Clinical Perineural Invasion and Immunotherapy for Head and Neck Cutaneous Squamous Cell Carcinoma

Abstract

Objectives/Hypothesis To describe outcomes of advanced head and neck cutaneous squamous cell carcinoma (cSCC) with clinical perineural invasion (cPNI) treated with immune checkpoint inhibitor (ICI) therapy, and to describe post‐treatment radiographic findings in the context of clinical response to treatment using a new grading system. Study Design Retrospective chart review. Methods Retrospective chart review was performed for 11 patients treated with ICI for head and neck cSCC with cPNI of large named nerves. The primary outcome was response to treatment as defined by radiographic and clinical evidence. Clinical responses were defined as improvement in symptoms of neuropathic pain, hypoesthesia, nerve weakness, or decrease in visible tumor. Imaging studies were graded based on a new classification system for perineural invasion and reviewed by two neuroradiologists since RECISTv1.1 is inadequate to adjudicate response in these patients. Results Nine (82%) patients had radiographic perineural disease control on ICI. Eight patients had improved radiographic perineural disease and one had stable disease. Of these, complete resolution of radiographic evidence of perineural disease was seen in only one patient. Seven (64%) patients had clinical responses, with either improved or stable radiographic disease. Conclusions ICI therapy is a viable treatment option for head and neck cSCC with cPNI. Radiographic and clinical evidence of response correlate well, with improvement in neuropathic pain being the most sensitive clinical marker of response. Even with favorable findings on repeat imaging and stable clinical course, complete resolution of perineural thickening and enhancement is rare. A grading system for classifying changes in perineural disease over time is proposed. Level of Evidence 4 Laryngoscope, 132:1213–1218, 2022

Immunotherapy response in patients with cutaneous squamous cell carcinoma of head and neck with cranial nerve involvement

“…4,12,13 The most common AEs were fatigue, diarrhea, and rash; but more serious events such as pneumonitis, hepatitis, colitis, and endocrine disorders (adrenal insufficiency, thyroid dysregulation, diabetes mellitus) have also been reported. 22 Our findings are consistent with results from studies by Wu et al Patients with HNcSCC with CNI who received IO monotherapy, mainly cemiplimab 350 mg every 3 weeks, had clinical benefit, evidenced by stable disease or partial response on imaging, and are alive at last followup. Moreover, treatment was well tolerated with minimal toxicity that allowed for continued IO use despite irAEs.…”

“…About 7%–8% of patients in phase II and I trials, respectively, discontinued treatment with cemiplimab due to AEs 4,12,13 . The most common AEs were fatigue, diarrhea, and rash; but more serious events such as pneumonitis, hepatitis, colitis, and endocrine disorders (adrenal insufficiency, thyroid dysregulation, diabetes mellitus) have also been reported 22 …”

Perineural invasion and perineural spread in periocular squamous cell carcinoma

“…Progressive and often concentric neural enlargement will cause secondary erosion and widening of the neural foramina at the midface and skull base [ 55 , 64 ]. It should be noted that despite treatment response, there is often persistent perineural thickening or enhancement [ 68 ]. Therefore, on imaging surveillance, stabilisation or regression of the signal without further nerve enlargement represents disease control [ 64 ].…”

“…There was one case report of a primary suprabrow SCC with orbital extension that recurred following radical surgical resection and radiotherapy, and was eventually amenable to cemiplimab [ 94 ]. A separate case series investigated the efficacy of pembrolizumab and cemiplimab for head and neck cSCC with perineural spread that was refractory to prior radical treatments [ 68 ]. Nine patients (82%) attained stabilisation or improved disease control, which compares favourably with the data from metastatic cSCC.…”

Benchmarking Survival Outcomes Following Surgical Management of pT3 and pT4 Cutaneous Squamous Cell Carcinoma of the Head and Neck

“…24 On the other hand, Wu and colleagues recently reported on a series of 11 patients with advanced cSCC and clinical PNI treated with ICI therapy, in which 9 patients showed radiographic evidence of perineural disease control (median follow-up 13 months). 25…”