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Initial cognitive impairment predicts shorter survival of patients with glioblastoma
Linköping University, Department of Biomedical and Clinical Sciences, Division of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences. Region Jonkoping Cty, Sweden.
Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).ORCID iD: 0000-0002-8857-5698
Linköping University, Department of Biomedical and Clinical Sciences, Division of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Neurosurgery.
Linköping University, Department of Biomedical and Clinical Sciences, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Närvårdskliniken.ORCID iD: 0000-0001-8410-4939
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2022 (English)In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 145, no 1, p. 94-101Article in journal (Refereed) Published
Abstract [en]

Objectives Seizures as presenting symptom of glioblastoma (GBM) are known to predict prolonged survival, whereas the clinical impact of other initial symptoms is less known. Our main objective was to evaluate the influence of different presenting symptoms on survival in a clinical setting. We also assessed lead times, tumour size and localization. Methods Medical records of 189 GBM patients were reviewed regarding the first medical appointment, presenting symptom/s, date of diagnostic radiology and survival. Tumour size, localization and treatment data were retrieved. Overall survival was calculated using Kaplan-Meier and Mann-Whitney U test. Cox regression was used for risk estimation. Results Cognitive impairment as the initial symptom was often misinterpreted in primary health care leading to a delayed diagnosis. Initial global symptoms (66% of all patients) were associated with reduced survival compared to no global symptoms (median 8.4 months vs. 12.6 months). Those with the most common cognitive dysfunctions: change of behaviour, memory impairment and/or disorientation had a reduced median survival to 6.4 months. In contrast, seizures (32%) were associated with longer survival (median 11.2 months vs. 8.3 months). Global symptoms were associated with larger tumours than seizures, but tumour size had no linear association with survival. The setting of the first medical appointment was evenly distributed between primary health care and emergency units. Conclusion Patients with GBM presenting with cognitive symptoms are challenging to identify, have larger tumours and reduced survival. In contrast, epileptic seizures as the first symptom are associated with longer survival and smaller tumours.

Place, publisher, year, edition, pages
Wiley , 2022. Vol. 145, no 1, p. 94-101
Keywords [en]
cognitive functions; epilepsy; glioblastoma; neuro-oncology; radiation; seizures; survival; temozolomide
National Category
Surgery
Identifiers
URN: urn:nbn:se:liu:diva-179431DOI: 10.1111/ane.13529ISI: 000695135800001PubMedID: 34514585OAI: oai:DiVA.org:liu-179431DiVA, id: diva2:1596769
Note

Funding Agencies|Gustav Lindholm Foundation for malignant brain tumours

Available from: 2021-09-23 Created: 2021-09-23 Last updated: 2025-03-26
In thesis
1. PROGNOSTIC FACTORS FOR GLIOBLASTOMA SURVIVAL IN A CLINICAL CONTEXT: The role of presenting symptoms and treatments
Open this publication in new window or tab >>PROGNOSTIC FACTORS FOR GLIOBLASTOMA SURVIVAL IN A CLINICAL CONTEXT: The role of presenting symptoms and treatments
2025 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Glioblastoma is the most common and most malignant primary brain tumour. Survival is short, only around 15 months. This thesis explores factors influencing survival time.

The first article showed that survival was significantly prolonged in the County of Jönköping, after the implementation of a new treatment regimen in 2006. In this regimen, patients receive chemotherapy and radiotherapy concomitantly, over six weeks followed by adjuvant chemotherapy given every four weeks over six months. The study shows that survival was prolonged by 110 days.

For the second article, a review of patient records of all 189 glioblastoma patients diagnosed in the County of Jönköping 2001-2016 was performed. Patients with cognitive impairment were more difficult to diagnose, had larger tumours, and survived four months shorter than patients without cognitive impairment. If epileptic seizures were the presenting symptom, the tumours were found to be smaller at the time of diagnosis and patients lived three months longer than patients with no seizures at onset.

To further explore the difference in survival for patients with different presenting symptoms the Swedish Brain Tumour Registry (SBTR) was used in the third paper. Using the SBTR, we analysed 1458 glioblastoma patients diagnosed between 2018 and 2021. Cognitive impairment was linked to significantly shorter survival—even after adjusting for age, performance status, tumour size, MGMT methylation, surgical resection grade, and oncological treatment—while epileptic seizures initially appeared beneficial on univariate analysis but lost significance after adjustment.

The fourth study analysed 7669 glioblastoma patients from SBTR (1999–2023). Survival has improved across all age groups, almost all treatments, and regions, and analysis of relative survival demonstrated that patients primarily died from their brain tumour rather than other causes. Although initial data showed regional differences in survival, these differences diminished after adjusting for demographic data (age and sex) and tumour-related factors (preoperative performance status, tumour size), highlighting the need to control for such factors when comparing treatment outcomes between hospitals, regions and countries.

In summary, this thesis shows that while glioblastoma survival has improved over time, the overall prognosis remains poor. Patients presenting with cognitive dysfunction have a significantly shorter survival—even after adjusting for age, tumour size, and treatment—which is a novel finding. These patients are also less likely to receive oncological treatment, likely due to concerns about their understanding and ability to cope with therapy. Although earlier studies suggested that epileptic seizures at presentation were a positive prognostic factor, our larger study indicates that this association is explained by other factors. Finally, we confirm the prognostic impacts of age, tumour size, preoperative performance status, MGMT promoter methylation status (in patients treated with alkylating agents), extent of surgery, and oncological treatment.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2025. p. 108
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1963
Keywords
Glioblastoma, Survival, Relative survival, Prognostic factors, Presenting symptoms, Cognitive impairment, Seizures at onset
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:liu:diva-212630 (URN)10.3384/9789180759793 (DOI)9789180759786 (ISBN)9789180759793 (ISBN)
Public defence
2025-04-25, Aulan, Länssjukhuset Ryhov, Jönköping, 09:00
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Supervisors
Note

Funding: Gustav Lindholms stiftelse för elakartade hjärntumörer, Cancer Foundation North and Futurum.

Available from: 2025-03-26 Created: 2025-03-26 Last updated: 2025-03-26Bibliographically approved

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Bruhn, HelenaBlystad, IdaMilos, PeterMalmström, AnnikaDahle, CharlotteVrethem, MagnusLind, Jonas
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Division of NeurobiologyFaculty of Medicine and Health SciencesDivision of Diagnostics and Specialist MedicineDepartment of Radiology in LinköpingCenter for Medical Image Science and Visualization (CMIV)Department of NeurosurgeryDivision of Cell BiologyNärvårdsklinikenDivision of Inflammation and InfectionDepartment of Clinical Immunology and Transfusion MedicineNeurologiska kliniken i Linköping
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