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
11 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.
- Quantitative imaging parameters to predict the local staging of prostate cancer in intermediate- to high-risk patients(2022) LAUDICELLA, Riccardo; SKAWRAN, Stephan; FERRARO, Daniela A.; MUHLEMATTER, Urs J.; MAURER, Alexander; GRUNIG, Hannes; RUSCHOFF, Hendrik J.; RUPP, Niels; DONATI, Olivio; EBERLI, Daniel; BURGER, Irene A.Objectives PSMA PET/MRI showed the potential to increase the sensitivity for extraprostatic disease (EPD) assessment over mpMRI; however, the interreader variability for EPD is still high. Therefore, we aimed to assess whether quantitative PSMA and mpMRI imaging parameters could yield a more robust EPD prediction. Methods We retrospectively evaluated PCa patients who underwent staging mpMRI and [Ga-68]PSMA-PET, followed by radical prostatectomy at our institution between 01.02.2016 and 31.07.2019. Fifty-eight cases with PET/MRI and 15 cases with PET/CT were identified. EPD was determined on histopathology and correlated with quantitative PSMA and mpMRI parameters assessed by two readers: ADC (mm(2)/1000 s), longest capsular contact (LCC, mm), tumor volume (cm(3)), PSMA-SUVmax and volume-based parameters using a fixed threshold at SUV > 4 to delineate PSMA(total) (g/ml) and PSMA(vol) (cm(3)). The t test was used to compare means, Pearson's test for categorical correlation, and ROC curve to determine the best cutoff. Interclass correlation (ICC) was performed for interreader agreement (95% CI). Results Seventy-three patients were included (64.5 +/- 6.0 years; PSA 14.4 +/- 17.1 ng/ml), and 31 had EPD (42.5%). From mpMRI, only LCC reached significance (p = 0.005), while both volume-based PET parameters PSMA(total) and PSMA(vol) were significantly associated with EPD (p = 0.008 and p = 0.004, respectively). On ROC analysis, LCC, PSMA(total), and PSMA(vol) reached an AUC of 0.712 (p = 0.002), 0.709 (p = 0.002), and 0.718 (p = 0.002), respectively. ICC was moderate-good for LCC 0.727 (0.565-0.828) and excellent for PSMA(total) and PSMA(vol) with 0.944 (0.990-0.996) and 0.985 (0.976-0.991), respectively. Conclusions Quantitative PSMA parameters have a similar potential as mpMRI LCC to predict EPD of PCa, with a significantly higher interreader agreement.
- 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.- Ga-68-PSMA-11 PET/MRI versus multiparametric MRI in men referred for prostate biopsy: primary tumour localization and interreader agreement(2022) FERRARO, Daniela A.; HOETKER, Andreas M.; BECKER, Anton S.; MEBERT, Iliana; LAUDICELLA, Riccardo; BALTENSPERGER, Anka; RUPP, Niels J.; RUESCHOFF, Jan H.; MUELLER, Julian; MORTEZAVI, Ashkan; SAPIENZA, Marcelo T.; EBERLI, Daniel; DONATI, Olivio F.; BURGER, Irene A.Background Magnetic resonance imaging (MRI) is recommended by the European Urology Association guidelines as the standard modality for imaging-guided biopsy. Recently positron emission tomography with prostate-specific membrane antigen (PSMA PET) has shown promising results as a tool for this purpose. The aim of this study was to compare the accuracy of positron emission tomography with prostate-specific membrane antigen/magnetic resonance imaging (PET/MRI) using the gallium-labeled prostate-specific membrane antigen (Ga-68-PSMA-11) and multiparametric MRI (mpMRI) for pre-biopsy tumour localization and interreader agreement for visual and semiquantitative analysis. Semiquantitative parameters included apparent diffusion coefficient (ADC) and maximum lesion diameter for mpMRI and standardized uptake value (SUVmax) and PSMA-positive volume (PSMA(vol)) for PSMA PET/MRI. Results Sensitivity and specificity were 61.4% and 92.9% for mpMRI and 66.7% and 92.9% for PSMA PET/MRI for reader one, respectively. RPE was available in 23 patients and 41 of 47 quadrants with discrepant findings. Based on RPE results, the specificity for both imaging modalities increased to 98% and 99%, and the sensitivity improved to 63.9% and 72.1% for mpMRI and PSMA PET/MRI, respectively. Both modalities yielded a substantial interreader agreement for primary tumour localization (mpMRI kappa = 0.65 (0.52-0.79), PSMA PET/MRI kappa = 0.73 (0.61-0.84)). ICC for SUVmax, PSMA(vol) and lesion diameter were almost perfect (>= 0.90) while for ADC it was only moderate (ICC = 0.54 (0.04-0.78)). ADC and lesion diameter did not correlate significantly with Gleason score (rho = 0.26 and rho = 0.16) while SUVmax and PSMA(vol) did (rho = - 0.474 and rho = - 0.468). Conclusions PSMA PET/MRI has similar accuracy and reliability to mpMRI regarding primary prostate cancer (PCa) localization. In our cohort, semiquantitative parameters from PSMA PET/MRI correlated with tumour grade and were more reliable than the ones from mpMRI.
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.- Bone marrow uptake of 18F-fluorodeoxyglucose in Hodgkin lymphoma without bone involvement: comparison between patients with and without B symptoms(2018) VALE, Rômulo Hermeto Bueno do; FERRARO, Daniela Andrade; DUARTE, Paulo Schiavom; CARVALHO, Giovana; LIMA, Marcos Santos; COURA FILHO, George Barbério; SAPIENZA, Marcelo Tatit; BUCHPIGUEL, Carlos AlbertoAbstract Objective: To compare the degree of benign bone marrow uptake of 18F-fluorodeoxyglucose (18F-FDG) between Hodgkin lymphoma patients with and without B symptoms. Materials and Methods: We analyzed the medical charts of 74 Hodgkin lymphoma patients who underwent 18F-FDG positron emission tomography/computed tomography (PET/CT) prior to the initiation of therapy between October 2010 and September 2013. In all of the patients, the bone marrow biopsy was negative and the 18F-FDG PET/CT images did not suggest bone marrow involvement. Of the 74 patients evaluated, 54 presented inflammatory (B) symptoms and 20 did not. Regions of interest (ROIs) were drawn on the sternum, the proximal thirds of the humeri, the proximal thirds of the femora, and both iliac wings (totaling seven ROIs per patient). To compare the patients with and without B symptoms, in terms of standardized uptake values (SUVs) for the seven ROIs, we used the Mann-Whitney U test. Results: For six of the ROIs, the SUVs were higher in the patients with B symptoms than in those without, and the difference was statistically significant (p < 0.05). There was also a tendency toward a statistically significant difference between the two groups in terms of the SUV for the right iliac wing ROI (p = 0.06). Conclusion: In our sample, the presence of B symptoms was associated with increased 18F-FDG uptake in bone marrow.