Non-Small Cell Lung Cancer Treated with Erlotinib: Heterogeneity of (18)F-FDG Uptake at PET-Association with Treatment Response and Prognosis

Radiology. 2015 Sep;276(3):883-93. doi: 10.1148/radiol.2015141309. Epub 2015 Apr 17.


Purpose: To determine if first-order and high-order textural features on fluorine 18 ((18)F) fluorodeoxyglucose (FDG) positron emission tomography (PET) images of non-small cell lung cancer (NSCLC) (a) at baseline, (b) at 6 weeks, or (c) the percentage change between baseline and 6 weeks can predict response or survival in patients treated with erlotinib.

Materials and methods: Institutional review board approval was obtained for post hoc analysis of data from a prospective single-center study for which informed consent was obtained. The study included 47 patients with NSCLC who underwent (18)F-FDG PET/computed tomography (CT) at baseline (n = 47) and 6 weeks (n = 40) after commencing treatment with erlotinib. First-order and high-order primary tumor texture features reflecting image heterogeneity, standardized uptake values, metabolic tumor volume, and total lesion glycolysis were measured for all (18)F-FDG PET studies. Response to erlotinib was assessed by using the Response Evaluation Criteria in Solid Tumors (RECIST) on CT images obtained at 12 weeks (n = 32). Associations between PET parameters, overall survival (OS), and RECIST-based treatment response were tested by Cox and logistic regression analyses, respectively.

Results: Median OS was 14.1 months. According to CT RECIST at 12 weeks, there were 21 nonresponders and 11 responders. Response to erlotinib was associated with reduced heterogeneity (first-order standard deviation, P = .01; entropy, P = .001; uniformity, P = .001). At multivariable analysis, high-order contrast at 6 weeks (P = .002) and percentage change in first-order entropy (P = .03) were independently associated with survival. Percentage change in first-order entropy was also independently associated with treatment response (P = .01).

Conclusion: Response to erlotinib is associated with reduced heterogeneity at (18)F-FDG PET. Changes in first-order entropy are independently associated with OS and treatment response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Non-Small-Cell Lung / diagnostic imaging*
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Erlotinib Hydrochloride
  • Female
  • Fluorodeoxyglucose F18* / pharmacokinetics
  • Humans
  • Lung Neoplasms / diagnostic imaging*
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / metabolism
  • Male
  • Middle Aged
  • Positron-Emission Tomography*
  • Prognosis
  • Prospective Studies
  • Protein Kinase Inhibitors / therapeutic use*
  • Quinazolines / therapeutic use*
  • Radiopharmaceuticals* / pharmacokinetics
  • Treatment Outcome


  • Protein Kinase Inhibitors
  • Quinazolines
  • Radiopharmaceuticals
  • Fluorodeoxyglucose F18
  • Erlotinib Hydrochloride