Faculty Bibliography

BACKGROUND:Satellitosis or in-transit metastasis (S-ITM) from cutaneous squamous cell carcinoma (cSCC) is associated with poor outcomes but is not included in current staging guidelines. OBJECTIVE:To determine risk factors and prognostic significance of S-ITM. METHODS:This cohort study included 8,901 patients with cSCC from 12 institutions (1998-2023). Risk factors for S-ITM were calculated using logistic regression. Outcomes were compared with 1:2 propensity score matched controls using a Fine-Gray subdistribution hazard model. RESULTS:Seventy-seven patients developed S-ITM. Increased patient age (OR 1.03, 95% CI 1.01-1.05, p<0.01), history of immunosuppression (OR 4.31, 95% CI 2.59-7.10, p<0.001), higher BWH stage (T2a OR 4.14, 95% CI 2.05-8.41; T2b OR 15.96, 95% CI 8.58-31.19; T3 OR 30.27, 95% CI 10.70-79.04, all p<0.001) and LVI (OR 4.57, 95% CI 1.80-10.38, p=0.001) were independent risk factors for S-ITM. S-ITM was associated with LR (SHR 2.40, 95% CI 1.43-4.04, p<0.001), NM (SHR 1.89 (95% CI .02-3.49, p=0.04), DM (SHR 4.41, 95% CI 1.45-13.27, p=0.01), and DSD (SHR 4.48, 95% CI 2.34-8.58, p<0.001). LIMITATIONS/CONCLUSIONS:Retrospective cohort study. The rarity of S-ITM may limit statistical power. CONCLUSION/CONCLUSIONS:Patients with cSCC and S-ITM are at higher risk for poor outcomes independent of patient, tumor, and treatment characteristics.

IMPORTANCE/OBJECTIVE:Risk stratification of cutaneous squamous cell carcinoma (CSCC) is central to effective management. Despite advancements in the 8th edition of the American Joint Committee on Cancer (AJCC8) staging system, the distinctiveness of T-stages remains limited. OBJECTIVE:To evaluate the effectiveness of the Brigham and Women's Hospital (BWH) and the AJCC8 staging systems in predicting poor outcomes in head and neck (HN) CSCC. DESIGN/METHODS:A retrospective, multinational cohort study of CSCCs diagnosed between January 10, 1991, and December 31, 2023. SETTING/METHODS:Twelve centers across the United States (10), Spain (1), and Brazil (1). PARTICIPANTS/METHODS:Patients with invasive CSCC who underwent curative-intent surgical treatment. Exclusions included cases of lip CSCC, cases with prior HN cancer with associated regional disease, patients with a history of chemotherapy/radiotherapy for other HN neoplasms, and recurrent primary tumors. EXPOSURE/METHODS:Tumors were staged according to both the AJCC8 TNM staging system and the BWH tumor classification. MAIN OUTCOMES AND MEASURES/METHODS:Local recurrence (LR), nodal recurrence (NR), distant recurrence (DR), and disease-specific death (DSD). RESULTS:A total of 9852 excised tumors from 3168 patients were included. The 2 systems had comparable monotonicity and homogeneity. Significant differences could be observed in 5-year cumulative incidence for DSD in both BWH and AJCC8, and also for LR in BWH. Higher T-stages exhibited similar curves regarding NR and DR for both AJCC8 and BWH staging systems. Overall, we observed high specificity and NPV, low sensitivity and PPV, and moderately high c-indices for both the BWH and AJCC8 staging systems in predicting the main outcomes for HNCSCC. CONCLUSION AND RELEVANCE/CONCLUSIONS:Current AJCC8 and BWH staging systems can accurately predict survival in HNCSCC, although there are still important characteristics to be addressed in future staging systems for better stratification according to the other main outcomes.

Gene expression profiling (GEP) is making a significant impact in dermatology by providing molecular insights that complement traditional diagnostic methods for skin cancer and inflammatory dermatoses. GEP evaluates messenger RNA levels to identify disease-specific patterns that can aid in diagnosis, prognostication, and/or treatment planning. Currently, commercially available tests for melanoma and cutaneous squamous cell carcinoma are available. The development of GEP tests follows a stepwise process, including discovery, validation, and clinical implementation. Despite challenges such as cost and the need for further prospective studies, advancements in GEP hold promise for supporting more personalized approaches to patient care.

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.