Article
Extent of resection, MGMT promoter methylation status and tumour location independently predict progression-free survival in adult sporadic pilocytic astrocytomas
Einfluss von Resektionsausmaß, MGMT-Promoter-Methylierung und Tumorlokalisation auf das progressionsfreie Überleben von erwachsenen Patienten mit sporadischen pilozytischen Astrozytomen
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Authors
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Christine Jungk
- Universitätsklinikum Heidelberg, Neurochirurgische Klinik, Heidelberg, Deutschland; Universitätsklinikum Heidelberg, Experimentelle Neurochirurgie, Heidelberg, Deutschland
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Annekathrin Reinhardt
- Deutsches Konsortium für Translationale Krebsforschung (DKTK), Neuropathologie, Heidelberg, Deutschland; Ruprecht-Karls-Universität, Neuropathologie, Heidelberg, Deutschland
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Rolf Warta
- Universitätsklinikum Heidelberg, Neurochirurgische Klinik, Heidelberg, Deutschland; Universitätsklinikum Heidelberg, Experimentelle Neurochirurgie, Heidelberg, Deutschland
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Andreas von Deimling
- Deutsches Konsortium für Translationale Krebsforschung (DKTK), Neuropathologie, Heidelberg, Deutschland; Ruprecht-Karls-Universität, Neuropathologie, Heidelberg, Deutschland
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Christel Herold-Mende
- Universitätsklinikum Heidelberg, Neurochirurgische Klinik, Heidelberg, Deutschland; Universitätsklinikum Heidelberg, Experimentelle Neurochirurgie, Heidelberg, Deutschland
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Andreas W. Unterberg
- Universitätsklinikum Heidelberg, Neurochirurgische Klinik, Heidelberg, Deutschland
| Published: | May 8, 2019 |
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Outline
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Objective: While common in children, sporadic pilocytic astrocytomas (PA) account for less than 2% of adult brain tumours, resulting in uncertainty on the clinical course and optimal treatment. Extrapolated from paediatric cases, complete resection (CR) may impact outcome and preliminary evidence exists that promoter methylation of distinct genes, including MGMT, is associated with inferior survival. Therefore, we set out to analyse clinical and molecular prognosticators in our institutional series of this rare disease.
Methods: After exclusion of anaplastic and NF2-related cases, 58 patients older than 17 years with histologically confirmed intracranial PA WHO grade I were identified from a consecutive series treated between 1996 and 2017. Clinical data were retrieved from medical charts and extent of resection (EOR) was valued on post-op MRI. MGMT promoter methylation status was determined by 450K/850K methylation array or pyrosequencing. Prognostic factors were identified by univariate log-rank test and multivariate unbiased stepwise forward selection.
Results: Median age was 30 years (range 17–66); no gender prevalence was observed. Tumours were equally distributed among supra- vs. infratentorial (47% vs. 53%) and hemispheric vs. midline location (57% vs. 43%). MGMT promoter methylation was present in 8 patients (14%) and was independent of age, sex or tumour location. CR was achieved in 44 patients (76%) and was more likely in hemispheric tumours (p=0.028). 6 patients (10%) received adjuvant treatment at 1st diagnosis, all after incomplete resection or biopsy. Tumour relapse occurred in 14 patients (24%) after a median progression-free survival (PFS) of 44.5 months; there was 1 tumour-related death. PFS and OS at 10 years were 76% and 98%, respectively. In multivariate survival analysis (n=38 patients with follow-up>24 months), PFS was significantly prolonged in patients with CR (HR 0.10; CI 0.02–0.38; p<0.001), unmethylated MGMT promoter (HR 0.18; CI 0.05–0.69; p=0.012) and midline tumours (HR 0.12; CI 0.03–0.56; p=0.006).
Conclusion: Based on these findings, a maximized EOR, when feasible, should be the goal of surgery also in adult PAs since CR was determined as the major positive prognosticator. Moreover, MGMT promoter methylation and hemispheric location were identified as novel predictors of inferior PFS independent of demographic, tumour- and treatment-related factors, pointing at distinct molecular subtypes and detecting patients in need of close observance and intensified treatment.
