Accelerated progression of IDH mutant glioma after first recurrence.

Accelerated progression of IDH mutant glioma after first recurrence.

Neuro Oncol. 2019 Jan 22;:

Authors: Miller JJ, Loebel F, Juratli TA, Tummala SS, Williams EA, Batchelor TT, Arrillaga-Romany I, Cahill DP

Abstract
Background: Isocitrate dehydrogenase (IDH) mutant gliomas are a distinct subtype, reflected in WHO 2016 revised diagnostic criteria. To inform IDH-targeting trial design, we sought to characterize outcomes exclusively within IDH mutant gliomas.
Methods: We retrospectively analyzed 275 IDH mutant glioma patients treated at our institution. Progression was determined using low-grade glioma RANO criteria. We calculated survival statistics with the Kaplan-Meier method and survival proportions were correlated with molecular, histologic and clinical factors.
Results: During a median follow-up of 6.4 years, 44 deaths (7.6%) and 149 first progression (PFS1) events (54.1%) were observed. Median PFS1 was 5.7 years (95% CI 4.7-6.4) and OS was 18.7 years (95% CI 12.2 years - not reached). Consistent with prior studies, we observed an association of grade, molecular diagnosis and treatment with PFS1. Following the first progressive episode, 79 second progression events occurred during a median follow-up period of 4.1 years. Median PFS following an initial progressive event (PFS2) was accelerated at 3.1 years (95% CI 2.1-4.1). PFS2 was a surrogate prognostic marker, identifying patients with poorer overall survival.
Conclusion: We report outcomes in a large cohort of IDH mutant glioma, providing a well-characterized historical control population for future clinical trial design. Notably, the interval between first to second recurrence (PFS2 - 3.0 years) is shorter than time from diagnosis to first recurrence (PFS1 - 5.7 years), evidence that these tumors clinically degenerate from an indolent course to an accelerated malignant phase. Thus, PFS2 represents a relevant outcome for trials investigating drug efficacy at recurrence.

PMID: 30668823 [PubMed - as supplied by publisher]

from A via a.sfakia on Inoreader http://bit.ly/2AZvZtz