Survival and Patterns of Relapse of Head and Neck Malignancies with Large Nerve Perineural Spread after Skull Base Surgery and Postoperative Radiation Therapy

Purpose: Cutaneous head and neck malignancies can undergo perineural spread (PNS) due to the rich innervation. Patients with large nerve PNS of the head and neck region commonly had cranial nerves five and seven affected. Our aim study was to evaluate the survival and pattern of relapse for patients with PNS of cutaneous head and neck malignancies, predominantly squamous cell carcinoma (SCC), staged with a high-resolution MRI neurogram,who have undergone curative intent skull base surgery and/or radiation therapy.

Method and Materials: A review of a prospective database identified 47 patients diagnosed with PNS of head and neck cancer between the years 2013 and 2018. Kaplan–Meier methods were used to estimate relapse free survival (RFS) and overall survival (OS). Multivariant analysis of patient age, sex, histological subtype, zone of spread, and margin status was performed to identify patients with a higher propensity for relapse and death.

Results: Forty-seven patients with a median follow-up of 17 months (range = 3–59) from the time of diagnosis were identified with head and neck malignant PNS from our institutions database. The overall 2-year RFS from time of diagnosis was 54% and overall survival 88%. The most common histological type was SCC (SCC: 38 patients; basal cell carcinoma: 1; adenoid cystic carcinoma: 6; mucosal SCC: 1; and mucoepidermoid carcinoma: 1). Patients aged 65 years or older at time of diagnosis had a statically significant worse relapse free survival. The most commonly affected nerve was V2. Out of these 46 patients, 21 had zone 1 (PNS to but not involving the skull base foramen: 46%), 12 had zone IIa (PNS to the foramen but not the ganglion: 26%), 11 had zone IIb (PNS to the ganglion: 24%), and 2 had zone III (PNS to the preganglionic segment: 4%) involvement. Patients with central PNS to zones IIb and/or III did not appear to have worse outcomes compared with the more peripheral PNS (zones I and IIa; HR: 1.1; p = 0.9). Those with involved surgical margins demonstrated higher trend of relapse (HR: 2.5; p = 0.08). Patients with >1 involved nerve also showed a trend of higher relapse (HR: 2.5; p = 0.08). A total of 14 patients developed recurrence (1 dermal metastasis, 2 at the in-field primary tumor sites, 1 at the lymph node in-field, 1 at both in-field primary site and nodal site, 1 at the primary site and distal PNS, 6 had distant metastasis, 1 at central PNS out-field, and 1 had distal PNS out-field).

Conclusion: Failure at primary tumor site and peripheral PNS represent a common mode of relapse. Treatment to the peripheral nerve track and the primary tumor should be optimized by improving the surgical margins and more extensive peripheral nerve coverage by postoperative radiotherapy.