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Updated: Jul 2, 2026
A Model for Perineural Invasion in Head and Neck Squamous Cell Carcinoma
Published on: January 5, 2017
PD-1 Inhibitors for Periocular Squamous Cell Carcinoma With Perineural Spread to the Orbit and Skull Base
Tracy J Lu1, Janet Fan1, Luana Guimaraes de Sousa2
1Orbital Oncology and Ophthalmic Plastic Surgery, Department of Plastic Surgery.
Purpose:
Periocular squamous cell carcinoma with perineural spread and orbital and skull base involvement is challenging to treat, as complete surgical resection is usually not feasible and radiotherapy carries a high risk of ocular toxic effects. PD-1 inhibitors have emerged as an alternative treatment for such cases.
Methods:
A retrospective study of all consecutive patients with periocular squamous cell carcinoma and perineural spread to the orbit treated with PD-1 inhibitors was carried out. Patients who had concurrent radiotherapy were excluded. The main outcome measure was treatment response.
Results:
Most patients had recurrent squamous cell carcinoma that had been heavily treated with Mohs surgery, radiotherapy, chemotherapy, or a combination of these modalities before referral with perineural spread to the orbit and skull base. All patients had V1 involvement; other cranial nerves involved were III (n = 1), V2 (n = 1), V3 (n = 1), VI (n = 1), VII (n = 2), and VIII (n = 1). The PD-1 inhibitors cemiplimab and pembrolizumab were used in 9 patients and 1 patient, respectively. The treatment duration ranged from 2 to 24 months (median, 19 months). Six patients had a partial response, and 4 had a complete response. With a median follow-up time of 16 months, all patients were without evidence of progressive disease at last contact.
Conclusion:
Treatment with PD-1 inhibitors can lead to meaningful responses in patients with periocular squamous cell carcinoma with perineural spread to the orbit and skull base and avoids the need for radiotherapy, which is toxic to the eye. Careful long-term follow-up is needed to assess long-term response durability.
Insights
Programmed cell death protein 1 (PD-1) inhibitors show promise for treating advanced periocular squamous cell carcinoma with perineural spread. This approach offers an alternative to radiotherapy, potentially reducing ocular toxicity and achieving significant patient responses.
Area of Science:
- Oncology
- Dermatology
- Immunotherapy
Background:
- Periocular squamous cell carcinoma with perineural spread presents treatment challenges due to surgical limitations and radiotherapy's ocular toxicity.
- Programmed cell death protein 1 (PD-1) inhibitors offer a potential alternative treatment modality for these complex cases.
Purpose of the Study:
- To evaluate the efficacy of PD-1 inhibitors in patients with periocular squamous cell carcinoma involving the orbit and skull base.
- To assess treatment response in patients with advanced periocular squamous cell carcinoma treated with PD-1 inhibitors.
Main Methods:
- Retrospective study of consecutive patients with periocular squamous cell carcinoma and perineural spread treated with PD-1 inhibitors.
- Exclusion of patients who received concurrent radiotherapy.
- Assessment of treatment response as the primary outcome measure.
Main Results:
- Most patients had heavily pre-treated, recurrent squamous cell carcinoma with perineural spread to the orbit and skull base.
- All patients had V1 involvement; other cranial nerves were also affected.
- Six partial and four complete responses were observed; all patients remained without progressive disease at median follow-up of 16 months.
Conclusions:
- PD-1 inhibitors can achieve meaningful responses in advanced periocular squamous cell carcinoma with perineural spread.
- This immunotherapy approach avoids radiotherapy, mitigating ocular toxicity.
- Long-term follow-up is essential to determine the durability of responses.
