Dataset Information

Prediction of PSA Progression in Castration-Resistant Prostate Cancer Based on Treatment-Associated Change in Tumor Burden Quantified by 18F-Fluorocholine PET/CT.

ABSTRACT: Measurements of metabolically active tumor volume (MATV) can be applied to (18)F-fluorocholine PET/CT to quantify whole-body tumor burden. This study evaluated the serial application of these measurements as systemic treatment response markers and predictors of disease progression in patients with castration-resistant prostate cancer (CRPC).Forty-two patients completed sequential (18)F-fluorocholine PET/CT scans before and 1-3 mo after starting treatment for CRPC. Whole-body tumor segmentation was applied to determine net MATV from each scan. Changes in net MATV were evaluated as predictors of time to prostate-specific antigen (PSA) progression by Kaplan-Meier and proportional hazards regression analysis.Treatments consisted of chemotherapy in 16 patients, antiandrogens in 19 patients, (223)Ra-dichloride in 5 patients, and sipuleucel-T in 2 patients. A significant MATV response (defined as a ?30% decrease in net MATV) was observed in 20 patients on the basis of in-treatment PET/CT performed an average of 51 d (median, 49 d) into treatment. Significantly longer times to PSA progression were observed in patients who exhibited an MATV response (418 d vs. 116 d, P = 0.0067). MATV response was associated with a hazard ratio of 0.246 (P = 0.0113) for PSA progression, which remained significant when adjusted for treatment type.Significant changes in whole-body tumor burden can be measured on (18)F-fluorocholine PET/CT over the course of contemporary treatments for CRPC. In this study, these changes were found to be predictive of PSA progression as a potential surrogate marker of treatment outcome. Because (18)F-fluorocholine PET/CT can also be used for localizing resistant tumors, this modality can potentially complement other measures of response in the precision management of advanced prostate cancer.

SUBMITTER: Lee J

PROVIDER: S-EPMC5153372 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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Prediction of PSA Progression in Castration-Resistant Prostate Cancer Based on Treatment-Associated Change in Tumor Burden Quantified by 18F-Fluorocholine PET/CT.

Lee Joohee J Sato Miles M MM Coel Marc N MN Lee Kyung-Han KH Kwee Sandi A SA

Journal of nuclear medicine : official publication, Society of Nuclear Medicine 20160216 7

<h4>Unlabelled</h4>Measurements of metabolically active tumor volume (MATV) can be applied to (18)F-fluorocholine PET/CT to quantify whole-body tumor burden. This study evaluated the serial application of these measurements as systemic treatment response markers and predictors of disease progression in patients with castration-resistant prostate cancer (CRPC).<h4>Methods</h4>Forty-two patients completed sequential (18)F-fluorocholine PET/CT scans before and 1-3 mo after starting treatment for CR ...[more]

PMID: 26912444

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Project description:The purpose of this study was to compare the diagnostic performance of 18F-DCFBC PET/CT, a first-generation 18F-labeled prostate-specific membrane antigen (PSMA)-targeted agent, and 18F-NaF PET/CT, a sensitive marker of osteoblastic activity, in a prospective cohort of patients with metastatic prostate cancer. Methods: Twenty-eight prostate cancer patients with metastatic disease on conventional imaging prospectively received up to 4 PET/CT scans. All patients completed baseline 18F-DCFBC PET/CT and 18F-NaF PET/CT scans, and 23 patients completed follow-up imaging, with a median follow-up interval of 5.7 mo (range, 4.2-12.6 mo). Lesion detection was compared across the 2 PET/CT agents at each time point. Detection and SUV characteristics of each PET/CT agent were compared with serum prostate-specific antigen (PSA) levels and treatment status at the time of baseline imaging using nonparametric statistical testing (Spearman correlation, Wilcoxon rank). Results: Twenty-six patients had metastatic disease detected on 18F-NaF or 18F-DCFBC at baseline, and 2 patients were negative on both scans. Three patients demonstrated soft tissue-only disease. Of 241 lesions detected at baseline, 56 were soft-tissue lesions identified by 18F-DCFBC only and 185 bone lesions detected on 18F-NaF or 18F-DCFBC. 18F-NaF detected significantly more bone lesions than 18F-DCFBC (P < 0.001). Correlation of PSA with patient-level SUV metrics was strong in 18F-DCFBC (? > 0.5, P < 0.01) and poor in 18F-NaF (? < 0.3, P > 0.1). When PSA levels were combined with treatment status, patients with below-median levels of PSA (<2 ng/mL) on androgen deprivation therapy (n = 11) demonstrated more lesions on 18F-NaF than 18F-DCFBC (P = 0.02). In PSA greater than 2 ng/mL, patients on androgen deprivation therapy (n = 8) showed equal to or more lesions on 18F-DCFBC than on 18F-NaF. Conclusion: The utility of PSMA-targeting imaging in metastatic prostate cancer appears to depend on patient disease course and treatment status. Compared with 18F-NaF PET/CT, 18F-DCFBC PET/CT detected significantly fewer bone lesions in the setting of early or metastatic castrate-sensitive disease on treatment. However, in advanced metastatic castrate-resistant prostate cancer, 18F-DCFBC PET/CT shows good concordance with NaF PET/CT.

Project description:UnlabelledConventional imaging modalities (CIMs) have limited sensitivity and specificity for detection of metastatic prostate cancer. We examined the potential of a first-in-class radiofluorinated small-molecule inhibitor of prostate-specific membrane antigen (PSMA), N-[N-[(S)-1,3-dicarboxypropyl]carbamoyl]-4-(18)F-fluorobenzyl-l-cysteine ((18)F-DCFBC), to detect metastatic hormone-naïve (HNPC) and castration-resistant prostate cancer (CRPC).MethodsSeventeen patients were prospectively enrolled (9 HNPC and 8 CRPC); 16 had CIM evidence of new or progressive metastatic prostate cancer and 1 had high clinical suspicion of metastatic disease. (18)F-DCFBC PET/CT imaging was obtained with 2 successive PET scans starting at 2 h after injection. Patients were imaged with CIM at approximately the time of PET. A lesion-by-lesion analysis of PET to CIM was performed in the context of either HNPC or CRPC. The patients were followed with available clinical imaging as a reference standard to determine the true nature of identified lesions on PET and CIM.ResultsOn the lesion-by-lesion analysis, (18)F-DCFBC PET was able to detect a larger number of lesions (592 positive with 63 equivocal) than CIM (520 positive with 61 equivocal) overall, in both HNPC and CRPC patients. (18)F-DCFBC PET detection of lymph nodes, bone lesions, and visceral lesions was superior to CIM. When intrapatient clustering effects were considered, (18)F-DCFBC PET was estimated to be positive in a large proportion of lesions that would be negative or equivocal on CIM (0.45). On follow-up, the sensitivity of (18)F-DCFBC PET (0.92) was superior to CIM (0.71). (18)F-DCFBC tumor uptake was increased at the later PET time point (~2.5 h after injection), with background uptake showing a decreasing trend on later PET.ConclusionPET imaging with (18)F-DCFBC, a small-molecule PSMA-targeted radiotracer, detected more lesions than CIM and promises to diagnose and stage patients with metastatic prostate cancer more accurately than current imaging methods.

Project description:BACKGROUND:Recently, the block-sequential regularized expectation maximization (BSREM) reconstruction algorithm was commercially introduced (Q.Clear, GE Healthcare, Milwaukee, WI, USA). However, the combination of noise-penalizing factor (β), acquisition time, and administered activity for optimal image quality has not been established for 18F-fluorocholine (FCH). The aim was to compare image quality and diagnostic performance of different reconstruction protocols for patients with prostate cancer being examined with 18F-FCH on a silicon photomultiplier-based PET-CT. Thirteen patients were included, injected with 4 MBq/kg, and images were acquired after 1 h. Images were reconstructed with frame durations of 1.0, 1.5, and 2.0 min using β of 150, 200, 300, 400, 500, and 550. An ordered subset expectation maximization (OSEM) reconstruction with a frame duration of 2.0 min was used for comparison. Images were quantitatively analyzed regarding standardized uptake values (SUV) in metastatic lymph nodes, local background, and muscle to obtain contrast-to-noise ratios (CNR) as well as the noise level in muscle. Images were analyzed regarding image quality and number of metastatic lymph nodes by two nuclear medicine physicians. RESULTS:The highest median CNR was found for BSREM with a β of 300 and a frame duration of 2.0 min. The OSEM reconstruction had the lowest median CNR. Both the noise level and lesion SUVmax decreased with increasing β. For a frame duration of 1.5 min, the median quality score was highest for β 400-500, and for a frame duration of 2.0 min the score was highest for β 300-500. There was no statistically significant difference in the number of suspected lymph node metastases between the different image series for one of the physicians, and for the other physician the number of lymph nodes differed only for one combination of image series. CONCLUSIONS:To achieve acceptable image quality at 4 MBq/kg 18F-FCH, we propose using a β of 400-550 with a frame duration of 1.5 min. The lower β should be used if a high CNR is desired and the higher if a low noise level is important.

Dataset Information

Prediction of PSA Progression in Castration-Resistant Prostate Cancer Based on Treatment-Associated Change in Tumor Burden Quantified by 18F-Fluorocholine PET/CT.

Publications

Prediction of PSA Progression in Castration-Resistant Prostate Cancer Based on Treatment-Associated Change in Tumor Burden Quantified by 18F-Fluorocholine PET/CT.

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