Abstract
Positron emission tomography (PET) with [(18)F]fluorodeoxyglucose (FDG) is increasingly used in early assessment of tumor response after chemotherapy. We investigated whether a change in [(18)F]FDG uptake at 2 days of gefitinib treatment predicts outcome in patients with lung adenocarcinoma. Twenty patients were enrolled. [(18)F]FDG-PET/computed tomographic (CT) scan was carried out before and 2 days after gefitinib treatment. Maximum standardized uptake values (SUV) were measured, and post-gefitinib percentage changes in SUV were calculated. Early metabolic response (SUV decline < -25%) was compared with morphologic response evaluated by CT scan and with progression-free survival (PFS). At 2 days of gefitinib treatment, 10 patients (50%) showed metabolic response, 8 had metabolic stable disease, and 2 had progressive metabolic disease. Percentage changes of SUV at 2 days were correlated with those of tumor size in CT at 1 month (R(2) = 0.496; P = 0.0008). EGFR gene was assessable in 15 patients, and of 12 patients with EGFR mutations, 8 showed metabolic response at 2 days and 6 showed morphologic response at 1 month. None of 3 patients with wild-type EGFR showed metabolic or morphologic response. Metabolic response at 2 days was not statistically associated with PFS (P = 0.095), but when a cutoff value of -20% in SUV decline was used, metabolic responders had longer PFS (P < 0.0001). Early assessment of [(18)F]FDG tumor uptake with PET at 2 days of gefitinib treatment could be useful to predict clinical outcome earlier than conventional CT evaluation in patients with lung adenocarcinoma.
Highlights
Treatment of non–small cell lung cancer (NSCLC) has made remarkable progress in the last decade; the epidermal growth factor receptor (EGFR), which is expressed in more than 60% of patients with metastatic NSCLC and correlatesAuthors' Affiliations: Departments of 1Respiratory Medicine, Allergy and Rheumatic Diseases, 2Nuclear Medicine, and 3General Thoracic Surgery, Osaka University Graduate School of Medicine; and 4Osaka Prefectural Medical Center for Respiratory and Allergic Diseases, Osaka, JapanNote: Supplementary data for this article are available at Clinical Cancer Research Online.R
Partial metabolic response (PMR) was defined as percentage change of the sum of standardized uptake values (SUV) (DSUV%) < À25%, stable metabolic disease (SMD) was À25% DSUV% < þ25%, and progressive metabolic disease (PMD) was defined as þ25% DSUV% or when the extent of [18F]FDG increased greater than 20% in the longest dimension or when new [18F]FDG uptake appeared in metastatic lesions
Median time between the baseline Positron emission tomography (PET)/computed tomographic (CT) and the start of gefitinib treatment was 4 days, and no chemotherapy was administered during this period
Summary
Gefitinib as first-line and single-agent therapy improved progressionfree survival (PFS) of patients with NSCLC with the EGFR mutations when compared with standard chemotherapy [8,9,10]. These genetic markers may be used to predict therapeutic response, they do not guarantee successful treatment as a portion of marker-positive patients did not respond to the EGFR TKIs, whereas a portion of marker-negative patients did respond [11]. A secondary mutation in the EGFR gene or amplification of c-Met negates the sensitizing effect, leading to acquired
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