On the Prognosis of Multifocal Glioblastoma: An Evaluation Incorporating Volumetric MRI

Abstract

Primary glioblastoma (GBM), IDH-wildtype, especially with multifocal appearance/growth (mGBM), is associated with very poor prognosis. Several clinical parameters have been identified to provide prognostic value in both unifocal GBM (uGBM) and mGBM, but information about the influence of radiological parameters on survival for mGBM cohorts is scarce. This study evaluated the prognostic value of several volumetric parameters derived from magnetic resonance imaging (MRI). Data from the Department of Neurosurgery, Leipzig University Hospital, were retrospectively analyzed. Patients treated between 2014 and 2019, aged older than 18 years and with adequate peri-operative MRI were included. Volumetric assessment was performed manually. One hundred and eighty-three patients were included. Survival of patients with mGBM was significantly shorter (p < 0.0001). Univariate analysis revealed extent of resection, adjuvant therapy regimen, residual tumor volume, tumor necrosis volume and ratio of tumor necrosis to initial volume as statistically significant for overall survival. In multivariate Cox regression, however, only EOR (for uGBM and the entire cohort) and adjuvant therapy were independently significant for survival. Decreased ratio of tumor necrosis to initial tumor volume and extent of resection were associated with prolonged survival in mGBM but failed to achieve statistical significance in multivariate analysis.

Prognostic factors affecting outcome of multifocal or multicentric glioblastoma: A scoping review

“…In multivariate Cox regression, however, only resection and adjuvant therapy retained statistical significance. [ 15 ]…”

“…In multivariate Cox regression, however, only resection and adjuvant therapy retained statistical significance. [15] In a study by Kong et al, total 20 out of 51 treatment naïve GBM patients had mGBM. Kaplan-Meier survival analysis suggested that multicentric mGBM patients had worse title, year of study, authors name, year, country of origin, total number of patients, total number of patients with mGBM, mean age, gender, KPS/performance status (in any other reported scale), treatment details (extent of surgery/ radiotherapy/chemotherapy), and information on survival outcome were collected [Table 2].…”

“…Multifocality was divided (i) glioblastoma infiltration in a singular lobe, (ii) infiltration of>1 lobe within 1 hemisphere, and (iii) tumor infiltration of both hemispheres Armocida et al, 2021 [12] Tumors classified as Type I: Multicentric or multifocal supratentorial enhancing-contrast lesion at first diagnostic MRI Type II: Single enhancing contrast lesion Baro et al, 2022 [25] Patients with multiple lesions were defined as those having at least two separate foci of enhancing tumor on MRI, separated by at least 1 cm Fleischmann et al, 2021 [13] Based on MRI with contrast-enhanced T1 and T2 or FLAIR sequences, only patients with multifocal growth pattern at the time of first diagnosis were included Multifocal: At least two independent contrast-enhancing foci in the MRI T1 contrast-enhanced sequence Guerrini et al, 2021 [6] To distinguish between MC and MF, FLAIR T2-weighted MRI sequences were used and in case a diffusion pathway was found between one or more lesions, the case was classified as a MF glioma. Haque et al, 2020 [14] Not mentioned Hassaneen et al, 2011 [24] Group A: Multifocal or multicentric glioblastomas, who underwent resection of all lesions through multiple craniotomies in a single session (patients with multifocal glioblastomas who were treated via a single craniotomy were excluded) two subgroups based on MR imaging-documented tumor characteristics Group A1 (multicentric lesions) widely separated lesions having no connection when visualized on FLAIR MR sequences and no identified route of dissemination Group A2 (multifocal lesions) multiple separate lesions seen to be connected on FLAIR sequences and/or there was evidence of leptomeningeal, subependymal, or CSF dissemination Kasper et al, 2021 [15] Multifocality was defined as separate (distance greater than 1 cm) contrast-enhancing lesions, independently from FLAIR hyperintensity. Kong et al, 2016 [16] This assessment was based on the patients' MR contrast enhancement of T1-weighted images and FLAIR images.…”

Performance of 18 F-FAPI PET/CT in assessing glioblastoma before radiotherapy: a pilot study

“…To this day MRI remains the most used imaging modality for glioblastoma diagnosis and evaluation of treatment response and prognosis [ 1 , 4 , 10 ]. A number of advanced MRI techniques such as functional MRI (fMRI), diffusion tensor imaging (DTI), and MRS have been adopted for tumor treatment including preoperative surgical planning or as an instrument to distinguish post-operative vascular damage from residual enhancing tumor[ 9 , 12 , 13 , 39 ]. However, it is highly challenging to assess sub-regions of tumors in MRI scans visually because of their anatomic complexity.…”

“…Only some 6.8% of glioblastoma patients survive beyond five years [ 2 ]. As the most common non-invasive imaging technique to assess glioblastoma [ 3 , 4 ], magnetic resonance imaging (MRI) has been employed as a diagnostic instrument for glioblastoma diagnosis, prognostication, and monitoring of therapy response [ 5 – 9 ]. Other methods, such as diffusion-weighted imaging (DWI), apparent diffusion coefficient (ADC), perfusion-weighted imaging (FWI), and magnetic resonance spectrum imaging (MRS) are also widely used in addition to conventional sequences [ 4 , 6 , 7 , 10 – 13 ].…”