Incidental Ring-hyperenhancing Liver Micronodules at CT Hepatic Arteriography-guided Percutaneous Thermal Ablation of Colorectal Liver Metastases.

CT during hepatic arteriography (CTHA) is a highly sensitive imaging method for detecting colorectal liver metastases (CLMs), which supports its use during percutaneous thermal liver ablation. In contrast to its high sensitivity, its specificity for incidental small CLMs not detected at preablation cross-sectional imaging is believed to be low given the absence of specific imaging signatures and the common presence of pseudolesions. In this retrospective study of 22 patients (mean age, 55 years ± 10.6 [SD]; 63.6% male, 36.4% female) with CLMs undergoing CTHA-guided microwave percutaneous thermal ablation between November 2017 and October 2022, the authors provided a definition of incidental ring-hyperenhancing liver micronodules (RHLMs) and investigated whether there is a correlation of RHLMs with histologic analysis or intrahepatic tumor progression at imaging follow-up after applying a biomechanical deformable image registration method. The analysis revealed 25 incidental RHLMs in 41.7% (10 of 24) of the CTHA images from the respective guided ablation sessions. Of those, four RHLMs were ablated. Among the remaining 21 RHLMs, 71.4% (15 of 21) were confirmed to be CLM with either histology (n = 3) or imaging follow-up (n = 12). The remaining 28.6% (six of 21) of RHLMs were not observed at follow-up imaging. This suggests that RHLMs at CTHA may be an early indicator of incidental small CLMs. Keywords: Colorectal Neoplasms, Liver, Angiography, CT, Incidental Findings, Ablation Supplemental material is available for this article. © RSNA, 2024.

Ablative margin quantification using deformable versus rigid image registration in colorectal liver metastasis thermal ablation: a retrospective single-center study.

PURPOSE: To investigate the correlation of minimal ablative margin (MAM) quantification using biomechanical deformable (DIR) versus intensity-based rigid image registration (RIR) with local outcomes following colorectal liver metastasis (CLM) thermal ablation. METHODS: This retrospective single-institution study included consecutive patients undergoing thermal ablation between May 2016 and October 2021. Patients who did not have intraprocedural pre- and post-ablation contrast-enhanced CT images for MAM quantification or follow-up period less than 1 year without residual tumor or local tumor progression (LTP) were excluded. DIR and RIR methods were used to quantify the MAM. The registration accuracy was compared using Dice similarity coefficient (DSC). Area under the receiver operating characteristic curve (AUC) was used to test MAM in predicting local tumor outcomes. RESULTS: A total of 72 patients (mean age 57; 44 men) with 139 tumors (mean diameter 1.5 cm ± 0.8 (SD)) were included. During a median follow-up of 29.4 months, there was one residual unablated tumor and the LTP rate was 17% (24/138). The ranges of DSC were 0.96-0.98 and 0.67-0.98 for DIR and RIR, respectively (p < 0.001). When using DIR, 27 (19%) tumors were partially or totally registered outside the liver, compared to 46 (33%) with RIR. Using DIR versus RIR, the corresponding median MAM was 4.7 mm versus 4.0 mm, respectively (p = 0.5). The AUC in predicting residual tumor and 1-year LTP for DIR versus RIR was 0.89 versus 0.72, respectively (p < 0.001). CONCLUSION: Ablative margin quantified on intra-procedural CT imaging using DIR method outperformed RIR for predicting local outcomes of CLM thermal ablation. CLINICAL RELEVANCE STATEMENT: The study supports the role of biomechanical deformable image registration as the preferred image registration method over rigid image registration for quantifying minimal ablative margins using intraprocedural contrast-enhanced CT images. KEY POINTS: • Accurate and reproducible image registration is a prerequisite for clinical application of image-based ablation confirmation methods. • When compared to intensity-based rigid image registration, biomechanical deformable image registration for minimal ablative margin quantification was more accurate for liver registration using intraprocedural contrast-enhanced CT images. • Biomechanical deformable image registration outperformed intensity-based rigid image registration for predicting local tumor outcomes following colorectal liver metastasis thermal ablation.

Intraprocedural Versus Initial Follow-up Minimal Ablative Margin Assessment After Colorectal Liver Metastasis Thermal Ablation: Which One Better Predicts Local Outcomes?

OBJECTIVES: The aim of this study was to investigate the prognostic value of 3-dimensional minimal ablative margin (MAM) quantified by intraprocedural versus initial follow-up computed tomography (CT) in predicting local tumor progression (LTP) after colorectal liver metastasis (CLM) thermal ablation. MATERIALS AND METHODS: This single-institution, patient-clustered, tumor-based retrospective study included patients undergoing microwave and radiofrequency ablation between 2016 and 2021. Patients without intraprocedural and initial follow-up contrast-enhanced CT, residual tumors, or with follow-up less than 1 year without LTP were excluded. Minimal ablative margin was quantified by a biomechanical deformable image registration method with segmentations of CLMs on intraprocedural preablation CT and ablation zones on intraprocedural postablation and initial follow-up CT. Prognostic value of MAM to predict LTP was tested using area under the curve and competing-risk regression model. RESULTS: A total of 68 patients (mean age ± standard deviation, 57 ± 12 years; 43 men) with 133 CLMs were included. During a median follow-up of 30.3 months, LTP rate was 17% (22/133). The median volume of ablation zone was 27 mL and 16 mL segmented on intraprocedural and initial follow-up CT, respectively ( P < 0.001), with corresponding median MAM of 4.7 mm and 0 mm, respectively ( P < 0.001). The area under the curve was higher for MAM quantified on intraprocedural CT (0.89; 95% confidence interval [CI], 0.83-0.94) compared with initial follow-up CT (0.66; 95% CI, 0.54-0.76) in predicting 1-year LTP ( P < 0.001). An MAM of 0 mm on intraprocedural CT was an independent predictor of LTP with a subdistribution hazards ratio of 11.9 (95% CI, 4.9-28.9; P < 0.001), compared with 2.4 (95% CI, 0.9-6.0; P = 0.07) on initial follow-up CT. CONCLUSIONS: Ablative margin quantified on intraprocedural CT significantly outperformed initial follow-up CT in predicting LTP and should be used for ablation endpoint assessment.

Thermal ablation with configurable shapes: a comprehensive, automated model for bespoke tumor treatment.

BACKGROUND: Malignant tumors routinely present with irregular shapes and complex configurations. The lack of customization to individual tumor shapes and standardization of procedures limits the success and application of thermal ablation. METHODS: We introduced an automated treatment model consisting of (i) trajectory and ablation profile planning, (ii) ablation probe insertion, (iii) dynamic energy delivery (including robotically driven control of the energy source power and location over time, according to a treatment plan bespoke to the tumor shape), and (iv) quantitative ablation margin verification. We used a microwave ablation system and a liver phantom (acrylamide polymer with a thermochromic ink) to mimic coagulation and measure the ablation volume. We estimated the ablation width as a function of power and velocity following a probabilistic model. Four representative shapes of liver tumors < 5 cm were selected from two publicly available databases. The ablated specimens were cut along the ablation probe axis and photographed. The shape of the ablated volume was extracted using a color-based segmentation method. RESULTS: The uncertainty (standard deviation) of the ablation width increased with increasing power by ± 0.03 mm (95% credible interval [0.02, 0.043]) per watt increase in power and by ± 0.85 mm (95% credible interval [0, 2.5]) per mm/s increase in velocity. Continuous ablation along a straight-line trajectory resulted in elongated rotationally symmetric ablation shapes. Simultaneous regulation of the power and/or translation velocity allowed to modulate the ablation width at specific locations. CONCLUSIONS: This study offers the proof-of-principle of the dynamic energy delivery system using ablation shapes from clinical cases of malignant liver tumors. RELEVANCE STATEMENT: The proposed automated treatment model could favor the customization and standardization of thermal ablation for complex tumor shapes. KEY POINTS: • Current thermal ablation systems are limited to ellipsoidal or spherical shapes. • Dynamic energy delivery produces elongated rotationally symmetric ablation shapes with varying widths. • For complex tumor shapes, multiple customized ablation shapes could be combined.

Bayesian parametric models for survival prediction in medical applications.

BACKGROUND: Evidence-based treatment decisions in medicine are made founded on population-level evidence obtained during randomized clinical trials. In an era of personalized medicine, these decisions should be based on the predicted benefit of a treatment on a patient-level. Survival prediction models play a central role as they incorporate the time-to-event and censoring. In medical applications uncertainty is critical especially when treatments differ in their side effect profiles or costs. Additionally, models must be adapted to local populations without diminishing performance and often without the original training data available due to privacy concern. Both points are supported by Bayesian models-yet they are rarely used. The aim of this work is to evaluate Bayesian parametric survival models on public datasets including cardiology, infectious diseases, and oncology. MATERIALS AND METHODS: Bayesian parametric survival models based on the Exponential and Weibull distribution were implemented as a Python package. A linear combination and a neural network were used for predicting the parameters of the distributions. A superiority design was used to assess whether Bayesian models are better than commonly used models such as Cox Proportional Hazards, Random Survival Forest, and Neural Network-based Cox Proportional Hazards. In a secondary analysis, overfitting was compared between these models. An equivalence design was used to assess whether the prediction performance of Bayesian models after model updating using Bayes rule is equivalent to retraining on the full dataset. RESULTS: In this study, we found that Bayesian parametric survival models perform as good as state-of-the art models while requiring less hyperparameters to be tuned and providing a measure of the uncertainty of the predictions. In addition, these models were less prone to overfitting. Furthermore, we show that updating these models using Bayes rule yields equivalent performance compared to models trained on combined original and new datasets. CONCLUSIONS: Bayesian parametric survival models are non-inferior to conventional survival models while requiring less hyperparameter tuning, being less prone to overfitting, and allowing model updating using Bayes rule. Further, the Bayesian models provide a measure of the uncertainty on the statistical inference, and, in particular, on the prediction.

Study Protocol STEREOLAB: Stereotactic Liver Ablation Assisted with Intra-Arterial CT Hepatic Arteriography and Ablation Confirmation Software Assessment.

PURPOSE: This study aims to evaluate the technical efficacy and local tumor progression-free survival (LTPFS) of a standardized workflow for thermal ablation of colorectal liver metastases (CRLM) consisting of CT during hepatic arteriography (CTHA)-based imaging analysis, stereotactic thermal ablation, and computer-based software assessment of ablation margins. MATERIALS AND METHODS: This investigator initiated, single-center, single-arm prospective trial will enroll up to 50 patients (≤ 5 CRLM, Measuring ≤ 5 cm). Procedures will be performed in an angio-CT suite under general anesthesia. The primary objective is to estimate LTPFS with a follow-up of up to 2 years and secondary objectives are analysis of the impact of minimal ablative margins on LTPFS, adverse events, contrast media utilization and radiation exposure, overall oncological outcomes, and anesthesia/procedural time. Adverse events (AE) will be recorded by CTCAE (Common Toxicity Criteria for Adverse Events), and Bayesian optimal phase-2 design will be applied for major intraprocedural AE stop boundaries. The institutional CRLM ablation registry will be used as benchmark for comparative analysis with the historical cohort. DISCUSSION: The STEREOLAB trial will introduce a high-precision and standardized thermal ablation workflow for CRLM consisting of CT during hepatic arteriography imaging, stereotactic guidance, and ablation confirmation. Trial Registration ClinicalTrials.gov identifier: (NCT05361551).

Salvage Locoregional Therapy Following Progression After Radiotherapy for Hepatocellular Carcinoma Is Associated with Improved Outcomes.

PURPOSE: To evaluate the impact of salvage locoregional therapy (salvage-LT) on survival of hepatocellular carcinoma (HCC) patients presenting with intrahepatic tumor progression following radiotherapy. METHODS: This single-institution retrospective analysis included consecutive HCC patients having intrahepatic tumor progression following radiotherapy during 2015-2019. Overall survival (OS) was calculated from the date of intrahepatic tumor progression after initial radiotherapy by using the Kaplan-Meier method. Log-rank tests and Cox regression models were used for univariable and multivariable analyses. An inverse probability weighting was used to estimate treatment effect of salvage-LT considering confounding factors. RESULTS: A total of 123 patients (mean age ± SD, 70 years ± 10; 97 men) were evaluated. Among those, 35 patients underwent 59 sessions of salvage-LT, including transarterial embolization/chemoembolization (n = 33), ablation (n = 11), selective internal radiotherapy (n = 7), and external beam radiotherapy (n = 8). At a median follow-up of 15.1 months (range, 3.4-54.5 months), the median OS was 23.3 months in patients who received salvage-LT and 6.6 months who did not. At multivariate analysis, ECOG performance status, Child-Pugh class, albumin-bilirubin grade, extrahepatic disease, and lack of salvage-LT were independent predictors of worse OS. After inverse probability weighting, salvage-LT was associated with a survival benefit of 8.9 months (95% CI: 1.1, 16.7 months; p = 0.03). CONCLUSIONS: Salvage locoregional therapy is associated with increased survival in HCC patients suffering from intrahepatic tumor progression following initial radiotherapy.

Use of Contrast Media During CT-guided Thermal Ablation of Colorectal Liver Metastasis for Procedure Planning is Associated with Improved Immediate Outcomes.

PURPOSE: The aim of this study was to analyze the impact of using intra-procedural pre-ablation contrast-enhanced CT prior to percutaneous thermal ablation (pre-ablation CECT) of colorectal liver metastases (CLM) on local outcomes. MATERIALS AND METHODS: This retrospective analysis of a prospectively collected liver ablation registry included 144 consecutive patients (median age 57 years IQR [49, 65], 60% men) who underwent 173 CT-guided ablation sessions for 250 CLM between October 2015 and March 2020. In addition to oncologic outcomes, technical success was retrospectively evaluated using a biomechanical deformable image registration software for 3D-minimal ablative margin (3D-MAM) quantification. Bayesian regression was used to estimate effects of pre-ablation CECT on residual unablated tumor, 3D-MAM, and local tumor progression-free survival (LTPFS). RESULTS: Pre-ablation CECT was acquired in 71/173 (41%) sessions. Residual unablated tumor was present in one (0.9%) versus nine tumors (6.6%) ablated with versus without using pre-ablation CECT, respectively (p = 0.024). Pre-ablation CECT use decreased the odds of residual disease on first follow-up by 78% (CI95% [5, 86]) and incomplete ablation (3D-MAM ≤ 0 mm) by 58% (CI95% [13, 122]). The odds ratio for residual unablated tumor for larger CLM was lower when pre-ablation CECT was used (odds ratio 1.0 with pre-ablation CECT vs. 2.52 without). Pre-ablation CECT use was not associated with improvements on LTPFS. CONCLUSIONS: Pre-ablation CECT is associated with improved immediate outcomes by significantly reducing the incidence of residual unablated tumor and by mitigating the risk of incomplete ablation for larger CLM. We recommend performing baseline intra-procedural pre-ablation CECT as a standard imaging protocol. LEVEL OF EVIDENCE: Level 3 (retrospective cohort study).

Ablative Margins of Colorectal Liver Metastases Using Deformable CT Image Registration and Autosegmentation.

Background Confirming ablation completeness with sufficient ablative margin is critical for local tumor control following colorectal liver metastasis (CLM) ablation. An image-based confirmation method considering patient- and ablation-related biomechanical deformation is an unmet need. Purpose To evaluate a biomechanical deformable image registration (DIR) method for three-dimensional (3D) minimal ablative margin (MAM) quantification and the association with local disease progression following CT-guided CLM ablation. Materials and Methods This single-institution retrospective study included patients with CLM treated with CT-guided microwave or radiofrequency ablation from October 2015 to March 2020. A biomechanical DIR method with AI-based autosegmentation of liver, tumors, and ablation zones on CT images was applied for MAM quantification retrospectively. The per-tumor incidence of local disease progression was defined as residual tumor or local tumor progression. Factors associated with local disease progression were evaluated using the multivariable Fine-Gray subdistribution hazard model. Local disease progression sites were spatially localized with the tissue at risk for tumor progression (<5 mm) using a 3D ray-tracing method. Results Overall, 213 ablated CLMs (mean diameter, 1.4 cm) in 124 consecutive patients (mean age, 57 years ± 12 [SD]; 69 women) were evaluated, with a median follow-up interval of 25.8 months. In ablated CLMs, an MAM of 0 mm was depicted in 14.6% (31 of 213), from greater than 0 to less than 5 mm in 40.4% (86 of 213), and greater than or equal to 5 mm in 45.1% (96 of 213). The 2-year cumulative incidence of local disease progression was 72% for 0 mm and 12% for greater than 0 to less than 5 mm. No local disease progression was observed for an MAM greater than or equal to 5 mm. Among 117 tumors with an MAM less than 5 mm, 36 had local disease progression and 30 were spatially localized within the tissue at risk for tumor progression. On multivariable analysis, an MAM of 0 mm (subdistribution hazard ratio, 23.3; 95% CI: 10.8, 50.5; P < .001) was independently associated with local disease progression. Conclusion Biomechanical deformable image registration and autosegmentation on CT images enabled identification and spatial localization of colorectal liver metastases at risk for local disease progression following ablation, with a minimal ablative margin greater than or equal to 5 mm as the optimal end point. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Sofocleous in this issue.

Targeted exome-based predictors of patterns of progression of colorectal liver metastasis after percutaneous thermal ablation.

BACKGROUND: Percutaneous thermal ablation is a curative-intent locoregional therapy (LRT) for selected patients with unresectable colorectal liver metastasis (CLM). Several factors have been identified that contribute to local tumour control after ablation. However, factors contributing to disease progression outside the ablation zone after ablation are poorly understood. METHODS: In this retrospective study, using next-generation sequencing, we identified genetic biomarkers associated with different patterns of progression following thermal ablation of CLM. RESULTS: A total of 191 ablation naïve patients between January 2011 and March 2020 were included in the analysis, and 101 had genomic profiling available. Alterations in the TGFß pathway were associated with increased risk of development of new intrahepatic tumours (hazard ratio [HR], 2.75, 95% confidence interval [95% CI] 1.39-5.45, P = 0.004); and alterations in the Wnt pathway were associated with increased probability of receiving salvage LRT for any intrahepatic progression (HR, 5.8, 95% CI 1.94-19.5, P = 0.003). CONCLUSIONS: Our findings indicate that genomic alterations in cancer-related signalling pathways can predict different progression patterns and the likelihood of receiving salvage LRT following percutaneous thermal ablation of CLM.

Study Protocol COVER-ALL: Clinical Impact of a Volumetric Image Method for Confirming Tumour Coverage with Ablation on Patients with Malignant Liver Lesions.

PURPOSE: This study aims to evaluate the intra-procedural use of a novel ablation confirmation (AC) method, consisting of biomechanical deformable image registration incorporating AI-based auto-segmentation, and its impact on tumor coverage by quantitative three-dimensional minimal ablative margin (MAM) CT-generated assessment. MATERIALS AND METHODS: This single-center, randomized, phase II, intent-to-treat trial is enrolling 100 subjects with primary and secondary liver tumors (≤ 3 tumors, 1-5 cm in diameter) undergoing microwave or radiofrequency ablation with a goal of achieving ≥ 5 mm MAM. For the experimental arm, the proposed novel AC method is utilized for ablation applicator(s) placement verification and MAM assessment. For the control arm, the same variables are assessed by visual inspection and anatomical landmarks-based quantitative measurements aided by co-registration of pre- and post-ablation contrast-enhanced CT images. The primary objective is to evaluate the impact of the proposed AC method on the MAM. Secondary objectives are 2-year LTP-free survival, complication rates, quality of life, liver function, other oncological outcomes, and impact of AC method on procedure workflow. DISCUSSION: The COVER-ALL trial will provide information on the role of a biomechanical deformable image registration-based ablation confirmation method incorporating AI-based auto-segmentation for improving MAM, which might translate in improvements of liver ablation efficacy. CONCLUSION: The COVER-ALL trial aims to provide information on the role of a novel intra-procedural AC method for improving MAM, which might translate in improvements of liver ablation efficacy. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04083378.

Volumetric analyses of ablation dimensions in microwave ablation for colorectal liver metastases.

BACKGROUND: In thermal ablation of malignant liver tumors, ablation dimensions remain poorly predictable. This study aimed to investigate factors influencing volumetric ablation dimensions in patients treated with stereotactic microwave ablation (SMWA) for colorectal liver metastases (CRLM). METHODS: Ablation volumes from CRLM ≤3 cm treated with SMWA within a prospective European multicentre trial were segmented. Correlations between applied ablation energies and resulting effective ablation volumes (EAV) and ablation volume irregularities (AVI) were investigated. A novel measure for AVI, including minimum enclosing and maximum inscribed ellipsoid ablation volumes, and a surrogate parameter for the expansion of ablation energy (EAV per applied energy), was introduced. Potential influences of tumor and patient-specific factors on EAV per applied energy and AVI were analyzed using multivariable mixed-effects models. RESULTS: A total of 116 ablations from 71 patients were included for analyses. Correlations of EAV or AVI and ablation energy were weak to moderate, with a maximum of 25% of the variability in EAV and 13% in AVI explained by the applied ablation energy. On multivariable analysis, ablation expansion (EAV per applied ablation energy) was influenced mainly by the tumor radius (B = -0.03, [CI -0.04, -0.007]). AVI was significantly larger with higher applied ablation energies (B = 0.002 [CI 0.0007, 0.002]]); liver steatosis, KRAS mutation, subcapsular location or proximity to major blood vessels had no influence. CONCLUSIONS: This study confirmed that factors beyond the applied ablation energy might affect volumetric ablation dimensions, resulting in poor predictability. Further clinical trials including tissue sampling are needed to relate physical tissue properties to ablation expansion.

3D Quantitative Ablation Margins for Prediction of Ablation Site Recurrence After Stereotactic Image-Guided Microwave Ablation of Colorectal Liver Metastases: A Multicenter Study.

BACKGROUND: Three-dimensional (3D) volumetric ablation margin assessment after thermal ablation of liver tumors using software has been described, but its predictive value on treatment efficacy when accounting for other factors known to correlate ablation site recurrence (ASR) remains unknown. PURPOSE: To investigate 3D quantitative ablation margins (3D-QAMs) as an algorithm to predict ASR within 1 year after stereotactic microwave ablation (SMWA) for colorectal liver metastases (CRLM). MATERIALS AND METHODS: Sixty-five tumors in 47 patients from a prospective multicenter study of patients undergoing SMWA for CRLM were included in this retrospective 3D-QAM analysis. Using a previously developed algorithm, 3D-QAM defined as the distribution of tumor to ablation surface distances was assessed in co-registered pre- and post-ablation CT scans. The discriminatory power and optimal cutoff values for 3D-QAM were assessed using receiver operating characteristic (ROC) curves. Multivariable logistic regression analysis using generalized estimating equations was applied to investigate the impact of various 3D-QAM outputs on 1-year ASR while accounting for other known influencing factors. RESULTS: Ten of the 65 (15.4%) tumors included for 3D-QAM analysis developed ASR. ROC analyses identified i) 3D-QAM <1 mm for >23% of the tumor surface, ii) 3D-QAM <5 mm for >45%, and iii) the minimal ablation margin (MAM) as the 3D-QAM outputs with optimal discriminatory qualities. The multivariable regression model without 3D-QAM yielded tumor diameter and KRAS mutation as 1-year ASR predictors. When adding 3D-QAM, this factor became the main predictor of 1-year ASR [odds ratio (OR) 21.67 (CI 2.48, 165.21) if defined as >23% <1 mm; OR 0.52 (CI 0.29, 0.95) if defined as MAM]. CONCLUSIONS: 3D-QAM allows objectifiable and standardized assessment of tumor coverage by the ablation zone after SMWA. Our data shows that 3D-QAM represents the most important factor predicting ASR within 1 year after SMWA of CRLM.

Stereotactic and Robotic Minimally Invasive Thermal Ablation of Malignant Liver Tumors: A Systematic Review and Meta-Analysis.

BACKGROUND: Stereotactic navigation techniques aim to enhance treatment precision and safety in minimally invasive thermal ablation of liver tumors. We qualitatively reviewed and quantitatively summarized the available literature on procedural and clinical outcomes after stereotactic navigated ablation of malignant liver tumors. METHODS: A systematic literature search was performed on procedural and clinical outcomes when using stereotactic or robotic navigation for laparoscopic or percutaneous thermal ablation. The online databases Medline, Embase, and Cochrane Library were searched. Endpoints included targeting accuracy, procedural efficiency, and treatment efficacy outcomes. Meta-analysis including subgroup analyses was performed. RESULTS: Thirty-four studies (two randomized controlled trials, three prospective cohort studies, 29 case series) were qualitatively analyzed, and 22 studies were included for meta-analysis. Weighted average lateral targeting error was 3.7 mm (CI 3.2, 4.2), with all four comparative studies showing enhanced targeting accuracy compared to free-hand targeting. Weighted average overall complications, major complications, and mortality were 11.4% (6.7, 16.1), 3.4% (2.1, 5.1), and 0.8% (0.5, 1.3). Pooled estimates of primary technique efficacy were 94% (89, 97) if assessed at 1-6 weeks and 90% (87, 93) if assessed at 6-12 weeks post ablation, with remaining between-study heterogeneity. Primary technique efficacy was significantly enhanced in stereotactic vs. free-hand targeting, with odds ratio (OR) of 1.9 (1.2, 3.2) (n = 6 studies). CONCLUSIONS: Advances in stereotactic navigation technologies allow highly precise and safe tumor targeting, leading to enhanced primary treatment efficacy. The use of varying definitions and terminology of safety and efficacy limits comparability among studies, highlighting the crucial need for further standardization of follow-up definitions.

Image-Guided Ablation for Colorectal Liver Metastasis: Principles, Current Evidence, and the Path Forward.

Image-guided ablation can provide effective local tumor control in selected patients with CLM. A randomized controlled trial suggested that radiofrequency ablation combined with systemic chemotherapy resulted in a survival benefit for patients with unresectable CLM, compared to systemic chemotherapy alone. For small tumors, ablation with adequate margins can be considered as an alternative to resection. The improvement of ablation technologies can allow the treatment of tumors close to major vascular structures or bile ducts, on which the applicability of thermal ablation modalities is challenging. Several factors affect the outcomes of ablation, including but not limited to tumor size, number, location, minimal ablation margin, RAS mutation status, prior hepatectomy, and extrahepatic disease. Further understanding of the impact of tumor biology and advanced imaging guidance on overall patient outcomes might help to tailor its application, and improve outcomes of image-guided ablation.

Volumetric Quantitative Ablation Margins for Assessment of Ablation Completeness in Thermal Ablation of Liver Tumors.

BACKGROUND: In thermal ablation of liver tumors, complete coverage of the tumor volume by the ablation volume with a sufficient ablation margin is the most important factor for treatment success. Evaluation of ablation completeness is commonly performed by visual inspection in 2D and is prone to inter-reader variability. This work aimed to introduce a standardized approach for evaluation of ablation completeness after CT-guided thermal ablation of liver tumors, using volumetric quantitative ablation margins (QAM). METHODS: A QAM computation metric based on volumetric segmentations of tumor and ablation areas and signed Euclidean surface distance maps was developed, including a novel algorithm to address QAM computation in subcapsular tumors. The code for QAM computation was verified in artificial examples of tumor and ablation spheres simulating varying scenarios of ablation margins. The applicability of the QAM metric was investigated in representative cases extracted from a prospective database of colorectal liver metastases (CRLM) treated with stereotactic microwave ablation (SMWA). RESULTS: Applicability of the proposed QAM metric was confirmed in artificial and clinical example cases. Numerical and visual options of data presentation displaying substrata of QAM distributions were proposed. For subcapsular tumors, the underestimation of tumor coverage by the ablation volume when applying an unadjusted QAM method was confirmed, supporting the benefits of using the proposed algorithm for QAM computation in these cases. The computational code for developed QAM was made publicly available, encouraging the use of a standard and objective metric in reporting ablation completeness and margins. CONCLUSION: The proposed volumetric approach for QAM computation including a novel algorithm to address subcapsular liver tumors enables precision and reproducibility in the assessment of ablation margins. The quantitative feedback on ablation completeness opens possibilities for intra-operative decision making and for refined analyses on predictability and consistency of local tumor control after thermal ablation of liver tumors.

Ultrasound Based Planning and Navigation for Non-Anatomical Liver Resections - An Ex-Vivo Study.

Goal: Non-anatomical resections of liver tumors can be very challenging as the surgeon cannot use anatomical landmarks on the liver surface or in the ultrasound image for guidance. This makes it difficult to achieve negative resection margins (R0) and still preserve as much healthy liver tissue as possible. Even though image-guided surgery systems have been introduced to overcome this challenge, they are still rarely used due to their inaccuracy, time-effort and complexity in usage and setup. Methods: We have developed a novel approach, which allows us to create an intra-operative resection plan using navigated ultrasound. First, the surface is scanned using a navigated ultrasound, followed by tumor segmentation on a midsection ultrasound image. Based on this information, the navigation system calculates an optimal resection strategy and displays it along with the tracked surgical instruments. In this study, this approach was evaluated by three experienced hepatobiliary surgeons on ex-vivo porcine models. Results: Using this technique, an R0 resection could be achieved in 22 out of 23 (95.7% R0 resection rate) cases with a median resection margin of 5.9 mm (IQR 3.5-7.7 mm). The resection margin between operators 1, 2 and 3 was 7.8 mm, 4.15 mm and 5.1 mm respectively (p = 0.054). Conclusions: This approach could represent a useful tool for intra-operative guidance in non-anatomical resection alongside conventional ultrasound guidance. However, instructions and training are essential especially if the operator has not used an image-guidance system before.

Efficiency, Accuracy and Clinical Applicability of a New Image-Guided Surgery System in 3D Laparoscopic Liver Surgery.

BACKGROUND: To investigate efficiency, accuracy and clinical benefit of a new augmented reality system for 3D laparoscopic liver surgery. METHODS: All patients who received laparoscopic liver resection by a new image-guided surgery system with augmented 3D-imaging in a university hospital were included for analysis. Digitally processed preoperative cross-sectional imaging was merged with the laparoscopic image. Intraoperative efficiency of the procedure was measured as time needed to achieve sufficient registration accuracy. Technical accuracy was reported as fiducial registration error (FRE). Clinical benefit was assessed trough a questionnaire, reporting measures in a 5-point Likert scale format ranging from 1 (high) to 5 (low). RESULTS: From January to March 2018, ten laparoscopic liver resections of a total of 18 lesions were performed using the novel augmented reality system. Median time for registration was 8:50 min (range 1:31-23:56). The mean FRE was reduced from 14.0 mm (SD 5.0) in the first registration attempt to 9.2 mm (SD 2.8) in the last attempt. The questionnaire revealed the ease of use of the system (1.2, SD 0.4) and the benefit for resection of vanishing lesions (1.0, SD 0.0) as convincing positive aspects, whereas image registration accuracy for resection guidance was consistently judged as too inaccurate. CONCLUSIONS: Augmented reality in 3D laparoscopic liver surgery with landmark-based registration technique is feasible with only little impact on the intraoperative workflow. The benefit for detecting particularly vanishing lesions is high. For an additional benefit during the resection process, registration accuracy has to be improved and non-rigid registration algorithms will be required to address intraoperative anatomical deformation.

Design and implementation of an electromagnetic ultrasound-based navigation technique for laparoscopic ablation of liver tumors.

BACKGROUND: Efficient laparoscopic ablation of liver tumors relies on precise tumor visualization and accurate positioning of ablation probes. This study evaluates positional accuracy and procedural efficiency of a dynamic navigation technique based on electromagnetic-tracked laparoscopic ultrasound (ELUS) for laparoscopic ablation of liver tumors. METHODS: The proposed navigation approach combines intraoperative 2D ELUS-based planning for navigated positioning of ablation probes, with immediate 3D ELUS-based validation of intrahepatic probe position. The environmental influence on electromagnetic-tracking stability was evaluated in the operation room. Accuracy of navigated ablation probe positioning assessed as the target-positioning error (TPE), and procedural efficiency defined as time efforts for target definition/navigated targeting and number of probe repositionings, were evaluated in a laparoscopic model and compared with conventional laparoscopic ultrasound (LUS) guidance. RESULTS: The operation-room environment showed interferences < 1 mm on the EM-tracking system. A total of 60 targeting attempts were conducted by three surgeons, with ten targeting attempts using ELUS and ten using conventional LUS each. Median TPE and time for targeting using ELUS and LUS were 4.2 mm (IQR 2.9-5.3 mm) versus 6 mm (IQR 4.7-7.5 mm), and 39 s (IQR 24-47 s) versus 76 s (IQR 47-121 s), respectively (p < 0.01 each). With ELUS, median time for target definition was 48.5 s, with 0 ablation probe repositionings compared to 17 when using LUS. The navigation technique was rated with a mean score of 85.5 on a Standard Usability Scale. CONCLUSIONS: The proposed ELUS-based navigation approach allows for accurate and efficient targeting of liver tumors in a laparoscopic model. Focusing on a dynamic and tumor-targeted navigation technique relying on intraoperative imaging, this avoids potential inaccuracies due to organ deformation and yields a user-friendly technique for efficient laparoscopic ablation of liver tumors.