Total-liver-volume perfusion CT using 3-D image fusion to improve detection and characterization of liver metastases

The purpose of this study was to evaluate the feasibility of a totalliver- volume perfusion CT (CTP) technique for the detection and characterization of livermetastases. Twenty patients underwent helical CT of the total liver volume before and 11 times after intravenous contrast-material injection. To decrease distortion artifacts, all phases were co-registered using 3-D image fusion before creating blood-flow maps. Lesion-based sensitivity and specificity for liver metastases of first the conventional four phases (unenhanced, arterial, portal venous, and equilibrium) and later all 12 phases including blood-flow maps were determined as compared to intraoperative ultrasound and surgical exploration. Arterial and portal venous perfusion was calculated for normalappearing and metastatic liver tissue. Total-liver-volume perfusion values were comparable to studies using single-level CTP. Compared to fourphase CT, total -liver-volume CTP increased sensitivity to 89.2 from 78.4% (P=0.046) and specificity to 82.6 from 78.3% (P=0.074). Total - liver-volume CTP is a noninvasive, quantitative, and feasible technique. Preliminary results suggest an improved detection of liver metastases for CTP compared to four-phase CT

Advances in Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma

Stereotactic Body Radiation Therapy (SBRT) is an emerging effective treatment for hepatocellular carcinoma (HCC) associated with acceptable rates of toxicity in appropriately selected patients. Despite often being reserved for patients unsuitable for other local treatments, prospective and retrospective studies have demonstrated excellent long-term control. SBRT may be used as a stand-alone treatment, or as an adjunct to other HCC therapies. Based on available data, SBRT appears to complement existing local liver therapies. Randomized and nonrandomized comparative studies are required to better determine the optimal role of SBRT in HCC treatment

PET/MRI of Hepatic 90Y Microsphere Deposition Determines Individual Tumor Response.

PurposeThe purpose of our study is to determine if there is a relationship between dose deposition measured by PET/MRI and individual lesion response to yttrium-90 ((90)Y) microsphere radioembolization.Materials and methods26 patients undergoing lobar treatment with (90)Y microspheres underwent PET/MRI within 66 h of treatment and had follow-up imaging available. Adequate visualization of tumor was available in 24 patients, and contours were drawn on simultaneously acquired PET/MRI data. Dose volume histograms (DVHs) were extracted from dose maps, which were generated using a voxelized dose kernel. Similar contours to capture dimensional and volumetric change of tumors were drawn on follow-up imaging. Response was analyzed using both RECIST and volumetric RECIST (vRECIST) criteria.ResultsA total of 8 hepatocellular carcinoma (HCC), 4 neuroendocrine tumor (NET), 9 colorectal metastases (CRC) patients, and 3 patients with other metastatic disease met inclusion criteria. Average dose was useful in predicting response between responders and non-responders for all lesion types and for CRC lesions alone using both response criteria (p < 0.05). D70 (minimum dose to 70 % of volume) was also useful in predicting response when using vRECIST. No significant trend was seen in the other tumor types. For CRC lesions, an average dose of 29.8 Gy offered 76.9 % sensitivity and 75.9 % specificity for response.ConclusionsPET/MRI of (90)Y microsphere distribution showed significantly higher DVH values for responders than non-responders in patients with CRC. DVH analysis of (90)Y microsphere distribution following treatment may be an important predictor of response and could be used to guide future adaptive therapy trials

Registration of Untracked 2D Laparoscopic Ultrasound to CT Images of the Liver using Multi-Labelled Content-Based Image Retrieval

Laparoscopic Ultrasound (LUS) is recommended as a standard-of-care when performing laparoscopic liver resections as it images sub-surface structures such as tumours and major vessels. Given that LUS probes are difficult to handle and some tumours are iso-echoic, registration of LUS images to a pre-operative CT has been proposed as an image-guidance method. This registration problem is particularly challenging due to the small field of view of LUS, and usually depends on both a manual initialisation and tracking to compose a volume, hindering clinical translation. In this paper, we extend a proposed registration approach using Content-Based Image Retrieval (CBIR), removing the requirement for tracking or manual initialisation. Pre-operatively, a set of possible LUS planes is simulated from CT and a descriptor generated for each image. Then, a Bayesian framework is employed to estimate the most likely sequence of CT simulations that matches a series of LUS images. We extend our CBIR formulation to use multiple labelled objects and constrain the registration by separating liver vessels into portal vein and hepatic vein branches. The value of this new labeled approach is demonstrated in retrospective data from 5 patients. Results show that, by including a series of 5 untracked images in time, a single LUS image can be registered with accuracies ranging from 5.7 to 16.4 mm with a success rate of 78%. Initialisation of the LUS to CT registration with the proposed framework could potentially enable the clinical translation of these image fusion techniques

Vandetanib-eluting radiopaque beads and stereotactic body radiotherapy in the treatment of liver cancers

Background: Current treatment options for unresectable hepatocellular carcinoma (HCC) and colorectal liver metastases (mCRC) include transarterial chemoembolisation (TACE) and stereotactic body radiotherapy (SBRT). The objectives of this project were: 1. To assess a novel drug-eluting bead for TACE / 2. To report on the safety and efficacy of SBRT in HCC / 3. To assess the feasibility of using radiopaque beads as fiducial markers for SBRT / Methods: In Part 1, a first-in-human trial was performed in patients with HCC and mCRC using a novel vandetanib-eluting radiopaque bead, BTG-002814. Primary trial endpoints were safety/tolerability and the concentrations of vandetanib and its major metabolite in plasma and resected tissue. Biomarker studies included blood cytokines and perfusion imaging parameters. In Part 2, the efficacy of SBRT was explored in a retrospective study of 31 patients with HCC tumours ≤5 cm and in a phase II study of 13 patients with larger tumours. In Part 3 the feasibility of using radiopaque beads as fiducial markers for SBRT was investigated. / Results: BTG-002814 was shown to have a satisfactory safety profile in 8 patients. Vandetanib was present in the plasma of all patients 12 days post-TACE, and present in resected liver tissue up to 32 days post-treatment. There were no significant changes in perfusion parameters. Blood biomarker studies showed increases in leptin, osteopontin and sTie2. SBRT offered 1-year local control rates of 94% in small HCCs and 92% in larger tumours. Radiopaque beads were visible on 4D-CT and CBCT images in all 8 cases and matching successfully performed. / Conclusions: The safety profile and pharmacokinetic characteristics for this novel technology are adequate to proceed to a Phase I/II trial. SBRT is an effective local treatment for HCC. The role of radiopaque beads as fiducial markers is feasible and warrants further exploration as a clinical trial of TACE with SBRT

The combination of transcatheter arterial chemoembolisation (TACE) and thermal ablation versus TACE alone for hepatocellular carcinoma

BACKGROUND: Hepatocellular carcinoma is the sixth most common cancer worldwide. Hepatic resection is regarded as the curative therapy for hepatocellular carcinoma. However, only about 20% of people with hepatocellular carcinoma are candidates for resection, which highlights the importance of effective nonsurgical therapies. Until now, transcatheter arterial chemoembolisation (TACE) is the most common palliative therapy for hepatocellular carcinoma, but its clinical benefits remain unsatisfactory. During recent years, some studies have reported that the combination of TACE plus thermal ablation can confer a more favourable prognosis than TACE alone. However, clear and compelling evidence to prove the beneficial or harmful effects of the combination of TACE and thermal ablation therapy is lacking. OBJECTIVES: To assess the beneficial and harmful effects of the combination of thermal ablation with TACE versus TACE alone in people with hepatocellular carcinoma. SEARCH METHODS: We performed searches in the Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials in the Cochrane Library, MEDLINE, Embase, LILACS, Science Citation Index Expanded, and Conference Proceedings Citation Index-Science. We endeavoured to identify relevant randomised clinical trials also in the China National Knowledge Infrastructure (CNKI) and Wanfang databases. We searched trial registration websites for ongoing studies. We also handsearched grey literature sources. The date of last search was 22 December 2020. SELECTION CRITERIA: We planned to include all randomised clinical trials comparing the combination of TACE plus thermal ablation versus TACE alone for hepatocellular carcinoma, no matter the language, year of publication, publication status, and reported outcomes. DATA COLLECTION AND ANALYSIS: We planned to use standard methodological procedures expected by Cochrane. We planned to calculate risk ratios (RRs) with the corresponding 95% confidence intervals (CIs). For time-to-event variables, we planned to use the methods of survival analysis and express the intervention effect as a hazard ratio (HR) with 95% Cl. If the log HR and the variance were not directly reported in reports, we planned to calculate them indirectly, following methods for incorporating summary time-to-event data into meta-analysis. We planned to assess the risk of bias of the included studies using the RoB 2 tool. We planned to assess the certainty of evidence with GRADE and present the evidence in a summary of findings table. MAIN RESULTS: Out of 2224 records retrieved with the searches, we considered 135 records eligible for full-text screening. We excluded 21 of these records because the interventions used were outside the scope of our review or the studies were not randomised clinical trials. We listed the remaining 114 records, reporting on 114 studies, under studies awaiting classification because we could not be sure that these were randomised clinical trials from the information in the study paper. We could not obtain information on the registration of the study protocol for any of the 114 studies. We could not obtain information on study approval by regional research ethics committees, either from the study authors or through our own searches of trial registries. Corresponding authors did not respond to our enquiries about the design and conduct of the studies, except for one from whom we did not receive a satisfactory response. We also raised awareness of our concerns to editors of the journals that published the 114 studies, and we did not hear back with useful information. Moreover, there seemed to be inappropriate inclusion of trial participants, based on cancer stage and severity of liver disease, who should have obtained other interventions according to guidelines from learned societies. Accordingly, we found no confirmed randomised clinical trials evaluating the combination of TACE plus thermal ablation versus TACE alone for people with hepatocellular carcinoma for inclusion in our review. We identified five ongoing trials, by handsearching in clinical trial websites. AUTHORS' CONCLUSIONS: We could not find for inclusion any confirmed randomised clinical trials assessing the beneficial or harmful effects of the combination of TACE plus thermal ablation versus TACE alone in people with hepatocellular carcinoma. Therefore, our results did not show or reject the efficiency of the combination of TACE plus thermal ablation versus TACE alone for people with hepatocellular carcinoma. We need trials that compare the beneficial and harmful effects of the combination of TACE plus thermal ablation versus TACE alone in people with hepatocellular carcinoma, not eligible for treatments with curative intent (liver transplantation, ablation surgical resection) and who have sufficient liver reserve, as assessed by the Child Pugh score, and who do not have extrahepatic metastases. Therefore, future trial participants must be classified at Barcelona Clinic Liver Cancer Stage B (intermediate stage) (BCLC-B) or an equivalent, with other staging systems

Usefulness and pitfalls of MAA SPECT/CT in identifying digestive extrahepatic uptake when planning liver radioembolization

International audiencePURPOSE: Identifying gastroduodenal uptake of (99m)Tc-macroaggregated albumin (MAA), which is associated with an increased risk of ulcer disease, is a crucial part of the therapeutic management of patients undergoing radioembolization for liver tumours. Given this context, the use of MAA single photon emission computed tomography (SPECT)/CT may be essential, but the procedure has still not been thoroughly evaluated. The aim of this retrospective study was to determine the effectiveness of MAA SPECT/CT in identifying digestive extrahepatic uptake, while determining potential diagnostic pitfalls. METHODS: Overall, 139 MAA SPECT/CT scans were performed on 103 patients with different hepatic tumour types. Patients were followed up for at least 6 months according to standard requirements. RESULTS: Digestive, or digestive-like, uptake other than free pertechnetate was identified in 5.7% of cases using planar imaging and in 36.6% of cases using SPECT/CT. Uptake sites identified by SPECT/CT included the gastroduodenal region (3.6%), gall bladder (12.2%), portal vein thrombosis (6.5%), hepatic artery (6.5%), coil embolization site (2.1%) as well as falciform artery (5.0%). For 2.1% of explorations, a coregistration error between SPECT and CT imaging could have led to a false diagnosis by erroneously attributing an uptake site to the stomach or gall bladder, when the uptake actually occurred in the liver. CONCLUSION: SPECT/CT is more efficacious than planar imaging in identifying digestive extrahepatic uptake sites, with extrahepatic uptake observed in one third of scans using the former procedure. However, more than half of the uptake sites in our study were vascular in nature, without therapeutic implications. The risk of coregistration errors must also be kept in mind