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Background Radiofrequency ablation (RFA) and microwave ablation (MWA) are widely accepted techniques to eliminate small unresectable colorectal liver metastases (CRLM). Although previous studies labelled thermal ablation inferior to surgical resection, the apparent selection bias when comparing patients with unresectable disease to surgical candidates, the superior safety profile, and the competitive overall survival results for the more recent reports mandate the setup of a randomized controlled trial. The objective of the COLLISION trial is to prove non-inferiority of thermal ablation compared to hepatic resection in patients with at least one resectable and ablatable CRLM and no extrahepatic disease. Methods In this two-arm, single-blind multi-center phase-III clinical trial, six hundred and eighteen patients with at least one CRLM (≤3 cm) will be included to undergo either surgical resection or thermal ablation of appointed target lesion(s) (≤3 cm). Primary endpoint is OS (overall survival, intention-to-treat analysis). Main secondary endpoints are overall disease-free survival (DFS), time to progression (TTP), time to local progression (TTLP), primary and assisted technique efficacy (PTE, ATE), procedural morbidity and mortality, length of hospital stay, assessment of pain and quality of life (QoL), cost-effectiveness ratio (ICER) and quality-adjusted life years (QALY). Discussion If thermal ablation proves to be non-inferior in treating lesions ≤3 cm, a switch in treatment-method may lead to a reduction of the post-procedural morbidity and mortality, length of hospital stay and incremental costs without compromising oncological outcome for patients with CRLM. Trial registration NCT03088150 , January 11th 2017.

Objectives To obtain the diagnostic performance of diffusion-weighted (DW) and gadoxetic-enhanced magnetic resonance (MR) imaging in the detection of liver metastases. Methods A comprehensive search (EMBASE, PubMed, Cochrane) was performed to identify relevant articles up to June 2015. Inclusion criteria were: liver metastases, DW-MR imaging and/or gadoxetic acid-enhanced MR imaging, and per-lesion statistics. The reference standard was histopathology, intraoperative observation and/or follow-up. Sources of bias were assessed using the QUADAS-2 tool. A linear mixed-effect regression model was used to obtain sensitivity estimates. Results Thirty-nine articles were included (1,989 patients, 3,854 metastases). Sensitivity estimates for DW-MR imaging, gadoxetic acid-enhanced MR imaging and the combined sequence for detecting liver metastases on a per-lesion basis was 87.1 %, 90.6 % and 95.5 %, respectively. Sensitivity estimates by gadoxetic acid-enhanced MR imaging and the combined sequence were significantly better than DW-MR imaging ( p  = 0.0001 and p  < 0.0001, respectively), and the combined MR sequence was significantly more sensitive than gadoxetic acid-enhanced MR imaging ( p  < 0.0001). Similar results were observed in articles that compared the three techniques simultaneously, with only colorectal liver metastases and in liver metastases smaller than 1 cm. Conclusions In patients with liver metastases, combined DW-MR and gadoxetic acid-enhanced MR imaging has the highest sensitivity for detecting liver metastases on a per-lesion basis. Key Points • DW-MRI is less sensitive than gadoxetic acid-enhanced MRI for detecting liver metastases • DW-MRI and gadoxetic acid-enhanced MRI is the best combination • Same results are observed in colorectal liver metastases • Same results are observed in liver metastases smaller than 1 cm • Same results are observed when histopathology alone is the reference standard

Purpose of ReviewThis review addresses the current landscape of colorectal cancer (CRC) with a focus on liver metastases, the third most common cancer globally. It explores recent findings in treatment strategies, emphasizing the dynamic interplay between surgery, systemic chemotherapy, and local therapies for synchronous colorectal liver metastases (CRLMs).Recent FindingsHighlighting the role of advanced imaging, the review underscores the significance of contrast-enhanced MRI in surgical planning for CRLMs. Surgical resection remains a primary choice for resectable cases, with considerations for oncologic scoring systems and tumor biology. Perioperative systemic chemotherapy plays a pivotal role, especially in conversion therapy for initially unresectable CRLMs. The review also explores various local therapies, including radiofrequency ablation, microwave ablation, stereotactic body radiotherapy, hepatic arterial infusional chemotherapy, selective internal radiation therapy, and transarterial chemoembolization for unresectable cases.SummaryA comprehensive approach, integrating surgery, systemic chemotherapy, and local therapies, is crucial for managing synchronous CRLMs. Surgical resection and perioperative chemotherapy are key players, guided by considerations of tumor biology and scoring systems. For unresectable cases, local therapies offer viable alternatives, emphasizing the need for tailored treatments. Multidisciplinary collaboration among medical oncologists, surgeons, and radiologists is essential. Ongoing research will refine treatment approaches, while emerging technologies hold promise for further advancements in managing colorectal liver metastases.

PurposeSBRT demonstrated to increase survival in oligometastatic patients. Nevertheless, little is known regarding the natural history of oligometastatic disease (OMD) and how SBRT may impact the transition to the polymetastatic disease (PMD).Methods97 liver metastases in 61 oligometastatic patients were treated with SBRT. Twenty patients (33%) had synchronous oligometastases, 41 (67%) presented with metachronous oligometastases. Median number of treated metastases was 2 (range 1–5).ResultsMedian follow-up was 24 months. Median tPMC was 11 months (range 4–17 months). Median overall survival (OS) was 23 months (range 16–29 months). Cancer-specific survival predictive factors were having further OMD after SBRT (21 months versus 15 months; p = 0.00), and local control of treated metastases (27 months versus 18 months; p = 0.031). Median PFS was 7 months (range 4–12 months). Patients with 1 metastasis had longer median PFS as compared to those with 2–3 and 4–5 metastases (14.7 months versus 5.3 months versus 6.5 months; p = 0.041). At the last follow-up, 50/61 patients (82%) progressed, 16 of which (26.6%) again as oligometastatic and 34 (56%) as polymetastatic.ConclusionIn the setting of oligometastatic disease, SBRT is able to delay the transition to the PMD. A proportion of patients relapse as oligometastatic and can be eventually evaluated for a further SBRT course. Interestingly, those patients retain a survival benefit as compared to those who had PMD. Further studies are needed to explore the role of SBRT in OMD and to identify treatment strategies able to maintain the oligometastatic state.

Colorectal cancer liver metastases (CRLM) represent most of the causes of death in patients with colorectal cancer. Surgical resection is the only treatment that can provide the possibility of prolonged survival, or even cure, for patients with CRLM. Over the last few decades, survival of these patients has improved dramatically thanks to more effective chemotherapy, extension of surgical indications, and development of new surgical procedures. In particular, patients with initially unresectable CRLM can achieve downsizing of the tumor by using various chemotherapies and the tumor can become resectable. It has been shown that such patients have a 33% 5‐year survival and a 23% 10‐year survival rate after surgery, which is a little bit lower than that of patents with resectable CRLM but significantly higher than patients without surgery. However, a decision‐making strategy for patients with CRLM is difficult because there is a wide variety of treatments and no definitive consensus. As an example, much variation among institutions exists on the resectability rate in patients with unresectable CRLM. Also, it is recommended that all patients with CRLM be managed by a multidisciplinary approach (MDA) to select the best strategy. In the future, new treatment procedures (e.g. immune checkpoint blockade, liver transplantation) may contribute to improve prognosis; hence, the necessity for MDA for the treatment of CRLM will further increase.

Mucinous adenocarcinoma represents a distinct histological subtype of colorectal cancer. To date there has been limited data available for patients with colorectal cancer liver metastases (CRCLM) derived from mucinous adenocarcinoma. This systematic review and meta-analysis aims to provide data on the clinicopathological and survival outcomes of this cohort. Databases were searched for studies comparing clinicopathological and survival outcomes between patients with mucinous CRCLM and CRCLM from adenocarcinoma not otherwise specified who underwent liver resection. A random-effects model was used for analysis. Eight studies describing 9157 patients were included. Mucinous CRCLM were positively associated with colon tumors (OR 1⋅64, P = 0⋅01), T3/T4 tumors (OR 1⋅58, P = 0⋅02), node positive tumors (OR 1⋅55, P = 0⋅005). The review also identified a trend towards worse overall survival in patients with mucinous CRCLM. Despite the distinct clinicopathological characteristics and impaired long term outcomes of mucinous CRCLM, resection should remain the gold standard where possible. •Mucinous CRC liver metastases are more likely to come from colon tumors.•Mucinous CRC liver metastases are more likely to come from T3 or T4 tumors.•Mucinous CRC liver metastases are more likely to come from node positive tumors.•Mucinous colorectal liver metastases are associated with worse overall survival.•Resection of the metastases should remain the main stay of treatment where possible.

Background Preoperative chemotherapy, or neoadjuvant therapy (NAC) can be used to improve resectability but can also have hepatotoxic effects on the future liver remnant. The purpose of this study was to investigate the impact of NAC on 30-day morbidity among patients undergoing a resection of primary colon cancer and synchronous liver metastases (sLM). Methods This was a retrospective study using the National Surgical Quality Improvement Program database (2012–2020). The association between NAC and 30-day overall morbidity, the primary outcome, was assessed. Subgroup analyses for low and high-risk procedures were performed. Results Among 968 patients who underwent the combined resection, 571 (58.99%) received NAC. There was a lower rate of 30-day overall morbidity among patients who received NAC (34.50% vs. 41.56%, p  = 0.026) and no difference in rates of postoperative liver failure, bile leak, need for invasive intervention for hepatic procedure, and anastomotic leak. On adjusted analyses, patients who received NAC had decreased odds of overall morbidity (OR 0.73, 95% CI 0.55–0.97, p  = 0.031) compared to patients who did not receive NAC. On subgroup analyses, patients who received NAC prior to a low risk combined resection had lower rates of overall morbidity on both adjusted and unadjusted analyses. Among those undergoing high-risk combined resections, there was no difference in overall morbidity. Discussion and Conclusion Patients who are deemed to be candidates for preoperative chemotherapy can proceed with planned neoadjuvant chemotherapy prior to combined resection of primary colon cancer and sLM as preoperative neoadjuvant chemotherapy does not appear to be associated with increased postoperative morbidity.

Introduction Cancer heterogeneity and degree of intra-tumoral immune cells represent variables affecting overall survival (OS). The present study investigated the impact of natural killer (NK) and T cells infiltrating colorectal liver metastases (CLM) in patients undergoing hepatectomy after neoadjuvant chemotherapy. Methods The frequencies of intra-tumoral, marginal, and peritumoral CD3+ T and NKp46+ NK cells were determined for 121 patients. OS was assessed in relation to prognostic factors. Results At univariate analysis, several variables, including T and N of the primary tumor, metachronous CLM, radiological response, and higher density of intra-tumoral CD3+ T cell (>1%/mm 2 ) and of NKp46+ NK cells (>1 cell/mm 2 ), were associated with OS. Only increased frequencies of intra-tumoral CD3+ T cells ( p  = 0.005) and NKp46+ NK cells ( p  = 0.004) correlated with OS at multivariate analysis. The logistic regression revealed that metachronous CLM (OR = 2.781; p  = 0.002), the use of an epidermal growth factor receptor inhibitor (OR = 3.891; p  = 0.001), and radiological response (OR = 3.219; p  = 0.001) were associated with higher infiltration of these cells. Conclusions High frequencies of NK and T cells in response to chemotherapy predict OS in CLM patients. These findings provide important insights that can help physicians to choose the best treatment option and adopt more predictive follow-up strategies for patients with CLM.

Objective To develop a prognostic model for optimizing management of colorectal liver oligometastases (CLOM) patients with different primary tumor locations who underwent thermal ablation (TA). Materials and Methods The reporting of this retrospective study conforms to STROBE guidelines. A total of 525 CLOM patients who underwent TA from 3 hospitals between 2011 and 2021 were enrolled. Firstly, intra and extrahepatic disease-free survival (DFS) and overall survival (OS) for CLOM patients with different primary tumor locations were analyzed. Then, cox regression models were used to identify independent factors predicting OS. Finally, a prognostic score was developed to identify CLOM patients benefiting from TA. All patient details were de-identified. Results A total of 423 eligible patients were identified, with 762 CLOM (121 male, median age 59 years) and a median follow-up of 45.8 (IQR, 7.3-114.8) months. Independent predictors of OS were identified, including multiple liver metastases (P = .0085), right-sided colon cancer (P = .0210), tumor size ≥2 cm (P = .0273), and lymph node metastasis of primary colorectal cancer (P = .0302), termed as the “MRSL” score. On the basis of the best separation of MRSL score, patients were divided into high-risk (cutoff value ≥8) and low-risk groups (cutoff value <8). Further stratified analysis indicated that right-sided CLOM patients had shorter OS than left-sided patients in the high-risk group (54.9 vs 92.5 months, P = .0156). However, no significant difference in OS was observed between right-sided and left-sided CLOM patients in the low-risk group (97.7 vs 102.2 months, P = .28). Conclusion The MRSL score-based model helps in selecting potential right-sided CLOM patients who benefit from TA.

Background: Liver metastases are a leading cause of cancer-associated deaths in patients affected by colorectal cancer (CRC). The multidisciplinary strategy to treat CRC is more effective when the radiological diagnosis is accurate and early. Despite the evolving technologies in radiological accuracy, the radiological diagnosis of Colorectal Cancer Liver Metastases (CRCLM) is still a key point. The aim of our study was to define a new patient representation different by Artificial Intelligence models, using Formal Methods (FMs), to help clinicians to predict the presence of liver metastasis when still undetectable using the standard protocols. Methods: We retrospectively reviewed from 2013 to 2020 the CT scan of nine patients affected by CRC who would develop liver lesions within 4 months and 8 years. Seven patients developed liver metastases after primary staging before any liver surgery, and two patients were enrolled after R0 liver resection. Twenty-one patients were enrolled as the case control group (CCG). Regions of Interest (ROIs) were identified through manual segmentation on the medical images including only liver parenchyma and eventual benign lesions, avoiding major vessels and biliary ducts. Our predictive model was built based on formally verified radiomic features. Results: The precision of our methods is 100%, scheduling patients as positive only if they will be affected by CRCLM, showing a 93.3% overall accuracy. Recall was 77.8%. Conclusion: FMs can provide an effective early detection of CRCLM before clinical diagnosis only through non-invasive radiomic features even in very heterogeneous and small clinical samples.