I. A. Soliman1, M. Renzetti1, H. Wu1, B. Luo1, A. Olszanski1, S. Movva1, M. Lango1, S. Reddy1, F. Zih1, J. Farma1 1Fox Chase Cancer Center,Surgical Oncology,Philadelphia, PA, USA
Introduction: Next generation sequencing (NGS) allows us to learn about the genetic components of cancer with the hope to improve detection, diagnosis, treatment, and outcomes. Our tertiary cancer center uses NGS to evaluate 50 targetable cancer-related genes. The goal of our study was to compare how age at diagnosis affects molecular profiling in patients with melanoma.
Methods: This was a retrospective review of a prospective database analyzing all patients with melanoma who underwent NGS. Clinical and pathologic data were evaluated.
Results: We analyzed specimens from 135 patients with malignant melanoma. Median age at diagnosis was 66(range 24-89), and 64.4% were male(n=87). At diagnosis, 48.1% of patients were below age 65(n=65) and 51.9% were age 65 or above(n=70). In patients <65, 20.0% were stage I(n=13), 55.4% were stage II(n=36), 13.8% were stage III(n=9), and 10.8% were stage IV(n=7). In patients ≥65, 12.9% were stage I(n=9), 61.4% were stage II(n=43), 10.0% were stage III(n=7), and 15.7% were stage IV(n=11). Patients <65 had an average of 1.55 gene mutations compared to ≥65 had an average of 1.64 mutations. In total, 216 mutations were identified, affecting 30 unique genes. In those <65, 4.6% had no mutations(n=3), 53.8% had 1 mutation(n=35), 26.2% had 2 mutations(n=17), and 15.4% had ≥3 mutations(n=10). In patients ≥65, 15.7% had no mutations(n=11), 45.7% had 1 mutation(n=32), 17.1% had 2 mutations(n=12), and 21.4% had ≥3 mutations(n=15). The most common mutations in those <65 were BRAF(n=29, 44.6%), NRAS(n=23, 35.4%), and TP53(n=12, 18.5%) while the most common mutations in those ≥65 were NRAS(n=22, 31.4%), TP53(n=17, 24.3%), and BRAF(n=13, 18.6%). Patients <65 with 1 or less mutations had an improved disease free survival, compared to patients ≥65 with mutations >1 (p=0.0493).
Conclusion: Using NGS in patients with malignant melanoma, we see a difference in the most common mutations in the patient group diagnosed <65 and those ≥65. Further studies will identify and correlate specific patterns of mutation based on age with response to therapy, outcomes, and recurrence.