Reference Range of Quantitative MRI Metrics Corrected T1 and Liver Fat Content in Children and Young Adults: Pooled Participant Analysis.

BACKGROUND: Multiparametric MRI markers of liver health corrected T1 (cT1) and proton density fat fraction (PDFF) have shown utility in the management of various chronic liver diseases. We assessed the normal population reference range of both cT1 and PDFF in healthy child and adult volunteers without any known liver disease. METHODS: A retrospective multi-centre pooled analysis of 102 child and young adult (9.1 years (6-18)) volunteers from three centres: Children's Memorial Health Institute (N = 21), University Hospital Southampton (N = 28) and Hospital Infantil de Mexico (N = 53). Sex and ethnic differences were investigated for both cT1 and PDFF. Age effects were investigated with comparison to a pooled adult cohort from the UK Biobank (N = 500) and CoverScan (N = 71), covering an age range of 21 to 81 years. RESULTS: cT1 values were normally distributed with a median of 748 ms (IQR: 725-768 ms; 2.5-97.5 percentiles: 683-820 ms). PDFF values followed a normal distribution with a median of 1.7% (IQR: 1.3-1.9%; 2.5-97.5 percentiles: 1-4.4%). There were no significant age and sex differences in cT1 and PDFF between children and young adults. No differences in cT1 and PDFF were found between ethnicities. Age comparisons showed statistically significant, but clinically negligible, cT1 (748 ms vs. 732 ms) and PDFF (2.4% vs. 1.9%) differences between paediatric and adult groups, respectively. CONCLUSIONS: Median healthy cT1 and PDFF reference ranges in children and young adults fall within the reported limits for normal of 800 ms and 5%, respectively.

Multivariable prognostic modelling to improve prediction of colorectal cancer recurrence: the PROSPeCT trial.

OBJECTIVE: Improving prognostication to direct personalised therapy remains an unmet need. This study prospectively investigated promising CT, genetic, and immunohistochemical markers to improve the prediction of colorectal cancer recurrence. MATERIAL AND METHODS: This multicentre trial (ISRCTN 95037515) recruited patients with primary colorectal cancer undergoing CT staging from 13 hospitals. Follow-up identified cancer recurrence and death. A baseline model for cancer recurrence at 3 years was developed from pre-specified clinicopathological variables (age, sex, tumour-node stage, tumour size, location, extramural venous invasion, and treatment). Then, CT perfusion (blood flow, blood volume, transit time and permeability), genetic (RAS, RAF, and DNA mismatch repair), and immunohistochemical markers of angiogenesis and hypoxia (CD105, vascular endothelial growth factor, glucose transporter protein, and hypoxia-inducible factor) were added to assess whether prediction improved over tumour-node staging alone as the main outcome measure. RESULTS: Three hundred twenty-six of 448 participants formed the final cohort (226 male; mean 66 ± 10 years. 227 (70%) had ≥ T3 stage cancers; 151 (46%) were node-positive; 81 (25%) developed subsequent recurrence. The sensitivity and specificity of staging alone for recurrence were 0.56 [95% CI: 0.44, 0.67] and 0.58 [0.51, 0.64], respectively. The baseline clinicopathologic model improved specificity (0.74 [0.68, 0.79], with equivalent sensitivity of 0.57 [0.45, 0.68] for high vs medium/low-risk participants. The addition of prespecified CT perfusion, genetic, and immunohistochemical markers did not improve prediction over and above the clinicopathologic model (sensitivity, 0.58-0.68; specificity, 0.75-0.76). CONCLUSION: A multivariable clinicopathological model outperformed staging in identifying patients at high risk of recurrence. Promising CT, genetic, and immunohistochemical markers investigated did not further improve prognostication in rigorous prospective evaluation. CLINICAL RELEVANCE STATEMENT: A prognostic model based on clinicopathological variables including age, sex, tumour-node stage, size, location, and extramural venous invasion better identifies colorectal cancer patients at high risk of recurrence for neoadjuvant/adjuvant therapy than stage alone. KEY POINTS: Identification of colorectal cancer patients at high risk of recurrence is an unmet need for treatment personalisation. This model for recurrence, incorporating many patient variables, had higher specificity than staging alone. Continued optimisation of risk stratification schema will help individualise treatment plans and follow-up schedules.

Oncological and Peri-Operative Outcomes of Percutaneous Cryoablation of Renal Cell Carcinoma for Patients with Hereditary RCC Diseases-An Analysis of European Multi-Centre Prospective EuRECA Registry.

This study aims to evaluate the safety, efficacy, and renal function preservation of percutaneous cryoablation (PCA) for small renal masses (SRMs) in inherited RCC syndromes. Patients with inherited T1N0M0 RCCs (<7 cm) undergoing PCA from 2015 to 2021 were identified from the European Registry for Renal Cryoablation (EuRECA). The primary outcome was local recurrence-free survival (LRFS). The secondary outcomes included technical success, peri-operative outcomes, and other oncological outcomes estimated using the Kaplan-Meier method. Simple proportions, chi-squared tests, and t-tests were used to analyse the peri-operative outcomes. A total of 68 sessions of PCA were performed in 53 patients with RCC and 85 tumours were followed-up for a mean duration of 30.4 months (SD ± 22.0). The overall technical success rate was 99%. The major post-operative complication rate was 1.7%. In total, 7.4% (2/27) of patients had >25% reduction in renal function. All oncological events were observed in VHL patients. Estimated 5-year LRFS, metastasis-free survival, cancer-specific survival, and overall survival were 96.0% (95% CI 75-99%), 96.4% (95% CI 77-99%), 90.9% (95% CI 51-99%), and 90.9% (95% CI 51-99%), respectively. PCA of RCCs for patients with hereditary RCC SRMs appears to be safe, offers low complication rates, preserves renal function, and achieves good oncological outcomes.

The changing trends of image-guided biopsy of small renal masses before intervention-an analysis of European multinational prospective EuRECA registry.

OBJECTIVES: To evaluate the use of pre-cryoablation biopsy for small renal masses (SRMs) and the effects of increasing uptake on histological results of treated SRMs. METHODS: From 2015 to 2019, patients with sporadic T1N0M0 SRMs undergoing percutaneous, laparoscopic, or open cryoablation from 14 European institutions within the European Registry for Renal Cryoablation (EuRECA) were included for the retrospective analysis. Univariate and multivariate logistic models were used to evaluate the trends, histological results, and the factors influencing use of pre-cryoablation biopsy. RESULTS: In total, 871 patients (median (IQR) age, 69 (14), 298 women) undergoing cryoablation were evaluated. The use of pre-cryoablation biopsy has significantly increased from 42% (65/156) in 2015 to 72% (88/122) in 2019 (p < 0.001). Patients treated for a benign histology are significantly more likely to have presented later in the trend, where pre-cryoablation biopsy is more prevalent (OR: 0.64, 95% CI 0.51-0.81, p < 0.001). Patients treated for undiagnosed histology are also significantly less likely to have presented in 2018 compared to 2016 (OR 0.31, 95% CI 0.10-0.97, p = 0.044). Patients aged 70+ are less likely to be biopsies pre-cryoablation (p < 0.05). R.E.N.A.L. nephrometry score of 10+ and a Charlson Comorbidity Index > 1 are factors associated with lower likelihood to not have received a pre-cryoablation biopsy (p < 0.05). CONCLUSION: An increased use of pre-cryoablation biopsy was observed and cryoablation patients treated with a benign histology are more likely to have presented in periods where pre-cryoablation biopsy is not as prevalent. Comparative studies are needed to draw definitive conclusions on the effect of pre-cryoablation biopsy on SRM treatments. KEY POINTS: • The use of biopsy pre-ablation session has increased significantly from 42% of all patients in 2015 to 74% in 2019. • Patients are less likely to be treated for a benign tumour if they presented later in the trend, where pre-cryoablation biopsy is more prevalent, compared to later in the trend (OR 0.64, 95% CI 0.51-0.81, p < 0.001). • Patients with comorbidities or a complex tumour (R.E.N.A.L. nephrometry score > 10) are less likely to not undergo biopsy as a separate session to cryoablation.

Comprehensive Imaging Characterization of Colorectal Liver Metastases.

Colorectal liver metastases (CRLM) have heterogenous histopathological and immunohistochemical phenotypes, which are associated with variable responses to treatment and outcomes. However, this information is usually only available after resection, and therefore of limited value in treatment planning. Improved techniques for in vivo disease assessment, which can characterise the variable tumour biology, would support further personalization of management strategies. Advanced imaging of CRLM including multiparametric MRI and functional imaging techniques have the potential to provide clinically-actionable phenotypic characterisation. This includes assessment of the tumour-liver interface, internal tumour components and treatment response. Advanced analysis techniques, including radiomics and machine learning now have a growing role in assessment of imaging, providing high-dimensional imaging feature extraction which can be linked to clinical relevant tumour phenotypes, such as a the Consensus Molecular Subtypes (CMS). In this review, we outline how imaging techniques could reproducibly characterize the histopathological features of CRLM, with several matched imaging and histology examples to illustrate these features, and discuss the oncological relevance of these features. Finally, we discuss the future challenges and opportunities of CRLM imaging, with a focus on the potential value of advanced analytics including radiomics and artificial intelligence, to help inform future research in this rapidly moving field.

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.

Synbiotics Alter Fecal Microbiomes, But Not Liver Fat or Fibrosis, in a Randomized Trial of Patients With Nonalcoholic Fatty Liver Disease.

BACKGROUND & AIMS: Dysbiosis of the intestinal microbiota has been associated with nonalcoholic fatty liver disease (NAFLD). We investigated whether administration of a synbiotic combination of probiotic and prebiotic agents affected liver fat content, biomarkers of liver fibrosis, and the composition of the fecal microbiome in patients with NAFLD. METHODS: We performed a double-blind phase 2 trial of 104 patients with NAFLD in the United Kingdom. Participants (mean age, 50.8 ± 12.6 years; 65% men; 37% with diabetes) were randomly assigned to groups given the synbiotic agents (fructo-oligosaccharides, 4 g twice per day, plus Bifidobacterium animalis subspecies lactis BB-12; n = 55) or placebo (n = 49) for 10-14 months. Liver fat content was measured at the start and end of the study by magnetic resonance spectroscopy, and liver fibrosis was determined from a validated biomarker scoring system and vibration-controlled transient elastography. Fecal samples were collected at the start and end of the study, the fecal microbiome were analyzed by 16S ribosomal DNA sequencing. RESULTS: Mean baseline and end-of-study magnetic resonance spectroscopy liver fat percentage values were 32.3% ± 24.8% and 28.5% ± 20.1% in the synbiotic group and 31.3% ± 22% and 25.2% ± 17.2% in the placebo group. In the unadjusted intention-to-treat analysis, we found no significant difference in liver fat reduction between groups (ß = 2.8; 95% confidence interval, -2.2 to 7.8; P = .30). In a fully adjusted regression model (adjusted for baseline measurement of the outcome plus age, sex, weight difference, and baseline weight), only weight loss was associated with a significant decrease in liver fat (ß = 2; 95% confidence interval, 1.5-2.6; P = .03). Fecal samples from patients who received the synbiotic had higher proportions of Bifidobacterium and Faecalibacterium species, and reductions in Oscillibacter and Alistipes species, compared with baseline; these changes were not observed in the placebo group. Changes in the composition of fecal microbiota were not associated with liver fat or markers of fibrosis. CONCLUSIONS: In a randomized trial of patients with NAFLD, 1 year of administration of a synbiotic combination (probiotic and prebiotic) altered the fecal microbiome but did not reduce liver fat content or markers of liver fibrosis. (ClinicalTrials.gov, Number: NCT01680640).

Adaptive statistical iterative reconstruction (ASIR) affects CT radiomics quantification in primary colorectal cancer.

OBJECTIVES: To investigate whether adaptive statistical iterative reconstruction (ASIR), a hybrid iterative CT image reconstruction algorithm, affects radiomics feature quantification in primary colorectal cancer compared to filtered back projection. Additionally, to establish whether radiomics from single-slice analysis undergo greater change than those from multi-slice analysis. METHODS: Following review board approval, contrast-enhanced CT studies from 32 prospective primary colorectal cancer patients were reconstructed with 20% ASIR level increments, from 0 to 100%. Radiomics analysis was applied to single-slice and multi-slice regions of interest outlining the tumour: 70 features, including statistical (first-, second- and high-order) and fractal radiomics, were generated per dataset. The effect of ASIR was calculated by means of multilevel linear regression. RESULTS: Twenty-eight CT datasets were suitable for analysis. Incremental ASIR levels determined a significant change (p < 0.001) in most statistical radiomics features, best described by a simple linear relationship. First-order statistical features, including mean, standard deviation, skewness, kurtosis, energy and entropy, underwent a relatively small change in both single-slice and multi-slice analysis (median standardised effect size B = 0.08). Second-order statistical features, including grey-level co-occurrence and difference matrices, underwent a greater change in single-slice analysis (median B = 0.36) than in multi-slice analysis (median B = 0.13). Fractal features underwent a significant change only in single-slice analysis (median B = 0.49). CONCLUSIONS: Incremental levels of ASIR affect significantly CT radiomics quantification in primary colorectal cancer. Second-order statistical and fractal features derived from single-slice analysis undergo greater change than those from multi-slice analysis. KEY POINTS: • Incremental levels of ASIR determine a significant change in most statistical (first-, second- and high-order) CT radiomics features measured in primary colorectal cancer, best described by a linear relationship. • First-order statistical features undergo a small change, both from single-slice and multi-slice radiomics analyses. • Most second-order statistical features undergo a greater change in single-slice analysis than in multi-slice analysis. Fractal features are only affected in single-slice analysis.

Image-guided Cryoablation for Sporadic Renal Cell Carcinoma: Three- and 5-year Outcomes in 220 Patients with Biopsy-proven Renal Cell Carcinoma.

Purpose To evaluate the long-term efficacy of image-guided cryoablation of sporadic clinical T1 (cT1) biopsy-proven renal cell carcinoma (RCC) and the technical success and safety of all cryoablation treatments. Materials and Methods For this retrospective single-institution study, 433 patients (median age, 68 years; range, 19-90 years), of whom 293 were men (median age, 69 years; range, 19-90 years) and 140 were women (median age, 68 years; range, 30-89 years), who had 484 cT1 renal masses (mean size, 33 mm) and who were treated between 2007 and 2016 were identified from a prospectively maintained tumor registry. Treatment efficacy for all treated lesions and complication rates of all procedures were computed. Oncologic outcomes for a subset of 220 patients with sporadic biopsy-proven RCC were analyzed. The Kaplan-Meier method was used to estimate local recurrence-free survival (LRFS), metastasis-free survival (MFS), and overall survival (OS) rates. Results Of the 484 treated cT1 renal masses, 474 were imaged subsequently, with a primary treatment efficacy of 96% (453 of 474), increasing to 98% (465 of 474) after secondary ablation, and a major complication rate (Clavien-Dindo grade ≥ III) of 4.9% (23 of 473 procedures). The estimated LRFS and MFS rates, respectively, for the 220 patients with biopsy-proven RCC were 97.2% (95% confidence interval [CI]: 92.6%, 99.0%) and 97.7% (95% CI: 93.3%, 99.1%) at 3 years and 93.9% (95% CI: 85.8%, 97.4%) and 94.4% (95% CI: 86.7%, 97.7%) at 5 years. The estimated OS of all 433 patients was 91.7% (95% CI: 87.5%, 94.5%) and 78.8% (95% CI: 71.1%, 84.6%) at 3 and 5 years, respectively. Conclusion Five-year oncologic outcomes after image-guided cryoablation for clinical T1 renal cell carcinoma are competitive with those of resection at a lower complication rate. © RSNA, 2018.

Multiparametric MRI for early detection of diffuse liver disease: an interview with David Breen.

David J Breen is Associate Professor of Radiology and previous Clinical Director of Radiology at University Hospital Southampton. His interests are in abdominal imaging and intervention, particularly of hepato-pancreato-biliary (HPB)and renal disease. He has a major interest in image-guided tumor ablation and improving outcomes from these procedures. He has previously served as Vice Chair of the NHS England Clinical Reference Group in Interventional Radiology and for the NIHR/NCRN Upper GI Clinical Studies Group.

Laparoscopic vs Percutaneous Cryotherapy for Renal Tumors: A Systematic Review and Meta-Analysis.

BACKGROUND: Cryoablation has emerged as an alternative to the more invasive partial nephrectomy for small renal masses. The approach can be carried out by two techniques, either laparoscopic cryoablation (LCA) or percutaneous cryoablation, (PCA) with CT guidance. We aimed to compare between the two procedures. MATERIALS AND METHODS: A systematic review and meta-analysis was conducted, including studies comparing the two techniques. Outcomes included incomplete ablation, late local recurrence, cancer-specific survival, procedure time, transfusion rates, hospital stay, and complications. RESULTS: A total of 1475 patients were included, 788 patients in the laparoscopic group and 687 patients in the percutaneous group. There was statistical difference favoring the laparoscopic group with regard to having less incomplete ablation (p = 0.0008) and higher cancer-specific survival patients (p = 0.04). However, there was longer hospital stays in the LCA group (p < 0.00001) and was found to be more costly than the PCA group. There was significantly more Clavien-I complications in the PCA group (p = 0.001) and more Clavien-III complications in the LCA group (p = 0.001). Otherwise, there were no differences in any other outcome parameter. CONCLUSION: LCA was found to have less incomplete tumor ablation rates and higher cancer-specific survival rates, however, higher hospitalization time, more major complications (Clavien III), and was costlier compared with PCA.

Cross-sectional study of the provision of interventional oncology services in the UK.

OBJECTIVE: To map out the current provision of interventional oncology (IO) services in the UK. DESIGN: Cross-sectional multicentre study. SETTING: All National Health Service (NHS) trusts in England and Scottish, Welsh and Northern Ireland health boards. PARTICIPANTS: Interventional radiology (IR) departments in all NHS trusts/health boards in the UK. RESULTS: A total of 179 NHS trusts/health boards were contacted. We received a 100% response rate. Only 19 (11%) institutions had an IO lead. 144 trusts (80%) provided IO services or had a formal pathway of referral in place for patients to a recipient trust. 21 trusts (12%) had plans to provide an IO service or formal referral pathway in the next 12 months only. 14 trusts (8%) did not have a pathway of referral and no plans to implement one. 70 trusts (39%) offered supportive and disease-modifying procedures. One trust had a formal referral pathway for supportive procedures. 73 trusts (41%) provided only supportive procedures (diagnostic or therapeutic). Of these, 43 (59%) had a referral pathway for disease-modifying IO procedures, either from a regional cancer network or through IR networks and 30 trusts (41%) did not have a referral pathway for disease-modifying procedures. CONCLUSION: The provision of IO services in the UK is promising; however, collaborative networks are necessary to ensure disease-modifying IO procedures are made accessible to all patients and to facilitate larger registry data for research with commissioning of new services.

Percutaneous image-guided cryoablation of small renal masses.

Renal cell carcinoma is a common malignancy with increasing incidence due to the incidental detection of non-symptomatic small renal masses on imaging. Management of these small tumors has evolved toward minimally invasive nephron-sparing techniques which include partial nephrectomy and image-guided ablation. Cryoablation and radiofrequency ablation are the most utilized ablation modalities with the former more suited for larger and central renal masses due to intra-procedural visualization of the ablation zone and reduced pelvicalyceal injury. In this article, we review the epidemiology and natural history of renal cell carcinoma, the role of biopsy, and the management options available-surgery, image-guided ablation, and active surveillance-with a focus on cryoablation. The clinical outcomes of the longer term maturing cryoablation data are discussed with reference to partial nephrectomy and radiofrequency ablation. Image-guided ablation has often been the management choice in patients deemed unfit for surgery; however, growing evidence from published series demonstrates image-guided ablation as a sound alternative treatment with equivalent oncological outcomes and minimal patient impact.

Image-guided ablation of primary liver and renal tumours.

Image-guided ablation (IGA) techniques have evolved considerably over the past 20 years and are increasingly used to definitively treat small primary cancers of the liver and kidney. IGA is recommended by most guidelines as the best therapeutic choice for patients with early stage hepatocellular carcinoma (HCC)-defined as either a single tumour smaller than 5 cm or up to three nodules smaller than 3 cm-when surgical options are precluded, and has potential as first-line therapy, in lieu of surgery, for patients with very early stage tumours smaller than 2 cm. With regard to renal cell carcinoma, despite the absence of any randomized trial comparing the outcomes of IGA with those of standard partial nephrectomy, a growing amount of data demonstrate robust oncological outcomes for this minimally invasive approach and testify to its potential as a standard-of-care treatment. Herein, we review the various ablation techniques, the supporting evidence, and clinical application of IGA in the treatment of primary liver and kidney cancers.

Image-guided tumor ablation: standardization of terminology and reporting criteria--a 10-year update.

Image-guided tumor ablation has become a well-established hallmark of local cancer therapy. The breadth of options available in this growing field increases the need for standardization of terminology and reporting criteria to facilitate effective communication of ideas and appropriate comparison among treatments that use different technologies, such as chemical (eg, ethanol or acetic acid) ablation, thermal therapies (eg, radiofrequency, laser, microwave, focused ultrasound, and cryoablation) and newer ablative modalities such as irreversible electroporation. This updated consensus document provides a framework that will facilitate the clearest communication among investigators regarding ablative technologies. An appropriate vehicle is proposed for reporting the various aspects of image-guided ablation therapy including classification of therapies, procedure terms, descriptors of imaging guidance, and terminology for imaging and pathologic findings. Methods are addressed for standardizing reporting of technique, follow-up, complications, and clinical results. As noted in the original document from 2003, adherence to the recommendations will improve the precision of communications in this field, leading to more accurate comparison of technologies and results, and ultimately to improved patient outcomes.

Image-guided tumor ablation: standardization of terminology and reporting criteria--a 10-year update.

Image-guided tumor ablation has become a well-established hallmark of local cancer therapy. The breadth of options available in this growing field increases the need for standardization of terminology and reporting criteria to facilitate effective communication of ideas and appropriate comparison among treatments that use different technologies, such as chemical (eg, ethanol or acetic acid) ablation, thermal therapies (eg, radiofrequency, laser, microwave, focused ultrasound, and cryoablation) and newer ablative modalities such as irreversible electroporation. This updated consensus document provides a framework that will facilitate the clearest communication among investigators regarding ablative technologies. An appropriate vehicle is proposed for reporting the various aspects of image-guided ablation therapy including classification of therapies, procedure terms, descriptors of imaging guidance, and terminology for imaging and pathologic findings. Methods are addressed for standardizing reporting of technique, follow-up, complications, and clinical results. As noted in the original document from 2003, adherence to the recommendations will improve the precision of communications in this field, leading to more accurate comparison of technologies and results, and ultimately to improved patient outcomes. Online supplemental material is available for this article .

Unusual radiological behaviour after cryoablation of renal cell carcinoma.

Cryoablation has evolved into an effective treatment option in patients with renal tumours. The procedure is minimally invasive, and patients are often spared the morbidity and hospital stay that is often associated with open or partial nephrectomy. We present an unusual case of a 62-year-old male patient who underwent cryoablation of a renal cell carcinoma. He subsequently developed apparent exuberant local disease progression, which spontaneously regressed on follow-up CT imaging.