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