Faculty Bibliography

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.

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.

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.

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.

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.

Imaging is used for lymphoma detection, Ann Arbor/Lugano staging, and treatment response assessment. [¹⁸F]FDG PET/CT should be used for most lymphomas, including Hodgkin lymphoma, aggressive/high-grade Non-Hodgkin lymphomas (NHL) such as diffuse large B-cell lymphoma, and many indolent/low-grade NHLs such as follicular lymphoma. Apart from these routinely FDG-avid lymphomas, some indolent NHLs, such as marginal zone lymphoma, are variably FDG-avid; here, [¹⁸F]FDG PET/CT is an alternative to contrast-enhanced CT at baseline and may be used for treatment response assessment if the lymphoma was FDG-avid at baseline. Only small lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL) should exclusively undergo CT at baseline and follow-up unless transformation to high-grade lymphoma is suspected. While [¹⁸F]FDG PET/CT is sufficient to rule out bone marrow involvement in Hodgkin lymphoma, biopsy may be needed in other lymphomas. The 5-point (Deauville) score for [¹⁸F]FDG PET that uses the liver and blood pool uptake as references should be used to assess treatment response in all FDG-avid lymphomas; post-treatment FDG uptake ≤ liver uptake is considered complete response. In all other lymphomas, CT should be used to determine changes in lesion size; for complete response, resolution of all extranodal manifestations, and for lymph nodes, long-axis decrease to ≤ 1.5 cm are required. KEY POINTS: [¹⁸F]FDG-PET/CT and contrast-enhanced CT are used to stage lymphoma depending on type. Imaging is required for staging, and biopsies may be required to rule out bone marrow involvement. For treatment response assessment, the 5-PS (Deauville) score should be used; in a few indolent types, CT is used to determine changes in lesion size.

CD19-directed chimeric antigen receptor T-cell (CAR-T) therapy has recently been approved as second-line treatment for relapsed/refractory large B-cell lymphoma (LBCL). This study compares patterns of disease relapse and progression across patients receiving CAR-T as second-line (early administration) versus third or subsequent lines (late administration). We analyzed 354 patients treated with Axicabtagene ciloleucel (71%) and Lisocabtagene maraleucel (29%); 80 (23%) received early administration, and 274 (77%) late administration. One-year overall survival was higher in the early group (82% [95% CI 72-93] vs. 71% [95% CI 66-77], p = 0.048). However, the survival benefit was not sustained in multivariable Cox regression modeling and propensity score matching. One-year cumulative incidences of relapse were similar (37% [95% CI 24-50] vs. 43% [95% CI 37-49], p = 0.2), as were 1-year progression-free survival probabilities (62% [95% CI 50-76] vs. 50% [95% CI 44-57], p = 0.14). The early group exhibited a favorable toxicity profile, with lower rate of grade ≥2 cytokine release syndrome (26% vs. 39%, p = 0.031) and reduced cumulative incidence of severe neutropenia (41% [95% CI 30-52] vs. 55% [95% CI 49-60], p = 0.027). Our results indicate favorable outcomes with CAR-T irrespective of treatment line. The equivalence in disease control suggests that CAR-T resistance mechanisms persist in LBCL failing first-line therapy.

PURPOSE/UNASSIGNED:Greater disease burden is a well-established predictor of poorer outcomes following chimeric antigen receptor T-cell (CAR T) therapy. Although bridging therapy (BT) is widely used between leukapheresis and CAR T infusion, limited data have evaluated the impact of BT on CAR T outcomes. In this study, we hypothesized that the quantitative dynamics of radiomic cytoreduction during bridging are prognostic. EXPERIMENTAL DESIGN/UNASSIGNED:Patients with large B-cell lymphoma treated with CD19-CAR T from 2016 to 2022 were included in the study. Metabolic tumor volume (MTV) was determined for all patients on pre-leukapheresis PET and on post-BT/pre-infusion PET in those who received BT. Patients were stratified into "High" and "Low" disease burden using an MTV cutpoint of 65.4cc established by maximally selected log-rank statistic for progression-free survival (PFS). RESULTS/UNASSIGNED:Of 191 patients treated with CAR T, 144 (75%) received BT. In the BT cohort, 56% had a reduction in MTV post-BT. On multivariate analysis, the MTV trajectory across the bridging period remained significantly associated with PFS (P < 0.001); however, notably, patients with improved MTV (High->Low) had equivalent PFS compared with those with initially and persistently low MTV (Low->Low; HR for High->Low MTV: 2.74; 95% confidence interval, 0.82-9.18). There was a reduction in any grade immune effector cell-associated neurotoxicity syndrome in the High->Low MTV cohort as compared with the High->High MTV cohort (13% vs. 41%; P = 0.05). CONCLUSIONS/UNASSIGNED:This is the first study to use radiomics to quantify disease burden pre- and post-BT in a large real-world large B-cell lymphoma cohort. We demonstrate that effective BT can enable initially high-disease burden patients to achieve post-CAR T outcomes comparable with low-disease burden patients.

OBJECTIVES/OBJECTIVE:The aim of this study was to determine whether MRI radiomic features of key cerebral structures differ between women and men, and whether detection of such differences depends on the image resolution. MATERIALS AND METHODS/METHODS:Ultrahigh resolution (UHR) 3D MP2RAGE (magnetization-prepared 2 rapid acquisition gradient echo) T1-weighted MR images (voxel size, 0.7 × 0.7 × 0.7 mm3) of the brain of 30 subjects (18 women and 12 men; mean age, 39.0 ± 14.8 years) without abnormal findings on MRI were retrospectively included. MRI was performed on a whole-body 7 T MR system. A convolutional neural network was used to segment the following structures: frontal cortex, frontal white matter, thalamus, putamen, globus pallidus, caudate nucleus, and corpus callosum. Eighty-seven radiomic features were extracted respectively: gray-level histogram (n = 18), co-occurrence matrix (n = 24), run-length matrix (n = 16), size-zone matrix (n = 16), and dependence matrix (n = 13). Feature extraction was performed at UHR and, additionally, also after resampling to 1.4 × 1.4 × 1.4 mm3 voxel size (standard clinical resolution). Principal components (PCs) of radiomic features were calculated, and independent samples t tests with Cohen d as effect size measure were used to assess differences in PCs between women and men for the different cerebral structures. RESULTS:At UHR, at least a single PC differed significantly between women and men in 6/7 cerebral structures: frontal cortex (d = -0.79, P = 0.042 and d = -1.01, P = 0.010), frontal white matter (d = -0.81, P = 0.039), thalamus (d = 1.43, P < 0.001), globus pallidus (d = 0.92, P = 0.020), caudate nucleus (d = -0.83, P = 0.039), and corpus callosum (d = -0.97, P = 0.039). At standard clinical resolution, only a single PC extracted from the corpus callosum differed between sexes (d = 1.05, P = 0.009). CONCLUSIONS:Nonnegligible differences in radiomic features of several key structures of the brain exist between women and men, and need to be accounted for. Very high spatial resolution may be required to uncover and further investigate the sexual dimorphism of brain structures on MRI.