Faculty Bibliography

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.

AIM/OBJECTIVE:To investigate the associations between the hour of the day and Prostate Imaging-Reporting and Data System (PI-RADS) scores assigned by radiologists in prostate MRI reports. MATERIALS AND METHODS/METHODS:Retrospective single-center collection of prostate MRI reports over an 8-year period. Mean PI-RADS scores assigned between 0800 and 1800 h were examined with a regression model. RESULTS: = 0.005, p < 0.001), with malignant scores more frequently assigned later in the day. CONCLUSION/CONCLUSIONS:These findings suggest chronobiological factors may contribute to variability in radiological assessments. Though the magnitude of the effect is small, this may potentially add variability and impact diagnostic accuracy.

OBJECTIVES/OBJECTIVE:To assess radiologists' current use of, and opinions on, structured reporting (SR) in oncologic imaging, and to provide recommendations for a structured report template. MATERIALS AND METHODS/METHODS:An online survey with 28 questions was sent to European Society of Oncologic Imaging (ESOI) members. The questionnaire had four main parts: (1) participant information, e.g., country, workplace, experience, and current SR use; (2) SR design, e.g., numbers of sections and fields, and template use; (3) clinical impact of SR, e.g., on report quality and length, workload, and communication with clinicians; and (4) preferences for an oncology-focused structured CT report. Data analysis comprised descriptive statistics, chi-square tests, and Spearman correlation coefficients. RESULTS:A total of 200 radiologists from 51 countries completed the survey: 57.0% currently utilized SR (57%), with a lower proportion within than outside of Europe (51.0 vs. 72.7%; p = 0.006). Among SR users, the majority observed markedly increased report quality (62.3%) and easier comparison to previous exams (53.5%), a slightly lower error rate (50.9%), and fewer calls/emails by clinicians (78.9%) due to SR. The perceived impact of SR on communication with clinicians (i.e., frequency of calls/emails) differed with radiologists' experience (p < 0.001), and experience also showed low but significant correlations with communication with clinicians (r = - 0.27, p = 0.003), report quality (r = 0.19, p = 0.043), and error rate (r = - 0.22, p = 0.016). Template use also affected the perceived impact of SR on report quality (p = 0.036). CONCLUSION/CONCLUSIONS:Radiologists regard SR in oncologic imaging favorably, with perceived positive effects on report quality, error rate, comparison of serial exams, and communication with clinicians. CLINICAL RELEVANCE STATEMENT/CONCLUSIONS:Radiologists believe that structured reporting in oncologic imaging improves report quality, decreases the error rate, and enables better communication with clinicians. Implementation of structured reporting in Europe is currently below the international level and needs society endorsement. KEY POINTS/CONCLUSIONS:• The majority of oncologic imaging specialists (57% overall; 51% in Europe) use structured reporting in clinical practice. • The vast majority of oncologic imaging specialists use templates (92.1%), which are typically cancer-specific (76.2%). • Structured reporting is perceived to markedly improve report quality, communication with clinicians, and comparison to prior scans.

Relapse and toxicity limit the effectiveness of chimeric antigen receptor T-cell (CAR-T) therapy for large B-cell lymphoma (LBCL), yet biomarkers that predict outcomes and toxicity are lacking. We examined radiomic features extracted from pre-CAR-T ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography ([¹⁸F]FDG PET/CT) scans (n = 341) of 180 patients (121 male; median age, 66 years). Three conventional (maximum standardized uptake value [SUVmax], metabolic tumor volume [MTV], total lesion glycolysis [TLG]) and 116 novel radiomic features were assessed, along with inflammatory markers, toxicities, and outcomes. At both pre-apheresis and pre-infusion time points, conventional PET features of disease correlated with elevated inflammatory markers. At pre-infusion, MTV was associated with grade ≥ 2 cytokine release syndrome (odds ratio [OR] for 100 mL increase: 1.08 [95% confidence interval (CI), 1.01-1.20], P = 0.031), and SUVmax was associated with failure to achieve complete response (CR) (OR 1.72 [95% CI, 1.24-2.43], P < 0.001). Higher pre-apheresis and pre-infusion MTV values were associated with shorter progression-free survival (PFS) (HR for 10-unit increase: 1.11 [95% CI, 1.05-1.17], P < 0.001; 1.04 [95% CI, 1.02-1.07], P < 0.001) and shorter overall survival (HR for 100-unit increase: 1.14 [95% CI, 1.07-1.21], P < 0.001; 1.04 [95% CI, 1.02-1.06], P < 0.001). A combined MTV and LDH measure stratified patients into high and low PFS risk groups. Multiple pre-infusion novel radiomic features were associated with CR. These quantitative conventional [¹⁸F]FDG PET/CT features obtained before CAR-T cell infusion, which were correlated with inflammation markers, may provide prognostic biomarkers for CAR-T therapy efficacy and toxicity. The use of conventional and novel radiomic features may thus help identify high-risk patients for earlier interventions.

BACKGROUND:F]FDG-PET-CT scans of patients with lymphoma with or without hypermetabolic tumour sites. METHODS:F]FDG-PET-CTs were obtained from a second centre (Medical University of Vienna, Vienna, Austria). Seven model variants were evaluated, including MIP-based LARS-avg (optimised for accuracy) and LARS-max (optimised for sensitivity), and 3D PET-CT-based LARS-ptct. Following expert curation, areas under the curve (AUCs), accuracies, sensitivities, and specificities were calculated. FINDINGS/RESULTS:In the internal test cohort (3325 PET-CTs, 1012 patients), LARS-avg achieved an AUC of 0·949 (95% CI 0·942-0·956), accuracy of 0·890 (0·879-0·901), sensitivity of 0·868 (0·851-0·885), and specificity of 0·913 (0·899-0·925); LARS-max achieved an AUC of 0·949 (0·942-0·956), accuracy of 0·868 (0·858-0·879), sensitivity of 0·909 (0·896-0·924), and specificity of 0·826 (0·808-0·843); and LARS-ptct achieved an AUC of 0·939 (0·930-0·948), accuracy of 0·875 (0·864-0·887), sensitivity of 0·836 (0·817-0·855), and specificity of 0·915 (0·901-0·927). In the external test cohort (1000 PET-CTs, 503 patients), LARS-avg achieved an AUC of 0·953 (0·938-0·966), accuracy of 0·907 (0·888-0·925), sensitivity of 0·874 (0·843-0·904), and specificity of 0·949 (0·921-0·960); LARS-max achieved an AUC of 0·952 (0·937-0·965), accuracy of 0·898 (0·878-0·916), sensitivity of 0·899 (0·871-0·926), and specificity of 0·897 (0·871-0·922); and LARS-ptct achieved an AUC of 0·932 (0·915-0·948), accuracy of 0·870 (0·850-0·891), sensitivity of 0·827 (0·793-0·863), and specificity of 0·913 (0·889-0·937). INTERPRETATION/CONCLUSIONS:F]FDG-PET-CT scans of lymphoma patients with and without hypermetabolic tumour sites. Deep learning might therefore be potentially useful to rule out the presence of metabolically active disease in such patients, or serve as a second reader or decision support tool. FUNDING/BACKGROUND:National Institutes of Health-National Cancer Institute Cancer Center Support Grant.

PURPOSE/OBJECTIVE:Neuroendocrine tumors (NETs) are a rare form of cancer that can occur anywhere in the body and commonly metastasizes. The large variance in location and aggressiveness of the tumors makes it a difficult cancer to treat. Assessments of the whole-body tumor burden in a patient image allow for better tracking of disease progression and inform better treatment decisions. Currently, radiologists rely on qualitative assessments of this metric since manual segmentation is unfeasible within a typical busy clinical workflow. METHODS:We address these challenges by extending the application of the nnU-net pipeline to produce automatic NET segmentation models. We utilize the ideal imaging type of 68Ga-DOTATATE PET/CT to produce segmentation masks from which to calculate total tumor burden metrics. We provide a human-level baseline for the task and perform ablation experiments of model inputs, architectures, and loss functions. RESULTS:Our dataset is comprised of 915 PET/CT scans and is divided into a held-out test set (87 cases) and 5 training subsets to perform cross-validation. The proposed models achieve test Dice scores of 0.644, on par with our inter-annotator Dice score on a subset 6 patients of 0.682. If we apply our modified Dice score to the predictions, the test performance reaches a score of 0.80. CONCLUSION/CONCLUSIONS:In this paper, we demonstrate the ability to automatically generate accurate NET segmentation masks given PET images through supervised learning. We publish the model for extended use and to support the treatment planning of this rare cancer.

OBJECTIVES/OBJECTIVE:The aims of this study were to determine whether ComBat harmonization improves multiclass radiomics-based tissue classification in technically heterogeneous MRI data sets and to compare the performances of 2 ComBat variants. MATERIALS AND METHODS/METHODS:One hundred patients who had undergone T1-weighted 3D gradient echo Dixon MRI (2 scanners/vendors; 50 patients each) were retrospectively included. Volumes of interest (2.5 cm3) were placed in 3 disease-free tissues with visually similar appearance on T1 Dixon water images: liver, spleen, and paraspinal muscle. Gray-level histogram (GLH), gray-level co-occurrence matrix (GLCM), gray-level run-length matrix (GLRLM), and gray-level size-zone matrix (GLSZM) radiomic features were extracted. Tissue classification was performed on pooled data from the 2 centers (1) without harmonization, (2) after ComBat harmonization with empirical Bayes estimation (ComBat-B), and (3) after ComBat harmonization without empirical Bayes estimation (ComBat-NB). Linear discriminant analysis with leave-one-out cross-validation was used to distinguish among the 3 tissue types, using all available radiomic features as input. In addition, a multilayer perceptron neural network with a random 70%:30% split into training and test data sets was used for the same task, but separately for each radiomic feature category. RESULTS:Linear discriminant analysis-based mean tissue classification accuracies were 52.3% for unharmonized, 66.3% for ComBat-B harmonized, and 92.7% for ComBat-NB harmonized data. For multilayer perceptron neural network, mean classification accuracies for unharmonized, ComBat-B-harmonized, and ComBat-NB-harmonized test data were as follows: 46.8%, 55.1%, and 57.5% for GLH; 42.0%, 65.3%, and 71.0% for GLCM; 45.3%, 78.3%, and 78.0% for GLRLM; and 48.1%, 81.1%, and 89.4% for GLSZM. Accuracies were significantly higher for both ComBat-B- and ComBat-NB-harmonized data than for unharmonized data for all feature categories (at P = 0.005, respectively). For GLCM (P = 0.001) and GLSZM (P = 0.005), ComBat-NB harmonization provided slightly higher accuracies than ComBat-B harmonization. CONCLUSIONS:ComBat harmonization may be useful for multicenter MRI radiomics studies with nonbinary classification tasks. The degree of improvement by ComBat may vary among radiomic feature categories, among classifiers, and among ComBat variants.