DANIELA ANDRADE FERRARO
Projetos de Pesquisa
Unidades Organizacionais
Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/43 - Laboratório de Medicina Nuclear, Hospital das Clínicas, Faculdade de Medicina
LIM/43 - Laboratório de Medicina Nuclear, Hospital das Clínicas, Faculdade de Medicina
8 resultados
Resultados de Busca
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- Diagnostic performance of Ga-68-PSMA-11 PET/MRI-guided biopsy in patients with suspected prostate cancer: a prospective single-center study(2021) FERRARO, Daniela A.; BECKER, Anton S.; KRANZBUHLER, Benedikt; MEBERT, Iliana; BALTENSPERGER, Anka; ZEIMPEKIS, Konstantinos G.; GRUNIG, Hannes; MESSERLI, Michael; RUPP, Niels J.; RUESCHOFF, Jan H.; MORTEZAVI, Ashkan; DONATI, Olivio F.; SAPIENZA, Marcelo T.; EBERLI, Daniel; BURGER, Irene A.Purpose Ultrasound-guided biopsy (US biopsy) with 10-12 cores has a suboptimal sensitivity for clinically significant prostate cancer (sigPCa). If US biopsy is negative, magnetic resonance imaging (MRI)-guided biopsy is recommended, despite a low specificity for lesions with score 3-5 on Prostate Imaging Reporting and Data System (PIRADS). Screening and biopsy guidance using an imaging modality with high accuracy could reduce the number of unnecessary biopsies, reducing side effects. The aim of this study was to assess the performance of positron emission tomography/MRI with Ga-68-labeled prostate-specific membrane antigen (PSMA-PET/MRI) to detect and localize primary sigPCa (ISUP grade group 3 and/or cancer core length >= 6 mm) and guide biopsy. Methods Prospective, open-label, single-center, non-randomized, diagnostic accuracy study including patients with suspected PCa by elevation of prostate-specific antigen (PSA) level and a suspicious lesion (PIRADS >= 3) on multiparametric MRI (mpMRI). Forty-two patients underwent PSMA-PET/MRI followed by both PSMA-PET/MRI-guided and section-based saturation template biopsy between May 2017 and February 2019. Primary outcome was the accuracy of PSMA-PET/MRI for biopsy guidance using section-based saturation template biopsy as the reference standard. Results SigPCa was found in 62% of the patients. Patient-based sensitivity, specificity, negative and positive predictive value, and accuracy for sigPCa were 96%, 81%, 93%, 89%, and 90%, respectively. One patient had PSMA-negative sigPCa. Eight of nine false-positive lesions corresponded to cancer on prostatectomy and one in six false-negative lesions was negative on prostatectomy. Conclusion PSMA-PET/MRI has a high accuracy for detecting sigPCa and is a promising tool to select patients with suspicion of PCa for biopsy.
conferenceObject Quantitative imaging parameters to predict local staging of prostate cancer in intermediate- to high-risk patients(2021) LAUDICELLA, R.; SKAWRAN, S.; FERRARO, D. A.; MUHLEMATTER, U.; MAURER, A.; GRUNIG, H.; DONATI, O.; EBERLI, D.; BURGER, I. A.- Infiltrative growth pattern of prostate cancer is associated with lower uptake on PSMA PET and reduced diffusion restriction on mpMRI(2022) LAUDICELLA, Riccardo; RUESCHOFF, Jan H.; FERRARO, Daniela A.; BRADA, Muriel D.; HAUSMANN, Daniel; MEBERT, Iliana; MAURER, Alexander; HERMANNS, Thomas; EBERLI, Daniel; RUPP, Niels J.; BURGER, Irene A.Purpose Recently, a significant association was shown between novel growth patterns on histopathology of prostate cancer (PCa) and prostate-specific membrane antigen (PSMA) uptake on [Ga-68]PSMA-PET. It is the aim of this study to evaluate the association between these growth patterns and ADC (mm(2)/1000 s) values in comparison to [Ga-68]PSMA uptake on PET/MRI. Methods We retrospectively evaluated patients who underwent [Ga-68]PSMA PET/MRI for staging or biopsy guidance, followed by radical prostatectomy at our institution between 07/2016 and 01/2020. The dominant lesion per patient was selected based on histopathology and correlated to PET/MRI in a multidisciplinary meeting, and quantified using SUVmax for PSMA uptake and ADC(mean) for diffusion restriction. PCa growth pattern was classified as expansive (EXP) or infiltrative (INF) according to its properties of forming a tumoral mass or infiltrating diffusely between benign glands by two independent pathologists. Furthermore, the corresponding WHO2016 ISUP tumor grade was evaluated. The t test was used to compare means, Pearson's test for categorical correlation, Cohen's kappa test for interrater agreement, and ROC curve to determine the best cutoff. Results Sixty-two patients were included (mean PSA 11.7 +/- 12.5). The interrater agreement between both pathologists was almost perfect with kappa=0.81. While 25 lesions had an EXP-growth with an ADC(mean) of 0.777 +/- 0.109, 37 showed an INF-growth with a significantly higher ADC(mean) of 1.079 +/- 0.262 (p < 0.001). We also observed a significant difference regarding PSMA SUVmax for the EXP-growth (19.2 +/- 10.9) versus the INF-growth (9.4 +/- 6.2, p < 0.001). Within the lesions encompassing the EXP- or the INF-growth, no significant correlation between the ISUP groups and ADC(mean) could be observed (p = 0.982 and p = 0.861, respectively). Conclusion PCa with INF-growth showed significantly lower SUVmax and higher ADC(mean) values compared to PCa with EXP-growth. Within the growth groups, ADC(mean) values were independent from ISUP grading.
- Hot needles can confirm accurate lesion sampling intraoperatively using [F-18]PSMA-1007 PET/CT-guided biopsy in patients with suspected prostate cancer(2022) FERRARO, Daniela A.; LAUDICELLA, Riccardo; ZEIMPEKIS, Konstantinos; MEBERT, Iliana; MUELLER, Julian; MAURER, Alexander; GRUENIG, Hannes; DONATI, Olivio; SAPIENZA, Marcelo T.; RUESCHOFF, Jan H.; RUPP, Niels; EBERLI, Daniel; BURGER, Irene A.Purpose Prostate-specific membrane antigen (PSMA)-targeted PET is increasingly used for staging prostate cancer (PCa) with high accuracy to detect significant PCa (sigPCa). [(68) Ga]PSMA-11 PET/MRI-guided biopsy showed promising results but also persisting limitation of sampling error, due to impaired image fusion. We aimed to assess the possibility of intraoperative quantification of [F-18]PSMA-1007 PET/CT uptake in core biopsies as an instant confirmation for accurate lesion sampling. Methods In this IRB-approved, prospective, proof-of-concept study, we included five consecutive patients with suspected PCa. All underwent [F-18]PSMA-1007 PET/CT scans followed by immediate PET/CT-guided and saturation template biopsy (3.1 +/- 0.3 h after PET). The activity in biopsy cores was measured as counts per minute (cpm) in a gamma spectrometer. Pearson's test was used to correlate counts with histopathology (WHO/ISUP), tumor length, and membranous PSMA expression on immunohistochemistry (IHC). Results In 43 of 113 needles, PCa was present. The mean cpm was overall significantly higher in needles with PCa (263 +/- 396 cpm) compared to needles without PCa (73 +/- 44 cpm, p < 0.001). In one patient with moderate PSMA uptake (SUVmax 8.7), 13 out of 24 needles had increased counts (100-200 cpm) but only signs of inflammation and PSMA expression in benign glands on IHC. Excluding this case, ROC analysis resulted in an AUC of 0.81, with an optimal cut-off to confirm PCa at 75 cpm (sens/spec of 65.1%/87%). In all 4 patients with PCa, the first or second PSMA PET-guided needle was positive for sigPCa with high counts (156-2079 cpm). Conclusions [F-18]PSMA-1007 uptake in PCa can be used to confirm accurate lesion sampling of the dominant tumor intraoperatively. This technique could improve confidence in imaging-based biopsy guidance and reduce the need for saturation biopsy.
- What's behind Ga-68-PSMA-11 uptake in primary prostate cancer PET? Investigation of histopathological parameters and immunohistochemical PSMA expression patterns(2021) RUSCHOFF, Jan H.; FERRARO, Daniela A.; MUEHLEMATTER, Urs J.; LAUDICELLA, Riccardo; HERMANNS, Thomas; RODEWALD, Ann-Katrin; MOCH, Holger; EBERLI, Daniel; BURGER, Irene A.; RUPP, Niels J.Purpose Prostate-specific membrane antigen (PSMA-) PET has become a promising tool in staging and restaging of prostate carcinoma (PCa). However, specific primary tumour features might impact accuracy of PSMA-PET for PCa detection. We investigated histopathological parameters and immunohistochemical PSMA expression patterns on radical prostatectomy (RPE) specimens and correlated them to the corresponding Ga-68-PSMA-11-PET examinations. Methods RPE specimens of 62 patients with preoperative Ga-68-PSMA-11-PET between 2016 and 2018 were analysed. WHO/ISUP grade groups, growth pattern (expansive vs. infiltrative), tumour area and diameter as well as immunohistochemical PSMA heterogeneity, intensity and negative tumour area (PSMA(%neg)) were correlated with spatially corresponding SUVmax on Ga-68-PSMA-11-PET in a multidisciplinary analysis. Results All tumours showed medium to strong membranous (2-3 +) and weak to strong cytoplasmic (1-3 +) PSMA expression. Heterogeneously expressed PSMA was found in 38 cases (61%). Twenty-five cases (40%) showed at least 5% and up to 80% PSMA(%neg). PSMA(%neg), infiltrative growth pattern, smaller tumour area and diameter and WHO/ISUP grade group 2 significantly correlated with lower SUVmax values. A ROC curve analysis revealed 20% PSMA(%neg) as an optimal cutoff with the highest sensitivity and specificity (89% and 86%, AUC 0.923) for a negative PSMA-PET scan. A multiple logistic regression model revealed tumoural PSMA(%neg) (p < 0.01, OR = 9.629) and growth pattern (p = 0.0497, OR = 306.537) as significant predictors for a negative PSMA-PET scan. Conclusions We describe PSMA(%neg), infiltrative growth pattern, smaller tumour size and WHO/ISUP grade group 2 as parameters associated with a lower Ga-68-PSMA-11 uptake in prostate cancer. These findings can serve as fundament for future biopsy-based biomarker development to enable an individualized, tumour-adapted imaging approach.
conferenceObject Hot needles can confirm accurate lesion sampling intraoperatively using [F-18]PSMA-1007 PET guided biopsy in patients with suspected prostate cancer(2021) LAUDICELLA, R.; FERRARO, D. A.; ZEIMPEKIS, K. G.; MEBERT, I.; MUELLER, J.; DONATI, O.; SAPIENZA, M. T.; RUSCHOFF, J. H.; RUPP, N.; EBERLI, D.; BURGER, I. A.conferenceObject Infiltrative growth-pattern on histopathology is associated with lower diffusion restriction: a potential reason for false-negative mpMRI in prostate cancer(2021) LAUDICELLA, R.; RUSCHOFF, J. H.; FERRARO, D. A.; HAUSMANN, D.; MEBERT, I.; MAURER, A.; HERMANNS, T.; EBERLI, D.; RUPP, N.; BURGER, I. A.- Development and external validation of a multivariable [68Ga]Ga-PSMA-11 PET-based prediction model for lymph node involvement in men with intermediate or high-risk prostate cancer(2023) MUEHLEMATTER, Urs J.; SCHWEIGER, Lilit; FERRARO, Daniela A.; HERMANNS, Thomas; MAURER, Tobias; HECK, Matthias M.; RUPP, Niels J.; EIBER, Matthias; RAUSCHER, Isabel; BURGER, Irene A.PurposeTo develop and evaluate a lymph node invasion (LNI) prediction model for men staged with [Ga-68]Ga-PSMA-11 PET.MethodsA consecutive sample of intermediate to high-risk prostate cancer (PCa) patients undergoing [Ga-68]Ga-PSMA-11 PET, extended pelvic lymph node dissection (ePLND), and radical prostatectomy (RP) at two tertiary referral centers were retrospectively identified. The training cohort comprised 173 patients (treated between 2013 and 2017), the validation cohort 90 patients (treated between 2016 and 2019). Three models for LNI prediction were developed and evaluated using cross-validation. Optimal risk-threshold was determined during model development. The best performing model was evaluated and compared to available conventional and multiparametric magnetic resonance imaging (mpMRI)-based prediction models using area under the receiver operating characteristic curves (AUC), calibration plots, and decision curve analysis (DCA).ResultsA combined model including prostate-specific antigen, biopsy Gleason grade group, [Ga-68]Ga Ga-PSMA-11 positive volume of the primary tumor, and the assessment of the [Ga-68]Ga-PSMA-11 report N-status yielded an AUC of 0.923 (95% CI 0.863-0.984) in the external validation. Using a cutoff of >= 17%, 44 (50%) ePLNDs would be spared and LNI missed in one patient (4.8%). Compared to conventional and MRI-based models, the proposed model showed similar calibration, higher AUC (0.923 (95% CI 0.863-0.984) vs. 0.700 (95% CI 0.548-0.852)-0.824 (95% CI 0.710-0.938)) and higher net benefit at DCA.ConclusionsOur results indicate that information from [Ga-68]Ga-PSMA-11 may improve LNI prediction in intermediate to high-risk PCa patients undergoing primary staging especially when combined with clinical parameters. For better LNI prediction, future research should investigate the combination of information from both PSMA PET and mpMRI for LNI prediction in PCa patients before RP.