MRI in addition to CT in patients scheduled for local therapy of colorectal liver metastases (CAMINO): an international, multicentre, prospective, diagnostic accuracy trial.

BACKGROUND: Guidelines are inconclusive on whether contrast-enhanced MRI using gadoxetic acid and diffusion-weighted imaging should be added routinely to CT in the investigation of patients with colorectal liver metastases who are scheduled for curative liver resection or thermal ablation, or both. Although contrast-enhanced MRI is reportedly superior than contrast-enhanced CT in the detection and characterisation of colorectal liver metastases, its effect on clinical patient management is unknown. We aimed to assess the clinical effect of an additional liver contrast-enhanced MRI on local treatment plan in patients with colorectal liver metastases amenable to local treatment, based on contrast-enhanced CT. METHODS: We did an international, multicentre, prospective, incremental diagnostic accuracy trial in 14 liver surgery centres in the Netherlands, Belgium, Norway, and Italy. Participants were aged 18 years or older with histological proof of colorectal cancer, a WHO performance status score of 0-4, and primary or recurrent colorectal liver metastases, who were scheduled for local therapy based on contrast-enhanced CT. All patients had contrast-enhanced CT and liver contrast-enhanced MRI including diffusion-weighted imaging and gadoxetic acid as a contrast agent before undergoing local therapy. The primary outcome was change in the local clinical treatment plan (decided by the individual clinics) on the basis of liver contrast-enhanced MRI findings, analysed in the intention-to-image population. The minimal clinically important difference in the proportion of patients who would have change in their local treatment plan due to an additional liver contrast-enhanced MRI was 10%. This study is closed and registered in the Netherlands Trial Register, NL8039. FINDINGS: Between Dec 17, 2019, and July 31, 2021, 325 patients with colorectal liver metastases were assessed for eligibility. 298 patients were enrolled and included in the intention-to-treat population, including 177 males (59%) and 121 females (41%) with planned local therapy based on contrast-enhanced CT. A change in the local treatment plan based on liver contrast-enhanced MRI findings was observed in 92 (31%; 95% CI 26-36) of 298 patients. Changes were made for 40 patients (13%) requiring more extensive local therapy, 11 patients (4%) requiring less extensive local therapy, and 34 patients (11%) in whom the indication for curative-intent local therapy was revoked, including 26 patients (9%) with too extensive disease and eight patients (3%) with benign lesions on liver contrast-enhanced MRI (confirmed by a median follow-up of 21·0 months [IQR 17·5-24·0]). INTERPRETATION: Liver contrast-enhanced MRI should be considered in all patients scheduled for local treatment for colorectal liver metastases on the basis of contrast-enhanced CT imaging. FUNDING: The Dutch Cancer Society and Bayer AG - Pharmaceuticals.

Adjuvant holmium-166 radioembolization after radiofrequency ablation in early-stage hepatocellular carcinoma patients: a dose-finding study (HORA EST HCC trial).

PURPOSE: The aim of this study was to investigate the biodistribution of (super-)selective trans-arterial radioembolization (TARE) with holmium-166 microspheres (166Ho-MS), when administered as adjuvant therapy after RFA of HCC 2-5 cm. The objective was to establish a treatment volume absorbed dose that results in an absorbed dose of ≥ 120 Gy on the hyperemic zone around the ablation necrosis (i.e., target volume). METHODS: In this multicenter, prospective dose-escalation study in BCLC early stage HCC patients with lesions 2-5 cm, RFA was followed by (super-)selective infusion of 166Ho-MS on day 5-10 after RFA. Dose distribution within the treatment volume was based on SPECT-CT. Cohorts of up to 10 patients were treated with an incremental dose (60 Gy, 90 Gy, 120 Gy) of 166Ho-MS to the treatment volume. The primary endpoint was to obtain a target volume dose of ≥ 120 Gy in 9/10 patients within a cohort. RESULTS: Twelve patients were treated (male 10; median age, 66.5 years (IQR, [64.3-71.7])) with a median tumor diameter of 2.7 cm (IQR, [2.1-4.0]). At a treatment volume absorbed dose of 90 Gy, the primary endpoint was met with a median absorbed target volume dose of 138 Gy (IQR, [127-145]). No local recurrences were found within 1-year follow-up. CONCLUSION: Adjuvant (super-)selective infusion of 166Ho-MS after RFA for the treatment of HCC can be administered safely at a dose of 90 Gy to the treatment volume while reaching a dose of ≥ 120 Gy to the target volume and may be a favorable adjuvant therapy for HCC lesions 2-5 cm. TRIAL REGISTRATION: Clinicaltrials.gov NCT03437382 . (registered: 19-02-2018).

Extrahepatic perfusion and incomplete hepatic perfusion after hepatic arterial infusion pump implantation: incidence and clinical implications.

INTRODUCTION: This study investigates the incidence of extrahepatic perfusion and incomplete hepatic perfusion at intraoperative methylene blue testing and on postoperative nuclear imaging in patients undergoing hepatic arterial infusion pump (HAIP) chemotherapy. METHODS: The first 150 consecutive patients who underwent pump implantation in the Netherlands were included. All patients underwent surgical pump implantation with the catheter in the gastroduodenal artery. All patients underwent intraoperative methylene blue testing and postoperative nuclear imaging (99mTc-Macroaggregated albumin SPECT/CT) to determine perfusion via the pump. RESULTS: Patients were included between January-2018 and December-2021 across eight centers. During methylene blue testing, 29.3% had extrahepatic perfusion, all successfully managed intraoperatively. On nuclear imaging, no clinically relevant extrahepatic perfusion was detected (0%, 95%CI: 0.0-2.5%). During methylene blue testing, 2.0% had unresolved incomplete hepatic perfusion. On postoperative nuclear imaging, 8.1% had incomplete hepatic perfusion, leading to embolization in only 1.3%. CONCLUSION: Methylene blue testing during pump placement for intra-arterial chemotherapy identified extrahepatic perfusion in 29.3% of patients, but could be resolved intraoperatively in all patients. Postoperative nuclear imaging found no clinically relevant extrahepatic perfusion and led to embolization in only 1.3% of patients. The role of routine nuclear imaging after HAIP implantation should be studied in a larger cohort.

Intraprocedural, Intra-Arterial CT Foot Perfusion Examination for Assessment of Endovascular Therapy in Patients With Critical Limb Ischemia: A Prospective Pilot Study.

BACKGROUND: Current techniques to evaluate computed tomography (CT) foot perfusion in patients with critical limb ischemia use high contrast doses and cannot be used during endovascular procedures. CT perfusion of the foot with intra-arterial contrast injection during endovascular treatment in a hybrid angiography CT suite might solve these problems. PURPOSE: The main objective of this study was to evaluate whether intra-arterial CT foot perfusion using a hybrid CT angiosystem is feasible during endovascular treatment for critical limb ischemia. MATERIAL AND METHODS: This prospective pilot study investigated intraprocedural, intra-arterial CT perfusion of the foot using a hybrid CT angiosystem in 12 patients before and after endovascular treatment for critical limb ischemia. Time to peak (TTP) and arterial blood flow were measured before and after treatment and compared using a paired t test. RESULTS: All 24 CT perfusion maps could be calculated adequately. The contrast volume used for one perfusion CT scan was 4.8 ml. The mean TTP before treatment was 12.8 seconds (standard deviation [SD] 2.8) and the mean TTP posttreatment was 8.4 seconds (SD 1.7), this difference being statistically significant (p=.001). Tendency toward increased blood flow after treatment, 340 ml/min/100 ml (SD 174) vs 514 ml/min/100 ml (SD 366) was noticed (p=.104). The mean effective radiation dose was 0.145 mSv per scan. CONCLUSION: Computed tomography perfusion of the foot with low contrast dose intra-arterial contrast injection during endovascular treatment in a hybrid angiography CT suite is a feasible technique. CLINICAL IMPACT: Intra-arterial CT foot perfusion using a hybrid CT-angiography system is a feasible new technique during endovascular therapy for critical limb ischemia to assess the results of the treament. Future research is necessary in defining endpoints of endovascular treatment and establishing its role in limb salvage prognostication.

Neoadjuvant Treatment with Angiogenesis-Inhibitor Dovitinib Prior to Local Therapy in Hepatocellular Carcinoma: A Phase II Study.

BACKGROUND: Hepatocellular carcinoma (HCC) recurrence rates following locoregional treatment are high. As multireceptor tyrosine kinase inhibitors targeting vascular endothelial growth factor receptors (VEGFRs) are effective in advanced HCC, we assessed the efficacy and safety of neoadjuvant systemic treatment with dovitinib in early- and intermediate-stage HCC. MATERIALS AND METHODS: Twenty-four patients with modified Child-Pugh class A early- and intermediate-stage HCC received neoadjuvant oral dovitinib 500 mg daily (5 days on/2 days off) for 4 weeks, followed by locoregional therapy. Primary endpoints were objective response rates and intratumoral blood flow changes. Secondary endpoints were safety, pharmacodynamical plasma markers of VEGFR-blockade, time to progression (TTP), and overall survival (OS). RESULTS: Modified RECIST overall response rate was 48%, including 13% complete remission, and despite dose reduction/interruption in 83% of patients, intratumoral perfusion index decreased significantly. Grade 3-4 adverse events, most frequently (on-target) hypertension (54%), fatigue (25%), and thrombocytopenia (21%), occurred in 88% of patients. Plasma VEGF-A, VEGF-D, and placental growth factor increased significantly, whereas sTie-2 decreased, consistent with VEGFR-blockade. Following neoadjuvant dovitinib, all patients could proceed to their original planned locoregional treatment. No delayed toxicity occurred. Seven patients (three early, four intermediate stage) underwent orthotopic liver transplant after median 11.4 months. Censoring at transplantation, median TTP and OS were 16.8 and 34.8 months respectively; median cancer-specific survival was not reached. CONCLUSION: Already after a short 4-week dovitinib treatment period, intratumoral blood flow reduction and modest antitumor responses were observed. Although these results support use of systemic neoadjuvant strategies, the poor tolerability indicates that dovitinib dose adaptations are required in HCC. IMPLICATIONS FOR PRACTICE: Orthotopic liver transplantation may cure early and intermediate-stage hepatocellular carcinoma. Considering the expected waiting time >6 months because of donor liver scarcity, there is an unmet need for effective neoadjuvant downsizing strategies. Angiogenesis inhibition by dovitinib does not negatively affect subsequent invasive procedures, is safe to administer immediately before locoregional therapy, and may provide a novel treatment approach to improve patient outcomes if tolerability in patients with hepatocellular carcinoma can be improved by therapeutic drug monitoring and personalized dosing.

Randomized Controlled Trial Comparing Drug-coated Balloon Angioplasty versus Conventional Balloon Angioplasty for Treating Below-the-Knee Arteries in Critical Limb Ischemia: The SINGA-PACLI Trial.

Background There is a paucity of randomized trials demonstrating superior efficacy of drug-coated balloon angioplasty (DCBA) compared with conventional percutaneous transluminal angioplasty (PTA) for below-the-knee arterial disease in patients with -critical limb ischemia. Purpose To compare DCBA versus PTA for below-the-knee lesions in participants with critical limb ischemia through 12 months. Materials and Methods In this prospective, randomized, two-center, double-blind superiority study, participants with critical limb ischemia with rest pain or tissue loss with atherosclerotic disease in the native below-the-knee arteries were randomly assigned (in a one-to-one ratio) to DCBA or PTA after stratification for diabetes and renal failure between November 2013 and October 2017. The primary efficacy end point was angiographic primary patency at 6 months analyzed on an intention-to-treat basis. Secondary end points through 12 months were composed of major adverse events including death and major amputations, wound healing, limb salvage, clinically driven target-lesion revascularization, and amputation-free survival. Primary and binary secondary end points, analyzed by using generalized-linear model and time-to-event analyses, were estimated with Kaplan-Meier survival curves and hazard ratios (Cox regression). Results Seventy participants (mean age, 61 years ± 10 [standard deviation]; 43 men) in the DCBA group and 68 (mean age, 64 years ± 10; 50 men) in the PTA group were evaluated. The percentage of patients with angiographic primary patency at 6 months was 43% (30 of 70) in the DCBA group and 38% (26 of 68) in the PTA group (P = .48). Through 12 months, the percentage of deaths was similar: 21% in the DCBA group and 16% in the PTA group (P = .43). Amputation-free survival rate assessed with Kaplan-Meier curves differed through 12 months: 59% (41 of 70) in the DCBA group compared with 78% (53 of 68) in the PTA group (P = .01). Conclusion In participants with critical limb ischemia, the drug-coated balloon angioplasty group and the conventional percutaneous transluminal angioplasty group had similar primary patency rates at 6 months after treatment of below-the-knee arteries. Amputation-free survival rates through 12 months were higher in the percutaneous transluminal angioplasty group. © RSNA, 2021 Online supplemental material is available for this article.

Percutaneous Hepatic Perfusion with Melphalan in Patients with Unresectable Ocular Melanoma Metastases Confined to the Liver: A Prospective Phase II Study.

BACKGROUND: Ocular melanoma is the most common primary intraocular malignancy and has a very poor prognosis once liver metastases occur. The aim of this study was to prospectively assess the efficacy and safety of percutaneous hepatic perfusion with melphalan (M-PHP) using the new second-generation (GEN 2) hemofiltration system in patients with ocular melanoma metastases confined to the liver. METHODS: Prospective, single-center, single-arm, phase II study including patients with unresectable ocular melanoma metastases confined to the liver. Treatment consisted of two M-PHP procedures at 6-8 weeks interval. Procedures were performed using the CHEMOSAT (GEN 2) system with 3 mg/kg melphalan. Primary endpoints were overall response rate (ORR) and best overall response (BOR). Secondary endpoints included overall survival (OS), progression-free survival (PFS), hepatic PFS (hPFS), and safety. RESULTS: Sixty-four M-PHP procedures were performed in 35 patients between February 2014 and June 2017. The ORR was 72%. BOR was as follows: complete response in 3%, partial response in 69%, stable disease in 13%, and progressive disease in 16%. There was no treatment-related mortality. Fourteen serious adverse events occurred. At a median follow-up of 19.1 months (range 5.6-69.5), median OS was 19.1 months and was significantly longer in responders than in nonresponders (27.5 vs. 11.9 months, p < 0.001). The 1- and 2-year OS was 77% and 43%, respectively. PFS and hPFS were 7.6 and 11.2 months, respectively. CONCLUSIONS: M-PHP using the GEN 2 filter can achieve a high ORR and prolonged survival in patients with liver-only ocular melanoma metastases.

Hospital variation in combined liver resection and thermal ablation for colorectal liver metastases and impact on short-term postoperative outcomes: a nationwide population-based study.

BACKGROUND: Combining resection and thermal ablation can improve short-term postoperative outcomes in patients with colorectal liver metastases (CRLM). This study assessed nationwide hospital variation and short-term postoperative outcomes after combined resection and ablation. METHODS: In this population-based study, all CRLM patients who underwent resection in the Netherlands between 2014 and 2018 were included. After propensity score matching for age, ASA-score, Charlson-score, diameter of largest CRLM, number of CRLM and earlier resection, postoperative outcomes were compared. Postoperative complicated course (PCC) was defined as discharge after 14 days or a major complication or death within 30 days of surgery. RESULTS: Of 4639 included patients, 3697 (80%) underwent resection and 942 (20%) resection and ablation. Unadjusted percentage of patients who underwent resection and ablation per hospital ranged between 4 and 44%. Hospital variation persisted after case-mix correction. After matching, 734 patients remained in each group. Hospital stay (median 6 vs. 7 days, p = 0.011), PCC (11% vs. 14.7%, p = 0.043) and 30-day mortality (0.7% vs. 2.3%, p = 0.018) were lower in the resection and ablation group. Differences faded in multivariable logistic regression due to inclusion of major hepatectomy. CONCLUSION: Significant hospital variation was observed in the Netherlands. Short-term postoperative outcomes were better after combined resection and ablation, attributed to avoiding complications associated with major hepatectomy.

CRIPTO promotes an aggressive tumour phenotype and resistance to treatment in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide. Despite increasing treatment options for this disease, prognosis remains poor. CRIPTO (TDGF1) protein is expressed at high levels in several human tumours and promotes oncogenic phenotype. Its expression has been correlated to poor prognosis in HCC. In this study, we aimed to elucidate the basis for the effects of CRIPTO in HCC. We investigated CRIPTO expression levels in three cohorts of clinical cirrhotic and HCC specimens. We addressed the role of CRIPTO in hepatic tumourigenesis using Cre-loxP-controlled lentiviral vectors expressing CRIPTO in cell line-derived xenografts. Responses to standard treatments (sorafenib, doxorubicin) were assessed directly on xenograft-derived ex vivo tumour slices. CRIPTO-overexpressing patient-derived xenografts were established and used for ex vivo drug response assays. The effects of sorafenib and doxorubicin treatment in combination with a CRIPTO pathway inhibitor were tested in ex vivo cultures of xenograft models and 3D cultures. CRIPTO protein was found highly expressed in human cirrhosis and hepatocellular carcinoma specimens but not in those of healthy participants. Stable overexpression of CRIPTO in human HepG2 cells caused epithelial-to-mesenchymal transition, increased expression of cancer stem cell markers, and enhanced cell proliferation and migration. HepG2-CRIPTO cells formed tumours when injected into immune-compromised mice, whereas HepG2 cells lacking stable CRIPTO overexpression did not. High-level CRIPTO expression in xenograft models was associated with resistance to sorafenib, which could be modulated using a CRIPTO pathway inhibitor in ex vivo tumour slices. Our data suggest that a subgroup of CRIPTO-expressing HCC patients may benefit from a combinatorial treatment scheme and that sorafenib resistance may be circumvented by inhibition of the CRIPTO pathway. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Intraprocedural assessment of ablation margins using computed tomography co-registration in hepatocellular carcinoma treatment with percutaneous ablation: IAMCOMPLETE study.

PURPOSE: The primary objective of this study was to determine the feasibility of ablation margin quantification using a standardized scanning protocol during thermal ablation (TA) of hepatocellular carcinoma (HCC), and a rigid registration algorithm. Secondary objectives were to determine the inter- and intra-observer variability of tumor segmentation and quantification of the minimal ablation margin (MAM). MATERIALS AND METHODS: Twenty patients who underwent thermal ablation for HCC were included. There were thirteen men and seven women with a mean age of 67.1 ± 10.8 (standard deviation [SD]) years (age range: 49.1-81.1 years). All patients underwent contrast-enhanced computed tomography examination under general anesthesia directly before and after TA, with preoxygenated breath hold. Contrast-enhanced computed tomography examinations were analyzed by radiologists using rigid registration software. Registration was deemed feasible when accurate rigid co-registration could be obtained. Inter- and intra-observer rates of tumor segmentation and MAM quantification were calculated. MAM values were correlated with local tumor progression (LTP) after one year of follow-up. RESULTS: Co-registration of pre- and post-ablation images was feasible in 16 out of 20 patients (80%) and 26 out of 31 tumors (84%). Mean Dice similarity coefficient for inter- and intra-observer variability of tumor segmentation were 0.815 and 0.830, respectively. Mean MAM was 0.63 ± 3.589 (SD) mm (range: -6.26-6.65 mm). LTP occurred in four out of 20 patients (20%). The mean MAM value for patients who developed LTP was -4.00 mm, as compared to 0.727 mm for patients who did not develop LTP. CONCLUSION: Ablation margin quantification is feasible using a standardized contrast-enhanced computed tomography protocol. Interpretation of MAM was hampered by the occurrence of tissue shrinkage during TA. Further validation in a larger cohort should lead to meaningful cut-off values for technical success of TA.

Ablation margin quantification after thermal ablation of malignant liver tumors: How to optimize the procedure? A systematic review of the available evidence.

Introduction: To minimize the risk of local tumor progression after thermal ablation of liver malignancies, complete tumor ablation with sufficient ablation margins is a prerequisite. This has resulted in ablation margin quantification to become a rapidly evolving field. The aim of this systematic review is to give an overview of the available literature with respect to clinical studies and technical aspects potentially influencing the interpretation and evaluation of ablation margins. Methods: The Medline database was reviewed for studies on radiofrequency and microwave ablation of liver cancer, ablation margins, image processing and tissue shrinkage. Studies included in this systematic review were analyzed for qualitative and quantitative assessment methods of ablation margins, segmentation and co-registration methods, and the potential influence of tissue shrinkage occurring during thermal ablation. Results: 75 articles were included of which 58 were clinical studies. In most clinical studies the aimed minimal ablation margin (MAM) was ≥ 5 mm. In 10/31 studies, MAM quantification was performed in 3D rather than in three orthogonal image planes. Segmentations were performed either semi-automatically or manually. Rigid and non-rigid co-registration algorithms were used about as often. Tissue shrinkage rates ranged from 7% to 74%. Conclusions: There is a high variability in ablation margin quantification methods. Prospectively obtained data and a validated robust workflow are needed to better understand the clinical value. Interpretation of quantified ablation margins may be influenced by tissue shrinkage, as this may cause underestimation.

Computational Modeling of Thermal Ablation Zones in the Liver: A Systematic Review.

PURPOSE: This systematic review aims to identify, evaluate, and summarize the findings of the literature on existing computational models for radiofrequency and microwave thermal liver ablation planning and compare their accuracy. METHODS: A systematic literature search was performed in the MEDLINE and Web of Science databases. Characteristics of the computational model and validation method of the included articles were retrieved. RESULTS: The literature search identified 780 articles, of which 35 were included. A total of 19 articles focused on simulating radiofrequency ablation (RFA) zones, and 16 focused on microwave ablation (MWA) zones. Out of the 16 articles simulating MWA, only 2 used in vivo experiments to validate their simulations. Out of the 19 articles simulating RFA, 10 articles used in vivo validation. Dice similarity coefficients describing the overlap between in vivo experiments and simulated RFA zones varied between 0.418 and 0.728, with mean surface deviations varying between 1.1 mm and 8.67 mm. CONCLUSION: Computational models to simulate ablation zones of MWA and RFA show considerable heterogeneity in model type and validation methods. It is currently unknown which model is most accurate and best suitable for use in clinical practice.

Sustainability within interventional radiology: opportunities and hurdles.

BACKGROUND: Healthcare is a highly polluting industry and attention to the need for making this sector more sustainable is growing. The interventional radiology (IR) department is a relatively unique department in the hospital because of its synergetic use of both imaging equipment and medical instruments. As a result, the interventional radiology department causes a significant environmental burden in terms of energy usage, waste and water pollution. The aim of this study was to explore the current state of sustainability within IR by conducting a survey and interviews among IR specialists in the Netherlands. RESULTS: The main findings of this study were that there is a high awareness for the need of sustainability within IR, but that there is still limited action. Previous studies point towards the various opportunities in the field of energy, waste and water pollution, yet our study unveils these opportunities are often not implemented because of (1) sustainability not being a priority, (2) a dependency on employees, and (3) factors that simply cannot be changed by an individual IR department or hospital. Generally, our study indicates that there is a willingness to become more sustainable, but that the current system involves a wide range barriers that hinder true change. Furthermore, it seems that no one is currently taking the lead and a leading role from higher management, government, healthcare authorities or professional societies is lacking. CONCLUSIONS: Despite the hurdles found in our study, IR departments can implement several improvements. An important factor is that sustainability should not lead to lower convenience for employees, which can be ensured by a sufficiently designed waste infrastructure and behavioral nudges. Furthermore, there lies an opportunity in more collaboration between IR departments in knowledge sharing and open innovation.

Time Trends in the Treatment and Survival of 5036 Uveal Melanoma Patients in The Netherlands over a 30-Year Period.

BACKGROUND: Uveal melanoma (UM) is a rare intraocular tumor with a dismal prognosis once metastasized. This study provides a nationwide overview and time trends of patients diagnosed with primary UM in the Netherlands between 1989 and 2019. METHODS: A retrospective population-based cohort study based on patients with primary UM from the database of the Netherlands Cancer Registry (NCR), linked with the national population registry Statistics Netherlands on inhabitants' cause of death. Two time periods (1989-2004, 2005-2019) were compared with descriptive statistics. Kaplan-Meier and (multivariate) Cox proportional hazard models were used to assess changes over time for overall survival (OS) and cancer-specific survival (CSS). RESULTS: In total, 5036 patients were analyzed with a median age of 64.0 years at the time of diagnosis. The number of patients increased over time. In the first (1989-2004) and second (2005-2019) period, 32% versus 54% of the patients received radiotherapy (p < 0.001). The median FU time was 13.4 years. The median OS of the first and second periods was 9.5 (95% CI 8.7-10.3) versus 11.3 years (95% CI 10.3-12.3; p < 0.001). The median CSS was 30.0 years (95% CI NA) in the first period and not reached in the second period (p = 0.008). In multivariate analysis (MVA), female gender (HR 0.85; 95% CI 0.79-0.92, p < 0.001) and radiotherapy treatment (HR 0.73; 95% CI 0.64-0.83, p < 0.001) were associated with better OS. Radiotherapy treatment (HR 0.74; 95% CI 0.61-0.90, p = 0.002) was also associated with better CSS. The period of diagnosis was not associated with OS or CSS. CONCLUSIONS: In this study of patients with primary UM, there was a shift to the diagnosis of smaller tumors, possibly due to stage migration. There was also an increase in eye-preserving treatments over time. OS and CSS were modestly improved in the second time period; however, the time period was not associated with OS or CSS in multivariate analyses.

Integration of Three-Dimensional Liver Models in a Multimodal Image-Guided Robotic Liver Surgery Cockpit.

Background: Robotic liver surgery represents the most recent evolution in the field of minimally-invasive liver surgery. For planning and guidance of liver resections, surgeons currently rely on preoperative 2-dimensional (2D) CT and/or MR imaging and intraoperative ultrasonography. Translating 2D images into digital 3-dimensional (3D) models may improve both preoperative planning and surgical guidance. The da Vinci® robotic surgical system is a platform suitable for the integration of multiple imaging modalities into one single view. In this study, we describe multimodal imaging options and introduce the Robotic Liver Surgery Cockpit; Methods: in-house developed software was used and validated for segmentation and registration to create a virtual reality 3D model of the liver based on preoperative imaging. The accuracy of the 3D models in the clinical setting was objectively assessed in 15 patients by measuring tumor diameters and subjectively with a postoperative conducted questionnaire; Results: Implementation and applicability of the 3D model in the surgical cockpit was feasible in all patients and the quality of the 3D reconstructions was high in 14 (93%) of cases. Tumor diameters measured on CT and/or MR imaging were comparable to automated measurements using the segmentation software and 3D models; Conclusions: the 3D model was successfully incorporated in the robotic surgery console as part of a multimodality imaging platform and aided the surgeon in planning and guidance of the resection. Future studies should focus on further automation of 3D rendering and progress into augmented reality.

Three-dimensional quantitative margin assessment in patients with colorectal liver metastases treated with percutaneous thermal ablation using semi-automatic rigid MRI/CECT-CECT co-registration.

PURPOSE: To assess the quantitative minimal ablation margin (MAM) in patients with colorectal liver metastases (CRLM) treated with percutaneous thermal ablation (TA) and correlate the quantitative MAM with local tumour recurrence (LTR). METHOD: Thirty-nine of 143 patients with solitary or multiple CRLM who underwent a first percutaneous TA procedure between January 2011 and May 2020 were considered eligible for study enrolment. Image fusion of pre- and post-ablation scans and 3D quantitative MAM assessment was performed using the in-house developed semi-automatic rigid MRI/CECT-CECT co-registration software deLIVERed. The quantitative MAM was analysed and correlated with LTR. RESULTS: Eighteen (46 %) patients were additionally excluded from further analyses due to suboptimal co-registration (quality co-registration score ≤ 3). The quality of co-registration was considered sufficient in 21 (54 %) patients with a total of 29 CRLM. LTR was found in 5 of 29 (17 %) TA-treated CRLM. In total, 12 (41 %) negative MAMs were measured (mean MAM -4.7 ± 2.7 mm). Negative MAMs were significantly more frequently seen in patients who developed LTR (100 %) compared to those without LTR (29 %; p = 0.003). The median MAM of patients who developed LTR (-6.6 mm (IQR -9.5 to -4.6)) was significantly smaller compared to the median MAM of patients without LTR (0.5 mm (IQR -1.8 to 3.0); p < 0.001). The ROC curve showed high accuracy in predicting LTR for the quantitative MAM (area under the curve of 0.975 ± 0.029). CONCLUSION: This study demonstrated the feasibility of 3D quantitative MAM assessment, using deLIVERed co-registration software, to assess technical success of TA in patients with CRLM and to predict LTR.

Prospective evaluation of percutaneous hepatic perfusion with melphalan as a treatment for unresectable liver metastases from colorectal cancer.

PURPOSE: Percutaneous hepatic perfusion with melphalan (M-PHP) is increasingly used in patients with liver metastases from various primary tumors, yet data on colorectal liver metastases (CRLM) are limited. The aim of this study was to prospectively evaluate the efficacy and safety of M-PHP in patients with CRLM. MATERIALS AND METHODS: Prospective, single-center, single-arm phase II study of M-PHP with hemofiltration in patients with unresectable CRLM. Proven, extrahepatic metastatic disease was one of the exclusion criteria. Primary outcomes were overall response rate (ORR) and best overall response (BOR). Secondary outcomes were overall survival (OS), progression-free survival (PFS), hepatic PFS (hPFS), and safety. RESULTS: A total of 14 M-PHP procedures were performed in eight patients between March 2014 and December 2015. All patients (median age 56 years, ranging from 46 to 68) had received (extensive) systemic chemotherapy before entering the study. The ORR was 25.0%, with two out of eight patients showing partial response as BOR. Median OS was 17.3 months (ranging from 2.6 to 30.9) with a one-year OS of 50.0%. Median PFS and hPFS were 4.4 and 4.5 months, respectively. No serious adverse events occurred. Grade 3/4 hematologic adverse events were observed in the majority of patients, though all were transient and well-manageable. CONCLUSION: M-PHP is a safe procedure with only limited efficacy in patients with unresectable CRLM who already showed progression of disease after receiving one or more systemic treatment regimens.

The Value of 18F-FDG-PET-CT Imaging in Treatment Evaluation of Colorectal Liver Metastases: A Systematic Review.

(1) Background: Up to 50% of patients with colorectal cancer either have synchronous colorectal liver metastases (CRLM) or develop CRLM over the course of their disease. Surgery and thermal ablation are the most common local treatment options of choice. Despite development and improvement in local treatment options, (local) recurrence remains a significant clinical problem. Many different imaging modalities can be used in the follow-up after treatment of CRLM, lacking evidence-based international consensus on the modality of choice. In this systematic review, we evaluated 18F-FDG-PET-CT performance after surgical resection, thermal ablation, radioembolization, and neoadjuvant and palliative chemotherapy based on current published literature. (2) Methods: A systematic literature search was performed on the PubMed database. (3) Results: A total of 31 original articles were included in the analysis. Only one suitable study was found describing the role of 18F-FDG-PET-CT after surgery, which makes it hard to draw a firm conclusion. 18F-FDG-PET-CT showed to be of additional value in the follow-up after thermal ablation, palliative chemotherapy, and radioembolization. 18F-FDG-PET-CT was found to be a poor to moderate predictor of pathologic response after neoadjuvant chemotherapy. (4) Conclusions: 18F-FDG-PET-CT is superior to conventional morphological imaging modalities in the early detection of residual disease after thermal ablation and in the treatment evaluation and prediction of prognosis during palliative chemotherapy and after radioembolization, and 18F-FDG-PET-CT could be considered in selected cases after neoadjuvant chemotherapy and surgical resection.