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- Carstam, Louise, et al.
(författare)
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Long-term follow up of patients with WHO grade 2 oligodendroglioma
- 2023
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Ingår i: Journal of Neuro-Oncology. - 0167-594X .- 1573-7373. ; 165, s. 65-74
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Tidskriftsartikel (refereegranskat)abstract
- Purpose Since the introduction of the molecular definition of oligodendrogliomas based on isocitrate dehydrogenase (IDH)-status and the 1p19q-codeletion, it has become increasingly evident how this glioma entity differs much from other diffuse lower grade gliomas and stands out with longer survival and often better responsiveness to adjuvant therapy. Therefore, apart from using a molecular oligodendroglioma definition, an extended follow-up time is necessary to understand the nature of this slow growing, yet malignant condition. The aim of this study was to describe the long-term course of the oligodendroglioma disease in a population-based setting and to determine which factors affect outcome in terms of survival.Methods All adults with WHO-grade 2 oligodendrogliomas with known 1p19q-codeletion from five Scandinavian neurosurgical centers and with a follow-up time exceeding 5 years, were analyzed regarding survival and factors potentially affecting survival.Results 126 patients diagnosed between 1998 and 2016 were identified. The median follow-up was 12.0 years, and the median survival was 17.8 years (95% CI 16.0-19.6).Factors associated with shorter survival in multivariable analysis were age (HR 1.05 per year; CI 1.02-1.08, p < 0.001), tumor diameter (HR 1.05 per millimeter; CI 1.02-1.08, p < 0.001) and poor preoperative functional status (KPS < 80) (HR 4.47; CI 1.70-11.78, p = 0.002). In our material, surgical strategy was not associated with survival.Conclusion Individuals with molecularly defined oligodendrogliomas demonstrate long survival, also in a population-based setting. This is important to consider for optimal timing of therapies that may cause long-term side effects. Advanced age, large tumors and poor function before surgery are predictors of shorter survival.
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| 4. |
- Latini, Francesco, M.D. 1982-, et al.
(författare)
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Role of Preoperative Assessment in Predicting Tumor-Induced Plasticity in Patients with Diffuse Gliomas
- 2021
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Ingår i: Journal of Clinical Medicine. - : MDPI. - 2077-0383. ; 10:5
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Tidskriftsartikel (refereegranskat)abstract
- When diffuse gliomas (DG) affect the brain's potential to reorganize functional networks, patients can exhibit seizures and/or language/cognitive impairment. The tumor-brain interaction and the individual connectomic organization cannot be predicted preoperatively. We aimed to, first, investigate the relationship between preoperative assessment and intraoperative findings of eloquent tumors in 36 DG operated with awake surgery. Second, we also studied possible mechanisms of tumor-induced brain reorganization in these patients. FLAIR-MRI sequences were used for tumor volume segmentation and the Brain-Grid system (BG) was used as an overlay for infiltration analysis. Neuropsychological (NPS) and/or language assessments were performed in all patients. The distance between eloquent spots and tumor margins was measured. All variables were used for correlation and logistic regression analyses. Eloquent tumors were detected in 75% of the patients with no single variable able to predict this finding. Impaired NPS functions correlated with invasive tumors, crucial location (A4C2S2/A3C2S2-voxels, left opercular-insular/sub-insular region) and higher risk of eloquent tumors. Epilepsy was correlated with larger tumor volumes and infiltrated A4C2S2/A3C2S2 voxels. Language impairment was correlated with infiltrated A3C2S2 voxel. Peritumoral cortical eloquent spots reflected an early compensative mechanism with age as possible influencing factor. Preoperative NPS impairment is linked with high risk of eloquent tumors. A systematic integration of extensive cognitive assessment and advanced neuroimaging can improve our comprehension of the connectomic brain organization at the individual scale and lead to a better oncological/functional balance.
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| 5. |
- Latini, Francesco, M.D. 1982-
(författare)
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Significance of white matter anatomy in interpreting features and behaviour of low-grade gliomas and implications for surgical treatment
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Diffuse gliomas are extremely heterogeneous tumours characterized by slow growth but extensive infiltration. Their kinetic features reflect the complex interaction over time with the surrounding brain, influencing treatment planning and outcome. Indeed, resection of diffuse gliomas present a surgical challenge due to their invasiveness and the preferential location in eloquent regions. White matter bundles are the main eloquent limit to surgical resection, but this anatomical-functional information cannot be predicted preoperatively on the individual level. The incomplete description of the human brain connectome, the complex application of pathological/lesion model to the brain connectomic organization, and the underestimated role of white matter anatomy in radiological classification systems are among the major limitations for the comprehension of the glioma/white matter interaction. The overall aim of this thesis was to explore a new approach and new techniques to study the glioma/white matter interaction. A combination of white matter dissection and diffusion tensor tractography (DTT) was used to describe the connectomic organization of two major temporo-occipital connections, the inferior and the middle longitudinal fasciculus. This information was applied to patients with diffuse gliomas, demonstrating how white matter analysis was important to decode patient specific cognitive and language impairment. A new classification system for diffuse gliomas, the Brain-Grid, was created, merging local radiological anatomy with a DTT atlas for infiltration analysis. This standardized radiological tool provided information on subcortical extension (tumour invasiveness), speed, and preferential direction of glioma progression. Applied to a larger cohort of patients, differences were detected between diffuse gliomas subtypes. Tumour invasiveness and the preferential location, type, and extent of white matter involvement differed, impacting overall survival. Regional differences in white matter infiltration were detected among five major white matter bundles, and possible favourable morphological and diffusion features were investigated with transmission electron microscopy and DTT. Fibre diameter, myelin thickness, and the organization of the white matter fibres were different in regions with high infiltration frequency, providing a possible link to the preferential location of diffuse gliomas. Finally, the white matter connectivity, tumour-induced neuroplasticity, clinical and demographic information, preoperative assessment (neuropsychological and language evaluation) were compared with intraoperative findings during awake surgery. Neuropsychological impairment was associated with more invasive tumours and a higher risk of the intraoperative finding of eloquent tumour. The pattern of early cortical neuroplasticity seemed exhausted at the time of diagnosis, with age as a factor predicting the neuroplasticity potential. The combined use of these new techniques revealed new insights into the glioma/white matter interaction. The results provided in this thesis, describe a new way to structure the multidisciplinary perioperative management of these patients. This new information may improve the functional outcome at the individual level, resulting in prolonged survival for adults with diffuse gliomas.
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| 6. |
- Latini, Francesco, M.D. 1982-, et al.
(författare)
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The link between gliomas infiltration and white matter architecture investigated with electron microscopy and diffusion tensor imaging
- 2021
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Ingår i: NeuroImage. - : Elsevier. - 2213-1582. ; 31, s. 102735-
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Tidskriftsartikel (refereegranskat)abstract
- Diffuse low-grade gliomas display preferential locations in eloquent and secondary associative brain areas. The reason for this tendency is still unknown. We hypothesized that the intrinsic architecture and water diffusion properties of the white matter bundles in these regions may facilitate gliomas infiltration. Magnetic resonance imaging of one hundred and two low-grade gliomas patients were normalized to/and segmented in MNI space to create a probabilistic infiltration weighted gradient map. Diffusion tensor imaging (DTI)- based parameters were derived for five major white matter bundles, displaying high- and low grade of infiltration, (corpus callosum, cingulum, arcuate fasciculus, inferior fronto-occipital fasciculus and cortico-spinal tract), averaged over 20 healthy individuals acquired from the Human connectome project (HCP) database. Transmission electron microscopy (TEM) was used to analyze fiber density, diameter and g-ratio in 100 human white matter regions, sampled from cadaver specimens, reflecting areas with different gliomas infiltration frequency. Histological results and DTI-based parameters were compared in anatomical regions of high- and low grade of infiltration respectively. We detected differences in the infiltration frequency of five major white matter bundles. Regional differences within the same white matter bundles were detected by both TEM- and DTI analysis. Regions with high infiltration frequency (HIF) displayed a higher fiber density, smaller fiber diameter but higher myelin thickness and lower axial diffusivity compare compared with low infiltration frequency (LIF) regions. Our results seem to indicate that the fiber diameter, myelin thickness and the possible organization of the fibers are different in HIF compared to LIF regions and may be linked to the preferential location of diffuse low-grade gliomas.
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