Clinical and the Prognostic Characteristics of Lung Adenocarcinoma Patients with ROS1 Fusion in Comparison with Other Driver Mutations in East Asian Populations

Abstract

The ROS1 fusion gene can be successfully detected in East Asian patients with lung adenocarcinoma using multiplex reverse transcription-polymerase chain reaction. These patients tend to be younger and have characteristic histologic subtypes. Due to the small number of ROS1 fusion patients, the prognostic value of ROS1 fusion need further studies to confirm.

Factors associated with the prognosis and long-term survival of patients with metastatic lung adenocarcinoma: a retrospective analysis

“…KRAS mutation is the major genetic alteration in lung adenocarcinoma of Western countries (37). In contrast, KRAS mutation appears to negatively affect overall survival (38,39). However, our study is also limited to identify the potential long-term survival impact of ALK, ROS1, KRAS and other oncogenic mutations.…”

Analytical Validation of BRAF Mutation Testing from Circulating Free DNA Using the Amplification Refractory Mutation Testing System

“…The strength of evidence supporting the use of any clinical characteristic to identify patients who should receive ROS1 testing was adequate. This recommendation is evidence based and supported by 9 studies, 30e38 6 of which informed on the association between ROS1 rearrangement and patient or tumor characteristics 30,31,34e37 and consisted of 1 prospective cohort study (PCS), 35 1 prospective-retrospective cohort study (PRCS), 31 and 4 retrospective cohort studies (RCSs). 30,34,36,37 The 3 remaining studies assessed clinical outcomes of patients treated with the ROS1-targeted therapy crizotinib 32,33,38 and included 1 nonrandomized clinical trial 33 and 3 RCSs.…”

“…Although relatively rare, accounting for <2% of nonesmall cell lung carcinomas 30,31,34 and 2% to 3% of lung adenocarcinomas, 30,34,35 structural rearrangements involving the ROS1 gene generate an oncogenic fusion that can be treated successfully with targeted inhibitors. A single phase I clinical trial of 50 NSCLC patients demonstrated that the presence of a ROS1 rearrangement by FISH or RT-PCR predicts response to targeted inhibition using crizotinib, with a response rate of 72% and median progression-free survival of 19.2 months.…”

“…34 Other clinical characteristics, such as younger age, female sex, and non-Asian ethnicity, have been associated with ROS1 rearrangement in isolated studies only. 30,31,35 Therefore, clinical characteristics should not be used to either select or exclude patients from testing for ROS1 rearrangements. ROS1 rearrangements occur in a mutually exclusive fashion with other oncogenic driver alterations (such as EGFR and KRAS mutation and ALK rearrangement).…”

“…30,35,181,215,216 Although other studies have indicated that these findings may reflect testing bias, 217 the documentation of an association between younger patient age and an actionable biomarker is another consideration in selecting patients for testing. The boundary between young and not young is not well defined, however, and a clear evidence-based cutoff for this guideline cannot be established.…”