Hypoxia imaging with 18F-FAZA PET/CT predicts radiotherapy response in esophageal adenocarcinoma xenografts.
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ABSTRACT:
SUBMITTER: Melsens E
PROVIDER: S-EPMC5842657 | biostudies-literature | 2018 Mar
REPOSITORIES: biostudies-literature
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Hypoxia imaging with <sup>18</sup>F-FAZA PET/CT predicts radiotherapy response in esophageal adenocarcinoma xenografts.
Melsens Elodie E De Vlieghere Elly E Descamps Benedicte B Vanhove Christian C Kersemans Ken K De Vos Filip F Goethals Ingeborg I Brans Boudewijn B De Wever Olivier O Ceelen Wim W Pattyn Piet P
Radiation oncology (London, England) 20180307 1
<h4>Background</h4>Esophageal cancer is an aggressive disease with poor survival rates. A more patient-tailored approach based on predictive biomarkers could improve outcome. We aimed to predict radiotherapy (RT) response by imaging tumor hypoxia with <sup>18</sup>F-FAZA PET/CT in an esophageal adenocarcinoma (EAC) mouse model. Additionally, we investigated the radiosensitizing effect of the hypoxia modifier nimorazole in vitro and in vivo.<h4>Methods</h4>In vitro MTS cell proliferation assays ( ...[more]
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Project description:BACKGROUND:To identify whether early metabolic responses as determined using 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) during radiotherapy (RT) predict outcomes in patients with esophageal cancer. METHODS:Twenty-one patients with esophageal cancer who received pre-treatment 18F-FDG PET/CT (PET1) and inter-fractional 18F-FDG PET/CT (PET2) after 11 fractions of RT (median 23.1?Gy, 2.1?Gy per fraction) were retrospectively reviewed. The region of interest for each calculation was delineated using "PET Edge". We calculated PET parameters including maximum and mean standardized uptake values (SUVmax and SUVmean, respectively), metabolic tumor volume (MTV), and total lesion glycolysis (TLG). The relative changes (%) were calculated using the logarithmically transformed parameter values for the PET1 and PET2 scans. Multivariate analysis of locoregional recurrence and distant failures were performed using Cox regression analysis. After identifying statistically significant PET parameters for discriminating responders from non-responders, receiver operating characteristics curve analyses were used to assess the potentials of the studied PET parameters. RESULTS:After a median follow-up of 13?months, the 1-year overall and progression-free survival rates were 79.0% and 34.4%, respectively. Four patients developed locoregional recurrences (LRRs) and 8 had distant metastases (DMs). The 1-year overall LRR-free rate was 76.9% while the DM-free rate was 60.6%. The relative changes in MTV (?MTV) were significantly associated with LRR (p =?0.03). Conversely, the relative changes in SUVmean (?SUVmean) were associated with the risk of DM (p =?0.02). An ?MTV threshold of 1.14 yielded a sensitivity of 60%, specificity of 94%, and an accuracy of 86% for predicting an LRR. Additionally, a ?SUVmean threshold of a 35% decrease yielded a sensitivity of 67%, specificity of 83%, and accuracy of 76% for the prediction DM. TRIAL REGISTRATION:Retrospectively registered. CONCLUSIONS:Changes in tumor metabolism during RT could be used to predict treatment responses, recurrences, and prognoses in patients with esophageal cancer.
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Project description:BACKGROUND:Although 18F- FDG PET/CT is validated in baseline workup of esophageal cancer to detect distant metastases, it remains underused in assessing local staging and biology of the primary tumor. This study aimed to evaluate the association between 18F- FDG PET/CT-derived parameters of esophageal cancer, and its clinico-pathological features and prognosis. METHODS:All patients (n = 86) with esophageal adenocarcinoma or squamous cell cancer operated between 2005 and 2014 were analyzed. Linear regression was used to identify clinico-pathologic features of esophageal cancer associated with the tumor's maximal Standardized Uptake Value (SUVmax), Total Lesion Glycolysis (TLG) and Metabolic Tumor Volume (MTV). ROC curve analysis was performed to precise the optimal cutoff of each variable associated with a locally advanced (cT3/4) status, long-term survival and recurrence. Kaplan Meier curves and Cox regression were used for survival analyses. RESULTS:High baseline SUVmax was associated with cT3/4 status and middle-third tumor location, TLG with a cT3/4 and cN+ status, whereas MTV only with active smoking. A cT3/4 status was significantly predicted by a SUVmax > 8.25 g/mL (p < 0.001), TLG > 41.7 (p < 0.001) and MTV > 10.70 cm3 (p < 0.01) whereas a SUVmax > 12.7 g/mL was associated with an early tumor recurrence and a poor disease-free survival (median 13 versus 56 months, p = 0.030), particularly in squamous cell cancer. CONCLUSIONS:Baseline 18F- FDG PET/CT has a high predictive value of preoperative cT stage, as its parameters SUVmax, TLG and MTV can predict a locally advanced tumor with high accuracy. A SUVmax > 12.7 g/mL may herald early tumor recurrence and poor disease-free survival.
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