Article

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

ABSTRACT

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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    • "Several clinical meta-analyses suggest that high FDG uptake in a tumor is associated with increased local failure for many tumor sites and reduced patient survival rates[11,12]. FDG-avid regions of a tumor are accordingly considered as a potential target for the application of radiation-dose escalation to counteract radioresistance[13]. A recent meta-analysis study showed that FDG-avid tumors in patients with head and neck carcinomas require a radiation dose increased 20% to match the local response rate of non-FDG avid tumors[14]. "
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    ABSTRACT: 18F-labeled fluorodeoxyglucose (FDG) uptake during FDG positron emission tomography seems to reflect increased radioresistance. However, the exact molecular mechanism underlying high glucose (HG)-induced radioresistance is unclear. In the current study, we showed that ionizing radiation-induced activation of the MEK-ERK-DAPK-p53 signaling axis is required for anoikis (anchorage-dependent apoptosis) of non-small cell lung cancer (NSCLC) cells in normal glucose media. Phosphorylation of DAPK at Ser734 by ERK was essential for p53 transcriptional activity and radiosensitization. In HG media, overexpressed DANGER directly bound to the death domain of DAPK, thus inhibiting the catalytic activity of DAPK. In addition, inhibition of the DAPK-p53 signaling axis by DANGER promoted anoikis-resistance and epithelial-mesenchymal transition (EMT), resulting in radioresistance of HG-treated NSCLC cells. Notably, knockdown of DANGER enhanced anoikis, EMT inhibition, and radiosensitization in a mouse xenograft model of lung cancer. Taken together, our findings offered evidence that overexpression of DANGER and the subsequent inhibitory effect on DAPK kinase activity are critical responses that account for HG-induced radioresistance of NSCLC.
    Preview · Article · Jan 2016 · Oncotarget
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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.
    Full-text · Article · Sep 2014 · Computational and Mathematical Methods in Medicine
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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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    Full-text · Article · Dec 2013 · EJNMMI Research
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