The Use of Induction Chemotherapy in Olfactory Neuroblastoma: A Multi-institutional Series

Introduction: Olfactory neuroblastoma (ONB) is a rare neuroectodermal tumor thought to originate from olfactory receptor cells of the nasal cavity. Negative-margin surgical resection may not be achievable in a subset of patients with locally advanced disease. Previous studies have shown that ONB is chemosensitive; further investigation is needed to explore the efficacy of induction chemotherapy (IC) to reduce tumor size and burden prior to definitive surgery. We present a modern-era multicenter ONB series of patients with locally advanced disease treated with IC.

Methods: A modern-era multicenter retrospective review of patients with ONB at 9 academic, tertiary-care centers within North America from 2005 to 2021 was performed. Only patients who were treated with induction chemotherapy were included in the study. Clinicopathologic features including histopathologic and imaging status, modified Kadish staging and Hyams grading systems, treatment modalities, margin status, follow-up time, and survival were collected for analysis.

Results: Fifteen patients with ONB were treated with induction chemotherapy. The patient population was predominantly male (60%) with a median age of 51 (IQR, 40.5–64) years. Regarding baseline tumor characteristics in patients with available MRI, 72.7% patients had dural invasion, 16.7% had cavernous sinus invasion, 30.8% had periorbital involvement, and 16.7% had intraconal orbital tissue involvement. Of the 14 patients with modified Kadish staging, 7 (50%) patients were stage C and 7 (50%) patients were stage D prior to treatment. Two (22.2%) patients were Hyams grade I, 3 (33.3%) patients were Hyams grade II, 1 (11.1%) patient was Hyams grade III, and 3 (33.3%) patients were Hyams grade IV. Two (13.3%) patients were treated with induction chemotherapy followed by chemo/radiotherapy and 13 (86.7%) patients with induction chemotherapy followed by resection and adjuvant chemo/radiotherapy. Nine patients had pathological data available following resection, including 5 (55.6%) patients with negative margins and 4 (44.4%) patients with positive margins. Of the four patients with positive margins, all four had adjuvant RT with intensity-modulated radiation therapy. The median follow-up period of the cohort was 46 (IQR, 19.1–130.6) months after diagnosis. Of 14 patients with sufficient data for analysis, 3 (21.4%) patients developed local disease recurrence after a median of 52.0 (IQR, 29.2–99.2) months. Three patients developed regional disease recurrence after 59.7 (IQR, 39–93.95) months. One patient with modified Kadish stage D ONB had both local and distant recurrence at 6.5 months. Overall, 6 patients experienced recurrence after a median of 52 (IQR, 29.2–99.2) months. Of the six patients who had recurrence after IC, two patients had prior neck radiation before recurrence. Both of these patients had local recurrence only. The 5-year recurrence-free survival and overall survival were 59.7 and 70.6%, respectively.

Conclusion: Patients with ONB treated with IC tended to have more advanced disease at the time of treatment. Advanced-stage ONB tends to have lower rates of recurrence-free survival and overall survival. IC provides an additional treatment modality that has the potential to improve prognosis for patients with advanced-stage disease. Future large multi-institutional matched cohort studies are needed to delineate the role of IC in the management of this rare disease.

Publication History

Article published online:
07 February 2025