IDH1-Mutant Malignant Astrocytomas May Be More Amenable to Surgical Resection and Linked to Better Prognosis
IDH1 mutation in patients with malignant astrocytomas may serve as a predictive molecular biomarker to guide aggressive surgical resection, according to the results of a study reported by Beiko et al in Neuro-Oncology. Maximal surgical resection may contribute a survival benefit in those who have malignant gliomas with this type of gene mutation.
Currently, malignant astrocytomas are categorized into two types: anaplastic (grade III) and glioblastoma (grade IV). Both glioblastoma and anaplastic astrocytoma patients have responded favorably after greater surgical resection of enhancing disease, and patients with IDH1-mutant astrocytomas have a better overall prognosis compared to those with wild-type lesions. However, the reason for this is not known, and the role of surgery in relation to IDH genotype in unclear. Thus, the investigators undertook a detailed study to determine the impact of surgical resection on survival for IDH1-mutant and wild-type malignant astrocytomas.
Study Details
This retrospective study included 128 patients with anaplastic astrocytomas and 207 patients with glioblastomas. Patients in both groups were analyzed for the presence of IDH1 mutation-specific antibody. In the anaplastic astrocytoma group, IDH1 mutations were identified in 86 patients. In the group with glioblastomas, IDH1 mutations were identified in 27 patients.
Patients were further analyzed according to tumor grade, age at tumor diagnosis, and tumor location. Tumor grades were categorized as eloquent, near-eloquent, and noneloquent. Locations were categorized as frontal, temporal, parietal, or other.
Study Results
Overall, IDH1-mutant tumors were more commonly found in younger patients and were more likely located in the frontal lobe (55% in IDH1-mutant tumors vs 40% for wild-type tumors; P = .008). Wild-type enhancing tumors had a significantly greater median preoperative volume of enhancing disease (31.0 cm3) compared with mutant enhancing tumors (11.1 cm3; P < .001). There was no significant difference between tumors diagnosed early and tumors diagnosed later. In addition, the patient’s age at the time of diagnosis was not a significant factor.
Over 90% of tumors with IDH1 mutations underwent complete resection of enhancing disease, compared with 67% of nonmalignant tumors. The average survival of patients with mutant tumors was 13.5 years, compared with less than 1.5 years in patients with nonmutant tumors. Almost all of those patients who received aggressive surgery are still alive 20 years afterward.
In both the anaplastic astrocytoma and the glioblastoma groups, complete surgical resection was associated with improved survival. In contrast, minimal surgical resection was not associated with improved survival. Based on the results of their study and data from previous studies, the investigators noted that patients with IDH1-mutant astrocytomas seem to have a better overall prognosis than patients with wild-type IDH astrocytomas,
Clinical Implications
For the first time, investigators demonstrated that IDH1 mutation is an independent predictor of improved survival from malignant astrocytomas in patients undergoing complete resection. Identification of IDH1 mutations may serve as a predictive biomarker to guide aggressive surgical resection. This initial attempt to understand the relationship between IDH1 mutation and resection may lead to other predictors such as age of the patient at tumor diagnosis and tumor location.
The investigators remarked, “The stability over time of clinical measures, including survival, and underlying molecular genotype within our cohort provides evidence that the intrinsic tumor composition of the study population was not impacted by variable diagnostic criteria (by either the inclusion or, more importantly, the selective exclusion of cases affecting the underlying composition of the patient population with malignant astrocytic gliomas over time). Thus, our findings are likely to be generalizable to the population of malignant astrocytomas … considered as a whole.”
Daniel P. Cahill, MD, PhD, Department of Neurosurgery, Massachusetts General Hospital, Boston, is the corresponding author of the article in Neuro-Oncology.
This study was supported by funding from the Burroughs Wellcome Trust, the James S. McDonnell Foundation, and the Texas Neurofibromatosis Foundation. The study authors reported no potential conflicts of interest.
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