Early reduction in tumour [18F]fluorothymidine (FLT) uptake in patients with non-small cell lung cancer (NSCLC) treated with radiotherapy alone

Abstract

PurposeChanges in tumour 3′-deoxy-3′-[18F]fluorothymidine (FLT) uptake during concurrent chemo-radiotherapy in patients with non-small cell lung cancer (NSCLC) have been reported, at variable time points, in two pilot positron emission tomography (PET) studies. The aim of this study was to assess whether FLT changes occur early in response to radiotherapy (RT) without concurrent chemotherapy and whether such changes exceed test-retest variability.MethodsSixteen patients with NSCLC, scheduled to have radical RT, underwent FLT PET once/twice at baseline to assess reproducibility and/or after 5–11 RT fractions to evaluate response. Primary and nodal malignant lesions were manually delineated on CT and volume, mean and maximum standardized uptake values (SUVmean and SUVmax) estimated. Analysis included descriptive statistics and parameter fitting to a mixed-effects model accounting for patients having different numbers of evaluable lesions.ResultsIn all, 35 FLT PET scans from 7 patients with a total of 18 lesions and 12 patients with a total of 30 lesions were evaluated for reproducibility and response, respectively. SUVmean reproducibility in primary tumours (SD 8.9 %) was better than SUVmax reproducibility (SD 12.6 %). In nodes, SUVmean and SUVmax reproducibilities (SD 18.0 and 17.2 %) were comparable but worse than for primary tumours. After 5–11 RT fractions, primary tumour SUVmean decreased significantly by 25 % (p = 0.0001) in the absence of significant volumetric change, whereas metastatic nodes decreased in volume by 31 % (p = 0.020) with a larger SUVmean decrease of 40 % (p < 0.0001). Similar changes were found for SUVmax.ConclusionAcross this group of NSCLC patients, RT induced an early, significant decrease in lesion FLT uptake exceeding test-retest variability. This effect is variable between patients, appears distinct between primary and metastatic nodal lesions, and in primary tumours is lower than previously reported for concurrent chemo-RT at a similar time point. These results confirm the potential for FLT PET to report early on radiation response and to enhance the clinical development of novel drug-radiation combinations by providing an interpretable, early pharmacodynamic end point.Electronic supplementary materialThe online version of this article (doi:10.1007/s00259-013-2632-3) contains supplementary material, which is available to authorized users.

Predictive Value of Early-Stage Uptake of 3′-Deoxy-3′-18F-Fluorothymidine in Cancer Cells Treated with Charged Particle Irradiation

“…The remarkable reductions in tumor uptake of 18 F-FLT preceded the changes in tumor volume, suggesting the prognostic potential of 18 F-FLT PET for monitoring early response after irradiation. These findings are consistent with previous studies using x-irradiation in murine SCCVII tumors (7,22), as well as with clinical trials (23), and a recent report demonstrated the usefulness of 18 F-FLT PET/CT imaging for predicting the therapeutic outcome of carbon ion radiotherapy in head and neck mucosal malignant melanoma (25). Furthermore, after 0.5 Gy of charged particle irradiation, tumor uptake of 18 F-FLT was significantly different from that in controls whereas tumor growth was not, indicating that the 0.5-Gy dose may not be sufficient to induce an anticancer effect in vivo.…”

“…because tumor hypoxia is considered an important factor for resistance to radiotherapy and appears to be an independent risk factor for tumor progression (34). 18 F-FLT, which allows monitoring of cell proliferation, is a promising tracer as a marker of early response of cell proliferation to radiotherapy (7,(22)(23)(24).…”

“…Several studies have suggested that 18 F-FLT is more cancer-specific (18)(19)(20) and sensitive (21) than 18 F-FDG. The potential detectability of 18 F-FLT during the early response to irradiation has also been reported (7,(22)(23)(24). However, because of the high cost and long treatment-planning time of charged particle therapy, few studies have evaluated the use of 18 F-FLT for monitoring the efficacy of proton and, especially, carbon ion radiotherapy.…”

Role of Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Imaging in Diagnosis and Staging of Lung Cancer

“…FLT PET görüntülemenin öncelikli kullanım alanı tedaviye yanıtın değerlendirilmesidir. KHDAK'sinde hem gefitinib (bir epidermal büyüme faktörü reseptör inhibitörü) tedavisi sonrasında (76) hem de radyoterapi sonrasında (77) erken dönemde tedaviye yanıtın FLT PET görüntüleme ile değerlendirilebildiği gösterilmiştir.…”

Molecular Imaging to Plan Radiotherapy and Evaluate Its Efficacy

“…In the context of radiotherapy, 18 F-FLT PET/CT first proved its sensitivity to ionizing radiation in preclinical tumor models (104,105). After promising results from 18 F-FLT PET/CT-based assessments of radiation response in these models, an increasing number of studies have shown that decreased 18 F-FLT uptake early (as early as 5 d/ 10 Gy) in the course of radiotherapy or chemoradiotherapy is a strong indicator of long-term outcome in a large-animal preclinical model (106) and humans (107)(108)(109)(110) (Fig. 2).…”