IDH1 status and survival benefit from surgical resection of enhancing and nonenhancing tumor in malignant astrocytomas.

Abstract

2019 Background: The value of maximal safe resection for malignant astrocytic gliomas (AA, WHO Grade III anaplastic astrocytoma and GBM, WHO Grade IV glioblastoma) has sometimes been controversial, because of confounding between measures of surgical resection and other prognostic factors. IDH1 gene mutations are associated with improved survival in glioma patients, and are thought to identify tumors with a distinct molecular evolutionary origin. We sought to determine the prognostic impact of surgical resection on survival after controlling for IDH1 status in malignant astrocytomas. Methods: Clinical parameters including preoperative and postoperative MRI-based tumor volume were recorded prospectively on 407 malignant astrocytoma patients – AA (n=157) and GBM (n=250). IDH1 status was assessed by sequencing and R132H-specific immunohistochemistry. Results: The measures of surgical resection associated with longer survival differed between IDH1 wild-type and mutant tumors. In multivariate analyses of IDH1 wild-type tumors (controlling for age, Karnofsky performance score, tumor location, and tumor grade), residual postoperative enhancement was associated with a median survival of 9.9 mo vs. 17.4 mo with no enhancement (HR=1.73, 95% CI, 1.19-2.52, p=.004). Residual non-enhancing disease, however, was not associated with survival (scored as continuous volumetric cc, 95% CI 0.99-1.01, p=.608). These results are consistent with prior studies of GBM, which are largely IDH1 wild-type lesions (Lacroix et al., J Neurosurg 95:190-8, 2001). In contrast, in IDH1 mutant tumors, both residual enhancing (HR=7.93, 95%CI 1.14-55.22, p=.037) and non-enhancing (HR=1.03, 95% CI 1.01-1.05, p=.005) postoperative tumor burden were associated with worse survival. Conclusions: These data suggest surgical resection in malignant astrocytic gliomas may be individualized based on IDH1 genotype. IDH1 mutant tumors have a better baseline overall prognosis, therefore more aggressive surgery and tolerance of temporary peri-operative neurologic deficits can be weighed in an attempt to gain the additional survival benefit that appears to be associated with reducing non-enhancing tumor burden.