IDH-Mutation Is a Weak Predictor of Long-Term Survival in Glioblastoma Patients

Abstract

Background: A very small proportion of patients diagnosed with glioblastoma (GBM) survive more than 3 years. Isocitrate dehydrogenase 1 or 2 (IDH1/2) mutations define a small subgroup of GBM patients with favourable prognosis. However, it remains controversial whether long-term survivors (LTS) are found among those IDH1/2 mutated patients.

Methods: We retrospectively analyzed 207 GBM patients followed at Lariboisière Hospital (Paris) between 2005 and 2010. Clinical parameters were obtained from medical records. Mutations of IDH1/2 were analyzed in these patients, by immunohistochemistry for the R132H mutation of IDH1 and by high-resolution melting-curve analysis, followed by Sanger sequencing for IDH1 and IDH2 exon 4 mutations. Mutation rates in LTS and non-LTS groups were compared by Chi square Pearson test.

Results: Seventeen patients with survival >3 years were identified (8.2% of the total series). The median overall survival in long-term survivors was 4.6 years. Subgroup analysis found that the median age at diagnosis was significantly higher for non long-term survivors (non-LTS) compared to LTS (60 versus 51 years, p <0.03). The difference in the rate of IDH mutation between non-LTS and LTS was statistically not significant (1.16% versus 5.9%, p = 0.144). Among LTS, 10 out of 16 tumors presented a methylation of MGMT promoter.

Conclusions: This study confirms that long-term survival in GBM patients is if at all only weakly correlated to IDH-mutation.

Fig 1. IDH1 immunohistochemistry in patient 6.

Strong immunolabelling of 100% of tumor cells; negativity on vessels.

Fig 2. MRI performed for a seventy-three-year-old man presented to the emergency department with bilateral muscular weakness members, cognitive disorders and KPS of 60.

The T1W sequence with gadolinium injection showed a large bifrontal GBM invading the corpus callosum. Stereotactic biopsy revealed the presence of a glioblastoma multiforme (confirmed by independent reviewing). This patient had almost all factors of poor prognosis (sex, age, low KPS, tumor localization, no surgical treatment) but received concomittant radiochemotherapy with temozolomide and survived 4 years.