title: From genotype to phenotype: Are there imaging characteristics associated with lung adenocarcinomas harboring RET and ROS1 rearrangements?
abstract: BACKGROUND
  Recurrent gene rearrangements are important drivers of oncogenesis in non-small cell lung cancers. RET and ROS1 rearrangements are each found in 1-2% of lung adenocarcinomas and represent distinct molecular subsets. This study assessed the computed tomography (CT) imaging features of patients with RET- and ROS1-rearranged lung cancers.
  
  
  METHODS
  Eligible patients included pathologically-confirmed lung adenocarcinomas of any stage with a RET or ROS1 rearrangement via fluorescence in-situ hybridization or next-generation sequencing, and available pre-treatment baseline imaging for review. A cohort of EGFR-mutant lung cancers was identified as a control group. CT features assessed included location, consistency, contour, presence of cavitation, and calcification of the primary tumor. Presence of an effusion, lung metastases, adenopathy and extrathoracic disease were recorded. The Wilcoxon rank-sum/Kruskal-Wallis and Fisher's exact tests were used to compare features between groups.
  
  
  RESULTS
  73 patients with lung adenocarcinomas were identified: 17 (23%) with ROS1 fusions, 25 (34%) with RET fusions and 31 (43%) with EGFR mutations. ROS1-rearranged lung cancers were more likely to present as peripheral tumors in comparison to EGFR-mutant lung cancers (32% vs. 65%, p=0.04). RET-rearranged lung cancers did not significantly differ from EGFR-mutant lung cancers radiographically. The consistency of the primary lesion for RET and ROS fusions and EGFR mutations were most frequently solid and spiculated.
  
  
  CONCLUSIONS
  Lung adenocarcinomas with RET and ROS1 fusions share many radiographic features and those with ROS1 fusions are more likely to present as peripheral lesions in comparison to EGFR-mutant lung cancers.
authors.affiliation: Department of Radiology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA. Electronic address: plodkowa@mskcc.org.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Plodkowski
authors.affiliation: Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial, Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA. Electronic address: DrilonA@mskcc.org.
authors.forename: Alexander
authors.initials: A
authors.lastname: Drilon
authors.affiliation: Department of Radiology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA. Electronic address: halpennd@mskcc.org.
authors.forename: Darragh F
authors.initials: DF
authors.lastname: Halpenny
authors.affiliation: Department of Radiology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA. Electronic address: dearbhailodriscoll@gmail.com.
authors.forename: Dearbhail
authors.initials: D
authors.lastname: O'Driscoll
authors.affiliation: Department of Radiology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA. Electronic address: djblair73@yahoo.com.
authors.forename: Donald
authors.initials: D
authors.lastname: Blair
authors.affiliation: Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial, Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA. Electronic address: alitvak@gmail.com.
authors.forename: Anya M
authors.initials: AM
authors.lastname: Litvak
authors.affiliation: Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA. Electronic address: ZhengJ@mskcc.org.
authors.forename: Junting
authors.initials: J
authors.lastname: Zheng
authors.affiliation: Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA. Electronic address: moskowc1@mskcc.org.
authors.forename: Chaya S
authors.initials: CS
authors.lastname: Moskowitz
authors.affiliation: Department of Radiology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA. Electronic address: ginsberm@mskcc.org.
authors.forename: Michelle S
authors.initials: MS
authors.lastname: Ginsberg
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics*; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D015321:Gene Rearrangement / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D010641:Phenotype; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics*
chemical_list: D015514:Oncogene Proteins, Fusion; D011518:Proto-Oncogene Proteins; C512478:EGFR protein, human; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human; C062333:ROS1 protein, human
keywords: Computed tomography; EGFR mutation; Lung adenocarcinoma; RET rearrangement; ROS1 rearrangement