Prognostic Impact of [18F]Fluorothymidine and [18F]Fluoro-D-Glucose Baseline Uptakes in Patients with Lung Cancer Treated First-Line with Erlotinib

<div><p>3′-deoxy-3′-[¹⁸F]fluoro-L-thymidine (FLT) and 2′-deoxy-2′-[¹⁸F]fluoro-D-glucose (FDG) are used to visualize proliferative and metabolic activity of tumors. In this study we aimed at evaluating the prognostic value of FLT and FDG uptake measured by positron emission tomography (PET) in patients with metastatic non-small cell lung cancer (NSCLC) prior to systemic therapy with erlotinib. FLT and FDG maximum standardized uptake (SUVmax) values per patient were analyzed in 40 chemotherapy naive patients with advanced NSCLC (stage IV) before treatment with erlotinib. Prior therapy median SUVmax was 6.6 for FDG and 3.0 for FLT, respectively. In univariate analysis, patients with an FDG SUVmax <6.6 had a significantly better overall survival (16.3 months [95% confidence interval [CI] 7.1–25.4 months]) compared to patients with an FDG SUVmax ≥6.6 (3.1 months [95% CI 0.6–5.5 months]) (p<0.001, log rank). Similarly, low FLT uptake (SUVmax <3.0) was associated with significantly longer survival (10.3 months (0–23.3 months, 95% CI) compared to high FLT uptake (3.4 months (0–8.1 months, 95% CI) (p = 0.027). The independent prognostic value of baseline FDG uptake was demonstrated in multivariate analysis (p = 0.05, Cox regression). These data suggest that baseline SUVmax values for both FDG and FLT PET might be further developed as markers for prognostic stratification of patients in advanced NSCLC treated with tyrosine kinase inhibitors (TKI) directed against the epidermal growth factor receptor (EGFR).</p> <h3>Trial Registration</h3><p>Clinicaltrials.gov, Identifier: <a href="http://clinicaltrials.gov/ct2/show/NCT00568841">NCT00568841</a></p> </div

Individual patient characteristics and PET results.

<p>Individual patient characteristics and PET results.</p

Example of two patients with low and high baseline uptake of FDG and FLT.

<p>The patient shown in figure A with low uptake is a 66-year old female patient who had an overall survival of 21.3 months, whereas the patient in B with a high uptake is a 56-year old female patient with an overall survival of only 1.5 months. In both cases, the respective most active lesion was chosen for assessment.</p

Patient characteristics.

<p>Patient characteristics.</p

Correlation of the EGFR mutational status with Ki-67 staining in %.

<p>Correlation of the EGFR mutational status with Ki-67 staining in %.</p

Kaplan Meier curves showing overall survival depending on SUVmax values.

<p>A) Overall survival of patients with high (>6.7; grey) or low (<6.7; red) baseline SUVmax in FDG-PET. (B) Overall survival of patients with high (>3; grey) or low (<3; red) baseline SUVmax in FLT-PET.</p

Agreement statistics for Deauville (D) scoring among five readers.

<p>Agreement statistics for Deauville (D) scoring among five readers.</p

Residual uptake in the mediastinum vs. thymus.

<p>Case 12: a) Lymphoma involvement of the upper and middle mediastinum including the thymus before treatment. b) and c) very slightly enhanced uptake as compared to the mediastinum after two cycles ChT. The interpretation might be complicated by the difficult decision whether this finding implies residual tumor uptake or physiological but inhomogeneous uptake in the thymus. Deauville score of the readers R1-5, respectively: 1-1-3-3-3. Courtesy Dept. Nuclear Medicine, Blackrock Clinic, Dublin, Ireland.</p

Discrepant D scoring of the mediastinum.

<p>Case 39: a) extensive lymphoma involvement of the left side of the upper mediastinum before treatment. b) residual mass after two cycles ChT. c) highest residual FDG uptake in the dorsal part of the residuum. D) It is difficult to decide if this highest FDG uptake is above or below the liver uptake. The interpretation is complicated by the small size of the hottest part of the residuum. Deauville score of the readers R1-5, respectively: 3-3-4-4-4. Courtesy M. Reinhardt, Dept. Nuclear Medicine, Pius-Hospital, Oldenburg, Germany.</p

Discrepant D scoring of the right supraclavicular region.

<p>Case 63. a) Tumour involvement before treatment. b) Residual mass in this region after two cycles of OEPA. c) and d) slightly enhanced FDG uptake above background in this area. Interpretation might be complicated by a slightly enhanced FDG uptake symmetrically in the left supraclavicular area which, however, is in the surrounding of a catheter and by the inhomogeneous uptake in the mediastinum. Deauville score of the readers R1-5, respectively: 1-1-3-1-2. Courtesy Dept. Nuclear Medicine, Karolinska University Hospital, Stockholm, Sweden.</p