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Adjuvant radiation improves survival in advanced squamous cell carcinoma with certain features

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February 11, 2019

Adjuvant radiation therapy improved survival outcomes among patients with advanced cutaneous squamous cell carcinoma that included perineural invasion and regional disease, according to findings published in JAMA Otolaryngology-Head & Neck Surgery.

 “Optimal treatment of advanced cutaneous squamous cell carcinoma remains controversial because there are only a few large retrospective series that describe clinical outcomes, and no randomized clinical trials are available to guide decision-making,” Brianna N. Harris, MD, resident physician in the department of otolaryngology at University of California, Davis, and colleagues wrote. “Dermatologic series for all cutaneous squamous cell carcinomas have demonstrated that tumor differentiation, diameter, depth of invasion and perineural invasion are indicative of recurrence and poor survival.”

Researchers conducted a retrospective analysis of 349 patients (mean age, 70 years; range, 32-94; 86.5% men) with head and neck cutaneous squamous cell carcinoma who had undergone primary resection with or without adjuvant radiation therapy at University of California, Davis, or Washington University School of Medicine between Jan. 1, 2008, and June 30, 2016.

More than half of the patients (58.5%, n = 204) had recurrent tumors, 39% (n = 136) had perineural invasion, 37% (n = 129) had regional disease, 24.4% (n = 85) had poorly differentiated histologic features and 19.2% (n = 67) had extracapsular tumor extension.

A total of 176 patients underwent adjuvant radiation therapy and an additional 15 (5.4%) were treated with adjuvant chemoradiation therapy. Adjuvant therapy was more commonly used for patients with larger, regionally metastatic, poorly differentiated tumors with perineural invasion, and for those who were younger and immunosuppressed.
Median follow-up was 37 months (standard deviation, 55).

Kaplan-Meier estimates showed 5-year DFS of 59.4% and OS of 47.4%.

Cox proportional hazards multivariate regression, controlling for patient and tumor data, showed poorer DFS among patients with periorbital tumors (HR = 2.48; 95% CI, 1-6.16), perineural invasion (HR = 1.9; 95% CI, 1.12-3.19), or nodal disease that was N2 or greater (HR = 2.16; 95% CI, 1.13-4.16).

Results also showed poorer OS among patients with immunosuppression (HR = 2.17; 95% CI, 1.12-4.17) and N2 or greater nodal disease (HR = 2.43; 95% CI, 1.42-4.17).

Univariate analysis found no association between adjuvant radiation therapy and OS or DFS. However, on multivariate analysis, researchers observed improved OS with adjuvant radiation therapy among the entire cohort (HR = 0.59; 95% CI, 0.38-0.9). A subset analysis of tumors with perineural invasion showed an association between adjuvant radiation therapy and improved DFS (HR = 0.47; 95% CI, 0.23-0.93) and OS (HR = 0.44; 95% CI, 0.24-0.86). Patients with regional disease who received adjuvant radiation therapy also demonstrated improved DFS (HR = 0.36; 95% CI, 0.15-0.84) and OS (HR = 0.3; 95% CI, 0.15-0.61).

“In our series of surgically treated advanced cutaneous squamous cell carcinoma of the head and neck, adjuvant radiation therapy was more commonly given to patients with perineural invasion, increased tumor diameter, poor differentiation or regionally metastatic disease,” the researchers wrote. “In patients with perineural invasion and regional disease, adjuvant radiation therapy was associated with improved survival compared with surgery alone.” – by Jennifer Byrne

Disclosures: Harris reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.

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