Abstract
In adults, pilocytic astrocytomas (PA) account for less than 2% of gliomas, resulting in uncertainty regarding the clinical course and optimal treatment, particularly in cases where gross total resection (GTR) could not be achieved. Moreover, information on molecular markers and their prognostic impact is sparse. In order to improve risk stratification, we analyzed our institutional series of 58 patients aged 17 years and older with histology-proven intracranial PA World Health Organization grade I for clinical and molecular prognosticators. Anaplastic and NF1-associated tumors were excluded. O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status was determined by pyrosequencing or 450k/850k DNA methylation array. A univariate log-rank test and multivariate StepAIC were applied to identify prognostic factors. The median age was 30 years (range 17–66). Tumors were located in the cerebral/cerebellar hemispheres, midline structures and cerebello-pontine angle in 53%, 38% and 9%. MGMT promoter methylation was present in eight patients (14%). GTR (39/58 patients) significantly reduced the likelihood of tumor recurrence (p = 0.0001). Tumor relapse occurred in 16 patients (28%) after a median progression-free survival (PFS) of 135 months (range 6–153 months); there was one tumor-related death. PFS at 5 and 10 years was 67% and 53%. In multivariate analysis, PFS was significantly prolonged in patients with GTR (HR 0.1; CI 0.03–0.37; p < 0.001), unmethylated MGMT promoter (HR 0.18; CI 0.05–0.64; p = 0.009) and midline tumors (HR 0.21; CI 0.06–0.78; p = 0.02). In conclusion, MGMT promoter methylation status and tumor location were identified as novel prognostic factors in adult PAs, pointing at distinct molecular subtypes and detecting patients in need of close observance and intensified treatment.
Highlights
A total of 10 patients were excluded due to insufficient follow-up, one patient due to a history of NF1, three patients due to initial diagnosis of an anaplastic Pilocytic astrocytoma (PA) and four patients due to discordant histopathological and molecular findings, leaving 58 adult patients with sporadic, intracranial PA World Health Organization (WHO) grade I for further analysis (Table 1)
Gross total resection (GTR) was an important prognostic factor for prolonged progression-free survival (PFS) in our cohort and significantly reduced the likelihood of progression/recurrence, a finding that was confirmed by multivariate analysis
Patients conferred a favorable overall survival (OS), the recurrence rate was high in this cohort of adult
Summary
Pilocytic astrocytoma (PA) World Health Organization (WHO) grade I is the most common pediatric brain tumor, but accounts for less than 2% of adult gliomas [1]. Information on patient outcome and potential prognostic factors is sparse due to the low incidence of PAs in this population (4.8/million/year [2]) and is extracted from a limited number of case reports, case series and one prospective trial including 20 patients (reviewed in [5]). While some series describe an indolent clinical course comparable to pediatric patients [6,7], others report increased recurrence rates and mortality in adults [8,9,10]. In line with the pediatric experience, a recent meta-analysis of seven case series including 254 patients confirmed GTR as a positive prognostic factor in adult PAs, but reported on a mean recurrence rate as high as 31% [5], underlining the need for optimization of risk stratification and treatment. The optimal treatment, in particular, the timing and modality of treatment after subtotal resection (STR) or biopsy, remains elusive since prognostic and predictive factors apart from GTR are lacking
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