Colorectal cancer (CRC) recurs at a striking rate, specifically in patients with liver metastasis. Dormant CRC cells disseminated following initial primary tumor resection or treatment often resurface years later to form aggressive, therapy-resistant tumors that result in high patient mortality. Routine imaging-based screenings often fail to detect dormant cancer cell clusters, and there are no overt symptomatic presentations, making dormant CRC a major clinical challenge to diagnose and treat. Tissue engineering approaches are ideally suited to model dormant cancer cells and enable the discovery of therapeutic vulnerabilities or unique mechanistic dependencies of dormant CRC. Emerging evidence suggests that tissue-engineered approaches have been successfully used to model dormant breast and lung cancer. With CRC responsible for the second most cancer-related deaths worldwide and CRC patients commonly experiencing recurrence, it is essential to expand dormancy models to understand this phenomenon in the context of CRC. Most published in vitro models of CRC dormancy simplify the complex tumor microenvironment with two-dimensional culture systems to elucidate dormancy-driving mechanisms. Building on this foundation, future research should apply tissue engineering methods to this growing field to generate competent three-dimensional models and increase mechanistic knowledge. This review summarizes the current state of in vitro CRC dormancy models, highlighting the techniques utilized to give rise to dormant CRC cells: nutrient depletion, anticancer drugs, physical extracellular matrix interactions, and genetic manipulation. The metrics used to validate dormancy within each model are also consolidated to demonstrate the lack of established standards and the ambiguity around comparing studies that have been validated differently. The methods of these studies are organized in this review to increase comprehensibility and identify needs and opportunities for future bioengineered in vitro models to address dormancy-driven mortality in patients with CRC liver metastasis. Impact Statement Dormant cancer drives high patient mortality, especially in metastatic colorectal cancer, owing to the clinical inability to identify dormant cells prior to their overt recurrence. Lacking clinical insights, in vitro modeling for mechanistic and therapeutic discovery is hindered. Here, we review models and methods of inducing colorectal cancer dormancy with the goal of consolidating findings for reference. We also highlight the need for advanced, tissue-engineered models to better mimic the organ-specific 3D microenvironment of metastatic colorectal cancer. New models would enable breakthroughs in understanding mechanisms driving dormancy progression and reversal, thereby providing context for therapeutic advances to improve patient survival.

Few studies have been conducted to evaluate the efficacy of HAIC using circulating tumour cells (CTCs). In this study, a total of 100 patients who received HAIC treatment and CTC detection were selected. The results showed that after HAIC treatment, the levels of CTC, carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA) decreased. Postoperative progression-free survival (PFS) rates between patients with positive and negative preoperative CTC results, and for CA19-9, CEA were significantly different. The positive rate of CTCs was 61% before chemotherapy and 23% after chemotherapy, and the correlation coefficient between the two was 0.385. Those whose CTC values increased after chemotherapy had shorter PFS rates. CTCs are an independent predictor of recurrence. Patients with CTC-positive results are more susceptible to recurrence. The CTC count in peripheral blood has a close bearing on the postoperative chemotherapy efficacy of patients with CRC and affects patients' PFS.

Colorectal cancer (CRC) is one of the leading cancers globally in terms of both incidence and cancer-related mortality. Liver metastatic disease is the main prognostic driver for patients with CRC. The management options for liver metastatic CRC continue to evolve, particularly with the incorporation of locoregional therapies into the treatment paradigm. Hepatic arterial infusion (HAI) chemotherapy is one such liver directed approach used with the goal of converting patients to liver resection, reducing the risk of recurrence, treating recurrent disease, and most importantly improving overall survival. This article summarizes the role of HAI chemotherapy in the treatment of liver metastatic CRC.

Reduction in skeletal muscle mass during chemotherapy is associated with poor outcomes. This study investigated the impact of changes in the psoas muscle index (PMI) on the prognosis of patients with unresectable colorectal liver metastases (CRLM) undergoing chemotherapy, including subgroup analyses based on the initial treatment response assessment.

We evaluated 47 patients with unresectable CRLM who underwent systematic chemotherapy and assessed changes in PMI to determine their prognosis.

Changes in PMI were significantly associated with the presence or absence of primary tumor resection and the chemotherapeutic responses to first-line chemotherapy. The PMI reduction group was significantly associated with poor prognosis in both overall survival (OS) and progression-free survival (PFS) in patients with CRLM, and in both OS and PFS in the partial response (PR) group at the initial chemotherapy response assessment.

Skeletal muscle loss at chemotherapy initiation was significantly associated with poorer survival in patients with unresectable CRLM. Maintaining muscle mass could serve as a new indicator for identifying patients with a PR at the initial chemotherapy response assessment for prognosis. Personalized interventions should be investigated to determine whether they can improve muscle mass and lead to better clinical outcomes.

Resection of primary tumor and liver metastases is the gold standard for colorectal cancer with liver-only metastases (CRLM). Although treatment options have expanded to enable conversion of unresectable to resectable CRLM, about 40% of patients will have definitively unresectable disease. Major advances in surgical techniques, immunosuppressive protocols and patient selection criteria for liver transplantation have resulted in improved outcomes.

A literature search has been conducted in Pubmed for articles published between 2014 and 2024. This review paper comments on current liver-directed treatment options for CRLM: resection, percutaneous ablation, conversion-chemotherapy, TACE, SIRT, and SABR. We explore evidence for liver transplantation in patients with unresectable CRLM, comment on possible limitations for implementation in clinical practice and give an overview of the current guidelines on liver transplantation in the USA, Europe, the United Kingdom, and Australia/New Zealand.

The recent randomized TRANSMET trial, investigating liver transplantation versus chemotherapy in unresectable CRLM, shows promising 5-year OS reaching similar values as for other accepted liver transplantation indications. Further investigations with RCTs to investigate reproducibility and feasibility in clinical practice are needed. Before liver transplantation can be implemented as a standard treatment option, reorganizations at federal, regional and hospital levels would be required.

The management of synchronous metastatic rectal cancer (SMRC) is complex and multimodal, involving chemotherapy, surgery and/or radiotherapy. The aim of this study was firstly to confirm the efficacy of the induction FOLFIRINOX, and secondly to evaluate the different therapeutic strategies and outcomes of patients.

This French study combined data from a prospective FFCD trial and a multicenter cohort. Patients included had SMRC and had undergone induction triplet chemotherapy. Two groups of patients were defined according to the resectability of metastases at baseline: resectable (Res) and unresectable (URes). The primary endpoint was the objective response rate.

146 patients were included in 16 French centers and 65 patients in the FFCD1102 trial. In overall population the median age of patients was 59 years, 86% of tumors were of the lower or middle rectum, 33% were well-differentiated, 53% were RAS mutated and 7% BRAF mutated. Triplet induction was associated with 80% of objective response and 92% of disease control. After the induction phase, 69% and 48% of patients of Res and URes groups underwent rectal surgery, and secondary metastases resection was done in 79% and 39% of patients, respectively. Median overall survival (OS) for Res was 56.3 months (95% CI: 22.54-NA). Median OS for URes who had or not secondary metastases resection were 45.1 months (95% CI: 39.89-NA) and 21.1 months (95% CI 17.31-27.1), respectively. Patients with BRAF mutated tumors were more likely to have unresectable disease, and had worse survivals than the patients with RAS mutated or RAS/BRAF wild-type.

Triplet induction chemotherapy is a treatment of choice in selected patients with SMRC, allowing to adapt the therapeutic strategy to the response and invasiveness of the various sites.

The management of metastatic rectal cancer is essentially based on three main therapeutic approaches: surgery, radiotherapy/chemoradiotherapy and chemotherapy. Induction triplet chemotherapy appears as a good choice for fit and young patients. It allows to adapt the therapeutic strategy to the response and invasiveness of the various sites. In this study dedicated to patients undergoing treatment for rectal cancer with synchronous metastases, FOLFIRINOX-based induction chemotherapy was associated with objective response rate of 77% and disease control rate of 92%. These results are similar with those of the FFCD 1102 trial and confirm the efficacy of induction chemotherapy with FOLFIRINOX with or without targeted therapy in these patients in daily routine practice. Surgery for metastases is a key factor in determining patient's outcome and triplet induction chemotherapy, associated with high response rates, enables a significant percentage of patients to undergo surgery and appears therefore to be a treatment of choice, particularly for patients whose disease is unresectable at baseline.

Primary tumor resection and metastasectomy are curative for metastatic colorectal cancer. However, there is still a paucity of data regarding the clinical outcomes and risk factors after disease recurrence and second metastasectomy.

We retrospectively evaluated the clinical outcomes of patients who underwent the second metastasectomy. In addition, risk factors for the outcomes were analyzed.

A total of 94 patients (39 females and 55 males) received a second metastasectomy after the recurrence. Recurrent sites included the lung (47 patients), liver (36 patients), both lung and liver (four patients), and non-lung/non-liver (seven patients). Among them, 89 (94.7 %) patients achieved R0 resection, while three (3.2 %) and two (2.1 %) patients achieved R1 and R2 resections, respectively. The 5-year disease-free survival (DFS) and overall survival (OS) were 42.8±5.3 % and 67.2±4.9 %, respectively. Multivariable analysis for DFS identified that primary rectal cancer (hazard ratio [HR] 0.45, P=0.033) and disease-free interval after the first metastasectomy of ≥12 months (HR 0.39, P=0.002) were good predictive factors; in contrast, non-lung/non-liver metastasis (HR 3.32, P=0.020) was a poor predictive factor. Multivariable analysis for OS showed that age ≥70 years (HR 3.27, P=0.011), non-lung/non-liver metastasis (HR 4.04, P=0.024), and lesion number ≥2 (HR 2.25, P=0.023) were poor prognostic factors.

Patients who underwent a second metastasectomy had a long-term disease-free state and good OS. Our data suggest that a second metastasectomy should be considered if a patient has a limited number of metastases confined to the liver and/or lung and long DFS after the first metastasectomy.

Individualized treatment of colorectal cancer liver metastases (CRLM) remains challenging due to differences in the severity of metastatic disease and tumour biology. Exploring specific prognostic risk subgroups is urgently needed. The current study aimed to investigate the prognostic value of chromosomal instability (CIN) in patients with initially resectable CRLM and the predictive value of CIN for the efficacy of bevacizumab.

Ninety-one consecutive patients with initially resectable CRLM who underwent curative liver resection from 2006 to 2018 at Sun Yat-sen University Cancer Center were selected for analysis. CIN was evaluated by automated digital imaging systems. Immunohistochemistry (IHC) was performed to detect interleukin-6 (IL-6), vascular endothelial growth factor A (VEGFA) and CD31 expression in paraffin-embedded specimens. Recurrence-free survival (RFS) and overall survival (OS) were analysed using the Kaplan-Meier method and Cox regression models.

Patients with high chromosomal instability (CIN-H) had a worse 3-year RFS rate (HR, 1.953; 95% CI, 1.001-3.810; p = 0.049) and a worse 3-year OS rate (HR, 2.449; 95% CI, 1.150-5.213; p = 0.016) than those with low chromosomal instability (CIN-L). CIN-H was identified as an independent prognostic factor for RFS (HR, 2.569; 95% CI, 1.078-6.121; p = 0.033) and OS (HR, 3.852; 95% CI, 1.173-12.645; p = 0.026) in the multivariate analysis. The protein levels of IL-6, VEGFA and CD31 were upregulated in patients in the CIN-H group compared to those in the CIN-L group in both primary tumour and liver metastases tissues. Among them, 22 patients with recurrent tumours were treated with first-line bevacizumab treatment and based on the clinical response assessment, disease control rates were adversely associated with chromosomal instability (p = 0.043).

Our study showed that high chromosomal instability is a negative prognostic factor for patients with initially resectable CRLM after liver resection. CIN may have positive correlations with angiogenesis through expression of IL-6-VEGFA axis and be used as a potential predictor of efficacy of bevacizumab.

Our study aims to determine the predictors and patterns of relapses after curative colorectal liver metastasis (CRLM) resection.

A single-centre, retrospective study of CRLM patients operated between 2010 and 2022 was performed. The site of first recurrence was either hepatic (marginal (≤ 1 cm) or extramarginal), extrahepatic, or both. Factors that predicted relapse patterns and overall survival were determined by multivariable Cox regression analysis with backward elimination of variables.

The study consisted of 258 patients, with a similar proportion of synchronous (144; 56%) and metachronous(114; 43%) metastasis. At a 43-month median follow-up, 156 patients (60.4%) developed recurrences with 33 (21.1%) in the liver, 62(24.03%) extra-hepatic recurrences, and 58 (22.48%) having both. Isolated marginal liver relapses were seen in seven (9.89%) liver recurrence patients. The median overall and relapse-free survivals were 38 months (30-54) and 13 months (11-16), respectively. The 3-year liver-relapse-free survival was 54.4% (44.9-60.6). Size of liver metastases > 5 cm (HR 2.06 (1.34-3.17), involved surgical margins (HR 2.16 (1.27-3.68)), and adjuvant chemotherapy (HR 1.89 (1.07-3.35)) were predictors of hepatic recurrences. Node positivity of primary (HR 1.61 (1.02-2.56)), presence of baseline extra-hepatic metastases (HR 0.30 (0.18-0.51)), size of liver metastases > 5 cm (HR 2.02 (1.37-2.99)), poorly differentiated histology (HR 2.25 (1.28-3.49)), presence of LVI (HR 2.25 (1.28-3.94)), and adjuvant chemotherapy (HR 2.15 (1.28-3.61)) were predictors of extra-hepatic recurrences.

The study found majority relapses occurred at extrahepatic sites whilst isolated marginal recurrences were few. The consistent predictors of recurrence were size and inability to deliver adjuvant therapy. A tailored adjuvant therapy might improve outcomes after liver metastasectomy in colorectal cancers.

The combination of preoperative chemotherapy and surgical treatment has been shown to significantly enhance the prognosis of colorectal cancer with liver metastases (CRLM) patients. Nevertheless, as a result of variations in clinicopathological parameters, the prognosis of this particular group of patients differs considerably. This study aimed to develop and evaluate Cox proportional risk regression model and competing risk regression model using two patient cohorts. The goal was to provide a more precise and personalized prognostic evaluation system.

We collected information on individuals who had a pathological diagnosis of colorectal cancer between 2000 and 2019 from the Surveillance, Epidemiology, and End Results (SEER) Database. We obtained data from patients who underwent pathological diagnosis of colorectal cancer and got comprehensive therapy at the hospital between January 1, 2010, and June 1, 2022. The SEER data collected after screening according to the inclusion and exclusion criteria were separated into two cohorts: a training cohort (training cohort) and an internal validation cohort (internal validation cohort), using a random 1:1 split. Subgroup Kaplan-Meier (K-M) survival analyses were conducted on each of the three groups. The data that received following screening from the hospital were designated as the external validation cohort. The subsequent variables were chosen for additional examination: age, gender, marital status, race, tumor site, pretreatment carcinoembryonic antigen level, tumor size, T stage, N stage, pathological grade, number of tumor deposits, perineural invasion, number of regional lymph nodes examined, and number of positive regional lymph nodes. The primary endpoint was median overall survival (mOS). In the training cohort, we conducted univariate Cox regression analysis and utilized a stepwise regression approach, employing the Akaike information criterion (AIC) to select variables and create Cox proportional risk regression models. We evaluated the accuracy of the model using calibration curve, receiver operating characteristic curve (ROC), and area under curve (AUC). The effectiveness of the models was assessed using decision curve analysis (DCA). To evaluate the non-cancer-related outcomes, we analyzed variables that had significant impacts using subgroup cumulative incidence function (CIF) and Gray's test. These analyses were used to create competing risk regression models. Nomograms of the two models were constructed separately and prognostic predictions were made for the same patients in SEER database.

This study comprised a total of 735 individuals. The mOS of the training cohort, internal validation cohort, and QDU cohort was 55.00 months (95%CI 46.97-63.03), 48.00 months (95%CI 40.65-55.35), and 68.00 months (95%CI 54.91-81.08), respectively. The multivariate Cox regression analysis revealed that age, N stage, presence of perineural infiltration, number of tumor deposits and number of positive regional lymph nodes were identified as independent prognostic risk variables (p < 0.05). In comparison to the conventional TNM staging model, the Cox proportional risk regression model exhibited a higher C-index. After controlling for competing risk events, age, N stage, presence of perineural infiltration, number of tumor deposits, number of regional lymph nodes examined, and number of positive regional lymph nodes were independent predictors of the risk of cancer-specific mortality (p < 0.05).

We have developed a prognostic model to predict the survival of patients with synchronous CRLM who undergo preoperative chemotherapy and surgery. This model has been tested internally and externally, confirming its accuracy and reliability.

As the hallmark of cancer, genetic and phenotypic heterogeneity leads to biomarkers that are typically tailored to specific cancer type or subtype. This specificity introduces complexities in facilitating streamlined evaluations across diverse cancer types and optimizing therapeutic outcomes. In this study, we comprehensively characterized the radiological patterns underlying liver cancer (LC) by integrating radiomics profiles from computed tomography (CT) images of hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC), and colorectal cancer liver metastases (CRLM) through unsupervised clustering analysis. We identified three distinct radiomics clusters, displaying heterogeneity in prognosis. Subsequently, we formulated a shared prognosticator, the liver cancer radiomics signature (LCRS), by discovering and manifesting connectivity among radiomics phenotypes using GGI strategy. We validated that the LCRS is independent prognostic factor after adjusting for clinic-pathologic variables (all P < 0.05), with the LCRS-High group consistently associated with worse survival outcomes across HCC, ICC, and CRLM. However, the LCRS-High group showed clinical benefit from adjuvant chemotherapy, leading to reduced disease recurrence risk and improved survival. By contrast, the LCRS-Low group, including a subset of gastric cancer liver metastases (GCLM), exhibited more favorable response to immune checkpoint inhibitors (ICIs)-based combinational therapy (P = 0.02, hazard ratio (HR): 0.34 [95 % confidence interval (CI): 0.13-0.88]). Further analysis revealed that Notch signaling pathway was enriched in LCRS-High tumors, while LCRS-Low tumors exhibited higher infiltration of natural killer cell. These findings highlight the promise of this universal scoring model to personalize management strategies for patients with LC.

Approximately 25% of patients with stage III colorectal cancer experience liver metastasis after radical resection; however, there is currently a lack of methods to predict liver metastasis. This study aims to develop and validate a pathomics nomogram to predict liver metastasis in patients with stage III colorectal cancer.

A total of 318 enrolled patients were divided into three cohorts: a training cohort (n = 139), a validation cohort (n = 69), and an external cohort (n = 110). A competitive risk nomogram was established by the pathomics signature and clinicopathological characteristics and assessed by calibration, discrimination, and clinical usefulness.

A significant correlation between the pathomics signature and liver metastasis in stage III colorectal cancer was found. Multivariate Fine-Gray analysis indicated that preoperative carcinoembryonic antigen level, postoperative chemotherapy, and pathomics signature were independent predictors of liver metastasis. A competitive risk nomogram was developed to predict liver metastasis in patients with stage III colorectal cancer. The predicting nomogram shows good discrimination and calibration, with C-indexes of 0.811 (95% confidence interval [CI] 0.651-0.971), 0.759 (95% CI 0.531-0.987), and 0.845 (95% CI 0.641-0.999), with area under the receiver operating characteristic (AUROC) curves at 5 years of 0.833 (95% CI 0.742-0.925), 0.760 (95% CI 0.652-0.893), and 0.812 (95% CI 0.692-0.931) in the training, validation, and external cohorts, respectively. Compared with the clinicopathological nomogram, the nomogram combined with the pathomics signature had better performance (AUROC 0.823 [95% CI 0.764-0.881] vs. 0.678 [95% CI 0.606-0.751]; p < 0.001).

The pathomics signature is a predictive indicator for liver metastasis in patients with stage III colorectal cancer, and the integrated nomogram can be used to predict liver metastasis better than the clinicopathological nomogram alone.

Literature shows differences in pain experiences between sexes. The exact influence of thermal liver ablation on experienced pain is still not well-known. This study aims to investigate the maximum pain intensity at the recovery between men and women after percutaneous thermal liver ablation.

Patients treated with percutaneous thermal liver ablation (radiofrequency or microwave ablation) in Maastricht University Medical Center + between 2018 and 2022 for primary or secondary liver tumors were included retrospectively. Outcomes included maximum numerical rating scale (NRS, scale:0-10) score at the recovery room, prevalence of post-procedural pain (defined as NRS score ≥ 4), duration of anesthesia, length of stay at recovery, and complications. Regression analyses were adjusted for age, ASA-score, BMI, tumor type, maximum diameter of lesion, chronic pain in patients' history, and history of psychological disorder.

183 patients were included of which 123 men (67%). Results showed higher average maximum NRS scores in women patients compared to men (mean:3.88 versus 2.73), but not after adjustments (aß:0.75, 95%CI:-0.13-1.64). Women suffered more from acute post-procedural pain (59% versus 35%; aOR:2.50, 95%CI:1.16-5.39), and needed analgesics more often at the recovery room (aOR:2.43, 95%CI:1.07-5.48) compared to men. NRS score at recovery arrival did not significantly differ (aß:0.37, 95%CI:-0.48-1.22). No differences were seen in the length of stay at the recovery, duration of anesthesia, procedure time, and complication rate. Location of the tumor (subcapsular or deep), total tumors per patient, and distinction between primary and secondary tumors had no influence on the NRS.

This retrospective single-center study shows higher post-procedural pain rates after thermal liver ablation in women, resulting in higher analgesics use at the recovery room. The results suggest considering higher dosage of analgesics during thermal liver ablation in women to reduce post-procedural pain. LEVEL OF EVIDENCE 3: Non-controlled retrospective cohort study.

We evaluated modulation of the immunosuppressive tumor microenvironment in both local and liver metastatic colorectal cancer (LMCC), focusing on tumor-associated macrophages, which are the predominant immunosuppressive cells in LMCC. We developed an orally administered metronomic chemotherapy regimen, oral CAPOX. This regimen combines capecitabine and a nano-micelle encapsulated, lysine-linked deoxycholate and oxaliplatin complex (OPt/LDC-NM). The treatment effectively modulated immune cells within the tumor microenvironment by activating the cGAS-STING pathway and inducing immunogenic cell death. This therapy modulated immune cells more effectively than did capecitabine monotherapy, the current standard maintenance chemotherapy for colorectal cancer. The macrophage-modifying effect of oral CAPOX was mediated via the cGAS-STING pathway. This is a newly identified mode of immune cell activation induced by metronomic chemotherapy. Moreover, oral CAPOX synergized with anti-PD-1 antibody (αPD-1) to enhance the T-cell-mediated antitumor immune response. In the CT26. CL25 subcutaneous model, combination therapy achieved a 91 % complete response rate with a confirmed memory effect against the tumor. This combination also altered the immunosuppressive tumor microenvironment in LMCC, which αPD-1 monotherapy could not achieve. Oral CAPOX and αPD-1 combination therapy outperformed the maximum tolerated dose for treating LMCC, suggesting metronomic therapy as a promising strategy.

While thermal ablation is now a standard treatment option for oligometastatic colorectal cancer patients, selecting those who will benefit most from locoregional therapies remains challenging. This proof-of-concept study is the first to assess the feasibility of routine testing of ctDNA before and after thermal ablation with curative intent, analyzed by next-generation sequencing (NGS) and methylation specific digital droplet PCR (ddPCR). Our prospective study primary objective was to assess the prognostic value of ctDNA before thermal ablation.

This single-center prospective study from November 2021 to June 2022 included colorectal cancer patients referred for curative-intent thermal ablation. Cell-free DNA was tested at different time points by next-generation sequencing and detection of WIF1 and NPY genes hypermethylation using ddPCR. The ctDNA was considered positive if either a tumor mutation or hypermethylation was detected; recurrence-free survival was used as the primary endpoint.

The study enrolled 15 patients, and a total of 60 samples were analyzed. The median follow-up after ablation was 316 days, and median recurrence-free survival was 250 days. CtDNA was positive for 33% of the samples collected during the first 24 h. The hazard ratio for progression according to the presence of baseline circulating tumor DNA was estimated at 0.14 (CI 95%: 0.03-0.65, p = 0.019). The dynamics are provided, and patients with no recurrence were all negative at H24 for ctDNA.

This study shows the feasibility of routine testing of ctDNA before and after thermal ablation with curative intent. We report that circulating tumor DNA is detectable in patients with low tumor burden using 2 techniques. This study emphasizes the potential of ctDNA for discerning patients who are likely to benefit from thermal ablation from those who may not, which could shape future referrals. The dynamics of ctDNA before and after ablation shed light on the need for further research and larger studies.

The present study aimed to validate the accuracy of a tumor-specific antibody to target liver metastases of colorectal cancer.

A humanized anti-CEA antibody conjugated to a fluorescent dye (M5A-IR800) was tested for targeting human colorectal cancer liver metastases (CRLMs) expressing luciferase in an orthotopic mouse model. Orthotopic mouse models of CRLMs were established by implanting fragments of a luciferase-expressing human colorectal cancer cell line, LS174T, in the liver of nude mice. Mice received 50 µg M5A-IR800 72 h prior to imaging. To test co-localization, bioluminescence imaging was performed using D-luciferin, which was given via intraperitoneal injection just prior to imaging.

Tumors were able to be visualized non-invasively through the skin with the luciferase-luciferin signal. Intra-abdominal imaging showed accurate labeling of CRLMs with M5A-IR800, which co-localized with the luciferase-luciferin signal.

The present results validate the accuracy of a tumor-specific anti-CEA antibody in targeting liver metastases of colorectal cancer.

Tertiary lymphoid structures (TLSs) are associated with enhanced immunity in tumors. However, their formation and functions in colorectal cancer liver metastasis (CRLM) remain unclear. Here, we reveal that intra- and peri-tumor mature TLSs (TLS+) are associated with improved clinical outcomes than TLS- tumors. Using single-cell-RNA-sequencing and spatial-enhanced-resolution-omics-sequencing (Stereo-seq), we reveal that TLS+ tumors are enriched with IgG+ plasma cells (PCs), while TLS- tumors are characterized with IgA+ PCs. By generating TLS-associated PC-derived monoclonal antibodies in vitro, we show that TLS-PCs secrete tumor-targeting antibodies. As the proof-of-concept, we demonstrate the anti-tumor activities of TLS-PC-mAb6 antibody in humanized mouse model of colorectal cancer. We identify a fibroblast lineage secreting CCL19 that facilitates lymphocyte trafficking to TLSs. CCL19 treatment promotes TLS neogenesis and prevents tumor growth in mice. Our data uncover the central role of CCL19+ fibroblasts in TLS formation, which in turn generates therapeutic antibodies to restrict CRLM.

This study aimed to assess the prognostic value of total tumor volume (TTV) for early recurrence (within 6 months) and overall survival (OS) in patients with colorectal liver metastases (CRLM), treated with induction systemic therapy followed by complete local treatment.

Patients with initially unresectable CRLM from the multicenter randomized phase 3 CAIRO5 trial (NCT02162563) who received induction systemic therapy followed by local treatment were included. Baseline TTV and change in TTV as response to systemic therapy were calculated using the CT scan before and the first after systemic treatment, and were assessed for their added prognostic value. The findings were validated in an external cohort of patients treated at a tertiary center.

In total, 215 CAIRO5 patients were included. Baseline TTV and absolute change in TTV were significantly associated with early recurrence (P = 0.005 and P = 0.040, respectively) and OS in multivariable analyses (P = 0.024 and P = 0.006, respectively), whereas RECIST1.1 was not prognostic for early recurrence (P = 0.88) and OS (P = 0.35). In the validation cohort (n = 85), baseline TTV and absolute change in TTV remained prognostic for early recurrence (P = 0.041 and P = 0.021, respectively) and OS in multivariable analyses (P < 0.0001 and P = 0.012, respectively), and showed added prognostic value over conventional clinicopathological variables (increase C-statistic, 0.06; 95 % CI, 0.02 to 0.14; P = 0.008).

Total tumor volume is strongly prognostic for early recurrence and OS in patients who underwent complete local treatment of initially unresectable CRLM, both in the CAIRO5 trial and the validation cohort. In contrast, RECIST1.1 did not show prognostic value for neither early recurrence nor OS.

To compare the results of CT- vs MR-guided radiofrequency ablation (RFA) of liver metastases (LM) from colorectal cancer after 10 years of follow-up in an observational, retrospective, and multicentric study.

A total of 238 patients with 496 LM were treated with RFA either with CT (CT group) or magnetic resonance (MR group) guidance. Every ablated LM was assessed and followed up with diagnostic MRI. Technical success, technique efficacy, predictive factors, recurrence rates, and overall survival were assessed.

The CT group comprised 143 patients and the MR group 77 patients. Eighteen patients underwent ablation with both modalities. Technical success per patient and per lesion was 88% and 93% for CT and 87% and 89.6% for MR, and technique efficacy was 97.1% and 98.6% for CT and 98.7% and 99.3% for MR respectively. Local recurrence following the first ablation (primary patency) occurred in 20.1% (CT) vs 4.6% (MR) (p < 0.001). Residual liver tumor, size of LM, and advanced N and M stage at initial diagnosis were independent predictors for overall survival in both groups. The median overall survival measured from first RFA treatment was 2.6 years. The 1-year, 5-year, and 10-year survival were 85.9%, 25.5%, and 19.1% respectively.

The MR group had significantly better local control compared to the CT group. There was no significant difference in patient survival between the two groups.

MR-guided radiofrequency ablation of colorectal liver metastases is safe and effective, and offers better local control than CT-guided ablation.

• Imaging modality for radiofrequency ablation guidance is an independent predictor of local recurrence in colorectal liver metastases. • MR-guided radiofrequency ablation achieved better local control of liver metastases from colorectal cancer than CT-guided. • The number and size of liver metastases are, among others, independent predictors of survival. Radiofrequency ablation with MR guidance improved clinical outcome but does not affect survival.

Carcinoembryonic antigen (CEA) is a broad-spectrum tumor marker for differential diagnosis, monitoring, and response assessment of a variety of malignancies. This meta-analysis was aimed at evaluating whether serum CEA could predict the prognosis in patients with colorectal cancer liver metastasis (CRCLM) before and after liver resection (LR).

PubMed, Embase, Cochrane, and Web of Science were systematically searched to retrieve literature, with a search cutoff date of 27 February 2023. Articles were strictly screened for inclusion according to pre-specified inclusion and exclusion criteria. Data were pooled and analyzed using Stata 16.0.

This meta-analysis included 36 studies involving a total of 11 143 CRCLM patients. The results showed that a high pre-LR serum CEA level was correlated with poor overall survival (OS: HR = 1.61, 95% CI = 1.49-1.75, P  < 0.001) and recurrence-free survival (RFS: HR = 1.27, 95% CI = 1.11-1.45, P  < 0.001) in CRCLM patients. A high post-LR serum CEA level predicted poor overall survival (OS: HR = 2.66, 95% CI = 2.10-3.38, P  < 0.001).

High preoperative and postoperative serum CEA levels in patients with CRCLM were significantly associated with poor prognosis, independent of treatment modality, mode of analysis, case origin, and cutoff value classification.

Plasma circulating tumor DNA (ctDNA) is a promising biomarker for metastatic colorectal cancer (mCRC); however, its role in characterizing recurrence sites after mCRC resection remains poorly understood. This single-institution study investigated the timing of ctDNA detection and its levels in the context of recurrence at different sites after mCRC resection.

Patients who underwent optimal resection of CRC metastases involving the peritoneum, distant lymph nodes, or liver, with serial postoperative tumor-informed ctDNA assessments (Signatera) were included. Recurrence sites, as defined by surveillance imaging or laparoscopy, were categorized as peritoneal-only and other distant sites (liver, lung, lymph nodes, or body wall).

Among the 31 included patients, ctDNA was detected in all 26 (83.4%) patients with postoperative recurrence and was persistently undetectable in 5 patients who did not experience recurrence. At 3 months postsurgery, ctDNA was detected in 2 (25%) of 8 patients with peritoneal-only recurrence and 17 (94.4%) of 18 patients with distant recurrence (p < 0.001). Beyond 3 months, ctDNA was detected in the remaining 6 patients with peritoneal-only disease and 1 patient with distant disease. ctDNA detection preceded the clinical diagnosis of recurrence by a median of 9 weeks in both groups. At recurrence, peritoneal-only recurrent cases exhibited lower ctDNA levels (median 0.4 mean tumor molecules/mL, interquartile range 0.1 to 0.8) compared with distant recurrence (median 5.5 mean tumor molecules/mL, interquartile range 0.8 to 33.3, p = 0.004).

Peritoneal-only recurrence was associated with delayed ctDNA detection and low levels of ctDNA after optimal resection for mCRC. ctDNA testing may effectively characterize recurrence sites and may help guide subsequent treatments specific to the disease sites involved.

Approximately 60% of patients with colorectal liver metastases (CRLM) experience relapse within 2 years after radical resection, previous studies have proven that repeat local treatment (LT) could prolong survival, however, it is difficult to seize the window for LT due to the lack of a high-sensitive surveillance method. In this study, the authors aim to examine the value of longitudinal circulating tumor DNA (ctDNA) in guiding adjuvant chemotherapy, optimizing clinical surveillance strategy, and thereby improving CRLM outcomes.

The authors conducted a prospective clinical trial using a personalized, tumor-informed ctDNA assay to monitor 60 CRLM patients undergoing resection with curative intent. Formalin-fixed paraffin-embedded tumor samples were collected after surgery. Blood samples were collected before surgery, 30 days after surgery (post-OP), and every third month until relapse or up to 2 years.

A total of 394 plasma samples from 60 eligible patients were analyzed, with a median follow-up time of 31.3 months. Landmark analyses revealed that detectable ctDNA at post-OP (HR, 4.8), postadjuvant chemotherapy (HR, 6.0), and end-of-treatment (HR, 5.6) were associated with higher recurrence risk ( P <0.001). Post-OP ctDNA positivity served as the only independent prognostic marker in the multivariant analysis (HR, 5.1; P <0.001). Longitudinal ctDNA analysis identified relapsed patients at both sensitivity and specificity of 100%. Most (75%) patients were found with radiological relapse within 6 months after the first detectable ctDNA with a median lead time of 3.5 months. In relapsed patients, 73.2% had oligometastatic disease and 61% were liver-restricted, of which 72.0% received repeat LTs, and 60.0% achieved a secondary no evidence of disease status.

Longitudinal ctDNA monitoring assists in early prediction of relapse, and thereby improves survival of CRLM patients by increased secondary resection rate and secondary no evidence of disease rate.

Colorectal cancer is the second most common cause of cancer death in the United States, and up to half of patients develop colorectal liver metastases (CRLMs). Notably, somatic genetic mutations, such as mutations in RAS, BRAF, mismatch repair (MMR) genes, TP53, and SMAD4, have been shown to play a prognostic role in patients with CRLM. This review summarizes and appraises the current literature regarding the most relevant somatic mutations in surgically treated CRLM by not only reviewing representative studies, but also providing recommendations for areas of future research. In addition, advancements in genetic testing and an increasing emphasis on precision medicine have led to a more nuanced understanding of these mutations; thus, more granular data for each mutation are reviewed when available. Importantly, such knowledge can pave the way for precision medicine with the ultimate goal of improving patient outcomes.

More accurate prediction of distant metastases (DM) in patients with colorectal cancer (CRC) would optimize individualized treatment and follow-up strategies. Multiple prediction models based on machine learning have been developed to assess the likelihood of developing DM.

Clinicopathological features of patients with CRC were obtained from the National Cancer Center (NCC, China) and the Surveillance, Epidemiology, and End Results (SEER) database. The algorithms used to create the prediction models included random forest (RF), logistic regression, extreme gradient boosting, deep neural networks, and the K-Nearest Neighbor machine. The prediction models' performances were evaluated using receiver operating characteristic (ROC) curves.

In total, 200,958 patients, 3241 from NCC and 197,717 CRC from SEER were identified, of whom 21,736 (10.8%) developed DM. The machine-learning-based prediction models for DM were constructed with 12 features remaining after iterative filtering. The RF model performed the best, with areas under the ROC curve of 0.843, 0.793, and 0.806, respectively, on the training, test, and external validation sets. For the risk stratification analysis, the patients were separated into high-, middle-, and low-risk groups according to their risk scores. Patients in the high-risk group had the highest incidence of DM and the worst prognosis. Surgery, chemotherapy, and radiotherapy could significantly improve the prognosis of the high-risk and middle-risk groups, whereas the low-risk group only benefited from surgery and chemotherapy.

The RF-based model accurately predicted the likelihood of DM and identified patients with CRC in the high-risk group, providing guidance for personalized clinical decision-making.

Colorectal cancer is the third most common cancer in the United States and the second most common cause of cancer-related death. Approximately 20-30% of patients will develop hepatic metastasis in the form of synchronous or metachronous disease. The treatment of colorectal liver metastasis (CRLM) has evolved into a multidisciplinary approach, with chemotherapy and a variety of locoregional treatments, such as ablation and portal vein embolization, playing a crucial role. However, resection remains a core tenet of management, serving as the gold standard for a curative-intent therapy. As such, the input of a dedicated hepatobiliary surgeon is paramount for appropriate patient selection and choice of surgical approach, as significant advances in the field have made management decisions extremely nuanced and complex. We herein aim to review the contemporary surgical management of colorectal liver metastasis with respect to both perioperative and operative considerations.

In 2007, the ASSO-LM1 trial, a multicenter prospective study, was initiated to investigate the resectability (R0) rate following preoperative combination therapy with XELOX and bevacizumab in patients with potentially resectable colorectal liver metastases. Six cycles of systemic therapy were administered preoperatively, although the sixth cycle did not include bevacizumab, resulting in 5 weeks between the last bevacizumab dose and surgery. Treatment with bevacizumab plus XELOX was restarted for another six cycles postoperatively. In total, 43 patients were enrolled in the ASSO-LM1 trial. Eight patients were ineligible for resection due to protocol violation and progression in two patients. The resectability of operated patients was 97% with 34 R0 resections and one R1 resection. Postoperative morbidity occurred in 22% of patients, of which three operative revisions were related to the primary tumor resection. Efficacy results for response in 38 eligible patients confirmed an ORR of 66%, 31% SD and 3% PD according to RECIST. Preoperative grade 3/4 adverse events were 17% diarrhea, 5% HFS and 5% thromboembolic events. Overall survival significantly differed depending upon the fulfillment of adjuvant treatment in curative resected patients (59.1 mo vs. 30.8 mo). In conclusion, the ASSO-LM1 trial is a hypothesis-generating study confirming the prognostic benefits of perioperative therapy with XELOX and bevacizumab in patients with metastatic colorectal cancer confined to the liver.

To investigate the prognostic impact of RAS mutations on the Japanese Society of Hepatobiliary and Pancreatic Surgeons (JSHBPS) nomogram score in patients with colorectal cancer liver metastasis (CRLM) following hepatectomy.

We included 218 consecutive patients undergoing hepatectomy for CRLM between 2004 and 2020. The JSHBPS nomogram score was calculated using six preoperative clinical factors. The score ranged from 0 to 25, and higher scores indicated greater tumor burden. Associations of RAS mutations with disease-free survival (DFS) and overall survival (OS) by the JSHBPS nomogram score were examined. Multivariable Cox proportional hazard regression models were used to estimate adjusted hazard ratios (HRs) and confidence intervals (CIs).

RAS mutations were detected in 72 (33%) of the 218 patients. Multivariate analyses revealed that RAS mutations were independently associated with poor DFS (HR, 1.93; 95% CI: 1.20-3.10; p = .007) and OS (HR, 2.65; 95% CI: 1.59-4.71; p = .001) compared with wild-type RAS with JSHBPS nomogram scores ≤ 10. However, in patients with scores ≥ 11, the association of RAS mutations with DFS or OS was not statistically significant (p > .08).

RAS mutation status in combination with the JSHBPS nomogram may be useful for preoperatively identifying CRLM with high risk of recurrence and mortality after hepatectomy.

Colorectal cancer (CRC) is the third most commonly diagnosed cancer in men and women (Siegel et al. in CA Cancer J Clin 72(1):7-33). Over one-half of newly diagnosed individuals will develop liver metastases. Among those with liver-only metastatic disease, only about one in five will be candidates for potentially curable resection.

In two-stage hepatectomy for bilobar liver metastases from colorectal cancer, future liver remnant (FLR) growth can be achieved using several techniques, such as right portal vein ligation (RPVL) or right portal vein embolization (RPVE). A few heterogeneous studies have compared these two techniques with contradictory results concerning FLR growth. The objective of this study was to compare FLR hypertrophy of the left hemi-liver after RPVL and RPVE.

This was a retrospective comparative study using a propensity score of patients who underwent RPVL or RPVE prior to major hepatectomy between January 2010 and December 2020. The endpoints were FLR growth (%) after weighting using the propensity score, which included FLR prior to surgery and the number of chemotherapy cycles. Secondary endpoints were the percentage of patients undergoing simultaneous procedures, the morbidity and mortality, the recourse to other liver hypertrophy procedures, and the number of invasive procedures for the entire oncologic program in intention-to-treat analysis.

Fifty-four consecutive patients were retrospectively included and analyzed, 18 in the RPVL group, and 36 in the RPVE group. The demographic characteristics were similar between the groups. After weighting, there was no significant difference between the RPVL and RPVE groups for FLR growth (%), respectively 32.5% [19.3-56.0%] and 34.5% [20.5-47.3%] (p = 0.221). There was no significant difference regarding the secondary outcomes except for the lower number of invasive procedures in RPVL group (median of 2 [2.0, 3.0] in RPVL group and 3 [3.0, 3.0] in RPVE group, p = 0.001)).

RPVL and RPVE are both effective to provide required left hemi-liver hypertrophy before right hepatectomy. RPVL should be considered for the simultaneous treatment of liver metastases and the primary tumor.

Carcinoembryonic antigen (CEA) is a broad-spectrum tumor marker for differential diagnosis, monitoring, and response assessment of a variety of malignancies.

To evaluate whether serum CEA could predict the prognosis in patients with colorectal cancer liver metastasis (CRCLM) before and after liver resection (LR).

PubMed, Embase, Cochrane, and Web of Science were systematically searched to retrieve literature, with a search cut-off date of February 27, 2023. Articles were strictly screened for inclusion according to pre-specified inclusion and exclusion criteria. Data were pooled and analyzed using Stata 16.0.

This meta-analysis included 36 studies involving a total of 11143 CRCLM patients. The results showed that a high pre-LR serum CEA level was correlated with poor overall survival (OS) [hazard ratio (HR) = 1.61, 95% confidence interval (CI): 1.49-1.75, P < 0.001] and recurrence-free survival (HR = 1.27, 95%CI: 1.11-1.45, P < 0.001) in CRCLM patients. A high post-LR serum CEA level predicted poor OS (HR = 2.66, 95%CI: 2.10-3.38, P < 0.001). A comparison by treatment modality, analysis modality, patient source, and cutoff-value showed that overall, high preoperative and postoperative serum CEA levels remained correlated with a poor prognosis.

This study concluded that high pre-LR and post-LR serum CEA levels were significantly correlated with a poor prognosis in CRCLM patients.

Liver metastasis is one of the most common causes of death in patients with colorectal cancer. Therefore, improving the treatment effect of liver metastatic carcinoma of colorectal cancer is also one of the effective ways to improve the survival time of patients with colorectal cancer. The main treatment method for liver metastasis of colorectal cancer is preoperative neoadjuvant chemotherapy through intravenous administration. However, no one has reported a conversion therapy approach for the treatment of colorectal cancer liver metastases patients through arterial infusion chemotherapy combined with targeted agents and PD-1 monoclonal antibody. This case reports a conversion therapy method of liver metastases of colorectal cancer by hepatic arterial infusion chemotherapy (HAIC), sintilimab injection combined with lenvatinib to achieve radical resection of liver metastatic carcinoma after treatment.

The patient was a 69-year-old man who had previously undergone laparoscopic left hemicolectomy for descending colorectal cancer and multiple interventional and surgical treatments for hepatocellular carcinoma. During this treatment, the patient underwent radiological and serological tests, and primary liver cancer was considered at the initial diagnosis stage. Therefore, this liver malignant tumor lesion was treated according to the primary liver cancer treatment protocol before surgical resection. Therefore, the patient received HAIC combined with sintilimab injection and lenvatinib. After three treatment cycles, radiological examination showed no obvious tumor activity, alpha-fetoprotein (AFP) decreased to normal, protein induced by vitamin K absence or antagonist II (PIVKA II) decreased significantly, and the curative effect was evaluated as complete remission. Subsequently, we performed surgical resection of this liver lesion. The pathological response of left lobe tumor was partial remission (PR). Most of the tumors were necrotic and the necrosis rate was greater than 95%. A small amount of live tumor tissue remains (<5%). The pathological classification of this tumor was confirmed as moderately differentiated adenocarcinoma by immunohistochemical staining of multiple tumor indicators in the pathology department. No significant adverse drug events were observed in this patient during treatment.

Hepatic arterial infusion chemotherapy combined with sintilimab injection and lenvatinib conversion therapy provides the opportunity for radical surgical resection of colorectal cancer liver metastases.

Introduction: ALPPS (Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy), is a recently developed procedure, first performed by HJ Schlitt in Regensburg, Germany. The technique developed two stages of hepatectomy. The ALPPS procedure has been introduced to increase the volume of future liver remnant, much more than the other technique, such as PVE (portal vein embolization). The first ALPPS in our country was introduced and performed by our team on May 15th, 2018. Results: The 60-year-old patient was previously operated on for rectal cancer in 2017 at another institution. The operation was performed with anterior resection and the patient was in long term adjuvant chemotherapy. One year after surgery, the patient has multiple bilobar liver metastases and increased tumor markers that led to instant admission to our institution for liver resection. In the first stage, we performed four metastasectomies on the left lobe with right portal vein ligation and transection on the Cantlie line. The second stage was performed after a CT evaluation on the eighth day, with significant hypertrophy on the left lobe. Pathological findings reported ten metastases on the right lobe with a diameter 1-3 cm. The patient was on the long-term chemotherapy, and after one year he had other MS in the IVa segment of the liver. We also performed a metastasectomy. The patient died 32 months after ALPPS. Conclusion: ALPPS is a safe and feasible procedure for the treatment of bilobar liver metastasis from colorectal cancer. It could provide long-term survival for patients.

More than 50% of patients with colorectal cancer develop liver metastases. Hepatectomy is the preferred treatment for resectable liver metastases. This review provides a perspective on the utility and relevant prognostic factors of repeat hepatectomy in recurrent colorectal liver metastasis (CRLM).

The keywords "recurrent colorectal liver metastases", "recurrent hepatic metastases from colorectal cancer", "liver metastases of colorectal cancer", "repeat hepatectomy", "repeat hepatic resection", "second hepatic resection", and "prognostic factors" were used to retrieve articles published in the PubMed database up to August 2020. Additional articles were identified by a manual search of references from key articles.

Despite improvements in surgical methods and perioperative chemotherapy, recurrence remains common in 37%-68% of patients. Standards or guidelines for the treatment of recurrent liver metastases are lacking. Repeat hepatectomy appears to be the best option for patients with resectable metastases. The commonly reported prognostic factors after repeat hepatectomy were R0 resection, carcinoembryonic antigen level, the presence of extrahepatic disease, a short disease-free interval between initial and repeat hepatectomy, the number (> 1) and size (≥ 5 cm) of hepatic lesions, requiring blood transfusion, and no adjuvant chemotherapy after initial hepatectomy. The median overall survival after repeat hepatectomy ranged from 19.3 to 62 months, and the 5-year overall survival ranged from 21% to 73%. Chemotherapy can act as a test for the biological behavior of tumors with the goal of avoiding unnecessary surgery, and a multimodal approach involving aggressive chemotherapy and repeat hepatectomy might be the treatment of choice for patients with early recurrent CRLM.

Repeat hepatectomy is a relatively safe and effective treatment for resectable recurrent CRLM. The presence or absence of prognostic factors might facilitate patient selection to improve short- and long-term outcomes.

Although surgical resection could provide better survival for patients with colorectal cancer liver metastases (CRLM), the recurrence rate after resection of CRLM remains high. The progress of genome sequencing technologies has greatly improved the molecular understanding of colorectal cancer. In the era of genomics and targeted therapy, genetic mutation analysis is of great significance to guide systemic treatment and identify patients who can benefit from resection of CRLM. RAS and BRAF mutations and microsatellite instability/deficient deoxyribonucleic acid (DNA) mismatch repair status have been incorporated into current clinical practice. Other promising molecular biomarkers such as coexisting gene mutations and circulating tumor DNA are under active investigation. This study aimed to review the prognostic significance of molecular biomarkers in patients with CRLM undergoing metastasectomy based on the current evidence.

Various predictive scoring systems have been developed to estimate outcomes of patients undergoing surgery for colorectal liver metastases (CRLM). However, data regarding their effectiveness in recurrent CRLM (recCRLM) are very limited.

Patients who underwent repeat hepatectomy for recCRLM at the University Hospital RWTH Aachen, Germany from 2010 to 2021 were included. Nine predictive scoring systems (Fong's, Nordlinger, Nagashima, RAS mutation, Tumor Burden, GAME, CERR, and Glasgow Prognostic score, Basingstoke Index) were evaluated by likelihood ratio (LR) χ2, linear trend (LT) χ2 and Akaike Information Criterion (AIC) for their predictive value regarding overall survival (OS) and recurrence free survival (RFS).

Among 150 patients, median RFS was 9 (2-124) months with a 5-year RFS rate of 10%. Median OS was 39 (4-131) months with a 5-year OS rate of 32%. For RFS and OS, the Nagashima score showed the best prognostic ability (LT χ2 3.00, LR χ2 9.39, AIC 266.66 and LT χ2 2.91, LR χ2 20.91, 290.36).

The Nagashima score showed the best prognostic stratification to predict recurrence as well as survival, and therefore might be considered when evaluating patients with recCRLM for repeat hepatectomy.