(18)F-FDG PET/CT for monitoring treatment responses to the epidermal growth factor receptor inhibitor erlotinib.
ABSTRACT Response rates of unselected non-small cell lung cancer (NSCLC) patients to the epidermal growth factor receptor inhibitor erlotinib are low and range from 10% to 20%. Early response assessments are needed to avoid costs and side effects of inefficient treatments. Here we determined whether early changes in tumor uptake of (18)F-FDG can predict progression-free and overall survival in NSCLC patients who are treated with erlotinib.
Twenty-two patients (6 men, 16 women; mean age ± SD, 64 ± 13 y) with stage III or stage IV NSCLC who received erlotinib treatment were enrolled prospectively. (18)F-FDG PET/CT was performed before the initiation of treatment (n = 22), after 2 wk (n = 22), and after 78 ± 21 d (n = 11). Tumor maximum standardized uptake values were measured for a maximum of 5 lesions for each patient. Tumor responses were classified using modified PET Response Criteria in Solid Tumors (use of maximum standardized uptake values). Median overall survival by Kaplan-Meier analysis was compared between groups using a log-rank test.
The overall median time to progression was 52 d (95% confidence interval, 47-57 d). The overall median survival time was 131 d (95% confidence interval, 0-351 d). Patients with progressive metabolic disease on early follow-up PET showed a significantly shorter time to progression (47 vs. 119 d; P < 0.001) and overall survival (87 vs. 828 d; P = 0.01) than patients classified as having stable metabolic disease or partial or complete metabolic response.
These data suggest that (18)F-FDG PET/CT performed early after the start of erlotinib treatment can help to identify patients who benefit from this targeted therapy.
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ABSTRACT: The aim of this prospective study was to evaluate whether [(18)F]FDG-PET/CT, performed within two weeks of starting erlotinib therapy can predict tumor response defined by RECIST 1.1 criteria after 8 weeks of treatment in patients with inoperable (stage IIIA to IV) non-small cell lung cancer patients. Three [(18)F]FDG-PET/CT scans were acquired in 12 patients before (5±4 days) and after 9±3 days (early PET) and 60±6 days (late PET) of erlotinib therapy. Conventional evaluation, including at least chest CT (baseline versus after 8 weeks of treatment), was performed according to RECIST 1.1 criteria. Change in [(18)F]FDG uptake was compared with conventional response, progression-free survival (PFS), and overall survival (OS). By using ROC analysis, the Area Under the Curve for prediction of metabolic non-progressive disease (mNP) by early PET was 0.86 (95% CI, 0.62 to 1.1; P = 0.04) at a cut-off of 21.6% reduction in maximum Standardized Uptake Value (SUVmax). This correctly classified 11/12 patients (7 with true progressive disease; 4 with true non-progressive disease; 1 with false progressive disease). Non-progressive disease after 8 weeks of treatment according to RECIST 1.1 criteria was significantly more frequent in patients classified mNP (P = 0.01, Fisher's exact test). mNP patients showed prolonged PFS (HR = 0.27; 95% CI, 0.04 to 0.59; P<0.01) and OS (HR = 0.34; 95% CI, 0.06 to 0.84; P = 0.03). Late PET analysis provided concordant results. Morphologic response, PFS and OS survival in non-small cell lung cancer patients can be predicted by [(18)F]FDG-PET/CT scan within 2 weeks after starting erlotinib therapy.PLoS ONE 01/2014; 9(2):e87629. · 3.73 Impact Factor
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ABSTRACT: [18F]fluorodeoxyglucose (FDG)-PET is being evaluated as a tool for the early detection of response to various targeted agents in solid tumors. The aim of this study was to evaluate the predictive value of PET response after 2 days of erlotinib in unselected pretrated patients with stage IV NSCLC. FDG-PET/CT scans were conducted at baseline and after 2 days of erlotinib, with a CT evaluation performed at baseline and after 45-60 days of therapy. PET responses were evaluated by quantitative changes on SUVmax tumor/non-tumor ratio and classified according to EORTC criteria. PET responses were compared with RECIST responses and related to progression-free (PFS) and overall (OS) survival. Erlotinib effects on glucose uptake were also studied in a panel of NSCLC cell lines. Fifty-three patients were enrolled. At 2 days of erlotinib, 20 (38 %) patients showed partial metabolic response (PMR), 25 (47 %) had stable metabolic disease (SMD) and 8 (15 %) had progressive metabolic disease (PMD). All patients with PMD had confirmed RECIST progression at 45-60 days. Patients with early PMR and SMD had significantly longer PFS (p < 0.001 and p = 0.001, respectively) and OS (p = 0.001 for both) than PMD patients. FDG-PET assessment after 2 days of erlotinib could be useful to identify early resistent patients and to predict survival in unselected NSCLC pretreated population.Cancer Chemotherapy and Pharmacology 11/2013; · 2.80 Impact Factor
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ABSTRACT: As the culprit behind most cancer-related deaths, metastasis is the ultimate challenge in our effort to fight cancer as a life-threatening disease. The explosive growth of metastasis research in the past decade has yielded an unprecedented wealth of information about the tumor-intrinsic and tumor-extrinsic mechanisms that dictate metastatic behaviors, the molecular and cellular basis underlying the distinct courses of metastatic progression in different cancers and what renders metastatic cancer refractory to available therapies. However, integration of such new knowledge into an improved, metastasis-oriented oncological drug development strategy is needed to thwart the development of metastatic disease at every stage of progression.Nature medicine 11/2013; 19(11):1450-64. · 27.14 Impact Factor