MD-PhD trainee, MS4 Dept. of Otolaryngology-Head & Neck Surgery, University of Washington
Background: Cutaneous cancers of the head and neck with perineural invasion (PNI) are associated with neurologic dysfunction, local recurrence, and inferior survival. Resection followed by radiotherapy (RT) or RT alone for unresectable disease remain the mainstays of treatment. PNI is classified as clinical/gross (cgPNI) or microscopic (mPNI) based on clinical, radiographic, and histopathologic analysis. cgPNI includes clinical or radiographic involvement of cranial nerves. mPNI is evident on histologic examination alone with subsets of extensive invasion of nerves (ePNI) or invasion of large nerves (diameter ≥ 0.1 mm) (lnPNI), suggesting higher risk pathologic findings. There is no consensus to what extent nerve pathways should be treated with radiation with varying risk of PNI. The aims of this study were to examine oncologic outcomes and patterns of treatment failure in cutaneous malignancies of the head and neck with low and high-risk PNI.
Materials & Methods: A retrospective review of patients (2010-2021) who completed definitive or adjuvant RT for squamous cell carcinoma (SCC) or basal cell carcinoma (BCC) of the head and neck with PNI was performed. Patient demographics, RT treatment, clinicopathologic data, oncologic outcomes, and patterns of failure were recorded. Patients with cgPNI, ePNI, or lnPNI were classified as high-risk PNI. Fischer’s exact tests and unpaired t-tests were used to examine relationships of age, sex, and margin status between the high and low risk groups. Log-rank tests were used to compare disease-free, disease-specific, and overall survival.
Results: A total of 51 patients were included, 45 (88%) with SCC and 6 (12%) with BCC. 29 patients had high-risk PNI: 18 (35%) cgPNI, 6 (12%) lnPNI, and 5 (10%) ePNI. 22 patients (43%) had mPNI (low-risk). Surgical resection was performed in 20 (69%) high-risk PNI and 21 (95%) low-risk patients. All 18 (100%) patients with cgPNI, 1 (20%) with ePNI, and 3 (50%) with lnPNI underwent RT to the skull base and neural pathway(s). The mean follow-up time was 23 months. Nineteen (66%) high-risk PNI and 5 (23%) low risk patients presented with recurrent disease following previous treatment. In-field recurrences occurred in 5 (23%) patients with cgPNI, three of which had undergone prior treatment. Three mPNI patients (14%) who underwent RT to the wound bed experienced an in-field recurrence. When comparing the high-risk vs. low-risk groups, there were no statistically significant differences in disease-free survival (p=0.60, 2-year: 57% vs. 71%), disease-specific survival (p=0.73, 2-year: 86% vs. 85%), or overall survival (p=0.98, 2-year: 75% vs. 85%).
Conclusions: In this single-institution cohort, neither recurrence nor survival outcomes significantly differed between patients with high-risk and mPNI. This suggests local control rates in high-risk PNI are on par with low-risk/mPNI following a comprehensive multi-modality approach. Furthermore, in field failures were rare and occurred largely in patients who underwent prior treatment.