Abstract
ObjectivesNon-small cell lung cancer (NSCLC) tumors harboring common (exon19del, L858R) and uncommon (e.g. G719X, L861Q) activating epidermal growth factor receptor (EGFR) mutations are best treated with EGFR tyrosine kinase inhibitors (TKI) such as the first-generation EGFR TKI erlotinib, second-generation afatinib or third-generation osimertinib. However, identifying these patients through biopsy is not always possible. Therefore, our aim was to evaluate whether 18F-afatinib PET/CT could identify patients with common and uncommon EGFR mutations. Furthermore, we evaluated the relation between tumor 18F-afatinib uptake and response to afatinib therapy. Materials and methods18F-afatinib PET/CT was performed in 12 patients: 6 EGFR wild type (WT), 3 EGFR common and 3 EGFR uncommon mutations. Tumor uptake of 18F-afatinib was quantified using TBR_WB60−90 (tumor-to-whole blood activity ratio 60−90 min post-injection) for each tumor. Response was quantified per lesion using percentage of change (PC): [(response measurement (RM)–baseline measurement (BM))/BM]×100. Statistical analyses were performed using t-tests, correlation plots and sensitivity/specificity analysis. ResultsTwenty-one tumors were identified. Injected dose was 348 ± 31 MBq. Group differences were significant between WT versus EGFR (common and uncommon) activating mutations (p = 0.03). There was no significant difference between EGFR common versus uncommon mutations (p = 0.94). A TBR_WB60−90 cut-off value of 6 showed the best relationship with response with a sensitivity of 70 %, a specificity of 100 % and a positive predictive value of 100 %. Conclusion18F-afatinib uptake was higher in tumors with EGFR mutations (common and uncommon) compared to WT. Furthermore, a TBR_WB60−90 cut-off of 6 was found to best predict response to therapy. 18F-afatinib PET/CT could provide a means to identify EGFR mutation positive patients who benefit from afatinib therapy.
Highlights
With over 2 million new cases each year, lung cancer is one of the most prevalent cancer types worldwide, and is associated with the highest cancer-related mortality, accounting for over 22 % of cancerrelated deaths [1,2,3]
Lung Cancer 155 (2021) 156–162 pharmacokinetic model, the results of which have already been previ ously published by van de Stadt et al Here, we present the correlation of the tumor 18F-afatinib uptake and the clinical outcomes of afatinib therapy, which was a secondary endpoint of this study
Twelve consecutive evaluable patients were included in this study. 6 patients were epidermal growth factor receptor (EGFR)-wild type (WT), 3 patients had an EGFR common mutation (EGFR com) and 3 patients had an EGFR uncommon mutation (EGFR uncom)
Summary
With over 2 million new cases each year, lung cancer is one of the most prevalent cancer types worldwide, and is associated with the highest cancer-related mortality, accounting for over 22 % of cancerrelated deaths [1,2,3]. Advanced stage non-small cell lung cancer (NSCLC) was treated with chemotherapy. Over the past decade, targeted therapies directed against oncogenic driver pathways (i.e. pathways promoting cell growth) have revolutionized the treatment of NSCLC tumors One such targetable oncogenic driver is the epidermal growth factor receptor (EGFR) pathway. Mutations in the kinase domain of this EGFR pathway can lead to a constitutive, ligand-independent activation of the EGF receptor [4]. Examples of such activating EGFR mutations are exon deletions or the exon 21 L858R point mutation
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