ROS1 Gene Fusion in Advanced Lung Cancer in Women: A Systematic Analysis, Review of the Literature, and Diagnostic Algorithm

Antonio Marchetti; Massimo Barberis; Alessia Di Lorito; Maria Vittoria Pace; Chiara Di Lisio; Lara Felicioni; Elena Guerini-Rocco; Andrea Vingiani; Tommaso D'Antuono; Marcella Liberatore; Giampaolo Filice; Graziano De Luca; Filippo De Marinis; Antonio Passaro; Luigi Guetti; Luciana Irtelli; Lucio Crinò; Felice Mucilli; Fiamma Buttitta

doi:10.1200/PO.16.00010

ROS1 Gene Fusion in Advanced Lung Cancer in Women: A Systematic Analysis, Review of the Literature, and Diagnostic Algorithm

JCO Precis Oncol. 2017 Nov:1:1-9. doi: 10.1200/PO.16.00010.

Authors

Antonio Marchetti¹, Massimo Barberis¹, Alessia Di Lorito¹, Maria Vittoria Pace¹, Chiara Di Lisio¹, Lara Felicioni¹, Elena Guerini-Rocco¹, Andrea Vingiani¹, Tommaso D'Antuono¹, Marcella Liberatore¹, Giampaolo Filice¹, Graziano De Luca¹, Filippo De Marinis¹, Antonio Passaro¹, Luigi Guetti¹, Luciana Irtelli¹, Lucio Crinò¹, Felice Mucilli¹, Fiamma Buttitta¹

Affiliation

¹ Antonio Marchetti, Alessia Di Lorito, Maria Vittoria Pace, Chiara Di Lisio, Lara Felicioni, Tommaso D'Antuono, Marcella Liberatore, Giampaolo Filice, Graziano De Luca, Luigi Guetti, Luciana Irtelli, Felice Mucilli, and Fiamma Buttitta, University of Chieti-Pescara, Chieti; Massimo Barberis, Elena Guerini-Rocco, Andrea Vingiani, Filippo De Marinis, and Antonio Passaro, European Institute of Oncology, Milan; and Lucio Crinò, Istituto Oncologico Romagnolo IRCCS Meldola Forli, Meldola, Italy.

PMID: 35172481
DOI: 10.1200/PO.16.00010

Abstract

Purpose: Crizotinib, a mesenchymal-epithelial transition/anaplastic lymphoma kinase/c-ros oncogene 1 (ROS1) inhibitor, has recently been approved by the US Food and Drug Administration for the treatment of patients with advanced ROS1-positive non-small-cell lung cancer (NSCLC). Therefore, interest in ROS1 testing is growing. ROS1 gene fusions affect approximately 0.5% to 2% of unselected NSCLCs. Limited data are available on the prevalence and distribution of ROS1 fusions in patients with advanced-stage NSCLC.

Material and methods: A series of 727 lung adenocarcinomas from patients with stage IV disease, negative for epidermal growth factor receptor and anaplastic lymphoma kinase alterations, were tested for ROS1 fusions by fluorescent in situ hybridization analysis, with confirmation by immunohistochemistry. Results were correlated with clinicopathologic parameters and compared with data from the literature.

Results: ROS1 fusions were detected in 29 patients (4%), including 27 of 266 females (10.2%) and two of 461 males (0.4%; P = 1.2^E-10). The mean age of patients with ROS1-positive disease was lower than that of patients with ROS1-negative disease (49.21 v 62.96 years, respectively; P = 1.1^E-10). Eleven of 583 smokers (1.9%) and 18 of 144 nonsmokers (12.5%) showed ROS1 rearrangement (P = 4.05^E-7). By logistic regression analysis, ROS1 fusions were independently associated with female sex, younger age at diagnosis, and absence of smoking history, (odds ratios, 12.4, 7.9, and 3.6, respectively). These data, integrated with those reported in the literature, indicate that the prevalence of ROS1 fusions in females and in nonsmokers was higher in patients with advanced disease than in patients with operable disease (11.2% v 3.1%, P < .001; 11.6% v 2.8%, P < .001, respectively). The mean age at diagnosis was significantly lower in patients with advanced disease (49.8 years) than in patients with operable disease (55.6 years; P < .001).

Conclusion: Our data indicate that ROS1 fusions in patients with advanced-stage lung adenocarcinoma are more frequent in females, particularly if young and nonsmokers. A diagnostic algorithm for an accurate screening of ROS1 alterations was elaborated.