Abstract 6742: Genomic profiling and sites of metastasis in non-small cell lung cancer (NSCLC)
Authors: Chan Kok Hoe , Lin Ji , Sridhar Arthi , Jafri Syed H. 
Published: April 2023

Introduction: Molecular genotyping of metastatic NSCLC adenocarcinoma subtypes using next generation sequencing (NGS) is currently the standard practice. However, there is limited data on the biological predisposition to site of metastasis in patients with NSCLC based on their molecular profiling. We sought to identify any association between metastatic site and molecular profile in NSCLC patients.

Method: This is a retrospective analysis conducted at UTHealth Houston/Memorial Hermann Cancer Center from January 2014 to June 2022. Clinical characteristics, pathology, NGS panel reports, and imaging were retrieved and reviewed. The χ2 test was used for categorical variables. Continuous variables were compared using Kruskal-Wallis one-way analysis of variance. Progression-free survival (PFS) and overall survival (OS) were analyzed using the Kaplan-Meier test.

Results: After excluding patients who did not have complete clinical data, a total of 143 patients were included, and their NGS panels analyzed. Median age was 65 years, with an equal number of men (n=71) and women (n=72). The most common histology was adenocarcinoma (81.8%), followed by squamous cell cancer (11.9%) and large cell carcinoma (3.5%). At least one genetic mutation was discovered in 100 patients. Mutations with a targetable drug were found in 86 patients, and many patients had &gt;1 genetic mutation. The most common mutations were TP53 (25.2%), EGFR (24.5%), KRAS/NRAS (20.3%), and CDKN2A/2B (7.7%). Patients with any mutation were significantly more likely to have metastatic disease to the brain (57% vs 37%, p=0.03), but there was no difference in metastatic disease to bone (34% vs 26%, p=0.32). Patients without a discoverable mutation were significantly more likely to have metastatic disease to other sites (e.g., adrenal gland, liver; 91% vs 66%, p=0.002). There was no difference in PFS or OS between those with versus without mutations. Median PFS was significantly longer in patients with EGFR mutation than those with KRAS/NRAS or TP53 mutations (36 vs 16.2 vs 11.9 months, p=0.03). Median OS for patients with EGFR mutation was not reached and was significantly longer than in patients with TP53 (28.7 months) or KRAS/NRAS (26 months) mutations (p=0.003).Patients with PDL-1 &gt;1% or TP53 were significantly more likely to have metastatic disease to organs other than bone or brain (p=0.047 and p=0.023, respectively). There was also no difference between rates of brain and bone metastasis with regards to mutational profile.

Conclusion: Metastatic lung cancer patients with discoverable mutations on NGS are more likely to have metastatic disease to the brain. PDL-1 expression and TP53 mutation tend to lead to disease metastatic to organs other than brain or bone. Patients with EGFR mutations, despite having a great propensity to brain metastasis, have significantly better PFS and OS than patients with KRAS/NRAS and TP53 mutations, likely due to targeted therapy options.

Citation Format: Kok Hoe Chan, Ji Lin, Arthi Sridhar, Syed H. Jafri. Genomic profiling and sites of metastasis in non-small cell lung cancer (NSCLC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6742.