IDH1 Status Determines the Survival Benefit of Surgical Resection for Malignant Astrocytomas

Keywords: anaplastic astrocytoma, gene, glioblastoma multiforme, brain tumor, glioma

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     The optimal surgical strategy for malignant astrocytic gliomas (AA, WHO Grade III anaplastic astrocytoma and GBM, WHO Grade IV glioblastoma) can be controversial, as it is difficult to isolate the impact of surgical resection from the bias of other prognostic factors. Mutations of the IDH1 gene are associated with improved survival in glioma patients. 
     We sought to determine the impact of surgical resection after controlling for IDH1 status in malignant astrocytomas.
       407 patient samples were studied.
     Clinical parameters including volumetric assessment of preoperative and postoperative MRI were recorded prospectively on 407 malignant astrocytoma patients – AA (n=157) and GBM (n=250). IDH1 status was assessed by sequencing and immunohistochemistry.
     IDH1 mutants were identified in 67% of AAs (87/130 evaluable samples). Preoperative tumor enhancement was more prevalent in wild-type IDH1 AAs (42% vs. 24%, p=.04), but was not independently associated with survival after controlling for IDH1 status. In multivariate analyses of AA patients, age (?40 years), lower Karnofsky score (KPS), wild-type IDH1 status, and residual postoperative tumor volume (T2/FLAIR in cm3) associated with worse survival. Notably, minimization of both enhancing and non-enhancing disease burden is associated with improved survival in IDH1 mutant AAs. In contrast, only residual enhancing disease is prognostic for IDH1 wild-type tumors, which are more aggressive lesions regardless.
     Data was collected prospectively.
     Minimized postoperative residual disease and mutant IDH1 status are associated with improved survival for AA patients.
     Wild-type IDH1 malignant astrocytomas are aggressive lesions distinct from mutant IDH1 tumors, and our data suggest that the surgical strategy for resection of non-enhancing disease may differ based on tumor genotype.


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