Examining the Natural History and Patterns of Disease Recurrence in Patients with Positive Margin Esthesioneuroblastoma

Background: Esthesioneuroblastoma (ESB) is a rare, malignant tumor of the sinonasal tract that arises from olfactory epithelium. Although surgery is the preferred first-line treatment, tumor involvement of adjacent structures may preclude the ability to achieve negative margins during initial resection. Currently, data regarding the natural history of patients with positive margin ESB is lacking. Herein, we present our institutional experience in treating positive margin ESB with the aim of determining predictors of disease recurrence. Along with describing the natural history of positive margin ESB, we also aim to characterize the patterns of recurrence and outcomes of this patient population.

Methods: We performed an institutional retrospective chart review of 21 patients with positive margin ESB. In addition to descriptive statistics, we performed univariate analysis to determine any statistically significant predictors of disease recurrence.

Results: Query of our institutional patient database from January 1, 1960, to September 1, 2018, identified 143 patients that were treated for ESB, of which 21 patients had positive margins following their first resection. Of these patients, 10 had 'delayed' positive margins that were initially negative in the operating room but returned as positive on final pathology (48%). All patients received adjuvant radiotherapy, while 13 additionally received adjuvant chemotherapy (62%). Eleven patients (52%) experienced recurrence at a median time of 40 months following resection (IQR: 22–66 months). Local disease recurrence occurred in 7 patients (33%), regional recurrence in 8 patients (38%), and distant metastasis in 2 patients (10%). Treatment for recurrence included local subtotal resection in 1 patient (9%), neck dissections in 4 (36%), radiotherapy in 5 (45%), and chemotherapy in 4 (36%). In univariate analysis, only modified Kadish Stage D at presentation was predictive of future disease recurrence (HR: 17.21, 95% CI: 2.79–106.30, p = 0.002). Hyam's grade, extent of resection, adjuvant chemotherapy, and primary radiotherapy were not associated with disease recurrence. At most recent follow-up (median: 75 months; IQR: 47–84 months), 3 patients in the recurrence group were dead (14%) and 8 patients were alive (38%), while in the no recurrence group, 1 patient was dead (5%) and 9 patients were alive (43%). There were no statistically significant differences of survival between positive and negative margin ESB (p = 0.071), between recurrence and no recurrence in positive margin ESB (p = 0.71), and between the location of recurrence (p = 0.80).

Conclusions: Approximately half of patients with positive margin ESB may experience disease recurrence. Further, patients with advanced disease stage at presentation may have a higher likelihood of developing recurrence. However, secondary treatment of recurrence with neck dissection +/− chemoradiotherapy can lead to similar patient survival as those without recurrence in positive margin ESB ([Figs. 1] [2] [3] [4]).

Fig. 1 Locations of positive-margins following initial surgical resection of ESB.

Fig. 2 Kaplan–Meier survival curves comparing (A) negative-margin versus positive-margin in ESB; (B) no recurrence versus recurrence in positive-margin ESB; (C) local versus regional versus distant recurrence in positive-margin ESB.

Fig. 3 Demographics, treatments, recurrence, and outcomes.

Fig. 4 Univariate analysis of factors predictive of future disease recurrence.

 

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No conflict of interest has been declared by the author(s).

Publication History

Article published online:
01 February 2023