Unresectable Colorectal Liver Metastases Research Articles

Cetuximab plus FOLFOXIRI versus cetuximab plus FOLFOX as conversion regimen in RAS/BRAF wild-type patients with initially unresectable colorectal liver metastases (TRICE trial): A randomized controlled trial.

It remains unclear whether intensification of the chemotherapy backbone in tandem with an anti-EGFR can confer superior clinical outcomes in a cohort of RAS/BRAF wild-type colorectal cancer (CRC) patients with initially unresectable colorectal liver metastases (CRLM). To that end, we sought to comparatively evaluate the efficacy and safety of cetuximab plus FOLFOXIRI (triplet arm) versus cetuximab plus FOLFOX (doublet arm) as a conversion regimen (i.e., unresectable to resectable) in CRC patients with unresectable CRLM. This open-label, randomized clinical trial was conducted from April 2018 to December 2022 in 7 medical centers across China, enrolling 146 RAS/BRAF wild-type CRC patients with initially unresectable CRLM. A stratified blocked randomization method was utilized to assign patients (1:1) to either the cetuximab plus FOLFOXIRI (n = 72) or cetuximab plus FOLFOX (n = 74) treatment arms. Stratification factors were tumor location (left versus right) and resectability (technically unresectable versus ≥5 metastases). The primary outcome was the objective response rate (ORR). Secondary outcomes included the median depth of tumor response (DpR), early tumor shrinkage (ETS), R0 resection rate, progression-free survival (PFS), overall survival (not mature at the time of analysis), and safety profile. Radiological tumor evaluations were conducted by radiologists blinded to the group allocation. Primary efficacy analyses were conducted based on the intention-to-treat population, while safety analyses were performed on patients who received at least 1 line of chemotherapy. A total of 14 patients (9.6%) were lost to follow-up (9 in the doublet arm and 5 in the triplet arm). The ORR was comparable following adjustment for stratification factors, with 84.7% versus 79.7% in the triplet and doublet arms, respectively (odds ratio [OR] 0.70; 95% confidence intervals [CI] [0.30, 1.67], Chi-square p = 0.42). Moreover, the ETS rate showed no significant difference between the triplet and doublet arms (80.6% (58/72) versus 77.0% (57/74), OR 0.82, 95% CI [0.37, 1.83], Chi-square p = 0.63). Although median DpR was higher in the triplet therapy group (59.6%, interquartile range [IQR], [50.0, 69.7] versus 55.0%, IQR [42.8, 63.8], Mann-Whitney p = 0.039), the R0/R1 resection rate with or without radiofrequency ablation/stereotactic body radiation therapy was comparable with 54.2% (39/72) of patients in the triplet arm versus 52.7% (39/74) in the doublet arm. At a median follow-up of 26.2 months (IQR [12.8, 40.5]), the median PFS was 11.8 months in the triplet arm versus 13.4 months in the doublet arm (hazard ratio [HR] 0.74, 95% CI [0.50, 1.11], Log-rank p = 0.14). Grade ≥ 3 events were reported in 47.2% (35/74) of patients in the doublet arm and 55.9% (38/68) of patients in the triplet arm. The triplet arm was associated with a higher incidence of grade ≥ 3 neutropenia (44.1% versus 27.0%, p = 0.03) and diarrhea (5.9% versus 0%, p = 0.03). The primary limitations of the study encompass the inherent bias in subjective surgical decisions regarding resection feasibility, as well as the lack of a centralized assessment for ORR and resection. The combination of cetuximab with FOLFOXIRI did not significantly improve ORR compared to cetuximab plus FOLFOX. Despite achieving an enhanced DpR, this improvement did not translate into improved R0 resection rates or PFS. Moreover, the triplet arm was associated with an increase in treatment-related toxicity. ClinicalTrials.gov Identifier: NCT03493048.

Estimating Efficacy of Conversion Therapy on Patients with Initially Unresectable Colorectal Cancer Liver Metastases by using MRI: Development of a Predictive Score

The conversion success rate (CSR) has crucial implication for clinical outcomes of initially unresectable colorectal liver metastases (CRLM) following conversion therapy. This study aimed to develop a simple predictive scoring model for identifying CSR according to baseline magnetic resonance imaging (MRI) features, and confirm its performance and prognostic significance in a validation cohort. A total of 155 consecutive patients with initially unresectable CRLM were retrospectively reviewed in the study. A simple MRI-based predictive scoring model for identifying CSR was developed in the development cohort (n=104) by using multivariable logistic regression analyzes. The diagnostic performance was evaluated for the predictive score. Thereafter, patients in the validation cohort (n=51) were stratified into groups with predicted high CSR or low CSR according to the score. The progression-free survival (PFS) and overall survival (OS) were compared between two groups using the log-rank test. The predictive score of CSR, named mrNISE, incorporated the number of CRLM ≥10, the largest size ≥50mm, poorly defined tumor-liver interface, and peritumoral enhancement. The AUC of the mrNISE score was 0.845 for the development cohort and 0.776 for the validation cohort. According to the score, patients with predicted high CSR had better PFS and OS than those with low CSR in both development and validation cohorts. The predictive score demonstrated great performance for identifying CSR of initially unresectable CRLM. Stratifying patients by the score, personalized treatment goals can be formulated before conversion therapy to improve clinical prognosis and reduce adverse events caused by ineffective treatment.

ASO Visual Abstract:Outcomesof HepaticArtery-BasedTherapiesand Systemic Multiagent Chemotherapy in Unresectable Colorectal Liver Metastases: A Systematic Review and Meta-analysis.

ASO Visual Abstract:Outcomesof HepaticArtery-BasedTherapiesand Systemic Multiagent Chemotherapy in Unresectable Colorectal Liver Metastases: A Systematic Review and Meta-analysis.

ASO Author Reflections: Outcomes of Hepatic Artery-Based Therapies and Systemic Multiagent Chemotherapy in Unresectable Colorectal Liver Metastases: A Systematic Review and Meta-analysis.

ASO Author Reflections: Outcomes of Hepatic Artery-Based Therapies and Systemic Multiagent Chemotherapy in Unresectable Colorectal Liver Metastases: A Systematic Review and Meta-analysis.

Drug-eluting beads transcatheter arterial chemoembolization combined with systemic therapy versus systemic therapy alone as first-line treatment for unresectable colorectal liver metastases.

The purpose of this retrospective study was to compare the therapeutic efficacy and safety of drug-eluting bead transarterial chemoembolization (DEB-TACE) combined with systemic therapy to systemic therapy alone as first-line treatment for unresectable patients with colorectal liver metastases (CRLM). From December 2017 to December 2022, patients with unresectable CRLM who received systemic therapy with or without DEB-TACE as first-line treatment were included in the study. The primary endpoint was progression-free survival (PFS). Secondary endpoints were tumor response, conversion rate and adverse events. Ninety-eight patients were enrolled in this study, including 46 patients who received systemic therapy combined with DEB-TACE (DEB-TACE group) and 52 patients who received systemic therapy alone (control group). The median PFS was elevated in the DEB-TACE group compared with the control group (12.1 months vs 8.4 months, p = 0.008). The disease control rate was increased in the DEB-TACE group compared with the control group (87.0% vs 67.3%, p = 0.022). Overall response rates (39.1% vs 25.0%; p = 0.133) and conversion rate to liver resection (33.8% vs 25.0%; p = 0.290) were no different between the two groups. The multivariate analysis showed that treatment options, size of liver metastasis, number of liver metastasis, synchronous metastases, and extrahepatic metastases were independent prognostic factor of PFS. Further subgroup analyses illustrated that PFS was beneficial with the DEB-TACE group in patients with age ≥ 60, male, left colon, synchronous metastases, bilobar, number of liver metastasis > 5, extrahepatic metastases, non-extrahepatic metastases, CEA level < 5 (ng/ml), and KRAS wild-type. No grade 4 or 5 toxicities related to DEB-TACE procedures were observed. In patients with unresectable CRLM, systemic chemotherapy with DEB-TACE as first-line treatment may improve progression-free survival and disease control rate outcomes over systemic chemotherapy alone with manageable safety profile.

High-risk Patients With Colorectal Liver Metastases Assessed by the Beppu Score Can Have Excellent Survival Through Multidisciplinary Treatment Including Local Ablation.

The Beppu score assessed by the Japanese Society of Hepato-Biliary-Pancreatic Surgery nomogram helps predict postoperative disease-free survival for patients with resectable colorectal liver metastases (CRLM). Using the Beppu score, patients with resectable CRLM were divided into three groups according to recurrence risk: low (≤6 points), moderate (7-10 points), and high-risk (≥11 points). Hepatectomy following preoperative chemotherapy is recommended for high-risk patients. The surgical outcome, local recurrence rates, and long-term survival were assessed, focusing on local ablation. Twenty high-risk and unresectable CRLM patients were enrolled between April 2016 and April 2022. Hepatectomy with or without local ablation was performed after induction chemotherapy. Local ablation was permissive for patients with effective chemotherapy (partial response and stable disease) with CRLM ≤2 cm and ≥5 mm distant from major vessels. The median diameters and numbers of CRLM were 26 (10-150) mm and 9 (1-46). All 18 patients who received preoperative chemotherapy were disease controls. Local ablation was performed simultaneously on hepatectomy in 14 patients. The median diameters and numbers of the ablated nodules were 12 (5-17) mm and 3 (1-21). Local recurrence was 8.5% per 82 ablative nodules. Three-year disease-free and five-year overall survival was 57.4% and 56.2%, respectively. There was no significant difference in patients with or without local ablation. Our treatment strategy for high-risk CRLM patients is feasible and can provide an excellent long-term prognosis regardless of adding local ablation to hepatectomy.

Outcomes of Hepatic Artery-Based Therapies and Systemic Multiagent Chemotherapy in Unresectable Colorectal Liver Metastases: A Systematic Review and Meta-analysis.

Treatment of unresectable colorectal liver metastases (UCRLM) includes locoregional and systemic therapy. A comprehensive analysis capturing long-term outcomes of these treatment options has not been performed. A systematic review and meta-analysis was performed to calculate pooled outcomes of hepatic artery infusion with systemic chemotherapy (HAI-S), transarterial chemoembolization with systemic chemotherapy (TACE-S), transarterial radioembolization with systemic chemotherapy (TARE-S), doublet (FOLFOX, FOLFIRI), and triplet chemotherapy (FOLFOXIRI). Outcomes included overall survival (OS), progression-free survival (PFS), rate of conversion to resection (CTR), and response rate (RR). A total of 32, 7, 9, and 14 publications were included in the HAI-S, TACE-S, and TARE-S chemotherapy arms. The 6/12/24/36-month OS estimates for HAI-S, TACE-S, TARE-S, FOLFOX, FOLFIRI, and FOLFOXIRI were 97%/80%/54%/35%, 100%/83%/40%/14%, 82%/61%/34%/21%, 96%/83%/53%/36%, and 96%/93%/72%/55%. Similarly, the 6/12/24/36-month PFS estimates were 74%/44%/19%/14%, 66%/20%/9%/3%, 57%/23%/10%/3%, 69%/30%/12%/7%, and 88%/55%/18%/11%. The corresponding CTR and RR rates were 31, 20%, unmeasurable (TARE-S), 35, 53; and 49, 45, 45, 50, 80%, respectively. The majority of chemotherapy studies included first-line therapy and liver-only metastases, whereas most HAI-S studies were pretreated. On subgroup analysis in first-line setting with liver-only metastases, the HAI-S arm had comparable outcomes to FOLFOXIRI and outperformed doublet chemotherapy regimens. Although triplet chemotherapy appeared to outperform other arms, high toxicity and inclusion of potentially resectable patients must be considered while interpreting results. HAI-S and multiagent chemotherapy are effective therapies for UCRLM. To make definitive conclusions, a randomized trial with comparable patient characteristics and line of therapy will be required. The upcoming EA2222 PUMP trial may help to address this question.

Debulking hepatectomy for colorectal liver metastasis: Analysis of risk factors for progression free survival

BackgroundThe study explores the role of liver debulking surgery in cases of unresectable colorectal liver metastases (CRLM), challenging the traditional notion that surgery is not a valid option in such scenarios. Materials and methodsPatients with advanced but resectable disease who underwent surgery with a curative intent (Group I) and those with advanced incompletely resectable disease who underwent a “debulking” hepatectomy (Group II) were compared. ResultsThere was no difference in the intra-operative and post-operative results between the two groups. The 3-year and 5-year OS rates were 69% and 47% for group 1 vs 64% and 35% for group 2 respectively (p = 0.14). The 3-year and 5-year PFS rates were 32% and 21% for group 1 vs 12% and 8% for group 2 respectively (p = 0.009). Independent predictors of PFS in the debulking group were bilobar metastases (HR = 2.70; p = 0.02); the presence of extrahepatic metastasis (HR = 2.65, p = 0.03) and the presence of more than 9 metastases (HR = 2.37; p = 0.04). Iterative liver surgery for CRLM was a significant protective factor (HR = 0.34, p = 0.04). ConclusionAn aggressive palliative surgical approach may offer a survival benefit for selected patients with unresectable CRLM, without increasing the morbidity. The decision for surgery should be made on a case-by-case basis.

Liver Transplantation for Unresectable Colorectal Liver Metastasis: Perspective and Review of Current Literature.

The treatment of unresectable colorectal liver metastasis (CRLM) has previously been limited to palliative chemotherapy. Traditionally, the role of liver transplant has not been associated with sufficient survival to justify a patient undergoing a major operation with the associated requirement for postoperative immunosuppression. With improvements in chemotherapy options, a certain subset of patients can experience stable disease for years, which has prompted investigation into the role of liver transplant in these patients. Several recent studies have shown promising results in well-selected patients, with posttransplant survival approaching that of liver transplant recipients for other diseases. Here, we present a review of the data and current protocols for liver transplant for unresectable CRLM.

4D-MRI assisted stereotactic body radiation therapy for unresectable colorectal cancer liver metastases

This study evaluated the feasibilities and outcomes following four-dimensional magnetic resonance imaging (4D-MRI) assisted stereotactic body radiation therapy (SBRT) for unresectable colorectal liver metastases (CRLMs). From March 2018 to January 2022, we identified 76 unresectable CRLMs patients with 123 lesions who received 4D-MRI guided SBRT in our institution. 4D-MRI simulation with or without abdominal compression was conducted for all patients. The prescription dose was 50–65 Gy in 5–12 fractions. The image quality of computed tomography (CT) and MRI were compared using the Clarity Score. Clinical outcomes and toxicity profiles were evaluated. 4D-MRI improved the image quality compared with CT images (mean Clarity Score: 1.67 vs 2.88, P < 0.001). The abdominal compression reduced motions in cranial–caudal direction (P = 0.03) with two phase T2 weighted images assessing tumor motion. The median follow-up time was 12.5 months. For 98 lesions assessed for best response, the complete response, partial response and stable disease rate were 57.1 %, 30.6 % and 12.2 %, respectively. The local control (LC) rate at 1 year was 97.3 %. 46.1 % of patients experienced grade 1–2 toxicities and only 2.6 % patients experienced grade 3 hematologic toxicities. The 4D-MRI technique allowed accurate target delineation and motion tracking in unresectable CRLMs patients. Favorable LC rate and mild toxicities were achieved. This study provided evidence for using 4D-MRI assisted SBRT as an alternative treatment in unresectable CRLMs.

Safety and feasibility of establishing an adjuvant hepatic artery infusion program

BackgroundHepatic artery infusion (HAI) is less frequently used in the adjuvant setting for resectable colorectal liver metastasis (CRLM) due to concerns regarding toxicity. Our objective was to evaluate the safety and feasibility of establishing an adjuvant HAI program. MethodsPatients who underwent HAI pump placement between January 2019 and February 2023 for CRLM were identified. Complications and HAI delivery were compared between patients who received HAI in the unresectable and adjuvant settings. ResultsOf 51 patients, 23 received HAI for unresectable CRLM and 28 in the adjuvant setting. Patients with unresectable CRLM more commonly had bilobar disease (n = 23/23 vs n = 18/28, p < 0.01) and more preoperative liver metastases (median 10 [IQR 6–15] vs 4 [IQR 3–7], p < 0.01). Biliary sclerosis was the most common complication (n = 2/23 vs n = 4/28); however, there were no differences in postoperative or HAI-specific complications. In the most recent two years, 0 patients in the unresectable group vs 2 patients in the adjuvant group developed biliary sclerosis. All patients were initiated on HAI with no difference in treatment times or dose reductions. ConclusionAdjuvant HAI is safe and feasible for patients with resectable CRLM. HAI programs can carefully consider including patients with resectable CRLM if managed by an experienced multidisciplinary team with quality assurance controls in place.

Deep learning models for automatic tumor segmentation and total tumor volume assessment in patients with colorectal liver metastases

BackgroundWe developed models for tumor segmentation to automate the assessment of total tumor volume (TTV) in patients with colorectal liver metastases (CRLM).MethodsIn this prospective cohort study, pre- and post-systemic treatment computed tomography (CT) scans of 259 patients with initially unresectable CRLM of the CAIRO5 trial (NCT02162563) were included. In total, 595 CT scans comprising 8,959 CRLM were divided into training (73%), validation (6.5%), and test sets (21%). Deep learning models were trained with ground truth segmentations of the liver and CRLM. TTV was calculated based on the CRLM segmentations. An external validation cohort was included, comprising 72 preoperative CT scans of patients with 112 resectable CRLM. Image segmentation evaluation metrics and intraclass correlation coefficient (ICC) were calculated.ResultsIn the test set (122 CT scans), the autosegmentation models showed a global Dice similarity coefficient (DSC) of 0.96 (liver) and 0.86 (CRLM). The corresponding median per-case DSC was 0.96 (interquartile range [IQR] 0.95–0.96) and 0.80 (IQR 0.67–0.87). For tumor segmentation, the intersection-over-union, precision, and recall were 0.75, 0.89, and 0.84, respectively. An excellent agreement was observed between the reference and automatically computed TTV for the test set (ICC 0.98) and external validation cohort (ICC 0.98). In the external validation, the global DSC was 0.82 and the median per-case DSC was 0.60 (IQR 0.29–0.76) for tumor segmentation.ConclusionsDeep learning autosegmentation models were able to segment the liver and CRLM automatically and accurately in patients with initially unresectable CRLM, enabling automatic TTV assessment in such patients.Relevance statementAutomatic segmentation enables the assessment of total tumor volume in patients with colorectal liver metastases, with a high potential of decreasing radiologist’s workload and increasing accuracy and consistency.Key points• Tumor response evaluation is time-consuming, manually performed, and ignores total tumor volume.• Automatic models can accurately segment tumors in patients with colorectal liver metastases.• Total tumor volume can be accurately calculated based on automatic segmentations.Graphical

High-intensity focused ultrasound ablation combined with systemic therapy for unresectable colorectal cancer liver metastasis: A propensity score-matched analysis.

Unresectable colorectal cancer liver metastasis (CRLM) remains a challenging obstacle that often prevents curative treatment. In this study, we retrospectively analyzed the efficacy and safety of high-intensity focused ultrasound (HIFU) as a local adjuvant therapy for systemic chemotherapy for patients with unresectable CRLM. HIFU is a noninvasive method previously demonstrated as efficacious for various solid malignancies. Propensity score matching was used for the combination therapy group (HIFU group, n = 59) and the observation group receiving systemic therapy only (No-HIFU group, n = 59). In addition, the survival benefit, adverse effects, and factors affecting prognosis following HIFU were evaluated. The disease control rate was 77.9% and 62.7%, and the objective remission rate was 18.9% and 6.8% in the HIFU and non-HIFU groups, respectively. The survival analysis showed that median progression-free survival (mPFS) was 12.0 months and 11.0 months for the HIFU and non-HIFU groups, respectively (p = 0.002). The univariate and multivariate analysis showed that pre-treatment colorectal cancer liver metastasis lesion size was significantly associated with mPFS. In addition, patients that received a combination treatment for CRLM lesions <5.0 cm had a longer mPFS when compared to those receiving systemic therapy alone (13.0 months vs. 11.0 months, p = 0.001). In the HIFU group, patients with lesions <5.0 cm had a longer mPFS than patients with lesions ≥5.0 cm (13.0 months vs. 10.0 months, p = 0.04) (Figure3B,C). Most treatment-related adverse events observed in both groups were grade 1-2. Only four cases (6.8%) of grade 1-2 skin burns were observed in patients in the HIFU group; no other statistically significant adverse events were observed. Our study showed that HIFU ablation targeting unresectable CRLM alongside systemic therapy safely and significantly improved local control rates and prolonged mPFS, especially for lesions smaller than 5.0 cm.

Colorectal liver metastases: Correlations of contrast-enhanced ultrasound features with tumor clinicopathological factors and clinical outcomes following conversion therapy.

To explore the prognostic impact of contrast-enhanced ultrasound (CEUS) features for initially unresectable colorectal liver metastases (CLMs) in a clinical setting of conversion therapy. Between March 2015 and November 2020, consecutive patients with CLMs who received conversion treatment were prospectively enrolled. All participants underwent liver CEUS at baseline. The primary endpoint was conversion resection rate (R0 and overall resection). Secondary endpoints were objective response rate (ORR), overall survival (OS), and progression-free survival (PFS). 104 participants who completed conversion treatment were included. CEUS enhancement pattern was correlated with index lesion (size and echogenicity), primary (site, differentiation, perineural invasion, and RAS genotype) and serum (CA19-9 level) characteristics (P = <0.001-0.016). CEUS enhancement pattern was significantly associated with R0 resection rate, ORR, PFS, and OS (P = 0.001-0.049), whereas enhancement degree was associated with PFS and OS (P = 0.043 and 0.045). Multivariate analysis showed that heterogeneous enhancement independently predicted R0 and overall resection (P = 0.028 and 0.024) while rim-like enhancement independently predicted ORR and OS (P = 0.009 and 0.026). CEUS enhancement pattern was significantly associated with tumor characteristics and clinical outcomes following conversion therapy, and thus might be of prognosis impact for initially unresectable CLMs.

Hepatic arterial oxaliplatin plus intravenous 5-fluorouracil and cetuximab for first-line treatment of colorectal liver metastases: A multicenter phase II trial

BackgroundThe efficacy and tolerability of hepatic arterial infusion (HAI) oxaliplatin plus systemic 5-fluorouracil and cetuximab as frontline treatment in patients with colorectal liver metastases (CRLM) are unknown. MethodsIn this multicenter, single-arm phase II study, patients with CRLM not amenable to curative-intent resection or requiring complex/major liver resection, and no prior chemotherapy for metastatic disease, received HAI oxaliplatin and intravenous 5-fluorouracil, leucovorin and cetuximab, every two weeks until disease progression, limiting toxicity or at least 3 months after complete response or curative-intent resection/ablation. The primary endpoint was overall response rate (ORR). Results35 patients, mostly with bilateral (89%), multiple CRLM (>4, 86%; >10, 46%) were enrolled in eight centers. The ORR was 88% (95% CI, 71%−96%) among evaluable patients (n = 32), and 95% (95% CI 70–100%) among the 22 wild-type RAS/BRAF evaluable patients. After a median follow-up of 8.8 years (95% CI, 8.7-not reached), median progression-free survival was 17.9 months (95% CI, 15–23) and median overall survival (OS) was 46.3 months (95% CI, 40.0-not reached). 23 of the 35 patients (66%), including 22 (79%) of the 25 patients with wild-type RAS tumor, underwent curative-intent surgical resection and/or ablation of CRLM. HAI catheter remained patent in 86% of patients, allowing for a median of eight oxaliplatin infusions (range, 1–19). Treatment toxicity was manageable, without toxic death. ConclusionHAI oxaliplatin plus systemic 5-fluorouracil and cetuximab appears highly effective in the frontline treatment of patients with unresectable CRLM and should be investigated further.

4D-MRI Guided Stereotactic Body Radiation Therapy for Unresectable Colorectal Liver Metastases

This study evaluated the feasibilities and outcomes following four-dimensional magnetic resonance imaging (4D-MRI) guided stereotactic body radiation therapy (SBRT) for unresectable colorectal liver metastases (CRLM). From March 2018 to January 2022, we identified 76 unresectable CRLM patients with 123 lesions who received 4D-MRI guided SBRT in our institution. 4D-MRI simulation with or without abdominal compression was conducted for all patients. The prescription dose was 50-65 Gy in 5-12 fractions. The image quality of computed tomography (CT) and MRI were compared using the Clarity Score. Clinical outcomes and toxicity profiles were evaluated. The 4D-MRI significantly improved the image quality compared with CT images (mean Clarity Score: 1.67 vs 2.88, P < 0.001). The abdominal compression significantly reduced motions in cranial-caudal direction (P = 0.03) with 2 phase T2 weighted images assessing tumor motion. The median follow-up time was 12.5 months. For 98 lesions assessed for best response, the complete response, partial response and stable disease rate were 57.1 %, 30.6 % and 12.2 %, respectively. The local control (LC) rate at 2 year was 97.3%. 46.1% of patients experienced grade 1-2 toxicities and only 2.6% patients experienced grade 3 hematologic toxicities. The 4D-MRI technique allowed precise target delineation and motion tracking in unresectable CRLM patients. High LC rate and mild toxicities were achieved. This study provided evidence for using 4D-MRI guided SBRT as an alternative treatment in unresectable CRLM.

EORTC 1409 GITCG/ESSO 01 - A prospective colorectal liver metastasis database for borderline or initially unresectable diseases (CLIMB): Lessons learnt from real life. From paradigm to unmet need

AimMultidisciplinary management of metastatic colorectal liver metastases (CRLM) is still challenging. To assess postoperative complications in initially unresectable or borderline resectable CRLM, the prospective EORTC-1409 ESSO 01-CLIMB trial capturing ‘real-life data’ of European centres specialized in liver surgery was initiated. Material and methodsA total of 219 patients were registered between May 2015 and January 2019 from 15 centres in nine countries. Eligible patients had borderline or initially unresectable CRLM assessed by pre-operative multidisciplinary team discussion (MDT). Primary endpoints were postoperative complications, 30-day and 90-days mortality post-surgery, and quality indicators. We report the final results of the 151 eligible patients that underwent at least one liver surgery. ResultsPerioperative chemotherapy with or without targeted treatment were administered in 100 patients (69.4%). One stage resection (OSR) was performed in 119 patients (78.8%). Two stage resections (TSR, incl. Associating Liver Partition and Portal Vein Ligation for Staged hepatectomy (ALPPS)) were completed in 24 out of 32 patients (75%). Postoperative complications were reported in 55.5% (95% CI: 46.1–64.6%), 64.0% (95% CI: 42.5–82%), and 100% (95% CI: 59–100%) of the patients in OSR, TSR and ALPPS, respectively. Post-hepatectomy liver failure occurred in 6.7%, 20.0%, and 28.6% in OSR, TSR, and ALPPS, respectively. In total, four patients (2.6%) died after surgery. ConclusionAcross nine countries, OSR was more often performed than TSR and tended to result in less postoperative complications. Despite many efforts to register patients across Europe, it is still challenging to set up a prospective CRLM database.

Current Practices in Hepatic Artery Infusion (HAI) Chemotherapy: An International Survey of the HAI Consortium Research Network.

An increasing number of hepatic artery infusion (HAI) programs have been established worldwide. Practice patterns for this complex therapy across these programs have not been reported. This survey aimed to identify current practice patterns in HAI therapy with the long-term goal of defining best practices and performing prospective studies. Using SurveyMonkeyTM, a 28-question survey assessing current practices in HAI was developed by 12 HAI Consortium Research Network (HCRN) surgical oncologists. Content analysis was used to code textual responses, and the frequency of categories was calculated. Scores for rank-order questions were generated by calculating average ranking for each answer choice. Thirty-six (72%) HCRN members responded to the survey. The most common intended initial indications for HAI at new programs were unresectable colorectal liver metastases (uCRLM; 100%) and unresectable intrahepatic cholangiocarcinoma (uIHC; 56%). Practice patterns evolved such that uCRLM (94%) and adjuvant therapy for CRLM (adjCRLM; 72%) have become the most common current indications for HAI at established centers. Referral patterns for pump placement differed between uCRLM and uIHC, with most patients referred while receiving second- and first-line therapy, respectively, with physicians preferring to evaluate patients for HAI while receiving first-line therapy for CRLM. Concern for extrahepatic disease was ranked as the most important factor when considering a patient for HAI. Indication and patient selection factors for HAI therapy are relatively uniform across most HCRN centers. The increasing use of adjuvant HAI therapy and overall consistency of practice patterns among HCRN centers provides a robust environment for prospective data collection and randomized clinical trials.

Domino Liver Transplantation for Unresectable Colon Cancer Liver Metastasis From a Donor With Heterozygous Familial Hyperlipidemia: A Case Report

Liver transplantation (LT) is a potential curative treatment for unresectable colorectal cancer liver metastasis (CRLM). Familial hypercholesterolemia (FH) is an inherited condition characterized by elevated low-density lipoprotein cholesterol (LDL-C) levels. Liver transplantation is offered for selected cases, and an explanted liver can be used as a domino graft. We report the first report of domino LT for unresectable CRLM using a liver from a patient with heterozygous FH. The domino donor was a 30-year-old female with a history of heterozygous FH. She had failed medical therapies for FH, including plasmapheresis; therefore, she underwent living donor LT as a treatment for FH. The explanted liver was transplanted to the domino recipient. She has been doing well with normal LDL-C levels. The domino recipient was a 44-year-old female with a history of stage 4 sigmoid cancer with liver metastases, for which she underwent laparoscopic sigmoid colectomy and right hepatectomy. She developed unresectable lesions in the remnant left lobe, which were controlled well with chemotherapy; therefore, she underwent domino LT. She is doing well without recurrence at the 31-month follow-up. Domino LT from a donor with heterozygous FH is feasible for strictly selected patients with unresectable CRLM.

Efficacy of Thermal Ablation for Small-Size (0-3 cm) versus Intermediate-Size (3-5 cm) Colorectal Liver Metastases: Results from the Amsterdam Colorectal Liver Met Registry (AmCORE).

Thermal ablation is widely recognized as the standard of care for small-size unresectable colorectal liver metastases (CRLM). For larger CRLM safety, local control and overall efficacy are not well established and insufficiently validated. The purpose of this comparative series was to analyze outcomes for intermediate-size versus small-size CRLM. Patients treated with thermal ablation between December 2000 and November 2021 for small-size and intermediate-size CRLM were included. The primary endpoints were complication rate and local control (LC). Secondary endpoints included local tumor progression-free survival (LTPFS) and overall survival (OS). In total, 59 patients were included in the intermediate-size (3-5 cm) group and 221 in the small-size (0-3 cm) group. Complications were not significantly different between the two groups (p = 0.546). No significant difference between the groups was found in an overall comparison of OS (HR 1.339; 95% CI 0.824-2.176; p = 0.239). LTPFS (HR 3.388; p < 0.001) and LC (HR 3.744; p = 0.004) were superior in the small-size group. Nevertheless, the 1-, 3-, and 5-year LC for intermediate-size CRLM was still 93.9%, 85.4%, and 81.5%, and technical efficacy improved over time. Thermal ablation for intermediate-size unresectable CRLM is safe and induces long-term LC in the vast majority. The results of the COLLISION-XL trial (unresectable colorectal liver metastases: stereotactic body radiotherapy versus microwave ablation-a phase II randomized controlled trial for CRLM 3-5 cm) are required to provide further clarification of the role of local ablative methods for intermediate-size unresectable CRLM.