Faculty Bibliography

BACKGROUND:Data are limited regarding the performance of staging systems for non-head and neck cutaneous squamous cell carcinomas (non-HNCSCCs). OBJECTIVE:The aim of this study was to evaluate the performance of the Brigham and Women's Hospital (BWH) and American Joint Committee on Cancer 8th edition (AJCC8) staging system in predicting poor outcomes in non-HNCSCCs. PATIENTS AND METHODS/METHODS:Demographics, tumor features and stages, and outcomes for non-HNCSCCs were collected retrospectively from 11 institutions in two countries. Poor outcomes included local recurrence, metastasis, and disease-specific death; major poor outcomes excluded local recurrence. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), concordance index (c-index), and 3-year cumulative incidence were calculated. Cumulative incidence function (CIF) plots were created. RESULTS:9300 non-HNCSCCs were included. Ninety-five tumors (1%) resulted in major poor outcomes; 250 (2.7%) resulted in poor outcomes. The rate of local recurrence was 1.9%, and the rate of nodal metastasis was 0.74%. Major poor outcomes were predicted with sensitivities 0.48/0.49, specificities 0.98/0.96, PPVs 0.17/0.13, NPVs 0.99/0.99, and c-indices 0.73/0.74 for BWH/AJCC8. Poor outcomes were predicted with sensitivities 0.24/0.26, specificities 0.98/0.97, PPVs 0.22/0.17, NPVs 0.98/0.98, and c-indices 0.61/0.61 for BWH/AJCC8. CONCLUSIONS:Both systems performed similarly in predicting poor outcomes in non-HNCSCCs. Specificity and NPV were high, sensitivity and PPV were low, and c-indices were moderately high. As the c-indices were comparable to those seen in the HNCSCC literature, it is reasonable to use the BWH and AJCC8 staging systems for tumors located off the head and neck. However, further refinement of CSCC staging systems is needed to improve prognostication.

BACKGROUND:High-risk cutaneous squamous cell carcinomas (HRCSCC) have an increased likelihood of poor outcomes following surgery. Adjuvant radiation therapy (ART) may decrease this risk; however, there is limited data on its efficacy. OBJECTIVE:To evaluate whether ART is associated with reduced risks of local recurrence, locoregional recurrence, nodal metastasis, and disease-specific death in localized, fully resected HRCSCC. METHODS:A retrospective, multicenter cohort study was conducted. Competing risk modeling was performed to evaluate ART, controlling for patient, tumor, and treatment factors. RESULTS:This study included 1,267 HRCSCC, of which 155 (12.2%) received ART. ART was associated with a 50% reduction in the risk of local recurrence (CHR=0.47; 95% CI: 0.23, 0.96; p=0.04), locoregional recurrence (CHR=0.47; 95% CI: 0.26, 0.83; p=0.01), and nodal metastasis (CHR=0.45; 95% CI: 0.21, 0.98; p=0.04). The effect on disease-specific death was small and not statistically significant (CHR=0.83; 95% CI: 0.35, 1.94; p=0.66). In modeling, ART decreased the estimated 5-year cumulative incidence of local recurrence from 11.9% (95% CI, 9.4%-14.0%) to 5.9% (2.8%-9.8%), of locoregional recurrence from 17.8% (15.1%-20.3%) to 9.0% (5.1%-13.6%), and of nodal metastasis from 9.5% (7.3%-11.2%) to 4.6% (1.7%-8.5%). A subset of HRCSCC at greatest risk of poor outcomes was identified and comprised of tumors that were Brigham and Women's Hospital (BWH) stage T3, BWH stage T2 tumors with three risk factors, and/or tumors with lymphovascular invasion. Among these 246 HRCSCC, 74 (30.1%) received ART, and ART was associated with a decreased risk of locoregional recurrence (CHR=0.48; 95% CI: 0.26, 0.89; p=0.02) and nodal metastasis (CHR=0.43; 95% CI: 0.19, 0.97; p=0.04). On modeling, this subgroup experienced greater absolute reductions in the estimated 5-year incidence of locoregional recurrence from 36.6% (95% CI, 30.0%-45.3%) to 20.0% (11.1%, 31.1%) and of nodal metastasis from 21.1% (17.4%-30.9%) to 9.6% (4.2%-18.1%). CONCLUSION/CONCLUSIONS:In this retrospective multicenter cohort of HRCSCC, adjuvant radiation was associated with reduced risks of local recurrence and nodal metastasis. Prospective studies are required to further characterize the effect of adjuvant radiation on HRCSCC.

BACKGROUND:Immunosuppression is associated with a higher risk of developing cutaneous squamous cell carcinoma and more aggressive tumors, but its role as an independent predictor of poor outcomes remains unclear. OBJECTIVE:To determine whether immunosuppression independently predicts poor outcomes in cutaneous squamous cell carcinoma. METHODS:This was a retrospective cohort study with pooled data from 12 international centers. Demographics, immunosuppression status, tumor characteristics, treatment, and outcomes were collected. Univariable and multivariable marginal Fine and Gray competing risk analyses were performed. Subgroup multivariable analyses were performed on the organ transplant and chronic lymphocytic leukemia cohorts. RESULTS:A total of 11,930 patients with 18,760 tumors (14,766 in immunocompetent and 3,994 in immunosuppressed) were included. Immunosuppressed patients had a higher prevalence of high-risk tumor features and poor disease outcomes. On multivariable analysis, immunosuppression was independently associated with local recurrence, distant metastasis, disease-specific death, and major poor outcomes. Organ transplantation was predictive of local recurrence, distant metastasis, and disease-specific death, whereas chronic lymphocytic leukemia independently predicted local recurrence, disease-specific death, and major poor outcomes. LIMITATIONS/CONCLUSIONS:Retrospective design, potential for data heterogeneity. CONCLUSIONS:Immunosuppression is an independent risk factor for major poor outcomes in cutaneous squamous cell carcinoma and should be included in risk nomograms.