Impact of WHO 2016 update of brain tumor classification, molecular markers and clinical outcomes in pleomorphic xanthoastrocytoma

Abstract

We present outcomes of pleomorphic xanthoastrocytoma (PXA) and correlate the impact of clinical, pathologic and molecular markers. Between 2006 and 2016, 37 patients with histologically verified PXA form the study cohort. All underwent maximal safe resection; those who had good resection and young age were observed. Adjuvant radiotherapy was given in patients with some atypical features such as high MIB-1 index (> 5%), residual disease or at recurrence. Patients with anaplastic PXA were administered adjuvant radiotherapy and systemic therapy. Median age at diagnosis was 20 years (range 4-45). At median follow-up of 33 months, 3-year and 5-year overall survival (OS) was 80.2 and 74% respectively. Patients who underwent GTR (23 cases, 62%) had significantly better 3-year PFS of 85.6% compared to 32.3% (p = 0.001) achieved with STR (13 cases, 35%). PFS was significantly superior in PXA grade II as compared to anaplastic PXA group (3-year estimates 80.2 vs. 32%; p = 0.007). 13 out of 27 patients where BRAFV600E testing was successful showed a mutation (48%). 3-year PFS and OS survival in BRAFV600E mutated patients was 51.9 and 76.9% compared to 73 and 75% in BRAFV600E non-mutated patients, respectively. No patient had IDH1 mutation. This data may provide valuable insights and act as a benchmark for future studies.

BRAF inhibition with concomitant tumor treating fields for a multiply progressive pleomorphic xanthoastrocytoma

“…Recent work in PXA notes a 3 year survival of 80.2% and 5 year survival of 74%. Progression-free survival is 66.5% at 3 years and 60.5% at 5 years [ 13 ]. Recurrent PXA can be very refractory to treatment.…”

Genetic Abnormalities, Clonal Evolution, and Cancer Stem Cells of Brain Tumors

“…A recent study explored the genetic landscape of gangliogliomas, providing evidence that the vast majority of these tumors display genetic alterations at the level of BRAF ( BRAF V600E 46%; non-V600 BRAF mutations 12%; KIAA1549-BRAF fusion 5%; BRAF fusion with other partners 5%); FGFR1 or FGFR2 alterations are observed in 13% of cases and are mutually exclusive with BRAF alterations; CDKN2A deletion was observed in 8% of cases and co-occurs with BRAF V600E mutations; other gene alterations, such as NF1 or KRAS mutations, occur in a minority of patients (2–5%) and mutually are exclusive with BRAF V600E mutations [135] (Figure 4D). In a group of 37 patients with PXA it was shown that the presence or not of BRAF V600E mutations does not affect outcome; in contrast, tumor grade II patients had a progression-free survival (PFS) significantly superior compared to anaplastic PXA patients [136]. Lassaletta et al carried out a global analysis in BRAF V600E -mutated low-grade pediatric gliomas showing that the presence of this BRAF mutation confers a poor outcome with conventional therapies, comparing BRAF V600E -mutant gliomas either with BRAF WT gliomas or with KIAA1549-BRAF -mutant tumors [132].…”

Uncommon low-grade brain tumors

“…Adjuvant radiotherapy may be offered for residual tumors with high MIB index (>5%). 24 BRAF V600E mutation is detected in 60% to 70% of tumors and is associated with better outcomes. Four patients with recurrence after resection, adjuvant radiation, and alkylating chemotherapy received 4 weeks of vemurafenib with median PFS of 5 months and median OS of 8 months.…”