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Evaluating indeterminate bone lesions and lymph nodes on PSMA-PET: a multidisciplinary consensus algorithm and 1-year implementation results

Woo, Sungmin; Tong, Angela; Becker, Anton S; Friedman, Kent P; Leithner, Doris; Charbel, Charlotte; Mayerhoefer, Marius E; Kostakoglu Shields, Lale; Wysock, James S; Tan, Wei Phin; Pak, Jamie S; Lepor, Herbert; Aghdam, Nima; Mahadevan, Anand; Economides, Minas P; Deng, Fang-Ming; Taneja, Samir S; Zelefsky, Michael J; Wise, David R; Vargas, Hebert A
OBJECTIVE:Indeterminate lesions on prostate-specific membrane antigen (PSMA)-PET are challenging to address. We aimed to develop, implement, and evaluate a multidisciplinary consensus algorithm that integrates existing interpretation systems with multimodality imaging and clinicopathological information for interpreting indeterminate bone and lymph node lesions on PSMA-PET. MATERIALS AND METHODS/METHODS:This was a retrospective single-center study on a prospectively implemented algorithm. We included all consecutive prostate cancer patients whose PSMA-PET findings for indeterminate bone lesions or lymph nodes were discussed at a multidisciplinary tumor board (MDT) in 2024-2025. An algorithm determining the level of suspicion for metastasis was developed in a multidisciplinary fashion, incorporating lesion location, conventional imaging features, PSMA-PET characteristics, and clinicopathological information. The application of the algorithm and outcomes were documented, compared against a composite reference standard. Comparisons were made with PSMA-RADS and PROMISE V2 PSMA-expression scores. RESULTS:81 patients (median age 68, interquartile range 64-75) were included. Algorithm results were benign (48.1% [39/81]), equivocal (4.9% [4/81]), metastasis (40.7% [33/81]), and mixed (benign and metastatic lesions, 6.2% [5/81]). The algorithm was correct in 94.1% (64 of 68 patients with a sufficient reference standard). The algorithm was discordant with PSMA-RADS in 54.3% (44/81) and with PROMISE V2 PSMA-expression score in 71.6% (58/81). The frequency of equivocal lesions was lower using the algorithm (4.9% [4/81]) compared with PSMA-RADS (53.1% [43/81]) and PSMA-expression score (64.2% [52/81]). CONCLUSION/CONCLUSIONS:A multidisciplinary consensus algorithm for interpreting indeterminate bone lesions and lymph nodes on PSMA-PET was developed and implemented. Integrating clinicopathological information and multimodality imaging in an MDT setting reduced equivocal interpretations. KEY POINTS/CONCLUSIONS:Question While prostate-specific membrane antigen (PSMA)-PET has become essential in the management of prostate cancer, indeterminate bone lesions and lymph nodes remain challenging to address. Findings A multidisciplinary algorithm for interpreting indeterminate bone lesions and lymph nodes on PSMA-PET, incorporating clinicopathological information and multimodality imaging, reduced the frequency of equivocal interpretations. Clinical relevance An algorithm for interpreting indeterminate bone lesions and lymph nodes on PSMA-PET, incorporating clinicopathological information and multimodality imaging in a multidisciplinary tumor board setting, decreases the frequency of equivocal interpretations and can potentially help management decisions.
PMID: 41493546
ISSN: 1432-1084
CID: 5980782

Implementing a Combined Lesion Measurement Tool in Hybrid PET Imaging to Reduce Clicks in Routine Clinical Practice: a Single-Center Brief Report

Becker, Anton S; Lindow, Norbert; Noorily, Ariella; Masci, Benedetta; Woo, Sungmin; Leithner, Doris; Friedman, Kent; Mayerhoefer, Marius E; Westerhoff, Malte; Vargas, H Alberto
OBJECTIVE:To develop a tool for the clinical hybrid imaging workflow which combines morphologic and functional measurements. And to quantify the number of clicks saved per positron emission tomography/computed tomography (PET/CT) interpretation. METHODS:A tool was developed where a volume of interest (VOI) is automatically created around line distance measurements. VOI statistics for both PET and CT component, and line distances are generated and displayed. Usage data for the first two months after introduction of the tool was analyzed. RESULTS:Eleven radiologists and nuclear medicine physicians used the tool in 364 PET/CTs. In 19% of examinations, the novel tool was the only tool that needed to be used. The novel combined tool was used 1001 times, whereas the traditional spherical VOI had been placed 1131 times. The usage ratio of new to traditional tool differed significantly between examinations with ≤ 6 annotations (ratio 1.0) versus > 6 annotations (ratio 0.63, p = 0.030). The average number of saved clicks per PET/CT was estimated at 16.5. CONCLUSION/CONCLUSIONS:A novel combined measurement tool for hybrid imaging was implemented and saved on average 16.5 clicks per examination. These improvements contribute to a smoother workflow and demonstrate the positive impact of thoughtful software design in medical practice.
PMID: 41381982
ISSN: 1573-689x
CID: 5977942

Navigating discordant findings in multimodality imaging of prostate cancer in the MRI and PSMA-PET era

Woo, Sungmin; Masci, Benedetta; Becker, Anton S; Tong, Angela; Friedman, Kent P; de Galiza Barbosa, Felipe; Caruso, Damiano; Laghi, Andrea; Vargas, Hebert Alberto
Various imaging modalities play key roles throughout the different stages of prostate cancer. Each imaging modality has different strengths and weaknesses and various scoring systems or frameworks are used to interpret their findings. Discordances between imaging modalities or interpretation frameworks, and even with clinicopathological findings are not uncommon. Discordances often lead to challenges in the decision-making process, especially with dynamically changing indications for newer imaging modalities. While more research is needed on harmonizing interpretations across different modalities, multidisciplinary team discussion is key to optimizing management of patients with prostate cancer when such discordances are present. In this comprehensive review, we take a deep dive in to these various discordances seen in clinical practice and explore their clinical implications.
PMID: 41182592
ISSN: 1826-6983
CID: 5959432

Evaluating extraprostatic extension of prostate cancer: pragmatic integration of MRI and PSMA-PET/CT

Woo, Sungmin; Freedman, Daniel; Becker, Anton S; Leithner, Doris; Charbel, Charlotte; Mayerhoefer, Marius E; Friedman, Kent P; Tong, Angela; Wise, David R; Taneja, Samir S; Zelefsky, Michael J; Vargas, Hebert Alberto
PURPOSE/OBJECTIVE:To explore pragmatic approaches integrating MRI and PSMA-PET/CT for evaluating extraprostatic extension (EPE) of prostate cancer (PCa). METHODS:>12). Diagnostic performance was tested with receiver operating characteristic (ROC) curves and compared using DeLong and McNemar tests. RESULTS:>12 among which 87.5% (7/8) were corrected upgraded and had pathological EPE. CONCLUSION/CONCLUSIONS:Several pragmatic approaches were explored for integrating MRI and PSMA-PET/CT to assess EPE in PCa. Combining morphological information from MRI and PSMA expression on PET/CT demonstrated good diagnostic performance and may be a simple pragmatic integrated method that can be used.
PMID: 40252100
ISSN: 2366-0058
CID: 5829182

PSMA-avid rib lesions in prostate cancer patients: differentiating false positives from metastatic disease

Woo, Sungmin; Becker, Anton S; Leithner, Doris; Charbel, Charlotte; Mayerhoefer, Marius E; Friedman, Kent P; Tong, Angela; Murina, Sofya; Siskin, Matthew; Taneja, Samir S; Zelefsky, Michael J; Wise, David R; Vargas, Hebert A
OBJECTIVES/OBJECTIVE:Prostate-specific membrane antigen (PSMA)-PET/CT has become integral to management of prostate cancer; however, PSMA-avid rib lesions pose a diagnostic challenge. This study investigated clinicopathological and imaging findings that predict metastatic etiology of PSMA-avid rib lesions. MATERIALS AND METHODS/METHODS:), miPSMA score), CT features (sclerotic, lucent, fracture, no correlate), other sites of metastases, and primary tumor findings. A composite reference standard for rib lesion etiology (metastatic vs non-metastatic) based on histopathology, serial imaging, and clinical assessment was used. RESULTS:, miPSMA), more commonly involved multiple ribs, and were more often sclerotic (p < 0.01); lucency/fractures were only seen in benign lesions. CONCLUSION/CONCLUSIONS:Several imaging and clinicopathological factors differed between PSMA-avid metastatic and benign lesions. Isolated rib lesions without other sites of metastasis are almost always benign. Careful assessment of CT features can help diagnose benign lesions. KEY POINTS/CONCLUSIONS:Question While prostate-specific membrane antigen (PSMA)-PET/CT has become integral to the management of prostate cancer, PSMA-avid rib lesions pose a diagnostic challenge. Findings Approximately a quarter of patients who had PSMA-avid rib lesions were metastatic. However, only 2.1% of them had isolated rib metastasis (without PSMA-avid metastases elsewhere). Clinical relevance Isolated PSMA-avid rib lesions are almost always benign when there is no evidence of metastatic disease elsewhere. Scrutinizing CT features can help diagnose benign PSMA-avid lesions with greater certainty.
PMID: 40108014
ISSN: 1432-1084
CID: 5813442

CT, I-123-Ioflupane SPECT, and Integrated FDG PET-MRI of a Patient With Fahr Disease

Loftus, James Ryan; Friedman, Kent P; Wisniewski, Thomas M; Shepherd, Timothy M
Fahr disease is a rare neurodegenerative syndrome characterized by abnormal symmetric calcium deposition in the white matter, cerebral cortex, deep gray, and cerebellar nuclei. The characteristic CT pattern is well known, but descriptions of molecular imaging in Fahr disease remain sparse. We present the characteristic imaging patterns of Fahr disease by CT, I-123-Ioflupane SPECT, and integrated FDG PET/MRI in a single patient.
PMID: 40392166
ISSN: 1536-0229
CID: 5852972

Discordance between prostate MRI and PSMA-PET/CT: the next big challenge for primary prostate tumor assessment?

Woo, Sungmin; Becker, Anton S; Leithner, Doris; Mayerhoefer, Marius E; Friedman, Kent P; Tong, Angela; Wise, David R; Taneja, Samir S; Zelefsky, Michael J; Vargas, Hebert A
OBJECTIVES/OBJECTIVE:An increasing number of patients with prostate cancer (PCa) undergo assessment with magnetic resonance imaging (MRI) and prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA-PET/CT). This offers comprehensive multimodality staging but can lead to discrepancies. The objective was to assess the rates and types of discordance between MRI and PSMA-PET/CT for primary PCa assessment. MATERIALS AND METHODS/METHODS:Consecutive men diagnosed with intermediate and high-risk PCa who underwent MRI and PSMA-PET/CT in 2021-2023 were retrospectively included. MRI and PSMA-PET/CT were interpreted using PI-RADS v2.1 and PRIMARY scores. Discordances between the two imaging modalities were categorized as "minor" (larger or additional lesion seen on one modality) or "major" (positive on only one modality or different index lesions between MRI and PSMA-PET/CT) and reconciled using radical prostatectomy or biopsy specimens. RESULTS:Three hundred and nine men (median age 69 years, interquartile range (IQR) 64-75) were included. Most had Gleason Grade Group ≥ 3 PCa (70.9% (219/309)). Median PSA was 9.0 ng/mL (IQR 5.6-13.6). MRI and PSMA-PET/CT were concordant in 157/309 (50.8%) and discordant in 152/309 (49.1%) patients; with 39/152 (25.7%) major and 113/152 (74.3%) minor discordances. Of 27 patients with lesions only seen on MRI, 85.2% (23/27) were clinically significant PCa (csPCa). Of 23 patients with lesions only seen on PSMA-PET/CT, 78.3% (18/23) were csPCa. Altogether, lesions seen on only one modality were csPCa in 80.0% (36/45). CONCLUSION/CONCLUSIONS:MRI and PSMA-PET/CT were discordant in half of patients for primary PCa evaluation, with major discrepancies seen in roughly one out of eight patients. KEY POINTS/CONCLUSIONS:Question While both MRI and PSMA-PET/CT can be used for primary tumor assessment, the discordances between them are not well established. Findings MRI and PSMA-PET/CT were discordant in about half of the patients. Most prostate lesions seen on only one modality were significant cancer. Clinical relevance MRI and PSMA-PET/CT are often discordant for assessing the primary prostate tumor. Using both modalities for primary prostate tumor evaluation can provide complementary information that may substantially impact treatment planning.
PMID: 39853335
ISSN: 1432-1084
CID: 5787692

A Prospective Pilot Study Investigating Performance of 18F-Fluciclovine PET Imaging for Detection of Prostate Cancer 2 Years Following Primary Partial Gland Cryoablation

Nazemi, Azadeh; Huang, William C; Wysock, James; Taneja, Samir S; Friedman, Kent; Gogaj, Rozalba; Lepor, Herbert
Purpose/UNASSIGNED:The goal of partial gland ablation (PGA) is to eradicate focal lesions of clinically significant prostate cancer (csPCa) with minimal adverse impact on functional outcomes. The primary objective of this study is to characterize the performance of 18F-Fluciclovine PET imaging for detection of prostate cancer following PGA. Materials and Methods/UNASSIGNED:Subjects 2 years following primary partial gland cryoablation (PPGCA) were invited to participate in an IRB-approved study providing they met the following inclusion criteria: a single reported mpMRI region of interest (ROI) concordant with biopsy Gleason Grade Group (GGG) < 4, no gross extra-prostatic extension on mpMRI, and no GGG > 1 or GGG 1 with a core length > 6 mm on contralateral systematic biopsy. 18F-Fluciclovine PET MRI imaging of the prostate was performed followed by in and out-of-field biopsies. Results/UNASSIGNED:Twenty-seven men who met eligibility criteria participated in the prospective study. In-field and out-of-field csPCa recurrence rate was 7.4% and 22.2%, respectively. The sensitivity and positive predictive value of mpMRI and PET imaging did not reach performance to reliably inform who should undergo prostate biopsy. Conclusion/UNASSIGNED:At 2 years following PPGCA, the rate of in-field csPCa was exceedingly low indicating a limited role for imaging to inform in-field biopsy decisions. The csPCa detection rate of out-of-field recurrence was 22% which provides an opportunity for imaging to inform out-of-field biopsy decisions. Based on our findings, 18F-Fluciclovine PET MRI cannot be used to inform who should undergo out-of-field prostate biopsy at 2 years following PPGCA.
PMCID:9276896
PMID: 35846414
ISSN: 1869-3474
CID: 5278802

Assessment of salivary gland function after 177Lu-PSMA radioligand therapy: Current concepts in imaging and management

Mahajan, Sonia; Grewal, Ravinder K; Friedman, Kent P; Schöder, Heiko; Pandit-Taskar, Neeta
Prostate specific membrane antigen (PSMA) is a transmembrane protein that is highly expressed on prostate epithelial cells and is strongly upregulated in prostate cancer. Radioligand therapy using beta-emitting Lutetium-177 (177Lu)-labeled-PSMA-617, a radiolabeled small molecule, has gained attention as a novel targeted therapy for metastatic prostate cancer, given its high affinity and long tumor retention, and rapid blood pool clearance. In March 2022, the United States Food and Drug administration has granted approval to the targeted 177Lu-PSMA-617 therapy for treatment of patients with PSMA-positive metastatic castration resistant prostate cancer, who have been previously treated with an androgen-receptor pathway inhibitor and taxane-based chemotherapy. Studies have demonstrated the adverse effects of this treatment, mainly encountered due to radiation exposure to non-target tissues. Salivary glands show high PSMA-ligand uptake and receive increased radiation dose secondary to accumulation of 177Lu-PSMA-617. This predisposes the glands to radiation-mediated toxicity. The exact mechanism, scope and severity of radiation-mediated salivary gland toxicity are not well understood, however, the strategies for its prevention and treatment are under evaluation. This review will focus on the current knowledge about salivary gland impairment post 177Lu labeled PSMA-based radioligand therapies, diagnostic methodologies, and imaging with emphasis on salivary gland scintigraphy. The preventive strategies and known treatment options would also be briefly highlighted.
PMCID:9079342
PMID: 35523007
ISSN: 1936-5233
CID: 5216502

18F-Fluciclovine Uptake in Thymoma Demonstrated on PET/MRI

Tsikitas, Lucas; Karls, Shawn; Kranz, Anca-Oana; Friedman, Kent P; Mahajan, Sonia
A 68-year-old man with a history of prostate cancer post-primary treatment presented with rising prostate-specific antigen levels and was referred for F-fluciclovine PET/MRI to localize recurrent disease. PET/MRI revealed a solitary focus of uptake in a soft tissue nodule in the anterior mediastinum, which was resected and found to be a type B2 thymoma. F-fluciclovine uptake is mediated by amino acid transporters, primarily alanine-serine-cysteine transporter 2 and L-type amino acid transporter 1, previously demonstrated to be expressed on thymic carcinomas. This case highlights the possibility of overexpression of amino acid transporters in thymomas as well, rarely described before.
PMID: 32956127
ISSN: 1536-0229
CID: 4605472