Standardized uptake value on (18)F-FDG-PET/CT is a predictor of EGFR T790M mutation status in patients with acquired resistance to EGFR-TKIs

Lung Cancer. 2016 Oct:100:14-19. doi: 10.1016/j.lungcan.2016.07.022. Epub 2016 Jul 22.

Abstract

Background: The development of epidermal growth factor receptor (EGFR) T790M point mutation in exon 20 (T790M) is the most common mechanism of resistance to EGFR tyrosine kinase inhibitors (EGFR-TKIs). The purpose of this study was to determine the association of (18)F-2-fluoro-2-deoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) metrics with T790M status after acquiring resitance to EGFR-TKI resistance.

Methods: We retrospectively reviewed 34 advanced non-small cell lung cancer (NSCLC) patients harboring EGFR mutation who underwent rebiopsy and FDG-PET/CT before rebiopsy. These patients were evaluated for baseline characteristics, initial response to EGFR-TKIs, site of rebiopsy, overall survival, and FDG-PET/CT metrics, such as standardized uptake value (SUV), metabolic tumor volume, and total lesion glycolysis of the rebiopsy site.

Results: The median age was 67 years (range, 37-86 years); 19 of the patients (56%) were men. Histologic examination revealed adenocarcinoma in all but one patient, with 20 patients (59%) having stage IIIB and IV disease. Upon initial mutational analyses, the types of EGFR mutation included 17 (50%) deletions in exon 19 and 17 (50%) L858R point mutations in exon 21. At the time of acquired resistance to EGFR-TKIs, T790M mutation was identified in 20 (59%) patients. T790M-positive patients had significantly lower levels of median SUVmean and median SUVmax of the rebiopsy site on FDG-PET/CT, compared with T790M-negative patients (SUVmean: 4.57 vs. 9.91, P=0.0069; SUVmax: 7.26 vs. 16.06, P=0.0054). The survival in patients who acquired T790M after failure of EGFR-TKIs was significantly longer than those without T790M (10.2 mos. vs. 18.6 mos., P<0.05).

Conclusion: T790M status was associated with lower levels of SUVmean and SUVmax on FDG-PET/CT and significantly longer survival.

Keywords: Epidermal growth factor receptor (EGFR); Non-small cell lung cancer (NSCLC); Standardized uptake value (SUV); T790 M.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Non-Small-Cell Lung / diagnostic imaging
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • DNA Mutational Analysis / methods
  • Drug Resistance, Neoplasm / genetics*
  • ErbB Receptors / genetics*
  • ErbB Receptors / metabolism
  • Female
  • Fluorodeoxyglucose F18 / metabolism*
  • Humans
  • Male
  • Middle Aged
  • Mutation*
  • Positron Emission Tomography Computed Tomography / methods*
  • Predictive Value of Tests
  • Protein Kinase Inhibitors / therapeutic use*
  • Retrospective Studies

Substances

  • Protein Kinase Inhibitors
  • Fluorodeoxyglucose F18
  • EGFR protein, human
  • ErbB Receptors