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

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

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

Stereotactic Image-Guidance for Ablation of Malignant Liver Tumors

Stereotactic percutaneous ablation is a rapidly advancing modality for treatment of tumors in soft solid organs such as the liver. Each year, there are about 850,000 cases of primary liver cancer worldwide. Although surgical resection still is the gold standard for most cases, only 20–30% of patients are candidates for it, due to the advanced stage of the disease. Surgery can also be a huge burden to the patient and his/her quality of life might be temporarily severely reduced due to long hospital stays, complications, and slow recovery. To overcome these disadvantages, thermo-ablation of tumors of up to 3 cm has become a more viable alternative especially in the last decade, offering a potentially equally effective but minimally invasive and tissue sparing treatment alternative. In conjunction with improved CT imaging, stereotactic image-guidance techniques and image fusion technology were introduced to increase safety, efficacy, and accuracy of this treatment. Stereotactic image-guidance leads to a simple, fast, and accurate placement of the ablation probe into the liver tumor, which is a prerequisite for a complete destruction of the tumor by ablation. More and more physicians, including surgeons, consider ablation a viable alternative to resection whenever feasible. Patients undergoing such a minimally invasive treatment benefit from a shorter hospital stays, reduced complication rates, and faster recovery

Offset Calculation for Registration-Free EM-based Liver Navigation

Precise placement of ablation needles for the treatment of liver tumors remains difficult due to poor visibility of potential tumor targets in ultrasound imaging. Various groups have carried out extensive efforts to develop image-guidance and surgical navigation technology for the realm of oncologic liver surgery. Due to additional complexity and disruption in the clinical workflow, the barriers to introducing these systems on a larger clinical level remains high. In this work we present an initial evaluation towards a novel and simple method for accurate image-guided targeting of liver tumors based on EM-tracking and with-out requiring patient-to-image registration. The initial feasibility of the 3D offset calculation from fluoroscopy images is demonstrated

A prospective multicentre trial on survival after Microwave Ablation VErsus Resection for Resectable Colorectal liver metastases (MAVERRIC).

AIM This multi-centre prospective cohort study aimed to investigate non-inferiority in patients' overall survival when treating potentially resectable colorectal cancer liver metastasis (CRLM) with stereotactic microwave ablation (SMWA) as opposed to hepatic resection (HR). METHODS Patients with no more than 5 CRLM no larger than 30 mm, deemed eligible for both SMWA and hepatic resection at the local multidisciplinary team meetings, were deliberately treated with SMWA (study group). The contemporary control group consisted of patients with no more than 5 CRLM, none larger than 30 mm, treated with HR, extracted from a prospectively maintained nationwide Swedish database. After propensity-score matching, 3-year overall survival (OS) was compared as the primary outcome using Kaplan-Meier and Cox regression analyses. RESULTS All patients in the study group (n = 98) were matched to 158 patients from the control group (mean standardised difference in baseline covariates = 0.077). OS rates at 3 years were 78% (Confidence interval [CI] 68-85%) after SMWA versus 76% (CI 69-82%) after HR (stratified Log-rank test p = 0.861). Estimated 5-year OS rates were 56% (CI 45-66%) versus 58% (CI 50-66%). The adjusted hazard ratio for treatment type was 1.020 (CI 0.689-1.510). Overall and major complications were lower after SMWA (percentage decrease 67% and 80%, p < 0.01). Hepatic retreatments were more frequent after SMWA (percentage increase 78%, p < 0.01). CONCLUSION SMWA is a valid curative-intent treatment alternative to surgical resection for small resectable CRLM. It represents an attractive option in terms of treatment-related morbidity with potentially wider options regarding hepatic retreatments over the future course of disease

Management of patients at the hepatopancreatobiliary unit of a London teaching hospital during the COVID-19 pandemic

To mitigate COVID-19-related shortage of treatment capacity, the hepatopancreatobiliary (HPB) unit of the Royal Free Hospital London (RFHL) transferred its practice to independent hospitals in Central London through the North Central London Cancer Alliance. The aim of this study was to critically assess this strategy and evaluate perioperative outcomes. Prospectively collected data were reviewed on all patients who were treated under the RFHL HPB unit in six hospitals between November 2020 and October 2021. A total of 1541 patients were included, as follows: 1246 (81%) at the RFHL, 41 (3%) at the Chase Farm Hospital, 23 (2%) at the Whittington Hospital, 207 (13%) at the Princess Grace Hospital, 12 (1%) at the Wellington Hospital and 12 (1%) at the Lister Hospital, Chelsea. Across all institutions, overall complication rate were 40%, major complication (Clavien-Dindo grade ≥ 3a) rate were 11% and mortality rates were 1.4%, respectively. In COVID-19-positive patients (n = 28), compared with negative patients, complication rate and mortality rates were increased tenfold. Outsourcing HPB patients, including their specialist care, to surrounding institutions was safe and ensured ongoing treatment with comparable outcomes among the institutions during the COVID-19 pandemic. Due to the lack of direct comparison with a non-pandemic cohort, these results can strictly only be applied within a pandemic setting

Pancreatic surgery outcomes: multicentre prospective snapshot study in 67 countries

BACKGROUND: Pancreatic surgery remains associated with high morbidity rates. Although postoperative mortality appears to have improved with specialization, the outcomes reported in the literature reflect the activity of highly specialized centres. The aim of this study was to evaluate the outcomes following pancreatic surgery worldwide. METHODS: This was an international, prospective, multicentre, cross-sectional snapshot study of consecutive patients undergoing pancreatic operations worldwide in a 3-month interval in 2021. The primary outcome was postoperative mortality within 90 days of surgery. Multivariable logistic regression was used to explore relationships with Human Development Index (HDI) and other parameters. RESULTS: A total of 4223 patients from 67 countries were analysed. A complication of any severity was detected in 68.7 per cent of patients (2901 of 4223). Major complication rates (Clavien–Dindo grade at least IIIa) were 24, 18, and 27 per cent, and mortality rates were 10, 5, and 5 per cent in low-to-middle-, high-, and very high-HDI countries respectively. The 90-day postoperative mortality rate was 5.4 per cent (229 of 4223) overall, but was significantly higher in the low-to-middle-HDI group (adjusted OR 2.88, 95 per cent c.i. 1.80 to 4.48). The overall failure-to-rescue rate was 21 per cent; however, it was 41 per cent in low-to-middle- compared with 19 per cent in very high-HDI countries. CONCLUSION: Excess mortality in low-to-middle-HDI countries could be attributable to failure to rescue of patients from severe complications. The authors call for a collaborative response from international and regional associations of pancreatic surgeons to address management related to death from postoperative complications to tackle the global disparities in the outcomes of pancreatic surgery (NCT04652271; ISRCTN95140761

Outcomes of elective liver surgery worldwide: a global, prospective, multicenter, cross-sectional study

Background: The outcomes of liver surgery worldwide remain unknown. The true population-based outcomes are likely different to those vastly reported that reflect the activity of highly specialized academic centers. The aim of this study was to measure the true worldwide practice of liver surgery and associated outcomes by recruiting from centers across the globe. The geographic distribution of liver surgery activity and complexity was also evaluated to further understand variations in outcomes. Methods: LiverGroup.org was an international, prospective, multicenter, cross-sectional study following the Global Surgery Collaborative Snapshot Research approach with a 3-month prospective, consecutive patient enrollment within January–December 2019. Each patient was followed up for 90 days postoperatively. All patients undergoing liver surgery at their respective centers were eligible for study inclusion. Basic demographics, patient and operation characteristics were collected. Morbidity was recorded according to the Clavien–Dindo Classification of Surgical Complications. Country-based and hospital-based data were collected, including the Human Development Index (HDI). (NCT03768141). Results: A total of 2159 patients were included from six continents. Surgery was performed for cancer in 1785 (83%) patients. Of all patients, 912 (42%) experienced a postoperative complication of any severity, while the major complication rate was 16% (341/2159). The overall 90-day mortality rate after liver surgery was 3.8% (82/2,159). The overall failure to rescue rate was 11% (82/ 722) ranging from 5 to 35% among the higher and lower HDI groups, respectively. Conclusions: This is the first to our knowledge global surgery study specifically designed and conducted for specialized liver surgery. The authors identified failure to rescue as a significant potentially modifiable factor for mortality after liver surgery, mostly related to lower Human Development Index countries. Members of the LiverGroup.org network could now work together to develop quality improvement collaboratives

Stereostactic microwave ablation as an alternative to surgical resection for colorectal cancer liver metastates

Colorectal cancer (CRC) implies a substantial global burden of disease with a relevant impact on the general population and on healthcare systems in terms of morbidity, mortality, quality of life, and costs. A raising CRC incidence emphasises the need to refine screening and prevention strategies, and design optimal algorithms for treatment indication and outcome prediction. Around 25% to 30% of patients with CRC develop colorectal cancer liver metastases (CRLM) at any time point during their disease, with high variation in the disease presentation, severity, chronology and response to treatment. This and the increasing quantity and quality of available therapeutic options, enhance the complexity of defining treatment algorithms and designing feasible studies leading to meaningful results. Considering the high rate of tumour recurrence after initial CRLM treatment with curative intent, applying low-morbidity local treatments enhancing the possibilities of repeat treatments, are gaining importance. As such, thermal ablation (TA) promises high rates of local tumour control and favourable oncological outcomes comparable to the gold-standard surgical resection. Nevertheless, results from highquality prospective comparative studies are missing, hampering the integration of TA as a valid treatment alternative into current guidelines. The aims of the studies included in this thesis were to investigate i) non-inferiority in overall survival (OS), and compare healthcare consumption, costs and treatment-associated morbidity, when treating patients with potentially resectable CRLM with TA versus resection, while applying highlevel navigation technology for stereotactic microwave ablation (SMWA), and ii) the potential of a novel algorithm for computation of 3D quantitative ablation margins (QAM) to enhance treatment success and predict local tumour control after SMWA. Study I was a population-based analysis comparing 3-year OS after microwave ablation (MWA) versus resection using data from a nationwide Swedish patient registry. After adjusting for factors known to affect the treatment type and OS (confounding by indication) using propensity score (PS) analysis, 3-year OS probabilities were similar in patients treated with MWA (n = 70) (76%, CI 59% to 86%) versus resection (n = 201) (3- year OS 76%, CI 68% to 83%), with a change in the hazard of death of 1.43 (CI 0.77 to 2.65) induced by the treatment type in a multivariable model. Studies II, III and IV were analyses or sub-analyses of a prospective, multi-centre cohort study (MAVERRIC study), comparing patients with ≤ 5 CRLM ≤ 3cm in size, qualifying for both SMWA and resection and deliberately treated with SMWA (study group), to a contemporary cohort of patients treated with resection, extracted from a Swedish nationwide patient registry (control group). The primary outcome of 3-year OS after a prospective follow-up of 3 years was analysed in Study IV. PS analyses yielded comparable groups with a balanced distribution of baseline characteristics across the study (n = 98) and control (n = 158) cohorts. Three-year OS was non-inferior after SMWA (78%, CI 68% to 85%) versus resection (76% (CI 69% to 82%), with a hazard ratio (HR) of 1.09 (CI 0.69 to 1.51) for the treatment type (SMWA over resection). In the Swedish subgroup of patients included into the MAVERRIC study, a particular inclusion pattern (patients amenable to both ablation and resection treated with SMWA every even week and with resection every odd week) created a quasi-randomised situation, where healthcare related costs and OS were analysed (Study III). Overall costs (all inpatient hospital admissions, outpatient visits, oncological treatments and radiological imaging) from the time of index treatment indication and two years onwards, were significantly reduced in the SMWA versus resection cohorts. Two-year OS and disease-free survival were similar, while hepatic recurrence-free survival was shorter and hepatic re-treatments more frequent after SMWA. Morbidity and length of hospital stay were significantly reduced, and re-treatment significantly more frequent, after MWA / SMWA versus resection, in Studies I, III and IV. Study II was a secondary outcome-analysis applying a novel QAM metric on a subgroup of patients treated with SMWA within the MAVERRIC study. 3D-QAM was retrospectively computed to 65 CRLM treated with SMWA, and varying definitions investigated in a multivariable model. 3D-QAM was the most relevant factor affecting the occurrence of local recurrence within one year of treatment. In conclusion, OS at 3 years may be considered similar after SMWA versus resection in patients with potentially resectable small CRLM, with significantly reduced morbidity, time spent in medical facilities and healthcare related costs. In an ageing and more comorbid population, this supports the role of TA as a valid low-morbidity, tissue-sparing treatment alternative, enhancing options for re-treatments in case of hepatic recurrences. This and the potential of innovative technology to enhance safety, efficacy and reproducibility of results, might aid decision-making when designing individualised treatment algorithms for patients with CRLM