Systemic Neoadjuvant Therapies for Treatment of Cutaneous Squamous Cell Carcinoma of the Periorbital Region.

Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer after basal cell carcinoma.1 cSCC accounts for 5% to 10% of all eyelid cancers with an incidence rate estimated to be 1.37 per 100,000 individuals per year.2–4 Majority of patients with periorbital cSCC are older (60 years of age or older) and fair-skinned with significant sun exposure.3,5–7 Locally advanced cSCC in the periorbital region, when treated with current standard of care which is surgery followed by adjuvant radiotherapy (with or without concurrent chemotherapy) can lead to significant morbidity with poor cosmetic and functional outcome. An attempt for R0 resection (microscopically margin-negative resection) in such patients can be extensive, causing loss of lacrimal drainage apparatus and a significant distortion of the eyelid and orbit despite best efforts in reconstruction. Orbital exenteration is often required in locally advanced periorbital cases of cSCC. Orbital exenteration causes major functional impairment and aesthetic deformity, and is associated with substantial negative emotional and psychosocial impact.8–10 Highdose radiation therapy in the periorbital region is also associated with significant ocular toxicity, including dry eye syndrome, keratopathy, cataract, optic neuropathy, and radiation-induced retinopathy.11 Despite aggressive local treatments, the recurrence rate for locally advanced resectable cSCC of the head and neck region is up to 30% and can progress to death from disease in some patients.12,13 The 2-year diseasefree survival in locally advanced, resectable cSCC treated by current standard of care (surgery and adjuvant radiation) has been reported to be 78%.14