Concurrent classic driver oncogenes mutation with ROS1 rearrangement predicts superior clinical outcome in NSCLC patients

Abstract

Background: There is high mortality rate and poor prognosis in lung cancer, especially non-small-cell lung cancer (NSCLC). Recent study showed that concurrent classic driver oncogene mutation with ROS1 rearrangement was found in NSCLC patients. However, whether this would affect the development and prognosis of NSCLC is still unclear.

Objective: To explore the clinical characteristics and prognosis of NSCLC patients harboring concurrent classic driver oncogene mutation with ROS1 rearrangement.

Methods: A retrospective study was conducted on 220 patients diagnosed with NSCLC. All samples were screened for EGFR and KRAS using amplification-refractory mutation system assay, and for ALK, ROS1 using RT-PCR. The clinical characteristics and clinical outcomes of concurrent gene alterations with ROS1 rearrangement were analyzed.

Results: In 220 patients, 12 (5.45%) were ROS1 rearrangement, who tend to be younger, non-smokers. The mutation rates of EGFR, KRAS, ALK and ROS1 in NSCLC were 28.64%, 1.82%, 3.64% and 5.45%, respectively. ROS1 rearrangement was identified to co-occur in 5 (2.27%) NSCLC patients. ROS1/EGFR co-alterations were found in 3.17% of NSCLC patients, 16.67% of ROS1-positive NSCLC patients. Concomitant ROS1/ALK rearrangement constituted 37.50% in ALK-positive patients, and 25.00% in ROS1-positive patients. SDC4-ROS1 was the most common fusion partner in concurrent ROS1 rearrangement patients. The median overall survival of NSCLC with concurrent ROS1 rearrangement group and single ROS1 rearrangement group were 25 months and 14 months.

Conclusion: Concurrent driver oncogenes mutation with ROS1 rearrangement defines a unique subgroup of NSCLC. Patients with concomitant ROS1 rearrangement might have a better prognosis.

Keywords: ALK; Concurrent mutation; EGFR; NSCLC; ROS1.