Jonathan R. Young

Recurrent Glioblastoma Multiforme: ADC Histogram Analysis Predicts Response to Bevacizumab Treatment

PURPOSE To determine if apparent diffusion coefficient (ADC) histogram analysis can stratify progression-free survival in patients with recurrent glioblastoma multiforme (GBM) prior to bevacizumab treatment. MATERIALS AND METHODS The study was approved by the institutional review board and was HIPAA compliant; informed consent was obtained. Bevacizumab-treated and control patients (41 per cohort) diagnosed with recurrent GBM were analyzed by using whole enhancing tumor ADC histograms with a two normal distribution mixture fitting curve on baseline (pretreatment) magnetic resonance (MR) images to generate ADC classifiers, including the overall mean ADC as well as the mean ADC from the lower curve (ADC(L)). Overall and 6-month progression-free survival (as defined by the Macdonald criteria) was determined by using Cox proportional hazard ratios and the Kaplan-Meier method with log-rank test. RESULTS For bevacizumab-treated patients, the hazard ratio for progression by 6 months in patients with less than versus greater than mean ADC(L) was 4.1 (95% confidence interval: 1.6, 10.4), and there was a 2.75-fold reduction in the median time to progression. For the control patients, there was no significant difference in median time to progression for the patients with low versus high ADC(L) (hazard ratio, 1.8; 95% confidence interval: 0.9, 3.7). For bevacizumab-treated patients, pretreatment ADC more accurately stratified 6-month progression-free survival than did change in enhancing tumor volume at first follow-up (73% vs 58% accuracy, P = .034). CONCLUSION Pretreatment ADC histogram analysis can stratify progression-free survival in bevacizumab-treated patients with recurrent GBM.

Clear cell renal cell carcinoma: discrimination from other renal cell carcinoma subtypes and oncocytoma at multiphasic multidetector CT.

PURPOSE To determine whether enhancement at multiphasic multidetector computed tomography (CT) can help differentiate clear cell renal cell carcinoma (RCC) from oncocytoma, papillary RCC, and chromophobe RCC. MATERIALS AND METHODS With institutional review board approval for this HIPAA-compliant retrospective study, the pathology database was queried to derive a cohort of 298 cases of RCC and oncocytoma with preoperative multiphasic multidetector CT with as many as four phases (unenhanced, corticomedullary, nephrographic, and excretory). A total of 170 clear cell RCCs, 57 papillary RCCs, 49 oncocytomas, and 22 chromophobe RCCs were evaluated for multiphasic enhancement and compared by using t tests. Cutoff analysis was performed to determine optimal threshold levels to discriminate among the four groups. RESULTS Mean enhancement of clear cell RCCs and oncocytomas peaked in the corticomedullary phase; mean enhancement of papillary and chromophobe RCCs peaked in the nephrographic phase. Enhancement of clear cell RCCs was greater than that of oncocytomas in the corticomedullary (125 HU vs 106 HU, P = .045) and excretory (80 HU vs 67 HU, P = .034) phases. Enhancement of clear cell RCCs was greater than that of papillary RCCs in the corticomedullary (125 HU vs 54 HU, P < .001), nephrographic (103 HU vs 64 HU, P < .001), and excretory (80 HU vs 54 HU, P < .001) phases. Enhancement of clear cell RCCs was greater than that of chromophobe RCCs in the corticomedullary (125 HU vs 74 HU, P < .001) and excretory (80 HU vs 60 HU, P = .008) phases. Thresholding of enhancement helped to discriminate clear cell RCC from oncocytoma, papillary RCC, and chromophobe RCC with accuracies of 77% (83 of 108 cases), 85% (101 of 119 cases), and 84% (81 of 97 cases). CONCLUSION Enhancement at multiphasic multidetector CT, if prospectively validated, may assist in the discrimination of clear cell RCC from oncocytoma, papillary RCC, and chromophobe RCC.

Apparent Diffusion Coefficient Histogram Analysis Stratifies Progression-Free Survival in Newly Diagnosed Bevacizumab-Treated Glioblastoma

BACKGROUND AND PURPOSE: Currently it is difficult to predict tumor response to anti-angiogenic therapy in individual patients. Our aim was to determine if ADC histogram analysis can stratify progression-free and overall survival in patients with newly diagnosed GBM treated “up-front” (ie, before tumor recurrence) with bevacizumab. MATERIALS AND METHODS: Up-front bevacizumab-treated and control patients (n = 59 and 62, respectively) with newly diagnosed GBM were analyzed by using an ADC histogram approach based on enhancing tumor. Progression-free and overall survival was determined by using Cox proportional HRs and the Kaplan-Meier method with logrank and Wilcoxon tests. RESULTS: For up-front bevacizumab-treated patients, lower ADCL was associated with significantly longer progression-free survival (median, 459 days for ADCL < 1200 versus 315 days for ADCL ≥ 1200 10−6mm2/s; P = .008, logrank test) and trended with longer overall survival (581 versus 429 days, P = .055). ADC values did not stratify progression-free or overall survival for patients in the control group (P = .92 and P = .22, respectively). Tumors with MGMT promoter methylation had lower ADCL values than unmethylated tumors (mean, 1071 versus 1183 10−6mm2/s; P = .01, 2-group t test). CONCLUSIONS: Pretreatment ADC histogram analysis can stratify progression-free survival in bevacizumab-treated patients with newly diagnosed GBM. Lower ADC is associated with tumor MGMT promoter methylation, which may, in part, account for the favorable outcome associated with low ADCL tumors.

Advances in MRI assessment of gliomas and response to anti-VEGF therapy.

Bevacizumab is thought to normalize tumor vasculature and restore the blood–brain barrier, decreasing enhancement and peritumoral edema. Conventional measurements of tumor response rely upon dimensions of enhancing tumor. After bevacizumab treatment, glioblastomas are more prone to progress as nonenhancing tumor. The RANO (Response Assessment in Neuro-Oncology) criteria for glioma response use fluid-attenuated inversion recovery (FLAIR)/T2 hyperintensity as a surrogate for nonenhancing tumor; however, nonenhancing tumor can be difficult to differentiate from other causes of FLAIR/T2 hyperintensity (eg, radiation-induced gliosis). Due to these difficulties, recent efforts have been directed toward identifying new biomarkers that either predict treatment response or accurately measure response of both enhancing and nonenhancing tumor shortly after treatment initiation. This will allow for earlier treatment decisions, saving patients from the adverse effects of ineffective therapies while allowing them to try alternative therapies sooner. An active area of research is the use of physiologic imaging, which can potentially detect treatment effects before changes in tumor size are evident.

Qualitative and Quantitative MDCT Features for Differentiating Clear Cell Renal Cell Carcinoma From Other Solid Renal Cortical Masses

OBJECTIVE The purpose of this study was to differentiate clear cell renal cell carcinoma (RCC) from other solid renal masses on four-phase MDCT. MATERIALS AND METHODS Our study cohort included all pathologically proven solid renal masses that underwent pretreatment four-phase MDCT at our institution from 2001 to 2012. Both retrospective qualitative analysis (blinded dual-radiologist evaluation of morphologic features: enhancement pattern, lesion contour, neovascularity, and calcification) and quantitative analysis (mean absolute and relative attenuation and changes in attenuation across phases) were performed. ANOVA with post-hoc analysis, Pearson chi-square tests, and ROC analysis were used. RESULTS One hundred fifty-six consecutive patients (99 men, 57 women) with a mean age of 62.7 years (range, 26-91 years) had 165 solid renal masses (median size, 3.0 cm): 86 clear cell RCCs, 36 papillary RCCs, 10 chromophobe RCCs, 23 oncocytomas, and 10 lipid-poor angiomyolipomas. Kappa for interradiologist agreement regarding morphologic features was 0.33-0.76. There were significant associations between histologic subtype and enhancement pattern (p < 0.001), lesion contour (p < 0.014), and neovascularity (p < 0.001). Clear cell RCC had the highest mean relative corticomedullary attenuation (p < 0.02). Clear cell RCC had greater deenhancement than oncocytoma (p < 0.001); deenhancement less than 50 HU or relative corticomedullary attenuation greater than 0% differentiated clear cell RCC from oncocytoma with a positive predictive value of 90%. Lipid-poor angiomyolipoma had the highest mean absolute unenhanced attenuation (p < 0.01); absolute unenhanced attenuation greater than 45 HU and relative corticomedullary attenuation less than 10% differentiated lipid-poor angiomyolipoma from clear cell RCC with a negative predictive value of 97%. CONCLUSION Four-phase MDCT renal attenuation profiles enable differentiation of clear cell RCC from other solid renal cortical masses, most notably papillary RCC and lipid-poor angiomyolipoma.

Performance of relative enhancement on multiphasic MRI for the Differentiation of Clear Cell Renal Cell Carcinoma (RCC) from Papillary and Chromophobe RCC subtypes and oncocytoma

OBJECTIVE The objective of our study was to investigate the performance of relative enhancement on multiphasic MRI to differentiate clear cell renal cell carcinoma (RCC) from other RCC subtypes (papillary and chromophobe) and oncocytoma. MATERIALS AND METHODS For this study, we derived a cohort of 34 clear cell RCCs, nine oncocytomas, 12 papillary RCCs, and 10 chromophobe RCCs with a preoperative multiphasic dynamic contrast-enhanced MRI study with up to four phases (i.e., unenhanced, corticomedullary, nephrographic, excretory) from 2005 to 2016. These groups were evaluated for multiphasic enhancement and were compared using Kruskal-Wallis and Mann-Whitney tests. ROC curves were constructed and logistic regression analyses were performed to evaluate the performance of multiphasic enhancement in differentiating clear cell RCCs from the other three groups. RESULTS Clear cell RCCs exhibited significantly greater relative signal intensity compared with uninvolved renal cortex in the corticomedullary phase (mean, 2.9) than oncocytomas (-21.7, p = 0.001), papillary RCCs (-53.0, p < 0.001), and chromophobe RCCs (-21.0, p < 0.001). Relative signal intensity in the corticomedullary phase differentiated clear cell RCCs from oncocytomas with an AUC of 0.90 and with an accuracy of 84% (32/38), sensitivity of 90% (27/30), and specificity of 63% (5/8) after controlling for lesion size, patient age, and patient sex. Relative corticomedullary signal intensity differentiated clear cell RCCs from oncocytomas and other RCC subtypes with an AUC of 0.93 and with an accuracy of 90% (53/59), sensitivity of 90% (27/30), and specificity of 90% (26/29) after controlling for lesion size, patient age, and patient sex. CONCLUSION Multiphasic MRI enhancement may assist in differentiating clear cell RCC from oncocytomas and other RCC subtypes, if validated in prospective studies.

Clear Cell Renal Cell Carcinoma: Identifying the Loss of the Y Chromosome on Multiphasic MDCT.

OBJECTIVE The objective of our study was to investigate whether multiphasic MDCT enhancement can help identify clear cell renal cell carcinomas (RCCs) with the loss of the Y chromosome. MATERIALS AND METHODS We derived a cohort of 43 clear cell RCCs in men who underwent preoperative four-phase renal mass MDCT from October 2000 to August 2013. Each lesion was segmented in its entirety on axial images. A computer-assisted detection algorithm selected a 0.5-cm-diameter region of maximal attenuation within each lesion in each phase. A 0.5-cm-diameter ROI was manually placed on uninvolved renal cortex in each phase. The relative attenuation of each lesion was calculated as follows: [(maximal lesion attenuation - cortex attenuation) / cortex attenuation] × 100. Absolute attenuation and relative attenuation in each phase were compared using t tests. RESULTS Both clear cell RCCs with the loss of the Y chromosome and clear cell RCCs without the loss of the Y chromosome exhibited peak enhancement in the corticomedullary phase. However, relative nephrographic attenuation of clear cell RCCs with the loss of Y was significantly less than that of clear cell RCCs without the loss of Y (mean, -8.9 vs 8.4 respectively; p = 0.013). A relative nephrographic attenuation threshold of -1.6 identified the loss of Y with an accuracy of 70% (30/43), sensitivity of 73% (16/22), and specificity of 67% (14/21). CONCLUSION Multiphasic MDCT enhancement may assist in identifying the loss of the Y chromosome in clear cell RCCs; this result should be validated in a large prospective trial.

Sarcomatoid Renal Cell Carcinoma and Collecting Duct Carcinoma: Discrimination From Common Renal Cell Carcinoma Subtypes and Benign RCC Mimics on Multiphasic MDCT

RATIONALE AND OBJECTIVES To investigate whether imaging features on multiphasic multidetector computed tomography (MDCT) can help discriminate sarcomatoid renal cell carcinoma (RCC) and collecting duct carcinoma (CDC) from other solid renal masses. MATERIALS AND METHODS With institutional review board approval for this HIPAA-compliant study, we derived a cohort of 7 sarcomatoid RCCs, 4 CDCs, 165 clear cell RCCs, 56 papillary RCCs, 22 chromophobe RCCs, 49 oncocytomas, and 16 lipid-poor angiomyolipomas with preoperative multiphasic MDCT with up to four phases (unenhanced, corticomedullary, nephrographic, and excretory). Each lesion was reviewed for contour, spread pattern, pattern of enhancement, neovascularity, and calcification. RESULTS Sarcomatoid RCCs and CDCs were more likely than other solid renal masses to have an irregular contour (64% vs 2%, P < 0.001) and an infiltrative spread pattern, defined as infiltration into adjacent renal parenchyma, collecting system, or neighboring structures (82% vs 7%, P < 0.001). When used to discriminate sarcomatoid RCC and CDC from other solid renal masses, an infiltrative spread pattern had a specificity of 93% (287/308) and sensitivity of 82% (9/11), and an irregular contour had a specificity of 98% (303/308) and sensitivity of 64% (7/11). CONCLUSIONS Solid renal lesions with an irregular contour or an infiltrative spread pattern are suspicious for sarcomatoid RCC or CDC.

MP22-07 CORRELATION OF CAD PEAK LESION ENHANCEMENT WITH QUANTITATIVE TUMOR ANGIOGENESIS TO NON-INVASIVELY ASSESS FURHMAN GRADES I-IV IN PATIENTS WITH CLEAR CELL RENAL CELL CARCINOMA

INTRODUCTION AND OBJECTIVES: To assess if Computer Aided Detection (CAD) of peak lesion attenuation discriminates among Fuhrman Grades I-IV and correlates with an increase in tumor angiogenesis in clear cell RCC (ccRCC) on four-phase MDCT. METHODS: We reviewed a cohort of patients with ccRCC and preoperative multiphasic multidetector CT imaged with a 4-phase renal mass protocol (unenhanced, corticomedullary (C), nephrographic (N), and excretory (E)). A whole lesion 3D contour was obtained in all phases with proprietary software. The CAD algorithm determined a 0.5cm diameter region of peak enhancement 300HU within the 3D lesion contour. For assessment of quantitative angiogenesis, immunohistochemical staining for CD34 to determine microvessel density (MVD) was performed. T-tests were used to compare peak multiphasic enhancement and microvessel density among Fuhrman grades I-IV. P values less than 0.05 were considered to be significant. RESULTS: 107 patients (71(64%) men and 40(35%) women) with 111 unique ccRCC lesions (16 (14%) Fuhrman grade I, 64 (58%) Fuhrman grade II, 23 (21%) Fuhrman Grade III, 8 (7%) Fuhrman grade IV) were analyzed. In the C phase, CAD peak lesion enhancement discriminated grade I from II (150 HU vs. 185 HU, p1⁄40.006), I from III (150 HU vs. 178 HU, p1⁄40.054), I from IV (150 HU vs 229HU, p<0.001). This directly correlated with an increase in quantitative angiogenesis (MVD): I from II (2134 mm2 vs. 4710 mm2, p1⁄40.004), I from III (2134 mm2 vs. 5162 mm, p1⁄40.001), I from IV (2134 mm2 vs 6076 mm2, p1⁄40.057). CONCLUSIONS: CAD peak lesion enhancement discriminates Fuhrman grades 1-IV on multiphasic CT and correlates with an increase in tumor angiogenesis. This may be helpful to triage patients to active surveillance, interventional therapy or, if validated, may be useful to monitor results with anti-angiogenic therapy.