Resection Of Colorectal Cancer Liver Metastases Research Articles

A New Automated Prognostic Prediction Method Based on Multi-Sequence Magnetic Resonance Imaging for Hepatic Resection of Colorectal Cancer Liver Metastases.

Colorectal cancer is a prevalent and life-threatening disease, where colorectal cancer liver metastasis (CRLM) exhibits the highest mortality rate. Currently, surgery stands as the most effective curative option for eligible patients. However, due to the insufficient performance of traditional methods and the lack of multi-modality MRI feature complementarity in existing deep learning methods, the prognosis of CRLM surgical resection has not been fully explored. This paper proposes a new method, multi-modal guided complementary network (MGCNet), which employs multi-sequence MRI to predict 1-year recurrence and recurrence-free survival in patients after CRLM resection. In light of the complexity and redundancy of features in the liver region, we designed the multi-modal guided local feature fusion module to utilize the tumor features to guide the dynamic fusion of prognostically relevant local features within the liver. On the other hand, to solve the loss of spatial information during multi-sequence MRI fusion, the cross-modal complementary external attention module designed an external mask branch to establish inter-layer correlation. The results show that the model has accuracy (ACC) of 0.79, the area under the curve (AUC) of 0.84, C-Index of 0.73, and hazard ratio (HR) of 4.0, which is a significant improvement over state-of-the-art methods. Additionally, MGCNet exhibits good interpretability.

Current landscape of preoperative neoadjuvant therapies for initial resectable colorectal cancer liver metastasis.

Colorectal cancer liver metastasis (CRLM) presents a clinical challenge, and optimizing treatment strategies is crucial for improving patient outcomes. Surgical resection, a key element in achieving prolonged survival, is often linked to a heightened risk of recurrence. Acknowledging the potential benefits of preoperative neoadjuvant chemotherapy in managing resectable liver metastases, this approach has gained attention for its role in tumor downsizing, assessing biological behavior, and reducing the risk of postoperative recurrence. However, the use of neoadjuvant chemotherapy in initially resectable CRLM sparks ongoing debates. The balance between tumor reduction and the risk of hepatic injury, coupled with concerns about delaying surgery, necessitates a nuanced approach. This article explores recent research insights and draws upon the practical experiences at our center to address critical issues regarding considerations for initially resectable cases. Examining the criteria for patient selection and the judicious choice of neoadjuvant regimens are pivotal areas of discussion. Striking the right balance between maximizing treatment efficacy and minimizing adverse effects is imperative. The dynamic landscape of precision medicine is also reflected in the evolving role of gene testing, such as RAS/BRAF and PIK3CA, in tailoring neoadjuvant regimens. Furthermore, the review emphasizes the need for a multidisciplinary approach to navigate the complexities of CRLM. Integrating technical expertise and biological insights is crucial in refining neoadjuvant strategies. The management of progression following neoadjuvant chemotherapy requires a tailored approach, acknowledging the diverse biological behaviors that may emerge. In conclusion, this review aims to provide a comprehensive perspective on the considerations, challenges, and advancements in the use of neoadjuvant chemotherapy for initially resectable CRLM. By combining evidence-based insights with practical experiences, we aspire to contribute to the ongoing discourse on refining treatment paradigms for improved outcomes in patients with CRLM.

Multicenter randomized phase II study on S-1 and oxaliplatin therapy as an adjuvant after hepatectomy for colorectal liver metastases (YCOG1001).

The high recurrence rate of colorectal cancer liver metastasis (CRCLM) after surgery remains a crucial problem. However, adjuvant chemotherapy after hepatectomy for CRCLM has not yet been established. This study evaluated the efficacy of adjuvant therapy with S-1 and oxaliplatin (SOX). In a multicenter, randomized, phase II study, patients undergoing curative resection of CRCLM were randomly enrolled in a 1:1 ratio to either the low- or high-dose group. S-1 and oxaliplatin were administered from days 1 to 14 of a 3-week cycle as a 2-h infusion every 3weeks. The dose of S-1 was fixed at 80mg/m2. The doses in the low- and high-dose oxaliplatin groups were 100mg/m2 (low-dose group) and 130mg/m2 (high-dose group), respectively. This treatment was repeated eight times. The primary endpoint was the rate of discontinuation owing to toxicity. The secondary endpoints were the relapse-free survival (RFS) and frequency of adverse events (AEs). Between August 2010 and March 2015, 44 patients (low-dose group: 31 patients and high-dose group: 13 patients) were enrolled in the study. Of these, one patient was excluded from the efficacy analysis. In the high-dose group, five of nine patients were unable to continue the study due to toxicity in February 2013. At that time, recruitment to the high-dose group was stopped from the protocol. The relative dose intensity (RDI) for S-1 in the low- and high-dose groups were 49.8 and 48.7% (p = 0.712), and that for oxaliplatin was 75.9 and 73.0% (p = 0.528), respectively. The rates of discontinuation due to toxicity were 60 and 53.8% in the low- and high-dose groups, respectively, with no marked difference noted between the groups (p = 0.747). The frequency of grade ≥ 3 common adverse events was neutropenia (23.3%/23.1%), diarrhea (13.3%/15.4%), and peripheral sensory neuropathy (6.7%/7.7%). The disease-free survival (DFS) at 3years was 52.9% in the low-dose group, which was not significantly different from that in the high-dose group (46.2%; p = 0.705). SOX regimens as adjuvant therapy after hepatectomy for CRCLM had high rates of discontinuation due to toxicity in both groups. In particular, the RDI of S-1 was < 50%. Therefore, the SOX regimen is not recommended as adjuvant chemotherapy after hepatectomy for CRCLM.

1282 Comparing Overall Survival and Oncological Recurrence in Laparoscopic and Open Hepatectomy for Colorectal Cancer Metastases: A Systematic Review

Abstract Aim The use of laparoscopic surgery (LS) for liver resection has risen exponentially and is competing, in popularity, with open surgery (OPS). The aim of this study is to compare the oncological recurrence and overall survival of LS and OPS approaches for colorectal cancer liver metastases resection. Method A literature search was conducted, in-line with the PRISMA guidelines, via Ovid and PubMed to collect manuscripts dated between 01/01/2010-01/03/2021. The outcomes of interest were recurrence-free survival (RFS), overall survival (OS), and negative resection margins (R0). A modified quality assessment was achieved using the Newcastle-Ottawa Score (NOS) and the ROBINS-I Tool, and the data was analysed using Stata 16.0. Results Overall, 10 studies were selected of which included a total of 1924 patients. The results show the 1-, 3- and 5-years RFS and OS for LS and OPS were comparable, therefore not significant. Whereas the R0 differences were small yet significant - the LS group had an 89.9% R0 (95% CI: 87% to 92.8%) and for OPS was 85.4% (95% CI: 81% to 88.9%), Z – score of 1.6550, p = 0.0490 (p &amp;lt; 0.05). Even though the results are not significant for RFS and OS, LS is preferable for patients in improving the quality of life in the long-term. Conclusions There is little difference between OPS and LS methods as it pertains to the quality of life. With LS being less invasive and having marginally better results, doctors should consider prioritising LS for patients with colorectal cancer liver metastasis as an alternative to OPS.

LM02 trial Perioperative treatment with panitumumab and FOLFIRI in patients with wild-type RAS, potentially resectable colorectal cancer liver metastases-a phase II study.

Twenty percent of colorectal cancer liver metastases (CLMs) are initially resectable with a 5-year survival rate of 25%-40%. Perioperative folinic acid, 5-fluorouracil, oxaliplatin (FOLFOX) increases progression-free survival (PFS). In advanced disease, the addition of targeting therapies results in an overall survival (OS) advantage. The aim of this study was to evaluate panitumumab and FOLFIRI as perioperative therapy in resectable CLM. Patients with previously untreated, wild-type Rat sarcoma virus (RAS), and resectable CLM were included. Preoperative four and postoperative eight cycles of panitumumab and folinic acid, 5-fluorouracil, irinotecan (FOLFIRI) were administered. Primary objectives were efficacy and safety. Secondary endpoints included PFS and OS. We enrolled 36 patients in seven centers in Austria (intention-to-treat analyses, 35 patients). There were 28 men and seven women, and the median age was 66 years. About 91.4% completed preoperative therapy and 82.9% underwent liver resection. The R0 resection rate was 82.7%. Twenty patients started and 12 patients completed postoperative chemotherapy. The objective radiological response rate after preoperative therapy was 65.7%. About 20% and 5.7% of patients had stable disease and progressive disease, respectively. The most common grade 3 adverse events were diarrhea, rash, and leukopenia during preoperative therapy. One patient died because of sepsis, and one had a pulmonary embolism grade 4. After surgery, two patients died because of hepatic failure. Most common grade 3 adverse events during postoperative therapy were skin toxicities/rash and leukopenia/neutropenia, and the two grade 4 adverse events were stroke and intestinal obstruction. Median PFS was 13.2 months. The OS rate at 12 and 24 months were 85.6% and 73.3%, respectively. Panitumumab and FOLFIRI as perioperative therapy for resectable CLM result in a radiological objective response rate in 65.7% of patients with a manageable grade 3 diarrhea rate of 14.3%. Median PFS was 13.2 months, and the 24-month OS rate was 73.3%. These data are insufficient to widen the indication of panitumumab from the unresectable setting to the setting of resectable CLM.

Radiomics using computed tomography to predict CD73 expression and prognosis of colorectal cancer liver metastases

BackgroundFinding a noninvasive radiomic surrogate of tumor immune features could help identify patients more likely to respond to novel immune checkpoint inhibitors. Particularly, CD73 is an ectonucleotidase that catalyzes the breakdown of extracellular AMP into immunosuppressive adenosine, which can be blocked by therapeutic antibodies. High CD73 expression in colorectal cancer liver metastasis (CRLM) resected with curative intent is associated with early recurrence and shorter patient survival. The aim of this study was hence to evaluate whether machine learning analysis of preoperative liver CT-scan could estimate high vs low CD73 expression in CRLM and whether such radiomic score would have a prognostic significance.MethodsWe trained an Attentive Interpretable Tabular Learning (TabNet) model to predict, from preoperative CT images, stratified expression levels of CD73 (CD73High vs. CD73Low) assessed by immunofluorescence (IF) on tissue microarrays. Radiomic features were extracted from 160 segmented CRLM of 122 patients with matched IF data, preprocessed and used to train the predictive model. We applied a five-fold cross-validation and validated the performance on a hold-out test set.ResultsTabNet provided areas under the receiver operating characteristic curve of 0.95 (95% CI 0.87 to 1.0) and 0.79 (0.65 to 0.92) on the training and hold-out test sets respectively, and outperformed other machine learning models. The TabNet-derived score, termed rad-CD73, was positively correlated with CD73 histological expression in matched CRLM (Spearman’s ρ = 0.6004; P < 0.0001). The median time to recurrence (TTR) and disease-specific survival (DSS) after CRLM resection in rad-CD73High vs rad-CD73Low patients was 13.0 vs 23.6 months (P = 0.0098) and 53.4 vs 126.0 months (P = 0.0222), respectively. The prognostic value of rad-CD73 was independent of the standard clinical risk score, for both TTR (HR = 2.11, 95% CI 1.30 to 3.45, P < 0.005) and DSS (HR = 1.88, 95% CI 1.11 to 3.18, P = 0.020).ConclusionsOur findings reveal promising results for non-invasive CT-scan-based prediction of CD73 expression in CRLM and warrant further validation as to whether rad-CD73 could assist oncologists as a biomarker of prognosis and response to immunotherapies targeting the adenosine pathway.

Adjuvant hepatic artery infusion pump chemotherapy for resected colorectal cancer liver metastases

First introduced in the late 1980s in the setting of unresectable liver metastasis, the use of the hepatic artery infusion pump was expanded to deliver chemotherapy in the adjuvant setting after hepatic resection about 1 decade later. Though the initial randomized clinical trial comparing the hepatic artery infusion pump to resection alone failed to show an improvement in overall survival, 2 large randomized clinical trials, namely the Memorial Sloan Kettering Cancer Center (1999) and European Cooperative Group (2002) trials, did report improved hepatic disease-free survival with the use of a hepatic artery infusion pump. There remained limited evidence of a replicable improvement in overall survival, and the expansion of hepatic artery infusion pump into the adjuvant space was cautioned by a Cochrane review in 2006, highlighting the need for further studies to establish a consistent benefit. Those data were forthcoming over the 2000s and 2010s in large-scale retrospective analyses for the most part, but the recommendations from international guidelines remain equivocal to this day.With widespread retrospective data and high-quality randomized clinical trial evidence that a hepatic artery infusion pump in the setting of resected hepatic metastasis from colorectal liver metastasis decreases hepatic recurrence and indications that it may improve overall survival, it is clear that there is a subset of patients that greatly benefit from this treatment modality. New randomized clinical trials, specifically in the adjuvant setting, are currently enrolling and should continue to elucidate the benefit that hepatic artery infusion pumps may confer. That being said, it remains a challenge to reliably identify these patients, and the procedure is limited by complexity and resources to high-volume academic centers, leaving accessibility as a further potential barrier for patients. It remains to be seen what volume of literature may shift the hepatic artery infusion pump into the standard of care, but adjuvant hepatic artery infusion pump in the setting of colorectal liver metastasis should certainly be explored further as a validated treatment for patients.

Adjuvant systemic chemotherapy with or without hepatic arterial infusion of floxuridine in patients following colorectal cancer liver metastases resection (HARVEST): A prospective, randomized controlled trial.

3516 Background: Several retrospective studies have previously demonstrated that a combination of adjuvant systemic chemotherapy and hepatic arterial infusion (HAI) could benefit patients following colorectal cancer liver metastases (CRLM) resection. This prospective clinical study aimed to determine whether adding HAI to adjuvant systemic chemotherapy could reduce the risk of recurrence following CRLM resection. Methods: The HARVEST study is an investigator-initiated, prospective, randomized controlled trial investigating the efficacy and safety of adjuvant intravenous chemotherapy with or without HAI floxuridine (FUDR) in CRLM patients that underwent liver metastasectomy. Patients in the systemic chemotherapy plus HAIC arm (HAI group) received systemic FOLFOX (q2w) plus HAI (FUDR, d1-14, q4w) for up to 6 months, while the systemic chemotherapy group without HAI (non-HAI group) received intravenous FOLFOX only. The primary study endpoint is the relapse-free survival in the modified intention-to-treat (mITT) population. Blood samples at different time points were also collected and circulating tumor DNA (ctDNA) was tested for NPY and SEPT9 methylation. Results: The study was prematurely terminated due to FUDR production halt in China. Ninety-two patients were randomized and seventy-seven patients (38 in the HAI group and 39 in the non-HAI group) were eventually included in our mITT analysis. After a median follow-up of 35.8 months, there were 22 (57.9%) and 25 (64.1%) recurrences in the HAI and non-HAI groups, respectively. The median relapse-free survival was 20.0 months in the HAI group and 11.7 months in the non-HAI group (p = 0.14; HR 0.65; 95% confidence interval [CI] 0.37 to 1.16). No significant difference was found in terms of overall survival between the two groups (p = 0.461). Our subgroup analysis revealed that patients with multiple liver metastases (p &lt; 0.01) and RAS/BRAF mutation (p &lt; 0.01) could benefit from adjuvant HAI treatment. Based on ctDNA status, patients with positive postoperative ctDNA methylation benefited from adjuvant HAI treatment (p &lt; 0.01), while those with negative postoperative ctDNA methylation status (p = 0.95) did not. Chemotherapy-related adverse events were comparable between the two groups. Conclusions: Adjuvant chemotherapy intensification using HAI did not significantly reduce recurrence following CRLM resection. However, patients with multiple liver metastases, RAS/BRAF mutation and those with positive postoperative ctDNA might benefit from adjuvant HAI treatment. Clinical trial information: NCT03500874 .

CtDNA as a prognostic biomarker in resectable CLM: Systematic review and meta-analysis.

Cell-free circulating tumor DNA (ctDNA) is synthesized by tumor cells, including metastatic tumors, and circulates in the bloodstream. Evidence suggests that ctDNA is a potential predictive and prognostic biomarker for colorectal cancer (CRC), but its predictive efficacy in detecting CRC liver metastasis (CLM) remains unclear. Additionally, its utility in the clinical setting needs further investigation. We conducted a meta-analysis to determine the utility of ctDNA as a biomarker for predicting the prognosis of CLM and investigate the relationship between CLM and ctDNA positivity. A literature search was performed in electronic databases to identify relevant studies published up to March 19, 2022. We retrieved data on overall survival (OS), disease-free survival (DFS), and recurrence-free survival (RFS) for both ctDNA-positive and ctDNA-negative colorectal liver metastasis (CLM) patients from the selected articles. Hazard ratios (HRs) were also calculated for these survival outcomes analysis was also performed. The stability of the combined meta-analysis was verified by sensitivity analysis and publication bias evaluation. Ten trials were included, and 615 patients were evaluated. In patients with CLM, pooled HRs revealed a substantial link between ctDNA positivity and RFS/DFS. Subgroup analysis revealed that ctDNA had a prospective detection value. Sensitivity analysis and publication bias evaluation indicated stable results. Although the results on pooled HR for OS suggested that ctDNA-positive patients had a shorter survival time, their pooled HRs had a relatively evident heterogeneity, and sensitivity analysis and publication bias evaluation indicated that pooled HRs were extremely unstable. In conclusion, our results demonstrate that ctDNA appears to be a prognostic biomarker for resectable CLM patients.

Combined ablation and resection (CARe) for resectable colorectal cancer liver Metastases-A propensity score matching study

BackgroundThe efficacy of combining ablation and resection (CARe) in treating unresectable colorectal cancer liver metastases (CRLM) was well established. This study aimed to investigate the surgical and oncological outcomes of CARe strategy focusing on initially resectable CRLM. Patients and methodsA total of 971 patients with resectable CRLM from a retrospective database of 1414 CRLM patients were enrolled, including 120 in the CARe group and 851 in the hepatectomy alone group. Short- and long-term outcomes were compared between groups using propensity score matching analysis. ResultsAfter propensity score matching, 96 matched pairs of patients from each group were included. General characteristics of primary tumour and liver metastases were not statistically different between the CARe group and hepatectomy alone group. Disease-free survival (p = 0.257), intrahepatic recurrence-free survival (p = 0.329), and overall survival (p = 0.358) were similar between the two groups. Patients in CARe group had significantly reduced rate of major hepatectomy (5.2% vs. 21.9%, p = 0.001), lower incidence of postoperative hepatic insufficiency (0.0% vs. 5.2%, p = 0.023), and shortened postoperative hospital stay (7 d vs. 8 d, p = 0.019). Multivariate analysis showed that surgical approach did not affect oncologic outcome; liver metastasis with diameter >3 cm was an independent prognostic factor for hepatic recurrence-free and disease-free survival, and RAS status and lymph node metastasis at the primary site were independent prognostic factors for overall survival. ConclusionFor patients with resectable CRLM, CARe may be a better treatment strategy than hepatectomy alone, as it could avoid major hepatectomy and get better surgical outcomes, while providing the similar oncologic results.

Intersurgeon Variability in Local Treatment Planning for Patients with Initially Unresectable Colorectal Cancer Liver Metastases: Analysis of the Liver Expert Panel of the Dutch Colorectal Cancer Group

BackgroundConsensus on resectability criteria for colorectal cancer liver metastases (CRLM) is lacking, resulting in differences in therapeutic strategies. This study evaluated variability of resectability assessments and local treatment plans for patients with initially unresectable CRLM by the liver expert panel from the randomised phase III CAIRO5 study.MethodsThe liver panel, comprising surgeons and radiologists, evaluated resectability by predefined criteria at baseline and 2-monthly thereafter. If surgeons judged CRLM as resectable, detailed local treatment plans were provided. The panel chair determined the conclusion of resectability status and local treatment advice, and forwarded it to local surgeons.ResultsA total of 1149 panel evaluations of 496 patients were included. Intersurgeon disagreement was observed in 50% of evaluations and was lower at baseline than follow-up (36% vs. 60%, p < 0.001). Among surgeons in general, votes for resectable CRLM at baseline and follow-up ranged between 0–12% and 27–62%, and for permanently unresectable CRLM between 3–40% and 6–47%, respectively. Surgeons proposed different local treatment plans in 77% of patients. The most pronounced intersurgeon differences concerned the advice to proceed with hemihepatectomy versus parenchymal-preserving approaches. Eighty-four percent of patients judged by the panel as having resectable CRLM indeed received local treatment. Local surgeons followed the technical plan proposed by the panel in 40% of patients.ConclusionConsiderable variability exists among expert liver surgeons in assessing resectability and local treatment planning of initially unresectable CRLM. This stresses the value of panel-baseddecisions, and the need for consensus guidelines on resectability criteria and technical approach to prevent unwarranted variability in clinical practice.

Impact of Molecular Status on Metastasectomy of Colorectal Cancer Liver Metastases.

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.

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

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

Abstract 4691: Spatially resolved transcriptomics deconvolutes histological prognostic subgroups in patients with colorectal cancer and synchronous liver metastases

Abstract Patients demonstrating strong immune responses to primary colorectal cancer (CRC) have a survival benefit following surgery, while those with predominantly stromal microenvironments do poorly. Biomarkers to identify patients with colorectal cancer liver metastases (CRLM) who have good prognosis following surgery for oligometastatic disease remain elusive. The aim of this study was to determine the practical application of a simple histological assessment of immune cell infiltration and stromal content in predicting outcome following synchronous resection of primary CRC and CRLM, and to interrogate the underlying functional biology that drives disease progression. Patients undergoing synchronous resection of primary CRC and CRLM underwent detailed histological assessment, panel genomic and bulk transcriptomic assessment, immunohistochemistry (IHC) and GeoMx Spatial Transcriptomics (ST) analysis. Integration with genomic features, pathway enrichment analysis and immune deconvolution were performed. High-immune metastases were associated with improved cancer specific survival (HR, 0.36, P=0.01). Bulk transcriptomic analysis was confounded by stromal content but ST demonstrated that the invasive edge of the metastases of long-term survivors was characterized by adaptive immune cell populations enriched for Type II Interferon signaling (NES=-2.05 P.Adj&amp;lt;0.005) and MHC-Class II Antigen Presentation (NES=-2.09 P.Adj&amp;lt;0.005). In contrast, patients with poor prognosis demonstrated increased abundance of regulatory T-cells and neutrophils with enrichment of Notch (NES=2.2 P.Adj=0.022) and TGF-β (NES=2.2 P.Adj=0.02) signaling pathways at the metastatic tumor center. In summary, histological assessment can stratify outcome in patients undergoing synchronous resection of CRLM and ST analysis has revealed significant intra-tumoral and inter-lesional heterogeneity with underlying transcriptomic programs identified in driving each phenotype. Citation Format: Colin S. Wood, Kathryn A. Pennel, Holly Leslie, Assya Legrini, Andrew J. Cameron, Paul Horgan, Joanne Edwards, Colin W. Steele, Nigel B. Jamieson. Spatially resolved transcriptomics deconvolutes histological prognostic subgroups in patients with colorectal cancer and synchronous liver metastases. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4691.

Optimizing Adjuvant Therapy after Surgery for Colorectal Cancer Liver Metastases: A Systematic Review

The liver is the most common site of colorectal cancer metastatic spread. Although metastasectomy is the gold standard for fit patients with resectable colorectal cancer liver metastases (CRLMs), their management after surgical treatment remains controversial. The objective of this systematic review was to collate the currently available data of the agents used in the adjuvant setting in order to define the most optimal therapeutic strategy. A systematic review of the literature was conducted by searching PubMed/Medline and Cochrane library databases. We included studies that evaluated the efficacy, the tolerability and the safety profile of various chemotherapeutic agents that are used as adjuvant treatment after surgical resection of CRLMs. The outcomes of interest were regression-free survival (RFS), disease-free survival (DFS), overall survival (OS) and severe toxicities. From 543 initial articles, 29 publications with 7028 patients were finally included. In general, the results of the eligible studies indicated that adjuvant therapy after resection of CRLMs led to improved RFS/DFS rates, but this benefit did not contribute to a statistically significant prolongation of OS. Moreover, the choice of the therapeutic strategy, namely systematic or regional chemotherapy or the combination of both, did not seem to have a differential impact on patient outcomes. However, these results should be interpreted with caution since the majority of the chosen studies are of low or moderate quality. In this context, further high-quality clinical trials conducted on patient sub-populations with modern therapies are required in order to reduce in-study and between-study heterogeneity and determine which patients are expected to derive the maximum benefit from adjuvant therapy after surgery for CRLMs.

Five-year survival post hepatectomy for colorectal liver metastases in a real-world Chinese cohort: Recurrence patterns and prediction for potential cure.

Patients with a 5-year recurrence-free survival post liver resection for colorectal cancer liver metastases (CRLM) are considered to be potentially cured. However, there is a deficit of data on long-term follow-up and the recurrence status among these patients in the Chinese population. We analyzed real-world follow-up data of patients with CRLM who underwent hepatectomy, explored the recurrence patterns, and established a prediction model for a potential cure scenario. Patients who underwent radical hepatic resection for CRLM during 2000-2016, with actual follow-up data for at least 5 years, were enrolled. The observed survival rate was calculated and compared among the groups with different recurrence patterns. The predictive factors for 5-year non-recurrence were determined using logistic regression analysis; a recurrence-free survival model was developed to predict long-term survival. A total of 433 patients were included, of whom 113 patients were found non-recurrence after 5 years follow-up, with a potential cure rate of 26.1%. Patients with late recurrence (>5 months) and lung relapse showed significantly superior survival. Repeated localized treatment significantly improved the long-term survival of patients with intrahepatic or extrahepatic recurrences. Multivariate analysis showed that RAS wild-type CRC, preoperative CEA <10 ng/ml, and liver metastases ≤3 were independent factors for a 5-year disease-free recurrence. A cure model was developed based on the above factors, achieving good performance in predicting long-term survival. About one quarter patients with CRLM could achieve potential cure with non-recurrence at 5-year after surgery. The recurrence-free cure model could well distinguish the long-term survival, which would aid clinicians in determining the treatment strategy.

A radiomic biomarker for prognosis of resected colorectal cancer liver metastases generalizes across MRI contrast agents.

Contrast-enhanced MRI is routinely performed as part of preoperative work-up for patients with Colorectal Cancer Liver Metastases (CRLM). Radiomic biomarkers depicting the characteristics of CRLMs in MRI have been associated with overall survival (OS) of patients, but the reproducibility and clinical applicability of these biomarkers are limited due to the variations in MRI protocols between hospitals. In this work, we propose a generalizable radiomic model for predicting OS of CRLM patients who received preoperative chemotherapy and delayed-phase contrast enhanced (DPCE) MRIs prior to hepatic resection. This retrospective two-center study included three DPCE MRI cohorts (n=221) collected between January 2006 and December 2012. A 10-minute delayed Gd-DO3A-butrol enhanced MRI discovery cohort was used to select features based on robustness across contrast agents, correlation with OS and pairwise Pearson correlation, and to train a logistic regression model that predicts 3-year OS. The model was evaluated on a 10-minute delayed Gd-DO3A-butrol enhanced MRI validation cohort (n=121), a 20-minute delayed Gd-EOB-DTPA (n=72) cohort from the same institute, and a 5-minute delayed Gd-DTPA cohort (n=28) from an independent institute. Two features were selected: minor axis length and dependence variance. The radiomic signature model stratified high-risk and low-risk CRLM groups in the Gd-DO3Abutrol (HR = 6.29, p = .007), Gd-EOB-DTPA (HR = 3.54, p = .003) and Gd-DTPA (HR = 3.16, p = .04) validation cohorts. While most existing MRI findings focus on a specific contrast agent, our study shows the potential of MRI features to be generalizable across main-stream contrast agents at delayed phase.

Effect of dynamic circulating tumor DNA minimal residual disease detection on recurrence surveillance and second resection rate after curative intent resection of colorectal liver metastasis: A prospective cohort study.

242 Background: Recurrence rates after curative intent resection of colorectal cancer liver metastases (CRLM) are nearly 50%. Standard of care surveillance includes intensive computed tomographic (CT) imaging and CEA measurements. However, recurrence detection often happens too late to resume a second resection. Previous studies have shown that circulating tumor DNA (ctDNA) detection, as a biomarker of minimal residual disease (MRD), is a robust prognostic factor for patients with colorectal cancers. Here, we performed a prospective study to explore the potential use for improving postoperative CRLM surveillance by dynamic ctDNA detection and its impact on the second resection of recurrent patients. Methods: Enrolled patients received curative intent resection of CRLM and were confirmed at the status of no evidence of disease (NED) by CT about one month after surgery. All patients received stand-of-care postoperative surveillance and serial plasma samples were collected, including presurgical and postsurgical samples (4-6 weeks after surgery) and every 3rd month until relapse or up to 24 months after resection. A personalized tumor-informed assay (Signatera/HuaJianwei bespoke multiplex-PCR NGS) was used to quantify ctDNA in plasma samples. Results: A total of 318 plasma samples from 60 patients recruited from July 2020 to July 2021 were included in our analysis. Twenty-five (41.6%) patients received neoadjuvant chemotherapy, and 46 patients (76.7%) received adjuvant chemotherapy after surgery. The median follow-up time was 18.0 months (range, 7.5 to 25.3 months). ctDNA was detectable in 58/60 (96.7%) patients before surgery, in 35/60 (58.3%) patients after surgery, and in 23/58 (39.7%) patients at the end of treatment (EOT). Patients with ctDNA/MRD positive status post-surgery or EOT experienced a significant shorter recurrence-free survival (RFS) than patients with negative ctDNA/MRD [hazard ratio (HR) 4.2; P &lt; 0.001 and HR 9.8; P &lt; 0.001]. The recurrence rate in MRD-positive patients (aka. positive predictive value, PPV) was 91.4% (32/35) at post-surgery and 91.3% (21/23) at EOT, respectively. In 93.0% of postoperative MRD-positive patients, ctDNA detected early relapse with a lead time up to 9.0 months (median 3.4 months) compared with standard radiological imaging. Among 40 patients with recurrence, the total secondary resection rate was 52.5% (21/40) with 40% (21/40) cases reached secondary NED. While among 24 recurrent cases with only liver metastases, the secondary resection rate was 66.7% (16/24) with 58.3% (14/24) cases reached secondary NED. Conclusions: Postoperative ctDNA status is strongly associated with shorter RFS. Serial ctDNA monitoring assists early detection of relapse, and therefore, improves patient outcomes by secondary resection. Clinical trial information: ChiCTR2000035677 .

Spatial transcriptomics deconvolves prognosis in colorectal cancer with synchronous liver metastases

Background: Patients demonstrating strong immune responses to primary colorectal cancer (CRC) have a survival benefit following surgery, while those with predominantly stromal microenvironments do poorly. Biomarkers to identify patients with colorectal cancer liver metastases (CRLM) who have good prognosis following surgery for oligometastatic disease remain elusive. The aim of this study was to determine the practical application of a simple histological assessment of immune cell infiltration and stromal content in predicting outcome following synchronous resection of primary CRC and CRLM, and to interrogate the underlying functional biology that drives disease progression.

Recent Advances in Minimally Invasive Liver Resection for Colorectal Cancer Liver Metastases—A Review

Minimally invasive surgical (MIS) approaches to liver resection have been increasingly adopted into use for surgery on colorectal cancer liver metastases. The purpose of this review is to evaluate the outcomes when comparing laparoscopic liver resection (LLR), robotic liver resection (RLR), and open liver resection (OLR) for colorectal cancer liver metastases (CRLM) in 39 studies (2009-2022) that include a case-matched series, propensity score analyses, and three randomized clinical trials. LLR is associated with less intraoperative blood loss and shorter hospital stay compared with OLR. LLR can be performed with comparable operative time. LLR has similar rates of perioperative complications and mortality as OLR. There were no significant differences in 5-year overall or disease-free survival between approaches. Robotic liver resection (RLR) has comparable perioperative safety to LLR and may improve rates of R0 resection in certain patients. Finally, MIS approaches to the hepatic resection of CRLM reduce the time from liver resection to initiation of adjuvant chemotherapy. Thus, MIS liver surgery should be considered in the array of options for patients with CRLM, though thoughtful patient selection and surgeon experience should be part of that decision.