P48: Increased Frequency of Gene Mutations Significantly Decreases Recurrence Risk In High-Risk Stage II Melanoma Patients.

Friday, March 24, 2023

3:31 PM – 3:36 PM

Location: SSO HUB: Melanoma & Sarcoma Zone

Poster Presenter(s)

Aikaterini Dedeilia, MD (she/her/hers)

Postdoctoral Research Fellow
Massachusetts General Hospital
Boston, Massachusetts, United States

Disclosure information not submitted.

Author(s)

Aikaterini Dedeilia, MD (she/her/hers)

Postdoctoral Research Fellow
Massachusetts General Hospital
Boston, Massachusetts, United States

Disclosure information not submitted.
TL

Thinzar Lwin, MD

Associate Professor of Surgery
City of Hope National Medical Center, Duarte, CA, United States, United States

Disclosure information not submitted.
ST

Sasha Tunsiricharoengul, n/a

Student
Harvard University, United States

Disclosure information not submitted.
Genevieve M. Boland, MD, PhD (she/her/hers)

Vice Chair of Research, Section Head Melanoma/Sarcoma Surgery
Massachusetts General Hospital

Disclosure(s): Ankyra Therapeutics: Advisor (Ongoing), Consultant (Ongoing), Stocks (Ongoing); InterVenn Bioscience: Advisor (Terminated, November 4, 2022), Consultant (Terminated, November 4, 2022), Research Grant (Terminated, November 4, 2022); Iovance Biotherapeutics: Advisor (Ongoing); Merck: Advisor (Ongoing), Consultant (Ongoing); Nektar Therapeutics: Advisor (Terminated, July 1, 2021); Novartis: Advisor (Terminated, November 4, 2022); Olink Proteomics: Research Grant (Ongoing); Palleon Pharmaceuticals: Research Grant (Terminated, November 4, 2022); Teiko Bio: Research Grant (Ongoing)

Disclosure(s):

Genevieve M. Boland, MD, PhD: Ankyra Therapeutics: Advisor (Ongoing), Consultant (Ongoing), Stocks (Ongoing); InterVenn Bioscience: Advisor (Terminated, November 4, 2022), Consultant (Terminated, November 4, 2022), Research Grant (Terminated, November 4, 2022); Iovance Biotherapeutics: Advisor (Ongoing); Merck: Advisor (Ongoing), Consultant (Ongoing); Nektar Therapeutics: Advisor (Terminated, July 1, 2021); Novartis: Advisor (Terminated, November 4, 2022); Olink Proteomics: Research Grant (Ongoing); Palleon Pharmaceuticals: Research Grant (Terminated, November 4, 2022); Teiko Bio: Research Grant (Ongoing)

Introduction: Patients with stage IIB and IIC melanomas have poorer 5-year survival than IIIA patients. Since histology fails to predict outcomes for these patients' other markers are needed to personalize treatment per patient. The goal of this study is to evaluate histopathologic and genomic data in parallel using NGS panel data in high-risk stage II patients to correlate to clinical outcomes.

Methods: We performed a single-center retrospective study based on data from a 14-year (2009-2022) cohort of melanoma patients. Patients with stage IIB and IIC melanoma were included, and their demographic and tumor data were collected. Genomic analysis of formalin-fixed, paraffin-embedded tissue samples was performed via an internal NGS platform (SNaPshot). Categorical variable rates were compared with the Chi-square test, Binary Logistic Regression, and Cox Regression, with the level of significance set at 95% (p=0.05).

Results: A total of 77 patients with a median age of 67 years (IQR: 59-76 years) were included, with a male/female ratio of 1.6/1. Post-surgical disease recurrence was observed in 48% of patients, with 16% of them having a local recurrence, 78% having a distant, and 6% having both. The median time to recurrence was 24 months (IQR: 7-42 months) and the median time of survival was 42 months (IQR: 17-60 months). Adjuvant therapy was administered to 16% of patients. A decrease in recurrence risk was significantly associated with the presence of TERT mutation (p=0.003), BRCA1/2 mutation (p=0.034), and FGFR2/3 mutations (p=0.025). Also, disease-associated death risk significantly decreased with BRAF mutation (p=0.03) and an NF1/2 mutation (p=0.023) but increased with an increase in the mitotic rate (p=0.010) and the presence of PIK3CA mutation (p=0.006).

Conclusions: In our study, traditional histopathologic factors, as well as genetic mutations displayed a significant correlation with disease recurrence and patient survival. This study lays the foundation for the rationale to apply genomic testing in high-risk stage II melanoma patients for prognostic prediction and risk stratification.

Learning Objectives:

Upon completion, participants will be able to define the major genetic mutations associated with the recurrence risk in patients with high-risk stage II melanoma.
Upon Completion, participants will be able to identify which histopathological and genetic variables increase and decrease the overall survival in patients with high-risk stage II melanoma.
Upon Completion, participants will be able to reflect on the importance of genetic testing for risk stratification and adjuvant treatment escalation in patients with high-risk stage II melanoma.