Brain Tumor Imaging and Treatment Effects. Imaging findings and cognitive function in glioblastoma patients.

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Abstract

Abstract
Background: Glioblastoma is the most common malignant brain tumor. Operation with maximal resection, if feasible, otherwise biopsy followed by radiotherapy and chemotherapy with temozolomide is standard therapy. The prognosis remains poor, with median overall survival being 15 months despite therapy. Improved monitoring and treatment response assessment will be important when seeking to improve treatment efficacy and patient quality of life.
Aims: The present work sought to follow newly diagnosed glioblastoma patients by imaging and clinical monitoring. Specific aims were to study the impact of surgical resection degree on prognosis and the effects of currently used therapies, including arc-based rotation radiotherapy, longitudinally. Aims were also to study radiological parameters with advanced magnetic resonance imaging (MRI) as well as patient neurological and cognitive functions in order to early identify prognostic factors.
Material and methods: In paper I, volumetric assessment by quantitative and subjective methods was retrospectively studied from pre- and postoperative MRI in glioblastoma patients undergoing tumor resection. Influence of extent of resection of contrast enhanced tumor on progression-free survival and overall survival was analyzed, measured as relative extent of resection (EOR) and absolute residual tumor volume (RTV).
In the present MRI brain tumor study, patients newly diagnosed with glioblastoma undergoing treatment with arc-based radiotherapy were studied longitudinally over a one-year period and constituted the patient cohort of papers II-IV, using advanced MRI, including diffusion-weighted imaging sequences. Microstructural changes in non-tumorous brain structures, including white matter (corpus callosum, centrum semiovale) and the limbic system (hippocampus, amygdala), were assessed by diffusion tensor imaging (DTI) during and after irradiation. By parametric response mapping (PRM) changes of mean diffusivity (MD) in tumor regions were analyzed as MD-PRM. Baseline examinations were compared with examinations 3 weeks into radiotherapy voxel-wise, analyzing the MD-difference as prediction of therapy response and survival. Clinical parameters were monitored from start of radiotherapy up to one year and included correlation of cognition, measured by the computerized test-battery CNS-vital signs (CNS-VS), with therapy and disease progression.
Results: Quantitative volumetric measurements, especially residual tumor volume of ≤1,6 mL, showed prognostic significance for longer progression-free and overall survival. The quantitative volumetric method was superior in reproducibility compared to conventional estimation. MD-PRM demonstrated that in patients only undergoing diagnostic biopsy MD-PRM, changes indicated prognostic specificity for treatment response at 8 months. Significant longitudinal DTI changes were only observed in the body of the corpus callosum during and up to one year from radiotherapy. Evaluation of cognitive performance in glioblastoma patients using cognitive test scores by CNS-VS at baseline were in lower-average or low, compared to standard test average in 4 main domains: executive function, visual and verbal memory and complex attention. Cognitive function remained stable without further deterioration during one year follow up after radiotherapy was initiated. Better cognitive function at therapy begin correlated with longer progression-free and overall survival.
Conclusion: Quantitative volumetric assessment has prognostic impact on glioblastoma patients progression-free and overall survival in favor of gross total resection. MD-PRM could not predict treatment response as assessed in the entire patient cohort, but may have predictive value in biopsied patients. Longitudinal monitoring up to one year after initiated radiotherapy did not reveal any major changes, neither in microstructural changes by diffusion tensor imaging (DTI) parameters, nor in patients cognitive function, indicating less neurotoxicity by arc-based radiotherapy.
Original languageEnglish
QualificationDoctor
Awarding Institution
  • Department of Clinical Sciences, Lund
Supervisors/Advisors
  • Sundgren, Pia C, Supervisor
  • Bengzon, Johan, Assistant supervisor
  • Lätt, Jimmy, Assistant supervisor
  • Kinhult, Sara, Assistant supervisor
  • van Westen, Danielle, Assistant supervisor
Award date2023 May 23
Place of PublicationLund
Publisher
ISBN (Print)978-91-8021-118-5
Publication statusPublished - 2023

Bibliographical note

Defence details
Date: 2023-05-23
Time: 13.00
Place: Segerfalksalen, BMC A10, Sölvegatan 17 i Lund. Zoom: https://lu-se.zoom.us/j/69757940343?pwd=aGZuaXBmS2pYUFF3NzlCOGFxL3lmdz09
External reviewer(s)
Name: Landtblom, Anne-Marie
Title: Professor em
Affiliation: Department of Medical Sciences, Neurology Uppsala University

Subject classification (UKÄ)

  • Neurology

Free keywords

  • Glioblastoma
  • Imaging finding
  • Quantitative volumetry
  • Cognitive function
  • Diffusion tensor imaging (DTI)
  • Treatment effect
  • Radiotherapy
  • VMAT
  • Parametric response maps (PRM)
  • Treatment responce prediction

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