2025 Proffered Presentations
S081: OUTCOMES OF SINONASAL CARCINOMAS DEFINED BY IDH2-MUTANT STATUS
Daniel W Scholfield, MD, FRCS1; Lucas Axiotakis, MD1; Robbie Woods, MD, FRCS2; Katherine Tai, MD1; Alana Eagan, MPH1; Lara Dunn, MD1; Nancy Lee, MD1; Ian Ganly, MD, PhD1; Marc Cohen, MD, MPH1; Snjezana Dogan, MD1; 1Memorial Sloan Kettering Cancer Center; 2Beaumont Hospital
Background: Sinonasal carcinomas are aggressive and often locally invasive at presentation, with no universally accepted treatment approach. While IDH2-mutant status appears to be associated with improved treatment response and survival, the clinical significance of SNUC versus non-SNUC diagnosis among IDH2-mutants is unclear, and long-term clinical outcomes data lacking.
Methods: Records from a prospectively maintained skull-base database at a large, tertiary care hospital system from 1986-2024 were reviewed. After histopathologic confirmation, 22 IDH2-mutant SNUC, 14 IDH2-mutant non-SNUC, and 8 IDH2-wildtype SNUC cases were amenable to comprehensive clinicopathologic data review. SMARCB-1 deficient cases were excluded. A presence of IDH2 R172 and pathogenic TP53 mutations was determined by molecular testing and/or by immunohistochemistry.
Results: Median follow-up was 28 months (interquartile range 11-64 months). The median age at diagnosis was 58 years and 61% of patients were male. The majority of patients presented with T4b disease (41% of IDH2-mutant SNUC; 57% of IDH2-mutant non-SNUC; 75% of IDH2-wildtype SNUC; p = 0.3). There was no significant difference in the proportion of patients that presented with orbital invasion (55% IDH2-mutant SNUC; 64% IDH2-mutant non-SNUC; 75% IDH2-wildtype SNUC; p=0.7) or intracranial invasion (82% IDH2-mutant SNUC; 79% IDH2-mutant non-SNUC; 75% IDH2-wildtype SNUC; p=0.7). On histopathology, there was no significant difference in perineural invasion and margin status between the three subgroups (p>0.6). However, it is worth noting that sinonasal resections are typically fragmented meaning it is usually difficult to accurately assess for PNI. A greater proportion of IDH2-mutant non-SNUCs had TP53 mutations (67%) than IDH2-mutant SNUC (31%) and IDH2-wildtype SNUC (29%) (p=0.13). Across the cohort, 41% of patients received neoadjuvant chemotherapy, with a partial response by RECIST criteria in 94% of patients across the subgroups. Surgery was part of the multimodality approach in 59% (13/22) of IDH2-mutant SNUC, 50% (7/14) of IDH2-mutant non-SNUC and 63% (5/8) of IDH2-wildtype SNUC. Eighty percent of the cohort received adjuvant radiotherapy and 63% received adjuvant chemotherapy.
There was a trend towards worse disease specific (DSS) and recurrence free survival (RFS) in IDH2-mutant SNUC, with a DSS of 60%, 75% and 75% in IDH2-mutant SNUC, IDH2-mutant non-SNUC and IDH2-wildtype SNUC, respectively (p = 0.35; Figure 1). RFS probability was 45% in IDH2-mutant SNUC, 71% in IDH2-mutant non-SNUC, 53% IDH2-wildtype SNUC (p = 0.85; Figure 2).
Conclusion: Upfront assessment of IDH2 mutation status in sinonasal carcinoma patients may be warranted to select patients for clinical trials with IDH-inhibitors. However, there was no difference in extent of disease at presentation and response to induction chemotherapy relative to the presence of IDH2 variants. Larger series are required to determine the prognostic significance of IDH2 mutation status in sinonasal carcinoma patients.
