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11C-acetate PET/MRI in bladder cancer staging and treatment response evaluation to neoadjuvant chemotherapy: a prospective multicenter study (ACEBIB trial).

ABSTRACT: BACKGROUND:To evaluate the accuracy of 11C-acetate Positron Emission Tomography/Magnetic Resonance Imaging (PET/MRI) in bladder cancer (BC) staging and monitoring response to neoadjuvant chemotherapy (NAC). METHODS:Eighteen patients were prospectively enrolled. Fifteen treatment naive patients underwent 11C-acetate PET/MRI before transurethral resection of bladder tumor (TUR-BT) for primary tumor evaluation. Five patients with muscle invasive BC were imaged after NAC and prior to radical cystectomy (RC) with extended pelvic lymph node dissection (ePLND) for NAC treatment response evaluation. Two patients were part of both cohorts. 11C-acetate PET/MRI findings were correlated with histopathology. Accuracy for lymph node detection was evaluated on patient and the ePLND template (10 regions) levels. RESULTS:The sensitivity, specificity and accuracy of 11C-acetate PET/MRI for the detection of muscle invasive BC was 1.00, 0.69 and 0.73 while the area under the receiver operating characteristic curve (95% confidence interval) was 0.85 (0.55-1.0), respectively. All five NAC patients underwent chemotherapy as planned and 11C-acetate PET/MRI correctly staged three patients, overstaged one and understaged one patient compared with RC and ePLND findings. A total of 175 lymph node were removed, median of 35 (range, 27-43) per patient in five patients who had RC and ePLND while 12 (7%) harboured metastases. Sensitivity, specificity, accuracy and AUC for N-staging were 0.20, 0.96, 0.80 and 0.58 on the ePLND template (10 regions) level. CONCLUSIONS:11C-acetate PET/MRI is feasible for staging of BC although sensitivity for the detection of nodal metastases is low. Monitoring response to NAC shows promise and warrants evaluation in larger studies. TRIAL REGISTRATION:ClinicalTrials.gov Identifier: NCT01918592 , registered August 8 2013.

SUBMITTER: Salminen A

PROVIDER: S-EPMC6090957 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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<sup>11</sup>C-acetate PET/MRI in bladder cancer staging and treatment response evaluation to neoadjuvant chemotherapy: a prospective multicenter study (ACEBIB trial).

Salminen Antti A Jambor Ivan I Merisaari Harri H Ettala Otto O Virtanen Johanna J Koskinen Ilmari I Veskimae Erik E Sairanen Jukka J Taimen Pekka P Kemppainen Jukka J Minn Heikki H Boström Peter J PJ

Cancer imaging : the official publication of the International Cancer Imaging Society 20180802 1

<h4>Background</h4>To evaluate the accuracy of <sup>11</sup>C-acetate Positron Emission Tomography/Magnetic Resonance Imaging (PET/MRI) in bladder cancer (BC) staging and monitoring response to neoadjuvant chemotherapy (NAC).<h4>Methods</h4>Eighteen patients were prospectively enrolled. Fifteen treatment naive patients underwent <sup>11</sup>C-acetate PET/MRI before transurethral resection of bladder tumor (TUR-BT) for primary tumor evaluation. Five patients with muscle invasive BC were imaged a ...[more]

PMID: 30068379

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Project description:Despite early detection programs, many patients with prostate cancer present with intermediate- or high-risk disease. We prospectively investigated whether (11)C-acetate PET/CT predicts lymph node (LN) metastasis and treatment failure in men for whom radical prostatectomy is planned.107 men with intermediate- or high-risk localized prostate cancer and negative conventional imaging findings underwent PET/CT with (11)C-acetate. Five underwent LN staging only, and 102 underwent LN staging and prostatectomy. PET/CT findings were correlated with pathologic nodal status. Treatment-failure-free survival was estimated by the Kaplan-Meier method. The ability of PET/CT to predict outcomes was evaluated by multivariate Cox proportional hazards analysis.PET/CT was positive for pelvic LN or distant metastasis in 36 of 107 patients (33.6%). LN metastasis was present histopathologically in 25 (23.4%). The sensitivity, specificity, and positive and negative predictive values of PET/CT for detecting LN metastasis were 68.0%, 78.1%, 48.6%, and 88.9%, respectively. Treatment failed in 64 patients: 25 with metastasis, 17 with a persistent postprostatectomy prostate-specific antigen level greater than 0.20 ng/mL, and 22 with biochemical recurrence (prostate-specific antigen level > 0.20 ng/mL after nadir) during follow-up for a median of 44.0 mo. Treatment-failure-free survival was worse in PET-positive than in PET-negative patients (P < 0.0001) and in those with false-positive than in those with true-negative scan results (P < 0.01), suggesting that PET may have demonstrated nodal disease not removed surgically or identified pathologically. PET positivity independently predicted failure in preoperative (hazard ratio, 3.26; P < 0.0001) and postoperative (hazard ratio, 3.07; P = 0.0001) multivariate models.In patients planned for or completing prostatectomy, (11)C-acetate PET/CT detects LN metastasis not identified by conventional imaging and independently predicts treatment-failure-free survival.

Project description:UNLABELLED:This work characterizes the uptake of (11)C-acetate in prostate cancer (PCa), benign prostate hyperplasia, and normal prostate tissue in comparison with multiparametric MRI, whole-mount histopathology, and clinical markers to evaluate the potential utility of (11)C-acetate for delineating intraprostatic tumors in a population of patients with localized PCa. METHODS:Thirty-nine men with presumed localized PCa underwent dynamic-static abdominal-pelvic (11)C-acetate PET/CT for 30 min and 3-T multiparametric MRI before prostatectomy. PET/CT images were registered to MR images using pelvic bones for initial rotation-translation, followed by manual adjustments to account for prostate motion and deformation from the MRI endorectal coil. Whole-mount pathology specimens were sectioned using an MRI-based patient-specific mold resulting in improved registration between the MRI, PET, and pathology. (11)C-acetate PET standardized uptake values were compared with multiparametric MRI and pathology. RESULTS:(11)C-acetate uptake was rapid but reversible, peaking at 3-5 min after injection and reaching a relative plateau at approximately 10 min. The average maximum standardized uptake value (10-12 min) of tumors was significantly higher than that of normal prostate tissue (4.4 ± 2.05 [range, 1.8-9.2] vs. 2.1 ± 0.94 [range, 0.7-3.4], respectively; P < 0.001); however, it was not significantly different from that of benign prostatic hyperplasia (4.8 ± 2.01 [range, 1.8-8.8]). A sector-based comparison with histopathology, including all tumors greater than 0.5 cm, revealed a sensitivity and specificity of 61.6% and 80.0%, respectively, for (11)C-acetate PET/CT and 82.3% and 95.1%, respectively, for MRI. The (11)C-acetate accuracy was comparable to that of MRI when only tumors greater than 0.9 cm were considered. In a small cohort (n = 9), (11)C-acetate uptake was independent of fatty acid synthase expression using immunohistochemistry. CONCLUSION:(11)C-acetate PET/CT demonstrates higher uptake in tumor foci than in normal prostate tissue; however, (11)C-acetate uptake in tumors is similar to that in benign prostate hyperplasia nodules. Although (11)C-acetate PET/CT is not likely to have utility as an independent modality for evaluation of localized PCa, the high uptake in tumors may make it useful for monitoring focal therapy when tissue damage after therapy may limit anatomic imaging methods.

Project description:INTRODUCTION:11C-acetate (ACE)-PET/CT is used for staging of high-risk prostate cancer. PET data is reconstructed with iterative algorithms, such as VUEPointHD ViP (VPHD) and VUEPoint HD Sharp IR (SharpIR), the latter with additional resolution recovery. It is expected that the resolution recovery algorithm should render more accurate maximum and mean standardized uptake values (SUVmax and SUVmean) and functional tumor volumes (FTV) than the ordinary OSEM. Performing quantitative analysis, choice of volume-of-interest delineation algorithm (SUV threshold) may influence FTV. Optimizing PET acquisition time is justified if image quality and quantitation do not deteriorate. The aim of this study is to identify the optimal reconstruction algorithm, SUV threshold and acquisition time for ACE-PET/CT. METHODS:ACE-PET/CT data acquired with a General Electric Discovery 690 PET/CT from 16 consecutive high-risk prostate cancer patients was reconstructed with VPHD and SharpIR. Forty pelvic lymph nodes (LNs) and 14 prostate glands were delineated with 42% and estimated threshold. SUVmax, SUVmean, FTV and total lesion uptake were measured. Default acquisition time was four minutes per bed position. In a subset of lesions, acquisition times of one, two and four minutes were evaluated. Structural tumor volumes (STV) of the LNs were measured with CT for correlation with functional volumetric parameters. To validate SUV quantification under different conditions with SharpIR 42%, recovery coefficients (RCs) of SUVmean and FTV were calculated from a phantom with 18F-fluoro-deoxy-glucose (FDG)-filled volumes 0.1-9.2cm3 and signal-to-background (S/B) ratios 4.3-15.9. RESULTS:With SharpIR, SUVmax and SUVmean were higher and FTV lower compared with VPHD, regardless of threshold method, in both prostates and LNs. Total lesion uptake determined with both threshold methods was lower with SharpIR compared with VPHD with both threshold methods, except in subgroup analysis of prostate targets where estimated threshold returned higher values. Longer acquisition times returned higher FTV for both threshold methods, regardless of reconstruction algorithm. The FTV difference was most pronounced with one minute's acquisition per bed position, which also produced visually the highest noise. SUV parameters were unaffected by varying acquisition times. FTV with SharpIR 42% showed the best correspondence with STV. SharpIR 42% gave higher RCs of SUVmean and FTV with increasing phantom size and S/B-ratio, as expected. CONCLUSIONS:Delineation with SharpIR 42% seems to provide the most accurate combined information from SUVmax, SUVmean, FTV and total lesion uptake. Acquisition time may be shortened to two minutes per bed position with preserved image quality.

Project description:BackgroundThe aim of this study was to evaluate whether MP [11C]Acetate PET-MRI enables an accurate differentiation of benign and malignant prostate tumors as well as local and distant staging.Materials and methodsFifty-six consecutive patients fulfilling the following criteria were included in this IRB-approved prospective study: elevated PSA levels or suspicious findings at digital rectal examination or TRUS; and histopathological verification. All patients underwent MP [11C]Acetate PET-MRI of the prostate performed on separate scanners with PET/CT using [11C]Acetate and 3T MP MR imaging. Appropriate statistical tests were used to determine diagnostic accuracy, local and distant staging.ResultsMP imaging with two MRI parameters (T2w and DWI) achieved the highest sensitivity, specificity, and diagnostic accuracy of 95%, 68.8%, and 88%, with an AUC of 0.82 for primary PCa detection. Neither assessments with a single parameter (AUC, 0.54-0.79), nor different combinations with up to five parameters (AUC, 0.67-0.79) achieved equally good results. MP [11C]Acetate PET-MRI improved local staging with a sensitivity, specificity, and diagnostic accuracy of 100%, 96%, and 97% compared to MRI alone with 72.2%, 100%, and 95.5%. MP [11C]Acetate PET-MRI correctly detected osseous and liver metastases in five patients.ConclusionsMP [11C]Acetate PET-MRI merges morphologic with functional information, and allows insights into tumor biology. MP [11C]Acetate PET-MRI with two MRI-derived parameters (T2 and DWI) yields the highest diagnostic accuracy. The addition of more parameters does not improve diagnostic accuracy of primary PCa detection. MP [11C]Acetate PET-MRI facilitates improved local and distant staging, providing "one-stop" staging in patients with primary PCa, and therefore has the potential to improve therapy.Patient summaryIn this report we investigated MP [11C]Acetate PET-MRI for detection, local and distant staging of prostate cancer. We demonstrate that MP [11C]Acetate PET-MRI with two MRI-derived parameters (T2 and DWI) achieves the best diagnostic accuracy for primary prostate cancer detection and that MP [11C]Acetate PET-MRI enables an improved local and distant staging.

Dataset Information

11C-acetate PET/MRI in bladder cancer staging and treatment response evaluation to neoadjuvant chemotherapy: a prospective multicenter study (ACEBIB trial).

Publications

<sup>11</sup>C-acetate PET/MRI in bladder cancer staging and treatment response evaluation to neoadjuvant chemotherapy: a prospective multicenter study (ACEBIB trial).

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