18F-Fluorodeoxyglucose PET/CT for Early Prediction of Outcomes in Patients with Advanced Lung Adenocarcinomas and EGFR Mutations Treated with First-Line EGFR-TKIs

Abstract

This study aims to investigate the role of ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) in early prediction of response and survival following epithelial growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) therapy in patients with advanced lung adenocarcinomas and EGFR mutations. Thirty patients with stage IIIB/IV lung adenocarcinomas and EGFR mutations receiving first-line EGFR-TKIs were prospectively evaluated between November 2012 and May 2015. EGFR mutations were quantified by delta cycle threshold (dCt). ¹⁸F-FDG PET/CT was performed before and 2 weeks after treatment initiation. PET response was assessed based on PET Response Criteria in Solid Tumors (PERCIST). Baseline and percentage changes in the summed standardized uptake value, metabolic tumor volume (bsumMTV and ΔsumMTV, respectively), and total lesion glycolysis of ≤5 target lesions/patient were calculated. The association between parameters (clinical and PET) and non-progression disease after 3 months of treatment in CT based on the Response Evaluation Criteria in Solid Tumors Version 1.1 (nPD_3mo), progression-free survival (PFS), and overall survival (OS) were tested. The median follow-up time was 19.6 months. The median PFS and OS were 12.0 and 25.3 months, respectively. The PERCIST criteria was an independent predictor of nPD_3mo (p = 0.009), dCt (p = 0.014) and bsumMTV (p = 0.014) were independent predictors of PFS, and dCt (p = 0.014) and ΔsumMTV (p = 0.005) were independent predictors of OS. ¹⁸F-FDG PET/CT achieved early prediction of outcomes in patients with advanced lung adenocarcinomas and EGFR mutations receiving EGFR-TKIs.

Keywords: 18F-FDG PET; adenocarcinoma of lung; early response evaluation; survival; tyrosine kinase inhibitors.

Figure 1

Patient flow diagram.

Figure 2

Illustrative images of ¹⁸F-FDG PET responses. (A) Maximum-intensity projection (MIP) ¹⁸F-FDG PET images at baseline and after 2 weeks of gefitinib treatment of a 58-year-old woman with stage IV lung adenocarcinoma and mutant EGFR (exon 19 del) showing marked ¹⁸F-FDG response visually. The SUL_max of the single hottest lesion decreased from 10.7 (left upper pleura, arrow) to 4.10 (lingula of left lung, arrowhead), with a ΔSUL of −61.5% and a PMR based on PERCIST 1.0. She achieved PR at 3 months. (B) MIP ¹⁸F-FDG PET images at baseline and after 2 weeks of gefitinib treatment of a 78-year-old man with stage IV lung adenocarcinoma and mutant EGFR (L858R) showing SMD (nMR) based on PERCIST 1.0. The SUL_max of the single hottest lesion decreased from 9.37 (right upper lobe pulmonary mass, arrow) to 8.91 (the same lesion, arrowhead), with a ΔSUL of −4.90%. There was also an incidental left parotid tumor. He had PD (a new left adrenal metastasis) at 3 months.

Figure 3

Kaplan–Meier survival curve showing differences in progression-free survival between patients with a dCt of ≥6 and those with a dCt of <6 (A) and between patients with a bsumMTV ≥ 40 cm³ and < 40 cm³ (B). (C) Kaplan–Meier survival curve showing differences in overall survival between patients with a ΔsumMTV of ≥−60% and those with a ΔsumMTV of <−60%. HR, hazard ratio.