Faculty Bibliography

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.

Tumor-agnostic precision medicine (PM) strategies promise to support treatment decisions in relapsed/refractory blood cancer patients. Genomic-based PM (gPM) and drug screening-based functional PM (fPM) currently represent the most prominent PM methodologies. In this study, we report the feasibility analysis of the first 55 patients enrolled in the multicentric, randomized controlled EXALT-2 trial (NCT04470947) comparing treatment recommendations of gPM, fPM, and physicians' choice (PC) head to head. In 54 patients (98%), the diagnostic workflow was successfully implemented, resulting in treatment recommendations for 42 patients (76%), of whom 29 (69%) received the suggested individualized treatments. Actionable targets were identified in 65% by gPM and 80% by fPM (64% microscopy-based, 86% flow cytometry-based fPM). The median time to report was shorter for fPM than for gPM testing. The two strategies revealed overlapping drug targets in 60% of cases. Both, gPM and fPM can efficiently be integrated into the clinical routine to guide therapy decisions for the majority of patients.

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.

Technological innovations in genomics and related fields have facilitated large sequencing efforts, supported new biological discoveries in cancer, and spawned an era of liquid biopsy biomarkers. Despite these advances, precision oncology has practical constraints, partly related to cancer's biological diversity and spatial and temporal complexity. Advanced imaging technologies are being developed to address some of the current limitations in early detection, treatment selection and planning, drug delivery, and therapeutic response, as well as difficulties posed by drug resistance, drug toxicity, disease monitoring, and metastatic evolution. We discuss key areas of advanced imaging for improving cancer outcomes and survival. Finally, we discuss practical challenges to the broader adoption of precision imaging in the clinic and the need for a robust translational infrastructure.

BRAF V600E mutations are frequently found in histiocytic/dendritic cell neoplasms such as Erdheim-Chester disease (ECD) and Langerhans cell histiocytosis (LCH), but few reports have also described BRAF mutations in Rosai-Dorfman disease (RDD), and even these cases may predominantly represent mixed histiocytosis. BRAF mutations have been studied in histiocytic/dendritic cell neoplasms and described to be associated with increased risk of relapse and long-term consequences, but few studies have examined BRAF V600E mutation in RDD, which is recognized as a neoplasm given the high frequency of MAPK pathway alterations. Here, we report a case of BRAF V600E-mutated RDD in a patient who presented with generalized lymphadenopathy. During our evaluation of this patient, we also found expression of PD-L1 in neoplastic histiocytes. During our review period, only few cases of RDD reported to harbor BRAF mutation or were evaluated for the expression of PDL1 by neoplastic cells. Given the potential challenges in distinguishing RDD from other histiocytic/dendritic cell neoplasms, including mixed histiocytosis with similar clinicopathological manifestations, we will discuss the current state of knowledge regarding the frequency and clinical impact of BRAF V600E in RDD, as well as the role of BRAF mutations in RDD pathogenesis. Distinction of BRAF V600E mutated histiocytic/dendritic cell neoplasms requires consideration of distinctive histopathological and immunophenotypic findings in appropriate clinical and radiologic setting. Given the increasing use of BRAF inhibitors as well as checkpoint blockade inhibitors to treat a number of cancers, we will discuss the clinical implications of the presence of BRAF V600E mutation and PD-L1 expression in RDD.

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.