3D Volumetric RANO Improves Progression Assessment and Correlation for IDH1/2-Mutant Diffuse Glioma: Findings from the Phase 3 INDIGO Trial
Key Clinical Takeaways
- Design/Population: Post hoc analysis of 331 patients with IDH1/2-mutated diffuse glioma enrolled in the phase 3 INDIGO trial compared 2D RANO per BIRC with 3D volumetric RANO to assess progression, correlation, and clinical outcomes.
- Key Outcomes:
- Strong correlation between 2D and 3D measurements (r = 0.858).
- 3D volumetric RANO demonstrated a stronger treatment effect (HR, 0.24 vs 0.35) and fewer progression events.
- 3D PFS closely aligned with time to next intervention, confirming consistent clinical relevance.
- Fair agreement between methods (κ = 0.325 to 0.382), with 3D RANO classifying more stable disease and fewer progressive disease cases.
- Clinical Relevance: The use of 3D volumetric RANO may offer a more accurate and stable assessment of tumor burden and disease progression than 2D RANO. These findings suggest that incorporating 3D volumetric methods into glioma trial design could enhance end point precision, reduce misclassification, and improve the evaluation of treatment benefit in patients with low-grade diffuse glioma.
According to results from a post hoc analysis, 3D volumetric Response Assessment in Neuro-Oncology (RANO) demonstrated stronger treatment effect estimates and improved correlation with clinical outcomes compared with traditional 2D RANO measurements among patients with IDH1/2-mutant diffuse glioma treated with vorasidenib or placebo.
These findings were presented by Benjamin Ellingson, PhD, University of California, Los Angeles, at the 2025 Society for Neuro-Oncology (SNO) Annual Meeting in Honolulu, Hawaii.
In this analysis, investigators evaluated data from 331 patients with low-grade glioma enrolled in the phase 3 INDIGO trial, who were randomized to receive either vorasidenib (n = 168) or placebo (n = 163). Tumor assessments were conducted using both 2D RANO and 3D volumetric RANO, as evaluated by a blinded independent central review. Primary end points included progression-free survival (PFS), correlation between measurements, time to next intervention, and response. Mixed models were used to assess longitudinal correlation, and weighted κ statistics were used to measure agreement in response classification.
At analysis, there was a strong positive correlation between 2D and 3D measurements (Pearson r = 0.858; mixed model r = 0.861). The 3D volumetric assessment yielded a stronger treatment effect (hazard ratio [HR], 0.24; 95% confidence interval [CI], 0.15 to 0.37) compared with 2D assessment (HR, 0.35; 95% CI, 0.25 to 0.49). Based on 3D assessment, PFS was 16.1% in the vorasidenib arm and 44.2% in the placebo arm, compared with 32.1% and 63.8%, respectively, using 2D assessment. 3D-assessed PFS visually aligned with time to next treatment intervention, demonstrating consistent treatment effect sizes across both measures.
Agreement between the 2 methods was fair for best overall response (κ = 0.382) and all timepoint assessments (κ = 0.325). Across all timepoints, 80 minor responses were identified by 2D assessment and 54 minor responses by 3D assessment. There were 389 progressive disease classifications using 2D assessment compared with 266 using 3D, and 1,410 stable disease classifications with 2D versus 1,552 with 3D.
“3D volumetric assessments demonstrated stronger treatment effects than 2D assessments, with similar treatment effect sizes for 3D PFS and time to next intervention,” said Dr Ellingson. “3D volumetric RANO provided a more conservative progression threshold and a stable tumor burden measurement over time.”
He added, “Volumetric assessment may provide a more clinically meaningful determination of progression in grade 2 glioma trials, potentially impacting future trial design and end point selection.”
Source:
Ellingson BM, Mellinghoff I, Van Den Bent MJ, et al. Volumetric (3D) compared with traditional bidirectional (2D) assessment in patients with grade 2, isocitrate dehydrogenase 1/2 mutant (mIDH1/2) glioma receiving vorasidenib or placebo in the phase 3 INDIGO trial. Presented at the Society for Neuro-Oncology (SNO) Annual Meeting; November 19–23, 2025; Honolulu, Hawaii. Abstract IMG-89.
