation) and in close collaboration with medical specialists Marike Broekman (Haaglanden MC and LUMC) and Filip de Vos (UMCU) , the study brought together researchers, clinicians and hospitals across the Netherlands. By analysing tumour and blood samples, researchers aimed to identify genetic changes that could help guide treatment decisions and identify potential treatment options that might otherwise go unnoticed.
The results showed that WGS can be successfully implemented in clinical practice and provide valuable information for patient care. In many cases, the analysis identified potential treatment options and offered insights beyond those available through conventional diagnostic approaches.
Edwin Cuppen reflects on the study:
Edwin Cuppen, Oncode Institute Alumnus, affiliated with UMC Utrecht and Hartwig Medical Foundation
Edwin Cuppen, Oncode Institute Alumnus, affiliated with UMC Utrecht and Hartwig Medical Foundation
The challenges with rare cancers, like glioblastoma, is that clinical trials with novel drugs are largely lacking. We reasoned that a systematic approach looking at all possible biomarkers, which is now routinely feasible with whole genome sequencing, could identify leads for off-label experimental use of drugs. We indeed identified potentially actionable mutations in ~65% of patients, but also inherited pathogenic variants in 11% of patients.
At the same time, the study revealed an important challenge.
Finding a possible treatment option is not the same as making it available to a patient.
Although potential treatment options were identified for many patients, only a limited number ultimately received a matched treatment. Limited access to suitable clinical trials and treatment eligibility requirements remained important barriers.
The GLOW study originated from an Oncode clinical workshop on glioblastoma in 2019 and evolved into a nationwide collaboration involving multiple centres and clinical experts. Beyond its scientific findings, the study also highlighted the practical challenges of implementing personalised treatment approaches for patients with brain tumours.
While the study has now concluded, its findings continue to inform future research. They have also contributed to follow-up initiatives, including the PePPer study, which aims to improve access to targeted treatments for patients with primary brain tumours.
Marike Broekman reflects on the clinical implications:
The GLOW study showed that WGS is feasible for recurrent glioblastoma patients, and that potential targets could be identified. We hope that this will result in more (experimental) therapeutic options for these patients and will continue to work on this.
Marike Broekman, neurosurgeon at Haaglanden MC and Leiden University Medical Center.
Marike Broekman, neurosurgeon at Haaglanden MC and Leiden University Medical Center.
By highlighting both the opportunities and the barriers, the GLOW study provides valuable insights for future efforts to improve personalised treatment for people living with glioblastoma.