Unresectable Colorectal Cancer Liver Metastases Research Articles

Prognostic factors for overall survival and safety of trans-arterial chemoembolization (TACE) with irinotecan-loaded drug-eluting beads (DEBIRI) in patients with colorectal liver metastases.

Transarterial chemoembolisation with irinotecan-loaded drug-eluting beads (DEBIRI TACE) can be considered in patients with unresectable colorectal cancer liver metastases (CRLM) who progress after all approved standard therapies or in patients unsuitable for systemic therapy. Between September 2010 and March 2020, thirty patients (22 men and 8 women; mean age 66.8 ± 13.2) were included in this retrospective study. DEBIRI TACE was conducted in 43% of patients unsuitable for systemic therapy as a first-line treatment and 57% as salvage therapy after the progression of systemic therapy. All the patients had liver-limited disease. In the case of unilobar disease, two treatments were performed at four-week intervals, and in the case of bilobar disease, four treatments were performed at two-week intervals. All patients were premedicated and monitored after the procedure. Adverse events were graded according to the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) classification system for complications. The median overall survival (OS) from the beginning of DEBIRI TACE in the salvage group was 17.4 months; in the group without prior systemic therapy, it was 21.6 months. The median overall survival of all patients was 17.4 months (95% confidence interval [CI]: 10.0-24.7 months), and progression-free survival (PFS) was 4.2 months (95% CI: 0.9-7.4 months). The one-year survival rate after the procedure was 61%, and the two-year rate was 25%. Univariate analysis showed better survival of patients with four or fewer liver metastases (p = 0.002). There were no treatment-related deaths or grade 4 and 5 adverse events. Nonserious adverse events (Grades 1 and 2) were present in 53% of patients, and Grade 3 adverse events were present in 6% of the patients. DEBIRI TACE is a well-tolerated treatment option for patients with liver metastases of colorectal cancer. Patients with four or fewer liver metastases correlated with better survival.

Expanding MELD exceptions for colorectal liver metastasis: data and policy.

While liver transplant for unresectable colorectal cancer liver metastases (CRLM) has been demonstrated to be a promising treatment in selected patients, the typically low MELD score of these patients and lack of exception points may lead to challenges in receiving a deceased donor liver for transplant. Several studies have shown improved outcomes in select patients with CRLM who undergo liver transplant, and several trials are ongoing and will conclude in the next several years. MELD exception points have recently been proposed in qualifying patients with CRLM to help this group obtain more timely quality allografts. Under the current proposal, patients with CRLM would receive a score of the median MELD at transplant (MMaT) for their center minus 20 with a minimum score of 15 in cases where MMaT minus 20 would be less than 15. This would allow them to receive transplants faster without competing unnecessarily with those with greater medical need. Giving MELD exception points to patients with colorectal cancer liver metastases in need of transplant may decrease time on the waitlist and improve outcomes for these patients.

Methylated ctDNA predicts early recurrence risk in patients undergoing resection of initially unresectable colorectal cancer liver metastases.

Patients with initially unresectable colorectal cancer liver metastases (IU-CRLM) might benefit from using an effective systemic treatment followed by resection of liver metastases but the curative success rate is quite low. Indeed, nearly one-third of patients exhibit early recurrence within the first 6 months after surgery, and these individuals often have poor overall survival. This study aims to clarify the application value of serial circulating tumor DNA (ctDNA) analysis in predicting the clinical outcome of IU-CRLM patients following liver metastasectomy. A retrospective study was conducted on a cohort of patients with IU-CRLM between February 2018 and April 2021. Plasma samples at different time points during CRLM treatment [baseline (BL), preoperation (PRE), postoperation (POST), end-of-treatment (EOT), and progressive disease (PD)] were retrospectively collected from patients with initially unresectable CRLM enrolled at the Sun Yat-sen University Cancer Center. Dynamic changes of SEPTIN 9 (SEPT9) and Neuropeptide Y (NPY) methylated circulating tumor DNA (MetctDNA) levels in serial plasma samples were detected using droplet-digital PCR (ddPCR). SEPT9 and NPY genes were hypermethylated in colon cancer cell lines and tissues while no difference was observed between primary and metastatic tumors. Patients with MetctDNA positive at POST or EOT had significantly lower recurrence-free survival (RFS) compared to patients with MetctDNA negative at these time points [POST: Hazard ratio (HR) 9.44, 95% confidence interval (CI) 5.15-17.30, p < 0.001; EOT: HR 11.48, 95% CI 3.27-40.31, p < 0.001]. Multivariate analysis demonstrated that POST (OR 33.96, 95% CI 4.03-286.10, p = 0.001) and EOT (OR 18.36, 95% CI 1.14-295.71, p = 0.04) MetctDNA was an independent risk factor for early recurrence. Time-dependent receiver operating characteristic curve (T-ROC) analysis revealed that area under the curve (AUC) value was greatest at the relapse time point of 6 months post-intervention, with POST-AUC and EOT-AUC values of 0.74 (95% CI 0.66-0.81) and 0.73 (95% CI 0.53-0.94), respectively. Serial MetctDNA analysis showed that RFS was significantly lower in patients with no MetctDNA clearance compared with those with MetctDNA clearance (HR 26.05, 95% CI 4.92-137.81, p < 0.001). Our study confirmed that serial ctDNA analysis of NPY and SEPT9 gene methylation could effectively predict early recurrence in IU-CRLM patients, especially at POST and EOT.

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

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

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

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

Identifying Genetic Mutation Status in Patients with Colorectal Cancer Liver Metastases Using Radiomics-Based Machine-Learning Models

For patients with colorectal cancer liver metastases (CRLM), the genetic mutation status is important in treatment selection and prognostication for survival outcomes. This study aims to investigate the relationship between radiomics imaging features and the genetic mutation status (KRAS mutation versus no mutation) in a large multicenter dataset of patients with CRLM and validate these findings in an external dataset. Patients with initially unresectable CRLM treated with systemic therapy of the randomized controlled CAIRO5 trial (NCT02162563) were included. All CRLM were semi-automatically segmented in pre-treatment CT scans and radiomics features were calculated from these segmentations. Additionally, data from the Netherlands Cancer Institute (NKI) were used for external validation. A total of 255 patients from the CAIRO5 trial were included. Random Forest, Gradient Boosting, Gradient Boosting + LightGBM, and Ensemble machine-learning classifiers showed AUC scores of 0.77 (95%CI 0.62–0.92), 0.77 (95%CI 0.64–0.90), 0.72 (95%CI 0.57–0.87), and 0.86 (95%CI 0.76–0.95) in the internal test set. Validation of the models on the external dataset with 129 patients resulted in AUC scores of 0.47–0.56. Machine-learning models incorporating CT imaging features could identify the genetic mutation status in patients with CRLM with a good accuracy in the internal test set. However, in the external validation set, the models performed poorly. External validation of machine-learning models is crucial for the assessment of clinical applicability and should be mandatory in all future studies in the field of radiomics.

Deep radiomics-based fusion model for prediction of bevacizumab treatment response and outcome in patients with colorectal cancer liver metastases: a multicentre cohort study

Accurate tumour response prediction to targeted therapy allows for personalised conversion therapy for patients with unresectable colorectal cancer liver metastases (CRLM). In this study, we aimed to develop and validate a multi-modal deep learning model to predict the efficacy of bevacizumab in patients with initially unresectable CRLM using baseline PET/CT, clinical data, and colonoscopy biopsy specimens. In this multicentre cohort study, we retrospectively collected data of 307 patients with CRLM from the BECOME study (NCT01972490) (Zhongshan Hospital of Fudan University, Shanghai) and two independent Chinese cohorts (internal validation cohort from January 1, 2018 to December 31, 2018at Zhongshan Hospital of Fudan University; external validation cohort from January 1, 2020 to December 31, 2020at Zhongshan Hospital-Xiamen, Shanghai, and the First Hospital of Wenzhou Medical University, Wenzhou). The main inclusion criteria were that patients with CRLM had pre-treatment PET/CT images as well as colonoscopy specimens. After extracting PET/CT features with deep neural networks (DNN) and selecting related clinical factors using LASSO analysis, a random forest classifier was built as the Deep Radiomics Bevacizumab efficacy predicting model (DERBY). Furthermore, by combining histopathological biomarkers into DERBY, we established DERBY+. The performance of model was evaluated using area under the curve (AUC), sensitivity, specificity, positive predictive value, and negative predictive value. DERBY achieved promising performance in predicting bevacizumab sensitivity with an AUC of 0.77 and 95% confidence interval (CI) [0.67-0.87]. After combining histopathological features, we developed DERBY+, which had more robust accuracy for predicting tumour response in external validation cohort (AUC 0.83 and 95% CI [0.75-0.92], sensitivity 80.4%, specificity 76.8%). DERBY+ also had prognostic value: the responders had longer progression-free survival (median progression-free survival: 9.6 vs 6.3 months, p=0.002) and overall survival (median overall survival: 27.6 vs 18.5 months, p=0.010) than non-responders. This multi-modal deep radiomics model, using PET/CT, clinical data and histopathological data, was able to identify patients with bevacizumab-sensitive CRLM, providing a favourable approach for precise patient treatment. To further validate and explore the clinical impact of this work, future prospective studies with larger patient cohorts are warranted. The National Natural Science Foundation of China; Fujian Provincial Health Commission Project; Xiamen Science and Technology Agency Program; Clinical Research Plan of SHDC; Shanghai Science and Technology Committee Project; Clinical Research Plan of SHDC; Zhejiang Provincial Natural Science Foundation of China; and National Science Foundation of Xiamen.

LBA27 First-line systemic treatment in patients with initially unresectable colorectal cancer liver metastases (CRLM): Overall survival of the phase III CAIRO5 study of the Dutch Colorectal Cancer Group

LBA27 First-line systemic treatment in patients with initially unresectable colorectal cancer liver metastases (CRLM): Overall survival of the phase III CAIRO5 study of the Dutch Colorectal Cancer Group

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

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

First-line systemic treatment strategies in patients with initially unresectable colorectal cancer liver metastases (CAIRO5): an open-label, multicentre, randomised, controlled, phase 3 study from the Dutch Colorectal Cancer Group

Patients with initially unresectable colorectal cancer liver metastases might qualify for local treatment with curative intent after reducing the tumour size by induction systemic treatment. We aimed to compare the currently most active induction regimens. In this open-label, multicentre, randomised, phase 3 study (CAIRO5), patients aged 18 years or older with histologically confirmed colorectal cancer, known RAS/BRAFV600E mutation status, WHO performance status of 0-1, and initially unresectable colorectal cancer liver metastases were enrolled at 46 Dutch and one Belgian secondary and tertiary centres. Resectability or unresectability of colorectal cancer liver metastases was assessed centrally by an expert panel of liver surgeons and radiologists, at baseline and every 2 months thereafter by predefined criteria. Randomisation was done centrally with the minimisation technique via a masked web-based allocation procedure. Patients with right-sided primary tumour site or RAS or BRAFV600E mutated tumours were randomly assigned (1:1) to receive FOLFOX or FOLFIRI plus bevacizumab (group A) or FOLFOXIRI plus bevacizumab (group B). Patients with left-sided and RAS and BRAFV600E wild-type tumours were randomly assigned (1:1) to receive FOLFOX or FOLFIRI plus bevacizumab (group C) or FOLFOX or FOLFIRI plus panitumumab (group D), every 14 days for up to 12 cycles. Patients were stratified by resectability of colorectal cancer liver metastases, serum lactate dehydrogenase concentration, choice of irinotecan versus oxaliplatin, and BRAFV600E mutation status (for groups A and B). Bevacizumab was administered intravenously at 5 mg/kg. Panitumumab was administered intravenously at 6 mg/kg. FOLFIRI consisted of intravenous infusion of irinotecan at 180 mg/m2 with folinic acid at 400 mg/m2, followed by bolus fluorouracil at 400 mg/m2 intravenously, followed by continuous infusion of fluorouracil at 2400 mg/m2. FOLFOX consisted of oxaliplatin at 85 mg/m2 intravenously together with the same schedule of folinic acid and fluorouracil as in FOLFIRI. FOLFOXIRI consisted of irinotecan at 165 mg/m2 intravenously, followed by intravenous infusion of oxaliplatin at 85 mg/m2 with folinic acid at 400 mg/m2, followed by continuous infusion of fluorouracil at 3200 mg/m2. Patients and investigators were not masked to treatment allocation. The primary outcome was progression-free survival, analysed on a modified intention-to-treat basis, excluding patients who withdrew consent before starting study treatment or violated major entry criteria (no metastatic colorectal cancer, or previous liver surgery for colorectal cancer liver metastases). The study is registered with ClinicalTrials.gov, NCT02162563, and accrual is complete. Between Nov 13, 2014, and Jan 31, 2022, 530 patients (327 [62%] male and 203 [38%] female; median age 62 years [IQR 54-69]) were randomly assigned: 148 (28%) patients to group A, 146 (28%) patients to group B, 118 (22%) patients to group C, and 118 (22%) patients to group D. Groups C and D were prematurely closed for futility. 521 patients were included in the modified intention-to-treat population (147 in group A, 144 in group B, 114 in group C, and 116 in group D). The median follow-up at the time of this analysis was 51·1 months (95% CI 47·7-53·1) in groups A and B and 49·9 months (44·5-52·5) in in groups C and D. Median progression-free survival was 9·0 months (95% CI 7·7-10·5) in group A versus 10·6 months (9·9-12·1) in group B (stratified hazard ratio [HR] 0·76 [95% CI 0·60-0·98]; p=0·032), and 10·8 months (95% CI 9·9-12·6) in group C versus 10·4 months (9·8-13·0) in group D (stratified HR 1·11 [95% CI 0·84-1·48]; p=0·46). The most frequent grade 3-4 events in groups A and B were neutropenia (19 [13%] patients in group A vs 57 [40%] in group B; p<0·0001), hypertension (21 [14%] vs 20 [14%]; p=1·00), and diarrhoea (five [3%] vs 28 [19%]; p<0·0001), and in groups C and D were neutropenia (29 [25%] vs 24 [21%]; p=0·44), skin toxicity (one [1%] vs 29 [25%]; p<0·0001), hypertension (20 [18%] vs eight [7%]; p=0·016), and diarrhoea (five [4%] vs 18 [16%]; p=0·0072). Serious adverse events occurred in 46 (31%) patients in group A, 75 (52%) patients in group B, 41 (36%) patients in group C, and 49 (42%) patients in group D. Seven treatment-related deaths were reported in group B (two due to multiorgan failure, and one each due to sepsis, pneumonia, portal vein thrombosis, septic shock and liver failure, and sudden death), one in group C (multiorgan failure), and three in group D (cardiac arrest, pulmonary embolism, and abdominal sepsis). In patients with initially unresectable colorectal cancer liver metastases, FOLFOXIRI-bevacizumab was the preferred treatment in patients with a right-sided or RAS or BRAFV600E mutated primary tumour. In patients with a left-sided and RAS and BRAFV600E wild-type tumour, the addition of panitumumab to FOLFOX or FOLFIRI showed no clinical benefit over bevacizumab, but was associated with more toxicity. Roche and Amgen.

Initially unresectable colorectal liver metastases: the best therapeutic regimens

Despite the advances in systemic chemotherapy and molecular targeted therapy, local treatment, including resection and local ablative treatment, is the only treatment of choice that can provide prolonged survival in patients with colorectal liver metastases. Therefore, for initially unresectable colorectal liver metastases, a sufficient response to optimal systemic chemotherapy with biological targeted drugs to allow subsequent surgical treatment would be an important development and could lead to improvemnts in long-term survival. However, the diversity of this complex disease, including molecular and genetic alterations and embryologic origin of the primary tumour, the small number of trials, and the absence of a universal definition for surgical resectability or unresectability complicates the development of a consensus on optimal therapeutic approaches. First-line systemic treatment strategies in patients with initially unresectable colorectal cancer liver metastases (CAIRO5): an open-label, multicentre, randomised, controlled, phase 3 study from the Dutch Colorectal Cancer GroupIn patients with initially unresectable colorectal cancer liver metastases, FOLFOXIRI-bevacizumab was the preferred treatment in patients with a right-sided or RAS or BRAFV600E mutated primary tumour. In patients with a left-sided and RAS and BRAFV600E wild-type tumour, the addition of panitumumab to FOLFOX or FOLFIRI showed no clinical benefit over bevacizumab, but was associated with more toxicity. Full-Text PDF

Liquid Biopsy by ctDNA in Liver Transplantation for Colorectal Cancer Liver Metastasis

IntroductionColorectal cancer is a leading cause of cancer-related death worldwide. Metastatic liver disease develops in 50% of cases and drives patient outcomes. Although the ideal treatment for colorectal cancer liver metastases (CRLM) is resection, only a third of patients are suitable for this approach. Reports of liver transplantation in selected patients with unresectable CRLM have shown encouraging results compared to conventional forms of therapy. No study to date has examined the utility of liquid biopsy circulating tumor DNA (ctDNA) for evaluation of residual disease in this cohort of patients. We report a small series of liver transplantation in patients with CRLM in whom ctDNA was assessed peri-operatively. MethodsFive patients underwent liver transplantation for unresectable CRLM or liver failure following CRLM treatment from 2018 to 2022. Clinical data, cross-sectional imaging, and serum biomarkers including peri-operative ctDNA were reviewed from electronic medical records. ResultsAll patients are alive without radiologic evidence of disease at time of this publication. Median time of follow-up was 32 months (IQR 6.6–40 months). ctDNA was assessed before (4 patients) and after transplant (6 patients). One patient experienced a pulmonary recurrence that was resected, for whom pre-recurrence ctDNA was not available; the remaining patients have not experienced recurrence. Four patients are without evidence of ctDNA following transplant, and two demonstrate persistent ctDNA positivity post-transplant. Three of four patients with positive pre-transplant ctDNA remain ctDNA-negative post-transplant. ConclusionsLiver transplantation for liver-confined unresectable CRLM is emerging as a valid surgical option in selected patients. The significance of liquid biopsy in this population remains elusive due to lack of data. The clearance of ctDNA after transplant in these patients with metastatic disease and despite their immunosuppression is notable. The significance and usefulness of liquid biopsy in patient selection, surveillance, and as an indication for treatment warrant further investigation.

Comparison of the therapeutic efficacy between systemic chemotherapy with and without radiofrequency ablation for colorectal cancer liver metastases: A propensity score matching study.

To compare therapeutic efficacy between systemic chemotherapy (SC) alone and preoperative SC followed by radiofrequency ablation (SC+RFA) in patients with colorectal cancer liver metastases (CRLM). This study identified a cohort of patients with CRLM after treatment between 2010 and 2016. Patients who received SC+RFA were compared with SC patients by propensity score matching. Overall survival (OS) and intrahepatic progression-free survival (PFS) were compared using stratified log-rank test. The outcomes after SC and SC+RFA were also assessed in patient subgroups. This study identified 338 patients with CRLM who had underwent SC and had different response to chemotherapy, including non-progressive disease (non-PD) or progressive disease (PD). Of this cohort, 64 patients in SC+RFA group were matched by propensity score to 64 patients who received SC alone. Compared with SC cohort, the SC+RFA cohort yielded better OS (HR, 0.403; 95% CI, 0.271-0.601) and PFS (HR, 0.190; 95% CI, 0.113-0.320). The estimated OS rates at 1, 3 and 5 years were 93.8%, 51.6% and 15.6% for SC+RFA group and 81.3%, 26.6% and 10.9% for SC group (p＜0.001). The cumulative PFS rates at 1, 3, and 5 years were 43.8 %, 14.1% and 3.1% for the SC+RFA group and 1.6%, 0 and 0% for SC group (p＜0.0001). In subgroup analysis, compared with patients with PD response, patients with non-PD response could gain better PFS (HR, 0.207; 95% CI, 0.121-0.354) and OS (HR, 0.390; 95% CI, 0.246-0.617). RFA was associated with improved OS and intrahepatic PFS in CRLM patients with preoperative SC,especially in non-PD response subgroup after SC. The addition of RFA was advocated for CRLM patients with preoperative SC. This study will provide important reference and evidence to better perform the management of unresectable CRLM.

Hepatic artery infusion for unresectable colorectal cancer liver metastases: Palliation and conversion

Patients with unresectable colorectal liver metastases are commonly treated with systemic chemotherapy to convert their disease to an operable state. Unfortunately, many patients remain unresectable after first-line chemotherapy and resort to second- and third-line regimens with poor results. Liver-directed strategies have historically been used in this setting. There has been a renewed interest in offering hepatic artery infusion chemotherapy combined with systemic chemotherapy to improve resectability or palliate disease. Prospective studies over the past 2 decades have produced encouraging data, even in chemorefractory patients. This therapy has expanded to multiple centers across North America and worldwide with similar results. This review addresses these data, specifically focusing on conversion to resection and palliation of colorectal liver metastases after patients have received multiple lines of systemic chemotherapy.

Invited Commentary: Living-Donor Liver Transplantation for Patients with Unresectable Colorectal Cancer Liver Metastasis: New Option for Highly Selected Patients.

Journal of the American College of Surgeons ():10.1097/XCS.0000000000000728, May 09, 2023. | DOI: 10.1097/XCS.0000000000000728

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.

ASO Author Reflections: Towards Consensus on Resectability Assessments and Local Treatment Planning for Patients with Initially Unresectable Colorectal Cancer Liver Metastases.

ASO Author Reflections: Towards Consensus on Resectability Assessments and Local Treatment Planning for Patients with Initially Unresectable Colorectal Cancer Liver Metastases.

CT-based radiomics for the identification of colorectal cancer liver metastases sensitive to first-line irinotecan-based chemotherapy.

Chemosensitivity prediction in colorectal cancer patients with liver metastases has remained a research hotspot. Radiomics can extract features from patient imaging, and deep learning or machine learning can be used to build models to predict patient outcomes prior to chemotherapy. In this study, the radiomics features and clinical data of colorectal cancer patients with liver metastases were used to predict their sensitivity to irinotecan-based chemotherapy. A total of 116 patients with unresectable colorectal cancer liver metastases who received first-line irinotecan-based chemotherapy from January 2015 to January 2020 in our institution were retrospectively collected. Overall, 116 liver metastases were randomly divided into training (n = 81) and validation (n = 35) cohorts in a 7:3 ratio. The effect of chemotherapy was determined based on Response Evaluation Criteria in Solid Tumors. The lesions were divided into response and nonresponse groups. Regions of interest (ROIs) were manually segmented, and sample sizes of 1×1×1, 3×3×3, 5×5×5 mm3 were used to extract radiomics features. The relevant features were identified through Pearson correlation analysis and the MRMR algorithm, and the clinical data were merged into the artificial neural network. Finally, the p-model was obtained after repeated learning and testing. The p-model could distinguish responders in the training (area under the curve [AUC] 0.754, 95% CI 0.650-0.858) and validation cohorts (AUC 0.752 95% CI 0.581-0.904). AUC values of the pure image group model are 0.720 (95% CI 0.609-0.827) and 0.684 (95% CI 0.529-0.890) for the training and validation cohorts respectively. As for the clinical data model, AUC values of the training and validation cohorts are 0.638 (95% CI 0.500-0.757) and 0.545 (95% CI 0.360-0.785), respectively. The performances of the latter two are less than that of the former. The p-model has the potential to discriminate colorectal cancer patients sensitive to chemotherapy. This model holds promise as a noninvasive tool to predict the response of colorectal liver metastases to chemotherapy, allowing for personalized treatment planning.

United Kingdom criteria for liver transplantation in the setting of isolated unresectable colorectal liver metastases.

Studies have demonstrated that liver transplantation may be an effective treatment for isolated unresectable colorectal cancer liver metastases (CRCLM). Published data suggest that 5-year survival may be as high as 80%; however, recurrent disease is commonplace. Consequently, the Liver Transplantation for Unresectable Colorectal Liver Metastases Fixed Term Working Unit recommended to the NHS Blood and Transplant Liver Advisory Group that while CRCLM is an appropriate indication for transplantation, selection criteria should be conservative and that it should be undertaken within a clinical service evaluation programme. The aim of this work is to outline the proposed UK selection criteria and follow-up process for CRCLM transplantation. Consensus statement by colorectal cancer/liver transplantation patient representatives, experts in colorectal cancer surgery/oncology, liver transplantation surgery, hepatology, hepatobiliary radiology, hepatobiliary pathology and nuclear medicine. This study provides a comprehensive outline of the inclusion/exclusion criteria for referral in the UK. Furthermore, the referral framework is also explained. Pretransplant assessment criteria for listing/delisting are outlined. Finally, the oncology-specific outcome measures posttransplant are described. It is anticipated this service will begin in December 2022. A series of educational events for the referrers and transplant units will be arranged throughout 2023 to highlight CRCLM as a newly accepted UK indication for transplantation. A national audit will be undertaken to identify patients currently on treatment who meet the criteria for transplant. Data will be collected in a national registry and reviewed on an ongoing basis to confirm the safety of this treatment and to determine if the inclusion criteria require revision.