Unresectable Colorectal Liver Metastases Research Articles

Efficacy and safety of irinotecan-eluting HepaSphere transarterial chemoembolization combined with hepatic arterial infusion chemotherapy for unresectable colorectal liver metastases.

3585 Background: Both drug-eluting bead transarterial chemoembolization (DEB-TACE) and hepatic arterial infusion chemotherapy (HAIC) are recommended for unresectable colorectal liver metastases (CRLM) treatment. However, the combined application of DEB-TACE and HAIC is not widely accepted. The aim of this single-center retrospective study was to evaluate the efficacy and safety of Irinotecan-eluting HepaSphere chemoembolization combined with HAIC for unresectable CRLM. Methods: Patients with age older than 18 years, histologically confirmed CRLM and treated with Irinotecan-eluting HepaSphere chemoembolization plus HAIC from Oct 2020 to Jan 2022 were enrolled. Patients who had synchronously received other local treatments were excluded. Hepatic progression-free survival (hPFS) and PFS were calculated using Kaplan-Meier method. Adverse events (AE) were evaluated with CTCAE 5.0. Results: The eligible population was 101, composed of 66 males and 35 females. Among them, 54% patients had one of KRAS or NRAS or BRAF gene mutation and ECOG of 62% patients was 1. In addition, 59% patients were refractory to second standard line or above systemic therapy and mean interventional treatment cycles were 3.3. As the follow-up cutoff date was Dec 31, 2022, median duration of follow-up was 17.9 months (95% CI,16.185-19.615). Median hPFS was 8.7 months (95% CI, 6.744-10.658) while median PFS was 6.2 months (95% CI, 5.048-7.352). For the patients who were refractory to second line or above systemic therapy, hPFS and PFS was 6.2 months (95% CI, 4.899-7.501) and 5.2 months (95% CI, 3.682-6.718) respectively. Overall survival has not been reached yet. There were 7 patients achieved clinical complete response. Overall response rate was 41.6% and disease control rate was 82.2%. There was no treatment-related death. 28 patients (27.7%) experienced grade 3 or higher toxicities. The most common treatment related AE were aspartate transaminase/alanine transaminase elevation (41.6%) and bilirubin elevation (40.6%). The hematologic AE included anemia (27.7%), leukopenia (27.7%), neutropenia (14.9%) and thrombocytopenia (28.7%). Conclusions: The combination of Irinotecan-eluting HepaSphere chemoembolization and HAIC is effective and safe for unresectable CRCLM, even for patients who are refractory to second or above systemic therapy, indicating it is a promising regional treatment with improved outcome.

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

Toronto Management of Initially Unresectable Liver Metastases from Colorectal Cancer in a Living Donor Liver Transplant Program.

Living donor liver transplantation (LDLT) is an attractive option for patients with unresectable, bilobar colorectal liver metastases (CRLM). However, it is not available in most centres beyond study protocols. This study describes the interim experience with LDLT for CRLM at a large North American transplant and hepatobiliary centre. Adults with unresectable CRLM, receiving systemic chemotherapy were recruited into a prospective clinical trial. Data on demographics, referral patterns, and clinical characteristics were extracted from October 2016 to February 2023. Patients were divided into three groups: transplanted, resected, and control (excluded, with continuation of systemic chemotherapy). Overall survival (OS) and recurrence-free survival (RFS) were compared. 81 referred patients were assessed for LDLT. 7 received transplants, 22 underwent resection, and 48 control. All had similar pre-assessment baseline characteristics. Median time from initial assessment to transplantation was 15.4 months. The control population had significantly worse post-assessment OS than the transplanted population (p=0.002) and resected population (p<0.001). The median post-operative follow-up duration was 21.4 months (resection) and 14.8 months (LDLT). There was no difference in OS between the transplanted and resected populations (1-year 100% vs. 93.8%; 3-year 100% vs. 43.3%, p=0.17). However, RFS was superior in the LDLT group (1-year 85.7% vs. 11.4%; 3-year 68.6% vs. 11.4%, p=0.012). Most patients with unresectable CRLM referred for LDLT are deemed ineligible for trial inclusion. However, the excellent oncologic outcomes in patients who meet criteria for LDLT supports its role in highly selected populations. Future results after the trial's completion will inform long-term outcomes.

New Insights in the Setting of Transplant Oncology.

Background and Objectives: Liver transplantation (LT) is the best strategy for curing several primary and secondary hepatic malignancies. In recent years, growing interest has been observed in the enlargement of the transplant oncology indications. This paper aims to review the most recent developments in the setting of LT oncology, with particular attention to LT for unresectable colorectal liver metastases (CRLM) and cholangiocellular carcinoma (CCA). Materials and Methods: A review of the recently published literature was conducted. Results: Growing evidence exists on the efficacy of LT in curing CRLM and peri-hilar and intrahepatic CCA in well-selected patients when integrating this strategy with (neo)-adjuvant chemotherapy, radiotherapy, or locoregional treatments. Conclusion: For unresectable CCA and CRLM management, several prospective protocols are forthcoming to elucidate LT's impact relative to alternative therapies. Advances in diagnosis, treatment protocols, and donor-to-recipient matching are needed to better define the oncological indications for transplantation. Prospective, multicenter trials studying these advances and their impact on outcomes are still required.

Liver transplantation for isolated unresectable colorectal liver metastases - Protocol for a service evaluation in the United Kingdom - UKCoMET study

BackgroundLiver transplantation (LT) for unresectable colorectal liver metastases (CRCLM) demonstrates good overall survival for selected patients in contemporary studies, with 5-year survival of 80%. A Fixed Term Working Group (FTWG), set up by NHS Blood and Transplant (NHSBT) Liver Advisory Group (LAG), advised whether CRCLM should be considered for LT in United Kingdom. Their recommendation was that LT may be undertaken for isolated and unresectable CRCLM using strict selection criteria as a national clinical service evaluation. MethodsOpinions were sought from colorectal cancer/LT patient representatives, experts in colorectal cancer surgery/oncology, LT surgery, hepatology, hepatobiliary radiology, pathology, and nuclear medicine, and appropriate patient selection criteria, referral and transplant listing pathways were identified. ResultsThis paper summarises selection criteria for LT in United Kingdom for isolated and unresectable CRCLM patients, and highlights referral framework and pre-transplant assessment criteria. Finally, oncology-specific outcome measures to be utilised for assessing applicability of LT are described. ConclusionThis service evaluation represents a significant development for colorectal cancer patients in United Kingdom and a meaningful step forward in the field of transplant oncology. This paper details the protocol for the pilot study, scheduled to begin in the fourth quarter of 2022 in United Kingdom.

Dynamic radiomics for predicting the efficacy of antiangiogenic therapy in colorectal liver metastases.

For patients with advanced colorectal liver metastases (CRLMs) receiving first-line anti-angiogenic therapy, an accurate, rapid and noninvasive indicator is urgently needed to predict its efficacy. In previous studies, dynamic radiomics predicted more accurately than conventional radiomics. Therefore, it is necessary to establish a dynamic radiomics efficacy prediction model for antiangiogenic therapy to provide more accurate guidance for clinical diagnosis and treatment decisions. In this study, we use dynamic radiomics feature extraction method that extracts static features using tomographic images of different sequences of the same patient and then quantifies them into new dynamic features for the prediction of treatmentefficacy. In this retrospective study, we collected 76 patients who were diagnosed with unresectable CRLM between June 2016 and June 2021 in the First Hospital of China Medical University. All patients received standard treatment regimen of bevacizumab combined with chemotherapy in the first-line treatment, and contrast-enhanced abdominal CT (CECT) scans were performed before treatment. Patients with multiple primary lesions as well as missing clinical or imaging information were excluded. Area Under Curve (AUC) and accuracy were used to evaluate model performance. Regions of interest (ROIs) were independently delineated by two radiologists to extract radiomics features. Three machine learning algorithms were used to construct two scores based on the best response and progression-free survival (PFS). For the task that predict the best response patients will achieve after treatment, by using ROC curve analysis, it can be seen that the relative change rate (RCR) feature performed best among all features and best in linear discriminantanalysis (AUC: 0.945 and accuracy: 0.855). In terms of predicting PFS, the Kaplan-Meier plots suggested that the score constructed using the RCR features could significantly distinguish patients with good response from those with poor response (Two-sided P<0.0001 for survival analysis). This study demonstrates that the application of dynamic radiomics features can better predict the efficacy of CRLM patients receiving antiangiogenic therapy compared with conventional radiomics features. It allows patients to have a more accurate assessment of the effect of medical treatment before receiving treatment, and this assessment method is noninvasive, rapid, and less expensive. Dynamic radiomics model provides stronger guidance for the selection of treatment options and precision medicine.

Improving Outcome of Selected Patients With Non-Resectable Hepatic Metastases From Colorectal Cancer With Liver Transplantation: A Prospective Parallel Trial (COLT trial)

BackgroundPatients with unresectable Colorectal Liver Metastases (CLM) receiving palliative chemotherapy have a 5-year overall survival (OS) of less than 30%. Liver transplantation (LT) can improve OS up to 60%-83% (SECA-I and SECA-II trials). The aim of the study is to assess the efficacy of LT in liver-only metastatic CRC compared with a matched cohort of patients included in a phase III trial on triplet chemotherapy + antiEGFR. Patients and MethodsThe COLT trial is an investigator-driven, multicenter, non-randomized, open-label, controlled, prospective, parallel trial (ClinicalTrials.gov NCT03803436). Hyperselected patients with liver-limited unresectable CLM, RAS and BRAF wild-type and curatively removed primary colon cancer are included. The observed post-transplant outcomes will be prospectively compared 1:5 with those obtained in a matched cohort from the TRIPLETE trial (NCT03231722). ResultsPrimary endpoint is to compare the 3 and 5-years OS of patients enrolled in the COLT trial with COLT-eligible population enrolled in the TRIPLETE trial. An expected gain in OS of 40% at 5-years is predicted for the COLT population (the expected OS at 5-years in COLT vs. TRIPLETE is 70% vs. 30%). Secondary endpoints are to compare the 5-years disease-free survival and to assess the safety of LT (Dindo-Clavien Classification and the Comprehensive Complication Index). ConclusionLT offers the longest OS reported in selected patients with CLM. Improving the selection strategies can give patients a 5-year OS similar to other indications for LT and a better outcome than those undergoing chemotherapy alone.

The High Incidence of Occult Carcinoma in Total Hepatectomy Specimens of Patients Treated for Unresectable Colorectal Liver Metastases With Liver Transplant.

To describe the rate of occult carcinoma deposits in total hepatectomy specimens from patients treated with liver transplant (LT) for colorectal liver metastases (CRLM). Previous studies have shown that patients with CRLM treated with systemic therapy demonstrate a high rate of complete radiographic response or may have disappearing liver metastases. However, this does not necessarily translate into a complete pathologic response, and residual invasive cancer may be found in up to 80% of the disappearing tumors after resection. Retrospective review of 14 patients who underwent LT for CRLM, at 2 centers. Radiographic and pathologic correlation of the number of tumors and their viability before and after LT was performed. The median (interquartile range) number of tumors at diagnosis was 11 (4-23). The median number of chemotherapy cycles was 24 (16-37). Hepatic artery infusion was used in 5 patients (35.7%); 6 (42.9%) underwent surgical resection, and 5 (35.7%) received locoregional therapy. The indication for LT was unresectability in 8 patients (57.1%) and liver failure secondary to oncologic treatment in the remaining 6 (42.9%). Before LT, 7 patients (50%) demonstrated fluorodeoxyglucose-avid tumors and 7 (50%) had a complete radiographic response. Histopathologically, 11 patients (78.6%) had a viable tumor. Nine (64.2%) of the 14 patients were found to have undiagnosed metastases on explant pathology, with at least 22 unaccounted viable tumors before LT. Furthermore, 4 (57.1%) of the 7 patients who demonstrated complete radiographic response harbored viable carcinoma on explant pathology. A complete radiographic response does not reliably predict a complete pathologic response. In patients with unresectable CRLM, total hepatectomy and LT represent a promising treatment options to prevent indolent disease progression from disappearing CRLM.

Combined CT-guided high-dose-rate brachytherapy (CT-HDRBT) and transarterial chemoembolization with irinotecan-loaded microspheres improve local tumor control and progression-free survival in patients with unresectable colorectal liver metastases compared with mono-CT-HDRBT.

To compare the effectivity and toxicity of monotherapy with computed tomography-guided high-dose-rate brachytherapy (CT-HDRBT) vs. combination therapy of transarterial chemoembolization with irinotecan (irinotecan-TACE) and CT-HDRBT in patients with large unresectable colorectal liver metastases (CRLM) with a diameter of > 3 cm. Forty-four retrospectively matched patients with unresectable CRLM were treated either with mono-CT-HDRBT or with a combination of irinotecan-TACE and CT-HDRBT (n = 22 in each group). Matching parameters included treatment, disease, and baseline characteristics. National Cancer Institute Common Terminology Criteria for Adverse Events (version 5.0) were used to evaluate treatment toxicity and the Society of Interventional Radiology classification was applied to analyze catheter-related adverse events. Statistical analysis involved Cox regression, Kaplan-Meier estimator, log-rank test, receiver operating characteristic curve analysis, Shapiro-Wilk test, Wilcoxon test, paired sample t-test, and McNemar test. P-values < 0.05 were deemed significant. Combination therapy ensued longer median progression-free survival (PFS: 5/2 months, p = 0.002) and significantly lower local (23%/68%, p < 0.001) and intrahepatic (50%/95%, p < 0.001) progress rates compared with mono-CT-HDRBT after a median follow-up time of 10 months. Additionally, tendencies for longer local tumor control (LTC: 17/9 months, p = 0.052) were found in patients undergoing both interventions. After combination therapy, aspartate and alanine aminotransferase toxicity levels increased significantly, while total bilirubin toxicity levels showed significantly higher increases after monotherapy. No catheter-associated major or minor complications were identified in each cohort. Combining irinotecan-TACE with CT-HDRBT can improve LTC rates and PFS compared with mono-CT-HDRBT in patients with unresectable CRLM. The combination of irinotecan-TACE and CT-HDRBT shows satisfying safety profiles.

Outcomes of patients with CRLM evaluated for liver transplant: Understanding the denominator

Background: A growing body of evidence has established the benefit of liver transplant (LT) for selected patients with unresectable colorectal liver metastases (urCRLM). However, a rigid criteria for patient selection are required to achieve acceptable long-term oncologic outcomes. The aim of this study is to analyze the protocol completion patterns, as well as alternative endpoints, of patients with urCRLM who were referred to a high-volume center for LT evaluation.

Intra-arterial hepatic bevacizumab and systemic chemotherapy in hepatic metastasis of colorectal cancer: A phase II multicentric trial in second-line treatment

IntroductionIntra-arterial hepatic (IAH) treatment has shown promising results in the management of patients with unresectable colorectal liver metastases (CRLM) the prognosis of which is poor. Bevacizumab adjunction to standard chemotherapy has been shown to improve survival of this patient population. This prospective study was conducted to assess the efficacy and safety of IAH bevacizumab combined to systemic chemotherapy after first-line treatment failure in patients with CRLM. MethodsIncluded patients had dominant or isolated unresectable CRLM progressing after standard first-line treatment for metastases of colorectal cancer. Three patients had less than 30% liver invasion, three patients between 30 and 50%, two more than 50% and data was missing in two patients. An intra-hepatic catheter was implanted surgically or percutaneously. Bevacizumab 7.5 mg/kg was administered once every 3 weeks in combination with capecitabine 2000 mg/m² per day for 2 weeks and oxaliplatin 130 mg/m² or irinotecan 200 mg/m² once every 3 weeks. The primary end-point was the objective response rate. ResultsBetween June 2013 and February 2015, 10 patients were included. The trial was prematurely closed because of the lack of financial support and poor accrual. The patients had a median of 6 [1–9] cycles of treatment. Partial response was achieved in 2 patients (20%) and a R0 liver metastases resection in one another. All patients died of disease progression. The median overall and progression-free survival rates were respectively 14.0 (95% IC [4.8 – 25.8] and 5.4 months (95% IC [1.6 – 6.2]). Four patients had severe side effects but no toxic death occurred. ConclusionIAH bevacizumab combined to systemic chemotherapy is feasible and safe in patients with unresectable isolated or dominant CRLM progressing after a first-line systemic treatment. Based on the low number of patients included in our study, our results suggest that this treatment does not increase dramatically the response rate versus an adapted systemic treatment. However, considering the safety data provided in this study, arterial infusion of bevacizumab in adjunction to chemotherapeutic agents could be evaluated in the future.

Efficacy and Safety of TACE Combined with Regorafenib versus TACE in the Third-Line Treatment of Colorectal Liver Metastases.

The liver is the most common site of metastasis in colorectal cancer. In patients with unresectable colorectal liver metastases, the 5-year survival rate is less than 5%. Many patients with colorectal liver metastases require effective subsequent therapy after the failure of standard first-line/second-line therapy. The purpose of this study is to investigate the efficacy and safety of TACE combined with Regorafenib versus TACE in the third-line treatment of patients with colorectal liver metastases. The clinical data of 132 patients with colorectal liver metastases were collected. There were two groups: TACE + Regorafenib group (N = 63); TACE group (N = 69). TACE uses CalliSpheres® drug-loaded microspheres (loaded with irinotecan). Regorafenib is administered at a dose of 120 mg once daily. If the patient is severely intolerable, the regorafenib dose is adjusted to 80 mg once daily. Primary study endpoints were (1) to evaluate the tumor response, ORR, and DCR and (2) to evaluate OS and PFS in the two groups. Secondary study endpoints were (1) to compare the performance status, CEA, CA19-9 after treatment between the two groups and (2) to compare the incidence of adverse events between the two groups. There were significant differences in tumor response, ORR, DCR, OS, and PFS after treatment between the two groups. TACE combined with the Regorafenib group versus the TACE group: ORR (57.1% vs 33.3%), DCR (82.5% vs 68.1%), mOS (18.2 months vs 11.3 months), and mPFS (8.9 months vs 5.3 months). The performance status after treatment was better in the TACE + Regorafenib group than in the TACE group (P < 0.05). The CEA and CA19-9 negative rates after treatment were higher in the TACE + Regorafenib group than in the TACE group (P < 0.05). For the third-line treatment of colorectal liver metastases, the combination of TACE + Regorafenib had better tumor response, OS, and PFS than TACE TACE + Regorafenib combination could be considered as salvage therapy for colorectal liver metastases who failed the first- and second-line standard therapy.

Targeted exome-based predictors of patterns of progression of colorectal liver metastasis after percutaneous thermal ablation.

Percutaneous thermal ablation is a curative-intent locoregional therapy (LRT) for selected patients with unresectable colorectal liver metastasis (CLM). Several factors have been identified that contribute to local tumour control after ablation. However, factors contributing to disease progression outside the ablation zone after ablation are poorly understood. In this retrospective study, using next-generation sequencing, we identified genetic biomarkers associated with different patterns of progression following thermal ablation of CLM. A total of 191 ablation naïve patients between January 2011 and March 2020 were included in the analysis, and 101 had genomic profiling available. Alterations in the TGFβ pathway were associated with increased risk of development of new intrahepatic tumours (hazard ratio [HR], 2.75, 95% confidence interval [95% CI] 1.39-5.45, P = 0.004); and alterations in the Wnt pathway were associated with increased probability of receiving salvage LRT for any intrahepatic progression (HR, 5.8, 95% CI 1.94-19.5, P = 0.003). Our findings indicate that genomic alterations in cancer-related signalling pathways can predict different progression patterns and the likelihood of receiving salvage LRT following percutaneous thermal ablation of CLM.

Metabolic tumor volume predicts long-term survival after transplantation for unresectable colorectal liver metastases: 15 years of experience from the SECA study

ObjectiveTo report 15 years of experience with metabolic tumor volume (MTV) of liver metastases from the preoperative 18F-FDG PET/CT to predict long-term survival after liver transplantation (LT) for unresectable colorectal liver metastases (CRLM).MethodsThe preoperative 18F-FDG PET/CT from all SECA 1 and 2 patients was evaluated. MTV was obtained from all liver metastases. The patients were divided into one group with low MTV (< 70 cm3) and one group with high MTV (> 70 cm3) based on a receiver operating characteristic analysis. Overall survival (OS), disease-free survival (DFS) and post recurrence survival (PRS) for patients with low versus high MTV were compared using the Kaplan–Meier method and log rank test. Clinopathological features between the two groups were compared by a nonparametric Mann–Whitney U test for continuous and Fishers exact test for categorical data.ResultsAt total of 40 patients were included. Patients with low MTV had significantly longer OS (p < 0.001), DFS (p < 0.001) and PRS (p = 0.006) compared to patients with high values. The patients with high MTV had higher CEA levels, number of liver metastases, size of the largest liver metastasis, N-stage, number of chemotherapy lines and more frequently progression of disease at LT compared to the patients with low MTV.ConclusionMTV of liver metastases is highly predictive of long-term OS, DFS and PRS after LT for unresectable CRLM and should be implemented in risk stratification prior to LT.

The Role of Biomarkers in the Management of Colorectal Liver Metastases.

Simple SummaryColorectal cancer remains one of the most significant sources of cancer-related morbidity and mortality worldwide. The liver is the most common site of metastatic spread. Multiple modalities exist to manage and potentially cure patients with metastatic colorectal cancer. However, reliable biomarkers to assist with clinical decision-making are limited. Recent advances in genomic sequencing technology have greatly expanded our knowledge of colorectal cancer carcinogenesis and significantly reduced the cost and timing of the investigation. In this article, we discuss the current utility of biomarkers in the management of colorectal cancer liver metastases.Surgical management combined with improved systemic therapies have extended 5-year overall survival beyond 50% among patients with colorectal liver metastases (CRLM). Furthermore, a multitude of liver-directed therapies has improved local disease control for patients with unresectable CRLM. Unfortunately, a significant portion of patients treated with curative-intent hepatectomy develops disease recurrence. Traditional markers fail to risk-stratify and prognosticate patients with CRLM appropriately. Over the last few decades, advances in molecular sequencing technology have greatly expanded our knowledge of the pathophysiology and tumor microenvironment characteristics of CRLM. These investigations have revealed biomarkers with the potential to better inform management decisions in patients with CRLM. Actionable biomarkers such as RAS and BRAF mutations, microsatellite instability/mismatch repair status, and tumor mutational burden have been incorporated into national and societal guidelines. Other biomarkers, including circulating tumor DNA and radiomic features, are under active investigation to evaluate their clinical utility. Given the plethora of therapeutic modalities and lack of evidence on timing and sequence, reliable biomarkers are needed to assist clinicians with the development of patient-tailored management plans. In this review, we discuss the current evidence regarding biomarkers for patients with CRLM.

Prognostic impact of conversion hepatectomy for initially unresectable colorectal liver metastasis

This study aimed to evaluate the prognostic impact of conversion hepatectomy in patients with initially unresectable colorectal liver metastasis (CRLM) and to identify prognostic factors after conversion hepatectomy. Correlations of conversion hepatectomy with relapse-free survival (RFS) and overall survival (OS) were retrospectively investigated in 554 consecutive patients who underwent hepatectomy for CRLM in 2000-2017. Prognostic factors after conversion hepatectomy were examined in multivariable analysis. Five hundred and nine patients (92%) had initially resectable CRLM at diagnosis and underwent hepatectomy (primary resection group) and 45 (8%) underwent conversion hepatectomy following chemotherapy (conversion group). The 5-year RFS was 30.0% in the primary resection group and 19.8% in the conversion group (p = 0.042); the respective 5-year OS rates were 62.0% and 52.4% (p = 0.253). Multivariable analysis did not identify conversion hepatectomy as a significant prognostic factor for RFS (hazard ratio [HR] 0.95, 95% confidence interval [CI] 0.64-1.37, p = 0.796) or OS (HR 1.12, 95% CI 0.67-1.79, p = 0.667). In the conversion group, multivariable analysis identified the following independent prognostic factors: timing of liver metastases for RFS (synchronous: HR 3.14, 95% CI 1.20-8.24, p = 0.020) and preoperative CEA level for RFS (> 5ng/ml: HR 3.10, 95% CI 1.45-6.61, p = 0.003) and OS (> 5ng/ml: HR 3.29, 95% CI 1.18-9.17, p = 0.023). RFS and OS rates after conversion hepatectomy were not inferior to those after primary resection in patients with CRLM. Patients with a normal CEA level before hepatectomy can be expected to have good long-term prognosis after conversion hepatectomy.

LBA21 FOLFOX/FOLFIRI plus either bevacizumab or panitumumab in patients with initially unresectable colorectal liver metastases (CRLM) and left-sided and RAS/BRAFV600E wild-type tumour: Phase III CAIRO5 study of the Dutch Colorectal Cancer Group

Patients (pts) with initially unresectable CRLM may qualify for curative-intent local therapy after downsizing by induction systemic therapy. CAIRO5 was designed to find the optimal induction regimen. We present results of pts with left-sided and RAS/BRAFV600E wild-type tumour. Pts were randomised between FOLFOX/FOLFIRI (patient preference) plus either bevacizumab (arm A) or panitumumab (arm B) up to 12 cycles. Prior systemic or local therapy for metastases was not allowed. (Un)resectability of CRLM was assessed by a liver expert panel of surgeons and radiologists, at baseline by predefined criteria and every 2 months thereafter by individual opinion. Primary endpoint was progression-free survival (PFS). Pts were stratified by potentially resectable vs permanently unresectable CRLM, serum LDH (normal/abnormal) and choice of irinotecan vs oxaliplatin. 256 events were required to detect a hazard ratio (HR) of 0.70 for PFS with 80% power and 2-sided log-rank test at 5% assuming a median PFS of 11.6 months in arm A. 236 pts (118 in each arm) were included in 43 Dutch sites from November 2014 until closure due to futility in March 2022. 6 ineligible pts were excluded. Median follow up was 44 months. Main characteristics were (arm A/B): median age 59/60, male 61/63%, synchronous CRLM 88/92%, prior adjuvant chemotherapy 4/3%, median number of CRLM 12/12. With 197 events, median PFS in arm A vs B was 10.6 vs 10.3 months (stratified HR 1.12, 95% CI 0.84-1.50, p=0.44). Response rate (RR) was 52% vs 76% (p<0.01). Median depth of response (DOR) was 33% vs 49% (p<0.01). R0/1 resection ± ablation rate was 58% vs 56% (p=0.79). Grade ≥3 toxicity occurred in 52% vs 69% (p=0.01), Clavien Dindo grade ≥3 surgical complications in 21% vs 14% (p=0.30). In first-line treatment of pts with initially unresectable CRLM and left-sided and RAS/BRAFV600E wild-type tumour there is no difference in median PFS between the addition of either bevacizumab or panitumumab to FOLFOX/FOLFIRI. The addition of panitumumab significantly increases RR and DOR but this does not translate in an increased local therapy rate of CRLM.

Rescue percutaneous transhepatic portal vein embolization after failed associated liver partition and portal vein ligation for staged hepatectomy in a patient with multiple liver metastases of rectal cancer: a case report

BackgroundLiver metastasis is the most common form of distant spread of colorectal cancer. Despite oncological and surgical advances, only about 25% of patients are eligible to undergo resection. As the liver has a limited resectable volume, tumor reduction and remnant liver hypertrophy are of critical importance in treating initially unresectable colorectal cancer liver metastasis. Associated liver partition and portal vein ligation for staged hepatectomy (ALPPS) allows rapid liver hypertrophy within a short period and has been reported to be useful in recent years.Case presentationA 29-year-old woman complaining of bloody stool was referred to our hospital. She was diagnosed with rectal cancer (Rb) with simultaneous multiple liver and lung metastases. The patient was then initially commenced on chemotherapy and completed it with a satisfactory response. Right trisectionectomy was necessary to achieve hepatic clearance; however, the future liver remnant (FLR) volume was insufficient. Therefore, we decided to perform totally laparoscopic ALPPS to obtain enough FLR volume. However, the FLR increase was slow, and FLR did not attain the required volume for right trisectionectomy. Computed tomography showed that right portal venous blood flow was increased via developed collateral vessels around the portal vein. We attempted to induce further liver growth by blocking portal blood flow using additional percutaneous transhepatic portal vein embolization (PTPE), and a rapid increase in FLR was obtained. The patient underwent right trisectionectomy and partial resection of S2 with negative margins, and the patient was discharged without postoperative liver failure.ConclusionsResumption of the portal venous blood flow through collateral vessels after ALPPS may have interfered with the planned residual liver hypertrophy. Performing PTPE in addition to ALPPS increased the FLR volume, and radical hepatectomy was completed safely. Remnant portal venous blood flow following ALPPS is an important issue to be considered in surgical planning, and early additional portal vein embolization could be effective.

FOLFOXIRI + bevacizumab versus FOLFOX/FOLFIRI + bevacizumab in patients with initially unresectable colorectal liver metastases (CRLM) and right-sided and/or RAS/BRAFV600E-mutated primary tumor: Phase III CAIRO5 study of the Dutch Colorectal Cancer Group.

LBA3506 Background: Patients (pts) with initially unresectable CRLM may qualify for curative-intent local therapy after downsizing by induction systemic therapy. The CAIRO5 study aims to find the optimal induction regimen. We present the results of pts with right-sided and/or RAS/ BRAFV600E mutated primary tumors. Accrual in pts with left-sided and RAS/ BRAFV600E wildtype tumors is ongoing. Methods: Pts were randomized between FOLFOX or FOLFIRI + bevacizumab (B) (arm A) and FOLFOXIRI-B (arm B), in both arms up to 12 cycles and followed by 5FU/LV/B maintenance. Prior systemic or local therapy for metastases was not allowed. Unresectability of CRLM at baseline was assessed by an online liver expert panel of surgeons and radiologists based on predefined criteria, and resectability every 2 months thereafter based on panel majority vote. The primary endpoint was progression-free survival (PFS). Secondary endpoints were R0/1 resection, overall survival, overall response rate (ORR), toxicity, pathologic response, postoperative morbidity and correlation of panel evaluations with outcome. Pts were stratified by potentially resectable vs permanently unresectable CRLM, serum LDH (normal/abnormal), BRAFV600E mutation, sidedness, choice of irinotecan vs oxaliplatin and institute. To detect a hazard ratio (HR) of 0.70 for PFS with 80% power and a 2-sided log-rank test at 5%, 257 events were required, assuming a median PFS of 8.7 months for arm A. Results: From December 2014 until March 2021, 294 pts were randomized, 148 in arm A and 146 in arm B in 43 Dutch and 1 Belgian sites. 3 ineligible pts were excluded. Median follow up was 40 months. Pts received a median of 10 vs 9 induction cycles in arm A vs B. Main characteristics were (arm A/B): median age 61/65 years, male 63.9/60.4%, right-sided primary tumor 39.5/41.7%, RAS mutant 85.7/86.1%, BRAFV600E mutant 6.8/8.3%, synchronous disease 86.4/89.6%, prior adjuvant chemotherapy 4.8/4.9%, median number of CRLM 12/12. With 259 events, median PFS in arm A vs B was 9.0 vs 10.6 months (stratified HR 0.74, 95% CI 0.57-0.96, p=0.02). ORR was 32.0% vs 52.1% (p&lt;0.001), any grade ≥3 adverse events occurred in 58.5% vs 75.0% (p=0.003), the most frequent were neutropenia (12.9/38.2%, p&lt;0.001), hypertension (14.3/13.9%, p=1) and diarrhea (3.4/19.4%, p&lt;0.001) in arm A vs B, respectively. R0/1 resection ± ablation rates were 37.4% vs 51.4% (p=0.02) with 2-stage procedures in 16.4% vs 32.4% (p=0.04), postoperative complications occurred in 38.2% vs 51.2% (p=0.14), Clavien Dindo grade ≥3 in 14.7% vs 26.8% (p=0.08). Conclusions: FOLFOXIRI-B vs FOLFOX/FOLFIRI-B significantly increases PFS, ORR and R0/1 resections at the cost of increased toxicity in pts with initially unresectable CRLM and right-sided and/or RAS/ BRAFV600E mutated primary tumor. Clinical trial information: NCT02162563.