The incidence and significance of multiple lesions in glioblastoma

Abstract

The location and distribution of glioblastoma (GBM) within the brain parenchyma plays an important role in surgical and radiation planning. Prior studies have reported incidences of multiple lesions at the time of diagnosis ranging from 0.5 to 20 %. Multiple lesions can be further categorized as multifocal (multiple areas involved, but with a clear path of spread from one lesion to another) or multicentric (multiple lesions, no clear path of spread). In this retrospective study, we reviewed our experience with GBM and found the incidence of multiple lesions at time of diagnosis was 35 %, much higher than previously suggested in the literature. Patients with single lesions had an improved overall survival when compared to patients with multiple lesions (18 vs. 10 months). Patients with multicentric lesions fared the worst, with average survival of 3 months. However, the difference between single and multiple lesions (multifocal or multicentric) was no longer significant when taking into consideration age, Karnofsky performance score (KPS) and extent of resection by multivariate analysis. Age, KPS, gross total resection, and MGMT status were independent predictors of outcome. Multiple lesions did not independently confer a worse outcome, but were associated with lower KPS scores and inability to perform gross total resection. These findings suggest that single, multiple and multicentric imaging exams represent a spectrum of presentations of a single disease. The rate of multiple lesions reported here may be the result of improved imaging technology, suggesting that incidence of multiple lesions will continue to increase as imaging technology advances.

MR Fingerprinting of Adult Brain Tumors: Initial Experience

“…While history of previous malignancy and multiplicity of lesions is usually a reliable indicator of brain metastases, recent studies suggest that about 14% of all patients with brain metastases have an unknown primary malignancy and up to 46% of patients present with single brain metastasis 2,3 . Conversely, using modern MR imaging techniques, nearly 35% of patients with newly diagnosed GBM have multiple enhancing lesions, significantly higher than previous estimates which ranged from 0.5–20% 34 . Early differentiation between primary and metastatic malignant brain tumors is essential for prompt, appropriate and cost-efficient diagnosis and treatment, coordination of multidisciplinary care, and assessment for clinical trials 3,4 .…”

Multifocal and multicentric glioblastoma: Improved characterisation with FLAIR imaging and prognostic implications

“…Definitively proving that the apparent increase in incidence is entirely due to improvements in imaging is not possible, however, as the assessment of any historical cohort is inevitably limited by the imaging available at that time. Thomas et al showed that patients with single, multifocal and multicentric lesions had different survival, but this was no longer significant after correcting for factors including Karnofsky Performance Score and extent of resection [6]. This correlates with our findings and is not surprising, as patients with multiple lesions are likely to have more disseminated disease, thus impacting their performance status, and are less likely to be amenable to aggressive resection, especially via a single craniotomy.…”

“…The advent of MRI has allowed the detection of further lesions, compared to CT scan in this setting [2], and ongoing improvements in imaging technology have likely improved detection even further. Our rate of multiple enhancing lesions occurring in 34%, compared to less than 10% in older imaging studies [1,3], supports the view by Thomas et al that ''there is a much higher incidence of multiple GBM lesions at time of diagnosis than previously assumed" [6]. Even though it has previously been suggested that the incidence of multifocal gliomas is increasing [1], much of this apparent increase is likely due to the improvements in neuroimaging, both the inherent greater sensitivity of MRI compared to CT scan, and the ongoing technological improvements in MRI techniques, such as the introduction of FLAIR imaging.…”

“…To illustrate, older studies have described the incidence of multiple enhancing lesions as 1-10% [2][3][4]1,5]. In contrast, a more recent study had a much higher incidence of 35% [6].…”

Mesenchymal/proangiogenic factor YKL-40 related to glioblastomas and its relationship with the subventricular zone

“…Presently, it is not clear what the origin of GSCs is, but presumably it may arise from SVZ stem cells. Based on in vivo evidence, GSCs are responsible for tumor growth, recurrence, and resistance to therapies [15,48,59] and endowed with unregulated self-renewal, robust proliferative potential, high motility, diversity of progeny association with blood vessels and white matter tracts, multi-lineage differentiation capacities, invasiveness [22,63], and relatively resistant to radio-and chemotherapies [56,80], which express markers of both undifferentiated and differentiated cells [73], with a similar behavior to neural stem cells (NSCs) [5], which are present during the early development of the brain [7]. Nevertheless, the specific intrinsic factors that govern such characteristics are not well understood [27,66,83].…”