Abstract
This study investigated the relationship between epidermal growth factor receptor (EGFR) and Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations in non-small-cell lung cancer (NSCLC) and quantitative FDG-PET/CT parameters including tumor heterogeneity. 131 patients with NSCLC underwent staging FDG-PET/CT followed by tumor resection and histopathological analysis that included testing for the EGFR and KRAS gene mutations. Patient and lesion characteristics, including smoking habits and FDG uptake parameters, were correlated to each gene mutation. Never-smoker (P < 0.001) or low pack-year smoking history (p = 0.002) and female gender (p = 0.047) were predictive factors for the presence of the EGFR mutations. Being a current or former smoker was a predictive factor for the KRAS mutations (p = 0.018). The maximum standardized uptake value (SUVmax) of FDG uptake in lung lesions was a predictive factor of the EGFR mutations (p = 0.029), while metabolic tumor volume and total lesion glycolysis were not predictive. Amongst several tumor heterogeneity metrics included in our analysis, inverse coefficient of variation (1/COV) was a predictive factor (p < 0.02) of EGFR mutations status, independent of metabolic tumor diameter. Multivariate analysis showed that being a never-smoker was the most significant factor (p < 0.001) for the EGFR mutations in lung cancer overall. The tumor heterogeneity metric 1/COV and SUVmax were both predictive for the EGFR mutations in NSCLC in a univariate analysis. Overall, smoking status was the most significant factor for the presence of the EGFR and KRAS mutations in lung cancer.
Highlights
Epidermal growth factor receptor (EGFR) [1, 2], Kirsten rat sarcoma viral oncogene homolog (KRAS) [3] and anaplastic lymphoma kinase (ALK) [4] are all significant biomarkers for the management of non-small-cell lung cancer (NSCLC)
This study investigated the relationship between epidermal growth factor receptor (EGFR) and Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations in non-small-cell lung cancer (NSCLC) and quantitative FDG-PET/CT parameters including tumor heterogeneity. 131 patients with NSCLC underwent staging FDG-PET/ CT followed by tumor resection and histopathological analysis that included testing for the EGFR and KRAS gene mutations
While the relationship between FDG uptake and EGFR mutations in NSCLC has previously been noted to have contradictory results [15, 16], and one notable study has shown that the KRAS mutations in lung cancer www.impactjournals.com/oncotarget showed significantly higher FDG uptake than wild type (WT) cancer [17]
Summary
Epidermal growth factor receptor (EGFR) [1, 2], Kirsten rat sarcoma viral oncogene homolog (KRAS) [3] and anaplastic lymphoma kinase (ALK) [4] are all significant biomarkers for the management of non-small-cell lung cancer (NSCLC). EGFR is a member of a larger family of closely related transmembrane receptor tyrosine kinases (TK), which activate cell growth and replication, differentiation and survival [5, 6]. Mutations in the TK domain of the EGFR in NSCLC predict the response to TK inhibitors such as Gefitinib and Erlotinib [7,8,9]. Akt activation may have a close relationship with EGFR mutations and fluorodeoxyglucose (FDG) uptake in NSCLC. Intra-tumor heterogeneity appears to correlate to the EGFR mutations in NSCLC and may predict tumor responsiveness to TK inhibitors therapy [20, 21].
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