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: 4.18). 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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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 · 1.02 Impact Factor
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    • "With acceptable acute toxicity, the approach resulted in a significant reduction of target volumes in head and neck cancer patients (Duprez et al., 2011). The feasibility of boosting areas with residual 18 F-FDG uptake at mid-treatment or later during radiotherapy in lung cancer is, however, controversial (Feng et al., 2009; Gillham et al., 2008). Overall, these studies confirm a value of 18 F-FDG-PET in monitoring of early treatment response and show the feasibility of integrating PET for radiotherapy optimization before initiation of treatment and/or early during therapy. "
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    ABSTRACT: Radiotherapy is today used in about 50% of all cancer patients, often in multidisciplinary approaches. With major advance in radiotherapy techniques, increasing knowledge on tumor genetics and biology and the continuous introduction of specifically targeted drugs into combined radio-oncological treatment schedules, individualization of radiotherapy is of high priority to further improve treatment outcomes, i.e. to increase long-term tumor cure and/or to reduce chronic treatment toxicity. This review gives an overview on the importance of predictive biomarkers for the field of radiation oncology. The current status of knowledge on potential biomarkers of tumor hypoxia, tumor cell metabolism, DNA repair, cancer stem cells and biomarkers for combining radiotherapy with inhibition of the epidermal growth factor receptor using monoclonal antibodies is described.
    Molecular oncology 02/2012; 6(2):211-21. DOI:10.1016/j.molonc.2012.01.007 · 5.94 Impact Factor
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    ABSTRACT: Purpose This study aimed to further stratify prognostic factors in patients with stage IV non-small cell lung cancer (NSCLC) by measuring their metabolic tumor volume (MTV) using F-18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT). Materials and Methods The subjects of this retrospective study were 57 patients with stage IV NSCLC. MTV, total lesion glycolysis (TLG), and maximum standardized uptake value (SUVmax) were measured on F-18 FDG PET/CT in both the primary lung lesion as well as metastatic lesions in torso. Optimal cutoff values of PET parameters were measured by receiver operating characteristic (ROC) curve analysis. Kaplan-Meier survival curves were used for evaluation of progression-free survival (PFS). The univariate and multivariate Cox proportional hazards models were used to select the significant prognostic factors. Results Univariate analysis showed that both MTV and TLG of primary lung lesion (MTV-lung and TLG-lung) were significant factors for prediction of PFS (P < 0.001, P = 0.038, respectively). Patients showing lower values of MTV-lung and TLG-lung than the cutoff values had significantly longer mean PFS than those with higher values. Hazard ratios (95 % confidence interval) of MTV-lung and TLG-lung measured by univariate analysis were 6.4 (2.5–16.3) and 2.4 (1.0–5.5), respectively. Multivariate analysis revealed that MTV-lung was the only significant factor for prediction of prognosis. Hazard ratio was 13.5 (1.6–111.1, P = 0.016). Conclusion Patients with stage IV NSCLC could be further stratified into subgroups of significantly better and worse prognosis by MTV of primary lung lesion.
    12/2012; 46(4). DOI:10.1007/s13139-012-0165-5
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