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ROS1 rearrangements in lung adenocarcinoma: prognostic impact, therapeutic options and genetic variability.

ABSTRACT: BACKGROUND:While recent data show that crizotinib is highly effective in patients with ROS1 rearrangement, few data is available about the prognostic impact, the predictive value for different treatments, and the genetic heterogeneity of ROS1-positive patients. PATIENTS AND METHODS:1137 patients with adenocarcinoma of the lung were analyzed regarding their ROS1 status. In positive cases, next-generation sequencing (NGS) was performed. Clinical characteristics, treatments and outcome of these patients were assessed. Overall survival (OS) was compared with genetically defined subgroups of ROS1-negative patients. RESULTS:19 patients of 1035 evaluable (1.8%) had ROS1-rearrangement. The median OS has not been reached. Stage IV patients with ROS1-rearrangement had the best OS of all subgroups (36.7 months, p < 0.001). 9 of 14 (64.2%) patients had at least one response to chemotherapy. Estimated mean OS for patients receiving chemotherapy and crizotinib was 5.3 years. Ten patients with ROS1-rearrangement (52.6%) harbored additional aberrations. CONCLUSION:ROS1-rearangement is not only a predictive marker for response to crizotinib, but also seems to be the one of the best prognostic molecular markers in NSCLC reported so far. In stage IV patients, response to chemotherapy was remarkable high and overall survival was significantly better compared to other subgroups including EGFR-mutated and ALK-fusion-positive NSCLC.

SUBMITTER: Scheffler M

PROVIDER: S-EPMC4496376 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature

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ROS1 rearrangements in lung adenocarcinoma: prognostic impact, therapeutic options and genetic variability.

Scheffler Matthias M Schultheis Anne A Teixido Cristina C Michels Sebastian S Morales-Espinosa Daniela D Viteri Santiago S Hartmann Wolfgang W Merkelbach-Bruse Sabine S Fischer Rieke R Schildhaus Hans-Ulrich HU Fassunke Jana J Sebastian Martin M Serke Monika M Kaminsky Britta B Randerath Winfried W Gerigk Ulrich U Ko Yon-Dschun YD Krüger Stefan S Schnell Roland R Rothe Achim A Kropf-Sanchen Cornelia C Heukamp Lukas L Rosell Rafael R Büttner Reinhard R Wolf Jürgen J

Oncotarget 20150401 12

<h4>Background</h4>While recent data show that crizotinib is highly effective in patients with ROS1 rearrangement, few data is available about the prognostic impact, the predictive value for different treatments, and the genetic heterogeneity of ROS1-positive patients.<h4>Patients and methods</h4>1137 patients with adenocarcinoma of the lung were analyzed regarding their ROS1 status. In positive cases, next-generation sequencing (NGS) was performed. Clinical characteristics, treatments and outco ...[more]

PMID: 25868855

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Project description:BackgroundBased on computed tomography (CT) findings of lung cancer, solid nodules have a much worse prognosis than subsolid nodules, even if the nodules are subcentimeter in size. There is, however, no systematic method for determining the prognosis of solid tumors on CT. This study aimed to discover the prognostic factor of early-stage solid lung adenocarcinoma using three-dimensional CT volumetry.MethodsPatients with pathological stage I solid lung adenocarcinoma who underwent complete resection between 2007 and 2012 were selected in this retrospective study. Clinicopathological data and preoperative multidetector CT findings, such as tumor size on the two-dimensional axial image, three-dimensional tumor volume between -600 and 199 HU, and three-dimensional solid volume between 0 and 199 HU, which corresponded to highly solid components, were compared between recurrence and non-recurrence. Furthermore, these radiological values were compared to pathological invasive volume (PIV).ResultsDuring this time, 709 patients had their lung cancer completely removed. From this cohort, 90 patients with pathological stage I solid lung adenocarcinoma were selected. In addition, recurrence was found in 26 patients (28.9%). Although two-dimensional axial image, serum carcinoembryonic antigen (CEA) level, and SUVmax on 18F fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) did not differ statistically between recurrent and non-recurrent patients, three-dimensional tumor and solid tumor volume did. Multivariate analysis indicated that three-dimensional solid tumor volume [hazard ratio: 2.440; 95% confidence interval (CI): 1.110-5.361, P=0.026] and epidermal growth factor receptor (EGFR) mutation (hazard ratio: 4.307; 95% CI: 1.328-13.977, P=0.015) were significantly associated with disease-free survival (DFS). When three-dimensional tumor and solid tumor volume were compared to PIV, three-dimensional solid tumor volume (3,091 mm3 on average) showed a highly similar value with PIV (2,930 mm3 on average), whereas three-dimensional tumor volume (6,175 mm3 on average) was significantly larger than PIV (P<0.001).ConclusionsIn patients with early-stage solid lung adenocarcinoma, the measurement of three-dimensional solid tumor volume, which is correlated with PIV, accurately predicted the postoperative outcome.

Dataset Information

ROS1 rearrangements in lung adenocarcinoma: prognostic impact, therapeutic options and genetic variability.

Publications

ROS1 rearrangements in lung adenocarcinoma: prognostic impact, therapeutic options and genetic variability.

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