title: IDH1 mutant malignant astrocytomas are more amenable to surgical resection and have a survival benefit associated with maximal surgical resection.
abstract: BACKGROUND
  IDH1 gene mutations identify gliomas with a distinct molecular evolutionary origin. We sought to determine the impact of surgical resection on survival after controlling for IDH1 status in malignant astrocytomas-World Health Organization grade III anaplastic astrocytomas and grade IV glioblastoma.
  
  
  METHODS
  Clinical parameters including volumetric assessment of preoperative and postoperative MRI were recorded prospectively on 335 malignant astrocytoma patients: n = 128 anaplastic astrocytomas and n = 207 glioblastoma. IDH1 status was assessed by sequencing and immunohistochemistry.
  
  
  RESULTS
  IDH1 mutation was independently associated with complete resection of enhancing disease (93% complete resections among mutants vs 67% among wild-type, P < .001), indicating IDH1 mutant gliomas were more amenable to resection. The impact of residual tumor on survival differed between IDH1 wild-type and mutant tumors. Complete resection of enhancing disease among IDH1 wild-type tumors was associated with a median survival of 19.6 months versus 10.7 months for incomplete resection; however, no survival benefit was observed in association with further resection of nonenhancing disease (minimization of total tumor volume). In contrast, IDH1 mutants displayed an additional survival benefit associated with maximal resection of total tumor volume (median survival 9.75 y for >5 cc residual vs not reached for <5 cc, P = .025).
  
  
  CONCLUSIONS
  The survival benefit associated with surgical resection differs based on IDH1 genotype in malignant astrocytic gliomas. Therapeutic benefit from maximal surgical resection, including both enhancing and nonenhancing tumor, may contribute to the better prognosis observed in the IDH1 mutant subgroup. Thus, individualized surgical strategies for malignant astrocytoma may be considered based on IDH1 status.
authors.affiliation: Corresponding author: Daniel P. Cahill, MD, PhD, Department of Neurosurgery, 32 Fruit Street - Yawkey 9E, Massachusetts General Hospital, Brain Tumor Center/Neuro-Oncology, Boston, MA 02114. cahill@mgh.harvard.edu.
authors.forename: Jason
authors.initials: J
authors.lastname: Beiko
authors.forename: Dima
authors.initials: D
authors.lastname: Suki
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Hess
authors.forename: Benjamin D
authors.initials: BD
authors.lastname: Fox
authors.forename: Vincent
authors.initials: V
authors.lastname: Cheung
authors.forename: Matthew
authors.initials: M
authors.lastname: Cabral
authors.forename: Nicole
authors.initials: N
authors.lastname: Shonka
authors.forename: Mark R
authors.initials: MR
authors.lastname: Gilbert
authors.forename: Raymond
authors.initials: R
authors.lastname: Sawaya
authors.forename: Sujit S
authors.initials: SS
authors.lastname: Prabhu
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Weinberg
authors.forename: Frederick F
authors.initials: FF
authors.lastname: Lang
authors.forename: Kenneth D
authors.initials: KD
authors.lastname: Aldape
authors.forename: Erik P
authors.initials: EP
authors.lastname: Sulman
authors.forename: Ganesh
authors.initials: G
authors.lastname: Rao
authors.forename: Ian E
authors.initials: IE
authors.lastname: McCutcheon
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Cahill
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001254:Astrocytoma / Q000235:genetics* / Q000401:mortality / Q000601:surgery; D001932:Brain Neoplasms / Q000235:genetics* / Q000401:mortality / Q000601:surgery; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D060787:Neoplasm Grading; D011379:Prognosis; D011446:Prospective Studies; D015996:Survival Rate; D055815:Young Adult
chemical_list: D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human
keywords: IDH1; anaplastic astrocytoma; glioblastoma; malignant glioma; surgical resection