e21043 Background: Perineural invasion (PNI) is associated with a high risk for recurrence and metastasis from cutaneous squamous cell carcinoma (cSCC). Recommendations vary regarding use of post-operative radiation therapy (PORT). Biomarkers for poor outcome from cSCC with PNI are lacking. We aimed to evaluate outcomes in high-risk cSCC with PNI treated surgically +/- PORT and to evaluate tissue from the primary tumor to identify biomarkers for highest risk. Methods: We conducted a retrospective chart review of PNI SCC patients seen between 2005 and 2014. We compared outcomes for surgery vs. surgery plus PORT. Gene expression from tumor debulk was evaluated via Nanostring. MAGEA3 function was evaluated using PAM 212 SCC cells in a BALB/c mouse model. CRISPR-Cas9 MAGEA3 PAM 212 knockouts were developed to assess role of MAGEA3 in SCC growth. Results: Thirty-two patients with PNI SCC were identified. All were treated surgically, and 18/32 elected to undergo PORT. Nodal metastases were noted in 5/14 patients who did not undergo PORT, whereas no metastases were noted in any patient who underwent PORT. Thus, surgery plus PORT was associated with better outcome than surgery alone (P < 0.01). Local recurrence was not observed in any patients treated by surgery, including 30 patients treated by Mohs micrographic surgery (MMS). MAGEA3 was highly expressed in PNI SCC. MAGEA3 expression in PAM 212 SCC was associated with tumor growth and increased expression of cyclins A, B, and E. CRISPR-Cas9 MAGEA3 PAM 212 knockouts exhibited reduced growth in BALB/c mice. Conclusions: MAGEA3 expression is increased in human PNI SCC. We can mitigate against worst case outcome with surgery plus PORT. MAGEA3 merits further investigation as a potential biomarker for best candidates for surgery plus PORT.
Treatment Recommendations among Radiation Oncologists in the Treatment of Cutaneous Squamous Cell Carcinoma with Perineural Invasion
