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PROGNOSTIC FACTORS FOR GLIOBLASTOMA SURVIVAL IN A CLINICAL CONTEXT: The role of presenting symptoms and treatments
Linköping University, Department of Biomedical and Clinical Sciences, The Division of Cell and Neurobiology. Linköping University, Faculty of Medicine and Health Sciences.
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 [en]
Glioblastoma, Survival, Relative survival, Prognostic factors, Presenting symptoms, Cognitive impairment, Seizures at onset
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:liu:diva-212630DOI: 10.3384/9789180759793ISBN: 9789180759786 (print)ISBN: 9789180759793 (electronic)OAI: oai:DiVA.org:liu-212630DiVA, id: diva2:1947583
Public defence
2025-04-25, Aulan, Länssjukhuset Ryhov, Jönköping, 09:00
Opponent
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
List of papers
1. Improved survival of Swedish glioblastoma patients treated according to Stupp
Open this publication in new window or tab >>Improved survival of Swedish glioblastoma patients treated according to Stupp
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2018 (English)In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 138, no 4, p. 332-337Article in journal (Refereed) Published
Abstract [en]

ObjectivesThe median survival in glioblastoma (GBM) patients used to be less than 1year. Surgical removal of the tumor with subsequent concomitant radiation/temozolomide (the Stupp regimen) has been shown to prolong survival. The Stupp protocol was implemented in the county of Jonkoping in 2006. The purpose of this study was to examine if the Stupp treatment has prolonged overall survival, in an unselected patient cohort with histologically verified GBM. Material and MethodThis study includes all patients from the county of Jonkoping, with a diagnosis of GBM from January 2001 to December 2012. Patients were divided into 2 cohorts, 2001-2005 and 2006-2012, that is before and after implementation of the Stupp regimen. By reviewing the medical case notes, the dates of the histological diagnosis and of death were identified. The median and mean overall survival and Kaplan-Meier survival analysis were calculated and compared between the 2 cohorts. ResultsThe mean survival was 110days longer in the cohort treated according to the Stupp regimen. Four patients in the 2006-2012 cohort and 1 patient in the 2001-2005 cohort are still alive. When comparing survival in patients with radical surgery vs biopsy, those that underwent radical surgery survived longer. The significance was slightly greater in the 2001-2005 cohort (mean 163 vs 344days, Pamp;lt;.001) than in the 2006-2012 cohort (mean 220 vs 397days, P=.02). ConclusionSurvival significantly improved after the implementation of the Stupp regimen in the study region of Sweden.

Place, publisher, year, edition, pages
WILEY, 2018
Keywords
glioblastoma; mortality; radiotherapy; Stupp treatment; survival; temozolomide
National Category
Surgery
Identifiers
urn:nbn:se:liu:diva-151465 (URN)10.1111/ane.12966 (DOI)000443931400010 ()29882211 (PubMedID)
Note

Funding Agencies|Gustav Lindholms Stiftelse for elakartade hjarntumorer; Futurum

Available from: 2018-09-24 Created: 2018-09-24 Last updated: 2025-03-26
2. Initial cognitive impairment predicts shorter survival of patients with glioblastoma
Open this publication in new window or tab >>Initial cognitive impairment predicts shorter survival of patients with glioblastoma
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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
Keywords
cognitive functions; epilepsy; glioblastoma; neuro-oncology; radiation; seizures; survival; temozolomide
National Category
Surgery
Identifiers
urn:nbn:se:liu:diva-179431 (URN)10.1111/ane.13529 (DOI)000695135800001 ()34514585 (PubMedID)
Note

Funding Agencies|Gustav Lindholm Foundation for malignant brain tumours

Available from: 2021-09-23 Created: 2021-09-23 Last updated: 2025-03-26
3. Do presenting symptoms predict treatment decisions and survival in glioblastoma? Real-world data from 1458 patients in the Swedish brain tumor registry
Open this publication in new window or tab >>Do presenting symptoms predict treatment decisions and survival in glioblastoma? Real-world data from 1458 patients in the Swedish brain tumor registry
2024 (English)In: Neuro-Oncology Practice, ISSN 2054-2577, E-ISSN 2054-2585, Vol. 11, no 5, p. 652-659Article in journal (Refereed) Published
Abstract [en]

Background Glioblastoma is the most common malignant brain tumor in adults. Non-invasive clinical parameters could play a crucial role in treatment planning and serve as predictors of patient survival. Our register-based real-life study aimed to investigate the prognostic value of presenting symptoms. Methods Data on presenting symptoms and survival, as well as known prognostic factors, were retrieved for all glioblastoma patients in Sweden registered in the Swedish Brain Tumor Registry between 2018 and 2021. The prognostic impact of different presenting symptoms was calculated using the Cox proportional hazard model. Results Data from 1458 adults with pathologically verified IDH wild-type glioblastoma were analyzed. Median survival time was 345 days. The 2-year survival rate was 21.5%. Registered presenting symptoms were focal neurological deficits, cognitive dysfunction, headache, epilepsy, signs of raised intracranial pressure, and cranial nerve symptoms, with some patients having multiple symptoms. Patients with initial cognitive dysfunction had significantly shorter survival than patients without; 265 days (245-285) vs. 409 days (365-453; P < .001). The reduced survival remained after Cox regression adjusting for known prognostic factors. Patients presenting with seizures and patients with headaches had significantly longer overall survival compared to patients without these symptoms, but the difference was not retained in multivariate analysis. Patients with cognitive deficits were less likely to have radical surgery and to receive extensive anti-neoplastic nonsurgical treatment. Conclusions This extensive real-life study reveals that initial cognitive impairment acts as an independent negative predictive factor for treatment decisions and adversely affects survival outcomes in glioblastoma patients.

Place, publisher, year, edition, pages
OXFORD UNIV PRESS, 2024
Keywords
cognition; glioblastoma; prognostic factors; survival; symptoms
National Category
Neurology
Identifiers
urn:nbn:se:liu:diva-204362 (URN)10.1093/nop/npae036 (DOI)001234683600001 ()2-s2.0-85199031357 (Scopus ID)
Note

Funding Agencies|Swedish Brain Tumour Registry; National Cancer Foundation; Cancer Foundation Northern Sweden; Futurum Academy for Health and Care

Available from: 2024-06-12 Created: 2024-06-12 Last updated: 2025-03-26Bibliographically approved

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