Survival Analysis of the Non-canonical Idh-mutant Astrocytoma

Introduction: Mutations of the IDH gene have been proposed to exhibit a significant role in the tumorigenesis, progression, and prognosis of gliomas. The most common mutation is a missense mutation that affects amino acid residue 132 and is associated with longer survival in patients with glioma than in patients with glioma without IDH1 mutations. Other non-R132H mutations known as non-canonical IDH mutations are less common (7-20%).

Methods: We identified 115 patients (1993–2022) with IDH1/2 mutated astrocytomas and analyzed the molecular markers, patient characteristics, histology, treatment, recurrence and/or progression, PFS, and OS.

Results: Eighteen patients (15.6%) were harboring the non-canonical IDH mutations (R132C 44%, R132S 33%, R132G 17%, and R172M 6%). Patients with non-canonical IDH-mutant astrocytomas were younger with a median age at diagnosis of 35-year (p=0.009). Right hemispheric involvement was more common in the non-canonical group (61%), with frontal lobe predominance (50%). In both groups, there was a higher prevalence of WHO grade 2/3 astrocytomas than grade four astrocytomas. Interestingly, 17% of the non-canonical were of grade 4 upon initial diagnosis. Longer PFS was observed in non-canonical astrocytomas with lower WHO grade (p=0.01), and in patients treated with GTR compared to STR (p= 0.035). Higher WHO grade of the non-canonical associated with shorter OS (p= 0.01). Similarly, a higher WHO grade of recurrence was associated with poor OS post-recurrence (p < 0.01). R132H-mutant astrocytomas showed longer OS when compared to the non-canonical IDH-mutant astrocytomas. However, the overall survival did not differ significantly between the two cohorts (p= 0.59).

Conclusion : Due to the nature of the study and the small sample size, our analysis failed to show a strong correlation between the non-canonical IDH-mutant astrocytomas and the R132H mutation and the OS. Additional studies should be conducted with larger sample sizes and should also assess the type and dose of chemotherapy/radiotherapy used in non-canonical IDH-mutant astrocytoma.