EGFR missense mutations to predict skeletal metastasis in lung cancer patients.

Abstract

e14541 Background: EGFR is a commonly mutated gene in several cancer types, particularly lung cancer. The specific mutation can cause susceptibility or resistance to treatments such as tyrosine kinase inhibitors (TKIs), which is first-line treatment for non-small cell lung cancer (NSCLC) patients with sensitive EGFR mutations. Patients develop resistance post-treatment and some may thus continue TKI treatment. Skeletal metastasis (SM) significantly impacts the quality of life for patients, increasing risk of skeletal-related events (SREs) such as fracture and spinal cord compression. Bone metastases occur in a significant proportion of patientswith advanced NSCLC. EGFR-mutated NSCLC patients have a long post-metastasis bone disease survival, increasing the risk of developing SREs. We investigated, EGFR mutational types and their association with skeletal metastasis to determine its molecular significance as an early indicator. Methods: We retrospectively analyzed 112 lung cancer patients with diverse mutational and metastatic profiles. These patients were further categorized into different types of EGFR alterations with their corresponding metastatic regions at any time in their disease history. The association between EGFR mutational types with their mutational regions was analyzed. Patient metastatic history was obtained from PET scans and HPE reports were collated for NGS testing. NGS test was performed using OncoIndx CGP Assay. Results: Retrospectively we analyzed 112 patients, 6 patients had dual EGFR mutations. 14.3% (n = 16/112) of patients had EGFR deletion/insertion mutations and another 14.3% (n = 16/112) of patients were detected with EGFR missense mutations. A negligible 1.8% (n = 2/112) of patients were detected with EGFR amplification while 75% (n = 84/112) of cohort were identified with no EGFR mutations. 50% (n = 8/16), 75% (12/16) and 35.7% (n = 30/84) were detected with metastasis in cohorts with EGFR deletion/insertion mutations, missense mutations and no EGFR mutational cohorts respectively. Interestingly, 66.7% (n = 8/12) of patients in the EGFR missense mutational cohort showed SM while only 37.5% (n = 3/8) of patients in the EGFR deletion/insertion mutational cohort showed SM. Conversely, 43.3% (n = 13/84) of patients in the cohort without EGFR mutations showed skeletal mutations. Highest cooccurrence of SM was observed in cohort with EGFR missense mutations. The cohort with EGFR deletion/insertion mutations and no EGFR mutations almost had a similar % of skeletal metastasis 37.5% and 43.3% respectively. Conclusions: We conclude that patients with EGFR missense mutations could be more vulnerable to skeletal metastasis and could be early indicators of treating it. With painful consequences, compromised quality of life, and high mortality rates faced by patients with skeletal metastasis, this study could be a new avenue to look for molecular identifiers for specific metastatic regions.