Colorectal Liver Metastases Patients Research Articles

Comparison of Complications in Patients with Ductal Cholangiocarcinoma (CCC) and Patients with Colorectal Liver Metastases (CRLMs) After Portal Vein Embolization (PVE): A Matched Cohort Study.

To compare complications in patients with cholangiocarcinoma (CCC) and patients with colorectal liver metastases (CRLMs) after portal vein embolization (PVE) and to identify possible predictive factors. Retrospective analysis of consecutive patients, who underwent PVE between July 2011 and March 2020. The study groups were matched for sex and age. Multivariable analysis was performed for the endpoints of complications categorized according for their respective effect on surgical treatment: "Minor" complications had no effect on subsequent surgical treatment, while "intermediate" and "severe" complications delayed or prevented surgery. A total of 160 patients with either CCC (n = 80) or CRLMs (n = 80) were included: 34/160 experienced complications: 27 (CCC: 21; CRLMs: 6) "minor", 4 (CCC: 3; CRLMs: 1) "intermediate", and 3 (CCC: 2; CRLMs: 1) "severe" complications respectively (p = .01). Patients with CCC received a biliary drainage 5days on average before PVE. Baseline bilirubin levels were 1.1mg/dl in CCC patients and 0.55mg/dl in CRLMs patients (p < .01). Postinterventional infections were more common in CCC patients. The preintervention future liver remnant volume (odds ratio (OR) 0.93; 95% confidence interval (CI) 0.88-0.99; p = .02), body mass index (OR 1.19; 95% CI 1.04-1.36; p = .01), age (OR 0,91; 95% CI 0.84-0.99; p = .01), chemotherapy before PVE (OR 0.03; 95% CI 0.01-0.23; p < .01) and severe liver steatosis (OR 29.52; 95% CI 1.87-467,13; p = .02) were the only significant predictive factors for the occurrence of (minor) complications. PVE can be performed in CCC patients with prior biliary drainage, with similar procedural safety as in patients with CRLMs.

Comparison of systemic treatments for previously treated patients with unresectable colorectal liver metastases: a systematic review and network meta-analysis.

There is limited evidence of comparative results among different treatments for patients with unresectable colorectal liver metastases (CRLM) who have failed at least one line of previous systemic therapy. We aimed to compare the efficacy of systemic treatments among these patients through this investigation. We collected randomized controlled trials (RCTs) reported in English up until July 2023, from databases including PubMed, Embase, Cochrane Library, ClinicalTrials.gov, and prominent conference databases, for this Bayesian network meta-analysis. Phase II or III trials that evaluated at least two therapeutic regimens were included. Primary outcome was overall survival (OS), secondary outcome was progression-free survival (PFS). Hazards ratios (HRs) with 95% confidence intervals (CIs) were used as effect size. Subgroup analysis was performed based on metastatic sites. The current systematic review protocol was registered on PROSPERO (CRD42023420498). 30 RCTs were included, with a total of 13,511 patients. Compared to chemotherapy, multi-targeted therapy (HR 0.57, 95% CI 0.37-0.87) and targeted therapy plus chemotherapy (HR 0.78, 95% CI 0.67-0.91) show significant advantages. Targeted therapy (HR 0.92, 95% CI 0.54-1.57) and local treatment plus chemotherapy (HR 1.03, 95% CI 0.85-1.23) had comparable performance. For patients with liver metastases, TAS-102 plus bevacizumab, aflibercept plus fluorouracil-based combination chemotherapy (CTFU), and bevacizumab plus capecitabine-based combination chemotherapy (CTCA) showed the best outcomes in terms of OS. Bevacizumab plus intensified CTFU, bevacizumab plus CTCA, and HAI followed by single-agent chemotherapy (SingleCT) performed the best regarding PFS. For patients with liver-limited metastases, aflibercept plus CTFU is the optimal choice in OS. For PFS, the best options were HAI followed by SingleCT, aflibercept plus CTFU, and panitumumab plus CTFU. For patients with multiple-site metastases, the best treatments were TAS-102 plus bevacizumab, bevacizumab plus CTCA, bevacizumab plus CTFU, and aflibercept plus CTFU. Multi-targeted therapy and targeted therapy plus chemotherapy are the best treatment mechanisms. TAS-102 plus bevacizumab is superior in OS, the combination of anti-VEGF drugs like bevacizumab and aflibercept with standard chemotherapy is the preferred option for CRLM patients.

Personalized prediction of postoperative complication and survival among Colorectal Liver Metastases Patients Receiving Simultaneous Resection using machine learning approaches: A multi-center study

BackgroundTo predict clinical important outcomes for colorectal liver metastases (CRLM) patients receiving colorectal resection with simultaneous liver resection by integrating demographic, clinical, laboratory, and genetic data. MethodsRandom forest (RF) models were developed to predict postoperative complications and major complications (binary outcomes), as well as progression-free survival (PFS) and overall survival (OS) (time-to-event outcomes) of the CRLM patients based on data from two hospitals. The models were validated on an external dataset from an independent hospital. The clinical utility of the models was assessed via decision curve analyses (DCA). ResultsThere were 1067 patients included in survival prediction analyses and 1070 patients included in postoperative complication prediction analyses. The RF models provided an assessment of the model contributions of features for outcomes and suggested KRAS, BRAF, and MMR status were salient for the PFS or OS predictions. RF model of PFS showed that the Brier scores at 1-, 3-, and 5-year PFS were 0.213, 0.202 and 0.188; and the AUCs of 1-, 3- and 5-year PFS were 0.702, 0.720 and 0.743. RF model of OS revealed that Brier scores of 1-,3-, and 5-year OS were 0.040, 0.183 and 0.211; and the AUCs of 1-, 3- and 5-year OS were 0.737, 0.706 and 0.719. RF model for postoperative complication resulted in an AUC of 0.716 and a Brier score of 0.196. DCA curves clearly demonstrated that the RF models for these outcomes exhibited a superior net benefit across a wide range of threshold probabilities, signifying their favorable clinical utility. The RF models consistently exhibited robust performance in both internal cross-validation and external validation. The individualized risk profile predicted by the models closely aligned with the actual survival outcomes observed for the patients. A web-based tool (https://kanli.shinyapps.io/CRLMRF/) was provided to demonstrate the practical use of the prediction models for new patients in the clinical setting. ConclusionThe predictive models and a web-based tool for personalized prediction demonstrated a moderate predictive performance and favorable clinical utilities on several key clinical outcomes of CRLM patients receiving simultaneous resection, which could facilitate the clinical decision-making and inform future interventions for CRLM patients.

Preoperative MRI radiomic analysis for predicting local tumor progression in colorectal liver metastases before microwave ablation

Purpose Radiomics may aid in predicting prognosis in patients with colorectal liver metastases (CLM). Consistent data is available on CT, yet limited data is available on MRI. This study assesses the capability of MRI-derived radiomic features (RFs) to predict local tumor progression-free survival (LTPFS) in patients with CLMs treated with microwave ablation (MWA). Methods All CLM patients with pre-operative Gadoxetic acid-MRI treated with MWA in a single institution between September 2015 and February 2022 were evaluated. Pre-procedural information was retrieved retrospectively. Two observers manually segmented CLMs on T2 and T1-Hepatobiliary phase (T1-HBP) scans. After inter-observer variability testing, 148/182 RFs showed robustness on T1-HBP, and 141/182 on T2 (ICC > 0.7). Cox multivariate analysis was run to establish clinical (CLIN-mod), radiomic (RAD-T1, RAD-T2), and combined (COMB-T1, COMB-T2) models for LTPFS prediction. Results Seventy-six CLMs (43 patients) were assessed. Median follow-up was 14 months. LTP occurred in 19 lesions (25%). CLIN-mod was composed of minimal ablation margins (MAMs), intra-segment progression and primary tumor grade and exhibited moderately high discriminatory power in predicting LTPFS (AUC = 0.89, p = 0.0001). Both RAD-T1 and RAD-T2 were able to predict LTPFS: (RAD-T1: AUC = 0.83, p = 0.0003; RAD-T2: AUC = 0.79, p = 0.001). Combined models yielded the strongest performance (COMB-T1: AUC = 0.98, p = 0.0001; COMB-T2: AUC = 0.95, p = 0.0003). Both combined models included MAMs and tumor regression grade; COMB-T1 also featured 10th percentile of signal intensity, while tumor flatness was present in COMB-T2. Conclusion MRI-based radiomic evaluation of CLMs is feasible and potentially useful for LTP prediction. Combined models outperformed clinical or radiomic models alone for LTPFS prediction.

Construction and validation of "WCH-nomogram" for predicting the prognosis after resection of colorectal liver metastases.

The prognostic predictive tool for patients with colorectal liver metastasis (CRLM) is limited and the criteria for administering preoperative neoadjuvant chemotherapy in CRLM patients remain controversial. This study enrolled 532 CRLM patients at West China Hospital (WCH) from January 2009 to December 2019. Prognostic factors were identified from the training cohort to construct a WCH-nomogram and evaluating accuracy in the validation cohort. Receiver operating characteristic (ROC) curve analysis was used to compare the prediction accuracy with other existing prediction tools. From the analysis of the training cohort, four independent prognostic risk factors, namely tumor marker score, KRAS mutation, primary lymph node metastasis, and tumor burden score were identified on which a WCH-nomogram was constructed. The C-index of the two cohorts were 0.674 (95% CI: 0.634-0.713) and 0.655 (95% CI: 0.586-0.723), respectively, which was better than the previously reported predication scores (CRS, m-CS and GAME score). ROC curves showed AUCs for predicting 1-, 3-, and 5-year overall survival (OS) of 0.758, 0.709, and 0.717 in the training cohort, and 0.860, 0.669, and 0.692 in the validation cohort, respectively. A cutoff value of 114.5 points was obtained for the WCH-nomogram total score based on the maximum Youden index of the ROC curve of 5-year OS. Risk stratification showed significantly better prognosis in the low-risk group, however, the high-risk group was more likely to benefit from neoadjuvant chemotherapy. The WCH-nomogram demonstrates superior prognostic stratification compared to prior scoring systems, effectively identifying CRLM patients who may benefit the most from neoadjuvant chemotherapy.

Personalized circulating tumor DNA monitoring improves recurrence surveillance and management after curative resection of colorectal liver metastases: a prospective cohort study.

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.

Exploring tumor heterogeneity in colorectal liver metastases by imaging: Unsupervised machine learning of preoperative CT radiomics features for prognostic stratification

ObjectivesThis study aimed to investigate tumor heterogeneity of colorectal liver metastases (CRLM) and stratify the patients into different risk groups of prognoses following liver resection by applying an unsupervised radiomics machine-learning approach to preoperative CT images. MethodsThis retrospective study retrieved clinical information and CT images of 197 patients with CRLM from The Cancer Imaging Archive (TCIA) database. Radiomics features were extracted from a segmented liver lesion identified at the portal venous phase. Those features which showed high stability, non-redundancy, and indicative information were selected. An unsupervised consensus clustering analysis on these features was adopted to identify subgroups of CRLM patients. Overall survival (OS), disease-free survival (DFS), and liver-specific DFS were compared between the identified subgroups. Cox regression analysis was applied to evaluate prognostic risk factors. ResultsA total of 851 radiomics features were extracted, and 56 robust features were finally selected for unsupervised clustering analysis which identified two distinct subgroups (96 and 101 patients respectively). There were significant differences in the OS, DFS, and liver-specific DFS between the subgroups (all log-rank p < 0.05). The subgroup with worse outcome using the proposed radiomics model was consistently associated with shorter OS, DFS, and liver-specific DFS, with hazard ratios of 1.78 (95 %CI: 1.12–2.83), 1.72 (95 %CI: 1.16–2.54), and 1.59 (95 %CI: 1.10–2.31), respectively. The general performance of this radiomics model outperformed the traditional Clinical Risk Score and Tumor Burden Score in the prognosis prediction after surgery for CRLM. ConclusionRadiomics features derived from preoperative CT images can reveal the heterogeneity of CRLM and stratify the patients with CRLM into subgroups with significantly different clinical outcomes.

Prognostic factors associated with early recurrence following liver resection for colorectal liver metastases: a systematic review and meta-analysis

BackgroundColorectal cancer (CRC) is the 3rd most common malignancy with the liver being the most common site of metastases. The recurrence rate of colorectal liver metastases (CRLM) after liver resection (LR) is notably high, with an estimated 40% of patients experiencing recurrence within 6 months. In this context, we conducted a meta-analysis to synthesize and evaluate the reliability of evidence pertaining to prognostic factors associated with early recurrence (ER) in CRLM following LR.MethodsSystematic searches were conducted from the inception of databases to July 14, 2023, to identify studies reporting prognostic factors associated with ER. The Quality in Prognostic Factor Studies (QUIPS) tool was employed to assess risk-of-bias for included studies. Meta-analysis was then performed on these prognostic factors, summarized by forest plots. The grading of evidence was based on sample size, heterogeneity, and Egger’s P value.ResultsThe study included 24 investigations, comprising 12705 individuals, during an accrual period that extended from 2007 to 2023. In the evaluation of risk-of-bias, 22 studies were rated as low/moderate risk, while two studies were excluded because of high risk. Most of the studies used a postoperative interval of 6 months to define ER, with 30.2% (95% confidence interval [CI], 24.1–36.4%) of the patients experiencing ER following LR. 21 studies were pooled for meta-analysis. High-quality evidence showed that poor differentiation of CRC, larger and bilobar-distributed liver metastases, major hepatectomy, positive surgical margins, and postoperative complications were associated with an elevated risk of ER. Additionally, moderate-quality evidence suggested that elevated levels of carcinoembryonic antigen (CEA) and carbohydrate antigen 19–9 (CA199), lymph node metastases (LNM) of CRC, and a higher number of liver metastases were risk factors for ER.ConclusionThis review has the potential to enhance the efficacy of surveillance strategies, refine prognostic assessments, and guide judicious treatment decisions for CRLM patients with high risk of ER. Additionally, it is essential to undertake well-designed prospective investigations to examine additional prognostic factors and develop salvage therapeutic approaches for ER of CRLM.

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

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

Abstract 925: Continuing anti-EGFR treatment prolonged survival in mCRC patients receiving conversion liver resection

Abstract Introduction: Anti-EGFR monoclonal antibody plus doublet chemotherapy is the mainstay of first-line treatment of RAS/BRAF wild-type metastatic colorectal cancer (mCRC) patients. Some of these patients might undergo secondary resection. However, there is no standardized suggestion on whether colorectal cancer liver metastasis patients should keep target therapy after secondary resection. NCCN guidelines suggest chemotherapy only in patients receiving primary liver resection. Whether we could spare the use of target therapy after secondary resection is the main aim of our study. Methods: Using Taiwan's National Health Insurance Research Database, we established a cohort of KRAS wild-type mCRC patients treated with first-line anti-EGFR therapy plus doublet chemotherapy between 2013 and 2018. Secondary surgery was defined as either resection of liver metastases or radiofrequency ablation. Results: 5694 stage IV mCRC patients received anti-EGFR MAb plus doublet chemotherapy as a first-line treatment between 2013 and 2018. 174 patients were enrolled in the final analysis, with 153 continuing anti-EGFR MAb after secondary resection and 21 patients without anti-EGFR MAb. Compared with those who without anti-EGFR therapy after secondary resection, patients who continued anti-EGFR MAb exhibited significantly longer overall survival (OS; median, 43.8 vs. 31.9 months, p = 0.031) but not in time to treatment failure (TTF; median, 22.2 vs. 26.6 months, p = 0.841). The OS benefits of continuing anti-EGFR MAb remained regardless of left-sided or right-sided primary tumors (40.9 vs. 43.0 months, p = 0.980). The patient cohort from 2016 to 2018 showed more prolonged survival than from 2012 to 2015 (not reached vs. 40.450, p = 0.0305). TTF has no statistical difference when considering patient cohort or primary tumor location. In multivariate analyses, continuing first-line anti-EGFR MAb therapy after secondary resection remained an independent predictor of longer OS. Conclusion: For mCRC patients who received secondary resection after first-line anti-EGFR and doublet chemotherapy, continuing anti-EGFR MAb after resection was associated with significantly longer OS regardless of primary tumor sidedness. Citation Format: Yao-Yu Hsieh, Chin-Wen Tsai, T-CARE Group, Yi-Hsieh Liang. Continuing anti-EGFR treatment prolonged survival in mCRC patients receiving conversion liver resection [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 925.

Association of preoperative aspartate aminotransferase to platelet ratio index with outcomes and tumour microenvironment among colorectal cancer with liver metastases

This study aims to investigate applicable robust biomarkers that can improve prognostic predictions for colorectal liver metastasis (CRLM) patients receiving simultaneous resection. A total of 1323 CRLM patients from multiple centres were included. The preoperative aspartate aminotransferase to platelet ratio index (APRI) level from blood of patients were obtained. Patients were stratified into a high APRI group and a low APRI group, and comparisons were conducted by analyzing progression-free survival (PFS), overall survival (OS) and postoperative early recurrence. Tumour samples of CRLM were collected to perform single-cell RNA sequencing and multiplex immunohistochemistry/immunofluorescence (mIHC/IF) to investigate the association of APRI levels and the tumour microenvironment of CRLM. Compared with APRI <0.33, PFS disadvantage (IPTW-adjusted HR = 1.240, P = 0.015) and OS disadvantage (IPTW- adjusted HR = 1.507, P = 0.002) of APRI ≥0.33 were preserved in the IPTW-adjusted Cox hazards regression analyses. An APRI ≥0.25 was associated with a significantly increased risk of postoperative early recurrence after adjustment (IPTW-adjusted OR = 1.486, P = 0.001). The external validation showed consistent results with the training cohort. In the high APRI group, the single-cell RNA sequencing results revealed a heightened malignancy of epithelial cells, the enrichment of inflammatory-like cancer-associated fibroblasts and SPP1+ macrophages associated with activation of malignant cells and fibrotic microenvironment, and a more suppressed-function T cells; mIHC/IF showed that PD1+ CD4+ T cells, FOXP3+ CD4+ T cells, PD1+ CD8+ T cells, FOXP3+ CD8+ T cells, SPP1+ macrophages and iCAFs were significantly increased in the intratumoral region and peritumoral region. This study contributed valuable evidence regarding preoperative APRI for predicting prognoses among CRLM patients receiving simultaneous resection and provided underlying clues supporting the association between APRI and clinical outcomes by single-cell sequencing bioinformatics analysis and mIHC/IF.

Riboflavin-LSD1 axis participates in the in vivo tumor-associated macrophage morphology in human colorectal liver metastases

Tumor-associated macrophages (TAMs) are key components of the tumor microenvironment (TME). In colorectal liver metastasis (CLM), TAM morphology correlates with prognosis, with smaller TAMs (S-TAMs) conferring a more favorable prognosis than larger TAMs (L-TAMs). However, the metabolic profile of in vivo human TAM populations remains unknown. Multiparametric flow cytometry was used to freshly isolate S- and L-TAMs from surgically resected CLM patients (n = 14S-, 14L-TAMs). Mass spectrometry-based metabolomics analyses were implemented for the metabolic characterization of TAM populations. Gene expression analysis and protein activity were used to support the biochemical effects of the enzyme–substrate link between riboflavin and (lysine-specific demethylase 1A, LSD1) with TAM morphologies. L-TAMs were characterized by a positive correlation and a strong association between riboflavin and TAM morphologies. Riboflavin in both L-TAMs and in-vitro M2 polarized macrophages modulates LSD1 protein expression and activity. The inflammatory stimuli promoted by TNFα induced the increased expression of riboflavin transporter SLC52A3 and LSD1 in M2 macrophages. The modulation of the riboflavin-LSD1 axis represents a potential target for reprogramming TAM subtypes, paving the way for promising anti-tumor therapeutic strategies.

Pre-hepatectomy dynamic circulating tumor DNA to predict pathologic response to preoperative chemotherapy and post-hepatectomy recurrence in patients with colorectal liver metastases.

To evaluate the predictive value of pre-hepatectomy dynamic circulating tumor DNA (ctDNA) on pathologic response to preoperative chemotherapy and recurrence after liver resection for colorectal liver metastases (CRLM). Pathologic response is a predictor of clinical outcomes for patients undergoing hepatectomy for CRLM. Postoperative ctDNA has been proven to be sensitive for recurrence detection. However, few studies investigate the impact of pre-hepatectomy ctDNA on pathologic response and recurrence. Patients with potential resectable CRLM underwent preoperative chemotherapy and hepatectomy between 2018 and 2021 was considered for inclusion. Plasma ctDNA was collected before and after preoperative chemotherapy. Pathologic response was analyzed for all patients after liver resection. Recurrence free survival was compared between patients with different ctDNA status and different pathologic response. The relation between ctDNA and pathologic response was also analyzed. A total of 114 patients were included. ctDNA was detectable in 108 of 114 patients (94.7%) before chemotherapy, in 56 of 114 patients (49.1%) after chemotherapy. Patients with ctDNA positive at baseline and negative after chemotherapy had significantly longer RFS (median RFS 17 vs 7months, p = 0.001) and HRFS (median HRFS unreached vs 8months, p < 0.001) than those with ctDNA persistently positive after chemotherapy. Two patients (1.6%) had a pathologic complete response and 56 patients (45.2%) had a pathologic major response. Post-chemotherapy ctDNA- was associated with improved major pathologic response (53.4% vs 32.1%, p = 0.011). In the multivariable analysis, ctDNA- after chemotherapy (HR 0.51, 95% CI 0.28-0.93), major pathologic response (HR 0.34, 95% CI 0.19-0.62) and surgery combined with radiofrequency ablation (HR 2.62, 95% CI 1.38-5.00) were independently associated with RFS (all p < 0.05). Pre-hepatectomy dynamic monitoring of ctDNA could predict pathologic response to preoperative chemotherapy and post-hepatectomy recurrence in CRLM patients. Negative ctDNA after preoperative chemotherapy was associated with better tumor regression grade and recurrence-free survival, which might be used to guide pre-hepatectomy chemotherapy and predict prognosis.

Prediction of transformation in the histopathological growth pattern of colorectal liver metastases after chemotherapy using CT-based radiomics.

Chemotherapy alters the prognostic biomarker histopathological growth pattern (HGP) phenotype in colorectal liver metastases (CRLMs) patients. We aimed to develop a CT-based radiomics model to predict the transformation of the HGP phenotype after chemotherapy. This study included 181 patients with 298 CRLMs who underwent preoperative contrast-enhanced CT followed by partial hepatectomy between January 2007 and July 2022 at two institutions. HGPs were categorized as pure desmoplastic HGP (pdHGP) or non-pdHGP. The samples were allocated to training, internal validation, and external validation cohorts comprising 153, 65, and 29 CRLMs, respectively. Radiomics analysis was performed on pre-enhanced, arterial phase, portal venous phase (PVP), and fused images. The model was used to predict prechemotherapy HGPs in 112 CRLMs, and HGP transformation was analysed by comparing these findings with postchemotherapy HGPs determined pathologically. The prevalence of pdHGP was 19.8% (23/116) and 45.8% (70/153) in chemonaïve and postchemotherapy patients, respectively (P < 0.001). The PVP radiomics signature showed good performance in distinguishing pdHGP from non-pdHGPs (AUCs of 0.906, 0.877, and 0.805 in the training, internal validation, and external validation cohorts, respectively). The prevalence of prechemotherapy pdHGP predicted by the radiomics model was 33.0% (37/112), and the prevalence of postchemotherapy pdHGP according to the pathological analysis was 47.3% (53/112; P = 0.029). The transformation of HGP was bidirectional, with 15.2% (17/112) of CRLMs transforming from prechemotherapy pdHGP to postchemotherapy non-pdHGP and 30.4% (34/112) transforming from prechemotherapy non-pdHGP to postchemotherapy pdHGP (P = 0.005). CT-based radiomics method can be used to effectively predict the HGP transformation in chemotherapy-treated CRLM patients, thereby providing a basis for treatment decisions.

Tumour response following preoperative chemotherapy is affected by body mass index in patients with colorectal liver metastases.

Colorectal cancer is the third most prevalent malignancy globally and ranks second in cancer-related mortality, with the liver being the primary organ of metastasis. Preoperative chemotherapy is widely recommended for initially or potentially resectable colorectal liver metastases (CRLMs). Tumour pathological response serves as the most important and intuitive indicator for assessing the efficacy of chemotherapy. However, the postoperative pathological results reveal that a considerable number of patients exhibit a poor response to preoperative chemotherapy. Body mass index (BMI) is one of the factors affecting the tumorigenesis and progression of colorectal cancer as well as prognosis after various antitumour therapies. Several studies have indicated that overweight and obese patients with metastatic colorectal cancer experience worse prognoses than those with normal weight, particularly when receiving first-line chemotherapy regimens in combination with bevacizumab. To explore the predictive value of BMI regarding the pathologic response following preoperative chemotherapy for CRLMs. A retrospective analysis was performed in 126 consecutive patients with CRLM who underwent hepatectomy following preoperative chemotherapy at four different hospitals from October 2019 to July 2023. Univariate and multivariate logistic regression models were applied to analyse potential predictors of tumour pathological response. The Kaplan-Meier method with log rank test was used to compare progression-free survival (PFS) between patients with high and low BMI. BMI < 24.0 kg/m2 was defined as low BMI, and tumour regression grade 1-2 was defined as complete tumour response. Low BMI was observed in 74 (58.7%) patients and complete tumour response was found in 27 (21.4%) patients. The rate of complete tumour response was significantly higher in patients with low BMI (29.7% vs 9.6%, P = 0.007). Multivariate analysis revealed that low BMI [odds ratio (OR) = 4.56, 95% confidence interval (CI): 1.42-14.63, P = 0.011], targeted therapy with bevacizumab (OR = 3.02, 95%CI: 1.10-8.33, P = 0.033), preoperative carcinoembryonic antigen level < 10 ng/mL (OR = 3.84, 95%CI: 1.19-12.44, P = 0.025) and severe sinusoidal dilatation (OR = 0.17, 95%CI: 0.03-0.90, P = 0.037) were independent predictive factors for complete tumour response. The low BMI group exhibited a significantly longer median PFS than the high BMI group (10.7 mo vs 4.7 mo, P = 0.011). In CRLM patients receiving preoperative chemotherapy, a low BMI may be associated with better tumour response and longer PFS.

Preoperative CT and survival data for patients undergoing resection of colorectal liver metastases

The liver is a common site for the development of metastases in colorectal cancer. Treatment selection for patients with colorectal liver metastases (CRLM) is difficult; although hepatic resection will cure a minority of CRLM patients, recurrence is common. Reliable preoperative prediction of recurrence could therefore be a valuable tool for physicians in selecting the best candidates for hepatic resection in the treatment of CRLM. It has been hypothesized that evidence for recurrence could be found via quantitative image analysis on preoperative CT imaging of the future liver remnant before resection. To investigate this hypothesis, we have collected preoperative hepatic CT scans, clinicopathologic data, and recurrence/survival data, from a large, single-institution series of patients (n = 197) who underwent hepatic resection of CRLM. For each patient, we also created segmentations of the liver, vessels, tumors, and future liver remnant. The largest of its kind, this dataset is a resource that may aid in the development of quantitative imaging biomarkers and machine learning models for the prediction of post-resection hepatic recurrence of CRLM.

Value of multiple models of diffusion-weighted imaging to predict hepatic lymph node metastases in colorectal liver metastases patients.

About 10%-31% of colorectal liver metastases (CRLM) patients would concomitantly show hepatic lymph node metastases (LNM), which was considered as sign of poor biological behavior and a relative contraindication for liver resection. Up to now, there's still lack of reliable preoperative methods to assess the status of hepatic lymph nodes in patients with CRLM, except for pathology examination of lymph node after resection. To compare the ability of mono-exponential, bi-exponential, and stretched-exponential diffusion-weighted imaging (DWI) models in distinguishing between benign and malignant hepatic lymph nodes in patients with CRLM who received neoadjuvant chemotherapy prior to surgery. In this retrospective study, 97 CRLM patients with pathologically confirmed hepatic lymph node status underwent magnetic resonance imaging, including DWI with ten b values before and after chemotherapy. Various parameters, such as the apparent diffusion coefficient from the mono-exponential model, and the true diffusion coefficient, the pseudo-diffusion coefficient, and the perfusion fraction derived from the intravoxel incoherent motion model, along with distributed diffusion coefficient (DDC) and α from the stretched-exponential model (SEM), were measured. The parameters before and after chemotherapy were compared between positive and negative hepatic lymph node groups. A nomogram was constructed to predict the hepatic lymph node status. The reliability and agreement of the measurements were assessed using the coefficient of variation and intraclass correlation coefficient. Multivariate analysis revealed that the pre-treatment DDC value and the short diameter of the largest lymph node after treatment were independent predictors of metastatic hepatic lymph nodes. A nomogram combining these two factors demonstrated excellent performance in distinguishing between benign and malignant lymph nodes in CRLM patients, with an area under the curve of 0.873. Furthermore, parameters from SEM showed substantial repeatability. The developed nomogram, incorporating the pre-treatment DDC and the short axis of the largest lymph node, can be used to predict the presence of hepatic LNM in CRLM patients undergoing chemotherapy before surgery. This nomogram was proven to be more valuable, exhibiting superior diagnostic performance compared to quantitative parameters derived from multiple b values of DWI. The nomogram can serve as a preoperative assessment tool for determining the status of hepatic lymph nodes and aiding in the decision-making process for surgical treatment in CRLM patients.

Differential cytokine and chemokine expression after ablation vs. resection in colorectal cancer liver metastasis

BackgroundSurgical resection remains the main curative treatment for colorectal liver metastases (CRLM). Radiofrequency ablation (RFA) is increasingly employed for small, deep lying or otherwise inoperable lesions. However, RFA can induce pro-tumorigenic effects on residual tumor cells, hereby possibly promoting tumor recurrence. Contrastingly, post-RFA tumor debris as an antigen source can also generate anti-cancer immune responses. Utilizing this, current studies on combining RFA with immune therapy appear promising. Here, in an attempt to shed light on this controversy, cytokines involved in inflammation, (lymph)angiogenesis, immune cell recruitment and tumor cell invasion were investigated post-RFA versus post-resection in CRLM patients. MethodsCytokine and chemokine serum levels pre-operation, 4 h and 24 h post-operation were analyzed in CRLM patients undergoing RFA (n = 8) or partial hepatectomy (n = 9) using Multiplex immunoassays. Statistical analyses were performed between as well as within individual intervention groups. ResultsPost-RFA, significantly increased levels of acute phase proteins SAA1 and S100A8, IL-6, IL-1Ra, MIP3b (CCL19) and MMP9 were observed along with decreases in Fibronectin, MCP-1 (CCL2), and Tie-2. Post-resection, increased levels of PDGFbb, I309 (CCL1), Apelin, MIF, IL-1b and TNFα were seen. All p-values <0.05. ConclusionPro-inflammatory responses mediated by different cytokines were seen after both RFA and resection, possibly influencing residual tumor cells and tumor recurrence. As both ablation and resection trigger inflammation and immune cell recruitment (albeit via distinct mechanisms), these data suggest that further research may explore combining immune therapy with not only RFA but also resection. Key messageAnalysis of patients' serum after radiofrequency ablation versus resection of colorectal liver metastases (CRLM) showed that these interventions trigger inflammation and immune cell recruitment, via different cyto- and chemokine pathways. This suggests a possible future strategy of combining immune therapy with not only ablative techniques but also with resection of CRLM.

Hepatic steatosis predicts metachronous liver metastasis in colorectal cancer patients: a nested case-control study and systematic review.

Nearly twenty-five percent of colorectal cancer (CRC) patients develop metachronous colorectal liver metastasis (CRLM) after curative surgery. Hepatosteatosis is the most prevalent liver condition worldwide, but its impact on the incidence of metachronous CRLM is understudied. In the present study, we aimed to investigate the predictive value of hepatic steatosis on the development of metachronous CRLM. First, a nested case-control study was conducted, enrolling stage I to III CRC patients in the National Colorectal Cancer Cohort (NCRCC) database. Metachronous CRLM patients and recurrence-free patients were matched via propensity-score matching. Fatty liver was identified based on treatment-naïve CT scans and the degree of hepatic fibrosis was scored. Multivariable analysis was conducted to investigate the association between fatty liver and metachronous CRLM. In our database, a total of 414 patients were included. Metachronous CRLM patients had considerably higher rates of hepatic steatosis (30.9% versus 15.9%, P<0.001) and highly fibrotic liver (11.6% versus 2.9%, P=0.001) compared to recurrence-free patients. Multivariable analysis showed that fatty liver (odds ratios [OR]=1.99, 95% confidence interval [CI] 1.19-3.30, P=0.008) and fibrotic liver (OR=4.27, 95% CI 1.54-11.81, P=0.005) were associated with high risk of metachronous CRLM. Further, a systematic literature review was performed to assess available evidence on the association between hepatosteatosis and development of metachronous CRLM. In the systematic review, 1815 patients were pooled from eligible studies, and hepatic steatosis remained a significant risk factor for metachronous CRLM (OR=1.90, 95% CI 1.35-2.66, P<0.001, I2=25.3%). In conclusion, our data suggest that patients with a steatotic liver and a high fibrosis score at CRC diagnosis have elevated risk of developing metachronous CRLM.

Treatment response assessment to chemotherapy with bevacizumab for colorectal liver metastasis by contrast-enhanced ultrasound.

Though contrast-enhanced ultrasound (CEUS) perfusion parameters have been approved to be potential indicators for response to chemotherapy in solid tumors, their ability in assessment of colorectal liver metastasis (CRLM) to chemotherapy with bevacizumab (Bev) has rarely been investigated. From March 2021 to May 2022, 115 consecutive CRLM patients with CEUS pre- and post-2 months' chemotherapy with Bev were prospectively enrolled. One target lesion per patient underwent CEUS quantitative analysis with SonoLiver software. Rise time, time-to-peak, mean transit time, maximal intensity (IMAX), and area under the time-intensity curve (AUC) were assessed with region of interest (ROI) selected on whole lesion, lesion periphery, and internal lesion, respectively. The reduction and ratio of post- to pre-treatment in parameters were investigated in development cohort (n=89) and validated in internal validation cohort (n=26) according to the chronological order. With modified Response Evaluation Criteria in Solid Tumor as reference, 48, 14 responders and 41, 12 non-responders were included in development and validation cohort, respectively. Significantly smaller values of IMAX and AUC on ROIwhole, ROIperipheral, and ROIinternal, were observed post-treatment in development cohort (all P<0.05). In predicting treatment response, the influence of ROI selection was observed when using ∆IMAX and ∆AUC, while no influence was observed using ratios. Areas under the receiver operating characteristic curve (AUROCs) for ∆IMAX and ∆AUC on ROIperipheral were 0.939 (0.867-0.979), 0.951 (0.883-0.985), and 0.917 (0.740-0.988), 0.923 (0.748-0.990) in development and validation cohort, respectively. For ratios of IMAX and AUC, AUROCs were 0.976 (0.919-0.997), 0.938 (0.865-0.978), and 0.899 (0.717-0.982), 0.982 (0.836-1.000) in development and validation cohort, respectively. IMAX and AUC showed significant reductions in responders, and different analyses ROIs influence the performance of ∆IMAX and ∆AUC in response assessment. Parameters derived from ROI peripheral exhibited the most promising results in predicting treatment response.