Time conditioning for arbitrary contrast phase generation in interventional computed tomography.

Minimally invasive ablation techniques for renal cancer are becoming more popular due to their low complication rate and rapid recovery period. Despite excellent visualisation, one drawback of the use of computed tomography (CT) in these procedures is the requirement for iodine-based contrast agents, which are associated with adverse reactions and require a higher x-ray dose. The purpose of this work is to examine the use of time information to generate synthetic contrast enhanced images at arbitrary points after contrast agent injection from non-contrast CT images acquired during renal cryoablation cases. To achieve this, we propose a new method of conditioning generative adversarial networks with normalised time stamps and demonstrate that the use of a HyperNetwork is feasible for this task, generating images of competitive quality compared to standard generative modelling techniques. We also show that reducing the receptive field can help tackle challenges in interventional CT data, offering significantly better image quality as well as better performance when generating images for a downstream segmentation task. Lastly, we show that all proposed models are robust enough to perform inference on unseen intra-procedural data, while also improving needle artefacts and generalising contrast enhancement to other clinically relevant regions and features.

Next-Generation Sequencing and Image-Guided Tissue Sampling: A Primer for Interventional Radiologists.

The discovery of increasing numbers of actionable molecular and gene targets for cancer treatment has driven the demand for tissue sampling for next-generation sequencing (NGS). Requirements for sequencing can be very specific, and inadequate sampling leads to delays in management and decision making. It is important that interventional radiologists are aware of NGS technologies and their common applications and be cognizant of the factors that contribute to successful sample sequencing. This review summarizes the fundamentals of cancer tissue collection and processing for NGS. It elaborates on sequencing technologies and their applications with the aim of providing readers with a working understanding that can enhance their clinical practice. It then describes imaging, tumor, biopsy, and sample collection factors that improve the chances of NGS success. Finally, it discusses future practice, highlighting the problem of undersampling in both clinical and research settings and the opportunities within interventional radiology to address this.

Multi-phase synthetic contrast enhancement in interventional computed tomography for guiding renal cryotherapy.

PURPOSE: Minimally invasive treatments for renal carcinoma offer a low rate of complications and quick recovery. One drawback of the use of computed tomography (CT) for needle guidance is the use of iodinated contrast agents, which require an increased X-ray dose and can potentially cause adverse reactions. The purpose of this work is to generalise the problem of synthetic contrast enhancement to allow the generation of multiple phases on non-contrast CT data from a real-world, clinical dataset without training multiple convolutional neural networks. METHODS: A framework for switching between contrast phases by conditioning the network on the phase information is proposed and compared with separately trained networks. We then examine how the degree of supervision affects the generated contrast by evaluating three established architectures: U-Net (fully supervised), Pix2Pix (adversarial with supervision), and CycleGAN (fully adversarial). RESULTS: We demonstrate that there is no performance loss when testing the proposed method against separately trained networks. Of the training paradigms investigated, the fully adversarial CycleGAN performs the worst, while the fully supervised U-Net generates more realistic voxel intensities and performed better than Pix2Pix in generating contrast images for use in a downstream segmentation task. Lastly, two models are shown to generalise to intra-procedural data not seen during the training process, also enhancing features such as needles and ice balls relevant to interventional radiological procedures. CONCLUSION: The proposed contrast switching framework is a feasible option for generating multiple contrast phases without the overhead of training multiple neural networks, while also being robust towards unseen data and enhancing contrast in features relevant to clinical practice.

Extracellular Volume Fraction by Computed Tomography Predicts Long-Term Prognosis Among Patients With Cardiac Amyloidosis.

BACKGROUND: Light chain (AL) and transthyretin (ATTR) amyloid fibrils are deposited in the extracellular space of the myocardium, resulting in heart failure and premature mortality. Extracellular expansion can be quantified by computed tomography, offering a rapid, cheaper, and more practical alternative to cardiac magnetic resonance, especially among patients with cardiac devices or on renal dialysis. OBJECTIVES: This study sought to investigate the association of extracellular volume fraction by computed tomography (ECVCT), myocardial remodeling, and mortality in patients with systemic amyloidosis. METHODS: Patients with confirmed systemic amyloidosis and varying degrees of cardiac involvement underwent electrocardiography-gated cardiac computed tomography. Whole heart and septal ECVCT was analyzed. All patients also underwent clinical assessment, electrocardiography, echocardiography, serum amyloid protein component, and/or technetium-99m (99mTc) 3,3-diphosphono-1,2-propanodicarboxylic acid scintigraphy. ECVCT was compared across different extents of cardiac infiltration (ATTR Perugini grade/AL Mayo stage) and evaluated for its association with myocardial remodeling and all-cause mortality. RESULTS: A total of 72 patients were studied (AL: n = 35, ATTR: n = 37; median age: 67 [IQR: 59-76] years, 70.8% male). Mean septal ECVCT was 42.7% ± 13.1% and 55.8% ± 10.9% in AL and ATTR amyloidosis, respectively, and correlated with indexed left ventricular mass (r = 0.426; P < 0.001), left ventricular ejection fraction (r = 0.460; P < 0.001), N-terminal pro-B-type natriuretic peptide (r = 0.563; P < 0.001), and high-sensitivity troponin T (r = 0.546; P < 0.001). ECVCT increased with cardiac amyloid involvement in both AL and ATTR amyloid. Over a mean follow-up of 5.3 ± 2.4 years, 40 deaths occurred (AL: n = 14 [35.0%]; ATTR: n = 26 [65.0%]). Septal ECVCT was independently associated with all-cause mortality in ATTR (not AL) amyloid after adjustment for age and septal wall thickness (HR: 1.046; 95% CI: 1.003-1.090; P = 0.037). CONCLUSIONS: Cardiac amyloid burden quantified by ECVCT is associated with adverse cardiac remodeling as well as all-cause mortality among ATTR amyloid patients. ECVCT may address the need for better identification and risk stratification of amyloid patients, using a widely accessible imaging modality.

In-Circuit High-Frequency Jet Ventilation for Radiological Tumor Ablation: A Case Series.

High-frequency jet ventilation (HFJV) can reduce organ movement that otherwise complicates percutaneous image-guided ablation (IGA) procedures. This study describes feasibility and safety of the technique in routine use. We describe our method for the use of HFJV and present 169 consecutive cases, including IGA of tumors of the lung, liver, kidney, and pancreas. Intended oncological treatment was delivered in all cases and HFJV used for the duration of treatment in all except one case. We describe the characteristics of patients, procedures, and adverse events. It is feasible to use HFJV as the routine standard of care for IGA.

Radioembolization With Chemotherapy for Colorectal Liver Metastases: A Randomized, Open-Label, International, Multicenter, Phase III Trial.

PURPOSE: To study the impact of transarterial Yttrium-90 radioembolization (TARE) in combination with second-line systemic chemotherapy for colorectal liver metastases (CLM). METHODS: In this international, multicenter, open-label phase III trial, patients with CLM who progressed on oxaliplatin- or irinotecan-based first-line therapy were randomly assigned 1:1 to receive second-line chemotherapy with or without TARE. The two primary end points were progression-free survival (PFS) and hepatic PFS (hPFS), assessed by blinded independent central review. Random assignment was performed using a web- or voice-based system stratified by unilobar or bilobar disease, oxaliplatin- or irinotecan-based first-line chemotherapy, and KRAS mutation status. RESULTS: Four hundred twenty-eight patients from 95 centers in North America, Europe, and Asia were randomly assigned to chemotherapy with or without TARE; this represents the intention-to-treat population and included 215 patients in the TARE plus chemotherapy group and 213 patients in the chemotherapy alone group. The hazard ratio (HR) for PFS was 0.69 (95% CI, 0.54 to 0.88; 1-sided P = .0013), with a median PFS of 8.0 (95% CI, 7.2 to 9.2) and 7.2 (95% CI, 5.7 to 7.6) months, respectively. The HR for hPFS was 0.59 (95% CI, 0.46 to 0.77; 1-sided P < .0001), with a median hPFS of 9.1 (95% CI, 7.8 to 9.7) and 7.2 (95% CI, 5.7 to 7.6) months, respectively. Objective response rates were 34.0% (95% CI, 28.0 to 40.5) and 21.1% (95% CI, 16.2 to 27.1; 1-sided P = .0019) for the TARE and chemotherapy groups, respectively. Median overall survival was 14.0 (95% CI, 11.8 to 15.5) and 14.4 months (95% CI, 12.8 to 16.4; 1-sided P = .7229) with a HR of 1.07 (95% CI, 0.86 to 1.32) for TARE and chemotherapy groups, respectively. Grade 3 adverse events were reported more frequently with TARE (68.4% v 49.3%). Both groups received full chemotherapy dose intensity. CONCLUSION: The addition of TARE to systemic therapy for second-line CLM led to longer PFS and hPFS. Further subset analyses are needed to better define the ideal patient population that would benefit from TARE.

Combination of ablation and embolization for intermediate-sized liver metastases from colorectal cancer: what can we learn from treating primary liver cancer?

Colorectal cancer liver metastases (CRLMs) are common. Treating CRLMs with thermal ablation can prolong survival, but compared to lesions smaller than 3 cm, local control rates and overall survival are relatively worse with larger, intermediate (3-5 cm) lesions. Local recurrence rates range between 1.7%-20.2% and 6.7%-68.9% for CRLMs less than 3 cm and greater than 3 cm, respectively. Worse outcomes are also present when ablating intermediate size hepatocellular carcinoma (HCC) and there are some pathological similarities with CRLMs, namely the presence of micrometastatic disease. Combining ablation with transarterial chemoembolization is more effective in treating intermediate-size HCC than ablation alone. A meta-analysis of robust randomized controlled trials demonstrated long-term improved survival with combination therapy compared to ablation alone (odds ratio at 1, 3 and 5 years of 2.74, 2.77 and 5.23, respectively). There is, however, minimal evidence for combination therapy in CRLMs, limited to a handful of studies that are predominantly retrospective and have heterogeneous inclusion criteria. Given the difficulty in successfully treating intermediate CRLMs, the strong evidence for combination therapy in intermediate HCC and potential pathological similarities, formal evaluation of combination treatment in CRLM is merited. This review highlights existing evidence for treatment of intermediate-size liver lesions and highlights where trials in CRLMs should focus.

MR Imaging‒Guided Intervention: Evaluation of MR Conditional Biopsy and Ablation Needle Tip Artifacts at 3T Using a Balanced Fast Field Echo Sequence.

PURPOSE: To systematically investigate artifacts produced by biopsy and ablation needles imaged at various trajectories with respect to the static magnetic field (B0). MATERIALS AND METHODS: An acrylic phantom was scanned using a rapid balanced fast field echo sequence with 3.0-T magnetic resonance imaging. A 15-gauge microwave needle, a 17-gauge cryoneedle, and an 18-gauge coaxial biopsy needle were imaged in sagittal and axial planes, in 7 different orientations to B0 (0°, 15°, 30°, 45°, 60°, 75°, and 90°). For 4 angles (15°, 30°, 60°, and 75°), images were acquired with the slice orientation aligned to the needle angulation, resulting in the frequency encoding direction being parallel to the needle's long axis for the sagittal slice and perpendicular to the needle angulation for the axial acquisition. The artifact length at the needle tip and maximum artifact width were recorded. RESULTS: No significant difference was noted in mean artifact length for the cryoneedle (13 mm; 95% confidence interval [CI], 7-19) and coaxial biopsy needle (8 mm; 95% CI, 5-10; P = .08). The mean artifact length was significantly smaller for the microwave ablation needle (1 mm; 95% CI, 0-2; P < .05). The mean artifact width was highest for the coaxial needle (17 mm; 95% CI, 14-19) and significantly higher than the cryoneedle (12 mm; 95% CI, 10-15; P = .024) and microwave ablation needle (8 mm; 95% CI, 6-10; P < .01). The needle tip artifact was significantly smaller when the slice orientation was aligned to the needle angulation for the coaxial and cryoablation needles (P < .01). CONCLUSIONS: Needle tip artifact length and width increase with increasing angulation to the static field. At large angles (>15°), the needle tip position can be predicted better from images acquired when the slice orientation is aligned to the needle's angulation.

Long-term biopsy outcomes in prostate cancer patients treated with external beam radiotherapy: a systematic review and meta-analysis.

BACKGROUND: Biopsy after external beam radiotherapy (EBRT) for localised prostate cancer (PCa) is an infrequently used but potentially valuable technique to evaluate local recurrence and predict long-term outcomes. METHODS: We performed a meta-analysis of studies until March 2020 where a post-EBRT biopsy was performed on patients with low-to intermediate risk PCa, according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement. The primary outcome was the aggregate post-EBRT positive biopsy rate (≥2 years after EBRT) and the associated odds ratio (OR) of a positive biopsy on biochemical failure (BCF), distant metastasis-free survival (DMFS) and prostate cancer-specific mortality (PCSM). A sensitivity analysis was performed which examined biopsy rate as a function of post-EBRT biopsy protocol, PCa risk, ADT usage and radiation dose. RESULTS: A total of 22 studies were included, of which 10 were randomised controlled trials and 12 were cohort studies. Nine out of the 22 studies used dosing regimens consistent with the 2020 NCCN radiotherapy guidelines. The weighted-average positive biopsy rate across all 22 studies was 32% (95%-CI: 25-39%, n = 3017). In studies where post-treatment biopsy was part of the study protocol, the rate was 35% (95%-CI: 21-38%, n = 2450). In the subgroup of studies that conformed to the 2020 NCCN radiotherapy guidelines, this rate was 22% (95% CI: 19-41%, n = 832). Patients with positive biopsy had a 10-fold higher odds of developing BCF (OR of 10.3, 95%-CI: 3.7-28.7, p < 0.00001), 3-fold higher odds of developing distant metastasis (OR 3.1, 95%-CI: 2.1-4.7, p < 0.00001) and 5-fold higher odds of dying from their PCa (OR 5.1, 95%-CI: 2.6-10, p < 0.00001). CONCLUSION: A positive biopsy after EBRT is associated with a poor prognosis compared to a negative biopsy. The post-EBRT positive biopsy rate is an important measure which provides additional insight when comparing EBRT to other treatment modalities for PCa.

Prostatic calcifications: Quantifying occurrence, radiodensity, and spatial distribution in prostate cancer patients.

BACKGROUND: To evaluate the prevalence, density, and distribution of prostate calcification in patients with prostate cancer. METHODS: Patients who underwent both Gallium-68 PSMA PET/CT and MRI of the prostate over the course of a year were selected for analysis. The CT images with visible calcifications within the prostate were included and calcifications automatically isolated using a threshold of 130 HU. The corresponding multiparametric MRI was assessed and the peripheral zone, transition zone, MRI-visible tumor, and urethra manually contoured. The contoured MRI and CT images were registered using rigid registration, and calcifications mapped automatically to the MRI contours. RESULTS: A total of 85 men (age range 50-88, mean 69 years, standard deviation 7.2 years) were assessed. The mean serum Prostate Specific Antigen PSA was 16.7, range 0.12 to 94.4. Most patients had intermediate-risk disease (68%; Gleason grade group 2 and 3), 26% had high-risk disease (Gleason grade group 4 and 5), and 6% had low-risk disease (Gleason grade group 1). Forty-six patients out of 85 (54%) had intraprostatic calcification. Calcification occurred more in transition zone than the peripheral zone (65% vs. 35%). The mean density of the calcification was 227 HU (min 133, max 1,966 HU). In 12 patients, the calcification was within an MRI-visible tumor, in 24 patients, there were calcifications within a 9 mm distance of the tumor border, and in 9 patients, there were calcifications located between the urethra and tumor. CONCLUSIONS: Calcifications are common in patients with prostate cancer. Their density and location may make them a significant consideration when planning treatment or retreatment with some types of minimally invasive therapy.

Renal cryoablation - a practical guide for interventional radiologists.

Renal cryoablation is a treatment option for early stage renal cell carcinomas with excellent oncological outcomes and low morbidity. This review outlines the technique of renal cryoablation and provides a guide for interventional radiologists on setting up an integrated service within a renal cancer network multidisciplinary setting. Patient selection and preparation, together with the technical aspects which ensure optimal oncological outcomes and avoid collateral damage to adjacent organs are highlighted.

Equilibrium CT Texture Analysis for the Evaluation of Hepatic Fibrosis: Preliminary Evaluation against Histopathology and Extracellular Volume Fraction.

BACKGROUND: Evaluate equilibrium contrast-enhanced CT (EQ-CT) texture analysis (EQ-CTTA) against histologically-quantified fibrosis, serum-based enhanced liver fibrosis panel (ELF) and imaging-based extracellular volume fraction (ECV) in chronic hepatitis. METHODS: This study was a re-analysis of image data from a previous prospective study. Pre- and equilibrium-phase post-IV contrast CT datasets were collected from patients with chronic hepatitis with contemporaneous liver biopsy and serum ELF measurement between April 2011 and July 2013. Biopsy samples were analysed to derive collagen proportionate area (CPA). EQ-CTTA was performed with a filtration histogram technique using texture analysis software, with texture quantification using statistical and histogram-based metrics (mean, skewness, standard deviation, entropy, etc.). Association between pre-contrast and EQ-CTTA against CPA, ECV and ELF was evaluated using Spearman's rank correlation coefficient (rs). RESULTS: Complete datasets collected in 29 patients (16 male; 13 female), mean age (range): 49 (22-66 years). Liver ECV, CPA and ELF had a median (interquartile range) of 0.26 (0.24-0.29); 5.0 (3.0-13.7) and 9.71 (8.39-10.92). Difference in segment VII hepatic CTTA (medium texture scale) between EQ-CT and pre-contrast images was significantly and positively associated with ELF score (mean: rs = 0.69, p < 0.001; skewness: rs = 0.57, p = 0.007). Significant negative associations were observed between pre-contrast and EQ-CT whole hepatic CTTA (coarse texture scale) with CPA (pre-contrast, SD: rs = -0.66, p < 0.001) and ECV (EQ-CT, entropy: rs = -0.58, p = 0.006). CONCLUSIONS: Hepatic EQ-CTTA demonstrates significant association with validated markers of liver fibrosis, suggesting a role in non-invasive quantification of severity in diffuse fibrosis.

Liver resection surgery compared with thermal ablation in high surgical risk patients with colorectal liver metastases: the LAVA international RCT.

BACKGROUND: Although surgical resection has been considered the only curative option for colorectal liver metastases, thermal ablation has recently been suggested as an alternative curative treatment. There have been no adequately powered trials comparing surgery with thermal ablation. OBJECTIVES: Main objective - to compare the clinical effectiveness and cost-effectiveness of thermal ablation versus liver resection surgery in high surgical risk patients who would be eligible for liver resection. Pilot study objectives - to assess the feasibility of recruitment (through qualitative study), to assess the quality of ablations and liver resection surgery to determine acceptable standards for the main trial and to centrally review the reporting of computed tomography scan findings relating to ablation and outcomes and recurrence rate in both arms. DESIGN: A prospective, international (UK and the Netherlands), multicentre, open, pragmatic, parallel-group, randomised controlled non-inferiority trial with a 1-year internal pilot study. SETTING: Tertiary liver, pancreatic and gallbladder (hepatopancreatobiliary) centres in the UK and the Netherlands. PARTICIPANTS: Adults with a specialist multidisciplinary team diagnosis of colorectal liver metastases who are at high surgical risk because of their age, comorbidities or tumour burden and who would be suitable for liver resection or thermal ablation. INTERVENTIONS: Thermal ablation conducted as per local policy (but centres were encouraged to recruit within Cardiovascular and Interventional Radiological Society of Europe guidelines) versus surgical liver resection performed as per centre protocol. MAIN OUTCOME MEASURES: Pilot study - patients' and clinicians' acceptability of the trial to assist in optimisation of recruitment. Primary outcome - disease-free survival at 2 years post randomisation. Secondary outcomes - overall survival, timing and site of recurrence, additional therapy after treatment failure, quality of life, complications, length of hospital stay, costs, trial acceptability, and disease-free survival measured from end of intervention. It was planned that 5-year survival data would be documented through record linkage. Randomisation was performed by minimisation incorporating a random element, and this was a non-blinded study. RESULTS: In the pilot study over 1 year, a total of 366 patients with colorectal liver metastases were screened and 59 were considered eligible. Only nine participants were randomised. The trial was stopped early and none of the planned statistical analyses was performed. The key issues inhibiting recruitment included fewer than anticipated patients eligible for both treatments, misconceptions about the eligibility criteria for the trial, surgeons' preference for one of the treatments ('lack of clinical equipoise' among some of the surgeons in the centre) with unconscious bias towards surgery, patients' preference for one of the treatments, and lack of dedicated research nurses for the trial. CONCLUSIONS: Recruitment feasibility was not demonstrated during the pilot stage of the trial; therefore, the trial closed early. In future, comparisons involving two very different treatments may benefit from an initial feasibility study or a longer period of internal pilot study to resolve these difficulties. Sufficient time should be allowed to set up arrangements through National Institute for Health Research (NIHR) Research Networks. TRIAL REGISTRATION: Current Controlled Trials ISRCTN52040363. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 21. See the NIHR Journals Library website for further project information.

In about 50% of people with bowel cancer, cancer spreads to the liver (colorectal liver metastases) within 5 years of detection and treatment. Liver resection (i.e. surgical removal of a portion of the liver) is the standard treatment in people below 70 years of age who are otherwise well, provided that the liver cancer is confined to a limited part of the liver. Such patients are considered 'low-risk' patients. Older patients and those with major medical problems or extensive cancers are considered 'high-risk' patients, as they are at a higher risk of developing complications following liver resection. Thermal ablation destroys the liver cancers using a needle that heats the cancer deposits until they are destroyed. There is significant uncertainty as to whether or not ablation can offer equivalent survival compared with surgery for 'high-risk' patients. We planned and conducted a randomised controlled trial comparing ablation with surgery to resolve this uncertainty. In this trial, some patients received ablation and others received surgery. The treatment was allocated at random with neither patients nor the study organisers choosing the treatment. The trial had an internal pilot (i.e. a smaller version of the full trial to resolve any 'teething problems' and ensure that a sufficient number of participants can be included in the full trial). Only nine patients were recruited in the 1-year internal pilot, compared with the anticipated recruitment of 45 patients. Therefore, the trial closed early as a result of poor recruitment, and the uncertainty about the best treatment for high-risk patients with colorectal liver metastases continues. The main reasons for the poor recruitment included fewer than anticipated eligible participants, clinicians' unconscious bias towards surgery, and patients' preference for one treatment or the other. In the future, comparisons involving two very different treatments may benefit from a feasibility study or a longer period of pilot study to resolve any difficulties.

Outcomes of Renal Tumors Treated by Image-Guided Percutaneous Cryoablation: Immediate and 3- and 5-Year Outcomes at a Regional Center.

OBJECTIVE. The purpose of this study was to evaluate the immediate and 3- and 5-year outcomes of patients with clinical stage T1 (cT1) biopsy-proven renal cell carcinoma (RCC) treated by image-guided percutaneous cryoablation at a regional interventional oncology center. MATERIALS AND METHODS. A prospectively maintained local interventional radiology database identified patients with cT1 RCC lesions that were treated by percutaneous cryoablation. Technical success, procedural complications (graded using the Clavien-Dindo classification system), and the residual unablated tumor rate were collated. Local tumor progression-free survival was estimated using Kaplan-Meier estimates. RESULTS. A total of 180 patients with 185 separate cT1 RCC lesions were identified. Mean patient age was 68.4 years (range, 34.1-88.9 years) and 52 patients (28.9%) were women. There were 168 (90.8%) and 17 (9.2%) cT1a and cT1b lesions, respectively, with a mean lesion size of 28.5 mm (range, 11-58 mm). Technical success was achieved in 183 of 185 (98.9%) patients. The major complication rate (Clavien-Dindo classification ≥ grade III) was 2.2% (four out of 185). Residual unablated tumor on the first follow-up scan was identified in four of 183 tumors (2.2%). Estimated local tumor progression-free survival at 3 and 5 years was 98.3% and 94.9%, respectively. No distant metastases or deaths attributable to RCC occurred. Mean estimated glomerular filtration rate (eGFR) before the procedure was 72.4 ± 18.5 (SD) mL/min/1.73 m2 and this was not statistically significantly different after the procedure (69.7 ± 18.8 mL/min/1.73 m2), at 1 year (70.7 ± 16.4 mL/min/1.73 m2), or at 2 years (69.8 ± 18.9 mL/min/1.73 m2) (p > 0.05). CONCLUSION. These data add to the accumulating evidence that image-guided cryoablation is an efficacious treatment for selected cT1 RCC with a low complication rate and ro bust 3- and 5-year outcomes.

Protocol for a feasibility study of a cohort embedded randomised controlled trial comparing NEphron Sparing Treatment (NEST) for small renal masses.

INTRODUCTION: Small renal masses (SRMs; ≤4 cm) account for two-thirds of new diagnoses of kidney cancer, the majority of which are incidental findings. The natural history of the SRM seems largely indolent. There is an increasing concern regarding surgical overtreatment and the associated health burden in terms of morbidity and economy. Observational data support the safety and efficacy of percutaneous cryoablation but there is an unmet need for high-quality evidence on non-surgical management options and a head-to-head comparison with standard of care is lacking. Historical interventional trial recruitment difficulties demand novel study conduct approaches. We aim to assess if a novel trial design, the cohort embedded randomised controlled trial (RCT), will enable carrying out such a comparison. METHODS AND ANALYSIS: Single-centre prospective cohort study of adults diagnosed with SRM (n=200) with an open label embedded interventional RCT comparing nephron sparing interventions. Cohort participants will be managed at patient and clinicians' discretion and agree with longitudinal clinical data and biological sample collection, with invitation for trial interventions and participation in comparator control groups. Cohort participants with biopsy-proven renal cell carcinoma eligible for both percutaneous cryoablation and partial nephrectomy will be randomly selected (1:1) and invited to consider percutaneous cryoablation (n=25). The comparator group will be robotic partial nephrectomy (n=25). The primary outcome of this feasibility study is participant recruitment. Qualitative research techniques will assess barriers and recruitment improvement opportunities. Secondary outcomes are participant trial retention, health-related quality of life, treatment complications, blood transfusion rate, intensive care unit admission and renal replacement requirement rates, length of hospital stay, time to return to pre-treatment activities, number of work days lost, and health technologies costs. ETHICS AND DISSEMINATION: Ethical approval has been granted (UK HRA REC 19/EM/0004). Study outputs will be presented and published. TRIAL REGISTRATION: ISRCTN18156881; Pre-results.

Transarterial Chemoembolisation of Colorectal Liver Metastases with Irinotecan-Loaded Beads: A Bi-institutional Analysis of 125 Treatments in 53 Patients.

PURPOSE: To retrospectively review outcomes in patients treated for colorectal liver metastases with DEBIRI. MATERIALS AND METHODS: A retrospective analysis of patients with CRLM treated with DEBIRI was performed between 2008 and 2017 between two tertiary centres. Outcome parameters were overall survival and hepatic progression-free survival, as well as safety. Subgroup analyses were performed to assess the impact on outcomes of hepatic tumour burden at time of treatment, the presence of extrahepatic disease, prior systemic chemotherapy and the prior administration of systemic irinotecan-containing chemotherapy. RESULTS: Fifty-three patients received 125 treatments with DEBIRI over the study period. Median age of patients was 71 (range 41-88). Patients previously received a median of 1 line of chemotherapy (range 1-5). Median number of DEBIRI treatments was 2 (range 1-6). The median survival from first treatment was 14.5 months (range 1-107). Median hepatic progression-free survival was 5 months (0-86.5 months). The presence of extrahepatic disease (seen in 45% of patients) correlated with lower OS. Prolonged OS was seen in patients who received previous ablation and systemic chemotherapy. Technical success rate was found to be 99%. Post-procedural complication rate was 6%. CONCLUSION: Our findings add to the growing body of literature to support the safety profile of DEBIRI in the treatment of CRLM. Further studies will be necessary to help establish the optimum berth of DEBIRI in the treatment algorithm for colorectal liver metastases.

How rapid advances in imaging are defining the future of precision radiation oncology.

Imaging has an essential role in the planning and delivery of radiotherapy. Recent advances in imaging have led to the development of advanced radiotherapy techniques-including image-guided radiotherapy, intensity-modulated radiotherapy, stereotactic body radiotherapy and proton beam therapy. The optimal use of imaging might enable higher doses of radiation to be delivered to the tumour, while sparing normal surrounding tissues. In this article, we review how the integration of existing and novel forms of computed tomography, magnetic resonance imaging and positron emission tomography have transformed tumour delineation in the radiotherapy planning process, and how these advances have the potential to allow a more individualised approach to the cancer therapy. Recent data suggest that imaging biomarkers that assess underlying tumour heterogeneity can identify areas within a tumour that are at higher risk of radio-resistance, and therefore potentially allow for biologically focussed dose escalation. The rapidly evolving concept of adaptive radiotherapy, including artificial intelligence, requires imaging during treatment to be used to modify radiotherapy on a daily basis. These advances have the potential to improve clinical outcomes and reduce radiation-related long-term toxicities. We outline how recent technological advances in both imaging and radiotherapy delivery can be combined to shape the future of precision radiation oncology.

High-Frequency Jet Ventilation During Cryoablation of Small Renal Tumours.

AIM: To evaluate the effect of high-frequency jet ventilation (HFJV) in place of standard intermittent positive-pressure ventilation (IPPV) on procedure duration, patient radiation dose, complication rates, and outcomes during CT-guided cryoablation of small renal tumours. MATERIALS AND METHODS: One hundred consecutive CT-guided cryoablation procedures to treat small renal tumours under general anaesthesia were evaluated-50 with standard IPPV and 50 after the introduction of HFJV as standard practice. Anaesthesia and procedural times, ionising radiation dose, complications, and 1-month post-treatment outcomes were collected. RESULTS: HFJV was feasible and safe in all cases. Mean procedure time and total anaesthetic time were shorter with HFJV (p = <0.0001). The number of required CT acquisitions (p = 0.0002) and total procedure patient radiation dose (p = 0.0027) were also lower in the HFJV group compared with the IPPV group. There were a total of four complications of Clavien-Dindo classification 3 or above-three in the IPPV group and one in the HFJV group. At 1-month follow-up, two cases (both in the IPPV group) demonstrated subtotal treatment. Both cases were subsequently successfully retreated with cryoablation. CONCLUSION: By reducing target tumour motion during CT-guided renal cryoablation, HFJV can reduce procedure times and exposure to ionising radiation. HFJV provides an important adjunct to complex image-guided interventions, with potential to improve safety and treatment outcomes.

Liver resection surgery versus thermal ablation for colorectal LiVer MetAstases (LAVA): study protocol for a randomised controlled trial.

BACKGROUND: Although surgical resection has been considered the only curative option for colorectal liver metastases (CLM), thermal ablation has recently been suggested as an alternative curative treatment. A prospective randomised trial is required to define the efficacy of resection vs ablation for the treatment of colorectal liver metastases. METHODS: Design and setting: This is a multicentre, open, randomised controlled non-inferiority trial design with internal pilot and will be performed in tertiary liver centres in UK and The Netherlands. PARTICIPANTS: Eligible patients will be those with colorectal liver metastases at high surgical risk because of their age, co-morbidities or tumour burden and who would be suitable for liver resection or thermal ablation. INTERVENTION: Thermal ablation as per local policy. CONTROL: Surgical liver resection performed as per centre protocol. Co-interventions: Further chemotherapy will be offered to patients as per current practice. Outcomes Pilot study: Same as main study and in addition patients and clinicians' acceptability of the trial to assist in optimisation of recruitment. PRIMARY OUTCOME: Disease-free survival (DFS) at two years post randomisation. SECONDARY OUTCOMES: Overall survival, timing and site of recurrence, additional therapy after treatment failure, quality of life, complications, length of hospital stay, costs, trial acceptability, DFS measured from end of intervention. FOLLOW-UP: 24 months from randomisation; five-year follow-up for overall survival. SAMPLE SIZE: 330 patients to demonstrate non-inferiority of thermal ablation. DISCUSSION: This trial will determine the effectiveness and cost-effectiveness of thermal ablation vs surgical resection for high-risk people with colorectal liver metastases, and guide the optimal treatment for these patients. TRIAL REGISTRATION: ISRCTN Registry, ISRCTN52040363 . Registered on 9 March 2016.

Automatic quantification of the myocardial extracellular volume by cardiac computed tomography: Synthetic ECV by CCT.

BACKGROUND: The quantification of extracellular volume fraction (ECV) by Cardiac Computed Tomography (CCT) can identify changes in the myocardial interstitium due to fibrosis or infiltration. Current methodologies require laboratory blood hematocrit (Hct) measurement - which complicates the technique. The attenuation of blood (HUblood) is known to change with anemia. We hypothesized that the relationship between Hct and HUblood could be calibrated to rapidly generate a synthetic ECV without formally measuring Hct. METHODS: The association between Hct and HUblood was derived from forty non-contrast thoracic CT scans using regression analysis. Synthetic Hct was then used to calculate synthetic ECV, and in turn compared with ECV using blood Hct in a validation cohort with mild interstitial expansion due to fibrosis (aortic stenosis, n = 28, ECVCT = 28 ± 4%) and severe interstitial expansion due to amyloidosis (n = 27; ECVCT = 54 ± 11%, p < 0.001). For histological validation, synthetic ECV was correlated with collagen volume fraction (CVF) in a separate cohort with aortic stenosis (n = 18). All CT scans were performed at 120 kV and 160 mAs. RESULTS: HUblood was a good predictor of Hct (R2 = 0.47; p < 0.01), with the regression model (Hct = [0.51 * HUblood] + 17.4) describing the association. Synthetic ECV correlated well with conventional ECV (R2 = 0.96; p < 0.01) with minimal bias and 2SD difference of 5.7%. Synthetic ECV correlated as well as conventional ECV with histological CVF (both R2 = 0.50, p < 0.01). Finally, we implemented an automatic ECV plug-in for offline analysis. CONCLUSION: Synthetic ECV by CCT provides instantaneous quantification of the myocardial extracellular space without the need for blood sampling.