Exploring Spatial Overlap of High-Uptake Regions Derived From Dual Tracer Positron Emission Tomography–Computer Tomography Imaging Using 18F-Fluorodeoxyglucose and 18F-Fluorodeoxythymidine in Nonsmall Cell Lung Cancer Patients

Interest is growing in radiotherapy to nonuniformly boost radioresistant regions within nonsmall cell lung cancer (NSCLC) using molecular imaging techniques. The complexity of tumor behavior is beyond the ability of any single radiotracer to reveal. We hold dual tracer positron emission tomography–computer tomography (PET/CT) imaging with fluorodeoxyglucose (FDG) and fluorodeoxythymidine (FLT) for NSCLC patients to offer an integrated overlook of tumor biological behaviors quantitatively and localizationally, which may help biological target volume delineation and subvolume boost. Pathological confirmed that NSCLC patients were eligible. FDG and FLT PET/CT were performed for each patient before anticancer treatment and coregistrated for analysis. Maximum and mean standardized uptake values (SUVmax and SUVmean) were calculated automatically. Metabolic volumes(MVs)weredelineatedbyafixed50%ofSUVmax inFDGPET/CT andproliferativevolumes(PVs)weredelineatedby50%to90%ofSUVmax with 10% interval in FLT PET/CT. Overlap ratio (OR) were determined as overlapped volume between MV and PV divided PV. Conventional contrast-enhanced CT-based intensity-modulated radiotherapy (IMRT) plans with and without additional PET/CT-guided subtarget boost were made for each of the 5 typical NSCLC patients. Dosimetric parameters derived from dose–volume histogram, tumor control probability (TCP), and normal tissue complication probability (NTCP) of lung, esophagus, eng Fu, MD, Jinm hD, and D, PhD 15 metastatic lesions were positive in dual PET/CTs and included for analysis. Median ORs increased from 58.61% to 93.12% under thresholds of 50% of SUVmax in FDG PET/CT and increased thresholds from 50% to 90% of SUVmax in FLT PET/CT. Based on conventional IMRT, additional boost to union of high FDG (determined by 50% SUVmax) and FLT (determined by 80% SUVmax) uptake subtargets exhibited higher TCP without significant elevated NTCP of lung, esophagus, spinal cord, and heart. Dual tracer PET/CT of FDG and FLT is suggested for NSCLC patients to guide tumor target delineation in clinical practice. FDG PET/ CT is necessary whereas FLT PET/CT may be optional when guiding tumor target delineation clinically. Additional information from randomized trials is required to validate. (Medicine 94(17):e678) Abbreviations: BTVs = biological target volumes, CT = computer tomography, CTV = clinical target volume, Dmax = maximal irradiated dose, DVH = dose–volume histogram, FDG = fluorodeoxyglucose, FLT = fluorodeoxythymidine, GTV = gross tumor volume, IMRT = intensity-modulated radiation therapy, MV = metabolic volume, NSCLC = nonsmall cell lung cancer, NTCP = normal tissue complication probability, OAR = organ at risk, OR = overlap ratio, OV = overlap volume, PET = positron emission tomography, PTV = planning target volume, PV = proliferative volume, SUVmax = maximum standardized uptake value, SUVmean = mean standardized uptake value, TCP = tumor control probability, V20 = tissue volume receiving 20 Gy or more. INTRODUCTION R adiotherapy, which has been estimated to be applied in 70% of cancer patients, is adopted by almost all nonsmall cell lung cancer (NSCLC) patients to achieve local disease control and/or clinical symptoms relieve. Standard radiotherapy of NSCLC with 60 to 70 Gy is associated with an local recurrence rate of estimated 50%. Great efforts have been made to facilitate higher radiation dose under modern radiation techniques based on the clear existed association between total dose, local control, and survival of NSCLC patients. However, the interim analysis of the Radiation Therapy Oncology Group ed that the higher radiation dose of e a longer survival time than the standard h reported adverse events were similar, www.md-journal.com | 1 the injury of high-dose radiotherapy on normal lungs and heart may lead to more deaths than standard dose. Under the situation of higher radiation dose not performing better, radiation boost to biological target volumes (BTVs) nonuniformly to improve local control, may likely bring about new hope for dose escalation to radiation-resistant subregions. Ideal biological target delineation enables visualization of subvolumes exhibiting heterogeneous biological characteristics of pathophysiological processes, including glucose metabolism, proliferation, hypoxia, epidermal growth factor receptor expression, and choline metabolism, within tumor volume. Positron emission tomography (PET) with single radiotracer, such as typically well-studied fluorodeoxyglucose (FDG), fluorodeoxythymidine (FLT), and fluoromisonidazole, has been investigated as possible dose-painting targets. The fact that overexpression of glucose transporter 1 is consistent with increased cellular proliferation, as well as increased glucose uptake and glycolytic metabolism of tumor cells, laid a solid foundation for the tight linkage of glucose metabolic activity and cell proliferation, which were exhibited by PET tracers of FDG and FLT, respectively. Image presentation of tumor glucose metabolism and cellular proliferative activity provides relevant and complementary information for treatment choices made by radiation oncologists. Nevertheless, multitracer-guided subvolume boost in radiotherapy is urgently in need of research. For these reasons, we investigated the spatial distribution relationship of regional glucose metabolism and proliferation by comparing FLT and FDG uptake on PET/computer tomography (CT) images to explore the spatial location relation between high-uptake regions determined by baseline dual PET tracers of FDG and FLT in NSCLC patients. Additionally, we planned nonuniform radiation dose boost to high FDG and FLT uptake areas with intensity-modulated radiation therapy (IMRT) as a preclinical study to explore the efficacy and feasibility of BTV boost in NSCLC patients. MATERIALS AND METHODS