Faculty Bibliography

Purpose To evaluate interradiologist agreement on assessments of computed tomography (CT) imaging features of high-grade serous ovarian cancer (HGSOC), to assess their associations with time-to-disease progression (TTP) and HGSOC transcriptomic profiles (Classification of Ovarian Cancer [CLOVAR]), and to develop an imaging-based risk score system to predict TTP and CLOVAR profiles. Materials and Methods This study was a multireader, multi-institutional, institutional review board-approved, HIPAA-compliant retrospective analysis of 92 patients with HGSOC (median age, 61 years) with abdominopelvic CT before primary cytoreductive surgery available through the Cancer Imaging Archive. Eight radiologists from the Cancer Genome Atlas Ovarian Cancer Imaging Research Group developed and independently recorded the following CT features: characteristics of primary ovarian mass(es), presence of definable mesenteric implants and infiltration, presence of other implants, presence and distribution of peritoneal spread, presence and size of pleural effusions and ascites, lymphadenopathy, and distant metastases. Interobserver agreement for CT features was assessed, as were univariate and multivariate associations with TTP and CLOVAR mesenchymal profile (worst prognosis). Results Interobserver agreement for some features was strong (eg, α = .78 for pleural effusion and ascites) but was lower for others (eg, α = .08 for intraparenchymal splenic metastases). Presence of peritoneal disease in the right upper quadrant (P = .0003), supradiaphragmatic lymphadenopathy (P = .0004), more peritoneal disease sites (P = .0006), and nonvisualization of a discrete ovarian mass (P = .0037) were associated with shorter TTP. More peritoneal disease sites (P = .0025) and presence of pouch of Douglas implants (P = .0045) were associated with CLOVAR mesenchymal profile. Combinations of imaging features contained predictive signal for TTP (concordance index = 0.658; P = .0006) and CLOVAR profile (mean squared deviation = 1.776; P = .0043). Conclusion These results provide some evidence of the clinical and biologic validity of these image features. Interobserver agreement is strong for some features, but could be improved for others. ^© RSNA, 2017 Online supplemental material is available for this article.

The heterogeneity of an individual patient's tumor has been linked to treatment resistance, but quantitative biomarkers to rapidly and reproducibly evaluate heterogeneity in a clinical setting are currently lacking. Using established tools available in a College of American Pathologists-accredited and Clinical Laboratory Improvement Amendments-certified clinical laboratory, we quantified digital pathology features on 9,225 individual circulating tumor cells (CTC) from 179 unique metastatic castration-resistant prostate cancer (mCRPC) patients to define phenotypically distinct cell types. Heterogeneity was quantified on the basis of the diversity of cell types in individual patient samples using the Shannon index and associated with overall survival (OS) in the 145 specimens collected prior to initiation of the second or later lines of therapy. Low CTC phenotypic heterogeneity was associated with better OS in patients treated with androgen receptor signaling inhibitors (ARSI), whereas high heterogeneity was associated with better OS in patients treated with taxane chemotherapy. Overall, the results show that quantifying CTC phenotypic heterogeneity can help inform the choice between ARSI and taxanes in mCRPC patients. Cancer Res; 77(20); 5687-98. ©2017 AACR.

Historically, cancer treatment has emphasized measures for the "cure" regardless of the long-term consequences. Advances in cancer detection and treatment have resulted in improved outcomes bringing to the fore various quality of life considerations including future fertility. For many young cancer patients, fertility preservation is now an integral component of clinical decision-making and treatment design. Optimal fertility-sparing options for young patients with gynecologic cancer are influenced by patient age, primary cancer, treatment regimens, and patient preferences. Possible approaches include embryo or oocyte cryopreservation, ovarian transposition, conservative surgery, and conservative medical treatment to delay radical surgery. These may be used alone or in combination to maximize fertility preservation. Awareness of the various fertility-sparing options, eligibility criteria, and the central role of magnetic resonance imaging in the proper selection of patients will enable radiologists to produce complete clinically relevant imaging reports and serve as effective consultants to referring clinicians. Knowledge of the potential imaging pitfalls is essential to avoid misinterpretation and guide appropriate management.

Purpose To compare the diagnostic performance of a short dual-pulse sequence magnetic resonance (MR) imaging protocol versus a standard six-pulse sequence multiparametric MR imaging protocol for detection of clinically significant prostate cancer. Materials and Methods This HIPAA-compliant study was approved by the regional ethics committee. Between July 2013 and March 2015, 63 patients from a prospectively accrued study population who underwent MR imaging of the prostate including transverse T1-weighted; transverse, coronal, and sagittal T2-weighted; diffusion-weighted; and dynamic contrast material-enhanced MR imaging with a 3-T imager at a single institution were included in this retrospective study. The short MR imaging protocol image set consisted of transverse T2-weighted and diffusion-weighted images only. The standard MR imaging protocol image set contained images from all six pulse sequences. Three expert readers from different institutions assessed the likelihood of prostate cancer on a five-point scale. Diagnostic performance on a quadrant basis was assessed by using areas under the receiver operating characteristic curves, and differences were evaluated by using 83.8% confidence intervals. Intra- and interreader agreement was assessed by using the intraclass correlation coefficient. Transperineal template saturation biopsy served as the standard of reference. Results At histopathologic evaluation, 84 of 252 (33%) quadrants were positive for cancer in 38 of 63 (60%) men. There was no significant difference in detection of tumors larger than or equal to 0.5 mL for any of the readers of the short MR imaging protocol, with areas under the curve in the range of 0.74-0.81 (83.8% confidence interval [CI]: 0.64, 0.89), and for readers of the standard MR imaging protocol, areas under the curve were 0.71-0.77 (83.8% CI: 0.62, 0.86). Ranges for sensitivity were 0.76-0.95 (95% CI: 0.53, 0.99) and 0.76-0.86 (95% CI: 0.53, 0.97) and those for specificity were 0.84-0.90 (95% CI: 0.79, 0.94) and 0.82-0.90 (95% CI: 0.77, 0.94) for the short and standard MR protocols, respectively. Ranges for interreader agreement were 0.48-0.60 (83.8% CI: 0.41, 0.66) and 0.49-0.63 (83.8% CI: 0.42, 0.68) for the short and standard MR imaging protocols. Conclusion For the detection of clinically significant prostate cancer, no difference was found in the diagnostic performance of the short MR imaging protocol consisting of only transverse T2-weighted and diffusion-weighted imaging pulse sequences compared with that of a standard multiparametric MR imaging protocol. ^© RSNA, 2017 Online supplemental material is available for this article.

PURPOSE/OBJECTIVE:To evaluate the associations between clinical outcomes and radiomics-derived inter-site spatial heterogeneity metrics across multiple metastatic lesions on CT in patients with high-grade serous ovarian cancer (HGSOC). METHODS:IRB-approved retrospective study of 38 HGSOC patients. All sites of suspected HGSOC involvement on preoperative CT were manually segmented. Gray-level correlation matrix-based textures were computed from each tumour site, and grouped into five clusters using a Gaussian Mixture Model. Pairwise inter-site similarities were computed, generating an inter-site similarity matrix (ISM). Inter-site texture heterogeneity metrics were computed from the ISM and compared to clinical outcomes. RESULTS:Of the 12 inter-site texture heterogeneity metrics evaluated, those capturing the differences in texture similarities across sites were associated with shorter overall survival (inter-site similarity entropy, similarity level cluster shade, and inter-site similarity level cluster prominence; p ≤ 0.05) and incomplete surgical resection (similarity level cluster shade, inter-site similarity level cluster prominence and inter-site cluster variance; p ≤ 0.05). Neither the total number of disease sites per patient nor the overall tumour volume per patient was associated with overall survival. Amplification of 19q12 involving cyclin E1 gene (CCNE1) predominantly occurred in patients with more heterogeneous inter-site textures. CONCLUSION/CONCLUSIONS:Quantitative metrics non-invasively capturing spatial inter-site heterogeneity may predict outcomes in patients with HGSOC. KEY POINTS/CONCLUSIONS:• Calculating inter-site texture-based heterogeneity metrics was feasible • Metrics capturing texture similarities across HGSOC sites were associated with overall survival • Heterogeneity metrics were also associated with incomplete surgical resection of HGSOC.

We present an exceptional case of a patient with high-grade serous ovarian cancer, treated with multiple chemotherapy regimens, who exhibited regression of some metastatic lesions with concomitant progression of other lesions during a treatment-free period. Using immunogenomic approaches, we found that progressing metastases were characterized by immune cell exclusion, whereas regressing and stable metastases were infiltrated by CD8⁺ and CD4⁺ T cells and exhibited oligoclonal expansion of specific T cell subsets. We also detected CD8⁺ T cell reactivity against predicted neoepitopes after isolation of cells from a blood sample taken almost 3 years after the tumors were resected. These findings suggest that multiple distinct tumor immune microenvironments co-exist within a single individual and may explain in part the heterogeneous fates of metastatic lesions often observed in the clinic post-therapy. VIDEO ABSTRACT.

Endometrial cancer is the most common gynecologic malignancy in the United States, with recent increasing incidence mostly owing to obesity. Preoperative MR imaging is essential to stratify patients according to their risk of recurrence and to guide surgical management. In the combination of T2-weighted imaging, diffusion-weighted imaging, and dynamic contrast enhancement, MR imaging provides a "one-stop shop" approach for patient-specific accurate staging including the evaluation of the depth of myometrial invasion, cervical stromal invasion, extrauterine extension, and lymph node status.

PURPOSE/OBJECTIVE:To investigate whether qualitative magnetic resonance (MR) features can distinguish leiomyosarcoma (LMS) from atypical leiomyoma (ALM) and assess the feasibility of texture analysis (TA). METHODS:This retrospective study included 41 women (ALM = 22, LMS = 19) imaged with MRI prior to surgery. Two readers (R1, R2) evaluated each lesion for qualitative MR features. Associations between MR features and LMS were evaluated with Fisher's exact test. Accuracy measures were calculated for the four most significant features. TA was performed for 24 patients (ALM = 14, LMS = 10) with uniform imaging following lesion segmentation on axial T2-weighted images. Texture features were pre-selected using Wilcoxon signed-rank test with Bonferroni correction and analyzed with unsupervised clustering to separate LMS from ALM. RESULTS:Four qualitative MR features most strongly associated with LMS were nodular borders, haemorrhage, "T2 dark" area(s), and central unenhanced area(s) (p ≤ 0.0001 each feature/reader). The highest sensitivity [1.00 (95%CI:0.82-1.00)/0.95 (95%CI: 0.74-1.00)] and specificity [0.95 (95%CI:0.77-1.00)/1.00 (95%CI:0.85-1.00)] were achieved for R1/R2, respectively, when a lesion had ≥3 of these four features. Sixteen texture features differed significantly between LMS and ALM (p-values: <0.001-0.036). Unsupervised clustering achieved accuracy of 0.75 (sensitivity: 0.70; specificity: 0.79). CONCLUSIONS:Combination of ≥3 qualitative MR features accurately distinguished LMS from ALM. TA was feasible. KEY POINTS/CONCLUSIONS:• Four qualitative MR features demonstrated the strongest statistical association with LMS. • Combination of ≥3 these features could accurately differentiate LMS from ALM. • Texture analysis was a feasible semi-automated approach for lesion categorization.

PURPOSE:We report our initial experience with whole body and dedicated prostate magnetic resonance imaging as a single examination to assess local recurrence and metastatic disease in patients with suspected recurrent prostate cancer after radical prostatectomy. MATERIALS AND METHODS:In this institutional review board approved, retrospective, single center study 76 consecutive patients with clinically suspected recurrent prostate cancer following radical prostatectomy underwent combined whole body and dedicated prostate magnetic resonance imaging at a single session from October 2014 to January 2016. Scans were evaluated to detect disease in the prostate bed and regional nodes, and at distant sites. Comparison was made to other imaging tests, and prostate bed, node and bone biopsies performed within 90 days. RESULTS:F-fluorodeoxyglucose positron emission tomography/computerized tomography and subsequent negative bone biopsy. CONCLUSIONS:Combined whole body and dedicated prostate magnetic resonance imaging is feasible in a clinical practice setting. It can provide incremental information compared to standard imaging in men with suspected prostate cancer recurrence after radical prostatectomy.

PURPOSE:To assess the performance of the updated Prostate Imaging Reporting and Data System (PI-RADSv2) and the apparent diffusion coefficient (ADC) for predicting confirmatory biopsy results in patients considered for active surveillance of prostate cancer (PCA). METHODS:IRB-approved, retrospective study of 371 consecutive men with clinically low-risk PCA (initial biopsy Gleason score ≤6, prostate-specific antigen <10 ng/ml, clinical stage ≤T2a) who underwent 3T-prostate MRI before confirmatory biopsy. Two independent radiologists recorded the PI-RADSv2 scores and measured the corresponding ADC values in each patient. A composite score was generated to assess the performance of combining PI-RADSv2 + ADC. RESULTS:PCA was upgraded on confirmatory biopsy in 107/371 (29%) patients. Inter-reader agreement was substantial (PI-RADSv2: k = 0.73; 95% CI [0.66-0.80]; ADC: r = 0.74; 95% CI [0.69-0.79]). Accuracies, sensitivities, specificities, positive predicted value and negative predicted value of PI-RADSv2 were 85, 89, 83, 68, 95 and 78, 82, 76, 58, 91% for ADC. PI-RADSv2 accuracy was significantly higher than that of ADC for predicting biopsy upgrade (p = 0.014). The combined PI-RADSv2 + ADC composite score did not perform better than PI-RADSv2 alone. Obviating biopsy in patients with PI-RADSv2 score ≤3 would have missed Gleason Score upgrade in 12/232 (5%) of patients. CONCLUSION:PI-RADSv2 was superior to ADC measurements for predicting PCA upgrading on confirmatory biopsy.