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Introduction: National Comprehensive Cancer Network (NCCN) recommendations for adjuvant radiation therapy (ART) use are similar for High Risk and Very High Risk cutaneous squamous cell carcinoma (cSCC) with negative post-surgical margins. Although studies report reductions in disease progression following ART treatment, ART use is likely inconsistent when guided by available risk factors. This study evaluated the association of ART with clinical risk factors in ART-treated and untreated patients and showed the clinical utility of the 40-gene expression profile (40-GEP) for guiding ART. Methods: A multicenter study of 954 patients was conducted with institutional review board (IRB) approval. The 40-GEP test was performed using primary tumor tissue from patients with either a minimum of 3 years of follow-up or a documented regional or distant metastasis. Unsupervised hierarchical cluster analysis identified patterns of clinical risk factors for ART-treated patients, then identified untreated patients with matching risk factor profiles. Results were cross-referenced to 40-GEP test results to determine utility of the test to guide ART. Results: Analysis demonstrated inconsistent implementation of ART for eligible patients. Cluster analysis identified four patient profiles based on clusters of risk factors and, notably, matching profiles in ART-treated and untreated patients. Further, the analysis identified patients who received but could have deferred ART on the basis of 40-GEP test result and biologically low risk of metastasis, and untreated patients who likely would have benefitted from ART on the basis of their 40-GEP test result. Conclusions: ART guidance is not determined by the presence of specific clinicopathologic factors, with treated and untreated patients sharing the same risk factor profiles. cSCC risk determination based on NCCN recommendations for clinical factor assessment results in inconsistent use of ART. Including tumor biology-based prognostic information from the 40-GEP refines risk and identifies patients who are most appropriate and likely to benefit from ART, and those that can consider deferring ART. [ABSTRACT FROM AUTHOR]

Introduction: The validated 40-gene expression profile (40-GEP) test independently stratifies risk of regional or distant metastasis for cutaneous squamous cell carcinoma (cSCC) tumors with high-risk clinicopathologic features. This study evaluated the stratification of risk by the 40-GEP test in a large cohort of tumors with one or more high-risk factors and in clinically relevant subgroups, including tumors within National Comprehensive Cancer Network (NCCN) high- and very-high-risk groups, lower-stage BWH T1 and T2a tumors, and patients > 65 years old. Methods: This multicenter (n = 58) performance study of the 40-GEP included 897 patients. Kaplan-Meier analyses were performed to assess risk stratification profiles for 40-GEP Class 1 (low), Class 2A (higher) and Class 2B (highest) risk groups, while nested Cox regression models were used to compare risk prediction of clinicopathologic risk classification systems versus risk classification systems in combination with 40-GEP. Results: Patients classified as 40-GEP Class 1, Class 2A, or Class 2B had significantly different metastatic risk profiles (p < 0.0001). Integrating 40-GEP results into models with individual clinicopathologic risk factors or risk classification systems (Brigham and Women's Hospital, American Joint Committee on Cancer Staging Manual, 8th Edition) and NCCN demonstrated significant improvement in accuracy for prediction of metastatic events (ANOVA for model deviance, p < 0.0001 for all models). Conclusion: The 40-GEP test demonstrates accurate, independent, clinically actionable stratification of metastatic risk and improves predictive accuracy when integrated into risk classification systems. The improved accuracy of risk assessment when including tumor biology via the 40-GEP test ensures more risk-aligned, personalized patient management decisions. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Adjuvant radiation therapy (ART) is often recommended for high-risk cSCC patients but carries significant costs and risks. This study aims to determine if utilizing the 40-GEP test to guide ART can reduce healthcare costs in cSCC management. METHODS: Medical claims data with new diagnoses of cSCC for the 12 months ending June 2022 in the Medicare (≥65 years) population (source: IQVIA claims database) were obtained and normalized to the general population for missingness. CPT codes associated with radiation therapy within one-year post diagnosis were used to establish adjuvant RT use (defined as 'ART'). Average weighted direct costs for four major ART modalities were calculated from published studies and (IQVIA). Sensitivity analysis was used to assess the financial impact of ART treatment using varying distributions of 40-GEP Class results. RESULTS: Normalized medical claims data identified 22,917 Medicare-eligible cSCC patients who received ART within the United States. The weighted average direct cost for ART, which includes the four most used CPT code-defined modalities (IGRT, IMRT, IMPT, and XRT), was $60,693 per patient, amounting to an annual projected ART cost of $1.4 billion. Using the distribution of 40-GEP results from published studies, utilization of a 40-GEP test result to avoid ART in these patients could save up to $972 million in Medicare-eligible population. Sensitivity analysis shows, depending upon the distribution of the 40-GEP results, that for every 10% of Class 2A test results omitting ART, an extra $38-66 million in annual savings is expected. LIMITATIONS: Potential limitations include a need for more comprehensive patient information and the cost of ART-related complications. CONCLUSION: Utilizing the 40-GEP test results to guide ART decision-making would result in material savings to Medicare. [ABSTRACT FROM AUTHOR]

Aim: To clinically validate the 40-gene expression profile (40-GEP) test for cutaneous squamous cell carcinoma patients and evaluate coupling the test with individual clinicopathologic risk factor-based assessment methods. Patients & methods: In a 33-site study, primary tumors with known patient outcomes were assessed under clinical testing conditions (n = 420). The 40-GEP results were integrated with clinicopathologic risk factors. Kaplan-Meier and Cox regression analyses were performed for metastasis. Results: The 40-GEP test demonstrated significant prognostic value. Risk classification was improved via integration of 40-GEP results with clinicopathologic risk factor-based assessment, with metastasis rates near the general cutaneous squamous cell carcinoma population for class 1 and ≥50% for class 2B. Conclusion: Combining molecular profiling with clinicopathologic risk factor assessment enhances stratification of cutaneous squamous cell carcinoma patients and may inform decision-making for risk-appropriate management strategies. [ABSTRACT FROM AUTHOR]

Objective: Over 50% of newly diagnosed cutaneous squamous cell carcinoma (cSCC) lesions occur in the head and neck (cSCC‐HN), and metastasis to nodal basins in this region further complicates surgical and adjuvant treatment. The current study addressed whether the 40‐gene expression profile (40‐GEP) test can predict metastatic risk in cSCC‐HN with improved accuracy and provide independent prognostic value to complement current risk assessment methods. Study Design: Multicenter, retrospective cohort study. Methods: Formalin‐fixed paraffin‐embedded primary tumor tissue and associated clinical data from patients with cSCC‐HN (n = 278) were collected from 33 independent centers. Samples were analyzed via the 40‐GEP test. Cases were staged per American Joint Committee on Cancer, Eighth Edition (AJCC8) and Brigham and Women's Hospital (BWH) criteria after comprehensive medical record and pathology report review. Metastasis‐free survival (MFS) rates were determined, and risk factors were analyzed via Cox regression. Results: The 40‐GEP test classified the cohort into low (Class 1, n = 126; 45.3%), moderate (Class 2A, n = 134; 48.2%), and high (Class 2B, n = 18; 6.5%) metastatic risk at 3 years postdiagnosis. Regional/distant metastasis occurred in 54 patients (19.4%). MFS rates were 92.1% (Class 1), 76.1% (Class 2A), and 44.4% (Class 2B; p <.0001). Multivariate analysis of 40‐GEP results with AJCC8 or BWH tumor stage, or clinicopathologic risk factors, demonstrated independent prognostic value of the 40‐GEP test (p <.03). Accuracy of predicting metastatic risk was also improved using 40‐GEP classification (p <.02). Conclusions: Improved metastatic risk stratification through the 40‐GEP test could complement cSCC‐HN risk assessment for better‐informed decision‐making for treatment and surveillance and ultimately improve patient outcomes. Level of Evidence: 3 [ABSTRACT FROM AUTHOR]

Introduction: While improvements have been made to risk assessment of cutaneous squamous cell carcinoma (cSCC) patients, there is a critical need for a uniform and more precise stratification system of their care. To address this unmet clinical need, a prognostic 40-gene expression profile (40-GEP) test has recently been developed and independently validated to show improved stratification of metastatic risk in high-risk cSCC patients compared with current staging systems. Methods: Two cSCC cases, both male with similar patient profiles and the same staging status across two different staging systems, yet with opposing outcomes, were chosen for retrospective review of their primary biopsy using the 40-GEP test. Results: Case 1 declined further treatment, even when presented with evidence of a small focus of cSCC found in the last layer of nonmarginal tissue obtained from Mohs micrographic surgery (MMS). Case 1 remained recurrence free, and retrospective analysis of the initial biopsy with the 40-GEP test provided a Class 1 result (low likelihood of metastasis). Case 2, even with subsequent clearing of the primary cSCC with MMS, noted another metastatic cSCC 3 months later. Case 2, after multimodal adjuvant treatments, died due to disease progression. Retrospective analysis of the initial biopsy with the 40-GEP test provided a Class 2B result (high likelihood of metastasis). Conclusions: The cases discussed highlight the utility in 40-GEP to provide additional information to guide treatment decisions and improve outcomes. Integrating novel molecular prognostication with traditional clinicopathological risk factors can improve stratification of high-risk cSCC patients and may inform selection of risk-appropriate treatment and surveillance strategies. [ABSTRACT FROM AUTHOR]

The article describes the case of a 46-year-old woman who was referred for Mohs micrographic surgery by dermatology for treatment of a well-differentiated squamous cell carcinoma (SCC) on the left dorsal hand and the use of small intestinal submucosa extracellular matrix (SIS-ECM) for a Mohs surgical defect on her lateral foot.

Background Squamous cell carcinoma ( SCC), which has one of the highest incidences of all cancers in the United States, is an age-dependent disease, with the majority of these cancers diagnosed in people age 70 and older. Recent findings have led to a new hypothesis on the pathogenesis of SCC. Objectives To evaluate the potential of preventive therapies to reduce the incidence of SCC in at-risk geriatric patients. Materials and Methods Survey of current literature on wounding therapies to prevent SCCs. Results This new hypothesis of SCC photocarcinogenesis states that senescent fibroblasts accumulate in the dermis, resulting in a reduction in dermal insulin-like growth factor-1 ( IGF-1) expression. This lack of IGF-1 expression sensitizes epidermal keratinocytes to fail to suppress ultraviolet light B ( UVB)-induced mutations, leading to increased proclivity to photocarcinogenesis. Recent evidence suggests that dermal wounding therapies, specifically dermabrasion and fractionated laser resurfacing, can decrease the proportion of senescent dermal fibroblasts, increase dermal IGF-1 expression, and correct the inappropriate UVB response found in geriatric skin, protecting geriatric keratinocytes from UVB-induced SCC initiation. Conclusions In this review, we will discuss the translation of pioneering basic science results implicating commonly used dermal fibroblast rejuvenation procedures as preventative treatments for SCC. [ABSTRACT FROM AUTHOR]

The article presents the case studies of four patients who developed scar contractures on free margins after Mohs micrographic surgery (MMS) for basal cell carcinoma (BCC) or squamous cell carcinoma. The authors found that microsecond-pulsed 1,064-nanometer neodymium-doped yttrium aluminum garnet (Nd:YAG) laser is an effective and safe treatment option for surgical scar contractures. Details on the methods of the case studies are also given.