Perineural invasion (PNI) is an uncommon (<5%) which refers to tumor cell invasion extensive enough to cause clinically detectable deficits of the involved nerve. It is a high-risk feature observed with non-melanomatous skin cancer (NMSC) more commonly seen in those with squamous cell carcinoma. The primary management options including radiotherapy with or without surgery, with local control rates exceeding 50%.

Given the overwhelming influence of local control on disease control and survival, dose escalation and complication mitigation through hyperfractionated and high-dose conformal skull-base proton therapy are strategies to improving the therapeutic window in patients with cutaneous head and neck cancer with clinical PNI.