A Single-Institute Experience with C-ros Oncogene 1 Translocation in Non-Small Cell Lung Cancers in Taiwan

(1) Background: The C-ros oncogene 1 (<i>ROS1</i>) gene translocation is an important biomarker for selecting patients for crizotinib-targeted therapy. The aim of this study was to understand the incidence, diagnostic algorithm, clinical course and objective response to crizotinib in <...

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Bibliographic Details
Main Authors: Hsiang-Sheng Wang, Chien-Ying Liu, Sheng-Chi Hsu, Shih-Chiang Huang, Tsai-Hsien Hung, Kwai-Fong Ng, Tse-Ching Chen
Format: Article
Language:English
Published: MDPI AG 2022-05-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/23/10/5789
Description
Summary:(1) Background: The C-ros oncogene 1 (<i>ROS1</i>) gene translocation is an important biomarker for selecting patients for crizotinib-targeted therapy. The aim of this study was to understand the incidence, diagnostic algorithm, clinical course and objective response to crizotinib in <i>ROS1</i> translocated lung non-small cell lung cancers (NSCLCs) in Taiwan. (2) Methods: First, we retrospectively studied the <i>ROS1</i> status in 100 NSCLC samples using break-apart fluorescent in situ hybridization (FISH) and immunohistochemical (IHC) staining to establish a diagnostic algorithm. Then, we performed routine ROS1 IHC tests in 479 NSCLCs, as crizotinib was available from 2018 in Taiwan. We analyzed the objective response rate and the survival impact of crizotinib. (3) Results: Four <i>ROS1</i> translocations were clustered in epidermal growth factor receptor (<i>EGFR)</i> wild-type adenocarcinomas but not in cases with <i>EGFR</i> mutations. Strong ROS1 expression was positively correlated with <i>ROS1</i> translocation (<i>p</i> < 0.001). NSCLCs with <i>ROS1</i> translocation had a poor prognosis compared to those without <i>ROS1</i> translocation (<i>p</i> = 0.004) in the pre-crizotinib stage. Twenty NSCLCs were detected with <i>ROS1</i> translocation in 479 wild-type <i>EGFR</i> specimens from 2018. Therefore, the incidence of <i>ROS1</i> translocation is approximately 4.18% in <i>EGFR</i> wild-type NSCLCs. In these 20 <i>ROS1</i> translocation cases, 19 patients received crizotinib treatment, with an objective response rate (ORR) of 78.95% (confidence interval = 69.34% to 88.56%), including 1 complete response, 14 partial responses, 3 stable cases and 1 progressive case. Overall survival and progression-free survival were better in the 19 ROS1-translocated NSCLCs of the prospective group with crizotinib treatment than the four ROS1-translocated NSCLCs of the retrospective group without crizotinib treatment. (4) Conclusions: <i>ROS1</i>-translocated NSCLCs had a poor prognosis and could have a beneficial outcome with crizotinib.
ISSN:1661-6596
1422-0067