NEOadjuvant therapy monitoring with PET and CT in Esophageal Cancer (NEOPEC-trial)

Contains fulltext : 70883.pdf (publisher's version ) (Open Access)ABSTRACT: BACKGROUND: Surgical resection is the preferred treatment of potentially curable esophageal cancer. To improve long term patient outcome, many institutes apply neoadjuvant chemoradiotherapy. In a large proportion of patients no response to chemoradiotherapy is achieved. These patients suffer from toxic and ineffective neoadjuvant treatment, while appropriate surgical therapy is delayed. For this reason a diagnostic test that allows for accurate prediction of tumor response early during chemoradiotherapy is of crucial importance. CT-scan and endoscopic ultrasound have limited accuracy in predicting histopathologic tumor response. Data suggest that metabolic changes in tumor tissue as measured by FDG-PET predict response better. This study aims to compare FDG-PET and CT-scan for the early prediction of non-response to preoperative chemoradiotherapy in patients with potentially curable esophageal cancer. METHODS/DESIGN: Prognostic accuracy study, embedded in a randomized multicenter Dutch trial comparing neoadjuvant chemoradiotherapy for 5 weeks followed by surgery versus surgery alone for esophageal cancer. This prognostic accuracy study is performed only in the neoadjuvant arm of the randomized trial. In 6 centers, 150 consecutive patients will be included over a 3 year period. FDG-PET and CT-scan will be performed before and 2 weeks after the start of the chemoradiotherapy. All patients complete the 5 weeks regimen of neoadjuvant chemoradiotherapy, regardless the test results. Pathological examination of the surgical resection specimen will be used as reference standard. Responders are defined as patients with < 10% viable residual tumor cells (Mandard-score).Difference in accuracy (area under ROC curve) and negative predictive value between FDG-PET and CT-scan are primary endpoints. Furthermore, an economic evaluation will be performed, comparing survival and costs associated with the use of FDG-PET (or CT-scan) to predict tumor response with survival and costs of neoadjuvant chemoradiotherapy without prediction of response (reference strategy). DISCUSSION: The NEOPEC-trial could be the first sufficiently powered study that helps justify implementation of FDG-PET for response-monitoring in patients with esophageal cancer in clinical practice. TRIAL REGISTRATION: ISRCTN45750457

Response monitoring of neoadjuvant therapy using CT, EUS, and FDG-PET

Neoadjuvant or adjuvant multimodality therapy in oesophageal cancer is introduced in an effort to improve prognosis. However, in a substantial fraction of patients there is no response to this non-surgical therapy. Non-invasive imaging modalities such as computed tomography (CT), endoscopic ultrasound (EUS) and 18F-2-fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) have been evaluated for assessing patient response to therapy, and these are described in this review. Currently, FDG-PET seems to be the best available tool for neoadjuvant therapy response assessment in oesophageal cance

Role of positron emission tomography in the (re-)staging of oesophageal cancer

Background. Various studies have demonstrated that 18F-Fluorodeoxyglucose-positron emission tomography (FDG-PET), measuring altered tissue glucose metabolism, is a promising non-invasive method for detecting both distant nodal and haematogenous metastases in patients with oesophageal carcinoma (OC) and might thus prevent futile oesophagectomies. Moreover, FDG-PET is a promising tool in assessing response to non-surgical treatment, and might therefore be used for an early decision on whether treatment should be stopped or continued. Material and methos. Review of the recent literature regarding the diagnostic performance of FDG-PET in the preoperative staging of patients with OC and regarding diagnostic accuracy of FDG-PET in assessing response to neoadjuvant therapy in patients with OC compared to conventional techniques (especially computed tomography (CT) and endoscopic ultrasonography (EUS)). Results. A search of the literature resulted in the inclusion of 16 studies on the diagnostic value of FDG-PET. Sensitivity and specificity for the detection of locoregional metastases were moderate. Sensitivity and specificity were reasonable for distant metastases. The diagnostic accuracy of FDG-PET in assessing response to treatment was similar to the accuracy of EUS, but significantly higher than that of CT. Conclusions. The staging value of FDG-PET in OC patients is limited in the detection of locoregional metastases; however; its value is higher in the detection of distant lymphatic and haematogenous metastases. Moreover, FDG-PET is a valuable tool for the non-invasive assessment of histopathologic tumour response after neoadjuvant therapy

18FDG uptake in oesophageal adenocarcinoma: linking biology and outcome

PURPOSE: Variable uptake of 18FDG has been noticed in positron emission tomography (PET) studies of patients with oesophageal adenocarcinoma. The aim of the present study was to investigate biological parameters involved in 18FDG uptake in oesophageal adenocarcinoma for selection of patients with increased 18FDG uptake and prediction of prognostic value of 18FDG PET. PATIENTS AND METHODS: Preoperative PET scans were performed in 26 patients with histologically proven oesophageal adenocarcinoma. 18FDG uptake was semiquantitatively measured by SUV(BSAg. )Tumour sections were stained by immunohistochemistry for angiogenic markers (VEGF, CD31), glucose transporter-1 (Glut-1), hexokinase (HK) isoforms, for proliferation marker (Ki67), for macrophage marker (CD68) and for apoptosis marker (cleaved caspase-3). Cell densities, differentiation grade, degree of necrosis and mucus, T-stage and tumour size were assessed. In addition follow-up was analysed. RESULTS: No association was found between 18FDG uptake and angiogenic markers. In contrast, a significant correlation was found between 18FDG uptake and Glut-1 expression. No correlations were found between 18FDG uptake and HK isoforms, Ki67 or cleaved caspase-3. Also, no correlations were found between 18FDG uptake and cell density, differentiation grade, CD68, mucus and necrosis. However, there was a significant correlation between 18FDG uptake and tumour size and between 18FDG uptake and tumour recurrence. CONCLUSIONS: Glut-1 expression and tumour size seem parameters associated with 18FDG uptake in patients with biopsy proven oesophageal adenocarcinoma, and may be used to select oesophageal cancer patients in whom 18FDG-PET is of diagnostic value and may predict disease outcom

Influence of ROI definition, partial volume correction and SUV normalization on SUV-survival correlation in oesophageal cancer

Objective An explanation for the discrepancies in the reported correlations between standardized uptake value (SUV) and survival might be the application of different SUV methodologies. The primary aim of this study was to examine the influence of using different methodologies on SUV-survival correlation. Methods Data were used from a prospective cohort study consisting of oesophageal cancer patients in whom preoperative fluorodeoxyglucose positron emission tomography was performed. Various methodologies of SUV calculation/correction were correlated with the default (SUV A41% corrected for body surface area): different volume of interest definitions, different SUV normalization, with and without serum glucose correction, and with (PVC+) and without partial volume correction (PVC-). Receiver operating characteristic (ROC) curves using any type of SUV for the identification of potential correlation with disease-free survival were also compared. Results Fifty-two patients were included for this study. Significant correlations were found between SUV A41% and all the other described SUVs: SUV 50% (r(2) = 0.99; P <0.001), SUV A50% (r(2) = 0.98; P <0.001), SUVmax (r(2) = 0.98; P <0.001), SUV A41% PVC+ (r(2) = 0.97; P <0.001) and SUV A41% glucose (r(2) = 0.93; P <0.001). No correlation was found between volume of interest 41% and SUV A41%, with or without, PVC (P = 0.85 and P = 0.41). Significant correlations were found between SUVmax corrected for body surface area, SUVmax corrected for body weight (r(2) = 0.96; P <0.001) and SUV corrected for lean body mass (r(2) = 0.98; P <0.001). ROC curves for various SUV methodologies showed an almost identical area under the curve for any type of SUV. Conclusion A strong correlation was found between all the investigated SUV methodologies. Moreover, when looking for correlations between SUV and disease-free survival, the areas under the ROC curves were almost identical for any type of SUV methodology. Nucl Med Commun 31:652-658 (C) 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkin

125I-BMIPP and 18F-FDG uptake in a transgenic mouse model of stunned myocardium

Reported metabolic patterns in myocardial stunning are not uniform. We investigated relative myocardial perfusion, glucose and fatty acid uptake using a technetium-99 hexakis-2-methoxyisobutyl-isonitrile (MIBI), fluorine-18 2-fluoro-2-deoxyglucose (FDG) and iodine-125 15-(p-iodo-phenyl)-3(R,S)-methylpentadecanoic acid (BMIPP) mixture, in a recently developed transgenic (TR) mouse model which mimics stunned myocardium. Twenty-seven mice - 14 TR and 13 age-matched wild type controls (C) - were divided into four groups: TR-fed, TR-fasted, C-fed and C-fasted. Animals were sacrificed 2 h after injection, tissue samples counted and percent-injected dose/gram tissue (% id/g) calculated for each radioisotope. Tissues were also Folch extracted and 125I incorporation into the various lipid pools (TG, triglycerides; DG, diglycerides; FFA, free fatty acids; PL, phospholipids) was determined by thin-layer chromatography (TLC). The pooled data for each of the four groups (TR-fed vs C-fed and TR-fed vs C-fasted) showed no differences in myocardial blood flow (% MIBI id/g), glucose uptake (% FDG id/g) or fatty acid uptake (% BMIPP id/g). Only minor differences were observed in the incorporation of 125I-BMIPP into the myocardial TG, DG, FFA and PL lipid pools. However, significantly decreased myocardial FDG uptake was observed in a subset of fasted mice - four out of ten TR-fasted mice (3.4% vs 20.5% id/g) and three out of nine C-fasted mice (5.5% vs 30.6% id/g). The transgenic mouse model of stunned myocardium shows normal myocardial perfusion and overall intact myocardial glucose and myocardial fatty acid uptake as determined with clinically applicable radiolabelled analogues. These data are in line with the hypothesis that the contractile inefficiency in stunned myocardium is not linked to metabolic alterations but is associated with an insufficient chemical to mechanical energy couplin