title: Noninvasive image texture analysis differentiates K-ras mutation from pan-wildtype NSCLC and is prognostic.
abstract: BACKGROUND
  Non-invasive characterization of a tumor's molecular features could enhance treatment management. Quantitative computed tomography (CT) based texture analysis (QTA) has been used to derive tumor heterogeneity information, and the appearance of the tumors has been shown to relate to patient outcome in non-small cell lung cancer (NSCLC) and other cancers. In this study, we examined the potential of tumoral QTA to differentiate K-ras mutant from pan-wildtype tumors and its prognostic potential using baseline pre-treatment non-contrast CT imaging in NSCLC.
  
  
  METHODS
  Tumor DNA from patients with early-stage NSCLC was analyzed on the LungCarta Panel. Cases with a K-ras mutation or pan-wildtype for 26 oncogenes and tumor suppressor genes were selected for QTA. QTA was applied to regions of interest in the primary tumor. Non-parametric Mann Whitney test assessed the ability of the QTA, clinical and patient characteristics to differentiate between K-ras mutation from pan-wildtype. A recursive decision tree was developed to determine whether the differentiation of K-ras mutant from pan-wildtype tumors could be improved by sequential application of QTA parameters. Kaplan-Meier survival analysis assessed the ability of these markers to predict survival.
  
  
  RESULTS
  QTA was applied to 48 cases identified, 27 had a K-ras mutation and 21 cases were pan-wildtype. Positive skewness and lower kurtosis were significantly associated with the presence of a K-ras mutation. A five node decision tree had sensitivity, specificity, and accuracy values (95% CI) of 96.3% (78.1-100), 81.0% (50.5-97.4), and 89.6% (72.9-97.0); respectively. Kurtosis was a significant predictor of OS and DFS, with a lower kurtosis value linked with poorer survival.
  
  
  CONCLUSIONS
  Lower kurtosis and positive skewness are significantly associated with K-ras mutations. A QTA feature such as kurtosis is prognostic for OS and DFS. Non-invasive QTA can differentiate the presence of K-ras mutation from pan-wildtype NSCLC and is associated with patient survival.
authors.affiliation: Cancer Treatment Centers of America, Goodyear, Arizona, United States of America; The Translational Genomics Research Institute (TGen), Phoenix, Arizona, United States of America.
authors.forename: Glen J
authors.initials: GJ
authors.lastname: Weiss
authors.affiliation: Institute of Nuclear Medicine, University College London, United Kingdom.
authors.forename: Balaji
authors.initials: B
authors.lastname: Ganeshan
authors.affiliation: Institute of Nuclear Medicine, University College London, United Kingdom.
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Miles
authors.affiliation: Imaging Endpoints Core Lab, Scottsdale, Arizona, United States of America.
authors.forename: David H
authors.initials: DH
authors.lastname: Campbell
authors.affiliation: The Translational Genomics Research Institute (TGen), Phoenix, Arizona, United States of America.
authors.forename: Philip Y
authors.initials: PY
authors.lastname: Cheung
authors.affiliation: Virginia G. Piper Cancer Center Clinical Trials at Scottsdale Healthcare, Scottsdale, Arizona, United States of America.
authors.forename: Samuel
authors.initials: S
authors.lastname: Frank
authors.affiliation: Imaging Endpoints Core Lab, Scottsdale, Arizona, United States of America; Virginia G. Piper Cancer Center Clinical Trials at Scottsdale Healthcare, Scottsdale, Arizona, United States of America.
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Korn
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D015996:Survival Rate; D018631:ras Proteins / Q000235:genetics*
chemical_list: C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins