Steve Bandula

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.

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.

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.

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 (r_s). 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: r_s = 0.69, p < 0.001; skewness: r_s = 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: r_s = −0.66, p < 0.001) and ECV (EQ-CT, entropy: r_s = −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.

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.

Objective: To report on the use of RFA for the treatment of symptomatic benign and autonomously functioning thyroid nodules (AFTNs) in the first reported UK cohort. Methods: Patients treated over a 19-month period were retrospectively reviewed. Nodules were assessed pre-treatment and at 1 and 6 months post-treatment. Nodule volume was calculated and cosmetic assessment and thyroid-related quality of life (QoL) scores were recorded at each time point. Thyroid function tests (TFTs) were recorded at all three time points for patients with ATFNs. Results: 46 patients with 50 nodules were treated with no complications. The mean volume reduction 1-month post-treatment was 53 +- 14.9 % ( p < 0.0001). Six month data was available for 31 nodules and showed a mean 67 +- 17.6% vol reduction ( p < 0.0001). Five of the six patients with ATFNs were euthyroid at 1-month post-procedure. 6-month data was available on three of these patients, and all remained euthyroid. The thyroid-related QoL and cosmetic scores also improved. Data from 23 patients was available pre-treatment and at 6 months post-treatment and there was a significant ( p < 0.0001) reduction in QoL score. Pre-treatment, 82 % of nodules were readily visible at rest, decreasing to 12.5 % 6 months after treatment ( p < 0.0001). Conclusions: Results align with published data suggesting that RFA is effective at reducing nodule volume and at treating ATFNs and leads to improvement in thyroid-related QoL and cosmetic scores. Advances in knowledge: This early UK experience demonstrates that day-case radiofrequency ablation can provide safe and effective treatment of benign symptomatic thyroid nodules.

BACKGROUND Transarterial chemoembolization (TACE) is the current standard of care for patients with intermediate-stage hepatocellular carcinoma (HCC) and is also a treatment option for patients with liver metastases from colorectal cancer. However, TACE is not a curative treatment, and tumor progression occurs in more than half of the patients treated. Despite advances and technical refinements of TACE, including the introduction of drug-eluting beads-TACE, the clinical efficacy of TACE has not been optimized, and improved arterial therapies are required. OBJECTIVE The primary objectives of the VEROnA study are to evaluate the safety and tolerability of vandetanib-eluting radiopaque embolic beads (BTG-002814) in patients with resectable liver malignancies and to determine concentrations of vandetanib and the N-desmethyl metabolite in plasma and resected liver following treatment with BTG-002814. METHODS The VEROnA study is a first-in-human, open-label, single-arm, phase 0, window-of-opportunity study of BTG-002814 (containing 100 mg vandetanib) delivered transarterially, 7 to 21 days before surgery in patients with resectable liver malignancies. Eligible patients have a diagnosis of colorectal liver metastases, or HCC (Childs Pugh A), diagnosed histologically or radiologically, and are candidates for liver surgery. All patients are followed up for 28 days following surgery. Secondary objectives of this study are to evaluate the anatomical distribution of BTG-002814 on noncontrast-enhanced imaging, to evaluate histopathological features in the surgical specimen, and to assess changes in blood flow on dynamic contrast-enhanced magnetic resonance imaging following treatment with BTG-002814. Exploratory objectives of this study are to study blood biomarkers with the potential to identify patients likely to respond to treatment and to correlate the distribution of BTG-002814 on imaging with pathology by 3-dimensional modeling. RESULTS Enrollment for the study was completed in February 2019. Results of a planned interim analysis were reviewed by a safety committee after the first 3 patients completed follow-up. The recommendation of the committee was to continue the study without any changes to the dose or trial design, as there were no significant unexpected toxicities related to BTG-002814. CONCLUSIONS The VEROnA study is studying the feasibility of administering BTG-002814 to optimize the use of this novel technology as liver-directed therapy for patients with primary and secondary liver cancer. CLINICALTRIAL ClinicalTrial.gov NCT03291379; https://clinicaltrials.gov/ct2/show/NCT03291379 INTERNATIONAL REGISTERED REPORT DERR1-10.2196/13696

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 = 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.

Automatic segmentation of abdominal anatomy on computed tomography (CT) images can support diagnosis, treatment planning, and treatment delivery workflows. Segmentation methods using statistical models and multi-atlas label fusion (MALF) require inter-subject image registrations, which are challenging for abdominal images, but alternative methods without registration have not yet achieved higher accuracy for most abdominal organs. We present a registration-free deep-learning-based segmentation algorithm for eight organs that are relevant for navigation in endoscopic pancreatic and biliary procedures, including the pancreas, the gastrointestinal tract (esophagus, stomach, and duodenum) and surrounding organs (liver, spleen, left kidney, and gallbladder). We directly compared the segmentation accuracy of the proposed method to the existing deep learning and MALF methods in a cross-validation on a multi-centre data set with 90 subjects. The proposed method yielded significantly higher Dice scores for all organs and lower mean absolute distances for most organs, including Dice scores of 0.78 versus 0.71, 0.74, and 0.74 for the pancreas, 0.90 versus 0.85, 0.87, and 0.83 for the stomach, and 0.76 versus 0.68, 0.69, and 0.66 for the esophagus. We conclude that the deep-learning-based segmentation represents a registration-free method for multi-organ abdominal CT segmentation whose accuracy can surpass current methods, potentially supporting image-guided navigation in gastrointestinal endoscopy procedures.