Comprehensive tissue deconvolution of cell-free DNA by deep learning for disease diagnosis and monitoring.

Plasma cell-free DNA (cfDNA) is a noninvasive biomarker for cell death of all organs. Deciphering the tissue origin of cfDNA can reveal abnormal cell death because of diseases, which has great clinical potential in disease detection and monitoring. Despite the great promise, the sensitive and accurate quantification of tissue-derived cfDNA remains challenging to existing methods due to the limited characterization of tissue methylation and the reliance on unsupervised methods. To fully exploit the clinical potential of tissue-derived cfDNA, here we present one of the largest comprehensive and high-resolution methylation atlas based on 521 noncancer tissue samples spanning 29 major types of human tissues. We systematically identified fragment-level tissue-specific methylation patterns and extensively validated them in orthogonal datasets. Based on the rich tissue methylation atlas, we develop the first supervised tissue deconvolution approach, a deep-learning-powered model, cfSort, for sensitive and accurate tissue deconvolution in cfDNA. On the benchmarking data, cfSort showed superior sensitivity and accuracy compared to the existing methods. We further demonstrated the clinical utilities of cfSort with two potential applications: aiding disease diagnosis and monitoring treatment side effects. The tissue-derived cfDNA fraction estimated from cfSort reflected the clinical outcomes of the patients. In summary, the tissue methylation atlas and cfSort enhanced the performance of tissue deconvolution in cfDNA, thus facilitating cfDNA-based disease detection and longitudinal treatment monitoring.

Characterization of Microwave Generator Energy and Ablation Volumes following Transarterial Embolization in an In Vivo Porcine Liver Model.

PURPOSE: To characterize the relationship between ablation zone volume (AZV) and microwave ablation (MWA) energy in an in vivo porcine liver model following arterial embolization. MATERIALS AND METHODS: With Institutional Animal Care and Use Committee (IACUC) approval, 11 female swine underwent either right (n = 5) or left (n = 6) hepatic artery embolization under fluoroscopic guidance. Subsequently, ultrasound (US)-guided MWA was performed in each liver segment (left lateral, left medial, right medial, and right lateral) at either 30 W (n = 4 lobes), 60 W (n = 4), 65 W (n = 20), 90 W (n = 8), 120 W (n = 4), or 140 W (n = 4) continuously for 5 minutes. Postprocedural volumetric segmentation was performed on standardized multiphase T1 magnetic resonance (MR) imaging sequences. RESULTS: Mean AZVs in embolized lobes (15.8 mL ± SD 10.6) were significantly larger than those in nonembolized lobes (11.2 mL ± SD 6.5, P < .01). MWA energy demonstrated significant positive linear correlation with both embolized (R2 = 0.66, P < .01) and nonembolized (R2 = 0.64, P < .01) lobes. The slope of the linear models corresponded to a 0.95 mL/kJ (SD ± 0.16) and 0.54 mL/kJ (SD ± 0.09) increase in ablation volume per applied kilojoule of energy (E) in embolized and nonembolized lobes, respectively. In the multivariate model, embolization status significantly modified the relationship between E and AZV as described by the following interaction term: 0.42∗E∗(embolization status) (P = .031). CONCLUSIONS: Linear models demonstrated a near 1.8-fold increase in ratio of AZV per unit E, R(AZV:E), when applied to embolized lobes relative to nonembolized lobes. Absolute AZV differences between embolized and nonembolized lobes were greater at higher-power MWA.

MR imaging biomarkers in HCC: outcomes correlation in liver transplant listed patients.

PURPOSE: To determine hepatocellular carcinoma (HCC) magnetic resonance imaging (MRI) biomarkers that enable the prediction of delisting from tumor progression versus successful transplantation in patients listed for orthotopic liver transplantation (OLT). METHODS: With IRB approval and HIPPA compliance, patients with HCC awaiting OLT who were delisted due to HCC progression from 2006 to 2015 were identified. Patients with adequate MR images for review were subsequently matched with a cohort of patients successfully bridged to OLT in the same time period. Matching considered the tumor stage and the dominant treatment strategy adopted to bridge the patient to OLT. Potential MRI features were evaluated by univariable and multivariable analysis using a conditional logistic model. RESULTS: There were 53 patients included in each cohort. On uni-variable analysis, significant unfavorable MR imaging features included T2 hyperintensity (odds ratio [OR], 19.0), infiltrative border (OR, 7.50), lobulated shape (OR, 4.5), T1 hypointensity (OR, 3.0), heterogeneous arterial enhancement (OR, 7.0), and corona venous enhancement (OR, 4.0). A significant favorable MR imaging feature was the presence of intralesional fat (OR = .36). The best multivariable logistic prediction model derived from the above notable features included only T1 and T2 signal intensity, border definition, and absence of intra-lesional fat as significant variables, with an area under the receiver operating characteristic curve (AUC) of .86 in the prediction of delisting. CONCLUSION: Select MR imaging features of HCC at presentation before any treatment are significantly associated with the risk of tumor progression regardless of tumor stage and treatment strategy in patients awaiting liver transplantation.

Hepatocellular Adenoma Subtypes Based on 2017 Classification System: Exploratory Study of Gadoxetate Disodium-Enhanced MRI Features With Proposal of a Diagnostic Algorithm.

BACKGROUND. The classification of hepatocellular adenomas (HCAs) was updated in 2017 on the basis of genetic and molecular analysis. OBJECTIVE. The purpose of this article was to evaluate features on gadoxetate disodium-enhanced MRI of HCA subtypes on the basis of the 2017 classification and to propose a diagnostic algorithm for determining subtype using these features. METHODS. This retrospective study included 56 patients (49 women, seven men; mean age, 37 ± 13 [SD] years) with histologically confirmed HCA evaluated by gadoxetate disodium-enhanced MRI from January 2010 to January 2021. Subtypes were reclassified using 2017 criteria: hepatocyte nuclear factor-1α mutated HCA (HHCA), inflammatory HCA (IHCA), ß-catenin exon 3 activated HCA (ß-HCA), mixed inflammatory and ß-HCA (ß-IHCA), sonic hedgehog HCA (shHCA), and unclassified HCA (UHCA). Qualitative MRI features were assessed. Liver-to-lesion contrast enhancement ratios (LLCERs) were measured. Subtypes were compared, and a diagnostic algorithm was proposed. RESULTS. The analysis included 65 HCAs: 16 HHCAs, 31 IHCAs, six ß-HCA, four ß-IHCA, five shHCA, and three UHCAs. HHCAs showed homogeneous diffuse intralesional steatosis in 94%, whereas all other HCAs showed this finding in 0% (p < .001). IHCAs showed the "atoll" sign in 58%, whereas all other HCAs showed this finding in 12% (p < .001). IHCAs showed moderate T2 hyperintensity in 52%, whereas all other HCAs showed this finding in 12% (p < .001). The ß-HCAs and ß-IHCAs occurred in men in 63%, whereas all other HCAs occurred in men in 4% (p < .001). The ß-HCAs and ß-IHCAs had a mean size of 10.1 ± 6.8 cm, whereas all other HCAs had a mean size of 5.1 ± 2.9 cm (p = .03). The ß-HCAs and ß-IHCAs showed fluid components in 60%, whereas all other HCAs showed this finding in 5% (p < .001). Hepatobiliary phase iso- or hyperintensity was observed in 80% of ß-HCAs and ß-IHCAs versus 5% of all other HCAs (p < .001). Hepatobiliary phase LLCER was positive in nine HCAs (eight ß-HCAs and ß-IHCAs; one IHCA). The shHCA and UHCA did not show distinguishing features. The proposed diagnostic algorithm had accuracy of 98% for HHCAs, 83% for IHCAs, and 95% for ß-HCAs or ß-IHCAs. CONCLUSION. Findings on gadoxetate disodium-enhanced MRI, including hepatobiliary phase characteristics, were associated with HCA subtypes using the 2017 classification. CLINICAL IMPACT. The algorithm identified common HCA subtypes with high accuracy, including those with ß-catenin exon 3 mutations.

Hepatocellular Adenomas: Molecular Basis and Multimodality Imaging Update.

Hepatocellular adenomas (HCAs) are a family of liver tumors that are associated with variable prognoses. Since the initial description of these tumors, the classification of HCAs has expanded and now includes eight distinct genotypic subtypes based on molecular analysis findings. These genotypic subtypes have unique derangements in their cellular biologic makeup that determine their clinical course and may allow noninvasive identification of certain subtypes. Multiphasic MRI performed with hepatobiliary contrast agents remains the best method to noninvasively detect, characterize, and monitor HCAs. HCAs are generally hypointense during the hepatobiliary phase; the ß-catenin-mutated exon 3 subtype and up to a third of inflammatory HCAs are the exception to this characterization. It is important to understand the appearances of HCAs beyond their depictions at MRI, as these tumors are typically identified with other imaging modalities first. The two most feared related complications are bleeding and malignant transformation to hepatocellular carcinoma, although the risk of these complications depends on tumor size, subtype, and clinical factors. Elective surgical resection is recommended for HCAs that are persistently larger than 5 cm, adenomas of any size in men, and all ß-catenin-mutated exon 3 HCAs. Thermal ablation and transarterial embolization are potential alternatives to surgical resection. In the acute setting of a ruptured HCA, patients typically undergo transarterial embolization with or without delayed surgical resection. This update on HCAs includes a review of radiologic-pathologic correlations by subtype and imaging modality, related complications, and management recommendations. © RSNA, 2023 Online supplemental material is available for this article. Quiz questions for this article are available through the Online Learning Center.

CT-monitored minimal ablative margin control in single-session microwave ablation of liver tumors: an effective strategy for local tumor control.

OBJECTIVES: To investigate the usefulness of minimal ablative margin (MAM) control by intra-procedural contrast-enhanced CT (CECT) in microwave ablation (MWA) of liver tumors. METHODS: A total of 334 consecutive liver tumors (240 hepatocellular carcinomas [HCCs] and 94 colorectal liver metastases [CRLMs]) in 172 patients treated with percutaneous MWA were retrospectively included. MAM of each tumor was assessed after expected ablation completion using intra-procedural CECT, allowing within-session additional ablation to any potentially insufficient margin. On immediate post-MWA MRI, complete ablation coverage of tumor and final MAM status were determined. The cumulative local tumor progression (LTP) rate was estimated by using the Kaplan-Meier method. To identify predictors of LTP, Cox regression analysis with a shared frailty model was performed. RESULTS: Intra-procedural CECT findings prompted additional ablation in 18.9% (63/334) of tumors. Final complete ablation coverage of tumor and sufficient MAM were determined by MRI to be achieved in 99.4% (332/334) and 77.5% (259/334), and their estimated 6-month, 1-year, and 2-year LTP rates were 3.2%, 7.5%, and 12.9%; and 1.0%, 2.1%, and 6.9%, respectively. Insufficient MAM on post-MWA MRI, perivascular tumor location, and tumor size (cm) were independent risk factors for LTP (hazard ratio = 14.4, 6.0, and 1.1, p < 0.001, p = 0.003, and p = 0.011, respectively), while subcapsular location and histology (HCC vs CRLM) were not. CONCLUSIONS: In MWA of liver tumors, intra-procedural CECT monitoring of minimal ablative margin facilitates identification of potentially suboptimal margins and guides immediate additional intra-session ablation to maximize rates of margin-sufficient ablations, the latter being a highly predictive marker for excellent long-term local tumor control. KEY POINTS: • In MWA of liver tumors, intra-procedural CECT can identify potentially suboptimal minimal ablative margin, leading to immediate additional ablation in a single treatment session. • Achieving a finally sufficient ablative margin through the MWA with intra-procedural CECT monitoring of minimal ablative margin results in excellent local tumor control.

Consensus Guidelines for the Definition of Time-to-Event End Points in Image-guided Tumor Ablation: Results of the SIO and DATECAN Initiative.

There is currently no consensus regarding preferred clinical outcome measures following image-guided tumor ablation or clear definitions of oncologic end points. This consensus document proposes standardized definitions for a broad range of oncologic outcome measures with recommendations on how to uniformly document, analyze, and report outcomes. The initiative was coordinated by the Society of Interventional Oncology in collaboration with the Definition for the Assessment of Time-to-Event End Points in Cancer Trials, or DATECAN, group. According to predefined criteria, based on experience with clinical trials, an international panel of 62 experts convened. Recommendations were developed using the validated three-step modified Delphi consensus method. Consensus was reached on when to assess outcomes per patient, per session, or per tumor; on starting and ending time and survival time definitions; and on time-to-event end points. Although no consensus was reached on the preferred classification system to report complications, quality of life, and health economics issues, the panel did agree on using the most recent version of a validated patient-reported outcome questionnaire. This article provides a framework of key opinion leader recommendations with the intent to facilitate a clear interpretation of results and standardize worldwide communication. Widespread adoption will improve reproducibility, allow for accurate comparisons, and avoid misinterpretations in the field of interventional oncology research. Published under a CC BY 4.0 license. Online supplemental material is available for this article. See also the editorial by Liddell in this issue.

Image-Guided Percutaneous Thermal Ablation of Oligometastatic Ovarian and Non-Ovarian Gynecologic Tumors.

PURPOSE: To assess the safety, feasibility, and efficacy of percutaneous thermal ablation (TA) in the treatment of metastatic gynecologic (GYN) tumors. MATERIALS AND METHODS: A study cohort of 42 consecutive women (mean age, 59. years; range, 25-78 years) with metastatic GYN tumors (119 metastatic tumors) treated with radiofrequency (n = 47 tumors), microwave (n = 47 tumors), or cryogenic (n = 30 tumors) ablation from over 2,800 ablations performed from January 2001 to January 2019 was identified. The primary GYN neoplasms consisted of ovarian (27 patients; 77 tumors; mean tumor diameter [MTD], 2.50 cm), uterine (7 patients; 26 tumors; MTD, 1.89 cm), endometrial (5 patients; 10 tumors; MTD, 2.8 cm), vaginal (2 patients; 5 tumors; MTD, 2.40 cm), and cervical (1 patient; 1 tumor; MTD, 1.90 cm) cancers. In order of descending frequency, metastatic tumors treated by TA were located in the liver or liver capsule (74%), lungs (13%), and peritoneal implants (9%). Single tumors were also treated in the kidneys, rectus muscle, perirectal soft tissue (2.5%), and retroperitoneal lymph nodes (1.6%). All efficacy parameters of TA and definitions of major and minor adverse events are categorized by the latest Society of Interventional Radiology reporting standards. RESULTS: The median follow-up of treated patients was 10 months. After the initial ablation, 95.6% of the patients achieved a complete tumor response confirmed by contrast-enhanced magnetic resonance imaging or computed tomography. On surveillance imaging, 8.5% of the ablated tumors developed local progression over a median follow-up period of 4.1 months. Five of 8 tumors with local recurrence underwent repeated treatment over a mean follow-up period of 18 months, and 4 of 5 tumors achieved complete eradication after 1 additional treatment session that resulted in a secondary efficacy of 80%. The overall technique efficacy of TA was 96.2% over a median follow-up period of 10 months. CONCLUSIONS: TA was safe and effective for the local control of metastatic GYN tumors in the lungs, abdomen, and pelvis, with an overall survival rate of 37.5 months and a local progression-free survival rate of 16.5 months, with only 4.8% of treated patients experiencing a major adverse event.

Percutaneous thermal ablation of subcapsular hepatocellular carcinomas: influence of tumor-surface contact and protrusion on therapeutic efficacy and safety.

PURPOSE: To evaluate therapeutic efficacy and complication of percutaneous thermal ablation of subcapsular hepatocellular carcinomas (HCCs), and how these may be influenced by the degree of tumor to liver surface contact and tumor protrusion from liver surface. MATERIALS AND METHODS: Our retrospective study was approved by the Institutional Review Board. Between January 2006 and December 2013, 290 patients (82 women, 208 men; mean age, 64.5 years; range, 33-89 years) with 474 subcapsular (within 1 cm to the liver surface) HCCs (mean size, 23.7 mm; range, 6-71 mm) underwent percutaneous thermal ablation. The HCCs were divided into surface contact group (n = 243) and non-surface contact group (n = 231). The former was further subdivided into exophytic and non-exophytic HCCs. Technical success, primary technique efficacy, local tumor progression (LTP), and secondary technique efficacy rates were analyzed and compared by the chi-square test or Fisher exact test. Prognostic factors for LTP and secondary technique efficacy were assessed using the Cox regression model. Major complications were also assessed. RESULTS: With median follow-up of 15 months (range, 1-87 months), technical success and primary technique efficacy were 98.7% and 95.7% % in the non-surface contact group; 96.4% and 94.0% in the non-exophytic group; and 100% and 94.7% in the exophytic group (p > 0.05). Tumor size > 3 cm was a significant predictor for LTP, but not for secondary efficacy. Overall major complication rate was 3.8% (24/624) and was not different among the three groups. CONCLUSION: Subcapsular HCCs can be effectively treated with thermal ablation techniques. Degree of tumor-surface contact including moderate protrusion does not appear to limit feasibility or procedure effectiveness. KEY POINTS: • Subcapsular HCCs can be effectively treated with thermal therapy when proper image-guided technique and assistive techniques are applied. • Degree of tumor surface contact including moderate protrusion does not appear to limit feasibility or procedure effectiveness. • Major complications after percutaneous thermal ablation of subcapsular HCCs such as tumor seeding can be minimized by avoiding breach of the tumor capsule exposed to the peritoneal surface and use of tract ablation.

Updated 10-year outcomes of percutaneous radiofrequency ablation as first-line therapy for single hepatocellular carcinoma < 3 cm: emphasis on association of local tumor progression and overall survival.

OBJECTIVES: The purpose of this study was to evaluate the 10-year overall survival and local tumor progression (LTP) of percutaneous radiofrequency ablation (RFA) for single nodular hepatocellular carcinoma (HCC) < 3 cm using a large longitudinal hospital registry and clinical factors associated with overall survival and LTP. METHODS: A total of 467 newly diagnosed patients with single nodular HCC < 3 cm who underwent RFA as first-line therapy between January 2008 to December 2016 were analyzed. Overall survival and LTP were estimated using the Kaplan-Meier method. Cox regression and competing risks Cox regression analysis were performed to identify prognostic factors for overall survival and LTP, respectively. RESULTS: The 5- and 10-year overall survival rates after RFA were 83.7% and 74.2%, respectively. LTP (hazard ratio (HR), 2.03; 95% confidence interval (CI), 1.19-3.47) was one of the important factors for overall survival after RFA. The 5- and 10-year LTP rates after RFA were 20.4% and 25.1%, respectively. Periportal location (subdistribution HR, 2.29; 95% CI, 1.25-4.21), subphrenic location (2.25, 1.34-3.86), size ≥ 1.5-< 2.0 cm (1.88, 1.05-3.39), and size ≥ 2.0 cm (2.10, 1.14-3.86) were independent factors for LTP. CONCLUSION: Ten-year therapeutic outcomes of percutaneous RFA as first-line therapy were excellent for single HCC < 3 cm. LTP was an important prognostic factor for overall survival after RFA. Periportal and subphrenic location of HCCs and tumor size were predictors for the development of LTP after RFA. KEY POINTS: • Updated 10-year survival outcome of percutaneous radiofrequency ablation as first-line therapy for single hepatocellular carcinoma < 3 cm was higher than previously reported. • Local tumor progression was an important prognostic factor for overall survival after percutaneous radiofrequency ablation. • Periportal and subphrenic location of hepatocellular carcinomas and tumor size were predictors for the development of local tumor progression after percutaneous radiofrequency ablation.

Long-Term Survival after Percutaneous Radiofrequency Ablation of Pathologically Proven Renal Cell Carcinoma in 100 Patients.

PURPOSE: To determine the long-term survival of patients treated with percutaneous radiofrequency (RF) ablation for pathologically proven renal cell carcinoma (RCC). MATERIALS AND METHODS: In this single-center retrospective study, 100 patients with 125 RCCs (100 clear-cell, 19 papillary, and 6 chromophobe) 0.8-8 cm in size treated with RF ablation were evaluated at a single large tertiary-care center between 2004 and 2015. Technical success, primary and secondary technique efficacy, and pre- and postprocedural estimated glomerular filtration rate (eGFR) at 3-6 months and 2-3 years were recorded. Overall survival, cancer-specific survival, and local tumor progression-free survival were calculated by Kaplan-Meier survival curves. Complications were classified per the Clavien-Dindo system. Statistical testing was done via χ2 tests for proportions and paired t test for changes in eGFR. Statistical significance was set at α = 0.05. RESULTS: Overall technical success rate was 100%, and primary and secondary technique efficacy rates were 90% and 100%, respectively. Median follow-up was 62.8 months, ranging from 1 to 120 months. The 10-year overall, cancer-specific, and local progression-free survival rates were 32%, 86%, and 92%, respectively. The number of ablation probes used was predictive of residual unablated tumor (P < .001). There were no significant changes in preprocedure vs 2-3-years postprocedure eGFR (65.2 vs 62.1 mL/min/1.73 m2; P = .443). There was a 9% overall incidence of complications, the majority of which were grade I. CONCLUSIONS: Image-guided percutaneous RF ablation of RCCs is effective at achieving local control and preventing cancer-specific death within 10 years from initial treatment.

Cirrhotic Nodule Transformation to Hepatocellular Carcinoma: Natural History and Predictive Biomarkers on Contrast-Enhanced Ultrasound.

OBJECTIVE. The objective of our study was to identify sonographic biomarkers predicting or indicating eventual malignant transformation of pathologically confirmed cirrhotic nodules. MATERIALS AND METHODS. Thirty-nine consecutive patients with 44 pathologically confirmed cirrhotic nodules (mean size, 17.5 ± 8.5 [SD] mm) who initially underwent contrast-enhanced ultrasound examination at detection and then underwent follow-up conventional ultrasound every 3-4 months thereafter were retrospectively included. Malignant transformation was identified on the basis of noninvasive diagnostic criteria for hepatocellular carcinoma or rebiopsy. Malignant transformation biomarkers were identified from clinical and sonographic variables and the performance thereof was evaluated using ROC curves. RESULTS. Fourteen nodules (31.8%) had eventual malignant transformation after a median follow-up time of 26.7 months. At initial detection, nodule size (hazard ratio [HR], 1.07; p = 0.019) and a contrast arrival time difference between the nodule and liver of more than 0.5 second (HR, 4.35; p = 0.011) were independent predictors for malignant transformation. The area under the ROC curve (Az) of initial nodule size (Az = 0.64, p = 0.131) and contrast arrival time difference between the nodule and liver (Az = 0.66, p = 0.029) improved after combining the two (Az = 0.75, p = 0.002). During follow-up, echogenicity change (p = 0.044), absolute growth rate (p < 0.001), and relative growth rate (p < 0.001) correlated with malignant transformation. Sensitivity analysis revealed that an absolute growth rate of 5 mm or greater in 6 months or a relative growth rate of 30% or greater in 6 months could be considered as threshold growth for identifying malignant transformation (specificity, 100.0%; positive predictive value, 100.0%). The absence of both echogenicity change and threshold growth was highly accurate in excluding malignant transformation (sensitivity, 100.0%; negative predictive value, 100.0%). CONCLUSION. The contrast arrival time difference between the nodule and liver at initial detection was useful in stratifying eventual malignant transformation risk for cirrhotic nodules. During follow-up, growth rate and echogenicity change correlated with malignant transformation; threshold growth on ultrasound may be considered a potential major feature in noninvasive diagnostic criteria of hepatocellular carcinoma.

Influence of the Location and Zone of Tumor in Prostate Cancer Detection and Localization on 3-T Multiparametric MRI Based on PI-RADS Version 2.

OBJECTIVE. The objective of our study was to determine the performance of 3-T multiparametric MRI (mpMRI) for prostate cancer (PCa) detection and localization, stratified by anatomic zone and level, using Prostate Imaging Reporting and Data System version 2 (PI-RADSv2) and whole-mount histopathology (WMHP) as reference. MATERIALS AND METHODS. Multiparametric MRI examinations of 415 consecutive men were compared with thin-section WMHP results. A genitourinary radiologist and pathologist collectively determined concordance. Two radiologists assigned PI-RADSv2 scores and sector location to all detected foci by consensus. Tumor detection rates were calculated for clinical and pathologic (tumor location and zone) variables. Both rigid and adjusted sector-matching models were used to account for fixation-related issues. RESULTS. Of 863 PCa foci in 16,185 prostate sectors, the detection of overall and index PCa lesions in the midgland, base, and apex was 54.9% and 83.1%, 42.1% and 64.0% (p = 0.04, p = 0.02), and 41.9% and 71.4% (p = 0.001, p = 0.006), respectively. Tumor localization sensitivity was highest in the midgland compared with the base and apex using an adjusted match compared with a rigid match (index lesions, 71.3% vs 43.7%; all lesions, 70.8% vs 36.0%) and was greater in the peripheral zone (PZ) than in the transition zone. Three-Tesla mpMRI had similarly high specificity (range, 93.8-98.3%) for overall and index tumor localization when using both rigid and adjusted sector-matching approaches. CONCLUSION. For 3-T mpMRI, the highest sensitivity (83.1%) for detection of index PCa lesions was in the midgland, with 98.3% specificity. Multiparametric MRI performance for sectoral localization of PCa within the prostate was moderate and was best for index lesions in the PZ using an adjusted model.

Utility of Multiparametric MRI for Predicting Residual Clinically Significant Prostate Cancer After Focal Laser Ablation.

OBJECTIVE. The purpose of this study was to compare in a multireader manner the diagnostic accuracies of 3-T multiparametric MRI interpretation and serial prostate-specific antigen (PSA) measurement in predicting the presence of residual clinically significant prostate cancer after focal laser ablation. MATERIALS AND METHODS. Eighteen men had undergone focal laser ablation for low- or intermediate-risk prostate cancer as part of two National Cancer Institute-funded phase 1 clinical trials. Multiparametric MRI was performed immediately after and 6 and 12 months after focal laser ablation. Serial PSA measurements after focal laser ablation were recorded, and MRI-ultrasound fusion biopsy was performed 6 and 12 months after ablation and served as the reference standard. Multiparametric MRI was performed at 3 T with pelvic phased-array coils. T2-weighted, DW, and dynamic contrast-enhanced MR images were retrospectively assessed by two blinded radiologists using a 3-point Likert scale (0-2). Inter-reader agreement was assessed with the Cohen kappa statistic. The diagnostic accuracies of multiparametric MRI and PSA measurement were compared. RESULTS. Residual clinically significant prostate cancer was identified in 11 of 18 (61%) men. Logistic regression analysis of serial PSA measurements yielded a correct classification rate of 61.1% (p > 0.05). Using a multiparametric MRI threshold score of 4 or greater, both radiologists made correct classifications for 16 of 18 men (89%) at 6 months and 15 of 17 men (88%) at 12 months. Interreader agreement was substantial to excellent for T2-weighted imaging, DWI, and dynamic contrast-enhanced MRI and improved uniformly from 6 to 12 months. Logistic regression analysis of the retrospectively reviewed multiparametric MR images yielded AUCs greater than 0.90 for each radiologist 6 and 12 months after focal laser ablation (p < 0.001). CONCLUSION. Multiparametric MRI 6 and 12 months after focal laser ablation significantly outperformed serial PSA measurements for predicting the presence of residual clinically significant prostate cancer.

Utility of Restriction Spectrum Imaging Among Men Undergoing First-Time Biopsy for Suspected Prostate Cancer.

OBJECTIVE. The purpose of this article is to evaluate restriction spectrum imaging (RSI) in men undergoing MRI-ultrasound fusion biopsy for suspected prostate cancer (PCa) and to compare the performance of RSI with that of conventional DWI. MATERIALS AND METHODS. One hundred ninety-eight biopsy-naïve men enrolled in a concurrent prospective clinical trial evaluating MRI-targeted prostate biopsy underwent multiparametric MRI with RSI. Clinical and imaging features were compared between men with and without clinically significant (CS) PCa (MRI-ultrasound fusion biopsy Gleason score ≥ 3 + 4). RSI z score and apparent diffusion coefficient (ADC) were correlated, and their diagnostic performances were compared. RESULTS. CS PCa was detected in 109 of 198 men (55%). Using predefined thresholds of ADC less than or equal to 1000 µm2/s and RSI z score greater than or equal to 3, sensitivity and specificity for CS PCa were 86% and 38%, respectively, for ADC and 61% and 70%, respectively, for RSI. In the transition zone (n = 69), the sensitivity and specificity were 94% and 17%, respectively, for ADC and 59% and 69%, respectively, for RSI. Among lesions with CS PCa, RSI z score and ADC were significantly inversely correlated in the peripheral zone (ρ = -0.4852; p < 0.01) but not the transition zone (ρ = -0.2412; p = 0.17). Overall diagnostic accuracies of RSI and DWI were 0.70 and 0.68, respectively (p = 0.74). CONCLUSION. RSI and DWI achieved equivalent diagnostic performance for PCa detection in a large population of men undergoing first-time prostate biopsy for suspected PCa, but RSI had superior specificity for transition zone lesions.

Detection and Localization of Prostate Cancer at 3-T Multiparametric MRI Using PI-RADS Segmentation.

OBJECTIVE. The purpose of this study is to determine the overall and sector-based performance of 3-T multiparametric MRI for prostate cancer (PCa) detection and localization by using Prostate Imaging-Reporting and Data System version 2 (PI-RADSv2) scoring and segmentation compared with whole-mount histopathologic analysis. MATERIALS AND METHODS. Multiparametric 3-T MRI examinations of 415 consecutive men were compared with thin-section whole-mount histopathologic analysis. A genitourinary radiologist and pathologist collectively determined concordance. Two radiologists assigned PI-RADSv2 categories and sectoral location to all detected foci by consensus. Tumor detection rates were calculated for clinical and pathologic (Gleason score) variables. Both rigid and adjusted sector-matching models were used to account for fixation-related issues. RESULTS. The 415 patients had 863 PCa foci (52.7% had a Gleason score ≥ 7, 61.9% were ≥ 1 cm, and 90.4% (375/415) of index lesions were ≥ 1 cm) and 16,185 prostate sectors. Multiparametric MRI enabled greater detection of PCa lesions 1 cm or larger (all lesions vs index lesions, 61.6% vs 81.6%), lesions with Gleason score greater than or equal to 7 (all lesions vs index lesions, 71.4% vs 80.9%), and index lesions with both Gleason score greater than or equal to 7 and size 1 cm or larger (83.3%). Higher sensitivity was obtained for adjusted versus rigid tumor localization for all lesions (56.0% vs 28.5%), index lesions (55.4% vs 34.3%), lesions with Gleason score greater than or equal to 7 (55.7% vs 36.0%), and index lesions 1 cm or larger (56.1% vs 35.0%). Multiparametric 3-T MRI had similarly high specificity (96.0-97.9%) for overall and index tumor localization with adjusted and rigid sector-matching approaches. CONCLUSION. Using 3-T multiparametric MRI and PI-RADSv2, we achieved the highest sensitivity (83.3%) for the detection of lesions 1 cm or larger with Gleason score greater than or equal to 7. Sectoral localization of PCa within the prostate was moderate and was better with an adjusted model than with a rigid model.

Propensity-Matched Analysis of Patients with Mixed Hepatocellular-Cholangiocarcinoma and Hepatocellular Carcinoma Undergoing Liver Transplantation.

Mixed hepatocellular-cholangiocarcinomas (HCC-CCAs) are rare tumors with both hepatocellular and biliary differentiation. While liver transplantation (LT) is the gold standard treatment for patients with unresectable hepatocellular carcinoma (HCC), it is contraindicated in known HCC-CCA because of concerns of poor prognosis. We sought to compare posttransplant oncologic outcomes for HCC-CCA and a matched cohort of HCC LT recipients. A retrospective, single-center analysis (1984-2015) identified 12 patients with mixed HCC-CCA who were matched 1:3 to patients with HCC on both pretransplant (radiologic diameter and alpha-fetoprotein) and explant (pathologic diameter, grade/differentiation, and vascular invasion) tumor characteristics. Compared with HCC patients matched on pretransplant characteristics (n = 36), HCC-CCA had higher explant tumor grade, more poorly differentiated tumors, but similar T stage and vascular invasion. HCC-CCA recipients trended toward inferior recurrence-free survival at 5 years (28% versus 61%; P = 0.12) and greater recurrence (HCC-CCA: 50%, median time to recurrence 297 days versus HCC: 22%, median time to recurrence 347 days; P = 0.07). However, when matched to a separate HCC cohort with similar explant pathology, HCC-CCA had similar 5-year recurrence-free survival (42% versus 44%; P = 0.45) and posttransplant recurrence (50% versus 27%; P = 0.13). All 6 HCC-CCA recurrences occurred with poorly differentiated tumors (median survival 21.3 months), without a single recurrence in 5 of the 12 HCC-CCA patients with well-moderately differentiated tumors (median survival 60.2 months). Mixed HCC-CCA tumors are more likely poorly differentiated tumors compared with HCC with similar pretransplant characteristics. However, compared with HCC with similar pathologic characteristics, they display similar recurrence-free survival and are not inherently more aggressive tumors. Low-grade, well-moderately differentiated HCC-CCAs have excellent survival with a low risk for post-LT recurrence, and they should not be excluded from LT. Improved pretransplant identification of pathologic characteristics in HCC-CCA may allow for successful utilization of LT in this subset of patients.

Radiofrequency ablation of hepatocellular carcinoma as bridge therapy to liver transplantation: A 10-year intention-to-treat analysis.

In a long-term (10-year) study of radiofrequency ablation (RFA) of hepatocellular carcinoma (HCC) as bridging therapy in patients listed for orthotopic liver transplantation (LT), we evaluated the impact of RFA on waiting list dropout rate, post-LT tumor recurrence, and long-term intention-to-treat, disease-specific survival (DSS). From March 2004 to October 2014, RFA was performed as the initial stand-alone bridge therapy to LT for 121 patients (men/women ratio, 83:38; mean age, 60.0 years) with 156 de novo HCCs (mean size, 2.4 cm). Follow-up period from initial RFA ranged from 1.3 to 128.0 months (median, 42.9 months). We assessed the overall and tumor-specific waiting list dropout rates, post-LT tumor recurrence, and 10-year post-LT and intention-to-treat survival rates. Dropout from the waiting list due to tumor progression occurred in 7.4% of patients. HCC recurrence after LT occurred in 5.6% of patients. The post-LT overall survival (OS) rate at 5 and 10 years was 75.8% and 42.2%, respectively, and the recurrence-free survival (RFS) rate was 71.1% and 39.6%, respectively. Intention-to-treat OS, RFS, and DSS rates for the entire study population at 5 and 10 years were 63.5% and 41.2%, 60.8% and 37.7%, and 89.5% and 89.5%, respectively. CONCLUSION: RFA as a first-line stand-alone bridge therapy to LT achieves excellent long-term overall and tumor-specific survivals, with a low dropout rate from tumor progression despite long wait list times and a sustained low tumor recurrence rate upon post-LT follow-up of up to 10 years. (Hepatology 2017;65:1979-1990).

Liver MR Elastography at 3 T: Agreement Across Pulse Sequences and Effect of Liver R2* on Image Quality.

OBJECTIVE: The objectives of our study were to compare MR elastography (MRE) based on gradient-recalled echo (GRE) imaging with spin-echo echo-planar imaging (SEEPI) and rapid fractional (RF)-GRE MRE sequences at 3 T in terms of liver stiffness (LS) and image quality and to evaluate the effect of liver R2* on image quality. MATERIALS AND METHODS: Eighty-one patients underwent 3-T liver MRE with GRE, SE-EPI, and RF-GRE sequences performed in variable order in this study. LS and ROI areas on the LS 95% confidence maps were compared among the three sequences. The relationship between liver R2* and ROI area was investigated. RESULTS: There was no significant difference in mean LS among the three sequences (p = 0.49). Mean ROI area was significantly larger for RF-GRE (18,213 ± 9292 [SD] mm2) than for GRE (13,196 ± 8149 mm2) and SE-EPI (12,896 ± 8656 mm2) (p < 0.0001). Liver R2* was significantly higher among patients with one or more failed sequences (mean ± SD, 116 ± 76 s-1) than for patients with no failed sequences (59 ± 26 s-1) (p = 0.001). Technical failure rates were 10% (8/81), 4% (3/81), and 2% (2/81) for GRE, SE-EPI, and RF-GRE, respectively. Among patients with iron overload (R2* ≥ 100 s-1), there was a trend toward larger ROI area for SE-EPI (p = 0.09). CONCLUSION: SE-EPI-and RF-GRE-based MRE sequences provide equivalent measures of LS compared with GRE-based MRE, and both have lower technical failure rates. The RF-GRE sequence yielded the largest measurable area of LS. Among patients with iron overload, there was a trend toward larger measurable area of LS for the SE-EPI sequence.

In-Bore 3-T MR-guided Transrectal Targeted Prostate Biopsy: Prostate Imaging Reporting and Data System Version 2-based Diagnostic Performance for Detection of Prostate Cancer.

Purpose To determine the diagnostic yield of in-bore 3-T magnetic resonance (MR) imaging-guided prostate biopsy and stratify performance according to Prostate Imaging Reporting and Data System (PI-RADS) versions 1 and 2. Materials and Methods This study was HIPAA compliant and institution review board approved. In-bore 3-T MR-guided prostate biopsy was performed in 134 targets in 106 men who (a) had not previously undergone prostate biopsy, (b) had prior negative biopsy findings with increased prostate-specific antigen (PSA) level, or (c) had a prior history of prostate cancer with increasing PSA level. Clinical, diagnostic 3-T MR imaging was performed with in-bore guided prostate biopsy, and pathology data were collected. The diagnostic yields of MR-guided biopsy per patient and target were analyzed, and differences between biopsy targets with negative and positive findings were determined. Results of logistic regression and areas under the curve were compared between PI-RADS versions 1 and 2. Results Prostate cancer was detected in 63 of 106 patients (59.4%) and in 72 of 134 targets (53.7%) with 3-T MR imaging. Forty-nine of 72 targets (68.0%) had clinically significant cancer (Gleason score ≥ 7). One complication occurred (urosepsis, 0.9%). Patients who had positive target findings had lower apparent diffusion coefficient values (875 × 10-6 mm2/sec vs 1111 × 10-6 mm2/sec, respectively; P < .01), smaller prostate volume (47.2 cm3 vs 75.4 cm3, respectively; P < .01), higher PSA density (0.16 vs 0.10, respectively; P < .01), and higher proportion of PI-RADS version 2 category 3-5 scores when compared with patients with negative target findings. MR targets with PI-RADS version 2 category 2, 3, 4, and 5 scores had a positive diagnostic yield of three of 23 (13.0%), six of 31 (19.4%), 39 of 50 (78.0%), and 24 of 29 (82.8%) targets, respectively. No differences were detected in areas under the curve for PI-RADS version 2 versus 1. Conclusion In-bore 3-T MR-guided biopsy is safe and effective for prostate cancer diagnosis when stratified according to PI-RADS versions 1 and 2. ©RSNA, 2016.