| 1. |
- Regula, Naresh, et al.
(författare)
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11c-acetate pet/ct accurately predicts prostate-cancer specific survival in patients with biochemical relapse after prostatectomy
- 2016
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Ingår i: Journal of Nuclear Medicine. ; 57:supplement 2, s. 521-
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Tidskriftsartikel (refereegranskat)abstract
- 521Objectives [11C]-acetate PET/CT is clinically used for re-staging of prostate cancer (PCa) at biochemical relapse after prostatectomy, but the long-term predictive value is not known. This study analysed the prognostic value of [11C]-acetate PET/CT and evaluated PET image metrics in relation to survival.Methods All patients undergoing acetate PET/CT in one institution from 2005-2012 due to PSA-relapse after previous prostatectomy were retrospectively evaluated and clinical data were recorded. Patients were grouped as PCa-specific deaths (Cohort I) or censored (Cohort II). All previously reported findings of local recurrence, regional or distal lymph node metastases and bone metastases were counted and evaluated regarding [11C]-acetate uptake intensity (SUVmax) and tumor volume (TV). Total TV and total lesion activity (TLA, summed SUVmax[asterisk]TV) were calculated. Survival analysis in the entire material was followed by Cox-proportional hazards ratios (HR) analysis in patients with at least one PET-positive finding.Results One-hundred twenty-one patients were included and 22 PCa-specific deaths were registered. Median follow-up time was 79 ± 28 months. Mean PSA at time of PET was 2.69 ± 4.35. Post-operative Gleason score (GS) and PSA at time of PET were higher in Cohort I (both p<0.05). PET/CT identified at least one PCa lesion in 53% of patients. Five-year survival was 79% and 100% for a positive and negative PET, respectively (p<0.001). Univariate HR in PET-positive patients was significantly increased for Post-op GS (1.77, p=0.01), tertile of SUVmax (2.35, p=0.005), tertile of TTV (2.74, p=0.001), tertile of TLA (3.33, p<0.001), number of distal lymph node lesions (1.29, p=0.001) and number of bone metastases (2.16, p<0.001). Stepwise multivariate analysis in PET-positive patients showed statistical significance for post-operative GS (HR 1.85, p=0.04), tertile of TLA (HR 5.51, p=0.03) and number of bone metastases (HR 1.75, p=0.01). Survival analysis of TLA showed statistically significant separation of all tertiles (p<0.001).Conclusions [11C]-acetate PET/CT predicts survival in the setting of PSA-relapse after prostatectomy. Volumetric analysis of tumor burden and metabolic activity has incremental value over anatomical and histopathological staging. A negative scan is associated with superior outcome.
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| 2. |
- Regula, Naresh Kumar, et al.
(författare)
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Dynamic Imaging of Prostate Cancer with 11C-acetate PET/CT
- 2017
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Ingår i: Journal of Nuclear Medicine. - 0161-5505 .- 1535-5667. ; 58:S1
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Objectives: Dynamic 11C-acetate PET/CT can be used to study tissue perfusion and carbon flux simultaneously, but studies in cancer are limited. We investigated the kinetics of 11C-acetate in prostate cancer subjects using parametric images with an image-derived input function (IDIF).Methods: Twenty-one patients with newly diagnosed low-moderate risk prostate cancer were studied. All underwent pelvic MRI. Dynamic 11C-acetate (5 MBq/kg) PET/CT of the pelvis was acquired for 32 minutes with 32 time frames. An IDIF was acquired from iliac vessels with multiple small regions of interest (ROIs) and a standardized metabolite correction. Parametric images of K1 (extraction), k2 (oxidative metabolism) and Vd (=K1/k2, anabolic metabolism defined as carbon retention) were constructed using a one-tissue compartment model. ROIs of the largest cancer region in each patient and normal prostate tissue were drawn using information from MRI (T2 and DWI images) and from post-surgical histopathology of whole prostate sections (n=7).Results: Mean PSA was 8.3±3.9. Median Gleason Sum was 6 (range 5-7). K1, Vd and SUVs were higher in cancerous regions compared to normal prostate for all patients (p<0.001). PSA correlated to early SUV (r=0.50, p=0.02) and K1 (r=0.48, p=0.03). Early and late SUVs were correlated to Vd (r>0.76, p<0.001) and K1 (r>0.61, p<0.005).Conclusion: Parametric images could be used to visualize the 11C-acetate kinetics of the prostate. In this cohort of relatively low-risk cancers, PSA values were related to cancer perfusion. SUV of cancerous regions at any time point is primarily associated with anabolic metabolism. Research Support: Swedish Cancer Foundation (Cancerfonden)
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| 3. |
- Regula, Naresh, et al.
(författare)
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Malignant lipogenesis defined by 11C-acetate PET/CT predicts prostate cancer-specific survival in patients with biochemical relapse after prostatectomy
- 2016
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Ingår i: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer Science and Business Media LLC. - 1619-7070 .- 1619-7089. ; 43:12, s. 2131-2138
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Tidskriftsartikel (refereegranskat)abstract
- Malignant de novo lipogenesis is strongly linked to the aggressiveness of prostate cancer (PCa) under experimental conditions. C-11-Acetate PET/CT is a potential noninvasive biomarker of malignant lipogenesis in PCa, but its prognostic value is not known. The objective of this study was to analyse C-11-acetate PET/CT image metrics in relation to survival. All patients undergoing C-11-acetate PET/CT in one university hospital from 2005 to 2011 due to PSA relapse after previous prostatectomy were retrospectively evaluated. Two groups of patients were compared: those who died from PCa and those who were censored. All previously reported findings of local recurrence, regional or distal lymph node metastases and bone metastases were counted and evaluated regarding C-11-acetate uptake intensity (SUVmax) and tumour volume. Total tumour volume and total lipogenic activity (TLA, summed SUVmax x TV) were calculated. Survival analysis in the entire study population was followed by Cox proportional hazards ratio (HR) analysis. A total of 121 patients were included, and 22 PCa-specific deaths were recorded. The mean PSA level at the time of PET was 2.69 +/- 4.35 ng/mL. The median follow-up of the study population was 79 +/- 28 months. PET identified at least one PCa lesion in 53 % of patients. Five-year PCa-specific survival after PET was 80 % and 100 % in patients with a positive and a negative PET scan, respectively (p < 0.001). Time-to-death was linearly correlated with highest SUVmax (r = -0.55, p = 0.01) and nonlinearly with TLA (r = -0.75, p < 0.001). Multivariate analysis showed statistical significance for number of bone metastases (HR 1.74, p = 0.01), tertile of TLA (HR 5.63, p = 0.029) and postoperative Gleason score (HR 1.84, p = 0.045). Malignant C-11-acetate accumulation measured with PET/CT is a strong predictor of survival in the setting of PSA relapse after prostatectomy. The study provides further evidence for a quantitative relationship between malignant de novo lipogenesis and early death. C-11-Acetate PET/CT might be useful for identifying a high-risk population of relapsing patients in which therapies targeting malignant lipogenesis might be of particular benefit.
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| 4. |
- Tammela, T L, et al.
(författare)
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An Intraprostatic Modified Release Formulation of Antiandrogen 2-Hydroxyflutamide for Localized Prostate Cancer
- 2017
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Ingår i: Journal of Urology. - : Ovid Technologies (Wolters Kluwer Health). - 0022-5347 .- 1527-3792. ; 198:6, s. 1333-1339
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To investigate tolerability, safety and antitumor effects of a novel intra-prostatic depot formulation of antiandrogen 2-hydroxyflutamide (2-HOF in NanoZolid(®)) in men with localized prostate cancer (PCa).MATERIALS AND METHODS: Two clinical trials, LPC-002 and LPC-003, were conducted on a total of 47 men. The formulation was injected transrectally into the prostate with ultrasound guidance. In LPC-002 the effects on prostate specific antigen (PSA) and prostate volume (PV) were measured over 6 months on 24 patients. In LPC-003, antitumor effects were evaluated with histopathology, magnetic resonance imaging (MRI) including spectroscopy (MRS) during 6 or 8 weeks on 23 patients. In both studies, testosterone and 2-HOF in plasma were measured, as well as quality-of-life parameters.RESULTS: In LPC-002 (mean dose 690 mg) a reduction in PSA and PV was observed. The nadir values for PSA and PV were on average 24.9 % and 14.0 % below baseline, respectively. When increasing the dose in LPC-003 (920 mg and 1740 mg), the average PSA dropped 16 % and 23 %, respectively, after 6 and 8 weeks. MRI/MRS showed morphological changes and a global drop in metabolite concentrations following treatment indicating an antitumor response. The injections did not result in hormone related side effects. In total, three serious adverse events were reported, all resolved by oral antibiotic treatment.CONCLUSIONS: The intraprostatic injections of 2-HOF depot formulations indicated anti-tumor effects and proved safe and tolerable. However, for better anti-cancer effects higher doses and better dose distribution are suggested.
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| 5. |
- von Below, Catrin, 1970-, et al.
(författare)
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Additional value of magnetic resonance-targeted biopsies to standard transrectal ultrasound-guided biopsies for detection of clinically significant prostate cancer
- 2017
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Ingår i: Scandinavian journal of urology. - : Medical Journals Sweden AB. - 2168-1805 .- 2168-1813. ; 51:2, s. 107-113
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The aim of this study was to evaluate the additional value of magnetic resonance imaging-targeted biopsy (MRI-TB) to standard transrectal ultrasound-guided biopsy (SB) for detection of clinically significant prostate cancer (PCa). An additional aim was to compare the biopsy results to MRI evaluation using a Likert scale.MATERIALS AND METHODS: Patients with newly diagnosed localized PCa (n = 53) by clinical routine SB were prospectively included. The majority of the patients were scheduled for curative therapy before enrollment. The patients underwent multiparametric MRI (mpMRI) at 3 T using an endorectal coil followed by two MRI-TBs, using ultrasound with cognitive fusion. All included patients underwent MRI-TB, even those who had low to very low suspicion of significant PCa on mpMRI. The detection rate of significant cancer on SB versus SB + MRI-TB was compared in the 53 included patients and with whole-mounted histopathology as reference in 34 cases. Comparison of the biopsy results to MRI evaluation and interreader agreement calculation of five-point Likert score evaluation were performed.RESULTS: In total, 32 significant (Gleason ≥7) PCa were detected by SB, while SB + MRI-TB detected an additional five significant PCa. MRI-TB alone detected 20 and missed 17 significant PCa. Ten of the significant PCa cases missed by MRI-TB had a Likert score of 3 or lower. Interreader agreement using the Likert scale was high, with a kappa value of 0.77 (95% confidence interval 0.63-0.92, p < 0.0001).CONCLUSION: Detection of significant PCa increased by adding MRI-TB to SB. This may not be of enough clinical value to justify the use of targeted biopsies in this patient group.
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| 6. |
- von Below, Catrin
(författare)
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PET and MRI of Prostate Cancer
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Prostate cancer (PCa) is the most common non-skin malignancy of men in developed countries. In spite of treatment with curative intent up to 30-40% of patients have disease recurrence after treatment, resulting from any combination of lymphatic, hematogenous, or contiguous local spread.The concept of early detection of PCa offer benefits in terms of reduced mortality, but at the cost of over-diagnosis and overtreatment of indolent disease. This is largely due to the random nature of conventional biopsies, with a risk of missing significant cancer and randomly hitting indolent disease.In the present thesis, diagnostic performance of MRI DWI and 11C Acetate PET/CT lymph node staging of intermediate and high risk PCa, was investigated, and additionally, predictive factors of regional lymph node metastases were evaluated. Further, additional value of targeted biopsies to conventional biopsies, for detection of clinically significant PCa, was investigated.In paper one and two, 53 and 40 patients with predominantly high risk PCa underwent 11C Acetate PET/CT and 3T MRI DWI, respectively, for lymph node staging, before extended pelvic lymph node dissection (ePLND). The sensitivity and specificity for PET/CT was 38% and 96% respectively. The sensitivity and specificity for MRI DWI was 55% and 90% respectively.In paper three, 53 patients with newly diagnosed PCa were included. All patients underwent multi-parametric MRI, followed by two cognitive targeted biopsies. Five more clinically significant cancers were detected by adding targeted biopsies to conventional biopsies.In paper four the value of quantitative and qualitative MRI DWI and 11C Acetate PET/CT parameters, alone and in combination, in predicting regional lymph node metastases were examined. ADCmean in lymph nodes and T-stage on MRI were independent predictors of lymph node metastases in multiple logistic regression analysis.In conclusion the specificity of diffusion weighted MRI and 11C Acetate PET/CT for lymph node staging was high, although the sensitivity was low. Predictive factors of regional lymph node metastases could be retrieved from diffusion weighted MRI and 11C Acetate PET/CT. By combining targeted biopsies with conventional biopsies the detection rate of clinically significant PCa could be increased.
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