Elsevier

Lung Cancer

Volume 67, Issue 1, January 2010, Pages 76-80
Lung Cancer

18F-FDG uptake and EGFR mutations in patients with non-small cell lung cancer: A single-institution retrospective analysis

https://doi.org/10.1016/j.lungcan.2009.03.010Get rights and content

Abstract

This retrospective study was performed to evaluate a possible association between the presence of epidermal growth factor receptor (EGFR) mutations and the standardized uptake value (SUV) of 18F-fluoro-2-deoxy-glucose (18F-FDG) uptake in patients with non-small cell lung cancer (NSCLC). We included 100 patients who were tested for EGFR mutations by direct sequencing of resected tissues and who underwent preoperative positron emission tomography/computed tomography at the time of diagnosis. The maximum SUV by the primary tumor was chosen for further analysis. EGFR mutations in exons 19 and 21 were detected in 21 NSCLC patients (21%). EGFR mutations were more frequent in never-smokers than ever-smokers (35% versus 11%; P = 0.003), in adenocarcinomas than non-adenocarcinomas (34% versus 6%; P = 0.001), and in females than males (41% versus 12%; P = 0.001). The SUV ranged from 1.3 to 33.0 (median 10.6). Area under receiver operating characteristic curve for SUVs in respect to the presence of EGFR mutations was 0.74 (95% CI: 0.62–0.85). When a cut off value was used, patients with low SUVs were more likely to have EGFR mutations than those with high SUVs (40% versus 11%; P = 0.001). On multivariate analysis, a low SUV remained a significant predictors for EGFR mutations (P = 0.025). 18F-FDG uptake was associated with the presence of EGFR mutation. These results extrapolate that 18F-FDG uptake might be helpful to discriminate patients who harbor EGFR mutations, especially when a genetic test is not feasible.

Introduction

Lung cancer is the leading cause of cancer-related death worldwide [1], [2]. The treatment outcome of patients with lung cancer remains poor [3]. To improve the clinical outcome of this type of cancer, novel treatment strategies targeting genetic abnormalities have been introduced.

Mutations in the epidermal growth factor receptor (EGFR) gene have been identified as a potential therapeutic target for the treatment of patients with non-small cell lung cancers (NSCLCs) [4]. EGFR mutations in four exons (18–21) are found in patients with NSCLC [5], of which approximately 90% are exon 19 deletions and exon 21 L858R substitutions [6]. Although clinicobiological differences by genotypes were suggested in previous studies [5], [7], [8], these two types of mutations seem to explain the clinical response to tyrosine-kinase inhibitor (TKI) in most cases of NSCLC [7]. Previous studies have shown that EGFR mutations are predominantly found in females, in never-smokers, in patients with adenocarcinoma, and in Asians [6], [9]. Researchers have also reported that EGFR mutation could predict favorable outcomes in TKI-treated patients [4], [10]. This finding might justify the confirmation of EGFR genotype prior to TKI treatment; however, in clinical practice, it is often difficult to obtain an amount of tumor tissue sufficient for the genetic test in patients with advanced cancer stages [11], [12].

Previous studies have suggested that the standardized uptake value (SUV), a quantitative measurement of 18F-fluoro-2-deoxy-glucose (18F-FDG) uptake on positron emission tomography (PET) [13], is associated with outcomes in patients with NSCLC [14], [15], [16], [17], [18]. Recently, we have reported that a low SUV is associated with favorable outcomes in gefitinib-treated patients with advanced NSCLC [19]. Given the results showing that patients carrying EGFR mutations have a better TKI responsiveness than those with the wild-type EGFR[4], [10], we surmised that tumors with low SUVs could have a higher probability of presence of EGFR mutations; however, to our knowledge, there are currently no data demonstrating a link between PET findings and the presence of EGFR mutations. Thus, we conducted this retrospective study to assess if 18F-FDG uptake is associated with the presence of EGFR mutations.

Section snippets

Patients

This analysis comprises 100 patients whose EGFR mutational status was tested and who underwent positron emission tomography/computed tomography (PET/CT) at the time of diagnosis. We initially identified patients who received surgical resection and who underwent PET/CT at diagnosis from March 2002 to January 2008. To be eligible for inclusion, patients had to have documented results for EGFR mutational status which were identified from the NSCLC pathology database of our institution. Informed

Patient characteristics and their associations with EGFR mutations

Table 1 shows the baseline characteristics of the patients. Sixty-eight patients (68%) were males and the median age was 64 years (range: 40–79 years). Fifty three percent of the patients had adenocarcinomas and 43 patients did not have a history of smoking. The SUV of primary tumors ranged from 1.3 to 33.0 (median 10.6).

EGFR mutations were found in 21 patients (21%); exon 19 deletions were found in 15 patients and the L858R substitution in exon 21 was found in six patients. Associations

Discussion

In the present study, we evaluated the clinical significance of 18F-FDG uptake as a predictor of the presence of the EGFR mutations. EGFR mutations were found to be associated with quantitative measurements of 18F-FDG uptakes (i.e., SUVs). As suggested in our previous study [19], we observed that patients with low SUVs in primary tumors harbored a higher incidence of EGFR mutations, when compared with those with high SUVs. Importantly, multivariate analysis confirmed that the SUV was a

Conflict of interest statement

None declared.

Acknowledgement

This work was supported in part by AstraZeneca Pharmaceuticals.

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    This work was partly presented at the 33rd European Society for Medical Oncology.

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