Comprehensive Genomic Profiling of Solid Tumor Patients with the OncoDEEP Assay for Broad Analysis in Clinical Diagnostics

Abstract

The Journal of Molecular Diagnostics ■ jmdjournal.org immunotherapies targeting programmed death-1 (PD-1)/PD ligand 1 (PD-L1) axis yield promising results. The current data are insufficient to characterize the molecular alterations in PPC. Methods: Our pathology and clinical information systems were searched for PPC that underwent resection between 2011 and 2023. Pathology, demographics, clinical, and tumor molecular profiles were reviewed. Results: Seventy-three cases of PPC were identified across 7 hospitals. Forty-eight (66%) were men (mean age 71.7y), and 25 (34%) were women (mean age 67.7y). Racial distribution was: 43 White, 4 Black/African American, 18 Asian, 7 Other, and 1 American Indian or Alaska native. Fifty-five (75%) had a history of smoking, 9 (12.3%) had never smoked, and 9 were unknowns. Seventy were unifocal, and 3 multifocal (all right lung), 46 (63%) in the right lung (RUL: 32, RML: 5, RLL: 11), and 24 (33%) in the left lung (LUL: 12, LLL: 10, Lingula: 2). Seven cases had chest wall invasion, and 3 had mediastinal invasion. Twenty-three (31%) cases had metastasis (10 brain, 8 bone, and 5 adrenal gland). Epithelial component types were: 38 adenocarcinoma, 16 squamous cell carcinoma, and 4 large cell carcinomas. T staging: T4: 6, T3: 12, T2b: 6, T2a: 26, T1c: 3, T1b: 8, T1a: 6, and Tx: 6. A total of 68.5% of cases were resected at stage ≥T2a. N staging was N2: 8, N1: 15, N0: 42, and Nx: 8. Programmed cell death 1 (PD-L1) was measured in 35 cases, and 29 (83%) were positive (24 with score >50). Molecular alterations (percent alteration/tested): TP53 85%/27, KRAS 75%/24, TERT 57%/7, STK11 57%/7, PIK3CA 20%/10, EGFR 17%/30, BRAF 15%/20, NRAS 12%/8, MAP2K1 11%/9, and MET 6%/18. No alteration was found in AKT1, ALK, ATR, CHEK1, CCND1, DDR2, ERBB2, ERBB3, FGFR1, NTRK, POLD1, POLE, RET, and ROS1. There were 3 alterations in DNMT3A, 3 in NF1, and 1 in HRAS, SMARCA4, and CDKN2A/B. Six-month, 1-year, and 5-year survival in patients with available survival data were 90.2%, 76.8%, and 37.4%, respectively. In patients with survival <1 year, co-mutation of KRAS and TP53 were identified (PD-L1 score >50, 85%). Conclusions: PPC is more prevalent in elderly men with a smoking history. TP53 and KRAS are the most common genetic mutations, followed by TERT, STK11, PIK3CA, EGFR, and BRAF. Higher TNM stage, metastasis, and co-mutation of KRAS and TP53 are associated with worse prognosis, and aggressive treatment should be considered. PPC has a high PD-L1 score rate, which makes immunotherapy a promising treatment. Identification of additional actionable mutations will improve treatment and overall survival of PPC.