Abstract 1684P
Background
Around 60% of lung cancers (LC) are radically treated with surgery or chemoradiation (CRT). 33-70% of patients develop recurrence (R) with a median time to relapse 11-16.8 months and approximately 80% of R [locally (LR) or distantly (DR)] occur within the first 2 years. Patients with LR usually do better. Previous studies have focused mainly on the role of clinico-pathological characteristics for the risk of R. The role of molecular mechanisms remains unclear. We aimed to analyze genomic features in LC patients with LR versus (vs) DR to predict the type and risk of R.
Methods
From the North Estonia Medical Centre (NEMC) Thoracic Oncology Database we retrospectively enrolled patients diagnosed LC recurrence from 2015 to 2017, who were previously treated with curative intent. All histological specimens (formalin-fixed paraffin-embedded tumor resection or biopsy samples) were sent for whole exome sequencing (WES). Genomic data was analyzed for small genetic alterations, namely single nucleotide polymorphisms (SNPs) and insertion-deletion mutations (INDELs).
Results
191 patients were included. 33% of patients had LR and 67% DR, with median recurrence-free survival 15.4 vs 11.2 months (m) (p=0.20) and overall survival after R 12.9 vs 8.5 m (p=0.007), respectively. We identified significant INDEL mutations in 38 and 98 genes and SNP mutations in 63 and 179 genes in DR and LR groups, respectively. DMXL2 mutations were specific only for samples in the DR group. Also, in DR group mutated genes, like STIM1, ITPR3 and RYR3, were significantly enriched in cytosolic Ca2+ related GO terms and pathways, whereas in LR group enrichment of terms related endoplasmic/sarcoplasmic reticulum Ca2+ was observed. Furthermore, ABCC9 gene mutations caused by INDELs were only prominent in the DR group. Association between those gene alterations and R in LC has not been published previously.
Conclusions
The addition of genomic markers to clinico-pathological characteristics may predict the type of R and prognosis for patients with LC. Our study highlights genetic alterations that warrant further analysis to improve patients’ management.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Kersti Oselin, MD, PhD.
Funding
North Estonia Medical Centre.
Disclosure
K. Oselin: Financial Interests, Institutional, Research Grant: Roche, Pfizer, Takeda. All other authors have declared no conflicts of interest.