Using Fluorodeoxyglucose Positron Emission Tomography to Assess Tumor Volume During Radiotherapy for Non-Small-Cell Lung Cancer and Its Potential Impact on Adaptive Dose Escalation and Normal Tissue Sparing

Department of Radiation Oncology, University of Michigan, Ann Arbor, MI 48109, USA.
International journal of radiation oncology, biology, physics (Impact Factor: 4.26). 04/2009; 73(4):1228-34. DOI: 10.1016/j.ijrobp.2008.10.054
Source: PubMed


To quantify changes in fluorodeoxyglucose (FDG)-avid tumor volume on positron emission tomography/computed tomography (PET/CT) during the course of radiation therapy and examine its potential use in adaptive radiotherapy for tumor dose escalation or normal tissue sparing in patients with non-small-cell lung cancer (NSCLC).
As part of a pilot study, patients with Stage I-III NSCLC underwent FDG-PET/CT before radiotherapy (RT) and in mid-RT (after 40-50 Gy). Gross tumor volumes were contoured on CT and PET scans obtained before and during RT. Three-dimensional conformal RT plans were generated for each patient, first using only pretreatment CT scans. Mid-RT PET volumes were then used to design boost fields.
Fourteen patients with FDG-avid tumors were assessed. Two patients had a complete metabolic response, and 2 patients had slightly increased FDG uptake in the adjacent lung tissue. Mid-RT PET scans were useful in the 10 remaining patients. Mean decreases in CT and PET tumor volumes were 26% (range, +15% to -75%) and 44% (range, +10% to -100%), respectively. Designing boosts based on mid-RT PET allowed for a meaningful dose escalation of 30-102 Gy (mean, 58 Gy) or a reduction in normal tissue complication probability (NTCP) of 0.4-3% (mean, 2%) in 5 of 6 patients with smaller yet residual tumor volumes.
Tumor metabolic activity and volume can change significantly after 40-50 Gy of RT. Using mid-RT PET volumes, tumor dose can be significantly escalated or NTCP reduced. Clinical studies evaluating patient outcome after PET-based adaptive RT are ongoing.

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Available from: feng-ming Kong, Jul 25, 2014
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    • "Many clinical outcome analyses have verified that high uptake of FDG in a tumor is correlated with increased local failure and shorter survival for many tumor sites, as summarized in several metaanalyses [4–7]. Therefore, FDG-avid regions in a tumor are recognized as a possible target for dose escalation to compensate for the radioresistance [8] [9]. Recently, utilizing a novel meta-analysis tool, we showed that FDG-avid head and neck tumors require about 20% more doses to equalize the local control rate with FDG nonavid tumors [10], although tumor size confounded that analysis to an unknown extent. "
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    ABSTRACT: High fluorodeoxyglucose positron emission tomography (FDG-PET) uptake in tumors has often been correlated with increasing local failure and shorter overall survival, but the radiobiological mechanisms of this uptake are unclear. We explore the relationship between FDG-PET uptake and tumor radioresistance using a mechanistic model that considers cellular status as a function of microenvironmental conditions, including proliferating cells with access to oxygen and glucose, metabolically active cells with access to glucose but not oxygen, and severely hypoxic cells that are starving. However, it is unclear what the precise uptake levels of glucose should be for cells that receive oxygen and glucose versus cells that only receive glucose. Different potential FDG uptake profiles, as a function of the microenvironment, were simulated. Predicted tumor doses for 50% control (TD50) in 2 Gy fractions were estimated for each assumed uptake profile and for various possible cell mixtures. The results support the hypothesis of an increased avidity of FDG for cells in the intermediate stress state (those receiving glucose but not oxygen) compared to well-oxygenated (and proliferating) cells.
    Computational and Mathematical Methods in Medicine 09/2014; 2014:847162. DOI:10.1155/2014/847162 · 0.77 Impact Factor
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    • "Apart from the established standardized uptake value (SUV) determination, more recently tumor volume measurements have been reported that could be of value especially in therapy assessment [10] and radiation oncology [11-13]. In addition to intrinsic hardware-based image fusion supplied by PET/CT-hybrid-devices, software-based fine-tuning is possible for correction of fusion artifacts or is even necessary, for example, for the planning of radiation therapy [11]. "
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    ABSTRACT: While non-rigid fusion is by definition expected to alter the information of positron emission tomography (PET) data, we assessed whether rigid transformation also influences metabolic tumor volume (MTV) determination. The PET/computed tomography (CT) data of 28 solid pulmonary lesions of 20 tumor patients examined with 18 F-Fluordeoxyglucose (FDG) was retrospectively analyzed. The original (OR) hardware-coregistered PET images were fused with contrast-enhanced diagnostic CT (CT1, 1 mm slices) and low dose CT (CT5, 5 mm slices). After automatic rigid transformation (Mirada Fusion7D) using two algorithms (rigid fast (RF), rigid slow (RS)), MTV and maximal standardized uptake value (SUVmax) were determined applying four different segmentation methods with either fixed or background-adapted thresholding and compared to OR-PET data. Relative differences in SUVmax compared to OR data revealed no significant differences for RF (median, -0.1%; interquartile range (IQR), -1.1% to 0.9%; p = 0.75) and RS (median, 0.5%; IQR, -0.6% to 1.3%; p = 0.19) in CT1, whereas in CT5 significant deviations were observed for RF (median, -9.0%; IQR, -10.9 to -6.1; p < 0.001) and RS (median, -8.4%; IQR, -11.1 to -5.6; p < 0.001). Relative MTV differences were 0.7% (IQR, -3.0% to 2.7%; p = 0.76) for RF and -1.3% (IQR, -3.6% to 0.9%; p = 0.12) for RS in CT1. Coregistration led to significant MTV differences in RF (median, 10.4%; IQR, 7.4% to 16.7%; p < 0.001) and RS (median, 10.6%; IQR, 5.4% to 17.7%; p < 0.001) in CT5. Rigid coregistration of PET data allows a quantitative evaluation with reasonable accuracy in most cases. However, in some cases, it can result in substantial deviations of MTV and SUVmax. Therefore, it is recommended to perform quantitative evaluation in the original PET data rather than in coregistered PET data.
    EJNMMI Research 12/2013; 3(1):85. DOI:10.1186/2191-219X-3-85
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    • "Feng et al. (2009) performed F18 FDG PET/CT in 14 patients with stage I–III NSCLC before RT and in mid-RT (after 40–50 Gy). 3D conformal RT plans were generated for each patient, first using only pre-treatment CT scans. "
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    ABSTRACT: Radiation therapy is an important component of cancer therapy for early stage as well as locally advanced lung cancer. The use of F18 FDG PET/CT has come to the forefront of lung cancer staging and overall treatment decision-making. FDG PET/CT parameters such as standard uptake value and metabolic tumor volume provide important prognostic and predictive information in lung cancer. Importantly, FDG PET/CT for radiation planning has added biological information in defining the gross tumor volume as well as involved nodal disease. For example, accurate target delineation between tumor and atelectasis is facilitated by utilizing PET and CT imaging. Furthermore, there has been meaningful progress in incorporating metabolic information from FDG PET/CT imaging in radiation treatment planning strategies such as radiation dose escalation based on standard uptake value thresholds as well as using respiratory-gated PET and CT planning for improved target delineation of moving targets. In addition, PET/CT-based follow-up after radiation therapy has provided the possibility of early detection of local as well as distant recurrences after treatment. More research is needed to incorporate other biomarkers such as proliferative and hypoxia biomarkers in PET as well as integrating metabolic information in adaptive, patient-centered, tailored radiation therapy.
    Frontiers in Oncology 07/2012; 2:71. DOI:10.3389/fonc.2012.00071
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