1065 - Use of the 40-Gene Expression Profile (40-GEP) Test to Identify Immune Suppressed Patients with Brigham and Womens Hospital (BWH) T1-T2a Cutaneous Squamous Cell Carcinoma (cSCC) at Higher Risk of Meta

K. Brito¹, B. Martin², J. Siegel³, S. R. Campbell⁴, M. McEnery-Stonelake⁵, J. G. Meine⁶, J. L. Geiger⁷, C. M. Poblete-Lopez⁶, A. Vij⁶, A. Vidimos⁶, and S. A. Koyfman⁸; ¹Department of Radiation Oncology, Cleveland Clinic, Cleveland, OH, ²Castle Biosciences, Inc., Friendswood, TX, ³Castle Biosciences Inc., Friendswood, TX, ⁴Cleveland Clinic, Cleveland, OH, ⁵Department of Dermatology, Cleveland Clinic, Cleveland, OH, ⁶Department of Dermatology, Cleveland Clinic Foundation, Cleveland, OH, ⁷Department of Hematology and Medical Oncology, Taussig Cancer Center, Cleveland Clinic, Cleveland, OH, ⁸Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH

Purpose/Objective(s): Patients with BWH stage T1-T2a cSCC can have favorable outcomes with surgery alone. Immune suppressed (IS) patients, however, have inferior outcomes in some studies, and a subset of them may benefit from treatment intensification. The 40-GEP test is validated to stratify patients with high-risk cSCC as low (Class 1) or high (Class 2, composed of 2A or 2B) risk of nodal or distant metastasis and may help identify IS patients with BWH T1-2a tumors who may benefit from additional therapy, such as adjuvant radiation. Materials/

Methods: Data from an independent validation cohort of 954 cSCC patients with at least one NCCN high-risk factor and 40-GEP test results were analyzed for patients with BWH T1 and T2a tumors with no residual tumor after definitive surgery. Three-year nodal and distant metastasis-free survival (MFS) were estimated and compared using Kaplan-Meier analysis and the log-rank test. Multivariable Analysis (MVA) using Cox regression was used to identify significant predictors of metastasis.
Results: A total of 441 pts with BWH T1 and 336 with BWH T2a tumors were included in this cohort. Median follow-up was 4.36 years (IQR: 3.6, 5.5). Of the 208 patients that were IS, the majority were either transplant recipients (68.8%) or had hematologic malignancies (23.1%). Adjuvant RT was delivered to 1.4% (3/208) of IS patients and 1.8% (10/569) of immune competent (IC) patients. In T1 tumors, IS and IC patients had similar MFS rates (93.1% vs. 93.8%, p>0.99), yet selection based on the 40-GEP stratified these patients into two distinct groups (3-year MFS: Class 1: 96.9% vs. Class 2: 88.6%, p<0.001). IS patients with T2a tumors had significantly worse MFS than IC patients with T2a tumors (71.4% vs. 91.2%, p<0.001). These IS patients also had a higher baseline rate of NCCN very high-risk tumors (58.7% [37/63]) compared to IC patients (40.7% [111/273]). In IS patients with T2a tumors, the 40-GEP further stratified MFS risk into cohorts with more favorable (Class 1: 3-yr MFS 83%) and less favorable survival (Class 2: 3-yr MFS 57%). In patients with T1-T2a tumors, MVA demonstrated that a Class 2 40-GEP result (HR=3.01, p<0.001), IS (HR=2.47, p<0.001), and NCCN very high risk (2.33, p=0.002) were all significant independent predictors of metastasis, while a T2a tumor itself was not an independent predictor (p=0.133).
Conclusion: While many patients with BWH T2a cSCC have favorable outcomes with surgery alone, IS patients in this cohort have inferior outcomes. The 40-GEP further stratifies this cohort into groups with more favorable (Class 1) and less favorable (Class 2) outcomes based on MFS. Additional treatment intensification, such as adjuvant radiation therapy, should be strongly considered in this biomarker-selected, higher-risk patient population.