A threshold for mitotic activity and post-surgical residual volume defines distinct prognostic groups for astrocytoma IDH-mutant

Aims: The distinction between CNS WHO grade 2 and grade 3 is instrumental in choosing between observational follow-up and adjuvant treatment for resected astrocytomas IDH-mutant. However, the criteria of CNS WHO grade 2 vs 3 have not been updated since the pre-IDH era.

Methods: Maximal mitotic activity in consecutive high-power fields corresponding to 3 mm² was examined for 118 lower-grade astrocytomas IDH-mutant. The prognostic value for time-to-treatment (TTT) and overall survival (OS) of mitotic activity and other putative prognostic factors (including age, performance status, pre-surgical tumour volume, multilobar involvement, post-surgical residual tumour volume and midline involvement) was assessed for tumours with ATRX loss and the absence of CDKN2A homozygous deletion or CDK4 amplification, contrast enhancement, histological necrosis and microvascular proliferation.

Results: Seventy-one per cent of the samples had <6 mitoses per 3 mm² . Mitotic activity, residual volume and multilobar involvement were independent prognostic factors of TTT. The threshold of ≥6 mitoses per 3 mm² identified patients with a shorter TTT (median 18.5 months). A residual volume ≥1 cm³ also identified patients with a shorter TTT (median 24.5 months). The group defined by <6 mitoses per 3 mm² and a residual volume <1 cm³ had the longest TTT (median 73 months) and OS (100% survival at 7 years). These findings were confirmed in a validation cohort of 52 tumours.

Conclusions: Mitotic activity and post-surgical residual volume can be combined to evaluate the prognosis for patients with resected astrocytomas IDH-mutant. Patients with <6 mitoses per 3 mm² and a residual volume <1 cm³ were the best candidates for observational follow-up.