Yulia Lakhman

Renal Cortical Tumors: Use of Multiphasic Contrast-enhanced MR Imaging to Differentiate Benign and Malignant Histologic Subtypes

PURPOSE To investigate the use of quantitative multiphasic contrast material-enhanced magnetic resonance (MR) imaging in differentiating between common benign and malignant histologic subtypes of renal cortical tumors. MATERIALS AND METHODS The institutional review board waived informed consent and approved this retrospective HIPAA-compliant study of 138 patients who underwent preoperative contrast-enhanced MR imaging during the period of January 2004-December 2008. At surgery, 152 renal tumors were identified (77 clear cell, 22 papillary, 18 chromophobe, and 10 unclassified carcinomas; 16 oncocytomas; nine angiomyolipomas). Three readers independently identified and measured the most-enhanced area in each tumor and placed corresponding regions of interest in similar positions on images from the precontrast, corticomedullary, nephrographic, and excretory phases. The percentage change in signal intensity (%SI change) between precontrast imaging and each postcontrast phase was calculated. Interreader agreement was evaluated by using the overall concordance correlation coefficient (OCC). A linear mixed-effects model was used to estimate and compare the trajectories of the means of log %SI change across all phases between the six histologic subtypes. RESULTS Interreader agreement was substantial to almost perfect (OCC, 0.77-0.88). The %SI change differed significantly between clear cell carcinomas and papillary and chromophobe carcinomas in all phases of enhancement (P < .0001-.0120). In addition, %SI change was significantly higher in angiomyolipomas than in clear cell carcinomas, but only in the corticomedullary phase (P = .0231). Enhancement did not differ significantly between clear cell carcinoma and oncocytoma in any phase (P = .2081-.6000). CONCLUSION Quantitative multiphase contrast-enhanced MR imaging offers a widely available, reproducible method to characterize several histologic subtypes of renal cortical tumors, although it does not aid differentiation between clear cell carcinomas and oncocytomas.

Intravoxel Incoherent Motion–derived Histogram Metrics for Assessment of Response after Combined Chemotherapy and Radiation Therapy in Rectal Cancer: Initial Experience and Comparison between Single-Section and Volumetric Analyses

Purpose To determine the diagnostic performance of intravoxel incoherent motion (IVIM) parameters and apparent diffusion coefficient (ADC) to assess response to combined chemotherapy and radiation therapy (CRT) in patients with rectal cancer by using histogram analysis derived from whole-tumor volumes and single-section regions of interest (ROIs). Materials and Methods The institutional review board approved this retrospective study of 31 patients with rectal cancer who underwent magnetic resonance (MR) imaging before and after CRT, including diffusion-weighted imaging with 34 b values prior to surgery. Patient consent was not required. ADC, perfusion-related diffusion fraction (f), slow diffusion coefficient (D), and fast diffusion coefficient (D*) were calculated on MR images acquired before and after CRT by using biexponential fitting. ADC and IVIM histogram metrics and median values were obtained by using whole-tumor volume and single-section ROI analyses. All ADC and IVIM parameters obtained before and after CRT were compared with histopathologic findings by using t tests with Holm-Sidak correction. Receiver operating characteristic curves were generated to evaluate the diagnostic performance of IVIM parameters derived from whole-tumor volume and single-section ROIs for prediction of histopathologic response. Results Extreme values aside, results of histogram analysis of ADC and IVIM were equivalent to median values for tumor response assessment (P > .06). Prior to CRT, none of the median ADC and IVIM diffusion metrics correlated with subsequent tumor response (P > .36). Median D and ADC values derived from either whole-volume or single-section analysis increased significantly after CRT (P ≤ .01) and were significantly higher in good versus poor responders (P ≤ .02). Median IVIM f and D* values did not significantly change after CRT and were not associated with tumor response to CRT (P > .36). Interobserver agreement was excellent for whole-tumor volume analysis (range, 0.91-0.95) but was only moderate for single-section ROI analysis (range, 0.50-0.63). Conclusion Median D and ADC values obtained after CRT were useful for discrimination between good and poor responders. Histogram metrics did not add to the median values for assessment of tumor response. Volumetric analysis demonstrated better interobserver reproducibility when compared with single-section ROI analysis. (©) RSNA, 2016 Online supplemental material is available for this article.

Stage IB1 Cervical Cancer: Role of Preoperative MR Imaging in Selection of Patients for Fertility-Sparing Radical Trachelectomy

PURPOSE To determine whether magnetic resonance (MR) imaging evaluation of key morphologic tumor characteristics can improve patient selection for radical trachelectomy. MATERIALS AND METHODS The institutional review board approved and waived informed consent for this study of 62 patients (mean age, 32 years; age range, 23-42 years) with International Federation of Gynecology and Obstetrics stage IB1 cervical carcinoma who underwent attempted radical trachelectomy between November 2001 and January 2011 and had preoperative MR imaging. Retrospectively, two radiologists reviewed MR images for tumor presence and size, distance between tumor and internal os, and presence of deep cervical stromal invasion. Associations between MR imaging findings and surgery type were tested. RESULTS Sensitivity and specificity of tumor detection were, respectively, 87% and 100% (reader 1) and 76% and 95% (reader 2). Six of six patients with negative cone biopsy margins and no tumor at postconization MR imaging were without tumor at trachelectomy pathologic analysis. Mean differences between MR imaging and histologic tumor sizes were 0.7 mm (range, -15 to 11 mm) for reader 1 and 2.2 mm (range, -9 to 15 mm) for reader 2. Sensitivities for deep cervical stromal invasion were 75% (reader 1) and 50% (reader 2). For each reader, nine of nine (100%) patients with tumor 5 mm or less from the internal os and three of five (60%) patients with tumor 6-9 mm from the internal os at MR imaging needed radical hysterectomy. For both readers, tumor size of 2 cm or larger (P < .001) and deep cervical stromal invasion (P ≤ .003) at MR imaging were associated with increased chance of radical hysterectomy. CONCLUSION Pretrachelectomy MR imaging can help identify high-risk patients likely to need radical hysterectomy or confirm the absence of residual tumor in the cervix after a cone biopsy with negative margins.

A Phase Ib Study of BEZ235, a Dual Inhibitor of Phosphatidylinositol 3-Kinase (PI3K) and Mammalian Target of Rapamycin (mTOR), in Patients With Advanced Renal Cell Carcinoma

Lessons Learned Our results highlight additional toxicities of dual PI3K/mTOR inhibition in the clinical setting that were unforeseen from preclinical models. Because of toxicity and lack of efficacy, BEZ235 should not be further developed in the current formulation for patients with renal cell carcinoma. Background. Allosteric inhibitors of the mammalian target of rapamycin complex 1 (mTORC1) are approved for advanced renal cell carcinoma (RCC). Preclinical models have suggested that dual inhibition of phosphatidylinositol 3-kinase (PI3K) and mTOR kinase may establish superior anticancer effect. We aimed to establish safety for BEZ235, a potent inhibitor of both PI3K and mTOR, in advanced RCC. Methods. Patients with advanced RCC who had previously failed standard therapy received escalating doses of BEZ235 in sachet formulation twice daily until progression or unacceptable toxicity. Primary endpoints were to identify the maximally tolerated dose (MTD) and to determine the recommended dose for the phase II study. Results. The study was terminated early because of high incidence of dose-limiting toxicities (DLTs) across all dose levels tested. Ten patients were treated with BEZ235—six with clear cell and four with non-clear cell subtypes. Five of these patients suffered DLTs: 2 of 2 patients in the original 400 mg b.i.d. cohort, 1 of 6 in the 200 mg b.i.d. cohort, and 2 of 2 in the 300 mg b.i.d. cohort. DLTs included fatigue, rash, nausea and vomiting, diarrhea, mucositis, anorexia, and dysgeusia. Five patients were evaluable for response: Two had stable disease as best response, and three had progressive disease. Conclusion. BEZ235 twice daily resulted in significant toxicity without objective responses; further development of this compound will not be pursued in this disease.

Magnetic resonance imaging/positron emission tomography provides a roadmap for surgical planning and serves as a predictive biomarker in patients with recurrent gynecological cancers undergoing pelvic exenteration.

Objective Magnetic resonance imaging (MRI) is the modality of choice for staging gynecological cancers owing to its superb soft tissue resolution, whereas 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) allows the assessment of glycolytic activity within the tumor microenvironment. In this study, we evaluated the incremental value of fused MRI/PET over MRI or fluorodeoxyglucose PET/CT alone for assessing local disease extent in patients with recurrent gynecological cancers undergoing pelvic exenteration and determined the associations between imaging findings and clinical outcomes in this patient population. Materials and Methods The institutional review board approved this retrospective, Health Insurance Portability and Accountability Act (HIPAA)-compliant study of 31 patients who underwent pelvic MRI and PET/CT 3 months or less before pelvic exenteration for recurrent cancers of the uterine cervix, corpus, or vulva/vagina. Using a 1 to 5 scale (1, definitely not present; 5, definitely present), 2 readers independently evaluated MRI, PET/CT, and fused MRI/PET images for the presence of bladder, rectum, and pelvic sidewall invasion. Surgical pathology constituted the reference standard. Measurements of diagnostic accuracy, interreader agreement, and associations between imaging findings and progression-free survival and overall survival were calculated. Results Compared with MRI or PET/CT, fused MRI/PET correctly improved readers’ diagnostic confidence in detecting bladder, rectum, or pelvic sidewall invasion in up to 52% of patients. Interreader agreement was consistently in the highest (“almost perfect”) range only for MRI/PET (&kgr; = 0.84–1.0). The highest sensitivities (0.82–1.0), specificities (0.91–1.0), and predictive values (0.80–1.0) were consistently achieved with fused MRI/PET (although the differences were not statistically significant [P > 0.05]). Pelvic sidewall invasion on MRI/PET was the only finding significantly associated with both progression-free and overall survival for both readers (P = 0.0067–0.0440). Conclusions In patients with recurrent gynecological cancers undergoing pelvic exenteration, fused MRI/PET served as a predictive biomarker and yielded greater diagnostic confidence and interreader agreement than either MRI or PET/CT.

Differentiation of Uterine Leiomyosarcoma from Atypical Leiomyoma: Diagnostic Accuracy of Qualitative MR Imaging Features and Feasibility of Texture Analysis

PurposeTo investigate whether qualitative magnetic resonance (MR) features can distinguish leiomyosarcoma (LMS) from atypical leiomyoma (ALM) and assess the feasibility of texture analysis (TA).MethodsThis 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.ResultsFour 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).ConclusionsCombination of ≥3 qualitative MR features accurately distinguished LMS from ALM. TA was feasible.Key Points• 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.

A novel representation of inter-site tumour heterogeneity from pre-treatment computed tomography textures classifies ovarian cancers by clinical outcome

AbstractPurposeTo 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).MethodsIRB-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.ResultsOf 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.ConclusionQuantitative metrics non-invasively capturing spatial inter-site heterogeneity may predict outcomes in patients with HGSOC.Key Points• 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.

Early Postoperative CT as a Prognostic Biomarker in Patients With Advanced Ovarian, Tubal, and Primary Peritoneal Cancer Deemed Optimally Debulked at Primary Cytoreductive Surgery

OBJECTIVE The purpose of this article is to determine whether early postoperative CT provides prognostic information in patients with advanced ovarian, tubal, or primary peritoneal carcinoma with optimal debulking reported at primary cytoreduction. MATERIALS AND METHODS Our study included 63 patients who underwent primary cytoreductive surgery for presumed advanced ovarian cancer, who had optimal debulking (residual disease ≤ 1 cm) reported at surgery, and who underwent CT before and 7-49 days after surgery. Two radiologists independently retrospectively interpreted all postoperative CT scans and scored lesions on a 5-point scale, where 1 indicates normal and 5 indicates definitely malignant. Lesions larger than 1 cm with a CT score of 4 or 5 were considered suboptimally debulked residual disease. RESULTS Suboptimally debulked residual disease on CT (range, 1.1-5.8 cm) was reported by reader 1 for 29 of 63 patients (46%) and by reader 2 for 31 of 63 patients (49%), with substantial interobserver agreement (κ = 0.75). Patients with suboptimally debulked residual disease on CT had significantly worse median progression-free survival (p = 0.001, both readers) and overall survival (p ≤ 0.010, both readers). By univariate and multivariate analyses, suboptimally debulked residual disease on CT remained a significant independent predictor of progression-free survival (p = 0.001, both readers) and overall survival (p ≤ 0.006, both readers). CONCLUSION Our study showed that residual disease larger than 1 cm was present on early postoperative CT in almost half of the patients deemed to have optimally debulked disease at primary cytoreduction. Residual disease larger than 1 cm detected on early postoperative CT was associated with significant decreases in both progression-free and overall survival.

Pattern and Prognostic Implications of Cardiac Metastases Among Patients With Advanced Systemic Cancer Assessed With Cardiac Magnetic Resonance Imaging.

Background Cardiac magnetic resonance (CMR) imaging is well validated for tissue characterization of cardiac masses but has not been applied to study pattern and prognostic implications of cardiac metastases (CMETs) among patients with systemic cancer. Methods and Results The population consisted of 60 patients with stage IV cancer (32 patients with CMETs, 28 diagnosis‐matched controls) undergoing CMR. CMET was defined as a discrete mass with vascular tissue properties on delayed enhancement CMR. CMET‐positive patients and controls had similar clinical characteristics, cardiac geometry, and function (P=NS). Leading cancer types associated with CMET were sarcoma, melanoma, and gastrointestinal. Patients with CMETs had similar distribution of extracardiac metastatic disease compared with controls (organs involved: 3.4±2.0 versus 2.7±1.9, P=0.17). In 94% of patients with CMETs, there were metastases involving ≥1 extracardiac organ (66% lung involvement). CMET location varied (right ventricle 44%, right atrium 19%, left ventricle 28%, left atrium 9%, pericardial 25%); 22% of cases had multichamber involvement. Right‐sided chamber involvement was common in hematologic/lymphatic spread (67%); pericardial involvement was common with direct spread (64%). Regarding tissue properties on delayed enhancement CMR, CMETs commonly (59%) demonstrated heterogeneous enhancement (41% diffuse enhancement). Heterogeneous lesions were larger and had increased border irregularity (P<0.05). Survival 6 months post‐CMR was numerically lower among patients with CMETs (56% [95% CI 39–74%]) versus stage IV cancer–matched controls (68% [95% CI 50–86%]), although differences between groups were nonsignificant (P=0.42). Conclusions CMETs vary regarding etiology, location, and tissue properties on CMR, highlighting need for comprehensive surveillance of cardiac involvement regardless of cancer origin. Prognosis remains poor with for patients with CMETs, albeit similar to that for stage IV cancer controls matched for cancer etiology.

Role of MR Imaging and FDG PET/CT in Selection and Follow-up of Patients Treated with Pelvic Exenteration for Gynecologic Malignancies

Pelvic exenteration (PE) is a radical surgical procedure used for the past 6 decades to treat locally advanced malignant diseases confined to the pelvis, particularly persistent or recurrent gynecologic cancers in the irradiated pelvis. The traditional surgical technique known as total PE consists of resection of all pelvic viscera followed by reconstruction. Depending on the tumor extent, the procedure can be tailored to remove only anterior or posterior structures, including the bladder (anterior exenteration) or rectum (posterior exenteration). Conversely, more extended pelvic resection can be performed if the pelvic sidewall is invaded by cancer. Preoperative imaging evaluation with magnetic resonance (MR) imaging and fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) is central to establishing tumor resectability and therefore patient eligibility for the procedure. These imaging modalities complement each other in diagnosis of tumor recurrence and differentiation of persistent disease from posttreatment changes. MR imaging can accurately demonstrate local tumor extent and show adjacent organ invasion. FDG PET/CT is useful in excluding nodal and distant metastases. In addition, FDG PET/CT metrics may serve as predictive biomarkers for overall and disease-free survival. This pictorial review describes different types of exenterative surgical procedures and illustrates the central role of imaging in accurate patient selection, treatment planning, and postsurgical surveillance.