The Impact of Adjuvant Radiation Therapy and Elective Nodal Irradiation in Early Stage/Low Grade versus Advanced Stage/High Grade Olfactory Neuroblastoma

Abstract

Olfactory neuroblastoma (ONB) is a rare head and neck cancer originating from neural crest cells of the olfactory membrane located in the roof of the nasal fossa. Several retrospective studies have shown surgical resection, followed by adjuvant radiotherapy, to be superior to either modality alone. However, even with bi-modality or even tri-modality therapy ONB patients with high Hyams grade (HHG) and advanced Kadish stages (AKS), C or D, have worse clinical outcomes compared to low Hyams grade (LHG) and early Kadish stages (EKS), A or B. This study evaluates clinical outcomes in ONB patients, comparing adjuvant radiation therapy versus surgery alone in EKS. In addition we evaluated the impact of adjuvant radiotherapy including elective nodal irradiation (ENI). Forty-one ONB patients treated with surgical resection at our institution from 1996 to 2017 were identified. Two patients died following surgery and were excluded from the analysis. Univariate, multivariate, and survival analysis was performed with comparative analysis between radiation of the primary site and ENI. Median follow-up time in this cohort was 59 months (range 5.2-236). The median overall survival (OS) and disease free survival (DFS) for the entire cohort was 15 years and 7.6 years, respectively. The five-year cumulative OS and DFS was 83% and 72%, respectively. Ten patients (26%) had ONBs classified as EKS and 29 patients (75%) had AKS tumors. The 5 year OS for ONBs with LHG was 100% compared to 65% for those with ONBs with HHG (p=.017). 66% of the EKS patients were also LHG compared to only 28% LHG in AKS patients (p=.057). The 5 year OS/DFS was 100%/100%, 100%/66%, 100%/75%, and 59%/47% for EKS/LHG, EKS/HHG, AKS/LHG, and AKS/HHG, respectively (p=0.07). Five patients in the EKS group received surgical resection alone, and there were no observed deaths or recurrences with a median follow up of 44 months (range 5-235 months). 31 (79%) patients in the entire cohort presented with node-negative disease. 13 (56%) of the node-negative patients received ENI. There were six nodal-failures in the entire cohort, with one failure 16 years following treatment (median 59 months, range 6-165 months). In node-negative patients the 10 year nodal-failure rate was reduced from 38% (3/8) in patients treated with primary site radiation alone to 0% (0/9) with the addition of ENI (p=.04). In this retrospective review, patients with both AKS and HHG have significant worse clinical outcomes compared to EKS and LHG. In EKS patients, surgery alone resulted in long term OS and DFS. For patients with node negative disease at presentation (other than those with EKS who did not undergo radiation), ENI resulted in significant reduction in the regional failure. In select patients presenting EKS and LHG ONB, surgical resection alone can be considered. Furthermore ENI should be standard of radiation therapy and long term follow up is recommended.