Solitary Colorectal Liver Metastasis Research Articles

Thermal ablation with and without adjuvant systemic therapy: a nationwide multicenter observational cohort study of solitary colorectal liver metastases.

Thermal ablation is routinely used for solitary colorectal liver metastases (SCLM), but the added value of adjuvant systemic therapy in SCLM remains unclear. This study aimed to compare the long-term outcomes for SCLM treated by ablation alone (AB) versus ablation plus systemic therapy (AS). This multicenter retrospective study using nationwide data from fourteen institutions between October 2010 and May 2023, 369 patients with initial SCLM smaller than 5cm, no extrahepatic metastases, and colorectal cancer R0 resection treated by thermal ablation were included. The crude analysis was used to analyze eligible cases between the two groups. The propensity score matching (PSM) to control for potential confounders in each matched group. Subgroup analyses were performed to identify specific survival benefits. 61.2% (226/369) of eligible patients were treated with AS and 38.8% (143/369) with AB. During the median follow-up period of 8.8 years, 1-/3-/5-year DFS/OS rates did not differ between the two groups, when analyzed via PSM (P=0.52/0.08). Subgroup analysis revealed that AS was significantly associated with better OS than AB in patients with plasma CEA >5ug/L (P=0.036), T (III-IV) category of primary cancer (P=0.034), or clinical risk score (1-2) (P=0.041). In each matched group, we did find a significant difference in drug-related adverse events (P<0.001) between AS group (24.1%, 28/116) and AB group (0.0%, 0/116). For patients with plasma CEA >5ug/L, T (III-IV) category of primary cancer, or clinical risk score (1-2), thermal ablation plus systemic therapy appeared to be associated with improved overall survival. Thermal ablation was equally effective in disease-free survival for treating solitary colorectal liver metastasis, whether with or without adjuvant systemic therapy.

The oncologic outcome and prognostic factors for solitary colorectal liver metastasis after liver resection

BackgroundStudies on prognostic factors for patients undergoing surgery to treat solitary liver metastases originating from colorectal cancer (CRC) are limited. This study aimed to analyze significant prognostic factors associated with tumor recurrence and long-term survival after liver resection for solitary colorectal liver metastasis. MethodsData from 230 patients with solitary liver metastases from CRC who received liver resection between 2010 and 2019 were retrospectively analyzed. Recurrence-free survival (RFS) and overall survival (OS) were accessed with the Kaplan–Meier method and log-rank test. Cox regression multivariate analysis identified independent variables associated with RFS and OS. Nomograms were developed to predict patient outcomes after surgery. ResultsThe 3- and 5-year OS rates were 72.3% and 59.8%, respectively. The 3- and 5-year RFS rates were 40.0% and 27.1%, respectively. Multivariate analysis revealed age ≥ 70 years, resection margin width < 10 mm, initial N2 stage, hypoalbuminemia before surgery, and neutrophil-to-lymphocyte ratio (NLR) ≥ 3 after surgery as independent prognostic factors for OS. For RFS, initial N2 stage, hypoalbuminemia before surgery, NLR ≥ 3 after surgery, elevated carcinoembryonic antigen (CEA) levels after surgery, and CEA ratio (after/before liver resection) < 0.3 were identified as independent prognostic factors. ConclusionThis study demonstrated that initial N2 stage, hypoalbuminemia before liver resection, and NLR ≥ 3 after liver resection exert a significant association on the RFS and OS of patients undergoing surgery for solitary liver metastases from CRC. Thus, upfront chemotherapy, prompt postoperative chemotherapy, and intensive postoperative surveillance are mandatory for patients having these adverse factors.

A convenient scoring system to distinguish intrahepatic mass-forming cholangiocarcinoma from solitary colorectal liver metastasis based on magnetic resonance imaging features

ObjectivesTo develop and validate a diagnostic scoring system to differentiate intrahepatic mass-forming cholangiocarcinoma (IMCC) from solitary colorectal liver metastasis (CRLM).MethodsA total of 366 patients (263 in the training cohort, 103 in the validation cohort) who underwent MRI examination with pathologically proven either IMCC or CRLM from two centers were included. Twenty-eight MRI features were collected. Univariate analyses and multivariate logistic regression analyses were performed to identify independent predictors for distinguishing IMCC from solitary CRLM. The independent predictors were weighted over based on regression coefficients to build a scoring system. The overall score distribution was divided into three groups to show the diagnostic probability of CRLM.ResultsSix independent predictors, including hepatic capsular retraction, peripheral hepatic enhancement, vessel penetrating the tumor, upper abdominal lymphadenopathy, peripheral washout at the portal venous phase, and rim enhancement at the portal venous phase were included in the system. All predictors were assigned 1 point. At a cutoff of 3 points, AUCs for this score model were 0.948 and 0.903 with sensitivities of 96.5% and 92.0%, specificities of 84.4% and 71.7%, positive predictive values of 87.7% and 75.4%, negative predictive values of 95.4% and 90.5%, and accuracies of 90.9% and 81.6% for the training and validation cohorts, respectively. An increasing trend was shown in the diagnostic probability of CRLM among the three groups based on the score.ConclusionsThe established scoring system is reliable and convenient for distinguishing IMCC from solitary CRLM using six MRI features.Clinical relevance statementA reliable and convenient scoring system was developed to differentiate between intrahepatic mass-forming cholangiocarcinoma from solitary colorectal liver metastasis using six MRI features.Key Points• Characteristic MRI features were identified to distinguish intrahepatic mass-forming cholangiocarcinoma (IMCC) from solitary colorectal liver metastasis (CRLM).• A model to distinguish IMCC from solitary CRLM was created based on 6 features, including hepatic capsular retraction, upper abdominal lymphadenopathy, peripheral washout at the portal venous phase, rim enhancement at the portal venous phase, peripheral hepatic enhancement, and vessel penetrating the tumor.

Resection vs radiofrequency or microwave ablation of small solitary colorectal liver metastasis

Resection vs radiofrequency or microwave ablation of small solitary colorectal liver metastasis

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

PurposeTo 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). MethodThirty-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. ResultsEighteen (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). ConclusionThis 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.

Chemotherapy in patients with a solitary colorectal liver metastasis – A nationwide propensity score matched study

IntroductionChemotherapy is widely used as an adjunct to surgery in the treatment of patients with resectable colorectal liver metastases. The aim of this study was to examine whether chemotherapy confers a survival benefit in patients with a solitary colorectal liver metastasis. MethodsAll consecutive patients between 2009 and 2017 in Sweden who were resected for a solitary colorectal liver metastasis were included. Patients treated with chemotherapy were compared with patients who had surgery alone. Unmatched and propensity score matched analyses were performed to compare overall survival, morbidity and mortality. ResultsOf 1224 eligible patients, 641 (52.4%) patients had chemotherapy, and 583 (47.6%) had surgery alone. After propensity score matching, two balanced groups with 102 patients in each, were analyzed. There was no difference in readmission within 30-days (p = 0.250), or morbidity, defined as Clavien-Dindo 3a or greater, between the groups (p = 0.761). There were no mortalities within ninety days. Radical resection margins were achieved in 92 (n = 94) per cent in the chemotherapy group, and 77 (n = 78) per cent in the surgery alone group (p = 0.016). Median overall survival was 91 (95% CI 73–109) months in the chemotherapy group, and 78 (95% CI 37–119) months in the surgery-alone group (p = 0.652). ConclusionThis nationwide register-based study showed no difference in overall survival between patients treated with chemotherapy compared to surgery alone. Upfront surgery may be advisable in resectable solitary colorectal liver metastasis.

BRAF V600E potentially determines “Oncological Resectability” for “Technically Resectable” colorectal liver metastases

Despite reports on poor survival outcomes after hepatectomy for colorectal liver metastases (CRLM) with BRAF V600E mutation (mBRAF) exist, the role of mBRAF testing for technically resectable cases remains unclear. A single‐center retrospective study was performed to investigate the survival outcomes of patients who underwent upfront hepatectomy for solitary resectable CRLM with mBRAF between January 2005 and December 2017 and to compare them with those of unresectable cases with mBRAF. Of 172 patients who underwent initial hepatectomy for solitary resectable CRLM, mBRAF, RAS mutations (mRAS), and wild‐type RAS/BRAF (wtRAS/BRAF) were observed in 5 (2.9%), 73 (42.4%), and 93 (54.7%) patients, respectively. With a median follow‐up period of 72.8 months, mBRAF was associated with a significantly shorter OS (median, 14.4 months) than wtRAS/BRAF (median, not reached [NR]) (hazard ratio [HR], 27.6; p < 0.001) and mRAS (median, NR) (HR, 9.9; p < 0.001), and mBRAF had the highest HR among all the indicators in the multivariable analysis (HR, 17.0; p < 0.001). The median OS after upfront hepatectomy for CRLM with mBRAF was identical to that of 28 unresectable CRLM with mBRAF that were treated with systemic chemotherapy (median, 17.2 months) (HR, 0.78; p = 0.65). When technically resectable CRLM are complicated with mBRAF, its survival outcome becomes as poor as unresectable cases; therefore, those with mBRAF should be considered as oncologically unresectable. Patients with CRLM should undergo pre‐treatment mBRAF testing regardless of technical resectability. Clinical trial registration number: UMIN000034557.

Liver-First Approach for Synchronous Colorectal Metastases: Analysis of 7360 Patients from the LiverMetSurvey Registry

BackgroundThe liver-first approach in patients with synchronous colorectal liver metastases (CRLM) has gained wide consensus but its role is still to be clarified. We aimed to elucidate the outcome of the liver-first approach and to identify patients who benefit at most from this approach.MethodsPatients with synchronous CRLM included in the LiverMetSurvey registry between 2000 and 2017 were considered. Three strategies were analyzed, i.e. liver-first approach, colorectal resection followed by liver resection (primary-first), and simultaneous resection, and three groups of patients were analyzed, i.e. solitary metastasis, multiple unilobar CRLM, and multiple bilobar CRLM. In each group, patients from the three strategy groups were matched by propensity score analysis.ResultsOverall, 7360 patients were analyzed: 4415 primary-first, 552 liver-first, and 2393 simultaneous resections. Compared with the other groups, the liver-first group had more rectal tumors (58.0% vs. 31.2%) and higher hepatic tumor burden (more than three CRLMs: 34.8% vs. 24.0%; size > 50 mm: 35.6% vs. 22.8%; p < 0.001). In patients with solitary and multiple unilobar CRLM, survival was similar regardless of treatment strategy, whereas in patients with multiple bilobar metastases, the liver-first approach was an independent positive prognostic factor, both in unmatched patients (3-year survival 65.9% vs. primary-first 60.4%: hazard ratio [HR] 1.321, p = 0.031; vs. simultaneous resections 54.4%: HR 1.624, p < 0.001) and after propensity score matching (vs. primary-first: HR 1.667, p = 0.017; vs. simultaneous resections: HR 2.278, p = 0.003).ConclusionIn patients with synchronous CRLM, the surgical strategy should be decided according to the hepatic tumor burden. In the presence of multiple bilobar CRLM, the liver-first approach is associated with longer survival than the alternative approaches and should be evaluated as standard.

Robotic Isolated Caudate Lobectomy for Solitary Colorectal Liver Metastasis.

Safety of liver resection for colorectal adenocarcinoma continues to improve due to decreased morbidity of resection. Minimally invasive techniques contribute greatly to this morbidity reduction. Isolated caudate lobectomy presents a unique technical challenge because of proximity to major vasculature. The video aims to review nuances of robotic isolated caudate lobectomy for metastatic colon adenocarcinoma.

Is percutaneous destruction of a solitary liver colorectal metastasis as effective as a resection?

Backgrounds/AimsSurgical resection remains the gold standard in the treatment of colorectal liver metastasis. However, when a patient presents with a deep solitary colorectal liver metastasis (S-CLM), the balance between the hepatic volume sacrificed and the S-CLM volume is sometimes clearly unappropriated. Thus, alternatives to surgery, such as operative and percutaneous radiofrequency ablation (RFA) and microwave ablation (MWA), have been developed. This study aimed to identify the prognostic factors affecting survival of patients with S-CLM who undergo curative-intent liver resection or local destruction (RFA or MWA).MethodsWe retrospectively identified 211 patients with synchronous or metachronous S-CLM who underwent either surgical resection (n=182) or local destruction (RFA or MWA; n=29) according to the S-CLM size, location, and surrounding Glissonian structures.ResultsPatients who underwent RFA or MWA had S-CLM of a smaller size than those who underwent resection (mean 19.7 vs. 37.3 mm, p<.01). The 1-, 3-, and 5-year overall survival (OS) rates were 97.4%, 84.9%, and 74.9%, respectively. The 1-, 3-, and 5-year disease-free survival (DFS) rates were 77.9%, 47%, and 38.9%, respectively. S-CLM located in the left liver (p=.04), S-CLM KRAS mutation (p<.01), and extra-hepatic recurrence (p<.01) were identified as independent poor risk factors for overall survival (OS); the OS and DFS were comparable in patients with surgical procedure or percutaneous MWA.ConclusionsIn eligible S-CLM cases, percutaneous MWA seems to be as oncologically efficient as surgical resection and should be include in the decision-tree for treatment strategies.

Impact of Preoperative Circulating Tumor DNA Status on Survival Outcomes After Hepatectomy for Resectable Colorectal Liver Metastases.

The optimal perioperative management of patients who undergo hepatectomy for resectable colorectal liver metastases (CRLM) remains unclear due to the lack of reliable methods to stratify the risk of recurrence. A single-center retrospective study was performed to investigate the impact of preoperative circulating tumor DNA (ctDNA) on survival outcomes of patients who underwent initial hepatectomy for solitary resectable CRLM between January 2005 and December 2017 using the comprehensive genotyping platform Guardant360®. Of 212 patients who underwent initial hepatectomy for solitary resectable CRLM, 40 patients for whom pre-hepatectomy plasma was available underwent ctDNA analysis. Among them, 32 (80%) had at least 1 somatic alteration in their ctDNA, while the other 8 (20%) had no detectable ctDNA. Among the patients with undetectable ctDNA, only one had recurrence and none died during a median follow-up period of 39.0months. The recurrence-free survival was significantly shorter in patients who were positive for ctDNA than in those who were negative for ctDNA [median, 12.5months vs not reached (NR); HR, 7.6; P = 0.02]. The overall survival also tended to be shorter in patients who were positive for ctDNA than those who were negative for ctDNA (median, 78.1months vs NR; P = 0.14; HR not available). In patients undergoing hepatectomy for solitary resectable CRLM, the absence of detectable preoperative ctDNA identified patients with a high chance for a cure. Risk stratification according to preoperative ctDNA analysis may be an effective tool that can improve the perioperative management of these patients.

Robotic redo hepatectomy: resection SG 4B seven years after open right hemihepatectomy

Purpose: Evidence shows that repeat liver resection is often the best treatment option for recurrent colorectal liver metastases. Although repeat resections can be complex due to adhesion and altered liver anatomy, laparoscopic liver resection has been shown to be feasible in selected patients, and has been associated with shorter operative time, less blood loss, and shorter hospital stay. Compared to laparoscopy, robotic liver surgery has the advantage of 3D visualization and a larger range of motion thanks to endowrist technology. This video aims to demonstrate the experience of a hepatopancreaticobiliary surgeon with robotic redo hepatectomy. Methods: This report describes a robotic segment 4B resection, seven years after open right hemihepatectomy, in a patient with a solitary colorectal liver metastasis. Surgical risk was assessed by the Southampton laparoscopic liver resection difficulty score, and was classified as extremely high-risk. The patient was placed in supine position with 12 degrees anti-Trendelenburg. Four robotic 8 mm ports were placed, and one assistant 12 mm port. Extensive adhesiolysis was performed with monopolar scissors and a bipolar sealing device. Intraoperative ultrasound was used to demarcate the transection line. The Pringle maneuver was applied by the Huang loop technique. Liver parenchyma transection was done by a bipolar sealing device. Locking polymer clips, hemostatic matrix and fibrillar absorbable haemostat were used to counter blood loss. Results: The Pringle maneuver was performed for 18 minutes. Operative time was 170 minutes, and blood loss was 30 cc. Pathology confirmed a R0 resection of the colorectal liver metastasis. There were no intraoperative complications encountered. The postoperative course was uneventful, and the patient was discharged on postoperative day 2. Conclusion: Robotic redo hepatectomy is feasible after previous open extensive liver surgery for repeat metastatic liver disease in selected patients.

Robotic central hepatectomy: technical tips and tricks

Purpose: Minimal invasive (MI) central hepatectomy is considered a technical complex procedure. The robotic approach could provide benefits over traditional laparoscopy, thanks to 3D visualization, endowrist technology and tremor filtration. Based on three different cases, this video aims to demonstrate technical tips and tricks for robotic central hepatectomy. Methods: The cases consisted of an anatomic segment 4 resection for two hepatocellular carcinoma (HCC), a MI resection of segment 5 and part of segment 8 for a solitary colorectal liver metastasis, and a MI resection of segment 4, 5 and 8 for a mixed cholangiocarcinoma and HCC. Results: A series of tips and tricks are proposed. (1) Installation: supine anti-Trendelenburg position with four robotic ports and an AirSeal port. (2) Exposure: optimal instrument and gauze placement, and application of a percutaneous traction suture to facilitate resection of segment 8 lesions. (3) Intraoperative ultrasound: demarcation of the tumor margins with monopolar scissors. (4) Pringle maneuver: an extracorporeal method with an umbilical tape encircling the hepatoduodenal ligament inserted in a chest tube, versus an intracorporeal method based on the Huang loop technique with application of a vascular bulldog clamp instead of a locking clip to apply tension, allowing to Pringle intermittently. (5) Parenchymal transection: in both healthy and cirrhotic liver tissue the combination of bipolar sealing device, Kelly-crush technique with fenestrated bipolar forceps, and monopolar scissors, proved to be highly efficient. (6) Hemostasis: achieved by preoperative hypovolemic phlebotomy with blood salvage, locking polymer clips, barbed resorbable sutures, hemostatic matrix, fibrillar absorbable haemostat and fibrin sealant patch. Operative time was 198 ± 12.6 minutes. The Pringle maneuver was applied 52.3 ± 8.7 minutes. Blood loss was 60 ± 26.5 cc. No intraoperative complications were encountered. R0-resection was obtained in all patients. The postoperative course was uneventful. Discharge happened on postoperative day 3 ± 1. Conclusion: A systematic approach of robotic central hepatectomy provides a technically feasible and adequate alternative for laparoscopy.

Prognostic value of tumor infiltrating lymphocytes combined with PD-L1 expression for patients with solitary colorectal cancer liver metastasis.

BackgroundThe aim of this study was to assess the prognostic value of CD8+ tumor infiltrating lymphocytes (TIL) combined with programmed cell death-ligand 1 (PD-L1) expression for patients with solitary colorectal cancer liver metastasis (SCLM) undergoing R0 resectionMethodsPatients undergoing curative hepatectomy for SCLM were reviewed. Immunohistochemical multiplex technique was used for quantifying CD8+ TIL, and immunohistochemical staining was used for assessing PD-L1 expression. The tumor immune microenvironment (TIME) was classified as strong for high CD8+ TIL and low PD-L1, weak for low CD8+ TIL and high PD-L1, and mild for the rest. Recurrence-free survival (RFS) and overall survival (OS) was compared between these groups.ResultsAmong the 94 patients included, a high CD8+ TIL and high PD-L1 expression was observed in 51 (54.3%) and 47 (50.0%) patients, respectively. Strong, mild, and weak TIME was observed in 24 (25.5%), 42 (44.7%), and 28 (29.8%) patients, respectively. Patients with a high CD8+ TIL had a significant longer RFS than patients with a low CD8+ TIL (3-year RFS rate, 71.6% vs. 55.3%, P=0.018). The 3-year RFS rate in the strong TIME group was significantly higher than that in the mild and weak TIME groups (89.5% vs. 71.7% and 28.8%, P<0.001), as was the 3-year rate of OS (93.8% vs. 81.8% and 61.6%, P<0.001). CD8+ TIL combined with PD-L1 expression showed better predicting accuracy for RFS than CD8+ TIL alone.ConclusionsThe density of CD8+ TIL combined with PD-L1 expression in liver metastasis was a predictor of RFS for patients with SCLM undergoing R0 resection, and therefore can be used for guiding the postoperative treatment of these patients.

Prognostic factors differ according to KRAS mutational status: A classification and regression tree model to define prognostic groups after hepatectomy for colorectal liver metastasis

BackgroundAlthough KRAS mutation status is known to affect the prognosis of patients with colorectal liver metastasis, the hierarchical association between other prognostic factors and KRAS status is not fully understood. MethodsPatients who underwent a hepatectomy for colorectal liver metastasis were identified in a multi-institutional international database. A classification and regression tree model was constructed to investigate the hierarchical association between prognostic factors and overall survival relative to KRAS status. ResultsAmong 1,123 patients, 29.9% (n = 336) had a KRAS mutation. Among wtKRAS patients, the classification and regression tree model identified presence of metastatic lymph nodes as the most important prognostic factor, whereas among mtKRAS patients, carcinoembryonic antigen level was identified as the most important prognostic factor. Among patients with wtKRAS, the highest 5-year overall survival (68.5%) was noted among patients with node negative primary colorectal cancer, solitary colorectal liver metastases, size <4.3 cm. In contrast, among patients with mtKRAS colorectal liver metastases, the highest 5-year overall survival (57.5%) was observed among patients with carcinoembryonic antigen <6 mg/mL. The classification and regression tree model had higher prognostic accuracy than the Fong score (wtKRAS [Akaike's Information Criterion]: classification and regression tree model 3334 vs Fong score 3341; mtKRAS [Akaike's Information Criterion]: classification and regression tree model 1356 vs Fong score 1396). ConclusionMachine learning methodology outperformed the traditional Fong clinical risk score and identified different factors, based on KRAS mutational status, as predictors of long-term prognosis.

599P - Clinical impact of BRAF V600E mutations in patients (pts) with resectable solitary colorectal liver metastases (CRLM)

BackgroundPatients (pts) who underwent a curative resection for solitary colorectal liver metastasis (CRLM) have a relatively favorable prognosis. Clinical impact of BRAF V600E mutations in those pts remains unclear. MethodsConsecutive pts who had undergone initial hepatectomy for histologically confirmed solitary CRLM were included. Tumor RAS (KRAS/NRAS)/BRAF V600E mutation tests were centrally performed by a PCR method. The association between BRAF V600E mutation and survival outcome in pts with resectable solitary CRLM was retrospectively investigated. ResultsFrom Jan 2005 to Dec 2017, 218 pts were included with a median follow-up of 52 months (m). BRAF mutant (mBRAF) was observed in 5 (2.3%) pts, while mRAS was in 92 (42.2%) pts and RAS/BRAF wild-type (wRAS/BRAF) was in 121 (55.5%) pts. mBRAF was associated with a higher serum CA19-9 level at pre-hepatectomy (p=0.03). Median longest diameter for solitary CRLM were similar among three cohorts (19mm vs. 25mm vs. 27mm, p=0.21). However, all the mBRAF pts experienced early recurrence within 9 m. In the univariate analysis, mBRAF was associated with a worse survival in terms of both recurrence-free survival (RFS) with the hazard ratio (HR) of 8.68 for mBRAF vs. wRAS/BRAF (mBRAF vs. mRAS vs. wRAS/BRAF; median, 4.8 m vs. 17.1 m vs. not reached, p<0.001: 3-year RFS rate, 0% vs 39.6% vs 56.2%, p<0.001) and overall survival (OS) with the HR of 20.8 for mBRAF vs. wRAS/BRAF (mBRAF vs. mRAS vs. wRAS/BRAF; median, 14.4 m vs. not reached vs. not reached, p<0.001: 3-year OS rate, 20.0% vs 78.9% vs 94.9%, p<0.001). In the multivariate analysis, mBRAF was strongly associated with a worse survival and had the highest HR among all the indicators in terms of both RFS (HR: 5.0, 95% CI: 1.8–13.8, p<0.001) and OS (HR: 15.4, 95% CI: 5.2–45.5, p<0.001). ConclusionsAmong resectable solitary CRLM pts, mBRAF was rare (2.3%). However, given that all the mBRAF pts experienced early recurrence and the striking value of HRs in the univariate and multivariate analyses on both RFS and OS, mBRAF itself may become the most relevant indicator beyond known clinicopathological indicators in pts with resectable solitary CRLM. A novel treatment strategy for these patients is warranted. Clinical trial identificationUMIN000034557. Legal entity responsible for the studyThe authors. FundingThe National Cancer Center Research Development Fund, Japan (Research number: 30-A-8, Principal investigator: Shinichiro Takahashi). DisclosureT. Yoshino: Research grant / Funding (self): Novartis Pharma K.K.; Research grant / Funding (self): MSD.K.K.; Research grant / Funding (self): Sumitomo Dainippon Pharma Co., Ltd.; Research grant / Funding (self): Chugai Pharmaceutical Co., Ltd.; Research grant / Funding (self): Sanofi K.K.; Research grant / Funding (self): Daiichi Sankyo Company, Limited; Research grant / Funding (self): PAREXEL International Inc.; Research grant / Funding (self): Ono Pharmaceutical Co., Ltd. H. Taniguchi: Research grant / Funding (self): Takeda; Research grant / Funding (self): Daiichi Sankyo; Research grant / Funding (self): Sysmex; Honoraria (self): Chugai; Honoraria (self): Taiho; Honoraria (self): Eli Lilly. All other authors have declared no conflicts of interest.

Quantitative margin assessment of radiofrequency ablation of a solitary colorectal hepatic metastasis using MIRADA RTx on CT scans: a feasibility study

BackgroundCompared to surgery, radiofrequency ablation(RFA) for colorectal liver metastasis(CRLM) is associated with higher local recurrence(LR) rates. A wide margin (at least 5 mm) is generally recommended to prevent LR, but the optimal method to assess ablation margins is yet to be established. The aim of our study was to evaluate the feasibility and reproducibility of CT-CT co-registration, using MIRADA software, in order to assess ablation margins of patients with CRLM.MethodsIn this retrospective study, pre- and post-ablation contrast-enhanced CT scans of 29 patients, treated with percutaneous RFA for a solitary CRLM, were co-registered. Co-registration was performed by two independent radiologist, based on venous structures in proximity to the tumor. Feasibility of CT-CT co-registration and inter-observer agreement for reproducibility and ablation margins was determined. Furthermore, the minimal ablation margin was compared with the occurrence of LR during follow-up.ResultsCo-registration was considered feasible in 18 patients (61% male, 63.1(±10.9) year), with a perfect inter-observer agreement for completeness of ablation: κ = 1.0(p < 0.001). And substantial inter-observer agreement for measurement of the minimal margin (≤ 0 mm, 1-5 mm, ≥ 5 mm): κ = 0.723(p-value < 0.001). LR occurred in eight of nine(88.9%) incompletely ablated CRLM and in one of the nine completely ablated CRLM(11.1%).ConclusionCo-registration using MIRADA is reproducible and potentially a valuable tool in defining technical success. Feasibility of co-registration of pre- and post-ablation CT scans is suboptimal if scans are not acquired concordantly. Co-registration may potentially aid in the prediction of LR after percutaneous ablation.

Predicting local regrowth after radiofrequency ablation of colorectal liver metastases by 3D merging of pre- and post-ablation imaging

Background: Radiofrequency ablation (RFA) as an alternative to surgery in patients with colorectal liver metastasis (CRLM) is associated with high local recurrence (LR) rates. RFA requires a wide margin to prevent LR. It is yet unclear how large the margin should be and how this can be measured reliably. The aim of our study was to evaluate the feasibility of 3D margin assessment and correlate the obtained margins to LR rates. Methods: Patients treated with percutaneous RFA for a solitary CRLM were included. Pre- and post-ablation CT scans were loaded into Mirada RTx (Mirada Medical, Oxford, UK) and merged based on venous structures in proximity of the tumor. Tumor and ablation volumes were determined on both scans based on automatic contour detection. Overlay of the pre- and post-scans allowed 3D assessment of ablation margins. The minimal margin was compared with the occurrence of LR during follow-up. Results: Ten patients were included so far (median follow-up 35 months). LR occurred in 5 patients (median tumor size 17mm, range 11-42) in which ablation was incomplete in 4 patients. Location of the LR was at the margin most-at-risk in all patients. Five patients did not develop LR and their tumors were ablated completely (margins: 1, 2 and ≥5mm (n=3)). Median tumor size was 19 mm, range 10-27. Conclusion: Automated 3D margin assessment is feasible and appears to aid in LR prediction. Real-time margin assessment can directly influence the precision and completeness of RFA, potentially achieving improved local control.

Predicting local regrowth after radiofrequency ablation of colorectal liver metastases by 3D merging of pre- and post-ablation imaging

Background: Radiofrequency ablation (RFA) as an alternative to surgery in patients with colorectal liver metastasis (CRLM) is associated with high local recurrence (LR) rates. RFA requires a wide margin to prevent LR. It is yet unclear how large the margin should be and how this can be measured reliably. The aim of our study was to evaluate the feasibility of 3D margin assessment and correlate the obtained margins to LR rates. Methods: Patients treated with percutaneous RFA for a solitary CRLM were included. Pre- and post-ablation CT scans were loaded into Mirada RTx (Mirada Medical, Oxford, UK) and merged based on venous structures in proximity of the tumor. Tumor and ablation volumes were determined on both scans based on automatic contour detection. Overlay of the pre- and post-scans allowed 3D assessment of ablation margins. The minimal margin was compared with the occurrence of LR during follow-up. Results: Ten patients were included so far (median follow-up 35 months). LR occurred in 5 patients (median tumor size 17mm, range 11-42) in which ablation was incomplete in 4 patients. Location of the LR was at the margin most-at-risk in all patients. Five patients did not develop LR and their tumors were ablated completely (margins: 1, 2 and ≥5mm (n=3)). Median tumor size was 19 mm, range 10-27. Conclusion: Automated 3D margin assessment is feasible and appears to aid in LR prediction. Real-time margin assessment can directly influence the precision and completeness of RFA, potentially achieving improved local control.

Analysis of prognostic factors after resection of solitary liver metastasis in colorectal cancer: a 22-year bicentre study

The investigation of the predictors of outcome after hepatic resection for solitary colorectal liver metastasis. We recruited 350 patients with solitary colorectal liver metastasis at the University Hospitals of Jena and Magdeburg, who underwent curative liver resection between 1993 and 2014. All patients had follow-up until death or till summer 2016. The follow-up data concern 96.6% of observed patients. The 5- and 10-year overall survival rates were 47 and 28%, respectively. The 5- and 10-year disease-free survival rates were 30 and 20%, respectively. The analysis of the prognostic factors revealed that the pT category of primary tumour, size and grade of the metastasis and extension of the liver resection had no statistically significant impact on survival and recurrence rates. In multivariate analysis, age, status of lymph node metastasis at the primary tumour, location of primary tumour, time of appearance of the metastasis, the use of preoperative chemotherapy and the presence of extrahepatic tumour proved to be independent statistically significant predictors for the prognosis. Moreover, patients with rectal cancer had a lower intrahepatic recurrence rate, but a higher extrahepatic recurrence rate. The long-term follow-up of patients with R0-resected liver metastasis is multifactorially influenced. Age and comorbidity have a role only in the overall survival. More than three lymph node metastasis reduced both the overall and disease-free survival. Extrahepatic tumour had a negative influence on the extrahepatic recurrence and on the overall survival. Neither overall survival nor recurrence rates was improved using neoadjuvant chemotherapy.