Abstract

PurposeEpidermal growth factor receptor (EGFR) mutations and the anaplastic lymphoma kinase (ALK) rearrangement are the two most common druggable targets in non-small cell lung cancer (NSCLC). However, genetic testing is sometimes unavailable. Previous studies regarding the predictive role of 18F–FDG PET/CT for EGFR mutations in NSCLC patients are conflicting. We investigated whether or not 18F–FDG PET could be a valuable noninvasive method to predict EGFR mutations and ALK positivity in NSCLC using the largest patient cohort to date.MethodsWe retrospectively reviewed and included 849 NSCLC patients who were tested for EGFR mutations or ALK status and subjected to 18F–FDG PET/CT prior to treatment. The differences in several clinical characteristics and three parameters based on 18F–FDG PET/CT, including the maximal standard uptake value (SUVmax) of the primary tumor (pSUVmax), lymph node (nSUVmax) and distant metastasis (mSUVmax), between the different subgroups were analyzed. Multivariate logistic regression analysis was performed to identify predictors of EGFR mutations and ALK positivity.ResultsEGFR mutations were identified in 371 patients (45.9%). EGFR mutations were found more frequently in females, non-smokers, adenocarcinomas and stage I disease. Low pSUVmax, nSUVmax and mSUVmax were significantly associated with EGFR mutations. Multivariate analysis demonstrated that pSUVmax < 7.0, female sex, non-smoker status and adenocarcinoma were predictors of EGFR mutations. The receiver operating characteristic (ROC) curve yielded area under the curve (AUC) values of 0.557 and 0.697 for low pSUVmax alone and the combination of the four factors, respectively. ALK-positive patients tended to have a high nSUVmax. Younger age and distant metastasis were the only two independent predictors of ALK positivity.ConclusionWe demonstrated that low pSUVmax is associated with mutant EGFR status and could be integrated with other clinical factors to enhance the discriminability on the EGFR mutation status in some NSCLC patients whose EGFR testing is unavailable.

Highlights

  • Over the last decade, the introduction of tyrosine-kinase inhibitors (TKIs) has enabled a remarkable paradigm shift in the treatment of non-small cell lung cancer (NSCLC), especially in advanced adenocarcinoma (ADC)

  • We demonstrated that low primary tumor SUVmax (pSUVmax) is associated with mutant Epidermal growth factor receptor (EGFR) status and could be integrated with other clinical factors to enhance the discriminability on the EGFR mutation status in some NSCLC patients whose EGFR testing is unavailable

  • Among the 849 NSCLC patients tested for EGFR and anaplastic lymphoma kinase (ALK) status in our hospital between January 2012 to September 2016, 808 were tested for EGFR, 223 were tested for ALK, and 182 were tested for both

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Summary

Introduction

The introduction of tyrosine-kinase inhibitors (TKIs) has enabled a remarkable paradigm shift in the treatment of non-small cell lung cancer (NSCLC), especially in advanced adenocarcinoma (ADC). Epidermal growth factor receptor (EGFR) mutations and the echinoderm microtubuleassociated protein-like 4 (EML4)-anaplastic lymphoma kinase (ALK) rearrangement are the two most-prevalent druggable targeting categories in NSCLC patients [1]. Randomized clinical trials have demonstrated that progression-free survival (PFS) is longer with TKIs than with chemotherapy when. The TKI efficacy is dependent on the presence of EGFR mutations or the ALK rearrangement. These discoveries have led to the recommendation of molecular profiling as the standard of care for advanced ADC patients [6, 7].

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